Diabetes Mellitus in the year 2000

Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus in the year 2000 Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus

Diabetes Mellitus in the year 2000 Definition Description Classification Diagnostic criteria Testing for diabetes

Definition Diabetes Mellitus is a group of metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The chronic hyperglycemia of diabetes is associated with log-term damage, dysfunction, and failure of various organs, especially the eyes, Kidneys, nerves, heart, and blood vessels.

Insulin deficiency Insulin resistance Description Blood glucose Symptoms: Polyuria and polydipsia. Weight loss with polyphagia. Blurred vision. Infection susceptibility. DKA or NKHS.

Types Type 1 Type 2 Types & Stages Normal Hyperglycemia Other Specific glucose regulation Impaired Glucose Tolerance or Impaired Fasting Glucose Diabetes Mellitus Not Insulin Insulin insulin requiring requiring requiring for control for survival Type 1 Type 2 Other Specific Types These patients can briefly return to normoglycemia Vacor toxicity may require insulin for survival Gestational Diabetes Type 1 diabetes presenting in pregnancy may require insulin for survival

Other specific types of diabetes Normal Hyperglycemia Stage & Aetiology Normal glucose tolerance ( achieved without Pharmacological agents) Impaired Glucose and / or fasting hyperglycemia Diabetes Mellitus Not Insulin Insulin insulin requiring requiring requiring for control for survival Aetiology Islet cell destruction: Autoimmune Idiopathic Predominantly insulin resistance Predominantly insulin secretory defects Other specific disorders ( eg MODY, Endocrinopathies ) Type 1 diabetes Type 2 diabetes Other specific types of diabetes Gestational Diabetes Gestational diabetes

III- Other specific types. Etiologic classification of diabetes mellitus I- Type 1 diabetes: II- Type 2 diabetes. III- Other specific types. IV- Gestational diabetes mellitus.

Etiologic classification of A. Immune mediated: diabetes mellitus I- Type 1 diabetes: A. Immune mediated: Cellular-mediated autoimmunity. Markers: Islet cell autoantibodies ( ICAs ). Autoantibodies to insulin ( IAAs ). Autoantibodies to glutamic acid decarboxylase ( GAD ). Autoantibodies to the tyrosine phosphatase IA-2 and IA-2B. HLA: HLA-DR/DQ alleles can be either predisposing or protective. B lymphocyte T lymphocyte Beta cell

Autoimmune destruction Etiologic classification of diabetes mellitus I- Type 1 diabetes: Autoimmune destruction Environmental: Viral infection Obesity Multiple genetic: Graves’ disease Hashimoto’s thyroiditis Addison’s disease Vitiligo Pernicious anemia

Etiologic classification of diabetes Presentation mellitus I- Type 1 diabetes: Presentation Beta cell destruction: Rapid infants and children Slow adults Presentation: DKA children and adolescents Hyperglycemia adults Hyperglycemia to DKA Adults

Etiologic classification of diabetes B. Idiopathic: mellitus I- Type 1 diabetes: B. Idiopathic: No autoimmunity DKA Minority of patients Strongly inherited No HLA association Insulin requirement may come and go

II- Type 2 diabetes. Etiologic classification of Pathology: diabetes mellitus II- Type 2 diabetes. Pathology: Relative insulin deficiency ( initially). No Autoimmune destruction of  -cell. Obesity ( insulin resistance ). No DKA (some times with stress ie infection). Pass undiagnosed. Macro- & micro-vascular complications. Insulin is normal or high.

II- Type 2 diabetes. Etiologic classification of Pathology: diabetes mellitus II- Type 2 diabetes. Pathology: Relative insulin deficiency ( initially). No Autoimmune destruction of  -cell. Obesity ( insulin resistance ). No DKA (some times with stress ie infection). Pass undiagnosed. Macro- & micro-vascular complications. Insulin is normal or high.

II- Type 2 diabetes. Etiologic classification of Pathology: diabetes mellitus II- Type 2 diabetes. Pathology: Relative insulin deficiency ( initially). No Autoimmune destruction of  -cell. Obesity ( insulin resistance ). No DKA (some times with stress ie infection). Pass undiagnosed. Macro- & micro-vascular complications. Insulin is normal or high.

II- Type 2 diabetes. Etiologic classification of Pathology: diabetes mellitus II- Type 2 diabetes. Pathology: Relative insulin deficiency ( initially). No Autoimmune destruction of  -cell. Obesity ( insulin resistance ). No DKA (some times with stress ie infection). Pass undiagnosed. Macro- & micro-vascular complications. Insulin is normal or high.

II- Type 2 diabetes. Etiologic classification of Pathology: diabetes mellitus II- Type 2 diabetes. Pathology: Relative insulin deficiency ( initially). No Autoimmune destruction of  -cell. Obesity ( insulin resistance ). No DKA (some times with stress ie infection). Pass undiagnosed. Macro- & micro-vascular complications. Insulin is normal or high.

II- Type 2 diabetes. Etiologic classification of diabetes mellitus II- Type 2 diabetes. Risk factors: Age Obesity Lack of physical activity Women H/O G.D.M Hypertension Dyslipidemia Ethnic and racial subgroups Strong genetic predisposition Diabetes

III- Other specific types. Etiologic classification of diabetes mellitus III- Other specific types. Genetic defects of -cell function: Chromosome 12, HNF-1 (MODY3) Chromosome 7, glucokinase (MODY2) Chromosome 20, HNF-4 (MODY1) Mitochondrial DNA Others Genetic defects in insulin action: Type A insulin resistance Leprechaunism Rabson-Mendenhall syndrome Lipoatrophic diabetes Disease of the exocrine pancreas: Pancreatitis Trauma/pancreatectomy Neoplasia Cystic fibrosis Hemochromatosis Fibrocalculous pancreatopathy

III- Other specific types. Etiologic classification of diabetes mellitus III- Other specific types. Endocrinopathies: Acromegaly Cushing’s syndrome Glucagonoma Pheochromocytoma Hyperthyroidism Somatostatinoma Aldosteronoma Others Drug or chemical-induced: Vacor Dilantin Thiazides Diazoxide Neoplasia Pentamidine  - interferon Nicotinic acid Cystic fibrosis Glucocorticoids Thyroid hormone Hemochromatosis  -adrenergic agonists Fibrocalculous pancreatopathy

III- Other specific types. Etiologic classification of diabetes mellitus III- Other specific types. Infections: Congenital rubella Cytomegalovirus Others Uncommon forms of immune-mediated diabetes: “ Stiff-man “ syndrome Anti-insulin receptor antibodies Other genetic syndromes some times associated with diabetes: Down’s syndrome Klinefelter’s 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. Etiologic classification of diabetes mellitus IV- Gestational diabetes mellitus. Definition: Any degree of glucose intolerance with onset or first recognition during pregnancy. Prevalence: - 1 ~ 14% of the total pregnancies. - 90% of pregnancies complicated by diabetes. Importance: - Perinatal morbidity and mortality - Maternal complications - Risk factor for glucose intolerance

IV- Gestational diabetes mellitus. Etiologic classification of diabetes mellitus IV- Gestational diabetes mellitus. Diagnostic criteria: 1964 O’Sullivan and Mahan 1979 NDDG (National Diabetes Data Group) 1997 American Diabetes Association’s Fourth International Workshop-Conference on Gestational Diabetes Mellitus.

Screen all pregnant women Etiologic classification of diabetes mellitus IV- Gestational diabetes mellitus. Screening American Diabetes Association’s (1997) fourth international workshop-conference on gestational diabetes recommendations Screen all pregnant women ( 24-28 weeks of gestation ) Including: Average risk group: Including: High risk group: Marked obesity H/O GDM Glycosuria Strong FH Excluding: Low risk group: < 25 years of age Normal body weight - ve family history - ve H/O abn. glucose metabolism H/O poor obstetric outcome Ethnic group of low diabetes risk

 IV- Gestational diabetes mellitus. Etiologic classification of Screening American Diabetes Association’s (1997) fourth international workshop-conference on gestational diabetes recommendations Low risk group: No screening Average risk group: Two step approach High risk group: One step approach Glucose Challenge Test GCT ( 50 gm oral glucose load ) Glucose after 1hr  Oral Glucose Tolerance Test OGTT 75 or 100 FBS, 1hr, & 2hrs

IV- Gestational diabetes mellitus. Etiologic classification of diabetes mellitus IV- Gestational diabetes mellitus. Screening American Diabetes Association’s (1997) fourth international workshop-conference on gestational diabetes recommendations Low risk group: No screening Average risk group: Two step approach High risk group: One step approach Oral Glucose Tolerance Test OGTT 75 or 100 FBS, 1hr, & 2hrs

IV- Gestational diabetes mellitus. Etiologic classification of diabetes mellitus IV- Gestational diabetes mellitus. Diagnostic criteria 100-g Glucose load mg/dl mmol/l Fasting 95 5.3 1-h 180 10.0 2-h 155 8.6 3-h 140 7.8 75-g Glucose load mg/dl mmol/l Fasting 95 5.3 1-h 180 10.0 2-h 155 8.6

Impaired glucose tolerance IGT Impaired fasting glucose IFG Etiologic classification of diabetes mellitus Impaired glucose tolerance IGT Impaired fasting glucose IFG Normal Diabetic IGT IGF IGT WHO criteria IGF FPG = 110 - 126 mg/dL 6.1 - 7.0 mmol/L Why

Impaired glucose tolerance IGT Impaired fasting glucose IFG Etiologic classification of diabetes mellitus Impaired glucose tolerance IGT Impaired fasting glucose IFG

Impaired glucose tolerance IGT Impaired fasting glucose IFG Etiologic classification of diabetes mellitus Impaired glucose tolerance IGT Impaired fasting glucose IFG They are known risk factors for future diabetes and cardiovascular disease. Intermediate stage for all types of diabetes. Associated with insulin resistance syndrome or : Syndrome X : Insulin resistance Hyperinsulinemia Obesity Dyslipidemia ( high triglyceride and/or low HDL ) Hypertension

1 2 3 Diagnostic criteria for diabetes mellitus Etiologic classification of diabetes mellitus Diagnostic criteria for diabetes mellitus The new criteria Symptoms of diabetes ( polyuria, polydepsia, and weight loss ) + Random Blood Sugar ( RBS ) casual plasma glucose = or > 200 mg/dL ( 11.1 mmol/L ) 1 2 3 Fasting plasma glucose ( FPG ) at least 8hours fast = or > 126 mg/dL ( 7.0 mmol/L ) Two hours plasma glucose (2PG ) after 75 anhydrous glucose in water = or > 200 mg/dL ( 11.1 mmol/L )

Impaired fasting glucose IFG Etiologic classification of diabetes mellitus Impaired fasting glucose IFG For epidemiological studies FPG is: standardization Facilitation Cheep Diagnosis New criteria WHO criteria mg/dL mmol/L mg/dL mmol/L Normal <110 <6.1 < 140 < 7.8 IFG / IGT 110 - <126 6.1- < 7.0 140 - < 200 7.8 - <11.1 ? DM = or > 126 = or > 7.0 = or > 200 = or > 11.1  8 hours over night fast.  2 hours post 75 gm glucose load.

Old and new diagnostic criteria Etiologic classification of diabetes mellitus Old and new diagnostic criteria The criteria New case Diabetes Discovered Prevalence Known cases No 7.92% WHO criteria 6.34% 14.26% New criteria 4.35% 12.27% - 1.99 14% The new criteria will lead to 14% ( slightly ) lower estimates of diabetes prevalence. Data from NHANES III for individuals 40-74 years old.

Testing healthy individuals Etiologic classification of diabetes mellitus Testing healthy individuals Type 1 diabetes: More than one antibodies ( ICA, IAA, GAD, IA-2 ) No effective method can prevent or delay the disease Screening is not cost-effective Type 2 diabetes: 50% of type 2 are undiagnosed Chronic complications precede diabetes ( Retinopathy 7 years ) Risk factors

HbA1c Etiologic classification of diabetes mellitus Not recommended for diagnosis of diabetes, but valuable for glycemic control of diabetes.

Criteria for testing asymptomatic individuals Etiologic classification of diabetes mellitus Criteria for testing asymptomatic individuals All individual above 45 years of age every 3 years Any individual with:  Obese ( > 120% desirable weight or BMI > 27 ).  +ve F/H first degree relatives.  High risk ethnic population.  H/O GDM or big baby ( > 9 lb ).  Hypertension > 140/90  HDL < 35mg/dl ( 0.9 mmol/l ) ±  Triglyceride > 250mg/dl ( 2.82 mmol/l )  Known to have IGT or IFG