Diabetes Mellitus 1
Diabetes Mellitus 1
Diabetes Mellitus 1
• 2. Glucokinase (MODY 2)
• 3. HNF-1 (MODY 3)
• 4. Insulin promoter factor-1 (IPF-1; MODY 4)
• 5. HNF-1 (MODY 5)
• 6. NeuroD1 (MODY 6)
• 7. Mitochondrial DNA
• 8. Subunits of ATP-sensitive potassium channel
• 9. Proinsulin or insulin conversion
Classification
• III. Other specific types of diabetes
– B. Genetic defects in insulin action
• 1. Type A insulin resistance
• 2. Leprechaunism
• 3. Rabson-Mendenhall syndrome
• 4. Lipodystrophy syndromes
– C. Diseases of the exocrine pancreas—pancreatitis,
pancreatectomy, neoplasia, cystic fibrosis,
hemochromatosis, fibrocalculous pancreatopathy,
mutations in carboxyl ester lipase
– D. Endocrinopathies—acromegaly, Cushing's
syndrome, glucagonoma, pheochromocytoma,
hyperthyroidism, somatostatinoma, aldosteronoma
Classification
• III. Other specific types of diabetes
– E. Drug- or chemical-induced—Vacor, pentamidine, nicotinic
acid, glucocorticoids, thyroid hormone, diazoxide, -adrenergic
agonists, thiazides, phenytoin, -interferon, protease inhibitors,
clozapine
– F. Infections—congenital rubella, cytomegalovirus, coxsackie
– G. Uncommon forms of immune-mediated diabetes—"stiff-
person" syndrome, anti-insulin receptor antibodies
– H. Other genetic syndromes sometimes associated with
diabetes—Down's syndrome, Klinefelter's syndrome, Turner's
syndrome, Wolfram's syndrome, Friedreich's ataxia, Huntington's
chorea, Laurence-Moon-Biedl syndrome, myotonic dystrophy,
porphyria, Prader-Willi syndrome
• IV. Gestational diabetes mellitus (GDM)
Epidemiology
• from an estimated 30 million cases in 1985
to 177 million in 2000
• Based on current trends, >360 million
individuals will have diabetes by the year
2030
• 6 of the top 10 countries with the highest
rates are in Asia
Epidemiology
• In the United States,
– 20.8 million persons (7%) of the population, had
diabetes in 2005
– ~30% of individuals with diabetes were undiagnosed
– Approximately 1.5 million individuals (>20 years) were
newly diagnosed with diabetes in 2005.
– DM increases with aging. In 2005, the prevalence of
DM in the United Sates was estimated to be 0.22% in
those <20 years and 9.6% in those >20 years. In
individuals >60 years, the prevalence of DM was
20.9%
Epidemiology
• Scandinavia has the highest incidence of type 1
DM
– Finland, the incidence is 35/100,000/year
– Japan and China, the incidence is 1–3 /100,000/year
of type 1 DM
– Northern Europe and the United States have an
intermediate rate (8–17/100,000 per year)
• Prevalence of type 2 DM and its harbinger, IGT
– Highest in certain Pacific islands
– Intermediate in countries such as India and the
United States
– Relatively low in Russia
Epidemiology
• Variability is due to genetic, behavioral, and
environmental factors DM prevalence also varies among
different ethnic populations within a given country
• In 2005, the CDC estimated that the prevalence of DM in
the United States (age > 20 years) was
– African Americans, 13.3%
– Latinos, 9.5%
– Native Americans (American Indians and Alaska natives), 15.1%
– non-Hispanic whites. 8.7%
– Individuals belonging to Asian-American or Pacific-Islander
ethnic groups in Hawaii are twice as likely to have diabetes
compared to non-Hispanic whites
Diagnosis
• Criteria for the Diagnosis of Diabetes Mellitus
– Symptoms of diabetes plus random blood glucose
concentration 11.1 mmol/L (200 mg/dL)aor
– Fasting plasma glucose 7.0 mmol/L (126 mg/dL)bor
– Two-hour plasma glucose 11.1 mmol/L (200 mg/dL)
during an oral glucose tolerance testc
– HbA1c of > 6.5
• aRandom is defined as without regard to time since the last meal.
• bFasting is defined as no caloric intake for at least 8 h.
• cThe test should be performed using a glucose load containing the equivalent of 75 g
anhydrous glucose dissolved in water; not recommended for routine clinical use.
• Note: In the absence of unequivocal hyperglycemia and acute metabolic decompensation,
these criteria should be confirmed by repeat testing on a different day.
• Source: Adapted from American Diabetes Association, 2007.
Diagnosis
• Glucose tolerance is classified into three
categories based on the FPG
– (1) FPG < 5.6 mmol/L (100 mg/dL) is considered normal
– (2) FPG = 5.6–6.9 mmol/L (100–125 mg/dL) is defined as IFG;
and
– (3) FPG 7.0 mmol/L (126 mg/dL) warrants the diagnosis of DM.
• Alimentary (postgastrectomy)
• Noninsulinoma pancreatogenous hypoglycemia
syndrome
– In the absence of prior surgery
– Following Roux-en-Y-gastric bypass
• Other causes of endogenous hyperinsulinism
• Hereditary fructose intolerance, galactosemia
• Idiopathic
Normal hypoglycemic counterregulation.
Response Glycemic Physiologic Role in the Prevention or
Threshold, mmol/L Effects Correction of
(mg/dL) Hypoglycemia (Glucose
Counterregulation)
Decrease Insulin 4.4–4.7 (80–85) Increase Ra Primary glucose regulatory
(decrease Rd) factor/first defense against
hypoglycemia
Increase 3.6–3.9 (65–70) Increase Ra Primary glucose
Glucagon counterregulatory factor/second
defense against hypoglycemia
Increase 3.6–3.9 (65–70) Increase Ra, Third defense against
Epinephrine Decrease Rc hypoglycemia, critical when
glucagon is deficient
Increase 3.6–3.9 (65–70) Increase Ra, Involved in defense against
Cortisol and growth Decrease Rc prolonged hypoglycemia, not
hormone critical