Diabetes Mellitus Dr. Meg-angela Christi Amores

Diabetes Mellitus refers to a group of common metabolic disorders that share the phenotype of hyperglycemia Factors: – reduced insulin secretion – decreased glucose utilization – increased glucose production

Classification

Diagnosis Criteria for the diagnosis of DM – Symptoms of diabetes plus random blood glucose concentration > 200 mg/dL – Fasting plasma glucose > 126 mg/dL – Two-hour plasma glucose > 200 mg/dL during an oral glucose tolerance test – FPG is the most reliable and convenient test for identifying DM in asymptomatic individuals

Risk Factors for Type 2 DM Family history of diabetes (i.e., parent or sibling with type 2 diabetes) Obesity (BMI 25 kg/m 2 ) Habitual physical inactivity Race/ethnicity Previously identified IFG or IGT History of GDM or delivery of baby >4 kg (>9 lb) Hypertension (blood pressure 140/90 mmHg) HDL cholesterol level 250 mg/dL (2.82 mmol/L) Polycystic ovary syndrome or acanthosis nigricans History of vascular disease

Insulin biosynthesis, Secretion, Action produced in the beta cells of the pancreatic islets PREPROINSULIN PROINSULIN A or B chains of INSULUN

Secretion Glucose is the key regulator of insulin secretion by the pancreatic beta cell Glucose levels > 70 mg/dL stimulate insulin synthesis

transport into the beta cell by the GLUT2 glucose transporter phosphorylation by glucokinase – rate-limiting step that controls glucose-regulated insulin secretion metabolism of glucose-6- phosphate via glycolysis generates ATP inhibits the activity of an ATP-sensitive K + channel opens voltage-dependent calcium channels stimulates insulin secretion

Action Once insulin is secreted into the portal venous system, ~50% is degraded by the liver Unextracted insulin enters the systemic circulation where it binds to receptors in target sites initiate a complex cascade of phosphorylation and dephosphorylation reactions resulting in the widespread metabolic and mitogenic effects of insulin

Action Glucose homeostasis reflects a balance between hepatic glucose production and peripheral glucose uptake and utilization Insulin is the most important regulator of this metabolic equilibrium

Type I DM the result of interactions of genetic, environmental, and immunologic factors that ultimately lead to the destruction of the pancreatic beta cells and insulin deficiency rate of decline in beta cell mass varies widely among individuals, with some patients progressing rapidly to clinical diabetes and others evolving more slowly

Type I DM Features of diabetes do not become evident until a majority of beta cells are destroyed (~80%)

Type II DM Insulin resistance and abnormal insulin secretion are central to the development of type 2 DM has a strong genetic component polygenic and multifactorial since in addition to genetic susceptibility, environmental factors (such as obesity, nutrition, and physical activity) modulate the phenotype

Type II DM Obesity, particularly visceral or central (as evidenced by the hip-waist ratio), is very common In the early stages of the disorder, glucose tolerance is normal, pancreatic beta cells compensate by increasing insulin output

Acute complications Diabetic ketoacidosis Hyperglycemic Hyperosmolar State

Chronic Complications

Approach to patient HISTORY – DM-relevant aspects such as weight, family history of DM and its complications, risk factors for cardiovascular disease, exercise, smoking, and ethanol use – Symptoms of hyperglycemia: polyuria, polydipsia, weight loss, fatigue, weakness, blurry vision, frequent superficial infections (vaginitis, fungal skin infections), and slow healing of skin lesions after minor trauma – Blurred vision

Approach to patient PHYSICAL EXAMINATION – weight or BMI, retinal examination, orthostatic blood pressure, foot examination, peripheral pulses, and insulin injection sites – Blood pressure > 130/80 mmHg is considered hypertension – peripheral neuropathy, calluses, superficial fungal infections, nail disease, ankle reflexes, and foot deformities

Treatment Overall goals of therapy (1) eliminate symptoms related to hyperglycemia (2) reduce or eliminate the long-term microvascular and macrovascular complications of DM (3) allow the patient to achieve as normal a lifestyle as possible

Treatment Patient education – nutrition, exercise, care of diabetes during illness, and medications – fruits, vegetables, fiber-containing foods, and low- fat milk is advised – Consumption of foods with a low glycemic index – Reduced calorie and nonnutritive sweeteners are useful

Assignment: List foods with a LOW GLYCEMIC INDEX

Treatment Achieve normoglycemia – Insulin – Glucose-lowering agents Sulfonylurea (Gliclazide) Biguanides (Metformin) a glucosidase inhibitors (Acarbose) Thiazilidinediones