Online Quiz 1

Question: Which factor does not predict relapse of diabetes in obese patients with DM2,
whom have experienced remission of diabetes following gastric bypass surgery?

Pre-operative glycemic control
Insulin therapy before surgery
Pre-operative BMI values
Pre-operative diabetes duration
Older age at surgery
Answer: The correct answer is pre-operative BMI values. Data was collected in a retrospective cohort study of 4,434
adults with type 2 diabetes who underwent gastric bypass from 1995 to 2008. Diabetes remission and relapse events
were recorded.Multivariate analysis showed older age at surgery was associated with higher risk of relapse (HR for 5year increase in age, 1.07; 95 % CI, 1.01 to 1.14). Subjects with poor preoperative glycemic control (HbA1c 6.5 %)
were significantly more likely to experience relapse than those with good preoperative control, (HR for HbA1c 6.5-8%
1.34; 95% CI 1.04-1.71, HR for HbA1c 8-9% 1.43; 95% CI 1.03-1.97, HR for HbA1c 9-10% 1.95; 95% CI, 1.34-2.84).
Subjects treated with insulin were significantly more likely to experience relapse than diabetic subjects not using insulin
before surgery (HR for patients on oral medication at surgery 1.37; 95% CI 1.10-1.70 and HR for patients on insulin at
surgery 1.91; 1.48-2.45). Longer diabetes duration was significantly associated with higher relapse rate (HR for each
additional year of diabetes, 1.13; 95 % CI, 1.09 to 1.17). However, pre-operative BMI values were not significantly
different (p = 0.93) between patients who never completely remitted their diabetes (BMI 45.5 kg/m2), patients who
completely remitted but relapsed (BMI 45.8 kg/m2), and patients who durably remitted their diabetes (BMI 45.6 kg/m2).
Arterburn D, et al. A Multisite Study of Long-term Remission and Relapse of Type 2 Diabetes Mellitus Following Gastric
Bypass. Obesity Surgery 2012
Question 1: Clinical characteristics of obese, ketosis-prone diabetes include which of the following:
Preserved beta cell function

Age at onset < 40 years
Presence of islet cell specific autoantibodies
Female sex predominance
DKA provoked by significant precipitating stress
Answer: The correct answer is preserved beta cell function. Other clinical characteristics of obese, ketosis-prone
diabetes are; absence of islet cell autoantibodies, male sex preponderance, DKA that is unprovoked by any significant
precipitating stress, and age at onset usually > 40 years.
The Endocrine Society; 2011:43.
Question 2: The most commonly reported adverse event with Janumet in the treatment of type 2 diabetes is:
Abdominal Pain
Nausea
Diarrhea
Upper respiratory infection
Headache
Answer: The correct answer is diarrhea. In clinical studies, the most common adverse reactions reported with Janumet
in 5% of patients and more commonly than in patients treated with placebo were as follows: diarrhea > upper
respiratory tract infection > headache.
Inc. DIAB-1002314-0000-05/11
Question 3: What is the best screening test for cystic fibrosis-related diabetes (CFRD)?
Urine glucose
HbA1c
Fructosamine
Oral glucose tolerance test (OGTT)
Fasting plasma glucose
Answer: The correct answer is OGTT. The American Diabetes Association and The Cystic Fibrosis Foundation
recommend the oral glucose tolerance test (OGTT) as the screening test of choice for CFRD. Although it is an imperfect
test due to the variability observed in individual CF patients over time, longitudinal studies demonstrate that a diabetes
diagnosis by OGTT correlates with clinically important CF outcomes including the rate of lung function decline over the
next 4 years, the risk of microvascular complications, and the risk of early death. The committee concluded that HbA1c is
not sufficiently sensitive for diagnosis of CFRD and should not be used as a screening test. Fasting plasma glucose does
not identify those patients without fasting hyperglycemia, and will miss the diagnosis of diabetes in approximately half of
CF patients. Fructosamine and urine glucose have low sensitivity in the CF population.
Diabetes Care. 2010;33(12):2697-2708.
Question 4: Patients with maturity-onset diabetes of the young (MODY )3 may respond to which of the following agents:
Glipizide
Pioglitazone
Metformin
Sitagliptin
Exenatide
Answer: The correct answer is glipizide. Patients with maturity-onset diabetes of the young (MODY)3 have a mutation in
TCF/HNF-alpha. Mutations of this gene lead to reduced beta cell mass or impaired function. About 70% of people
develop this type of diabetes by age 25 years, but it occurs at much later ages in a few. This type of diabetes can often
be treated with sulfonylureas with excellent results for decades.
Diabetes Res Clin Pract. 2008;81(1):e1-e3
Question 5: The American Association of Clinical Endocrinologist (AACE) recommends personal continuous glucose
monitoring for patients with type 1 diabetes and the following characteristics:
Hypoglycemic unawareness or frequent hypoglycemia

During preconception and pregnancy
All answer choices are correct
HbA1c over target
Excess glycemic variability
Answer: The correct answer is all answer choices are correct. The American Association of Clinical Endocrinologists
(AACE) recommends personal CGM for those with type 1 DM and the following characteristics: Hypoglycemic
unawareness or frequent hypoglycemia, HbA1c over target, excess glycemic variability (eg, hypoglycemia judged to be
excessive, potentially disabling, or life- threatening), requiring HbA1c lowering without increased hypoglycemia, and
during preconception and pregnancy.
Endocrine Practice. 2010;16(5):730-745.
Question : A randomized, double-blind, multicenter trial was conducted to investigate whether patients taking metformin
for type 2 diabetes mellitus (T2DM) have improved glycemic control without compromising tolerability by adding
saxagliptin vs. uptitrating metformin. Which of the following best describes the results?
Reduction in 120-minute Post Prandial Glucose (PPG) was not significantly greater with saxagliptin + metformin
XR than with uptitrated metformin XR
Reduction in Fasting Plasma Glucose (FPG) was significantly greater with uptitrated metformin XR than with
saxagliptin + metformin XR
The proportion of patients experiencing 1 adverse events was greater with saxagliptin + metformin XR than with
uptitrated metformin XR
Decreases in mean HbA1c were similar in patients receiving saxagliptin + metformin XR to those receiving
uptitrated metformin XR
The percentage of patients achieving HbA1c <7.0% was significantly greater with saxagliptin + metformin
XR than with uptitrated metformin XR
Answer: The correct answer is the percentage of patients achieving HbA1c <7.0% was significantly greater with
saxagliptin + metformin XR than with uptitrated metformin XR. Adults with T2DM and HbA1c between 7.0 and 10.5%
receiving metformin extended release (XR) 1500 mg/day for 8 weeks were randomized to receive saxagliptin 5 mg
added to metformin XR 1500 mg (n = 138) or metformin XR uptitrated to 2000 mg/day (n = 144). At week 18, the
adjusted mean reduction from baseline HbA1c was ?0.88% for saxagliptin + metformin XR and ?0.35% for uptitrated
metformin XR (difference, ?0.52%; p < 0.0001). For 120-min PPG and FPG, differences in adjusted mean change from
baseline between saxagliptin + metformin XR and uptitrated metformin XR were ?1.3 mmol/l (?23.32 mg/dl) (p = 0.0013)
and ?0.73 mmol/l (?13.18 mg/dl) (p = 0.0030), respectively. More patients achieved HbA1c <7.0% with saxagliptin +
metformin XR than with uptitrated metformin XR (37.2 vs. 26.1%; p = 0.0459). The proportions of patients experiencing
any adverse events (AEs) were generally similar between groups; neither group showed any notable difference in
hypoglycemia or gastrointestinal AEs. Adding saxagliptin to metformin XR provided superior glycemic control compared
with uptitrating metformin XR without the emergence of additional safety concerns
Fonseca V, et al. Adding saxagliptin to extended-release metformin vs. uptitrating metformin dosage. Diabetes, Obesity
and Metabolism. 2012;14(4):365-371.
Question: Diabetes is the leading cause of new blindness among people ages 20-74 years. Which of the following
statements is false regarding ranibizumab injection, (Lucentis)?
Its a promising therapy for DM macular edema, but isnt approved by FDA
It is used to treat age related macular degeneration
It is an anti-angiogenic VEGF inhibitor
The most common side effectis bleeding of the conjunctiva
Answer: The correct answer is: Its a promising therapy for DM macular edema, but isnt approved by FDA is false. In
August 2012, the Food and Drug Administration approved ranibizumab for the treatment of diabetic macular edema
(DME). The drugs safety and effectiveness to treat DME were established in two clinical studies involving 759 patients
who were treated and followed for three years. Patients were randomly assigned to receive monthly injections of Lucentis
or no injections for 24 months. Results showed that between 34 - 45 % of those treated withLucentis gained at least
three lines of vision compared with 12 -18 % of those who did not. The most common side effects of the drug were
bleeding of the conjunctiva, eye pain, and increased intraocular pressure.The FDA previously had approved Lucentis to
treat age-related macular degeneration and macular edema following retinal vein occlusion. Ranibizumab is an
monoclonal antibody fragment which inhibits a number of subtypes of vascular endothelial growth factors. VEGF
increases retinal vascular permeability, thereforeblocking VEGF in the eye may prevent and reverse vision loss caused
by macular degeneration. Ip MS, Domalpally A, et al. Long-term effects of intravitreal ranibizumab (RBZ) on diabetic
retinopathy severity and progression. Presented at the 2012 Annual Meeting of the Association for Research in Vision
and Ophthalmology (ARVO); May 610, 2012; Fort Lauderdale, Florida. Abstract 1336.
Nguyen Q, et al.Ranibizumab for diabetic macular edema results from 2 phase III randomized trials: RISE and RIDE.
Ophthalmology.2012;119:789801.
Question 1: Which of the following best describes the results of a recent cross-sectional study investigating the impact
of body mass index (BMI) status on the relationship of serum 25-hydroxyvitamin D (25OHD) concentration with insulin
sensitivity?
The correlation of serum 25OHD with insulin sensitivity was much stronger in the overweight group than
in the normal weight group.
The correlation of serum 25OHD with insulin sensitivity was similar in both the overweight and normal weight
group
The optimal serum 25OHD concentration for insulin sensitivity is about 46 ng mL?1.
The optimal serum 25OHD concentration for insulin sensitivity is about 34 ng mL?1.
Answer: The correct answer is the correlation of serum 25OHD with insulin sensitivity was much stronger in the
overweight group than in the normal weight group. Obesity is a risk factor for hypovitaminosis D, insulin resistance and
type 2 diabetes. This cross-sectional study enrolled 126 healthy and glucose-tolerant subjects. The participants were
divided into two groups based on BMI: normal weight (n = 68) and overweight (n = 58). Insulin sensitivity index (ISI) was
assessed by using hyperglycemic clamps. Serum 25OHD concentration was determined in the fasting samples. The
correlation of serum 25OHD with ISI was much stronger in the overweight group (r = 05271, P < 00001) than in the
normal weight group (r = 02836, P = 0002). The correlation remained significant in the overweight group (r = 03620, P
= 0002), but not in normal weight group after adjusting for age, gender, BMI, season of study, ethnicity and exercise.
Nonlinear regression analysis revealed that when serum 25OHD concentration was > 40 ng mL?1, the association
between serum 25D concentrations and insulin sensitivity plateaued. The results of this study suggested that overweight
subjects with hypovitaminosis D may benefit more from vitamin D replacement than normal weight subjects.
Furthermore, the optimal serum 25OHD concentration for insulin sensitivity is about 40 ng mL?1.
Horng-Yih Ou, et al Eur J Clin Invest 2011; 41 (11): 11951201
Question: The recommended glucose target for diabetic patients admitted to the intensive care unit (ICU) is:
100-140 mg/dl
140-180 mg/dl
120-160 mg/dl
80-110 mg/dl
Answer: The correct answer is 140-180 mg/dl. The American Association of Clinical Endocrinologists and the American
Diabetes Association recommends a glucose range of 140-180 mg/dl for critically ill diabetic patients. Although a very
tight glucose target 80110 mg/dl was beneficial in a predominantly surgical ICU population (Leuven trial-2001), this
target has been difficult to achieve in subsequent studies. Several randomized controlled trials (RCTs) investigating the
effect of intensive insulin therapy (IIT) on mortality with sub-analyses for patients with diabetes were performed at mixed
surgical and medical ICUs, without making distinction between surgical and medical patients. In all these studies IIT did
not show survival benefit over conventional glucose control in patients with diabetes. Also when analyzing pooled data
from both Leuven trials no benefit of IIT was seen in the diabetic patients. The achieved glucose levels in the IIT group of
the pooled analysis ranged from 104 to 117 mg/dl and in the conventional group from 144 mg/dl to 171 mg/dl. The NICESUGAR trial published in 2009 included the largest population of diabetes patients (n= 1211) and achieved mean (SD)
glucose values of 108 mg/dl and 144 mg/dl in the total population. In this subgroup the benefit tended towards the
conventional treatment, just like the overall outcome. The negative results in the mixed populations are supported by
analyses comparing mortality rates before and after the implementation of an IIT protocol showing no significant
decrease in mortality with IIT in patients with diabetes. S.E. Siegelaar 826 et al. Best Practice & Research Clinical
Endocrinology & Metabolism 25 (2011) 825834 Research Clinical Endocrinology
Question 1: True or False: In a randomized trial, duloxetine was found to be inferior to pregabalin for the treatment of
pain in patients with diabetic peripheral neuropathy (DPN) who had an inadequate pain response to gabapentin. (True or
False)?
True
False
Answer: The correct answer is False. The primary objective of this 12week,open-label, noninferiority study was to
determine whether treatment with duloxetine was at least as good as pregabalin in reducing pain associated with DPN in
patients who had an inadequate pain response to treatment with gabapentin. (900 mg/d) (defined as a daily pain score
of 4 on a numerical rating scale [010 points]). The mean change in the pain rating at end point was -2.6 for duloxetine
and -2.1 for pregabalin. The 97.5% lower confidence limit was a -0.05 difference in means, establishing noninferiority.
Tanenberg RJ et al. Mayo Clin Proc. July 2011,86(7):615-624
Question: Which of the following statements is true regarding the FREEDOM (Future
Revascularization Evaluation in Patients With Diabetes Mellitus: Optimal Management of
Multivessel cardiac Disease) trial?
CABG was associated with a lower risk of stroke
Patients in the PCI group had higher rates of acute renal failure
CABG was associated with a significant reduction in all-cause mortality
PCI was associated with a significant reduction in the risk of MI
Repeat revascularization was higher in the CABG treated patients
Answer: The correct answer is: CABG was associated with a significant reduction in all-cause mortality is false.
FREEDOM enrolled 1900 patients with diabetes and coronary artery disease, a majority of whom had three-vessel
disease, to treatment with CABG surgery or PCI with drug eluting stents. Dual antiplatelet therapy was recommended for
at least 12 months, and patients were followed for a minimum of two years. The primary outcome measure was a
composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke. The 5-year event rates were
26.6% in the PCI group, as compared with 18.7% in the CABG group, for an absolute difference of 7.9 percentage points
(95% confidence interval [CI], 3.3 to 12.5, P=0.005). There was increased all-cause mortality in the PCI group (P =
0.049), with 5-year rates of 16.3% in the PCI group versus 10.9% in the CABG group, for an absolute difference of 5.4
percentage points (95% CI, 1.5 to 9.2). There were fewer strokes in the PCI group with the 5-year rates being 2.4% in
the PCI group and 5.2% in the CABG group (P = 0.03). The excess of strokes in the CABG group occurred in the first 30
days after randomization. The repeat revascularization rate after 1 year was 12.6% in the PCI group, compared with
4.8% in the CABG group(hazard ratio, 2.74; 95% CI, 1.91 to 3.89; P<0.001). Acute renal failure requiring hemodialysis
within 30 days after revascularization was observed in 1 patient in the PCI group and 8 patients in the CABG group
(P=0.02).
Farkouh ME, Domanski M, Sleep LA, et al. Strategies for multivesselrevascularization in patients with diabetes. N Engl J
Med 2012.
Question: A comparative trial was performed between once-daily liraglutide and once-weekly
exenatide in patients with type 2 diabetes. Which of the following statements is false regarding
the trial results?
More nausea, diarrhea, and vomiting occurred with liraglutide
Injection-site nodules were more common with liraglutide
There were more serious adverse events in the exenatide group
The liraglutide group lost more weight, irrespective of BMI

Decrease in fasting glucose was greater in the liraglutide group
Answer: The correct answer is: Injection-site nodules were more common with liraglutide is false.The trial was a 26
week, open-label, randomized, parallel-group study at 105 sites in 19 countries between Jan 2010, and Jan 2011. Type II
diabetic patients on oralantihyperglycaemic drugs were randomly assigned (1:1) to receive injections of once-daily
liraglutide (1.8 mg) or once-weekly exenatide (2 mg). The primary endpoint was change in HbA from baseline to week
26. Both drugs were associated with a decrease in HbA1, but was greater in patients taking liraglutide (-1.28% vs.
-1.48%). However, the treatment difference (0.21%; 95% CI, 0.083-0.33) did not meet the predefined noninferiority
criteria. At 26 weeks, fasting serum glucose significantly decreased in both groups (p<0.0001), but the decrease was
greater in patients in the liraglutide group (-2.12 vs 1.76) with a treatment difference (0.36; 95% CI, 0.05-0.66). Both
treatments were associated with progressive decreases in bodyweight, but patients taking liraglutide lost more weight (3.57 vs -2.68) irrespective of BMI, with a treatment difference (0.9; 95% CI, 0.39-1.40). The most common adverse
events were mainly gastrointestinal in both groups, with a greater frequency of nausea, diarrhea, and vomiting in patients
in the liraglutide group. Injection-site nodules were more common with exenatide than with liraglutide. There were more
serious adverse events in the exenatide group (3% vs 2%) (including acute cholecystitis, myocardial infarction,
pancreatitis and prostate cancer) but with no identifiable pattern of events.
Buse JB. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a
randomised, open-label study. Published online November7, 2012
Question 1: A retrospective study found that implementing a mandatory, comprehensive protocol for treating adult
patients with diabetic ketoacidosis (DKA) resulted in:
Shorter time to clearance of the anion gap and ketones
Shorter ICU and hospital lengths of stay
No difference in the percentage of patients developing hypoglycemic episodes
Fewer recurrences of an anion gap acidosis.
Answer: The correct answer is all answer choices are correct. To determine the effect of a mandatory protocol for
treating DKA, a chart review was conducted, which included a total of 241 consecutive nonpregnant patients >18 yrs old
admitted to a medical intensive care unit for DKA between January 2000 and January 2005. The mandatory treatment
protocol was implemented in May 2003. Before protocol implementation, the mean &elusmn;SD ICU and hospital lengths
of stay were 44 &elusmn; 28 hrs and 91 &elusmn; 73 hrs, respectively. After implementation, ICU and hospital lengths of
stay decreased 23% and 30%, to 34 &elusmn;18 hrs and 64 &elusmn;41 hrs, respectively (both p < .007). Time to anion
gap closure and ketone clearance also decreased (both p < .05). No difference in the number of hypoglycemic episodes
was observed. This was the first report of a protocol for DKA decreasing the rate of anion gap recurrence after
discontinuation of an insulin infusion. Protocol-driven care can decrease intensive care unit (ICU) morbidity, mortality,
length of stay, errors, and costs. Several DKA treatment guidelines exist, but previous studies of their effectiveness show
no or limited benefit, perhaps because care was standardized for some but not all aspects of DKA or because their use
was not mandatory.
Bull, SV et al. Crit Care Med 2007 Vol. 35, No. 1
Question : A 52-year-old male with DM2 on insulin, reportsdysesthesia, numbness and tingling of extremities, and poor
sleep quality. You diagnosediabetic peripheral neuropathic pain. Which therapy would you prescribe for analgesia and
improved sleep?
Amitriptyline
Duloxetine
Pregabalin
Vitamin B12
Answer: The correct answer is pregabalin. A recently published, double-blind, randomized trial compared amitriptyline,
duloxetine and pregabalin in 104 diabetics with peripheral neuropathic pain. Subjective pain and sleep quality (using
polysomnography sleep records) were assessed over 28 days. Amitriptyline, duloxetine, and pregabalin, all reduced
subjective pain with no one drug being superior to another. Subjective pain ratings showed 50% improvement, in line
with previous studies. For sleep, pregabalin improvedsleep continuity (P< 0.001), reducing wake after sleep onset, in line
with previous reports. Duloxetine increased wake and reduced total sleep time (P< 0.01 and P< 0.001) and substantially
reduced REM sleep. Previous literature suggests that amitriptyline promotes sleep initiation and sleep continuity,
however there may be less impact of amitriptyline on sleep in patients with diabetic peripheral neuropathic pain.
Research has shown that people who take metformin may be at risk for developing vitamin B12 deficiency associated
peripheral neuropathy, however this patient is on insulin.
Boyle J, et al. Randomized, Placebo-Controlled Comparison of Amitriptyline, Duloxetine, and Pregabalin in Patients with
Chronic Diabetic Peripheral Neuropathic Pain. Impact on pain, polysomnographic sleep, daytime functioning, and quality
of life. Diabetes CareDecember 2012 vol. 35 no. 12 2451-2458
Question: Clinical characteristics of obese, ketosis-prone diabetes include which of the following: Correct!
Question: A randomized trial assessed the efficacy and safety of L-methylfolate calcium 3 mg, pyridoxal-5-phosphate
35 mg, and methylcobalamin 2 mg (LMF-MC-PP; Metanx ) in patients with diabetic peripheral neuropathy (DPN).
Which of the following best describes the results?
The rate of adverse events was significantly higher in the Metanx group compared to placebo
There was no significant improvement in inflammatory biomarkers in the Metanx group compared to placebo
There was no significant difference in the quality of life survey between the Metanx and placebo groups
The neuropathy total symptom score-6 (NTSS-6) improved significantly in the Metanx group compared to
placebo.
There was a significant improvement in vibratory perception threshold (VPT) in the Metanx group compared to
placebo.
Answer: The correct answer is the neuropathy total symptom score-6 (NTSS-6) improved significantly in the Metanx
group compared to placebo. DPN affects at least 1 in 5 persons with diabetes causing debilitating neuropathic pain or
partial to complete loss of sensation in the extremities. The cause is multifactorial and likely involves oxidative stress.
Unfortunately, the treatment options are limited. The effects of the B vitamins, L-methylfolate calcium 3 mg, pyridoxal-5phosphate 35 mg, and methylcobalamin 2 mg (LMF-MC-PP; Metanx ) on signs, symptoms, and biomarkers associated
with DPN were assessed in a 24-week, multicenter, randomized, double-blind, placebo-controlled trial involving 214
patients with DPN (baseline vibration perception threshold [VPT]: 25-45 volts) but without peripheral vascular disease.
Patients who had had previous surgery with residual neurologic deficit, or A1C >9% were excluded. Concomitant opiate
use was not permitted, but other DPN medications could be used as long as doses were kept constant during the study.
The mean patient age was 62.6 &elusmn; 8.9 years, and there were no differences between the LMF-MC-PP and
placebo groups at baseline in age, race, ethnicity, duration of diabetes or neuropathy, or baseline outcome measures. At
24 weeks, change in VPT, the primary outcome, did not differ between the LMF-MC-PP and placebo groups (Table 1). In
terms of secondary outcomes, a significant difference in mean neuropathy total symptom score-6 (NTSS-6) was
observed with LMF-MC-PP vs. placebo, and the mental component scale (MCS) of the short form 36 (SF-36, a validated
quality of life survey) improved significantly. Homocysteine, an inflammatory factor associated with diabetic complications
including DPN was also significantly reduced in the Metanx group compared to placebo [(-2.7 &elusmn;3.0) vs (0.5
&elusmn;2.4) P=0.0001] Adverse events were infrequent, occurring in <2% of all subjects; none were considered
serious. These findings suggest that LMF-MC-PP may be a safe and effective symptomatic therapy for patients with
DPN, leading to improvement in components of quality of life and inflammatory biomarkers, despite a lack of change in
vibration sensation.
Fonseca, V.A. et al., Abstract 1053-P. American Diabetes Association 71st Scientific Sessions June 24 - 28, 2011 San
Diego, California
Question : Which of the following best describes the results of the Bypass Angioplasty Revascularization Investigation 2
Diabetes (BARI 2D) trial?
The rates of death and major cardiovascular events were significantly greater in patients undergoing prompt
revascularization compared to those undergoing medical therapy.
None of the answers are correct
The survival rates in the insulin-sensitization group were significantly higher compared to the insulin-provision
group.
The survival rates in the insulin-provision group were significantly higher than in the insulin-sensitization group.
The rates of major cardiovascular events were significantly higher in the medical-therapy group compared to the
revascularization group
Answer: The correct answer choice is none of the answers are correct. The Bypass Angioplasty Revascularization
Investigation (BARI2D) trial was conducted to determine optimal treatments to prevent mortality and major
cardiovascular events in patients with T2DM and stable ischemic heart disease. Both prompt revascularization compared
with intensive medical therapy alone or with delayed revascularization, and insulin-sensitization compared with insulinprovisional therapeutic strategies were evaluated in 2368 patients over 5 years with the use of a 22 randomized
factorial trial design. At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%)
and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulinprovision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly
among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7%
in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no
significant difference in primary end points between the revascularization group and the medical-therapy group. In the
CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%)
than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Of note, in
secondary analysis, insulin-sensitization therapies appeared to enhance the benefit of revascularization in the higher-risk
subgroup of patients selected for CABG. Additionally, insulin sensitization was associated with lower body mass index,
higher high-density lipoprotein cholesterol level, and lower rates of severe hypoglycemia.
Goldfine AB, Fonseca V. Management of diabetes mellitus in patients with cardiovascular disease in the bypass
angioplasty revascularization investigation 2 diabetes (BARI 2D) trial. Circulation. 2010;121(22):2447-2449.
Question: A case series was conducted to evaluate the role of continuous subcutaneous insulin infusion (CSII) therapy
in patients with symptomatic diabetic gastroparesis and unstable glycemic control. Compared with multipledose insulin
(MDI) regimens, the use of CSII resulted in:
A higher median median capillary blood glucose (CBG)
A reduction in length of hospital stay related to gastroparesis and glycemic instability
No change in glycemic variability
No statistically significant reduction in HbA1c
All of the answer choices are correct
Answer: A reduction in length of hospital stay related to gastroparesis and glycemic instability. Following initiation of
CSII, the median length of inpatient bed days associated with hospital admissions related to gastroparesis and glycemic
instability was reduced from 8.5 (range 0144) days patient 1year 1 prior to CSII to 0 (range 015) days patient 1year
1. (p<0.05). The median HbA1c reduction with CSII was 1.8% (22 mmol/mol; p<0.05). The median capillary blood
glucose (CBG) with CSII was significantly lower than with MDI: 7.7 mmol/l (range 3.815.4 mmol/l) vs 9.8 mmol/l (range
2.327 mmol/l), respectively, (p <0.001) Glycemic variability with CSII was significantly reduced compared with MDI:
(p<0.001). The initial costs of CSII therapy are relatively high, but overall reduction in length of hospital stay may prove it
to be cost effective.
Sharma D et al. Diabetologia. Published online August 14, 2011
Question 1: A recent analysis of the HAPO study showed that measuring Hemoglobin A1c is a useful alternative to an
oral glucose tolerance test OGTT for assessing the risk of adverse outcomes in pregnant woman. (True or False)?
False
True
Answer: The correct answer is false. The objective of this study was to compare associations of maternal glucose and
A1C with adverse outcomes in the multinational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and
determine, based on those comparisons, if A1C measurement can provide an alternative to an oral glucose tolerance
test (OGTT) in pregnant women. Eligible pregnant women underwent a 75-g OGTT at 2432weeks gestation. A sample
for A1C was also collected. Neonatal anthropometrics and cord serum C-peptide were measured. Associations with
outcomes were assessed using multiple logistic regression with adjustment for potential confounders. Among the 23,316
HAPO Study participants with glucose levels blinded to caregivers, 21,064 had a nonvariant A1C result. The mean SD
A1C was 4.7960 40%. Associations were significantly stronger with glucose measures than with A1C for birth weight,
sum of skin folds, and percent body fat > 90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01).
For example, in fully adjusted models, odds ratios (ORs) for birth weight > 90th percentile. For each measure higher by 1
SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1- and 2-h plasma glucose and 1.15 for A1C. ORs for cord Cpeptide > 90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for
glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. On the basis of associations with
adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant
women. The correct answer is false. The objective of this study was to compare associations of maternal glucose and
sum of skin folds, and percent body fat
Lowe LP, et al. Hyperglycemia and adverse pregnancy outcome (HAPO) study: Associations of maternal A1C and
glucose with pregnancy outcomes. Diabetes Care.
Question: Which of the following best describes the results of a recent study evaluating the long-term safety, tolerability
and efficacy of linagliptin?
Incidence of adverse events leading to discontinuation was high
Significant weight loss was achieved with linagliptin.
Largest observed reduction of HbA1c with linagliptin was noted for those receiving the initial combination of linagliptin
plus metformin
HbA1c change from baseline to week 102 was 0.5% with linagliptin monotherapy.
Answer: The correct answer is: HbA1c change from baseline to week 102 was 0.5% with linagliptin monotherapy. The
aim of this 78-week open-label extension study was to evaluate the long-term safety, tolerability and efficacy of the
dipeptidyl peptidase-4 inhibitor linagliptin given either alone or in combination with other oral glucose-lowering agents in
persons with type 2 diabetes. Subjects participated in one of four preceding 24-week, randomized, double-blind, placebocontrolled parent trials and who received linagliptin, linagliptin + metformin, linagliptin + metformin + a sulfonylurea or
linagliptin + pioglitazone (all with linagliptin administered orally once daily). Individuals receiving one of these treatments
during a previous trial continued the same treatment (n = 1532) for up to a total of 102 weeks, whereas those previously
receiving placebo were switched to linagliptin (n = 589). All 2121 participants received at least one dose of the trial
medication and were included in the primary safety analysis. In subjects previously receiving active treatment, the A1c
reduction achieved during the 24-week parent trials was sustained through the 78-week extension period (change from
baseline to week 102:) 0.8%). In participants randomized to linagliptin in the four previous trials (group A), the glucoselowering effect of linagliptin achieved during the initial 24 weeks of treatment (mean change from baseline to week 24: 0.8% was maintained over the 78 weeks of the extension phase (change from baseline to week 102: - 0.8%). Coefficient
of durability per 78 weeks, 0.14% (p < 0.0001, non-inferiority 0.3%). The largest observed reduction of HbA1c with
linagliptin was noted for those receiving the initial combination of linagliptin plus pioglitazone (change from baseline to
week 102: -1.5%), followed by those receiving metformin background. Most AEs were mild or moderate and the
incidence of severe AEs was low (3.8%). The incidence of AEs leading to discontinuation also was low (3.4%). Drugrelated adverse events were experienced by 14.3% of participants. Hypoglycemia occurred in 13.9% of participants and
was similar between those previously receiving treatment (13.6%) and those switching from placebo to linagliptin
(14.6%). Hypoglycemia occurred most frequently with the use of metformin + a sulfonylurea background therapy (11%).
Overall, no clinically relevant changes in body weight were observed. In conclusion Long-term treatment with linagliptin
was well tolerated with no change in the safety profile observed during the extension study. Sustained long-term
glycemic control was maintained for up to 102 weeks with either linagliptin monotherapy or linagliptin in combination with
other oral glucose-lowering agents.
Gomis R., Owens D. R., Taskinen, M.R., et al. Int J Clin Pract, August 2012, 66, 8, 731740
Question: The results from a 26 week randomized trial, comparing the efficacy and safety between liraglutide once a
day versus exenatide twice a day for type 2 diabetes showed:
Overall treatment satisfaction was significantly better in the exenatide group than in the liraglutide group
Reduction of HbA1c values with liraglutide was statistically superior to that seen with exenatide
Patients receiving exenatide experienced less persistent nausea.
Patients receiving liraglutide experienced more episodes of hypoglycemia
Weight loss was greater in patients receiving liraglutide.
Answer: The correct answer is reduction of HbA1c values with liraglutide was statistically superior to that seen with
exenatide. The mean change in HbA1c from baseline to week 26 (-112% vs -079% p<00001); Minor hypoglycemia was
less frequent with liraglutide than with exenatide. Liraglutide and exenatide were associated with similar weight losses.
Overall treatment satisfaction was significantly better in the liraglutide group (n=161) than in the exenatide group (n=143)
(p=00004). The incidence of nausea was similar initially, but it was less persistent with liraglutide (estimated treatment
rate ratio 0448 for liraglutide vs exenatide; proportion of participants with nausea at week 26, 5 of 202 [3%] vs 16 of 186
[9%]/sub/sub
The Lancet. 2009;374(9683):39-47
Question: BC is a 47-year-old male non-smoker with T2DM, hypertension, and obesity. He is taking metformin 1000 mg
twice daily, lisinopril 40 mg each morning, and amlodipine 10 mg each morning. His blood pressure is 132/70 mm Hg.
Which of the following would you do next?
Add a beta-blocker
Change his lisinopril or amlodipine dose to the evening
Add a thiazide diuretic
Answer: The correct answer is: change his lisinopril or amlodipine dose to the evening. The benefits of lowering BP in
diabetes to <140 mm Hg systolic and <80 mm Hg diastolic have been established in randomized control trials. However,
the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial demonstrated that, in patients with T2DM,
intensive BP lowering to <120 mm Hg systolic yielded no significant differences in fatal and nonfatal cardiovascular
events compared with BP maintained between 130 and 140 mm Hg. Moreover, aggressive BP lowering may be
associated with serious adverse events. The 2012 ADA guidelines state that a systolic BP goal of <130 mm Hg is
appropriate for most patients; however, higher or lower BP targets may be individualized.If a patient is taking multiple BP
medications, one or more should be taken at bedtime. Administering an antihypertensive at night results in better
ambulatory BP control and reduces cardiovascular mortality. BC is on maximal doses of 2 antihypertensive agents, and
his BP is 132/70 mm Hg. His physician must individualize care and decide If adding a third agent is worth the risk of
another medication when clear benefit has not been demonstrated. It is reasonable to continue his current regimen with
the exception of changing either his lisinopril or amlodipine dose to the evening and reassessing his BP control at his
next visit.
Cusbman WC, Evans GW, Byington RP, et al. ACCORD Study Group. Effects of intensive blood-pressure control in type
2 diabetes mellitus. NEngUMed. 2010;362:15?5-1585.
Question: 1 A recent study has shown that the administration of glutamic acid
decarboxylase formulated with aluminium hydroxide (GAD-alum) preserves insulin production
in patients with recent-onset type 1 diabetes (True or False)
False
True
Answer: The correct answer is false. Glutamic acid decarboxylase (GAD) is a major target of the autoimmune response
that occurs in type 1 diabetes mellitus. In animal models of autoimmunity, treatment with a target antigen can modulate
aggressive autoimmunity. This study assessed whether immunisation with GAD formulated with aluminum hydroxide
(GAD-alum) would preserve insulin production in recent-onset type 1 diabetes. A total of 145 patients, aged 345 years,
who had been diagnosed with type 1 diabetes for less than 100 days were enrolled from 15 sites in the USA and
Canada, and randomly assigned to receive one of three treatments: three injections of 20 ?g GAD-alum, two injections of
20 ?g GAD-alum and one of alum, or 3 injections of alum. Injections were given subcutaneously at baseline, 4 weeks
later, and 8 weeks after the second injection. At 1 year, the 2-h AUC of C-peptide, adjusted for age, sex, and baseline Cpeptide value, was 0412 nmol/L (95% CI 03490478) in the GAD-alum group, 0382 nmol/L (03220446) in the
GAD-alum plus alum group, and 0413 nmol/L (03510477) in the alum group. The ratio of the population mean of the
adjusted geometric mean 2-h AUC of C-peptide was 0998 (95% CI 0779122; p=098) for GAD-alum versus alum,
and 0926 (0720113; p=050) for GAD-alum plus alum versus alum. HbA1c, insulin use, and the occurrence and
severity of adverse events did not differ between groups. Antigen-based immunotherapy therapy does not alter the
course of loss of insulin secretion during 1 year in patients with recently diagnosed type 1 diabetes. Although antigenbased therapy is a highly desirable treatment and is effective in animal models, translation to human autoimmune
disease remains a challenge.
Wherrett DK, Bundy B, Becker DJ, et al. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in
patients with recent-onset type 1 diabetes: A randomised double-blind trial.
Question: 2 A randomized clinical trial was conducted to assess the efficacy of a selfmonitoring-based disease management strategy in patients with type 2 diabetes treated with
oral agent monotherapy. After 6 months, mean HbA1c reduction in the intervention group was:
0.7%
0.5%
1.2%
1.6%
1.9%
Answer: The correct answer is 1.2%. This was an open-label, randomized, pilot study, primarily led by diabetes nurses.
Patients were randomly allocated to either a self-monitoring-based disease management strategy or usual care and
followed up for 6 months. Self-monitoring of blood glucose results were discussed during monthly telephone contact.
Patients were instructed how to modify lifestyle based on blood glucose readings. The primary endpoint was mean
change in HbA1c levels. After 6 months, mean HbA1c reduction was 1.2 &elusmn; 0.1% (13 &elusmn; 1 mmol/mol) in the
intervention group and 0.7 &elusmn; 0.2 (8 &elusmn; 2 mmol/mol) in the control group, with an absolute mean
difference between groups of 0.5% (95% CI ?0.9 to ?0.0%; P = 0.04) (?5 mmol/mol, 95% CI ?10 to 0).
Franciosi M, et al. Diabetic Medicine: (2011) 28: 789796
Question: 3 BC is a 47-year-old male non-smoker with T2DM, hypertension, and obesity.

He is current on his influenza and pneumococcal vaccinations. Should BC receive any other
vaccinations?
Yes, he should receive the hepatitis B virus vaccine

No
Yes, he should receive the chickenpox/varicella vaccine
Yes, he should receive the shingles/herpes zoster vaccine
Answer: The correct answer is: Yes, he should receive the hepatitis B virus vaccine. The ADA states that unless there
are contraindications, all diabetics should receive the pneumococcal and annual influenza vaccines. The Advisory
Committee on Immunization Practices of the CDC, as well as the most recent ADA guidelines, also recommend hepatitis
B virus (HBV) vaccinefor unvaccinated adults with diabetes from ages 19 to 59. Unvaccinated adults with diabetes ?60
should be vaccinated at the discretion of the provider after assessing risk and likelihood of an adequate immune
response. Diabetic patients may be at risk of contracting HBV in long-term care facilities where assisted blood sugar
monitoring commonly occurs. Studies have shown that diabetics may progress to chronic hepatitis B infection more often
than patients without diabetes, and are at higher risk for nonalcoholic liver disease and hepatocellular carcinoma. The
shingles vaccine is recommended for individuals over the age of 50, whether or not they have diabetes. The varicella
vaccine is recommend in adults who have never had chicken pox, regardless if they have diabetes or not.
American Diabetes Association. Standards of medical care in diabetes-2013.
Question: 4 The most commonly reported adverse event with Janumet in the treatment of
type 2 diabetes is:
Upper respiratory infection
Abdominal Pain
Nausea
Headache
Diarrhea
Answer: The correct answer is diarrhea. In clinical studies, the most common adverse reactions reported with Janumet
in 5% of patients and more commonly than in patients treated with placebo were as follows: diarrhea > upper
respiratory tract infection > headache.
Inc. DIAB-1002314-0000-05/11
Question: 5 A recent study was conducted to assess the long-term effects of posttransplant glycemia on long-term survival in renal transplant recipients without pre-existing
diabetes. Which of the following variables was found to be superior for predicting all-cause
and cardiovascular (CV) mortality after renal transplantation?
Hypertension
Fasting Plasma Glucose (FPG)
2-hr plasma glucose after an oral glucose tolerance test (OGTT)
LDL-cholesterol
HbA1c
Answer: The correct answer is 2-hr plasma glucose after an oral glucose tolerance test (OGTT). The main finding of this
large single-centre study of renal transplant recipients without pre-existing diabetes was that as a predictor of long-term
mortality, post-challenge 2hPG measured early after renal transplantation was superior to, and independent of, FPG,
even after adjustments for confounding risk factors. Each 18 mg/dl increment in 2hPG was associated with a 5% (95% CI
1%, 9%) increased risk of death from any cause and 6% (95% CI 1%, 12%) increased risk of death from CV disease.
Furthermore, the findings in this study first to indicate that renal transplant recipients with impaired glucose tolerance
have lower long-term chance of survival than those with normal glucose tolerance.
Valderhaug T. G., et al.
Question: A post hoc analysis of data from the DURABLE clinical trial was performed to compare outcomes in patients
with type 2 diabetes initiating Humalog 75/25 or insulin glargine therapy, stratified by baseline oral antihyperglycemic
agent (OHA). Which of the following OHA treatment groups had the greatest improvement in HbA1c?
Metformin/thiazolidinedione
Metformin/sulfonylurea/thiazolidinedione
Sulfonylurea/thiazolidinedione
Metformin/sulfonylurea
Answer: The correct answer is metformin/thiazolidinedione. A significantly greater proportion of patients in the
metformin/thiazolidinedione group achieved an A1C value less than 7.0% in comparison with the corresponding
proportion in the metformin/sulfonylurea group. In both insulin treatment groups, metformin/thiazolidinedione-treated
patients had significantly greater improvement in A1C levels (-2.19% to -2.36%) and lower end point A1C values, in
comparison with metformin/sulfonylurea-treated patients (all P<.05). Patients treated with sulfonylurea/thiazolidinedione
or metformin/sulfonylurea/thiazolidinedione did not differ significantly from metformin/sulfonylurea-treated patients in
A1C change (-1.56% to -1.84%). Although the analysis did not specificallycompare outcomes between insulin treatment
groups, both insulin treatment groups had relatively similar A1C reductions with metformin/thiazolidinedione therapy.
Herman WH, et al. Concomitant oral antihyperglycemic agent use and associated treatment outcomes after
initiation of insulin therapy.
Question 1: Which factor is associated with an increased risk of diabetic ketoacidosis (DKA) at the time of initial
diagnosis of type 1 diabetes mellitus (T1DM)?
Younger age
Close family history of diabetes
Higher BMI
Answer: Younger age. Children and adolescents presenting with a new diagnosis of T1DM were more likely to have
DKA if they were younger, especially below the age of 2 years. Thinner children also have a higher likelihood of DKA at
initial presentation. Having first or second degree relatives with T1DM reduced the likelihood of DKA at time of initial
diagnosis, suggesting that awareness of diabetes and its symptoms may lead to earlier diagnosis.
de Vries L, et al. Diabet Med. 2013;30(11):1360-1366.
Question 2: Which endpoint would significantly decrease in pediatric patients with type 1 diabetes who were using oncedaily insulin detemir compared to twice-daily insulin detemir?
Frequency of severe hypoglycemic episodes
HbA1c
Nocturnal hypoglycemic events/week
All of the answers are correct
Answer: Nocturnal hypoglycemic events/weeks. Though these did decrease with both treatments, the decrease was
significant only with the once-daily regimen. No clinical advantage was found for twice-daily detemir vs once-daily
detemir, though younger children and those in active puberty may need twice-daily therapy.
Nimri R, et al. Pediatr Diabetes. 2013;14(3):196-202.
Question 3: For children with type 1 diabetes mellitus (T1DM) who also have idiopathic growth hormone deficiency
(IGHD), what is the impact of growth hormone treatment?
Higher hemoglobin A1c levels
Increased insulin requirement
Increased insulin requirement and higher hemoglobin A1c levels
No difference in insulin requirement or hemoglobin A1c levels
Answer: Increased insulin requirement. A group of 37 children with T1DM were found to also have IGHD. When treated
with growth hormone, the daily insulin requirement was increased (1.0 units/kg/day in the T1DM and IGHD group
compared to 0.85 units/kg/day in controls with just T1DM). However, there was no significant difference in glycemic
control, assessed by hemoglobin A1c levels.
Bonfig W, et al. J Pediatr. 2013;163(4):1095-1098.e4.
Question 1: In the NAVIGATOR trial, participants who received nateglinide had a reduction in:
The incidence of diabetes, but not in cardiovascular outcomes.
The incidence of cardiovascular outcomes, but not in diabetes
The incidence of diabetes and in cardiovascular outcomes
Neither the incidence of diabetes nor in cardiovascular outcomes
Answer: The correct answer is neither the incidence of diabetes nor in cardiovascular outcomes. The results of the
NAVIGATOR trial (Long-term Study of Nateglinide+Valsartan to Prevent or Delay Type II Diabetes Mellitus and
Cardiovascular Complications) show that among persons with impaired glucose tolerance and cardiovascular disease or
cardiovascular risk factors, assignment to nateglinide, at a dose of 60 mg three times daily, as compared with placebo, in
addition to a lifestyle modification program, did not reduce the incidence of diabetes or cardiovascular outcomes.
N Engl J Med. 2010;362(16):1463-1476
Question 2: A recent analysis of the HAPO study showed that measuring Hemoglobin A1c is a useful alternative to an
oral glucose tolerance test OGTT for assessing the risk of adverse outcomes in pregnant woman. (True or False)?
False
True
Answer: The correct answer is false. The objective of this study was to compare associations of maternal glucose and
sum of skin folds, and percent body fat > 90th percentile and for fasting and 1-h glucose for cord C-peptide (all P < 0.01).
For example, in fully adjusted models, odds ratios (ORs) for birth weight > 90th percentile. For each measure higher by 1
SD were 1.39, 1.45, and 1.38, respectively, for fasting, 1- and 2-h plasma glucose and 1.15 for A1C. ORs for cord Cpeptide > 90th percentile were 1.56, 1.45, and 1.35 for glucose, respectively, and 1.32 for A1C. ORs were similar for
glucose and A1C for primary cesarean section, preeclampsia, and preterm delivery. On the basis of associations with
adverse outcomes, these findings suggest that A1C measurement is not a useful alternative to an OGTT in pregnant
women. The correct answer is false. The objective of this study was to compare associations of maternal glucose and
sum of skin folds, and percent body fat
Lowe LP, et al. Hyperglycemia and adverse pregnancy outcome (HAPO) study: Associations of maternal A1C
and glucose with pregnancy outcomes. Diabetes Care.
Question 3: In a randomized, active-control trial, a comparative evaluation of amitriptyline and duloxetine in painful
diabetic neuropathy (PDN) demonstrated:
Duloxetine was superior in efficacy to Amitriptyline
More patients preferred Amitriptyline over Duloxetine
The number of moderate to severe adverse events was higher with Duloxetine
Amitriptyline was superior in efficacy to Duloxetine
Both agents were similar in efficacy
Answer: Both agents were similar in efficacy. More patients preferred duloxetine over preferred amitriptyline, but it was
not statistically significant (P = 0.18). Moderate to severe averse events were more common with amitriptyline compared
with duloxetine (51 vs. 24% of patients; P < 0.01).
Diabetes Care. 2011;34(4):818-822.
Question 4: A case series was conducted to evaluate the role of continuous subcutaneous insulin infusion (CSII) therapy
Question 5: A comparative trial was performed between once-daily liraglutide and once-weekly exenatide in patients
with type 2 diabetes. Which of the following statements is false regarding the trial results?
The liraglutide group lost more weight, irrespective of BMI
There were more serious adverse events in the exenatide group
More nausea, diarrhea, and vomiting occurred with liraglutide
Decrease in fasting glucose was greater in the liraglutide group
Injection-site nodules were more common with liraglutide
Answer: The correct answer is: Injection-site nodules were more common with liraglutide is false.The trial was a 26
week, open-label, randomized, parallel-group study at 105 sites in 19 countries between Jan 2010, and Jan 2011. Type II
diabetic patients on oralantihyperglycaemic drugs were randomly assigned (1:1) to receive injections of once-daily
liraglutide (1.8 mg) or once-weekly exenatide (2 mg). The primary endpoint was change in HbA from baseline to week
26. Both drugs were associated with a decrease in HbA1, but was greater in patients taking liraglutide (-1.28% vs.
-1.48%). However, the treatment difference (0.21%; 95% CI, 0.083-0.33) did not meet the predefined noninferiority
criteria. At 26 weeks, fasting serum glucose significantly decreased in both groups (p<0.0001), but the decrease was
greater in patients in the liraglutide group (-2.12 vs 1.76) with a treatment difference (0.36; 95% CI, 0.05-0.66). Both
treatments were associated with progressive decreases in bodyweight, but patients taking liraglutide lost more weight (3.57 vs -2.68) irrespective of BMI, with a treatment difference (0.9; 95% CI, 0.39-1.40). The most common adverse
events were mainly gastrointestinal in both groups, with a greater frequency of nausea, diarrhea, and vomiting in patients
in the liraglutide group. Injection-site nodules were more common with exenatide than with liraglutide. There were more
serious adverse events in the exenatide group (3% vs 2%) (including acute cholecystitis, myocardial infarction,
pancreatitis and prostate cancer) but with no identifiable pattern of events.
Buse JB. Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (DURATION-6): a
randomised, open-label study. Published online November7, 2012
Question: The most significant reason for improved adherence/compliance with use of metformin XR is:
Decrease in incidence of diarrhea
Less frequent dosing
Decrease in incidence of nausea
Answer: The correct answer is: All of the answer choices are correct. Patients with T2DM have comorbidities and are on
multiple medications besides medications for treatment of diabetes. In a study done to address the compliance of antidiabetic medications, A1C level was positively related with frequency of anti-diabetic medications dosing. Only 46%
patients were reported to be optimally compliant with oral medications and there was A1C difference of 1.4% between
compliant and noncompliant group. GI side effects related to immediate-release formulation of metformin have shown to
have negative impact on health-related quality of life which leads to non-adherence and poor glycemic control. Incidence
of GI side effect with Metformin 1500mg IR; [Diarrhea 10.4%, Nausea 8.2%] vs. Metformin XR (AM/PM) [Diarrhea 8.3%,
Nausea 3.9%]. Discontinuation of Metformin IR treatment in first week of treatment; [due to diarrhea: 1.2%, due to
nausea 1.7%]. Discontinuation of Metformin XR treatment in first week of treatment was 0% for both diarrhea and
nausea. Incidence of GI side effects on Metformin IR: [Diarrhea 58%, Nausea 18%]. At 6 months after switchover to XR.
[Diarrhea 14%, Nausea 6%]. Metformin IR is recommended 2 to 3 times a day. Once-daily dosing with Metformin XR
simplifies treatment regimen and improves compliance, which results in improved glycemic control that would decrease
the risk of long-term complications of diabetes.
Ali S & Fonseca V. Expert Opin. Pharmacother. (2012) 13(12)
Question: The EUREXA trial compared add-on exenatide with glimepiride for durability of glycemic control in patients
with type 2 diabetes inadequately controlled by metformin alone. Which of the following best describes the results?
Reduction in bodyweight in the exenatide group was not statistically significant
Significantly more patients attained an A1C level of < 7% in the glimepiride group than in the exenatide group
There was no significant difference in A1C reduction between glimepiride and exenatide
Fasting plasma glucose concentration significantly lower in exenatide group
Symptomatic hypoglycemia were similar between both groups
Answer: The correct answer is: Fasting plasma glucose concentration significantly lower in exenatide group. Exenatide
twice daily versus glimepiride for prevention of glycemic deterioration in patients with type 2 diabetes with metformin
failure (EUREXA) trial is the longest randomized controlled study of a GLP-1 receptor agonist reported to datewith
comparative treatment for up to 4.5 years. 515 patients were randomly assigned to the exenatide group and 514 to the
glimepiride group, of whom 490 versus 487 were the intention-to-treat population. 203 (41%) patients had treatment
failure in the exenatide group compared with 262 (54%) in the glimepiride group (risk difference 124 [95% CI 62186],
hazard ratio 0748 [06230899]; p=0002). 218 (44%) of 490 patients in the exenatide group, and 150 (31%) of 487 in
the glimepiride group achieved an HbA1c concentration of less than 7% (p <00001), and 140 (29%) versus 87 (18%)
achieved concentrations of 65% and less (p=00001). Fasting plasma glucose concentration was significantly lower in
the exenatide group after years 1 (p=0.048), 2 (p=0.004), and 3 (p <00001) of treatment. A significantly greater decrease
in bodyweight in patients given exenatide than in those given glimepiride (p <00001) was noted. Significantly fewer
patients in the exenatide group than in the glimepiride group reported documented symptomatic (p <00001), nocturnal
(p=0007), and non-nocturnal (p <00001) hypoglycemia. Discontinuation because of adverse events (mainly
gastrointestinal) was significantly higher (p=00005) in the exenatide group than in the glimepiride group in the first 6
months of treatment, but not thereafter.

Gallwitz B, Guzman J, Dotta F, et al. Lancet 2012; 379: 227078
Question: Albuminuria and estimated glomerular filtration rate are independent risk factors for cardiovascular events and
death in type 2 diabetes mellitus.
True
False
Answer: The correct answer is true. Albuminuria is an independent risk marker for all-cause mortality and adverse
cardiovascular events, including myocardial infarction, stroke, hospitalization for congestive heart failure, and peripheral
vascular disease. Cardiovascular risk also increases proportionally and independently as the GFR declines in patients
with type 2 diabetes mellitus.
Mayo Clin Proc. May 2011 ;86(5):444-456
Question: A retrospective cohort study was conducted to investigate the risk of all-cause mortality associated with
individual glucose-lowering treatment regimens in heart failure patients with diabetes? Patients using ___ had a
significantly lower risk of death from diabetes or cardiovascular causes.
Insulin monotheraphy
Sulfonylurea monotherapy
Metformin + insulin
Metformin + sulfonylurea
Metformin monotherapy
Answer: The correct answer is metformin monotherapy. This study was conducted in Denmark in patients who were
hospitalized with heart failure for the first time during 19972006 and treated with metformin, sulfonylureas and/or insulin.
Compared with patients using sulfonylurea monotherapy, patients using metformin as monotherapy had a significantly
lower risk of death from diabetes or cardiovascular causes while the risk was significantly higher in patients using insulin
as monotherapy.
Andersson C, et al. Diabetologia (2010) 53:25462553
Question: A retrospective cohort study was conducted to investigate health care utilization, cost, and clinical outcomes
among non-insulin treated patients with type 2 diabetes mellitus (T2DM) initiating insulin glargine using either disposable
pen or vial and syringe. The patients initiating insulin glargine with a disposable pen experienced:
Lower discontinuation rates
Fewer hypoglycemic events
Fewer diabetes-related inpatient hospitalizations
A significantly larger decrease from baseline in A1C
Answer: The correct answer is all answer choices are correct. Patients initiating insulin glargine treatment with the
disposable pen were significantly less likely to discontinue or switch treatment during the 12-month follow-up period than
were patients who initiated treatment with the vial and syringe (42.4% vs. 50.8%, P<0.001) the proportion of patients who
experienced a hypoglycemic event was 6.35% in the disposable pen group versus 8.47% in the vial group (P=0.012).
Fewer diabetes-related inpatient hospitalizations were noted in the disposable pen group (P=0.04). Despite having a
higher mean baseline A1C, patients who initiated insulin glargine with the disposable pen experienced a significantly
larger decrease from baseline in A1C than those initiating insulin glargine with the vial (?1.32.1 vs ?0.82.1, P=0.01).
Davis S et al. Endocr Pract. 2011:1-27
Question : BC is a 47-year-old male non-smoker with T2DM, hypertension, and obesity. He is taking metformin 1000 mg
twice daily, lisinopril 40 mg each morning, and amlodipine 10 mg in the evening. His blood pressure is 138/76 mm Hg.
Make no anti-HTN medication changes
Add a vasodilator
Add a beta-blocker
Answer: The correct answer is: Make no anti-HTN medication changes. The new ADA guidelines raise the target for
systolic blood pressure from <130 mm Hg to <140 mm Hg based on evidence that there is not a great deal of additional
value in aiming for the lower target, but there is an increase in risk in pushing systolic pressure lower than 140 mm Hg.
The primary data for that recommendation came from a meta-analysis that demonstrated that although the use of
intensive versus standard blood-pressure targets in patients with type 2 diabetes was associated with a small reduction
in the risk for stroke, there was no evidence for decreased mortality or MI, but an increased risk for hypotension and
other adverse events. The previous target of <130 mm Hg had not been derived from randomized, controlled trials, but
from observational studies that seemed to suggest lower is better for blood pressure in those with diabetes. However, the
new ADA recommendations state lower targets (such as <130 mm Hg) may be appropriate in certain patients (such as
younger individuals) if target can be achieved without treatment burden.
American Diabetes Association.Standards of medical care in diabetes-2013. Diabetes Care. January 2013.
Question : The ORIGIN trial evaluated the effect of insulin glargine in patients with diabetes mellitus and prediabetes.
Based on the results of the trial, which of the following statements is true regarding insulin glargine?
It decreased the incidence of colon cancer
It slowed the progression of atherosclerosis
It reducedthe risk of developing DM2 by 28% in prediabetes patients
It slowed the progression of microalbuminuria
Answer: The correct answer is: It reducedthe risk of developing DM2 by 28% in prediabetes patients is true. Glargine
reduced the risk of developing type 2 diabetes by 28% among patients with prediabetes. 12,537 patients (mean age of
63.5) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or DM2were randomly
assigned to receive insulin glargine or standard care. Patients were followed for an average of 6 years. Glargine did not
slow the progression of atherosclerosis and had a neutral effect on cardiovascular outcomes with rates of incident
cardiovascular outcomes being similar in the glargine and standard-care groups: 2.94 and 2.85 per 100 person-years,
respectively, (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63).Glargine slowed the progression of
dysglycemia; patients who were assigned to glargine were 28% less likely to have diabetes develop from the time of
randomization until the first oral glucose-tolerance test than were participants assigned to standard care. Insulin glargine
also had a neutral effect on cancers (colon, prostate, melanoma, breast, lung) with hazard ratio for colon cancer of
1.09;95% CI, 0.79 to 1.51; P=0.61.There was also no significant difference microvascular events, (including
microalbuminuria[hazard ratio, 0.97; 95% CI, 0.90 to 1.05; P=0.43]).
The Origin Trial Investigators. Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia.N Engl J
Med 2012; 367:319-398 July 26, 2012.
Question : A randomized, double-blind, placebo-controlled study was conducted to compare the efficacy and safety of
initial combination therapy with linagliptin and pioglitazone in patients with inadequately controlled type 2 diabetes. What
was the mean change in HbA1c for patients with a baseline HbA1c ? 9.0%?
- 0.56%
- 0.9%
- 1.23%
- 1.49%
- 0.72%
Answer: The correct answer is - 1.49%. The reduction in HbA1c was greatest for patients with higher baseline HbA1c.
Linagliptin plus pioglitazone patients with a baseline HbA1c 9.0% had a larger reduction in HbA1c (?1.49%) than seen
in the overall patient group receiving linagliptin plus pioglitazone (?0.90%). The placebo corrected adjusted mean change
from baseline at 24 weeks for this subgroup was?0.65% (95% CI?1.02,?0.28; p = 0.0008). For the subgroups of patients
with baselineHbA1c 7.5 to<8.0 and 8.0 to<9.0%, the placebo-corrected adjusted mean changes from baseline at week
24 were ?0.48% (95% CI ?0.95, ?0.01; p = 0.048) and ?0.49% (95% CI ?0.82, ?0.16; p = 0.0031), respectively.
Gomis R et al.Diabetes, Obesity and Metabolism 13: 653661, 2011
Question : An open-label trial was conducted to assess the efficacy and safety of switching from sitagliptin to liraglutide
in metformin-treated adults with type 2 diabetes. Conversion to liraglutide was associated with which of the following?
Significant reduction in body weight

Significant reduction in fasting plasma glucose
Improvement in treatment satisfaction
Increased proportion of patients reaching A1C <7%
Answer: The correct answer is: All of the answer choices are correct. In an open-label trial, participants randomized to
receive either liraglutide (1.2 or 1.8 mg/day) or sitagliptin (100 mg/day), each added to metformin, continued treatment for
52 weeks. In a 26-week extension, sitagliptin-treated participants were randomly allocated to receive instead liraglutide at
either 1.2 or 1.8 mg/day, while participants originally randomized to receive liraglutide continued unchanged. Although 52
weeks of sitagliptin changed glycosylated hemoglobin (HbA 1c) by -0.9% from baseline, additional decreases occurred
after switching to liraglutide (1.2 mg/day, -0.2%, P = 0.006; 1.8 mg/day, -0.5%, P = 0.0001). Conversion to liraglutide was
associated with reductions in fasting plasma glucose (FPG) (1.2 mg/day, -0.8 mmol/L, P = 0.0004; 1.8 mg/day, -1.4
mmol/L, P < 0.0001) and body weight (1.2 mg/day, -1.6 kg; 1.8 mg/day, -2.5 kg; both P < 0.0001) and with an increased
proportion of patients reaching A1C <7% (from 30% to 50%). Overall treatment satisfaction, assessed by the
Diabetes Treatment Satisfaction Questionnaire, improved after switching to liraglutide (pooled 1.2 and 1.8 mg/day, 1.3; P
= 0.0189). Following changing over, mostly transient nausea occurred in 21% of participants, and minor hypoglycemia
remained low (34% of participants). Continuing liraglutide treatment at 1.2 mg/day and 1.8 mg/day for 78 weeks
reduced HbA1c (baseline 8.3 and 8.4%, respectively) by -0.9 and -1.3%, respectively; FPG by -1.3 and -1.7 mmol/L,
respectively; and weight by -2.6 and -3.1 kg, respectively, with 910% of participants reporting minor hypoglycemia.
Glycemic control, weight, and treatment satisfaction improved after switching from sitagliptin to liraglutide, even though
there was a transient increase in gastrointestinal reactions.
Pratley RE, Nauck MA, Bailey T, et al. Efficacy and safety of switching from the DPP-4 inhibitor sitagliptin to the
human GLP-1 analog liraglutide after 52 weeks in metformin-treated patients with type 2 diabetes. Diabetes
Care. 2012.
Question : True or False: In a randomized trial, duloxetine was found to be inferior to pregabalin for the treatment of pain
in patients with diabetic peripheral neuropathy (DPN) who had an inadequate pain response to gabapentin. (True or
False)?
False
True
Question: A variant in which of the following genes has been found to cause susceptibility to type 2 diabetes?
LYP/PTPN22
CTLA-4
CDKAL1
insVNTR
Answer: The correct answer is CDKAL1. Type 2 diabetes mellitus is caused by a combination of genetic and
environmental factors that result in decreased insulin function at sites of insulin action and a reduced ability of pancreatic
beta cells to elevate insulin secretion in response to increased blood glucose levels. The company, deCODE Genetics
confirmed previous genomewide studies and identified an association with variant CDKAL1. The production of mature
insulin takes place within the beta cell and depends on the cleavage of the preproinsulin and proinsulin molecules. The
cleavage site at the junction of the A chain and the C-peptide contains a lysine residue, which is critical for cleavage. The
gene, CDKAL1 plays a critical role in the production of lysine. Failure to incorporate lysine resulting in the misfolding of
proinsulin and thus preventing proteolytic processing. In addition, there are now many associations between oxidative
stress and beta-cell failure. CDKAL1 may be exquisitely sensitive to oxidation. As the molecular mechanisms of CDKAL1
are revealed, researchers may consider small-molecule mediators to prevent the progression of type 2 diabetes in
patients who carry CDKAL1 risk variants. LYP/PTPN22, insVNTR and CTLA-4 are all non-HLA genetic susceptibility
genes for type 1 diabetes.
Kaufman, R.J. N Engl J Med 2011; 365:1931-1933
Question: What are the recommended glucose level targets (whole blood) during pregnancy for women with gestational
diabetes?
Fasting 100 mg/dL
1-hour postprandial 150 mg/dL
None of the answer choices are correct
2-hour postprandial 120 mg/dL
Answer: The correct answer is 2-hour postprandial 120 mg/dL. Additional target glucose levels recommended by the
American College of Obstetrics and Gynecology (ACOG) and American Diabetes Association (ADA) are fasting 95
mg/dL and 1-hour postprandial 130140 mg/dL .
Int J Womens Health. 2010;2:339-351
Question: The risk of developing type 1 diabetes in the offspring of a mother with type 1 diabetes is:
1.5%
8%
6%
3%
Answer: The correct answer is 3%. The offspring of a mother with type 1 DM have a 3% risk of developing type 1
diabetes.
David G. Gardner, Dolores Shoback, ed. Greenspan's Basic & Clinical Endocrinology. Ninth ed.; 2011:589.
Question: A post-hoc analysis of pooled data from three pivotal studies evaluated the glucose and lipid-altering efficacy
of colesevelam HCl when added to background metformin therapy in patients with inadequately controlled type 2
diabetes mellitus (T2DM). The results showed that colesevelam HCl:)
Significantly increased high-density lipoprotein cholesterol (HDL-C)
Did not significantly reduce hemoglobin A1c (HbA1
Significantly reduced fasting plasma glucose
Significantly reduced triglyceride levels
Did not significantly reduce low-density lipoprotein cholesterol (LDL-C)
Answer: The correct answer choice is significantly reduced fasting plasma glucose. In this pooled analysis of 696 T2DM
patients receiving metformin monotherapy or metformin combined with other antidiabetes therapies, 355 were
randomized to colesevelam HCl and 341 to placebo. Compared to placebo, colesevelam HCl significantly reduced
hemoglobin A1c (HbA1c) and fasting plasma glucose (mean treatment difference: 0.50% and 15.7 mg/dL,
respectively; P<.001 for both), as well as significantly reduced levels of LDL-C; mean treatment difference: 16.5%
P<.0001). Median triglyceride levels were increased with colesevelam HCl (treatment difference: +12.8%; P<.0001). The
mean increase in HDL-C with colesevelam HCl was not significant. Colesevelam HCl therapy was generally well
tolerated.
Bays HE. Endocrine Practice, 2011
Question: Which of the following findings from the Look AHEAD trial is true?
Intensive lifestyle intervention (ILI) group experienced significantly greater average improvements in all risk
factors except LDL-C levels compared to DSE (the control group)
Intensive lifestyle intervention (ILI) group maintained greater improvements than DSE participants in body weight, fitness,
but not HbA1C
Intensive lifestyle intervention (ILI) group experienced significantly greater average improvements in all risk factors
except HDL-C levels compared to DSE (the control group)
There was no difference between intensive lifestyle intervention (ILI) and diabetes support and education (DSE; the
control group) on the incidence of major CVD events
Answer: The correct answer is Intensive lifestyle intervention (ILI) group experienced significantly greater average
improvements in all risk factors except LDL-C levels compared to DSE (the control group). The Look AHEAD (Action for
Health in Diabetes) trial is a multicenter randomized clinical trial comparing the effects of an intensive lifestyle
intervention (ILI) and diabetes support and education (DSE; the control group) on the incidence of major CVD events in
5145 overweight or obese individuals (59.5% female; mean age,58.7 years) with type 2 diabetes mellitus. Averaged
across 4 years, ILI participants had a greater percentage of weight loss than DSE participants (?6.15% vs ?0.88%;
P_.001) and greater improvements in treadmill fitness (12.74% vs 1.96%; P_.001), hemoglobin A1c level (?0.36% vs ?
0.09%; P_.001), systolic(?5.33 vs ?2.97 mm Hg; P_.001) and diastolic (?2.92 vs ?2.48mmHg; P=.01) blood pressure,
and levels of high-density lipoprotein cholesterol (3.67 vs 1.97 mg/dL; P_.001) and triglycerides (?25.56 vs ?19.75
mg/dL; P_.001). Reductions in low-density lipoprotein cholesterol levels were greater in DSE than ILI participants (?11.27
vs ?12.84 mg/dL; P=.009) owing to greater use of medications to lower lipid levels in the DSE group. At 4 years, ILI
participants maintained greater improvements than DSE participants in weight, fitness, hemoglobin A1c levels, systolic
blood pressure, and highdensity lipoprotein cholesterol levels.
The Look AHEAD Research Group. Arch Intern Med. 2010;170(17):1566-1575
Question : Your patient and his wife disagree about how much coffee he should drink each day and want your opinion.
With a family history of diabetes, he feels the more coffee the better, according to information he has read. She says he
should stick to only one cup of coffee a day, if that. What do you tell them?
Coffee has nothing to do with his risk of diabetes
His risk of diabetes will be reduced by coffee
His risk of diabetes will be increased by coffee
Answer: His risk of diabetes will be reduced by coffee. A recent meta-analysis of more than 1 million participants and
45,000 cases of diabetes found that coffee consumption was inversely associated with the risk of type 2 diabetes in a
dose-response manner.
Ding M, et al. Diabetes Care. 2014;37(2):569-586.
Question : Which type of coffee would reduce his risk of diabetes?
Caffeinated only
Decaffeinated only
Both caffeinated and decaffeinated
Answer: Both caffeinated and decaffeinated. In the same meta-analysis, both caffeinated and decaffeinated coffee were
associated with reduced diabetes risk. The relative risk of diabetes for a 1 cup/day increase was 0.91 for caffeinated
coffee consumption and 0.94 for decaffeinated coffee consumption.
Ding M, et al. Diabetes Care. 2014;37(2):569-586.
Question 1: The EUREXA trial compared add-on exenatide with glimepiride for durability of glycemic control in patients
Question: Which of the following statements is false regarding Qsymia (phentermine/topiramate ER)?
Post-marketing studies are under way to look for evidence of heart dz
Women on this medication are required to take monthly pregnancy tests
It was approved by the US FDA in 2012
Induced myopia and angle-closure glaucoma are adverse effects
It helps people lose about 5% of their body weight
Answer: The correct answer is: It helps people lose about 5% of their body weight. Once-daily Qsymia combines the
appetite suppressant phentermine with the seizure medication topiramate. The US FDA approved the prescription drug in
July 2012 as an adjunct to a reduced-calorie diet and exercise for chronic weight management in obese (body mass
index [BMI] >30 kg/m2) or overweight (BMI >27 kg/m2) adults with at least one weight-related co-morbidity, such as
hypertension, type 2 diabetes mellitus or dyslipidemia. The drug is expected to help obese patients drop about 10% of
their weight, more than any other approved obesity drug. Women are urged to use contraception, because fetal exposure
to topiramate has been linked to an increased risk for cleft lip, with or without cleft palate. Induced myopia and angleclosure glaucoma are the two main adverse ophthalmic effects of topiramate. Qsymia is not recommended for people
with recent or unstable heart disease or stroke and post-marketing studies are under way to look for increased evidence
of these diseases in patients taking this medication.
Cameron, Fiona. Phentermine and Topiramate Extended Release (Qsymia): First Global Approval. Drugs, 2012;
72, 15, 2033-2042
Question: What does not need to be considered when evaluating for individualized glycemic goals in type 2 diabetics?
Life expectancy
History of hypoglycemia
Ethnicity
Age of the patient
Significant comorbidities
Answer: The correct answer is: Ethnicity. Ethnicity does not play a role when evaluating for individualized glycemic
goals. The ADA guidelines state that goals for glycemic control should be based upon the individual's overall health and
projected period of survival, since the risk of complications is duration-dependent.A reasonable A1C goal for most nonpregnant adults is <7%. However, providers can reasonably suggest more stringent A1C goals (such as < 6.5%) for
selected individual patients (such as those with short duration of diabetes, long life expectancy, and no significant CVD).
Less stringent A1C goals (such as <8%) may be appropriate for patients with a history of severe hypoglycemia, limited
life expectancy, extensive comorbid conditions, and those with long-standing diabetes in whom the general goal is
difficult to attain despite diabetes self-management education, appropriate glucose monitoring, and effective doses of
multiple glucose-lowering agents including insulin.
Question : Which of the following best describes results from the Stop Atherosclerosis in Native Diabetics Study
(SANDS) trial?
Baseline A1c was related to the effects of lipid and BP lowering on carotid intima medial thickness (CIMT)
Baseline A1c predicted the progression of carotid intima medial thickness (CIMT) and left ventricular mass index
The degree of baseline glycemia was negatively correlated with the ability to achieve SBP, LDL-C and non-HDLC targets
Intensive lipid and BP treatment worsened glycemic control
Answer: The correct answer is the degree of baseline glycemia was negatively correlated with the ability to achieve
SBP, LDL-C and non-HDL-C targets. The Stop Atherosclerosis in Native Diabetics Study (SANDS) compared the effects
of reducing systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein
cholesterol (non-HDL-C) to standard targets of 130 mmHg, 100 mg/dl and 130 mg/dl versus aggressive targets of 115
mmHg, 70 mg/dl and 100 mg/dl on preclinical atherosclerosis in diabetic adults from a population with high rates of
diabetes and diabetes-associated CVD. In the group treated to lower targets, there was a reduction in carotid intima
medial thickness (CIMT) and a greater reduction in left ventricular (LV) mass. Glycemia control, however, varied widely
among the study participants. Therefore, the relation between baseline glycemia and ability to achieve the blood
pressure (BP), LDL-C and non-HDL-C targets and whether glycemia control affected the ability of lipid and BP lowering
to influence changes in carotid atherosclerosis and cardiac structure, as measured by CIMT and LV mass index (LVMI).
The SANDS trial is unique in that rather than comparing two pharmacologic regimens, it compared two cohorts treated to
aggressive versus standard targets for SBP and lipid control, including non-HDL-C, in diabetic individuals. The degree of
baseline glycemia was negatively correlated with the ability to achieve SBP, LDL-C and non-HDL-C targets, and the
likelihood of reaching these targets declined significantly in both groups with increasing tertile of baseline A1c. Although
carotid atherosclerosis, indexed by CIMT, was significantly and directly related to baseline A1c, A1c did not influence the
effects of lipid and SBP lowering on carotid atherosclerosis. These findings are noteworthy for several reasons. First,
they suggest that the improvements in subclinical measures of atherosclerosis and cardiac function observed in SANDS
did not differ as a result of differences in glycemia control. They also suggest that the treatment strategies used to
achieve the BP and lipid targets did not affect glycemia control, eliminating potential negative consequences of treatment
regimens. Thiazide diuretics and ?-blockers, which were steps 2 and 3 of the algorithm for BP control in SANDS (Weir et
al., 2009), have known potential adverse effects on glycemia management, whereas ACE inhibitors may have beneficial
effects. Had intensive lipid and BP treatment worsened glycemia control, that finding would have complicated clinical
decision making because of the known benefits of glycemia control on microvascular complications. Although a direct
relationship was observed between baseline glycemia and CIMT, as seen in other studies ( [McNeely et al., 2009] and
[Selvin et al., 2005] ), the degree of baseline glycemia did not significantly influence change in CIMT or LVMI over 36
months. This observation reinforces the need to focus on lipid and BP control in diabetes regardless of glycemia status,
with the implication that improvements in CVD risk are possible despite level of glycemia.
Mete M, et al. Journal of diabetes and its complications. 2011 vol:25 iss:6 pg:362 -367
Question: A recent study showed that ?-Cell function can be preserved for at least 3.5 years with early and intensive
therapy for type 2 diabetes. (True or False)
False
True
Answer: The correct answer is: True. A randomized trial of 58 patients with treatment-nave newly diagnosed type 2
diabetes was conducted to assess -cell function preservation after 3.5 years of intensive therapy with: Insulin plus
metformin (INS group) vs. Triple oral therapy (TOT group) with metformin, glyburide, and pioglitazone. All patients were
treated with insulin and metformin for a 3-month lead-in period followed by random assignment to the INS or TOT group.
-Cell function was assessed using a mixed-meal challenge test at randomization and 6, 12, 18, 30, and 42 months.
Analyses were intention to treat and performed with repeated-measures models. Completion rates at 3.5 years were
83% in the insulin group and 72% in the TOT group, with good compliance in both groups (87 6 20% in the INS group vs.
90 6 15% in the TOT group). -Cell function was preserved at 3.5 years after diagnosis, with no significant change from
baseline or difference between the two groups as measured by area under the curve (AUC) of C-peptide (P = 0.14) or
the ratio of C-peptide to glucose AUC (P = 0.7). Excellent glycemic control was maintained in both groups (end-of-study
HbA1c 6.35 0.84% in the INS group vs. 6.59 1.94% in the TOT group). Weight increased in both groups over time
(from 102.2 24.9 kg to 106.2 31.7 kg in the INS group and from100.9 23.0 kg to 110.5 31.8 kg in the TOT group),
with no significant difference between groups (P = 0.35). Hypoglycemic events decreased significantly over time (P =
0.01) but did not differ between groups (P = 0.83). This study concluded that -Cell function can be preserved for at least
3.5 years with early and intensive therapy for type 2 diabetes with either insulin plus metformin or triple oral therapy after
an initial 3-month insulin-based treatment period.
Harrison L et al. Diabetes Care 2012;35:1406-1412
Question: The TIMES2 Study evaluated the effects of testosterone replacement therapy (TRT) on Insulin resistance,
cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome.
Transdermal TRT was associated with which of the following?
Reduction in homeostasis model assessment of insulin resistance (HOMA-IR)
Increase in Non-fatal Cardiovascular Events
Increase in HDL cholesterol
Increase in LDL cholesterol
Increase in lipoprotein a (Lpa)
Answer: Reduction in homeostasis model assessment of insulin resistance (HOMA-IR). There were Improvements in
total and LDL cholesterol, and Lpa. HDL cholesterol decreased from baseline significantly more with TRT than placebo.
There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The
majority of AEs (>95%) were mild or moderate.
Diabetes Care. 2011;34(4):828-837.
Question: A mutation in the gene encoding the transcription factor HNF-1beta (HNF1B) in a young patient with diabetes
and early-onset kidney disease is associated with which monogenic form of diabetes?
MODY2
MODY3
MODY5
MODY1
MODY4
Answer: MODY5. Mutations in the hepatocyte nuclear factor?1? (HNF1B) account for approximately 2% of cases of
maturity-onset diabetes of the young (MODY). MODY5 has a progressive clinical course in terms of hyperglycemia, with
increasing treatment requirements. Additional clinical features include; presence of renal cysts and other renal
abnormalities as well as genital abnormalities and abnormal liver function. MODY2 involves mutations in glucokinase and
is associated with a mild form of nonprogressive hyperglycemia that is usually asymptomatic at diagnosis and is treated
with diet alone. MODY1 is due to mutations in HNF-4alpha. MODY3 is due to mutations in HNF1alpha. MODY4 is due to
a frame-shift mutation in the gene encoding a ?-cell transcription factor, Insulin promoter factor 1/ Pancreas?duodenum
homeobox protein 1(IPF1/PDX1 ). Genetic testing will disclose whether MODY is present and will distinguish between
subtypes of MODY, and thereby give clues to prognosis and treatment.
Stefan SF et al. MODY: History, genetics, pathophysiology, and clinical decision making Diabetes Care August
2011 34:1878-1884
Question: A retrospective chart review was conducted to determine the effect of metformin on 25-OH vitamin D and B12
levels in patients with diabetes mellitus type 2. What were the findings from this study?
Patients on metformin had statistically significant lower vitamin B12 levels than those not on metformin
No statistically significant difference was shown between users and nonusers of metformin in regard to vitamin B12
levels
Metformin use did adversely affect successful treatment of vitamin D deficiency in the subgroup with osteoporosis
Patients on metformin had statistically significant lower 25-OH vitamin D than those not on metformin
Answer: The correct answer is patients on metformin had statistically significant lower vitamin B12 levels than those not
on metformin. The effect of metformin on vitamin B12 levels in diabetic patients has been studied for decades, noting that
on average 10-30% of patients show a malabsorptive deficiency of vitamin B12. This study was a retrospective chart
review of patients treated between 2003-2009 at Loyola University Medical Center in both ambulatory primary care and
endocrinology clinics. 706 patients aged 20-93 with diabetes mellitus type 2 were included with a mean age of 63
&elusmn; 13 years and a mean BMI of 33.1 kg/m2. 34% of these patients used metformin, and 35% of these patients
had been diagnosed with osteoporosis/osteopenia. Patients on metformin had statistically significant lower vitamin B12
levels than those not on metformin (p<0.0001, 95% CI = (-220, -84)). No statistically significant difference was shown
between users and nonusers of metformin in regard to vitamin D levels when adjusted for variables (p=0.297, 95% CI for
mean difference = (-0.7, 2.2)). Metformin use did not adversely affect successful treatment of vitamin D deficiency in this
population as a whole, nor did it affect the subgroup with osteoporosis (p =0.956). Those with osteoporosis did have
statistically significant lower baseline vitamin D levels compared to those without when adjusted for all variables
(p=0.002, 95% CI = (0.8, 3.9)). This study confirms the higher prevalence of vitamin B12 deficiency in metformin treated
type 2 diabetic patients. This study also suggests that vitamin D deficiency is not a clinical concern among metformin
treated type 2 diabetics, and metformin does not negatively impact treatment of vitamin D deficiency in these patients.
Kos E et al. The effect of metformin therapy on vitamin D and B12 levels in patients with diabetes mellitus type
2. Endocr Pract. 2011:1-16.
twice daily, lisinopril 40 mg each morning, and amlodipine 10 mg each morning. His blood pressure is 132/70 mm Hg.
Change his lisinopril or amlodipine dose to the evening
Add a beta-blocker
Answer: The correct answer is: change his lisinopril or amlodipine dose to the evening. The benefits of lowering BP in
diabetes to <140 mm Hg systolic and <80 mm Hg diastolic have been established in randomized control trials. However,
the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial demonstrated that, in patients with T2DM,
intensive BP lowering to <120 mm Hg systolic yielded no significant differences in fatal and nonfatal cardiovascular
events compared with BP maintained between 130 and 140 mm Hg. Moreover, aggressive BP lowering may be
associated with serious adverse events. The 2012 ADA guidelines state that a systolic BP goal of <130 mm Hg is
appropriate for most patients; however, higher or lower BP targets may be individualized.If a patient is taking multiple BP
medications, one or more should be taken at bedtime. Administering an antihypertensive at night results in better
ambulatory BP control and reduces cardiovascular mortality. BC is on maximal doses of 2 antihypertensive agents, and
his BP is 132/70 mm Hg. His physician must individualize care and decide If adding a third agent is worth the risk of
another medication when clear benefit has not been demonstrated. It is reasonable to continue his current regimen with
the exception of changing either his lisinopril or amlodipine dose to the evening and reassessing his BP control at his
next visit.
Cusbman WC, Evans GW, Byington RP, et al. ACCORD Study Group. Effects of intensive blood-pressure control
in type 2 diabetes mellitus. NEngUMed. 2010;362:15?5-1585.
Question: Which of the following best describes the results of a recent cross-sectional study investigating the impact of
body mass index (BMI) status on the relationship of serum 25-hydroxyvitamin D (25OHD) concentration with insulin
sensitivity?
The optimal serum 25OHD concentration for insulin sensitivity is about 46 ng mL
The correlation of serum 25OHD with insulin sensitivity was much stronger in the overweight group than in the
normal weight group.
The optimal serum 25OHD concentration for insulin sensitivity is about 34 ng mL
Answer: The correct answer is the correlation of serum 25OHD with insulin sensitivity was much stronger in the
overweight group than in the normal weight group. Obesity is a risk factor for hypovitaminosis D, insulin resistance and
type 2 diabetes. This cross-sectional study enrolled 126 healthy and glucose-tolerant subjects. The participants were
divided into two groups based on BMI: normal weight (n = 68) and overweight (n = 58). Insulin sensitivity index (ISI) was
assessed by using hyperglycemic clamps. Serum 25OHD concentration was determined in the fasting samples. The
correlation of serum 25OHD with ISI was much stronger in the overweight group (r = 05271, P < 00001) than in the
normal weight group (r = 02836, P = 0002). The correlation remained significant in the overweight group (r = 03620, P
= 0002), but not in normal weight group after adjusting for age, gender, BMI, season of study, ethnicity and exercise.
Nonlinear regression analysis revealed that when serum 25OHD concentration was > 40 ng mL?1, the association
between serum 25D concentrations and insulin sensitivity plateaued. The results of this study suggested that overweight
subjects with hypovitaminosis D may benefit more from vitamin D replacement than normal weight subjects.
Furthermore, the optimal serum 25OHD concentration for insulin sensitivity is about 40 ng mL?1.
Horng-Yih Ou, et al Eur J Clin Invest 2011; 41 (11): 11951201
Question: The EUREXA trial compared add-on exenatide with glimepiride for durability of glycemic control in patients

Question 1: True or False: In a randomized trial, duloxetine was found to be inferior to pregabalin for the treatment of
pain in patients with diabetic peripheral neuropathy (DPN) who had an inadequate pain response to gabapentin. (True or
False)?
True
False
Question : What were the findings from a recent prospective study aimed to examine vitamin D status as a determinant
for development of type 2 diabetes and deterioration of glucose homeostasis?
Low 25(OH) D status was significantly associated with an increase in fasting blood glucose
Low 25(OH) D status was significantly associated with an increase in HbA1c.
Low 25 (OH) D status was significantly associated with incident diabetes after adjustment for confounders.
Low 25(OH) D status was not significantly associated with an increase in 2-hour glucose
Answer: The correct answer is: Low 25(OH) D status was significantly associated with an increase in fasting blood
glucose. This was population-based randomized controlled Trial which was conducted in Copenhagen, Denmark. It
included 6,405 men and women aged 3065 years at baseline (19992001), with 4,296 participating in the follow-up
examination 5 years later (20042006). Vitamin D was determined at baseline as serum 25-hydroxyvitamin D [25(OH)
D]. Diabetes was defined based on an oral glucose tolerance test and HbA1c. Secondary outcomes included continuous
markers of glucose homeostasis. The risk of incident diabetes associated with a 10 nmol/L increase in 25(OH) D was
OR) 0.91 (95% CI 0.840.97) in crude analyses. The association became statistically nonsignificant after adjustment for
confounders, with an OR per 10 nmol/L of 0.94 (0.861.03). Low 25(OH)D status was significantly associated with
unfavorable longitudinal changes in continuous markers of glucose homeostasis after adjustment for confounders.
Fasting and 2-h glucose and insulin as well as the degree of insulin resistance increased significantly more during followup among those with low 25(OH)D levels compared with those with higher levels. In conclusion, Low 25(OH)D status
was not significantly associated with incident diabetes after adjustment for confounders. However, it was significantly
associated with unfavorable longitudinal changes in continuous markers of glucose homeostasis, indicating that low
vitamin D status could be related to deterioration of glucose homeostasis.

Husemoen LLN, et al. Serum 25(OH)D and type 2 diabetes association in a general population. Diabetes Care.
2012.
Question: A retrospective cohort study was conducted to assess the relationship of individual sulfonylureas and the risk
of overall mortality in a large cohort of patients with type 2 diabetes. What were the findings in patients with underlying
coronary artery disease (CAD)?
Decreased overall mortality risk with glipizide versus glyburide
No statistically significant difference in the risk of overall mortality
Increased overall mortality risk with glimepiride versus glipizide
Increased overall mortality risk with glyburide versus glimepiride
Answer: The correct answer is increased overall mortality risk with glyburide versus glimepiride. This study was
conducted using an academic health center enterprise-wide electronic health record (EHR) system to identify 11,141
patients with type 2 diabetes (4,279 initiators of monotherapy with glyburide, 4,325 initiators of monotherapy with
glipizide, and 2,537 initiators of monotherapy with glimepiride), 18 years of age with and without a history of coronary
artery disease (CAD) and not on insulin or a noninsulin injectable at baseline. No statistically significant difference in the
risk of overall mortality observed among the individual sulfonylureas in the entire cohort. However, in the subanalysis of
patients with documented CAD, a trend toward an increased overall mortality risk with glyburide versus glimepiride
(hazard ratio 1.36 [95% CI 0.96 1.91]), and a trend toward an increased risk of mortality with the glipizide versus
glimepiride (1.39 [0.99 1.96]), were observed, suggesting that glimepiride may be the preferred sulfonylurea in those
with underlying CAD. Pantalone K et al. Diabetes Care 33:12241229, 2010
Question 1: A 52-year-old male with DM2 on insulin, reportsdysesthesia, numbness and tingling of extremities, and poor
improved sleep?
Vitamin B12
Duloxetine
Amitriptyline
Pregabalin
Boyle J, et al. Randomized, Placebo-Controlled Comparison of Amitriptyline, Duloxetine, and Pregabalin in
Patients with Chronic Diabetic Peripheral Neuropathic Pain. Impact on pain, polysomnographic sleep, daytime
functioning, and quality of life. Diabetes CareDecember 2012 vol. 35 no. 12 2451-2458
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Question: What is the best screening test for cystic fibrosis-related diabetes (CFRD)?
Correct! (Correct answer is highlighted below)

Fructosamine
Urine glucose
Oral glucose tolerance test (OGTT)
HbA1c
Answer: Oral glucose tolerance test (OGTT). The American Diabetes Association and The Cystic Fibrosis Foundation
recommend the OGTT as the screening test of choice for CFRD. Although it is an imperfect test due to the variability
observed in individual CF patients over time, longitudinal studies demonstrate that a diabetes diagnosis by OGTT
correlates with clinically important CF outcomes including the rate of lung function decline over the next 4 years, the risk
of microvascular complications, and the risk of early death. The committee concluded that HbA1c is not sufficiently
sensitive for diagnosis of CFRD and should not be used as a screening test. Fasting plasma glucose does not identify
those patients without fasting hyperglycemia, and will miss the diagnosis of diabetes in approximately half of CF patients.
Fructosamine and urine glucose have low sensitivity in the CF population.
Diabetes Care. 2010;33(12):2697-2708.
Question: A prospective intervention study was conducted to analyze glucostatic parameters in obese subjects with
T2DM before and after an equivalent amount of weight loss induced by either a low calorie diet (LCD) or Roux-en-Y
gastric bypass (RYGB).Which of the following findings of this study is correct?
The improvement in insulin sensitivity (Si) was similar between RYGB and LCD
The disposition index (DI) was significantly greater in RYGB compared with LCD subjects
The acute C-peptide response to glucose was significantly greater in LCD compared with RYGB subjects.
The equivalent weight loss was achieved in the same time in both groups
Answer: The correct answer is the disposition index (DI) was significantly greater in RYGB compared with LCD subjects.
A significant improvement in insulin secretion normalized to the degree of insulin resistance (disposition index) was
observed in both groups, but the mean increase was substantially greater in RYGB compared with LCD subjects (258.2
&elusmn; 86.6 vs. 55.9 &elusmn; 19.9; P = 0.04). Insulin sensitivity (Si) markedly improved only in the RYGB group (P =
0.002), but no significant change was detected in the LCD group (P = 0.30). When adjusted for baseline (Si), the change
remained significant in the RYGB group (P = 0.02) but still did not reach statistical significance in the LCD group (P =
0.09). Changes in acute C-peptide response to glucose (ACPRg) was not statistically significant in LCD group (P = 0.46),
but remained significant in RYGB group (P = 0.008). The equivalent weight loss was achieved in less than half the time
after RYGB as compared to LCD.
Plum L, et al. Obesity (2011)
Question: A recent study has shown that the administration of glutamic acid decarboxylase formulated with aluminium
hydroxide (GAD-alum) preserves insulin production in patients with recent-onset type 1 diabetes (True or False)
True
False
Answer: The correct answer is false. Glutamic acid decarboxylase (GAD) is a major target of the autoimmune response
that occurs in type 1 diabetes mellitus. In animal models of autoimmunity, treatment with a target antigen can modulate
aggressive autoimmunity. This study assessed whether immunisation with GAD formulated with aluminum hydroxide
(GAD-alum) would preserve insulin production in recent-onset type 1 diabetes. A total of 145 patients, aged 345 years,
who had been diagnosed with type 1 diabetes for less than 100 days were enrolled from 15 sites in the USA and
Canada, and randomly assigned to receive one of three treatments: three injections of 20 ?g GAD-alum, two injections of
20 ?g GAD-alum and one of alum, or 3 injections of alum. Injections were given subcutaneously at baseline, 4 weeks
later, and 8 weeks after the second injection. At 1 year, the 2-h AUC of C-peptide, adjusted for age, sex, and baseline Cpeptide value, was 0412 nmol/L (95% CI 03490478) in the GAD-alum group, 0382 nmol/L (03220446) in the
GAD-alum plus alum group, and 0413 nmol/L (03510477) in the alum group. The ratio of the population mean of the
adjusted geometric mean 2-h AUC of C-peptide was 0998 (95% CI 0779122; p=098) for GAD-alum versus alum,
and 0926 (0720113; p=050) for GAD-alum plus alum versus alum. HbA1c, insulin use, and the occurrence and
severity of adverse events did not differ between groups. Antigen-based immunotherapy therapy does not alter the
course of loss of insulin secretion during 1 year in patients with recently diagnosed type 1 diabetes. Although antigenbased therapy is a highly desirable treatment and is effective in animal models, translation to human autoimmune
disease remains a challenge.
Wherrett DK, Bundy B, Becker DJ, et al. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine
in patients with recent-onset type 1 diabetes: A randomised double-blind trial.
Question: Which of the following best describes the results of a study assessing the efficacy and safety of sitagliptin
(SITA) monotherapy and SITA/metformin (MET) vs. pioglitazone (PIO) in patients with type 2 diabetes and moderate-tosevere hyperglycemia (A1C = 7.512.0%)?
Improvement in 2-h postmeal glucose was similar in both groups.
There was no change in body weight with SITA/MET
Improvement in fasting plasma glucose was significantly greater with PIO
Improvement in A1C was significantly greater with PIO
Improvement in A1C was significantly greater with SITA/MET
Answer: The correst answer is improvement in A1C was significantly greater with SITA/MET. In an initial 12-week phase
(Phase A), 492 patients (aged 18 to 78 years) with T2DM were who were drug nave [not taking an
antihyperglycaemic agent (AHA) within the previous 3 months and not more than 4 weeks cumulatively in the previous 3
years] were randomized 1:1 in a double-blind fashion to SITA (100 mg qd) or PIO (15 mg qd, up-titrated to 30 mg after 6
weeks). In Phase B (28 additional weeks), the SITA group was switched to SITA/MET (up-titrated to 50/1000 mg bid over
4 weeks) and the PIO group was up-titrated to 45 mg qd. At the end of Phase A, mean changes from baseline were
-1.0% and -0.9% for A1C; -26.6 mg/dl and -28.0 mg/dl for fasting plasma glucose; and -52.8 mg/dl and -50.1 mg/dl for 2h post-meal glucose for SITA and PIO, respectively. At the end of Phase B, improvements in glycemic parameters were
greater with SITA/MET vs. PIO: -1.7% vs. -1.4% for A1C (p = 0.002); -45.8 mg/dl vs. -37.6 mg/dl for fasting plasma
glucose (p = 0.03); -90.3 mg/dl vs. -69.1 mg/dl for 2-h post meal glucose (p = 0.001); and 55.0% vs. 40.5% for patients
with A1C < 7% (p = 0.004). A numerically higher incidence of gastrointestinal adverse events and a significantly lower
incidence of edema were observed with SITA/MET vs. PIO. The incidence of hypoglycemia was similarly low in both
groups. Body weight decreased with SITA/MET and increased with PIO (-1.1 kg vs. 3.4 kg; p < 0.001).
Perez-Monteverde A et al. International Journal of Clinical Practice Vol 65, Issue 9;930938, September 2011
Question: A randomized placebo-controlled trial was conducted to investigate whether treatment with salsalate, an anti
inflammatory medication, improves glycemia in a group of newly diagnosed drugnaive patients with type 2 diabetes
mellitus (T2DM). Which of the following best describes the results?
Salsalate reduced fasting glucose
Salsalate did not reduce HbA1c
Fasting insulin levels were decreased in the salsalate group, while they increased in the placebo group.
HOMAIR did not change but HOMAB increased in the salsalate group.
Answer: The correct answer choice is salsalate reduced fasting glucose. There is a large body of evidence that suggest
that chronic inflammation plays a role in the pathogenesis of type 2 diabetes and that that anti-inflammatory therapy may
therefore be useful for treating diabete. Previous studies have shown that salicylate, a traditional anti-inflammatory agent,
inhibits activity of the transcription factor NF-?B, which regulates the production of multiple inflammatory mediators. The
TINSAL-T2D trial showed that salsalate was well tolerated in patients with T2DM and it improved measures of glycemic
control over a 3-month trial. The study in question was a randomized, double-blind, placebo-controlled trial. Diagnosis of
T2DM was made within 2 months of enrollment, and participants had not received any antiglycemic agent. Sixty adults
were randomized to receive salsalate (3 g/day) or placebo for 12 weeks. Salsalate reduced fasting glucose from 6.3
&elusmn; 0.2 mmol/l to 5.4 &elusmn; 0.2 mmol/l (P < 0.01). Fasting insulin levels were increased in the salsalate group
from 18.8 &elusmn; 1.6 to 21.6 &elusmn; 3.9, while they decreased in the placebo group. HbA1c rose in the placebo
group from 6.2% &elusmn; 0.2 to 7.9% &elusmn; 1.1 mmol/mol, but decreased in the intervention group from 6.1%
&elusmn; 0.5 to 5.6% &elusmn; 0.2 mmol/mol (P < 0.04 for betweengroup comparison). HOMAIR did not change but
HOMAB increased 1.7fold (P = 0.06) in the salsalate group . HOMA-IR, an indirect measure of insulin resistance, was
calculated as the product of FPG (mmol/l) and insulin (lIU/ml) divided by 22.5. HOMA-B, an indirect estimate of b-cell
function, was calculated as fasting insulin (lIU/ ml) 9 20/[FPG (mmol/l) - 3.5]. Consistent with the TINSAL-T2D trial, this
study demonstrated the positive effect of salsalate on control of hyperglycemia in patients with T2DM. The optimal
duration of treatment with salsalate and sustainability of its effect requires further study. elusmn; 1.6 to 21.6
Faghihimani E et al. Acta Diabetol. 2011 Sep 22
Question : A study was conducted to examine whether the effects of intensive glycemic control on major outcomes in
the ADVANCE trial differ between participants among different demographic regions. Which region had the highest
mortality?
Asia
North America
Eastern Europe.
Established market economies (EMEs)
Answer: The correct answer choice is none of the answers are correct. The ADVANCE (Action in Diabetes and Vascular
Disease: Preterax and Diamicron Modified Release (MR) Controlled Evaluation) trial had the broadest worldwide
coverage of patients of any trial of diabetes yet conducted, although relatively few participants (4%) came from North
America. Participants in ADVANCE were drawn from 20 different countries. A study was conducted to determine whether
the effects of intensive glycemic control on major outcomes in ADVANCE differ between participants from Asia,
established market economies (EMEs), and eastern Europe. Demographic and clinical characteristics were compared
across regions using generalized linear and mixed models. Effects on outcomes of the gliclazide modified releasebased
intensive glucose control regimen, targeting an AlC 6.5%, were compared across regions using Cox proportional
hazards models and revealed the effects of intensive glycemic control were not significantly different (P0.23) between
regions for any outcome, including mortality, vascular end points, and severe hypoglycemic episodes. This is evident,
regardless of differences in health care systems, clinical practice, and use of medications (including statins and blood
pressurelowering medication). Hence, according to this study the methods of glycemic control used in ADVANCE can
be safely recommended for Caucasian and Asian patients with type 2 diabetes in all three regions studied who are at
moderate to high risk of cardiovascular disease.
Woodward M, Patel A, Zoungas S, et al. Does glycemic control offer similar benefits among patients with
diabetes in different regions of the world? Diabetes Care.
Question : Which of the following best describes the results of the Bypass Angioplasty Revascularization Investigation 2
Diabetes (BARI 2D) trial
The survival rates in the insulin-sensitization group were significantly higher compared to the insulin-provision group.
The rates of death and major cardiovascular events were significantly greater in patients undergoing prompt
revascularization compared to those undergoing medical therapy.
The rates of major cardiovascular events were significantly higher in the medical-therapy group compared to the
revascularization group
The survival rates in the insulin-provision group were significantly higher than in the insulin-sensitization group.
Answer: The correct answer choice is none of the answers are correct. The Bypass Angioplasty Revascularization
Investigation (BARI2D) trial was conducted to determine optimal treatments to prevent mortality and major
cardiovascular events in patients with T2DM and stable ischemic heart disease. Both prompt revascularization compared
with intensive medical therapy alone or with delayed revascularization, and insulin-sensitization compared with insulinprovisional therapeutic strategies were evaluated in 2368 patients over 5 years with the use of a 22 randomized
factorial trial design. At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%)
and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulinprovision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly
among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7%
in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no
significant difference in primary end points between the revascularization group and the medical-therapy group. In the
CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%)
than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Of note, in
secondary analysis, insulin-sensitization therapies appeared to enhance the benefit of revascularization in the higher-risk
subgroup of patients selected for CABG. Additionally, insulin sensitization was associated with lower body mass index,
higher high-density lipoprotein cholesterol level, and lower rates of severe hypoglycemia.
Goldfine AB, Fonseca V. Management of diabetes mellitus in patients with cardiovascular disease in the bypass
angioplasty revascularization investigation 2 diabetes (BARI 2D) trial. Circulation. 2010;121(22):2447-2449.
Question: A retrospective cohort study was conducted to investigate the risk of all-cause mortality associated with
individual glucose-lowering treatment regimens in heart failure patients with diabetes? Patients using ___ had a
significantly lower risk of death from diabetes or cardiovascular causes.
Metformin + insulin
Sulfonylurea monotherapy
Metformin + sulfonylurea
Insulin monotheraphy
Metformin monotherapy
Answer: The correct answer is metformin monotherapy. This study was conducted in Denmark in patients who were
hospitalized with heart failure for the first time during 19972006 and treated with metformin, sulfonylureas and/or insulin.
Compared with patients using sulfonylurea monotherapy, patients using metformin as monotherapy had a significantly
lower risk of death from diabetes or cardiovascular causes while the risk was significantly higher in patients using insulin
as monotherapy.
Andersson C, et al. Diabetologia (2010) 53:25462553
Question: A study aimed to determine the effects on glycemic control after the implementation of a dedicated hospital
subcutaneous insulin prescription chart found:
A decrease in the use of supplemental insulin
No reduction in hypoglycemic events
An increase in the proportion of blood glucose levels within the ideal range
Answer: The correct answer is an increase in the proportion of blood glucose levels within the ideal range. A dedicated
subcutaneous insulin prescription chart incorporating glucose monitoring results and management guidelines was
introduced to facilitate better hospital diabetes control. Point of care capillary blood glucose monitoring charts for 99
people with diabetes from the period before the introduction of the new chart, and106 after its introduction were
reviewed. A total of 12,649 blood glucose levels (BGLs) were collected for glucometric analysis. Following the
introduction of the chart, there was an increase in the number of BGLs performed daily from 4.5 &elusmn; 1.2 to 4.9
&elusmn; 1.3 (p = 0.05). There was an increase in the proportion of BGLs within the ideal range (51.8% vs. 54.1%, p =
0.01). There was a reduction in hypoglycemic events (proportion of BGLs <70 mg/dl in the whole population decreased
from 5.2% to 3.4% (p < 0.001), proportion of BGLs < 70 mg/dl for each patient decreased from 5.6 &elusmn; 9.2% to 2.9
&elusmn; 5.4% (p = 0.01), proportion of days where patient had a BGL < 70 mg/dl decreased from 17.6 &elusmn; 22.6%
to 11.4 &elusmn; 18.8% (p = 0.03)), despite an increase in the use of supplemental insulin (14.2 &elusmn; 35.7 vs. 29.4
&elusmn; 51.4 units/patient, p = 0.02). This study concluded that the use of a dedicated hospital subcutaneous insulin
prescription chart can reduce hypoglycemia and improve some measures of glycemic control. Cheung N.W. et al.
Diabetes Research and Clinical Practice 92 (2011) 337341
Question: The American Diabetes Association recommends that testing to detect type 2 diabetes and assess risk for
future diabetes in asymptomatic people should be considered in adults of any age who are overweight or obese (BMI ?
25 kg/m2*) and who have one or more of the following additional risk factors:
Women who delivered a baby weighing > 10 lbs
Smoking
Women who delivered a baby weighing > 10 lbs
High-risk race/ethnicity
Second-degree relative with diabetes
Answer: The correct answer is: High-risk race/ethnicity. According to the American Diabetes Associations (ADA) most
recent position statement (Standards of Medical Care in Diabetes - released in January, 2012) testing should be
considered in all adults who are overweight (BMI 25 kg/m2*) and who have one or more additional risk factors: Physical
inactivity; First-degree relative with diabetes, high-risk race/ethnicity (e.g., African American, Latino, Native American,
Asian American, Pacific Islander); Women who delivered a baby weighing >9 lb or who were diagnosed with GDM;
Hypertension (blood pressure 140/90 mmHg or on therapy for hypertension); HDL cholesterol level <35 mg/dL (0.90
mmol/L) and/or a triglyceride level >250 mg/dL (2.82 mmol/L), women with PCOS; A1C 5.7%, IGT, or IFG on previous
testing; Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans), history of
CVD, In the absence of the above criteria, testing for diabetes should begin at age 45 years. If results are normal, testing
should be repeated at least at 3-year intervals, with consideration of more-frequent testing depending on initial results
(e.g., those with prediabetes should be tested yearly) and risk status.
Diabetes Care. 2012;35:S11-S63
Question: Diabetes is the leading cause of new blindness among people ages 20-74 years. Which of the following
statements is false regarding ranibizumab injection, (Lucentis)?
It is used to treat age related macular degeneration
The most common side effectis bleeding of the conjunctiva
It is an anti-angiogenic VEGF inhibitor
Its a promising therapy for DM macular edema, but isnt approved by FDA
Answer: The correct answer is: Its a promising therapy for DM macular edema, but isnt approved by FDA is false. In
August 2012, the Food and Drug Administration approved ranibizumab for the treatment of diabetic macular edema
(DME). The drugs safety and effectiveness to treat DME were established in two clinical studies involving 759 patients
who were treated and followed for three years. Patients were randomly assigned to receive monthly injections of Lucentis
or no injections for 24 months. Results showed that between 34 - 45 % of those treated withLucentis gained at least
three lines of vision compared with 12 -18 % of those who did not. The most common side effects of the drug were
bleeding of the conjunctiva, eye pain, and increased intraocular pressure.The FDA previously had approved Lucentis to
treat age-related macular degeneration and macular edema following retinal vein occlusion. Ranibizumab is an
monoclonal antibody fragment which inhibits a number of subtypes of vascular endothelial growth factors. VEGF
increases retinal vascular permeability, thereforeblocking VEGF in the eye may prevent and reverse vision loss caused
by macular degeneration. Ip MS, Domalpally A, et al. Long-term effects of intravitreal ranibizumab (RBZ) on diabetic
retinopathy severity and progression. Presented at the 2012 Annual Meeting of the Association for Research in Vision
and Ophthalmology (ARVO); May 610, 2012; Fort Lauderdale, Florida. Abstract 1336.
Nguyen Q, et al.Ranibizumab for diabetic macular edema results from 2 phase III randomized trials: RISE and
RIDE. Ophthalmology.2012;119:789801.
Question: Results from a post hoc analysis evaluating the efficacy of colesevelam when added to metformin, insulin or
sulfonyureas in patients with inadequately controlled type 2 diabetes showed:
A reduction in HbA1c levels by 0.5%
A reduction in fasting plasma glucose levels by a median of 15.7 mg/dL
A reduction in LDL-C by 16.5%
Answer: The correct answer is all answer choices are correct. The Post hoc analysis evaluated the results from 3
randomized, double-blind, placebo-controlled studies over the course of 16 or 26 weeks.
Medscape Medical News, May 9, 2011
twice daily, lisinopril 40 mg daily, and amlodipine 10 mg every evening. His lipid profile reveals the following:Total
cholesterol 185 mg/dL; HDL 40 mg/dL; TG 145 mg/dL; LDL 90 mg/dL.Should BC be started on a statin?
Physician dependent
Yes
No
Only after a 3 month trial of lifestyle changes
Answer: The correct answer is: Yes. In addition to lifestyle changes, statins are the primary means of achieving LDL
goals. Since BC is over 40 without known CVD and has a cardiac risk factor of hypertension, he should be started on
statin therapy regardless of his baseline LDL (90 mg/dL), which is already at goal (<100 mg/dL). The American Diabetes
Association recommends that all patients with overt coronary vascular disease (CVD) should receive a statin. Statins
should also be prescribed for patients with diabetes who do not have CVD, but who are older than 40 and have one or
more cardiac risk factors (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria) regardless of their
baseline LDL cholesterol. The recommended LDL goal in type II diabetics continues to be <100 mg/dL. However, <70
mg/dL is a reasonable goal for those with known CVD.
Question: A randomized trial was conducted to evaluate the efficacy and safety of initial combination therapy with
metformin plus colesevelam in patients with early type 2 diabetes. In post hoc analyses, what percentage of patients
achieved the composite dual goal of A1C <7.0% + LDL-C <100 mg/dl with metformin/colesevelam versus
metformin/placebo.
25%
56%
12%
40%
Answer: The correct answer is 40%. In post hoc analyses, composite dual glycemic and lipid goals achieved with
metformin/colesevelam versus metformin/placebo were: A1C <7.0% + LDL-C <100 mg/dL (40% versus 12% [P<.0001]).
In this study, initial treatment with the combination of metformin/colesevelam in patients with type 2 diabetes provided
synergistic effects, lowering both A1C and LDL-C levels. Safety and tolerability were similar between the treatment
groups. This combination therapy may be particularly beneficial for patients with recently diagnosed type 2 diabetes,
helping them to achieve the glycemic and lipid goals associated with overall risk reduction. Additional studies are
needed, however, to evaluate whether colesevelam preserves b-cell function in patients with type 2 diabetes and
whether it improves cardiovascular outcomes in these patients.
Rosenstock J, Fonseca VA, et al. Endocr Pract. 2010 Jul-Aug;16(4):629-40.
Question: Vegetarian diets were found to be associated with a substantial and independent reduction in diabetes
incidence. (True or False)
False
True
Answer: The correct answer is True. To evaluate the relationship of diet to incident diabetes among non-Black and Black
participants in the Adventist Health Study-2. Participants were 15,200 men and 26,187 women (17.3% Blacks) across the
U.S. and Canada who were free of diabetes and who provided demographic, anthropometric, lifestyle and dietary data.
Participants were grouped as vegan, lacto ovo vegetarian, pesco vegetarian, semi-vegetarian or non-vegetarian
(reference group). A follow-up questionnaire after two years elicited information on the development of diabetes. Cases
of diabetes developed in 0.54% of vegans, 1.08% of lacto ovo vegetarians, 1.29% of pesco vegetarians, 0.92% of semivegetarians and 2.12% of non-vegetarians. Blacks had an increased risk compared to non-Blacks (odds ratio [OR] 1.364;
95% confidence interval [CI], 1.093-1.702). In multiple logistic regression analysis controlling for age, gender, education,
income, television watching, physical activity, sleep, alcohol use, smoking and BMI, vegans (OR 0.381; 95% CI 0.2360.617), lacto ovo vegetarians (OR 0.618; 95% CI 0.503-0.760) and semi-vegetarians (OR 0.486, 95% CI 0.312-0.755)
had a lower risk of diabetes than non-vegetarians. In non-Blacks vegan, lacto ovo and semi-vegetarian diets were
protective against diabetes (OR 0.429, 95% CI 0.249-0.740; OR 0.684, 95% CI 0.542-0.862; OR 0.501, 95% CI 0.3030.827); among Blacks vegan and lacto ovo vegetarian diets were protective (OR 0.304, 95% CI 0.110-0.842; OR 0.472,
95% CI 0.270-0.825). These associations were strengthened when BMI was removed from the analyses.Vegetarian diets
(vegan, lacto ovo, semi-) were associated with a substantial and independent reduction in diabetes incidence. In Blacks
the dimension of the protection associated with vegetarian diets was as great as the excess risk associated with Black
ethnicity.
Tonstad S et al. Vegetarian diets and incidence of diabetes in the Adventist Health Study2. Nutr Metab
Cardiovasc Dis. 2011 Oct 7.
Question: Clinical characteristics of obese, ketosis-prone diabetes include which of the following:
Question: Which of the following statements is false regarding a recently published randomized trial compared insulin
degludec verses glargine?
Rates of confirmed hypoglycemia were similar in both groups
There was significantly more weight gain in the degludec group
Degludec achieved overall glycemic control similar to that of glargine
Similar percentages of pts in both groups achieved A1C levels <7%
Degludec had lower nocturnal hypoglycemia rates
Answer: The correct answer is: There was significantly more weight gain in the degludec group is false. In this 1-year,
parallel-group, randomized, open-label, treat-to-target trial, insulin naive adults with type 2 diabetes with A1C of 7-10%
were randomized to receive once daily degludec or glargine, both with metformin. There were 1,030 participants
(degludec 773, glargine 257) with mean age 59 years; baseline A1C 8.2%. Reduction of A1C from baseline to end of trial
was similar between treatments; mean A1C decreased by 1.06 to 7.1% with degludec and by 1.19 to 7.0% with glargine.
Rates of overall confirmed hypoglycemic episodes were similar (P = 0.106) between treatments. The rate of nocturnal
confirmed hypoglycemic episodes was significantly lower (by 36%) with degludec; the estimated rate ratio of degludec to
glargine was 0.64 (95% CI 0.420.98; P = 0.038). Observed mean weight gain at the end of the trial was similar between
degludec and glargine groups (2.4 and 2.1 kg; P = 0.28). End-of-trial mean daily insulin doses were 0.59 and 0.60
units/kg for degludec and glargine, respectively. Degludec is a long acting insulin developed by Novo Nordisk and is
currently under review by the FDA, although in Nov 2012, an advisory panel to the U.S. FDA, voted to recommend
approval.Combined data from 16 studies suggest degludec may trend toward higher incidence of cardiovascular events
compared to standard insulins (difference is not statistically significant and completed trials have not enrolled enough
patients, or lasted long enough, to ascertain heart risks).
ZinmanB, et al. Insulin Degludec Versus Insulin Glargine in Insulin-Naive Patients With Type 2 Diabetes.Diabetes
Care December 2012 vol. 35 no. 12 2464-2471
Question: A randomized clinical trial was conducted to assess the efficacy of a self-monitoring-based disease
management strategy in patients with type 2 diabetes treated with oral agent monotherapy. After 6 months, mean
HbA1c reduction in the intervention group was:
1.2%
1.6%
0.5%
1.9%
0.7%
Answer: The correct answer is 1.2%. This was an open-label, randomized, pilot study, primarily led by diabetes nurses.
Patients were randomly allocated to either a self-monitoring-based disease management strategy or usual care and
followed up for 6 months. Self-monitoring of blood glucose results were discussed during monthly telephone contact.
Patient
Franciosi M, et al. Diabetic Medicine: (2011) 28: 789796
Question: BC is a 57-year-old male non-smoker with T2DM, hypertension, and obesity. He has recently moved into the
neighborhood and this is his first physician encounter with you. He has made numerous lifestyle changes over the last 8
months including diet and exercise. He is taking metformin 1000 mg twice daily, aspirin 81 mg daily, lisinopril 40 mg daily,
amlodipine 10 mg every evening, and simvastatin 40 mg every evening. His Hem A1C is 6.9%, BP 128/76 mm Hg and
lipid profile: Total cholesterol 185 mg/dL; HDL 40 mg/dL; TG 145 mg/dL; LDL 110 mg/dL.Comprehensive metabolic panel
is normal. The patient feels well, has no complaints and reports no hypoglycemia. What is your next step?
Stop aspirin therapy.
Increase simvastatin to 80 mg daily.
Stop simvastatin and start atorvastatin.
Make no medication changes on this visit.
Decrease metformin to 500 mg twice daily.
Answer: The correct answer is: Stop simvastatin and start atorvastatin. The ADA recommends the low-density
lipoprotein-cholesterol (LDL-C) goal in patients with diabetes with no overt CVD to be <100 mg/dL (2.6 mmol/L). This
patient does not currently meet this goal, therefore choice A is incorrect. Simvastatin 80 mg is limited to patients that
have been taking this dose for >12 consecutive months without evidence of myopathy and are not currently taking or
beginning to take a simvastatin dose-limiting or contraindicated interacting medications.It is recommended that patients
who are unable to achieve LDL-C goal using the 40 mg dose of simvastatin, be switched to an alternative LDL-Clowering treatment that provides greater LDL-C reduction, than increasing the simvastatin dose to 80 mg. This patients
A1c is at goal, he is tolerating metformin without issue, and has no renal or liver dysfunction (normal CMP), therefore
there is no indication to decrease or stop metformin. The ADA currently recommends aspirin 75162 mg/day in patients
with DM2 at increased CVD risk (10-yr risk >10%). This patients Framingham risk score is 10%, thereforediscontinuing
aspirin therapy is incorrect.
FDA Drug Safety Communication: Restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce
the risk of muscle injury. Based on FDA's review of the Study of the Effectiveness of Additional Reductions in Cholesterol
and Homocysteine (SEARCH) trial.
Question: The risk of developing type 1 diabetes in the offspring of a mother with type 1 diabetes is:
1.5%
3%
8%
6%
Answer: The correct answer is 3%. The offspring of a mother with type 1 DM have a 3% risk of developing type 1
diabetes.
David G. Gardner, Dolores Shoback, ed. Greenspan's Basic & Clinical Endocrinology. Ninth ed.; 2011:589.
Question: The TIMES2 Study evaluated the effects of testosterone replacement therapy (TRT) on Insulin resistance,
cardiovascular risk factors, and symptoms in hypogonadal men with type 2 diabetes and/or metabolic syndrome.
Transdermal TRT was associated with which of the following?
Increase in Non-fatal Cardiovascular Events
Increase in LDL cholesterol
Increase in HDL cholesterol
Increase in lipoprotein a (Lpa)
Reduction in homeostasis model assessment of insulin resistance (HOMA-IR)
Answer: Reduction in homeostasis model assessment of insulin resistance (HOMA-IR). There were Improvements in
total and LDL cholesterol, and Lpa. HDL cholesterol decreased from baseline significantly more with TRT than placebo.
There were no significant differences between groups in the frequencies of adverse events (AEs) or serious AEs. The
majority of AEs (>95%) were mild or moderate.
Diabetes Care. 2011;34(4):828-837.
Question: Which of the following best describes the principal findings of SOLVE: Study of Once Daily Levemir: insights
into the timing of insulin initiation in people with poorly controlled type 2 diabetes in routine clinical practice?
Metformin, sulfonylurea and dual OAD (metformin plus sulfonylurea), remain the most common treatments prior to insulin
initiation.
All of the answer choices are correct.
The majority of patients with T2DM were poorly controlled at the point at which the decision was taken to initiate basal
insulin treatment.
Considerable regional differences exist in the timing of insulin initiation and in the use of OADs.
Answer: The correct answer is: All of the answer choices are correct. The aim of this analysis was to determine the
timing of insulin initiation in routine clinical practice, especially in relation to glycemic control and use of oral antidiabetic
drugs (OADs). Study of Once Daily Levemir was a 24-week international observational study involving 10 countries
(Canada, China, Germany, Israel, Italy, Poland, Portugal, Spain, Turkey and the UK). which evaluated the safety and
effectiveness of initiating once-daily insulin detemir in people with T2DM being treated with one or more OADs. A total of
17,374 participants were enrolled in the study: aged 62 12 years, 53% male, T2DM duration 10 7 years, body mass
index 29.3 5.4 kg/m2 Pre-insulin HbA1c was 8.9 1.6%. The proportion of patients with HbA1c 9.0% ranged from
64% (UK) to 23% (Poland). Pre-insulin OAD treatment included metformin (81%), sulfonylureas (59%), glinides (16%),
thiazolidinediones (TZD) (12%), -glucosidase inhibitors (12%) and dipeptidyl peptidase (DPP)-IV inhibitors (7%). The
mean starting dose of insulin detemir for the total cohort was 0.16 0.09 U/kg. Differences in OAD use and insulin doses
at initiation were evident among participating countries. The largest proportional changes in OAD prescribing at insulin
initiation were seen with glinides (+15%), sulfonylureas (-19%), TZD (-31%) and DPP-IV inhibitors (-28%). Despite the
well-documented benefits of timely blood glucose control and the availability of consensus guidelines encouraging the
earlier use of insulin replacement, a substantial delay remains with respect to the appropriate initiation of insulin
treatment in routine clinical practice. Nearly half of the patients had HbA1c 9.0% despite prolonged treatment with
multiple OADs. Considerable regional differences exist in both the timing of insulin initiation and in the use of OADs.
SOLVE provides an opportunity to better understand global and regional trends in the intensification of treatment in
patients with T2DM. These findings should facilitate the development of targeted treatment strategies in order to achieve
improved glycemic control earlier in the course of T2DM.alpha;-glucosidase inhibitors (12%) and dipeptidyl peptidase
(DPP)-IV inhibitors (7%). The mean starting dose of insulin detemir for the total cohort was 0.16 0.09 U/kg. Differences
in OAD use and insulin doses at initiation were evident among participating countries. The largest proportional changes
in OAD prescribing at insulin initiation were seen with glinides (+15%), sulfonylureas (-19%), TZD (-31%) and DPP-IV
inhibitors (-28%). Despite the well-documented benefits of timely blood glucose control and the availability of consensus
guidelines encouraging the earlier use of insulin replacement, a substantial delay remains with respect to the appropriate
initiation of insulin treatment in routine clinical practice. Nearly half of the patients had HbA1c alpha;-glucosidase
inhibitors (12%) and dipeptidyl peptidase (DPP)-IV inhibitors (7%). The mean starting dose of insulin detemir for the total
cohort was 0.16 0.09 U/kg. Differences in OAD use and insulin doses at initiation were evident among participating
countries. The largest proportional changes in OAD prescribing at insulin initiation were seen with glinides (+15%),
sulfonylureas (-19%), TZD (-31%) and DPP-IV inhibitors (-28%). Despite the well-documented benefits of timely blood
glucose control and the availability of consensus guidelines encouraging the earlier use of insulin replacement, a
substantial delay remains with respect to the appropriate initiation of insulin treatment in routine clinical practice. Nearly
half of the patients had HbA1c
Khunti K et al. Diabetes, Obesity and Metabolism, 2012 Jul;14(7):654-61.
Question 1: A 52-year-old male with DM2 on insulin, reportsdysesthesia, numbness and tingling of extremities, and poor
improved sleep?
Duloxetine
Vitamin B12
Amitriptyline
Pregabalin
Question: A post hoc analysis of data from the DURABLE clinical trial was performed to compare outcomes in patients
with type 2 diabetes initiating Humalog 75/25 or insulin glargine therapy, stratified by baseline oral antihyperglycemic
agent (OHA). Which of the following OHA treatment groups had the greatest improvement in HbA1c?
Metformin/sulfonylurea/thiazolidinedione
Metformin/thiazolidinedione
Sulfonylurea/thiazolidinedione
Metformin/sulfonylurea
Answer: The correct answer is metformin/thiazolidinedione. A significantly greater proportion of patients in the
metformin/thiazolidinedione group achieved an A1C value less than 7.0% in comparison with the corresponding
proportion in the metformin/sulfonylurea group. In both insulin treatment groups, metformin/thiazolidinedione-treated
patients had significantly greater improvement in A1C levels (-2.19% to -2.36%) and lower end point A1C values, in
comparison with metformin/sulfonylurea-treated patients (all P<.05). Patients treated with sulfonylurea/thiazolidinedione
or metformin/sulfonylurea/thiazolidinedione did not differ significantly from metformin/sulfonylurea-treated patients in
A1C change (-1.56% to -1.84%). Although the analysis did not specificallycompare outcomes between insulin treatment
groups, both insulin treatment groups had relatively similar A1C reductions with metformin/thiazolidinedione therapy.
Herman WH, et al. Concomitant oral antihyperglycemic agent use and associated treatment outcomes after
initiation of insulin therapy.
Question : A 26-year-old male with DM1 has an insulin regimen that includes insulin glargine26 units at bedtime and
insulin aspart1 unit per 16 g carbohydrate for breakfast and lunch, and 1 unit per 13 g carbohydrate for dinner. He has a
correction dose of 1 unit per 45 mg/dL, with a glucose goal of less than 120 mg/dL for corrections. He has normal renal
and liver function. His Hem A1c is 7.8%. The patient reports that his fasting glucose numbers are within goal. However,
he is using correction doses before bedtime as he has noticed high glucose levels at that time. He reports his evening
glucose levels rise even with initial response to the aspart dose he gives himself at dinner. What changes to his insulin
regimen is the most appropriate?
Split glargine into 13 units in the morning and 13 units in the evening
Change glargine from bedtime to morning
Increase glargine to 28 units at bedtime

Increase carbohydrate ratio to 1 unit per 10g of carbohydrate for dinner
Answer: The correct answer is: Split glargine into 13 units in the morning and 13 units in the evening. The patient is
having insufficient basal insulin late in the 24-hour dosing period. This is an issue for up to 20% of patients with once
daily glargine dosing. An overlapping effect is created by splitting the basal insulin into 2 doses, which would reduce any
decrease in the insulin level. Choice A is incorrect as changing the timing to the morning would shift the glucose rise to
another part of the day (before breakfast). The patients basal insulin dose is greater than 50% of the total daily insulin
dosage, and his fasting numbers are at goal, therefore increasing the glarginedose would not be helpful (choice B). The
patients dinner carbohydrate counting ratio is already more intense that the ratio he uses for breakfast and lunch.
Increasing it would decrease the glucose peak after dinner, but would not prevent the glucose rise later in the evening
(choice D).
Roach P 2008 New insulin analogues and routes of delivery: Pharmacodynamics and clinical considerations.
ClinPharmacokinet 47:595-610.
Question: The ACCORD Study Group investigated whether combination therapy with a statin plus a fibrate, as
compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes
mellitus who were at high risk for cardiovascular disease. Which of the following best describes the results?
The combination of fenofibrate and simvastatin reduced the rate of fatal nonfatal myocardial infarction only, as compared
with simvastatin alone.
Women seemed to benefit from fenofibrate therapy, whereas there was a trend toward harm among men.
The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal
myocardial infarction, or nonfatal stroke, as compared with simvastain alone
The combination of fenofibrate and simvastatin did reduce the rate of fatal cardiovascular events, nonfatal myocardial
infarction, and nonfatal stroke, as compared with simvastatin alone.
Answer: The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal
myocardial infarction, or nonfatal stroke, as compared with simvastain alone. The rates of the primary outcome did not
differ significantly between the fenofibrate group and the placebo group during 4.7 years of treatment and follow-up. The
annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the
fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P = 0.32). Prespecified subgroup analyses suggested
heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women. The primary
outcome for men was 11.2% in the fenofibrate group versus 13.3% in the placebo group, whereas the rate for women
was 9.1% in the fenofibrate group versus 6.6% in the placebo group (P = 0.01 for interaction).
ACCORD Study Group, Ginsberg HN, Elam MB, et al. Effects of combination lipid therapy in type 2 diabetes
mellitus. N Engl J Med. 2010;362(17):1563-1574.
Question : The ORIGIN trial evaluated the effect of insulin glargine in patients with diabetes mellitus and prediabetes.
Based on the results of the trial, which of the following statements is true regarding insulin glargine?
It decreased the incidence of colon cancer
It reducedthe risk of developing DM2 by 28% in prediabetes patients
It slowed the progression of microalbuminuria
It slowed the progression of atherosclerosis
Answer: The correct answer is: It reducedthe risk of developing DM2 by 28% in prediabetes patients is true. Glargine
reduced the risk of developing type 2 diabetes by 28% among patients with prediabetes. 12,537 patients (mean age of
63.5) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or DM2were randomly
assigned to receive insulin glargine or standard care. Patients were followed for an average of 6 years. Glargine did not
slow the progression of atherosclerosis and had a neutral effect on cardiovascular outcomes with rates of incident
cardiovascular outcomes being similar in the glargine and standard-care groups: 2.94 and 2.85 per 100 person-years,
respectively, (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63).Glargine slowed the progression of
dysglycemia; patients who were assigned to glargine were 28% less likely to have diabetes develop from the time of
randomization until the first oral glucose-tolerance test than were participants assigned to standard care. Insulin glargine
also had a neutral effect on cancers (colon, prostate, melanoma, breast, lung) with hazard ratio for colon cancer of
1.09;95% CI, 0.79 to 1.51; P=0.61.There was also no significant difference microvascular events, (including
microalbuminuria[hazard ratio, 0.97; 95% CI, 0.90 to 1.05; P=0.43]).
The Origin Trial Investigators. Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia.N Engl J
Med 2012; 367:319-398 July 26, 2012.
Question: A 52-year-old male with DM2 on insulin, reportsdysesthesia, numbness and tingling of extremities, and poor
improved sleep?
Duloxetine
Amitriptyline
Vitamin B12
Pregabalin
Question 1: Which of the following statements is true regarding the risk of coronary artery disease (CAD) in a patient
with T2DM and no known history of cardiovascular disease (CVD)?
About the same as that of a nondiabetic individual with CAD
About twice that of a nondiabetic individual with CAD
About the same as that of a nondiabetic individual without CAD
About half that of a nondiabetic individual with CAD
Answer: The correct answer is: About the same as that of a nondiabetic individual with CAD. Research has
substantiated that patients with type 2 diabetes mellitus are at increased risk for cardiovascular (CV) disease. The
hazard ratio for death from CAD for diabetic subjects without prior myocardial infarction was no different than in
nondiabetic subjects with prior MI, even correcting for other baseline risk factors. Diabetes is a risk factor for CVD,
equivalent to smoking and hyperlipidemia. More recent studies suggest that both early and late onset of diabetes are
associated with increased risk of major CVD events and mortality, but only early onset of diabetes (associated with >10
years' duration) appears to be a CVD equivalent. The risk is about 2-3 times that of non-diabetic individuals without
CAD.
Wannamethee SG, et al. Arch Intern Med. 2011;171(5):404-410.
Question: Which factor does not predict relapse of diabetes in obese patients with DM2, whom have experienced
remission of diabetes following gastric bypass surgery?
Pre-operative diabetes duration
Older age at surgery
Pre-operative glycemic control
Pre-operative BMI values

Insulin therapy before surgery
Answer: The correct answer is pre-operative BMI values. Data was collected in a retrospective cohort study of 4,434
adults with type 2 diabetes who underwent gastric bypass from 1995 to 2008. Diabetes remission and relapse events
were recorded.Multivariate analysis showed older age at surgery was associated with higher risk of relapse (HR for 5year increase in age, 1.07; 95 % CI, 1.01 to 1.14). Subjects with poor preoperative glycemic control (HbA1c 6.5 %)
were significantly more likely to experience relapse than those with good preoperative control, (HR for HbA1c 6.5-8%
1.34; 95% CI 1.04-1.71, HR for HbA1c 8-9% 1.43; 95% CI 1.03-1.97, HR for HbA1c 9-10% 1.95; 95% CI, 1.34-2.84).
Subjects treated with insulin were significantly more likely to experience relapse than diabetic subjects not using insulin
before surgery (HR for patients on oral medication at surgery 1.37; 95% CI 1.10-1.70 and HR for patients on insulin at
surgery 1.91; 1.48-2.45). Longer diabetes duration was significantly associated with higher relapse rate (HR for each
additional year of diabetes, 1.13; 95 % CI, 1.09 to 1.17). However, pre-operative BMI values were not significantly
different (p = 0.93) between patients who never completely remitted their diabetes (BMI 45.5 kg/m2), patients who
completely remitted but relapsed (BMI 45.8 kg/m2), and patients who durably remitted their diabetes (BMI 45.6 kg/m2).
Arterburn D, et al. A Multisite Study of Long-term Remission and Relapse of Type 2 Diabetes Mellitus Following
Gastric Bypass. Obesity Surgery 2012
Question: Exenatide once weekly (EQW) was compared to with insulin detemir in patients with type 2 diabetes
inadequately controlled with metformin. Which of the following statements is false regarding the trial results?
A1c targets were not different between the EQW and detemir groups
Injection siterelated adverse events occurred more often with EQW
GI-related adverse events occurred more frequently with EQW
Patients who received EQW had more weight loss
Patients who received EQW had a low risk of hypoglycemia
Answer: The correct answer is: A1c targets were not different between the EQW and detemir groups. A multicenter,
open-label, parallel-arm study compared the efficacy and safety of exenatide once weekly (EQW) with titrated insulin
detemir in 216 patients with type 2 diabetes inadequately controlled with metformin. Patients were randomized to EQW
(2 mg) or detemironce or twice daily, titrated to achieve target fasting plasma glucose for 26 weeks. The primary outcome
was proportion of patients achieving A1C?7.0% and weight loss ?1.0 kg. Therapy with EQW provided better glycemic
and weight control compared with detemir. Patients who received EQW were 6.6-times more likely to achieve A1C ?
7.0% with weight loss ?1.0 kg than patients who received detemir. Overall, 44.1% (95% CI, 34.753.9) of EQW-treated
patients compared with 11.4% (6.019.1) of detemir-treated patients achieved the primary outcome (P < 0.0001).
Treatment with EQW resulted in significantly greater reductions than detemir inweight (-2.7 +/- 0.3 kg vs. +0.8 +/- 0.4 kg;
P < 0.0001). Gastrointestinal-related and injection siterelated adverse events occurred more frequently with EQW than
with detemir. There was no major hypoglycemia in either group. Five (6%) patients in the EQW group and six (7%)
patients in the detemir group experienced minor hypoglycemia.
Melanie Davies, MD et. al. Once-Weekly Exenatide Versus Once- or Twice-Daily Insulin Detemir. Randomized,
open-label, clinical trial of efficacy and safety in patients with type 2 diabetes treated with metformin alone or in
combination with sulfonylureas.Diabetes Care,December 2012.
Question: A Japanese study recently assessed 35 type 1 diabetic patients without detectable Cpeptide using the
insulin pump and found that the basal insulin requirement of the total daily insulin dose was approximately:
35%
50%
40%
30%
45%
Answer: The correct answer is 30%. This study was done during 23 weeks of hospitalization in patients on diabetic
diets. Total daily insulin dose was 31.6 8.5 units, and total basal insulin requirement was 8.7 6 2.9 units, which was
27.7 6.9% of the total daily dose (TDD). In addition, the maximal basal insulin requirement in all patients was 43.8%
TDD, and no patients required 50% TDD.
Kuroda A, et al. Diabetes Care. 2011; 34(5):1089-1090
Question: Which of the following groups of patients is the least likely to need diabetic screening?
Patients with psoriasis
African American patients who are overweight (BMI 25)
Patients with crohn's disease
Patients who are 45 years old
Overweight females (BMI 25) with polycystic ovary syndrome
Answer: The correct answer is: Patients with crohn's disease are least likely to need diabetic screening. The ADA
recommends testing for diabetes in all adults with BMI 25kg/m2 and one or more additional risk factors for diabetes
(family history diabetes mellitus in a first-degree relative, habitual physical inactivity, belonging to a high-risk ethnic or
racial group [eg, African-American, Hispanic, Native American, Asian-American, and Pacific Islanders], history of
delivering a baby weighing >4.1 kg or >9 lb, or of gestational diabetes mellitus, hypertension, dyslipidemia, polycystic
ovary syndrome, history of vascular disease). In individuals without risk factors, testing should begin at age 45 years.
Patients withchronicdiseases such as psoriasis and crohn's may be on long term steroids that
American Diabetes Association. Standards of medical care in diabetes--2012. Diabetes Care 2012; 35 Suppl
1:S11.
twice daily, lisinopril 40 mg daily, and amlodipine 10 mg every evening. His lipid profile reveals the following:Total
cholesterol 185 mg/dL; HDL 40 mg/dL; TG 145 mg/dL; LDL 90 mg/dL.Should BC be started on a statin?
No
Only after a 3 month trial of lifestyle changes
Physician dependent
Yes
Answer: The correct answer is: Yes. In addition to lifestyle changes, statins are the primary means of achieving LDL
goals. Since BC is over 40 without known CVD and has a cardiac risk factor of hypertension, he should be started on
statin therapy regardless of his baseline LDL (90 mg/dL), which is already at goal (<100 mg/dL). The American Diabetes
Association recommends that all patients with overt coronary vascular disease (CVD) should receive a statin. Statins
should also be prescribed for patients with diabetes who do not have CVD, but who are older than 40 and have one or
more cardiac risk factors (family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria) regardless of their
baseline LDL cholesterol. The recommended LDL goal in type II diabetics continues to be <100 mg/dL. However, <70
mg/dL is a reasonable goal for those with known CVD.
Question: Results from a pooled analysis evaluating the benefits of initiating insulin to metformin at an earlier versus
later treatment stage, with or without sulfonylurea showed:
Patients taking metformin in combination with a sulfonylurea experienced the greatest HbA1c reductions after the
addition of basal insulin
Weight gain was significantly higher when basal insulin was added to a sulfonylurea alone
Patients taking metformin alone experienced the greatest HbA1c reductions after the addition of basal insulin
Answer: Patients taking metformin alone experienced the greatest HbA1c reductions after the addition of basal insulin.
In this large, pooled analysis of prospective, randomized, controlled clinical trials in patients with type 2 diabetes, more
than half of the patients previously uncontrolled on 0, 1 or 2 oral antidiabetic drugs (OADs) with baseline HbA1c of 8.7
9.1% achieved a target HbA1c 7.0% after 24 weeks of treatment with the addition of basal insulin, while continuing the
oral agent(s). Patients taking metformin (MET) alone before the initiation of basal insulin had the greatest HbA1c
reductions and the largest proportion of patients achieving glycemic goal at week 24 compared with patients taking an
sulfonylurea (SU) alone or in combination with MET. Of patients failing MET/SU monotherapy and MET + SU in
combination, 68.1, 50.4 and 56.4% achieved HbA1c 7.0%, respectively (p = 0.0006). Weight gain from baseline to
week 24 was not significantly different, based on either the number or type of OAD therapy at baseline However, the
MET-only group had the numerically lowest weight gain over 24 weeks (1.6 vs. 2.3 k in the SU-only group and 2.0 kg in
the combination group, p = 0.1830) after basal insulin initiation.These findings suggest that some patients may benefit
from the initiation of basal insulin to MET monotherapy earlier in the management of type 2 diabetes than often occurs in
this clinical practice, which supports the inclusion of insulin as a second step in the American Diabetes
Association/European Association for the Study of Diabetes treatment algorithm. Fonseca V et al. Diabetes, Obesity
and Metabolism 13: 814822, 2011.
Question: A randomized trial was conducted to evaluate the efficacy and safety of initial combination therapy with
metformin plus colesevelam in patients with early type 2 diabetes. In post hoc analyses, what percentage of patients
achieved the composite dual goal of A1C <7.0% + LDL-C <100 mg/dl with metformin/colesevelam versus
metformin/placebo.
25%
12%
56%
40%
Answer: The correct answer is 40%. In post hoc analyses, composite dual glycemic and lipid goals achieved with
metformin/colesevelam versus metformin/placebo were: A1C <7.0% + LDL-C <100 mg/dL (40% versus 12% [P<.0001]).
In this study, initial treatment with the combination of metformin/colesevelam in patients with type 2 diabetes provided
synergistic effects, lowering both A1C and LDL-C levels. Safety and tolerability were similar between the treatment
groups. This combination therapy may be particularly beneficial for patients with recently diagnosed type 2 diabetes,
helping them to achieve the glycemic and lipid goals associated with overall risk reduction. Additional studies are
needed, however, to evaluate whether colesevelam preserves b-cell function in patients with type 2 diabetes and
whether it improves cardiovascular outcomes in these patients. Rosenstock J, Fonseca VA, et al. Endocr Pract. 2010
Jul-Aug;16(4):629-40.
Question: Clinical characteristics of obese, ketosis-prone diabetes include which of the following:

Question: Which of the following mechanisms by which hypoglycemia may indirectly affect cardiovascular events is correct?
Hypoglycemia is associated with QTC prolongation
All of the answer choices are correct.
Hypoglycemia causes an increase in inflammatory cytokine secretion
Hypoglycemia induces abnormalities in platelet function and activation of the fibrinolytic system
Answer: The correct answer is: All of the answer choices are correct. Hypoglycemia induces several counterregulatory responses.
They include a decrease in pancreatic -cell insulin secretion, an increase in pancreatic -cell glucagon secretion, an increased
sympathoadrenal response with acute plasma increase in adrenaline and norepinephrine (in addition to its elevated tissue turnover),
as well as an increased secretion of ACTH/glucocorticoids. Besides these classical responses, there are several indirect changes
induced by hypoglycemia that affect inflammatory cytokine secretion, endothelial function, coagulation, and fibrinolysis. Several
studies have shown that hypoglycemia is associated with a significant lengthening of the corrected QT interval (QTC) in subjects with
and without diabetes. Other electrocardiographic abnormalities observed during hypoglycemia include a decrease in PR interval and
moderate ST segment depression. These changes are likely seen because of increased catecholamine release during hypoglycemia,
and QTC prolongation in particular could lead to a high risk of ventricular tachycardia and sudden death. Inflammation has been
associated with cardiovascular disease and diabetes. Several inflammatory markers including C-reactive protein, interleukin IL-6, IL-8,
tumor necrosis factor (TNF)- and endothelin-1 have been shown to be increased during hypoglycemia. This increase in
inflammatory cytokines could result in endothelial injury and abnormalities in coagulation, resulting in increased risk for cardiovascular
events. Certain growth factor levels such as vascular endothelial growth factor are also increased locally and in circulation after an
episode of hypoglycemia. Furthermore, some cytokines such as IL-1 have been shown to increase the severity of hypoglycemia, thus
perpetuating a positive feedback cycle. Hypoglycemia induces abnormalities in platelet function and activation of the fibrinolytic
system. Increased epinephrine levels lead to an increase in platelet activation, leukocyte mobilization, and blood coagulability.
Desouza CV, Bolli GB, Fonseca VA. Diabetes Care, 2010;33:1389-1391.
Question: Patients with metabolic syndrome and type 2 diabetes have an exacerbated vascular smooth muscle
dysfunction in micro- and macrocirculation compared to those with metabolic syndrome but without type 2 diabetes. True
or False?
False
True
Answer: True. Metabolic syndrome is associated with endothelial-dependent and endothelial-independent dysfunction,
affecting both the macro- and the microvascular systems.
Walther G, et al. Arterioscler Thromb Vasc Biol. 2015;35(4):1022-1029.
Question: In those same patients, indices of micro- and macrocirculation are predominantly inversely related to:
Inflammatory markers
Neither answer is correct positively associated
Abdominal fat
Both answers are correct
Answer: Both answers are correct. The presence of central abdominal fat and systemic inflammation seems implicated
in the pathogenesis of vascular dysfunctions in metabolic syndrome.
Walther G, et al. Arterioscler Thromb Vasc Biol. 2015;35(4):1022-1029.
Question: Anthocyanin supplementation in patients with type 2 DIABETES would significantly improve:
Serum adiponectin
None of the answers is correct
Serum LDL-C
Answer: All of the answers are correct. Study results suggest that anthocyanin supplementation exerts beneficial
metabolic effects in patients with type 2 DIABETES by improving dyslipidemia, enhancing antioxidant capacity and
preventing insulin resistance.
Li D, et al. J Nutr. 2015;145(4):742-748.
Question: Which outcome is observed when switching from insulin glargine to NPN insulin?
Higher frequencies of severe hypoglycemia
Increased rates of symptomatic hypoglycemia
Increased metabolic control
Greater treatment satisfaction
Answer: Higher frequencies of severe hypoglycemia. Switching to NPH insulin doubled the rate of severe
hypoglycemias and led to decreased metabolic control in the ACCORD trial.
Berard L, et al. Can J Diabetes. 2015 Mar 24. [Epub ahead of print]
Question: The major allele rs2431332 at the DMG-dehydrogenase-locus is significantly associated with:
Higher plasma insulin
Increased insulin resistance
Increased risk of incident DIABETES
Answer: All of the answers are correct. Study results are consistent with a possible causal role of DMG deficiency
in DIABETES development.
Magnusson M, et al. Diabetes. 2015 Mar 20. [Epub ahead of print]
The answers represent the best choice, based on the information provided in the question, generally referring to a specific indicated study.
Question: Which variable is associated with increased odds of malignancy in patients with thyroid follicular neoplasm?
Multinodularity on physical examination
Concomitant hyperthyroidism
History of head and neck radiation
Answer: History of head and neck radiation. Male sex and family history of thyroid cancer were also associated with
increased odds of malignancy.
Najafian A, et al. Ann Surg Oncol. 2015 Jan 7. [Epub ahead of print]
Question: Which variable is associated with increased odds of a benign lesion in patients with thyroid follicular
neoplasm?
Age >45 years
Dysphagia or pressure sensation
Nodules 4 cm
Answer: All of the answers are correct. Independent clinical predictors exist that might be helpful in preoperative
differentiation of benign and malignant follicular neoplasms.
Najafian A, et al. Ann Surg Oncol. 2015 Jan 7. [Epub ahead of print]
Question 3: Testosterone regulates thyroid cancer progression by reducing tumor-suppressor-gene expression and
tumor immunity. True or False?
True
False
Answer: True. This according to a recent study. Thyroid cancer has a higher incidence in women but more aggressive
disease in men.
Zhang LJ, et al. Carcinogenesis. 2015;36(4):420-428.
Question: Dabrafenib can stimulate radioiodine uptake in patients with metastatic BRAF V600E-mutant iodine-refractory
papillary thyroid cancer (PTC). True or False?
True
False
Answer: True. Thus representing a potential new therapeutic approach for these patients.
Rothenberg SM, et al. Clin Cancer Res. 2015;21(5):1028-1035.
Question: Which variable is associated with a higher risk of lateral neck recurrence in patients with papillary thyroid
carcinoma (PTC) with no ultrasonographic and/or cytological evidence of lymph node metastasis at diagnosis?
Central neck metastasis
Aggressive histological variants
Neither answer is correct
Answer: Both answers are correct. In these patients, a closer postsurgical ultrasound surveillance of the lateral neck
compartments seems worthwhile.
Giordano D, et al. Laryngoscope. 2014 Dec 15. [Epub ahead of print]
The answers represent the best choice, based on the information provided in the question, generally referring to a specific indicated study.
Question: Which characteristic differs between patients age 21 years and younger with papillary thyroid carcinomas 10
mm and older patients with papillary thyroid microcarcinomas?

Rate of lymph node metastases
Tumor size
Answer: Both answers are correct. In a recent study, mean tumor size was larger and the frequency of lymph node
metastases greater in the younger patients.
Pazaitou-Panayiotou K, et al. J Pediatr. 2015;166(2):451-456.e2.
Question: Exposure to which factor in the second or third trimester of pregnancy is associated with a higher risk of
childhood obesity?
Antibiotics
Cesarean section
Answer: Both answers are correct. The risk of childhood obesity was 84% higher after prenatal exposure to antibiotics
and 46% higher after cesarean section.
Mueller NT, et al. Int J Obes (Lond). 2015;39(4):665-670.
Question: True or false: Children with type 1 diabetes have impaired school performance compared with their
nondiabetic peers.
True
False
Answer: False. In a recent analysis, there were no differences between the groups for any of the educational outcome
domains tested. However, poorer glycemic control was associated with lower test scores and school attendance.
Cooper MN, et al. Pediatr Diabetes. 2014 Nov 25. [Epub ahead of print]
Question: True or false: Migraine and tension headache are associated with childhood obesity.
False
True
Answer: False. In a recent study, frequency and duration of headache attacks did not differ across BMI categories in
children.
Eidlitz-Markus T, et al. J Child Neurol. 2015;30(4):445-450.
Question: Atorvastatin therapy improves which lipid parameter in children with type 1 diabetes and elevated LDLAll of the answers are correct
Apolipoprotein B
LDL-C
Lipoprotein subparticles
Answer: All of the answers are correct. In addition to each answer choice, atorvastatin therapy also improved total
cholesterol and non-HDL-C in a placebo-controlled trial. Insulin sensitivity remained unchanged.
Canas JA, et al. Pediatr Diabetes. 2015;16(2):79-89.

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Question: Which factor does not predict relapse of diabetes in obese patients with DM2,

whom have experienced remission of diabetes following gastric bypass surgery?

Preserved beta cell function

Hypoglycemic unawareness or frequent hypoglycemia

The liraglutide group lost more weight, irrespective of BMI

Question: 3 BC is a 47-year-old male non-smoker with T2DM, hypertension, and obesity.

Yes, he should receive the hepatitis B virus vaccine

months of treatment, but not thereafter.

Significant reduction in body weight

Reduction in bodyweight in the exenatide group was not statistically significant

vitamin D status could be related to deterioration of glucose homeostasis.

You have successfully completed the 7/24/2014 Diabetes Quiz!

Your Score: 100%

Correct! (Correct answer is highlighted below)

Increase glargine to 28 units at bedtime

Pre-operative BMI values

Female sex predominance

Neither answer is correct

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