Diabetes mellitus definition,classification,clinical features ,investigation

1. DIABETES MELLITUS DEFINATION, CLASSIFICATION , CLINICAL FEATURES and Investigations Farrukh Masood , nmc

2. definition Diabetes 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 different organs, especially the eyes, kidneys, nerves, heart, and blood vessels . (American Diabetes Association) According to WHO Diabetes is if Fasting Glucose =>7mmol or 126mg/dl Random Glucose =>11.1mmol or 200mg/dl

3. insulin Human Insulin is a 51 amino acid dimeric protein composed of alpha and beta chains held together by disulphide bond. It is produced as a preproinsulin molecule by ribosomes, matures to proinsulin molecule in golgi apparatus and cleaves to insulin and C-peptide chain before its packing into secretory granules.

4. Mechanism of secretion

5. Metabolic actions of insulin

6. Classification of diabetes Type 1 Diabetes (IDDM) Type 2 Diabetes(NIDDM) Gestational Diabetes Other specific types

7. Type 1 diabetes mellitus(IDDM) It occurs mostly in young group of patients <30 years. Insulin deficiency results due to destruction of beta cells Etiology T cell mediated autoimmune destruction of beta cells /glutamic acid decarboxylase antibodies (GAD Abs) Genetic predisposition (HLA- DR3 DR4 genes) 30-50% concordance in identical twins Environmental factors (viruses, excessive coffee intake, stress, cow milk in newborn ) It is usually associated with thyroid disease, Addison disease ,Pernicious anemia, Coelic disease.

8. Type 2 Diabetes mellitus (NIDDM) It mostly affects middle age and older people (>30 years) It occurs due to Insulin resistance and beta cell exhaustion (relative insulin deficiency) High insulin levels in the early stage is characteristic. Etiology Central obesity ( ↑FFA compete with glucose for oxidation , adipokines decreases sensitivity of insulin receptors ,inhibits gluconeogenesis) Metabolic syndrome (obesity, hypertension,↑LDL,↑ TAGs,etc ) Genetic predisposition (TCFL2 gene) BMI >30 kg/m2 Pregnancy

9. Mature onset dm (MODY) A type of type 2 DM occurring in young people It is further divided into MODY 1 (HNF 4a deficiency) MODY 2 ( glucokinase deficiency) MODY 3 (HNF 1a deficiency) MODY 4 (IPF-1 deficiency) MODY 5 HNF-1b deficiency)

10. Gestational Diabetes It is the hyperglycemia occurring for the first time during pregnancy Placental hormones reduce the sensitivity of insulin receptors resulting in hyperglycemia and insulin doesn’t meet body requirement and beta cell exhaustion occurs

11. Other specific types Genetic defects of beta cells Genetic defects of insulin action e.g lipodystrophy Pancreatic disease ( pancreatitis,cystic fibrosis,neoplasm,hemochromatosis ) Drug induced DM ( steroids,thiazides,diuretics ) Viral (congenital rubella,mumps , coxasackie ) Uncommon form of immune mediated DM Endocrine Induced DM ( thyrotoxicosis,Cushing syndrome,acromegaly,pheochromocytoma )

12. Clinical Features Polyuria Polyphagia Polydipsia Fatigue Weight loss Dehydration Visual blurring Recurrent infections Delayed healing

13. In complicated case Peripheral gangrene Tingling and numbness Diabetic retinopathy Nephrosclerosis

14. Investigations Urine Testing Blood Testing Glycated hemoglobin Serum Electrolytes and renal parameters

15. Urine testing Testing the urine for glucose with dipsticks is a common practice for detecting diabetes. Preferably it should be checked after 2 hrs of meal for its maximum sensitivity It may be false positive in pregnancy and with some drugs Ketonuria can also be detected in the urine by dipsticks To check for ketone bodies in urine , nitroprusside reaction is used Ketonuria may aslo be false positive in case of prolonged strenuous exercise ,vomiting, dehydration but if with glycosuria diabetes is most likely diagnosis Standard dipstick testing for albumin detects urinary albumin at concentration >300mg/dl. Microalbuminuria in the absence of UTI is an indicator of diabetes.

16. Blood testing Normal fasting blood glucose =<7mmol or 126mg/dl Normal random blood glucose =<11.1mmol or 200mg/dl In diabetics FBG = ≥ 126mg/dl RBG = ≥200mg/dl Oral Glucose Tolerance Test (also called the OGTT) : The OGTT is a two-hour test that checks your blood glucose levels before and 2 hours after you drink a special sweet drink. It tells the doctor how your body processes glucose. Diabetes is diagnosed at 2 hour blood glucose of greater than or equal to 200 mg/dl

17. Pre diabetics Before people develop type 2 diabetes, they almost always have " prediabetes " — blood glucose levels that are higher than normal but not yet high enough to be diagnosed as diabetes. Doctors sometimes refer to prediabetes as impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), depending on what test was used when it was detected. This condition puts you at a higher risk for developing type 2 diabetes and cardiovascular disease . Results indicating prediabetes are: An A1C of 5.7% – 6.4% Fasting blood glucose of 100 – 125 mg/dl An OGTT 2 hour blood glucose of 140 mg/dl – 199 mg/dl

18. Glycated hemoglobin Glycated hemoglobin provides an accurate and objective measure of glycemic control over a period of 2-3 months In diabetes ,the slow non enzymatic covalent attachment of glucose to hemoglobin increases the amount of Hb1ac relative to HbA To be diabetic, Hb1ac should be ≥6.5%

19. Renal function tests should be evaluated as creatinine may raise in diabetes Electrolyte balance should be evaluated in case of diabetic ketoacidosis