DIABETES MELLITUS

DIABETES MELLITUS
Group of metabolic diseases characterized by hyperglycemia resulting form defects in insulin resistance, insulin action and/or both. Symptoms include: Polyuria Polydipsia Weight loss Polyphagia

Classification of DM
Type 1 diabetes 5-10% of patients with diabetes Has a genetic predisposition It is due to cellular mediated autoimmune destruction of B cells of the pancreas. Detected at an earlier age Ketoacidosis usually the first manifestation may need insulin therapy for life

 Type 2 Diabetes Mellitus 90 to 95% of patients with DM Due to 3 pathophysiologic mechanisms: Impaired insulin secretion Peripheral insulin resistance Excessive hepatic glucose production Risk factors: Obesity Age Lack of physical activity

Diagnostic Criteria for DM

1. Fasting plasma glucose of >126mg/dl (7.0mmol/L) . Fasting is defined as no caloric intake for at least 8 hours 2. 2 hours plasma glucose (OGTT) of >200mg/dl (11.1mmol/L), using a glucose load of 75g anhydrous glucose dissolved in water. 3. Symptoms of hyperglycemia plus random blood glucose of >200mg/dl (11.1mmol/L) 4. HBa1c of >6.5mg/dl

Who are those at increased risk for developing DM?

Impaired plasma glucose:

FPG of 100mg/dl to 125mg/dl 2 hours glucose tolerance test (OGTT) of 140mg/dl to 199mg/dl HbA1C of 5.7- 6.4%%

Patients who are overweight (BMI>25kg/m2) and are: Physically inactive With first degree relative who are diabetic Hypertensive HDL of <35mg/dl and triglyceride level of >250mg/dl With history of CVD Women who delivered a baby weighing >9lbs or was diagnosed to have GDM Women with Polycystic ovarian syndrome

 For those who are asymptomatic and without risk factors, screeening for DM begins at 45 years old If normal tests, repeat testing after 3 years

PATHOPHYSIOLOGY of TYPE 2 DM
A. Insulin resistance Result from genetic susceptibility and obesity Due to decreased sensitivity of insulin that is present in the tissues to hyperglycemia causing reduce in maximal response of insulin in ulitilization of plasma glucose (30 to 60%) Adipocytes secrete a number of biologic products ( leptin, TNF-a, FFA, resistins and adiponectin), which modulate insulin secretion and action contributing to insulin resistance

B. Impaired insulin secretion precise mechanism still unclear Some postulates: Initially, B cells secrete more insulin in response to continuous hyperglycemia despite insulin resistance Glucose toxicity wears out B cell function causing worsening of hyperglycemia

C. Increased Hepatic glucose production Increased in insulin resistance in the liver despite the presence of hyperinsulinemia reflect failure of the insulin to suppress gluconeogenesis accounting of fasting hyperglycemia

COMPREHENSIVE DIABETES EVALUATION

Medical history: Age and characteristics of onset of DM Eating patterns and physical activity, nutritional status and weight history Assess for symptoms of diabetic related complications: Microvascular: retinopathy, neuropathy, nephropathy Macrovascular: CHD, CVD, PAD Autonomic dysfunction

 Physical examination: Weight, height, BMI BP determination Fundoscopic examination Skin examination (acathosis nigricans) Comprehensive foot evaluation Neurologic examination; sensory deficits Laboratory examination Lipid profile Urine albumin excretion Serum creatine and BUN, determine GFR

Management OF DM
Glycemic goals of therapy: HbA1C of <6.5% Assessment and control of other co morbidities such as hypertension and dyslipidemia has been shown to improve microvascular and cardiovascular complications Weight loss and exercise: non pharmacologic therapy; shown to decrease the complications brought about by DM

Initiation of therapy

Baseline HBa1c?
Expected decrease in HBa1c: 1.0 to 2.0 (monotherapy)

Weight loss and physical activity Metformin

HBa1c: 1.5 to 3.5

Insulin Sulfonylurea
A glucosidase inhibitor Pramlintide DPP4 inhibitor

HBa1c:1.0 to 2.0

HBa1c: 0.5 to 1.0

PHARMACOLOGIC THERAPY
Types according to target/mechanism: 1. insulin secretion (insulin secretagogues) Sulfonylureas Repaglinide nateglinide 2. glucose production biguanides 3. insulin sensitivity thiazolidinediones, biguanides 4. GLP-1 action dipeptidyl peptidate IV inhibitors 5. Glucose absorption -glucosidase inhibitors

Side effects of medications

Metformin Interfere with vitamin B12 absorption Modest weight loss Not indicated to those with creatinine of >1.5 Insulin Weight gain hypoglycemia Sulfonylurea Hypoglycemia (chlorpropamide and glibenclamide) CVD mortality Weight gain of >2kgs

 Amylin Agonist Adjunct Weight of 1.5kgs in 6 months DPP4 inhibitor Interference with immune system

Thank you!!!