Você está na página 1de 5

Mayo Clin Proc. January 2009;84(1):38-42 www.mayoclinicproceedings.

com 38
SCREENING FOR TYPE 2 DIABETES MELLITUS
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings. For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
COMMENTARY
From the Department of Medicine (A.M.S., D.B.C.) and Department of Anes-
thesiology (D.B.C.), University of Wisconsin School of Medicine and Public
Health, Madison; and Penn State Diabetes and Obesity Institute, Penn State
College of Medicine, Hershey, PA (R.A.G.).
Individual reprints of this article are not available. Address correspondence to
Ann M. Sheehy, MD, MS, University of Wisconsin School of Medicine and Public
Health, 600 Highland Ave, H6/169, Madison, WI 53792 (asr@medicine
.wisc.edu).
2009 Mayo Foundation for Medical Education and Research
T
he US Preventive Services Task Force (USPSTF) op-
erates under the Agency for Healthcare Research and
Quality, one of 11 divisions of the US Department of
Health and Human Services. A panel of preventive medi-
cine and health care experts, the USPSTF reviews existing
literature and evidence to make recommendations regard-
ing preventive care measures.
1

Primary care practitioners
rely on such guidelines to make medical decisions, and
insurance companies and government agencies use this
information to determine payment for services rendered
and for credentialing of institutions.
Recently, the USPSTF updated its guidelines on screen-
ing adults for type 2 diabetes mellitus
2,3
(Table 1).
4
This
report was based on a literature review of the existing data
in both MEDLINE and the Cochrane Library databases.
Members of the USPSTF concluded that screening for dia-
betes in asymptomatic individuals with hypertension (blood
pressure >135/80 mm Hg) was merited. Unfortunately, they
did not recommend or highlight the importance of screening
other at-risk populations who would be screened under the
American Diabetes Association (ADA) guidelines, citing
lack of direct or indirect evidence supporting population
screening.
2

However, the authors acknowledge that direct
evidence, such as a randomized trial that compared treated
vs untreated persons in whom screening detected diabetes,
will not be available because withholding treatment from
persons with known diabetes is unethical. The ADA
also concluded that a study of this type is unlikely to occur
and developed guidelines based on existing data and expert
opinion that recommend screening for diabetes mellitus in
a much wider population because of the epidemic in the
United States.
4
In addition, the criteria used to develop these new
USPSTF recommendations have been a subject of interest.
Although USPSTF states its guidelines are based on ex-
plicit criteria,
1
experts have questioned its more restrictive
screening criteria used to develop its diabetes screening
Back to Wilson and Jungner:
10 Good Reasons to Screen for Type 2 Diabetes Mellitus
ANN M. SHEEHY, MD, MS; DOUGLAS B. COURSIN, MD; AND ROBERT A. GABBAY, MD, PHD
guidelines compared with that used for another chronic
disease, obesity.
5
This query has merit considering the
impact USPSTF guidelines have on population health.
Clearly, screening for disease must meet certain criteria
to be medically and financially acceptable. Perhaps the
most recognized criteria were determined by Wilson and
Jungner
6
in 1968. These principles (Table 2), which the
World Health Organization follows, define the basis of
preventive medicine 40 years later and are largely consid-
ered the standards by which screening tests are judged and
determined.
Because of the potential far-reaching implications of the
new USPSTF guidelines, it is important to examine the
merits of diabetes screening using the 10 criteria of Wilson
and Jungner since national screening recommendations
profoundly affect health care delivery and outcomes.
IMPORTANT HEALTH PROBLEM
Diabetes mellitus has reached epidemic proportions, and
the number of people with this condition continues to in-
crease. The 1999-2002 National Health and Nutrition Ex-
amination Survey identified 9.3% of the US population 20
years or older (19.3 million people) as having diabetes,
with approximately two-thirds diagnosed as having diabe-
tes and one-third not diagnosed. An additional 26.0% of the
population had impaired fasting glucose (IFG), making the
burden of disease estimate at 73.3 million people.
7
A pre-
dicted 48.3 million people in the United States will have
diabetes by 2050,
8

with a lifetime risk of disease being
32.8% and 38.5%, respectively, for US males and females
born in 2000.
9

Estimated quality-adjusted life years lost in
men and women diagnosed as having diabetes at age 50
years is 14.5 and 18.0 years, respectively, with greater years
lost at younger age of diagnosis because such individuals
have more years of life to lose.
9
ACCEPTED TREATMENT FOR RECOGNIZED DISEASE
Many treatment options are available for diabetes that im-
prove glycemic control and reduce risks of complications,
particularly microvascular disease. Numerous studies
have shown that treatment is effective. The UK Prospec-
tive Diabetes Study (UKPDS) found improved microvas-
cular outcomes for patients with a hemoglobin A
1c
(HbA
1c
)
value of 7.0% compared with the group that had a mean
HbA
1c
value of 7.9%.
10
The recently published 10-year
Mayo Clin Proc. January 2009;84(1):38-42 www.mayoclinicproceedings.com 39
SCREENING FOR TYPE 2 DIABETES MELLITUS
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings. For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
follow-up data from the UKPDS reported reduction in both
microvascular and macrovascular complications in the in-
tensive treatment arm.
11
A meta-analysis by Selvin et al
12
found better macrovascular outcomes in patients with type 2
diabetes mellitus who achieve tighter glycemic control.
These and other studies suggest improved outcomes with
treatment that results in moderate reduction in HbA
1c
values.
Recently, the glucose arm of the Action to Control
Cardiovascular Risk in Diabetes Study Group (ACCORD)
13
(a randomized controlled study that evaluated multiple car-
diovascular risk factors simultaneously) was terminated
early because of increased mortality in the tightly controlled
group. However, the absolute HbA
1c
value achieved (6.4%
vs 7.5%) may be less important than the rate of change (1.4%
in 4 months in the intensive group) or overall magnitude of
change (1.9% vs 0.8%). Additionally, hypoglycemia in
the intensive treatment arm may have contributed to ad-
verse outcomes, as well as the number and/or types of
medication used and amount of weight gain (27.8% vs
14.1% in the intensive vs standard therapy groups, respec-
tively, had >10-kg weight gain). The Action in Diabetes
and Vascular Disease: Preterax and Diamicron Modified
Release Controlled Evaluation (ADVANCE),
14
published
in parallel to ACCORD, achieved a similar HbA
1c
value
(6.5%) but did so more gradually and from a lower starting
point (7.5%-6.5%; 1.0). In contrast to ACCORD, AD-
VANCE showed an improved combined end point of mi-
crovascular and macrovascular events in the intensive
therapy arm. Given these findings, ADVANCE, as well as
previous studies such as the UKPDS, still confirms benefit
in reducing HbA
1c
values from the higher ranges, such as
from 8%, indicating mean glucose value of 183 mg/dL (to
convert to mmol/L, multipy by 0.0555), to 7%, mean glu-
cose level of 154 mg/dL.
4,15,16

Although primary care practi-
tioners who treat patients with cardiovascular disease or
those with several risk factors for cardiovascular disease
should use judgment in achieving glycemic targets in light
of the ACCORD data, this study should not in general
discourage practitioners from recommending the current
ADA target of an HbA
1c
of 7.0%, as compelling data exist
to support this glycemic goal.
10
AVAILABILITY OF FACILITIES FOR DIAGNOSIS AND TREATMENT
General practitioners in nearly any clinic can diagnose and
manage diabetes. Although access to health care and medi-
cal insurance in the United States is a problem for certain
patient populations, it is not a problem specific or unique to
patients with diabetes mellitus.
17
RECOGNIZABLE LATENT OR EARLY SYMPTOMATIC STAGE
Diabetes is the classic disease model for screening because
clinical disease is typically preceded by a lengthy asymp-
tomatic phase.
4
Several studies support the importance of
identifying the preclinical phase. For example, the Nurses
Health Study showed that women who eventually developed
diabetes had a higher risk of myocardial infarction (relative
risk, 3.75; 95% confidence interval, 3.10-4.53) even before
their diagnosis of diabetes compared with women who
never developed diabetes, with an increased risk likely
beginning as many as 15 years before actual diagnosis of
diabetes.
18
In a Wisconsin cohort, Harris et al
19
found a
TABLE 1. ADA and USPSTF

Criteria to Screen
for Diabetes Mellitus
a
ADA
1. Testing should be considered in all adults who are overweight
(BMI 25 kg/m
2
) and have the following additional risk factors
Physical inactivity
First-degree relative with diabetes
Member of high-risk ethnic populations
Women who were delivered of a baby weighing >4.1 kg or were
diagnosed as having gestational diabetes mellitus
Hypertension
HDL cholesterol level <35 mg/dL
b
or triglyceride level >250 mg/dL
b
Women with polycystic ovarian syndrome
Impaired glucose tolerance or impaired fasting glucose on
previous testing
Other clinical conditions associated with insulin resistance
History of cardiovascular disease
2. In the absence of the above criteria, testing for diabetes and
prediabetes should begin at age 45 y
3. If results for diabetes or prediabetes are normal, testing should be
repeated at least at 3-y intervals, with consideration of more
frequent testing depending on initial results and risk status
USPSTF
1. Screening is recommended for asymptomatic adults with sustained
blood pressure >135/80 mm Hg
2. No recommendation for asymptomatic adults with blood pressure
135/80 mm Hg
a
ADA = American Diabetes Association; BMI = body mass index; HDL =
high-density lipoprotein; USPSTF = US Preventive Services Task Force.
b
SI conversion factors: To convert cholesterol values to mmol/L, multiply
by 0.0259; to convert triglyceride values to mmol/L, multiply by 0.0114.
Adapted from Ann Intern Med
3
and Diabetes Care,
4
with permission.
TABLE 2. Wilson and Jungner Criteria for Disease Screening
(Adopted by the World Health Organization)
1. The condition sought should be an important health problem
2. There should be an accepted treatment for patients with recognized
disease
3. Facilities for diagnosis and treatment should be available
4. There should be a latent or early symptomatic stage
5. There should be a suitable test or examination
6. The test should be acceptable to the population
7. The natural history of the condition, including development from
latent to declared disease, should be adequately understood
8. There should be an agreed policy on who to treat as patients
9. The cost of case finding (including diagnosis and treatment of
patients diagnosed) should be economically balanced in relation
to possible expenditure on medical care as a whole
10. Case finding should be a continuing process and not a once and for
all project
From World Health Organization.
6
Mayo Clin Proc. January 2009;84(1):38-42 www.mayoclinicproceedings.com 40
SCREENING FOR TYPE 2 DIABETES MELLITUS
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings. For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
20.8% incidence of retinopathy at the time diabetes was
diagnosed. Using linear regression and statistical model-
ing, onset of diabetes was estimated at 4 to 7 years before
clinical diagnosis.

Taken together, these studies suggest
that both microvascular and macrovascular disease are
occurring before clinically apparent disease and formal
diagnosis.
Formal definitions exist for the prediabetic states IFG
and impaired glucose tolerance (IGT). These states are
detected with the same screening test as for diabetes.
4
Recognition of patients with prediabetes in and of itself is
important because of evidence of preclinical vascular dis-
ease (as aforementioned) and also because of the potential
to prevent or delay onset of actual diabetes mellitus with
lifestyle and pharmacological intervention.
SUITABLE TEST OR EXAMINATION
The fasting plasma glucose (FPG) is a simple, inexpensive
test with essentially no adverse effects or risk.
2
Although
the FPG is the recommended screening test, patients may
also be screened with a 75-g oral glucose tolerance test or
with a glucose value obtained randomly when patients are
symptomatic (Table 3).
4
In most cases, an abnormal test
result should be confirmed on a subsequent day.
Hemoglobin A
1c
is used as a marker of long-term glyce-
mic control and therefore is used to assess efficacy of
therapy, but it is not currently endorsed by the ADA,
American College of Endocrinology, or World Health Or-
ganization to diagnose diabetes. However, 1999-2004 data
from the National Health and Nutrition Examination Sur-
vey revealed that an HbA
1c
value of 5.8% had optimal
sensitivity (86%) and specificity (92%) for detecting undiag-
nosed diabetes. The authors suggest that this value could
be used as a trigger to formally screen with FPG.
20
Others
have independently recommended using an HbA
1c
value of
6.0% as a trigger to screen and have suggested that values
greater than 6.5% could be used in certain diagnostic crite-
ria.
21
This value, if standardized, could also be useful to further
characterize and stratify risk in certain populations, such as
hospitalized patients, in whom the prevalence of undiagnosed
diabetes is high; however, FPG values, elevated by counter-
regulatory hormone surge, cannot typically be used for dia-
betes screening and diagnosis.
22
ACCEPTABLE TEST TO THE POPULATION
As described in the USPSTF position statement, no data
suggest serious adverse outcomes to screening.
2
The ADA
recommends a FPG (with abnormal result confirmed on a
subsequent day) as the screening method of choice, an
intervention that is less invasive and less time-consuming
than other readily acceptable screening tests such as mam-
mography and colonoscopy.
NATURAL HISTORY OF THE CONDITION UNDERSTOOD
Not every person at risk will develop diabetes, and not
everyone who develops diabetes will have progressive
complications. The direct mechanism by which dys-
glycemia translates to vascular disease is an area of active
research
23
and is most likely multifactorial and polygenic.
Screening for disease is beneficial only if discovering
earlier or preclinical disease improves outcome. In both
type 1 and type 2 diabetes mellitus, periods of hyperglyce-
mic exposure can cause long-term adverse effects, the so-
called legacy effect.
24
Because glycemic control cannot be
achieved in patients in whom diabetes has not been diag-
nosed, screening plays an important role in preventing
long-term complications. In patients with type 1 diabetes,
the Diabetes Control and Complications Trial/Epidemiol-
ogy of Diabetes Interventions and Complications (DCCT/
EDIC) study group showed that the benefit of tighter glyce-
mic control (HbA
1c,
7.4% vs 9.1%) for an average of 6.5
years was still apparent 11 years later even though glyce-
mic control had equalized (7.9% vs 7.8%) during the 11-
year follow-up.
25
Patients with diabetes whose glycemia
was more tightly controlled during the 6.5 years of study
had significantly fewer cardiovascular events after the 11
years of follow-up. Importantly, 10-year follow-up data
from the UKPDS cohort, originally a group of 4209 per-
sons with newly diagnosed type 2 diabetes mellitus, were
recently published.
11
Like the DCCT/EDIC study, lasting
benefits of tighter glycemic control during the intervention
period were seen despite equalization of HbA
1c
values in
the follow-up period (8.0% vs 8.1%). These benefits were
apparent for both microvascular and macrovascular end
points. These studies suggest that glycemic effects are
lasting and irreversible and therefore advocate for early
diagnosis via screening so early and consistent glycemic
control can be achieved.
CONSENUS FOR TREATMENT
All patients with prediabetes and diabetes should be
treated. The ADA recommends that people with IFG or
IGT modify their lifestyle (5%-10% weight loss and 30
minutes of exercise daily).
4
For individuals with both IGF
TABLE 3. Criteria for Diagnosis of Diabetes Mellitus
a,b
1. Fasting plasma glucose level 126 mg/dL OR
2. Symptoms of hyperglycemia and a casual plasma glucose level
200 mg/dL OR
3. 2-h plasma glucose level 200 mg/dL during a 75-g oral glucose
tolerance test
a
In the absence of unequivocal hyperglycemia, these criteria should be
confirmed by repeated testing on a different day.
b
SI conversion factors: To convert glucose values to mmol/L, multiply by
0.0555.
Adapted from Diabetes Care,
4
with permission.
Mayo Clin Proc. January 2009;84(1):38-42 www.mayoclinicproceedings.com 41
SCREENING FOR TYPE 2 DIABETES MELLITUS
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings. For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
and IGT and an additional risk factor (in particular, body
mass index >35 kg/m
2
or age <60 years), metformin can
be considered.
4
These guidelines are based on a variety of
studies that have shown that these interventions delay or
prevent progression from prediabetes to diabetes.
26,27

All
patients with diabetes should receive education and un-
dergo a comprehensive evaluation, including screening for
known complications of diabetes.
4
Treatment is recom-
mended to achieve glycemic goals based on an HbA
1c
value
of 7.0% and preprandial and postprandial glycemic targets
of 70 to 130 mg/dL and less than 180 mg/dL, respectively.
4
COST OF CASE FINDING
Costs of discovering cases of diabetes, including diagnosis
and treatment, must make economic sense. The estimated
cost of diabetes in the United States in 2007 was $174
billion: $27 billion for direct diabetes treatment, $58 billion
for treatment of long-term complications of diabetes,
13
$31
billion for other medical costs, and $58 billion for lost
workforce productivity. The mean health care cost of a
patient with diabetes is 2.3 times the cost of a patient with-
out diabetes.
13
Preventing diabetes in patients with IFG or
managing risk factors in patients with diabetes is needed to
reduce these enormous health care expenditures.
28
PROCESS OF DETERMINING CASES OF DIABETES
Determining who has diabetes should be a continuing
process and not a once and for all project.
6
For patients
who meet criteria for testing, the ADA recommends
screening every 3 years after a normal result is ob-
tained.
4
For those with IFG and/or IGT, yearly evaluation
is recommended.
4
CONCLUSION
Screening for diabetes mellitus meets the Wilson and
Jungner criteria for screening for disease. The specific
patient population to screen may be less well defined, but
clearly a more inclusive screening plan than is outlined by
the USPSTF seems merited given the national diabetes
epidemic, the imperfect but compelling data regarding
risk reduction with glycemic control, and the ease of
screening. The USPSTF cites lack of direct data to support
its relatively restrictive guidelines yet acknowledges that a
clinical trial to assess treatment vs observation in patients
in whom diabetes has been detected by screening would
be unethical. However, endorsing only a limited screen-
ing program has the same clinical outcome and effect: a
large number of patients will not have diabetes diagnosed
and will not be treated because their disease is not known.
Long-term follow-up data from both the DCCT/EDIC and
UKPDS confirm that untreated periods of hyperglycemia,
as may be expected in undiagnosed (and therefore possi-
bly uncontrolled) diabetes, has lasting effects in regard to
microvascular and macrovascular disease progression.
With 2.8% of the US population having undiagnosed
diabetes, determining who these people are should be a
top priority. Incorporating other high-risk factors in the
decision to screen for diabetes, such as those recommended
by the ADA (Table 1), makes clinical and economic sense.
A large body of evidence shows that morbidity and
mortality due to diabetes can be reduced with proper di-
agnosis, treatment, and even actual disease prevention,
particularly microvascular complications such as nephrop-
athy. In patients with known diabetes, cholesterol and hy-
pertension management can be optimized to reduce risk of
macrovascular disease.
The USPSTF guidelines appear too restrictive and allow
information that is unknown to interfere with overwhelm-
ing evidence that is known. The bottom line is that our
current efforts are dismal, with one-third of persons with
diabetes in the United States being undiagnosed. We need
to improve our efforts in determining who has diabetes. We
need to seek out newer methods to screen patients with type
2 diabetes mellitus that include risk stratification, labora-
tory evaluation, probability analysis, and, in the future,
genomic screening. A more robust national database is
required to optimize the tracking and natural history of the
highest-risk patients with multiple risk factors compared
with those who have no risk factors. Finally, we need to
remember that in reality most clinical decision making is
based on imperfect evidence; however, as summarized by
British poet William Cowper (1731-1800), Absence of
proof is not proof of absence.
REFERENCES
1. AHRQ. Agency for Healthcare Research and Quality Web site. About
USPSTF: the new U.S. Preventive Services Task Force. www.ahrq.gov/clinic
/uspstfab.htm. Accessed November 10, 2008.
2. Norris SL, Kansagara D, Bougatsos C, Fu R. Screening adults for type 2
diabetes: a review of the evidence for the U.S. Preventive Services Task Force.
Ann Intern Med. 2008;148(11):855-868.
3. US Preventive Services Task Force. Screening for type 2 diabetes melli-
tus in adults: US Preventive Services Task Force recommendation statement
[published correction appears in Ann Intern Med. 2008;149(2):147]. Ann
Intern Med. 2008;148(11):846-854.
4. American Diabetes Association. Standards of medical care in diabetes
2008. Diabetes Care. 2008;31(suppl 1):S12-S54.
5. Williamson DF, Narayan KMV, Nathan DM. Criteria for screening for
type 2 diabetes vs. criteria for screening for obesity [on-line letter]. Ann Intern
Med. 2008;148:846-856. www.annals.org./cgi/eletters/148/11/846#96759.
Accessed November 11, 2008.
6. Wilson JMG, Jungner G. Principles and Practice of Screening for
Disease. World Health Organization Public Health Papers, No. 34; 1968.
http://whqlibdoc.who.int/php/WHO_PHP_34.pdf. Accessed November 28,
2008.
7. Cowie CC, Rust KF, Byrd-Holt DD, et al. Prevalence of diabetes and
impaired fasting glucose in adults in the U.S. population: National Health and
Nutrition Examination Survey 1999-2002. Diabetes Care. 2006;29(6):1263-
1268.
Mayo Clin Proc. January 2009;84(1):38-42 www.mayoclinicproceedings.com 42
SCREENING FOR TYPE 2 DIABETES MELLITUS
For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings. For personal use. Mass reproduce only with permission from Mayo Clinic Proceedings.
8. Narayan KM, Boyle JP, Geiss LS, Saaddine JB, Thompson TJ. Impact of
recent increase in incidence on future diabetes burden: U.S., 2005-2050. Dia-
betes Care. 2006;29(9):2114-2116.
9. Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF.
Lifetime risk for diabetes mellitus in the United States. JAMA. 2003;290(14):
1884-1890.
10. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glu-
cose control with sulphonylureas or insulin compared with conventional treat-
ment and risk of complications in patients with type 2 diabetes (UKPDS 33)
[published correction appears in Lancet. 1999;354(9178):602]. Lancet. 1998;
352(9131):837-853.
11. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA. 10-Year
follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008
Oct 9;359(15):1577-1589. Epub 2008 Sep 10.
12. Selvin E, Marinopoulos S, Berkenblit G, et al. Meta-analysis: glyco-
sylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern
Med. 2004;141(6):421-431.
13. Action to Control Cardiovascular Risk in Diabetes Study Group. Effects
of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008 Jun
12;358(24):2545-2559. Epub 2008 Jun 6.
14. ADVANCE Collaborative Group. Intensive blood glucose control and
vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008 Jun
12;358(24):2560-2572. Epub 2008 Jun 6.
15. US Department of Health and Human Services, Centers for Disease
Control and Prevention. National diabetes fact sheet: general information and
national estimates on diabetes in the United States, 2005. www.diabetes.org
/uedocuments/NationalDiabetesFactSheetRev.pdf. Accessed November 10,
2008.
16. Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ; A1c-
Derived Average Glucose (ADAG) Study Group. Translating the A1C assay
into estimated average glucose values. Diabetes Care. 2008 Aug;31(8):1473-
1478. Epub 2008 Jun 7.
17. Harris MI. Racial and ethnic differences in health insurance coverage for
adults with diabetes. Diabetes Care. 1999;22(10):1679-1682.
18. Hu FB, Stampfer MJ, Haffner SM, Solomon CG, Willett WC, Manson
JE. Elevated risk of cardiovascular disease prior to clinical diagnosis of type 2
diabetes. Diabetes Care. 2002;25(7):1129-1134.
19. Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs
at least 4-7 yr before clinical diagnosis. Diabetes Care.1992;15(7):815-819.
20. Buell C, Kermah D, Davidson MB. Utility of A
1c
for diabetes screening
in the 1999-2004 NHANES population. Diabetes Care. 2007 Sep;30(9):2233-
2235. Epub 2007 Jun 11.
21. Saudek CD, Herman WH, Sacks DB, Bergenstal RM, Edelman D,
Davidson MB. A new look at screening and diagnosing diabetes mellitus. J
Clin Endocrinol Metab. 2008 Jul;93(7):2447-2453. Epub 2008 May 6.
22. Clement S, Braithwaite SS, Magee MF, et al; Diabetes in Hospitals
Writing Committee. Management of diabetes and hyperglycemia in hospitals
[published corrections appear in Diabetes Care. 2004;27(3);856 and 2004;
27(5):1255]. Diabetes Care. 2004;27(2):553-591.
23. Basta G, Schmidt AM, De Caterina R. Advanced glycation end products
and vascular inflammation: implications for accelerated atherosclerosis in
diabetes. Cardiovasc Res. 2004;63(4):582-592.
24. Chalmers J, Cooper ME. UKPDS and the legacy effect [editorial]. N
Engl J Med. 2008;359(15):1618-1620.
25. Nathan DM, Cleary PA, Backlund JY, et al; Diabetes Control and
Complications Trial/Epidemiology of Diabetes Interventions and Complica-
tions (DCCT/EDIC) Study Research Group. Intensive diabetes treatment and
cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;
353(25):2643-2653.
26. Nathan DM, Davidson MB, DeFronzo RA, et al. Impaired fasting glu-
cose and impaired glucose tolerance: implications for care. Diabetes Care.
2007;30(3):753-759.
27. Diabetes Prevention Program Research Group. Reduction in the inci-
dence of type 2 diabetes with lifestyle intervention or metformin. N Engl J
Med. 2002;346(6):393-403.
28. Zhang P, Engelgau MM, Valdez R, Benjamin SM, Cadwell B, Narayan
KM. Costs of screening for pre-diabetes among US adults: a comparison of
different screening strategies. Diabetes Care. 2003;26(9):2536-2542.