DIABETES MELLITUS

DEFINATION, CLASSIFICATION ,CLINICAL FEATURES AND INVESTIGATIONS

FARRUKH MASOOD ,NMC

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

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.

MECHANISM OF SECRETION

METABOLIC ACTIONS OF INSULIN

CLASSIFICATION OF DIABETES

• Type 1 Diabetes (IDDM)

• Type 2 Diabetes(NIDDM)

• Gestational Diabetes

• Other specific types

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.

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

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)

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

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)

CLINICAL FEATURES

• Polyuria

• Polyphagia

• Polydipsia

• Fatigue

• Weight loss

• Dehydration

• Visual blurring

• Recurrent infections

• Delayed healing

• In complicated case

• Peripheral gangrene

• Tingling and numbness

• Diabetic retinopathy

• Nephrosclerosis

INVESTIGATIONS

• Urine Testing

• Blood Testing

• Glycated hemoglobin

• Serum Electrolytes and renal parameters

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.

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

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

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%

• Renal function tests should be evaluated as creatinine may raise in diabetes

• Electrolyte balance should be evaluated in case of diabetic ketoacidosis