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/m2) • 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 <35 mg/dL (0.90 mmol/L) and/or a

triglyceride 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