DIABETES

MELLITUS
 Worldwide prevalence of
diabetes in 2030 (projected)

Number of persons
< 5000
500074,000
75,000349,000
350,0001,499,000
1,500,0004,999,000
> 5,000,000
No data available
Total cases > 370 million adults
World Health Organization, 2003
www.who.int/diabetes/facts/world_figures/en/ (accessed September 2004).
Countries with the highest numbers of
estimated cases of diabetes for 2030
Egypt
Philippines
Japan
Bangladesh
Brazil
Pakistan
Indonesia
USA
China
India
0 20 40 60 80 100

People with diabetes (millions)

Adapted from Wild SH et al. Diabetes Care 2004; 27: 256970.

 DEFINITION OF DIABETES
MELLITUS
Diabetes mellitus is a group of metabolic
diseases characterized by hyperglycemia resulting
from defects in insulin secretion, insulin action,
or both.
The chronic hyperglycemia of diabetes is
associated with long-term damage, dysfunction,
and failure of various organs, especially the eyes,
kidneys, nerves, heart, and blood vessels.
 Common Symptoms
Classic symptoms Others sympmtoms
increased hunger fatigue

increased thirst tingling or numbness in

hands and feet
frequent urination
recurring infections
weight loss
gums, skin, lung, urinary
bladder
slow healing
blurred vision
pruritus vulvae
erectile dysfunction
 Diagnosis of Diabetes Mellitus
1. Symptoms of diabetes and a casual plasma glucose 200 mg/dl (11.1
mmol/l). Casual is defined as any time of day without regard to time
since last meal. The classic symptoms of diabetes include polyuria,
polydipsia, and unexplainedweight loss.
OR
2. FPG 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake
for at least 8 h.
OR
3. 2-h plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTT. The
test should be performed as described by the World Health
Organization, using a glucose load containing the equivalent of 75-g
anhydrous glucose dissolved in water.
In the absence of unequivocal hyperglycemia, these criteria should be confirmed by repeat testing on a different
day. The OGTT is not recommended for routine clinical use, but may be required in the evaluation of patients with
IFG (see text) or when diabetes is still suspected despite a normal FPG as with the postpartum evaluation of
women with GDM.
 ADA definition of hyperglycaemic states
Criteria for the diagnosis of diabetes
Symptoms of diabetes plus casual plasma glucose 200 mg/dl (11.1 mmol/l)
or

FPG
< 100 mg/dl (5.6 mmol/l) normal fasting glucose
100125 mg/dl (5.66.9 mmol/l) impaired fasting glucose
126 mg/dl (7.0 mmol/l) diabetes

or
OGTT 2-h post-load glucose
< 140 mg/dl (7.8 mmol/l) normal glucose tolerance
140199 mg/dl (7.811.1 mmol/l) impaired glucose tolerance
200 mg/dl (11.1 mmol/l) diabetes

ADA = American Diabetes Association

Adapted from American Diabetes Association. Diabetes Care 2004; 27:S5S10.

 Criteria for screening for diabetes in
asymptomatic adult individuals
Testing for diabetes should be considered in all individuals :
at age 45 years (BMI >25 kg/m2)
at a younger age ; overweight (BMI >23 kg/m2*) and have
additional risk factors, as follows:
are habitually physically inactive
have a first-degree relative with diabetes
have delivered a baby weighing >4 kg or have been diagnosed
with GDM
are hypertensive (>140/90 mmHg)
have an HDL-C level 35 mg/dl and/or a TG level 250 mg/dl
have PCOS
on previous testing, had IGT or IFG
have other clinical conditions associated with insulin resistance
have a history of vascular disease
CLASSIFICATION OF DIABETES
MELLITUS

1. Type 1 diabetes (cell destruction, usually

leading to absolute insulin deficiency)
2. Type 2 diabetes (ranging from predominantly
insulin resistance with relative insulin
deficiency to predominantly an insulin
secretory defect with insulin resistance)
3. Other specific types of diabetes
4. Gestational diabetes mellitus (GDM)
 Type 1 diabetes
Immune-mediated diabetes.
510% of those with diabetes;
absolute insulin deficiency (insulin dependent
diabetes, type I diabetes, or juvenile-onset diabetes)
cellular-mediated autoimmune destruction of the -
cells of the pancreas.
markers of the immune destruction of the -cell
include
islet cell autoantibodies, autoantibodies to insulin,
autoantibodies to glutamic acid decarboxylase (GAD65),
autoantibodies to the tyrosine phosphatases IA-2 and IA-2.

Idiopathic diabetes.
no known etiologies
 Other specific types of diabetes
A. Genetic defects of -cell function
Chromosome 12, HNF-1 (MODY3); Chromosome 7,
glucokinase (MODY2); Chromosome 20, HNF-4 (MODY1);
Chromosome 13, insulin promoter factor-1 (IPF-1;
MODY4); Chromosome 17, HNF-1 (MODY5);
Chromosome 2, NeuroD1 (MODY6); Mitochondrial DNA
B. Genetic defects in insulin action
Type A insulin resistance; Leprechaunism; Rabson-
Mendenhall syndrome; Lipoatrophic diabetes.
C. Diseases of the exocrine pancreas
Pancreatitis; Trauma/pancreatectomy; Neoplasia; Cystic
fibrosis; Hemochromatosis; Fibrocalculous pancreatopathy.
D. Endocrinopathies
Acromegaly; Cushings syndrome; Glucagonoma;
Pheochromocytoma; Hyperthyroidism; Somatostatinoma;
Aldosteronoma.
 Other specific types of diabetes
E. Drug- or chemical-induced
Vacor; Pentamidine; Nicotinic acid; Glucocorticoids; Thyroid
hormone; Diazoxide; adrenergic agonists; Thiazides; Dilantin;
Interferon.
F. Infections
Congenital rubella; Cytomegalovirus.
G. Uncommon forms of immune-mediated diabetes
Stiff-man syndrome; Antiinsulin receptor antibodies.
H. Other genetic syndromes sometimes associated with
diabetes
Downs syndrome; Klinefelters syndrome; Turners
syndrome; Wolframs syndrome; Friedreichs ataxia;
Huntingtons chorea; Laurence-Moon-Biedl syndrome;
Myotonic dystrophy; Porphyria; Prader-Willi syndrome
 Gestational diabetes mellitus (GDM)
Any degree of glucose intolerance with onset during
pregnancy
Return to normal glucose regulation after delivery is
common
Increased perinatal morbidity and mortality if untreated

Risk assessment for GDM should be

undertaken at the first prenatal visit.
Women with clinical characteristics
consistent with a high risk for GDM (those
with marked obesity, personal history of
GDM, glycosuria, or a strong family history
of diabetes) should undergo glucose testing
as soon as possible
Gestational diabetes mellitus (GDM)
Diagnostic criteria for the 100-g OGTT are as
follows:
95 mg/dl fasting, 180mg/dl at 1 h, 155 mg/dl
at 2 h, and 140 mg/dl at 3 h.
Two or more of the plasma glucose values must be
met or exceeded for a positive diagnosis.
The test should be done in the morning after an
overnight fast of 814 h.
 Type 2 diabetes

Type 2 diabetes is characterised by:

chronic hyperglycaemia with disturbances of
carbohydrate, fat and protein metabolism
defects in insulin secretion (-cell dysfunction)
and insulin action (insulin resistance)

Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Department of Noncommunicable
Disease Surveillance, World Health Organization, Geneva 1999.
What is insulin resistance?
Definition of Insulin Resistance :
Impaired response to the physiological effects of
insulin, including those on glucose, lipid, protein
metabolism and vascular endothelial function
Receptor:
Quantity / function
Post-receptor (mostly):
Translocation of GLUT
Synthesis of GLUT
ADA. Consensus Development on Insulin Resistance. 1997
Insulin resistance and -cell dysfunction
are fundamental to type 2 diabetes
Normal IGT Type 2 diabetes

Insulin Increased insulin

resistance resistance

Insulin Hyperinsulinaemia,
secretion then -cell failure

Post- Abnormal
prandial glucose tolerance
glucose
Fasting Hyperglycaemia
glucose

Adapted from Type 2 Diabetes BASICS. International Diabetes Center, Minneapolis, 2000.
 Insulin Resistance and -Cell Dysfunction
Produce Hyperglycemia in Type 2 Diabetes
-Cell Dysfunction Insulin Resistance
Increased
Pancreas Lipolysis

Elevated
Liver Plasma FFA

Islet -Cell Degranulation;

Reduced Insulin Content
+ -
Muscle Adipose Tissue
Increased Glucose Output

Reduced
Plasma Insulin
Decreased Glucose Transport
& Activity (expression) of GLUT4
Hyperglycemia

Courtesy of S. Smith, GlaxoSmithKline

 Role of Free Fatty Acids in Hyperglycemia
Adipose
tissue insulin
resistance
ADIPOSE TISSUE

MUSCLE
Lipolysis LIVER

Muscle FFA mobilization

insulin
resistance Liver insulin
resistance
FFA oxidation FFA oxidation

Glucose utilization Gluconeogenesis

Hyperglycemia

Boden G. Proc Assoc Am Physicians. 1999;111:241-248.

Insulin Resistance: An Underlying Cause of
Type 2 Diabetes
Aging
Obesity and Medications
inactivity

Genetic Rare
abnormalities disorders
INSULIN
RESISTANCE
Type 2
diabetes PCOS

Hypertension Atherosclerosis
Dyslipidemia
Reaven GM. Physiol Rev. 1995;75:473-486
Clauser, et al. Horm Res. 1992;38:5-12.
 -cell dysfunction
Reduced ability of -cells to secrete
insulin
Impaired ability of -cells to compensate
for insulin resistance
Genetic
and environmental
pathophysiology

DeFronzo RA et al. Diabetes Care 1992; 15: 31854.

 Multiple factors may drive
progressive decline of b-cell function
Hyperglycaemia
(glucose toxicity)
Insulin resistance

Protein -cell lipotoxicity

glycation elevated FFA,TG
(genetic background)

Amyloid
deposition
 Management of
Diabetes Mellitus
 General Therapeutic Objectives

Achieve a normal blood glucose level (reduced

symptoms)
Minimize risk of long-term complications
(microvascular and macrovascular) resulting from
sustained high blood sugar.
Gain adequate control of diabetes by ensuring
compliance with a management plan.
Maintain a healthy lifestyle as near normal as possible.
 The principle of management
Education of diabetes
Lifestyle management
Diet
Exercise

Interventional of pharmacology
Oral treatment
Insulin
 Basic education
1. Survival skills
How to make prescribe medication
Timing, action of medication, technique for
administration (insulin)
How to test blood glucose
Warning sign of hypo/hyperglycemia
Basic nutrition guidelines
Food types, timing of meal, balancing content and
quantity
2. Lifestyle management issues
 Lifestyle ManagementDiet &
Exercise
Diet -- Three important components
Enough nutrition to meet energy demands
Food intake distributed throughout the day
Feeding pattern and amounts should be consistent
Exercise
Helps decrease blood glucose levels
Have physician approve exercise program
Adjust meals & medications accordingly
3-4 times per week usually recommended (30
minute)
 Nutritional Recomendation
Energy needs
Basal energy requirements (BER) : 25-30 kcal/kg of
desirable body weight
Desirable body weight/Ideal body weight (IBW) :
Formula Brocca modified: 90%x {Body Length (cm)-
100}x1kg
Additional energy required for activity level
Sedentary 10% of BER
Moderate 20% of BER
Strenuous 50% of BER

Obese patients : reduced energy 20-30% of BER

 Nutritional Recommendations for All
Persons with Diabetes
Protein to provide 1520% of kcal/d (10% for those with
nephropathy)
Saturated fat to provide <7% of kcal/d (7% for those with
elevated LDL)
Polyunsaturated fat to provide <10% of kcal;avoid trans-
unsaturated fatty acids
6070% of calories to be divided between carbohydrate and
monounsaturated fat, based on medical needs and personal
tolerance;glycemic index of food not as important
Use of caloric sweeteners, including sucrose, is acceptable.
Fiber (2035 g/d) and sodium (<3000 mg/d) levels as
recommended for the general healthy population
Cholesterol intake <300 mg/d
 Physical exercise and insulin resistance
Exercise
muscle glucose uptake
whole body glucose disposal
} acute &
long-term

risk of developing Type 2 DM

GLUT4 is recruited to the plasma membrane
independently of insulin
Effective in Type 2 diabetics because muscle GLUT4
expression is normal
Regular exercise has been shown to improve blood
glucose control, reduce cardiovascular risk factors,
contribute to weight loss, and improve well-being.
Recommendations of physical activity
Initial physical activity recommendations should
be modest, based on the patients willingness
and ability, gradually increasing the duration and
frequency to 30 45 min of moderate aerobic
activity 35 days per week, when possible.
Greater activity levels of at least 1 h/day of
moderate (walking)or 30 min/day of vigorous
(jogging) activitymay be needed to achieve
successfullong-term weight loss.
 Oral Therapy for Type 2 Diabetes
Target Sites of Action
Sulfonylureas
Pancreas
Repaglinide Gut
Adipose
Insulin secretion
tissue
Glucose Acarbose
uptake
Miglitol
FFA output
Glucose
Rosiglitazone Hyperglycemia absorption
Pioglitazone

Liver Muscle
Metformin Rosiglitazone
Rosiglitazone Hepatic Pioglitazone Glucos
Pioglitazone glucose Metformin e uptake
output
 Oral Drug Therapy for Type 2 DM

Sulfonylureas
Repaglinide
Nateglinide
} Insulin secretagogues

Biguanides
Thiazolidinediones }
Insulin sensitizers

Acarbose
}
Inhibitors of CHO
absorption
Sulfonylureas : Mechanism action
Pancreatic effect
Specific receptor on the surface of pancreatic
beta cell bind the suflfonilurea receptors (SUR)
There is a family of SUR, Sur 1/Kir6.2 is found
in B cellsand the brain.
SUR 2A/Kir6.2 is found in cardiac and skeletal
muscle
Extrapancreatic effect
Studied in vitro and vitro
In human studies; enhances insulin-stimulated
perpheral glucose utilization in both adipose
tissue and skeletal muscle.
 Sulfonylureas: Mechanism of Action

Sulfonylureas
GLUT2 Na+
K+ -
Na+ KIR K+
K+
Vm
K+
Ca2+ -
Pancreatic Ca2+
Voltage-gated
cell Ca2+ channel
Ca2+

Insulin granules
 First Generation Sulfonylureas
Name Daily Max daily Doses/day
dose dose
range (mg/day)
Tolbutamide* 500-3000 3000 2-3
Chlorpropamide 100-500 500 1
Tolazamide * 100-1000 1000 1-2
Acetohexamide* 250-1500 1500 1-2

*not available
 Second Generation Sulfonylureas
Name Daily Max daily Doses/day
dose dose
range (mg/day)
(mg/day)
Glibenclamide 1.25-2.50 20 1-2
Glipizide 2.5-40 40 1-2
Glipizide XL 5-20 20 1
Gliclazide 40-320 320 1-2
Glimepiride 4-8 8 1
Sulfonylureas: Metabolism & Excretion
Metabolized in the liver
Hepatic dysfunction will alter pharmacokinetics
Excretion
Second generation: significant fecal excretion
Glybenclamide -50%
Glimeperide - 40%
 Clinical Uses of Sulfonylureas

Hypoglycemic agents for treatment of Type 2

diabetes mellitus
Act by increasing endogenous insulin secretion \
not indicated for Type 1
Most effective when cell function has not been
severely compromised
Increased insulin secretion favors lipogenesis
Most appropriate in non- or mildly obese
Up to 160 % of ideal body weight
 Adverse Effects of Sulfonylureas
Severe hypoglycemia
Overdose
Early in treatment
Most common with glybenclamide
Weight gain
Erythema, skin reactions
Blood dyscrasias (abnormal cellular elements)
Hepatic dysfunction and other GI disturbances
 Contraindications for Sulfonylureas
Pregnancy
Surgery
Severe infections
Severe stress or trauma
Severe hepatic or renal failure

Insulin therapy should be used in all of these

 Repaglinide and Nateglinide
Mechanism of action:
decrease ATP-sensitive K+ conductance
Additional high affinity binding site identified in
mouse -cells for repaglinide
Action is glucose dependent
High potency
Elicited insulin release is rapid and brief
Taken with meals for postprandial hyperglycemia
Reduced risk of long-lasting hypoglycaemia
 Biguanides
First Generation- Phenformin
Phenethylbiguanide
Adverse Effects
Lactic acidosis
Risk of cardiovascular disorder

Second Generation- Metformin

1,1-Dimethylbiguanide
Rarely produces lactic acidosis except
under predisposing conditions
 Biguanides
Mechanism of action: antihyperglycemic
Correct elevated hepatic glucose output
Inhibit gluconeogenesis
Inhibit glucose-6-phosphatase activity glycogen
sparing
insulin resistance
Mediated by activation of 5AMP-activated protein
kinase (AMPK) in hepatocytes and muscle
Do not increase insulin secretion
Not hypoglycemic, even at high doses
 Second Generation Biguanides
Do not produce hypoglycemia
Secondary beneficial effects on lipids
Reduced triglycerides
Reduced total cholesterol
Reduced LDL
Increased HDL

Insulin levels unchanged or reduced

Weight loss, some reduction of blood pressure
Appropriate for obese Type 2 diabetics
 Metformin
Excreted unchanged in the urine
Half-life - approximately 2 hours
Does not bind to plasma proteins
Should not be used with renal or hepatic
dysfunction
Also approved for prevention of Type 2
diabetes in high risk individuals
Use also for polycystic ovary syndrome:
insulin resistance with ovarian
hyperandrogenism
 Thiazolidinediones
CH3
Antihyperglycemic N N
O
S O

Do not increase NH
ROSIGLITAZONE O
insulin secretion
Increase insulin
sensitivity in liver N O
S O

and muscle PIOGLITAZONE O

NH

Reduce hepatic glucose output

Improve lipid profiles
Thiazolidinediones: Mechanism of Action

Ligands for PPARg:

(Peroxisome proliferator-activated receptorg)
Nuclear hormone receptor superfamily
Expressed primarily in fat, regulates differentiation
More limited expression in muscle, heart, liver,
kidney, gut, macrophages
Heterodimerizes with RXR, binds to hormone
response elements, regulates gene transcription
Known natural ligands (low affinity)
Prostanoid 15-deoxy12,14PG J2
Polyunsaturated fatty acids, such as linoleic acid
 Insulin resistance
Insulin Glucose

Translocation
Insulin
receptor
X

X Synthesis GLUT 4
PPARg +RXR mRNA

PPRE transcription
promoter Coding reg
Muscle
Cells

Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2nd Ed.
 TZD reduce insulin resistance
Insulin Glucose

Insulin
receptor

Synthesis GLUT 4
PPARg + RXR mRNA

PPRE transcription
promoter Coding reg
Muscle
Cells

Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2nd Ed.
 Thiazolidinediones: Rosiglitazone
Bioavailability of oral dose is 99%
Metabolites have no significant activity
Excreted in urine and feces
Half-life: plasma half-life is 3 to 4 hours
Extensively (99.8%) bound to albumin
Potency: 4 to 8 mg/day
As single dose or divided into 2 doses
No evidence of drug-induced hepatotoxicity
Should not be used in patients who experienced
jaundice
 Thiazolidinediones: Pioglitazone
Some metabolites pharmacologically active
Excreted primarily in the feces
Half-life: plasma half-life is 3 to 7 hours
16 to 24 hours for metabolites
Extensively (>99%) bound to albumin
Potency: 15 to 45 mg/day
Given as a single dose
No evidence of drug-induced hepatotoxicity
Should not be used in patients who experienced
jaundice
 a glucosidase inhibitors (Acarbose)
Mechanism of action: competitive and reversible
inhibitors of a glucosidase in the small intestine
Delay carbohydrate digestion and absorption
Smaller rise in postprandial glucose

Clinical use
For mild to moderate fasting hyperglycemia with significant
postprandial hyperglycemia
Taken with the first bite of a meal

Adverse effects:
Gastrointestinal
disturbances; Flatulence, nausea, diarrhea
Use gradual dose titration
 Clinical Uses of Insulin
Type 1 diabetes mellitus
Type 2 diabetes mellitus uncontrolled on maximal
combination therapy with oral agents
Gestational diabetes
Hyperglycemic emergencies
Total pancreatectomy patients
Acute or chronic hyperglycemia provoked by:
Infection or trauma
Steroid therapy
Endocrinopathies such as hyperthyroidism
Other types of secondary diabetes
 Insulin Preparations

Sources of Insulin for Clinical Use

Human insulin produced by recombinant technology has
replaced bovine and porcine insulin preparations
Insulin associates as hexamers in solution
The rate-limiting step for capillary absorption is the
subcutaneous dissociation into dimers and then
monomers
Insulin preparations are formulated to differ in their
peaks and durations of action on the basis of factors
which alter this rate of dissociation
Summary of bioavailability characteristic
of the insulin
Insulin Type Onset Peak Action Duration

Ultra short Insulin 5-15 1-1,5 hours 3-4 hours

acting lispro/aspart minutes
Short-acting regular 15-30 1-3 hours 5-7 hours
minutes
Intermediate Lente, NPH 2-4 hours 8-10 hours 18-24 hours
acting
Long acting Ultralente 4-5 hours 8-14 hours 25-36 hours

Insulin 6-8 hours - 24 hours

glargine
 Insulin Preparations
Ultra fast/ultra
Lispro/aspart
short-acting

Short-acting regular

Plasma [Insulin]
Intermediate- NPH
acting

lente
Long-acting ultralente

Ultra long-acting glargine

0 4 8 12 16 20 24
 Short-acting insulin
Ultra Short-acting insulin
Insulin lispro/aspart
monomeric
not antigenic
the most rapidly acting insulin
used within 15 minutes of beginning a meal
short duration of action- must be used with longer-acting preparation
for Type 1 diabetes unless used for continuous infusion
Regular insulin (insulin injection)
denoted on vial by R
zinc insulin crystals in a neutral, nonbuffered, suspending
solution
can be given I.V.
 Intermediate-acting insulin
NPH insulin (Neutral protamine Hagedorn,
isophane insulin suspension)
denoted on vial by N
stoichiometric mixture of regular and protamine zinc
insulin (complexed with excess of positively charged
fish sperm protamine)
LENTE insulin (insulin zinc suspension)
denoted on vial by L
30% SEMILENTE insulin (amorphous precipitate of
insulin with zinc in acetate buffer)
70% ULTRALENTE insulin
 Long-acting insulin
ULTRALENTE insulin (extended insulin zinc suspension)
denoted on vial by U
delayed onset
prolonged action
acetate buffer
excess zinc large crystals with low solubility
Insulin glargine
Recombinant insulin analog that precipitates in the neutral
environment of subcutaneous tissue
Peakless- prolonged action
Administered as single bedtime dose
 Insulin treatment regimens
Conventional insulin treatment
1 or 2 daily subcutaneous injections
mixture of short- and intermediate or long-acting
insulins
total

regular

lente

4 8 12 4 8 12 4 8 12
am pm am
 Insulin treatment regimens
Intensive insulin treatment
Frequent monitoring of blood glucose
3 or more daily injections of insulin
Some regular alone, some combined regular and
intermediate- or long-acting
Adjusted to needs of individual patient
4 8 12 4 8 12 4 8 12
regular am pm am
lente

4 8 12 4 8 12 4 8 12
am pm am
lispro
glargine

4 8 12 4 8 12 4 8 12
am pm am
 Insulin treatment regimens
Continuous subcutaneous insulin infusion
Insulin pump with lispro or regular insulin
Programmed basal delivery
allows control of dawn phenomenon
Patient-triggered bolus before meals

Continuous
infusion
regular or
4 8 12 4 8 12 4 8 12
lispro am pm am
 Other Factors Affecting Insulin
Pharmacokinetics
Method of injection
Standard- subcutaneous
Intradermal- poor absorption
Intramuscular - accelerated absorption
Rate of blood flow through injection site
Site of injection
absorption from abdomen or buttock faster than
from thigh or deltoid
Ambient temperature
Exercise
Adverse Effects of Insulin Therapy
Hypoglycemia
Especially dangerous in Type 1 diabetics
Glucose or glucagon treatment
Allergy and resistance to insulin
Local cutaneous reactions or systemic
Switch to less antigenic form or desensitization
Lipohypertrophy
Due to lipogenic effect of insulin when small area used for frequent
injections
Absorption from such sites is unpredictable
Lipoatrophy
Due to impurities: switch to highly purified insulin
Lipogenic effect of insulin can repair lesion
Insulin edema- transient, rare
 Treatment of Type 2 Diabetes
Diet and exercise
Monotherapy with oral agent
postprandial hyperglycemia: acarbose, repaglinide
normal weight: sulfonylurea
obese: biguanide, TZD
Combination therapy with oral agents: additive
acarbose with biguanide, sulfonylurea, or TZD
sulfonylurea with biguanide or TZD
biguanide with TZD
Insulin +/- oral agent
oral agent with bedtime insulin
oral agent with lispro
TERIMA KASIH