Chapter 19: Diabetes Mellitus

INTRODUCTION

• Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia and abnormalities in carbohydrate, fat, and protein metabolism. It may result in chronic microvascular, macrovascular, and neuropathic complications.

PATHOPHYSIOLOGY

• Type 1 DM (5%–10% of cases) results from autoimmune destruction of pancreatic β-cells, leading to absolute deficiency of insulin. It usually presents in children and adolescents but can occur at any age. The autoimmune process is mediated by macrophages and T lymphocytes with autoantibodies to β-cell antigens (eg, islet cell antibody, insulin antibodies). Amylin (a hormone cosecreted from pancreatic β-cells with insulin) suppresses inappropriate glucagon secretion, slows gastric emptying, and causes central satiety; amylin is also deficient in type 1 DM due to β-cell destruction.

• Type 2 DM (90% of cases) is characterized by multiple defects:

  • ✓ Impaired insulin secretion is a hallmark finding; β-cell mass and function are both reduced, and β-cell failure is progressive.

  • ✓ Normally, the gut incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and stimulate insulin secretion when nutrients enter the stomach and intestines. Patients with type 2 DM have a reduced incretin effect due to decreased concentrations of or resistance to the effects of these incretin hormones.

  • ✓ Insulin resistance is manifested by excessive hepatic glucose production, decreased skeletal muscle uptake of glucose, and increased lipolysis and free fatty acid production.

  • ✓ Excess glucagon secretion occurs because type 2 DM patients fail to suppress glucagon in response to meals because of GLP-1 resistance/deficiency and insulin resistance/deficiency, which directly suppress glucagon.

  • ✓ Sodium-glucose cotransporter-2 (SGLT-2) upregulation in the kidney increases reabsorption of glucose by proximal renal tubular cells, which may worsen hyperglycemia.

• The metabolic syndrome involves multiple metabolic abnormalities and confers a higher risk for developing type 2 DM and subsequent cardiovascular disease (CVD). The current definition includes central obesity (defined as waist circumference with ethnicity-specific values) plus any two of these four factors: (1) raised triglycerides (≥ 150 mg/dL [1.7 mmol/L]); (2) reduced HDL cholesterol (< 40 mg/dL [1.03 mmol/L] in males or < 50 mg/dL [1.29 mmol/L] in females); (3) increased blood pressure (systolic BP ≥ 130 mm Hg, diastolic BP ≥ 85 mm Hg, or treatment of previously-diagnosed hypertension); and (4) raised fasting plasma glucose (≥ 100 mg/dL [5.6 mmol/L] or previous diagnosis of type 2 DM.

• Uncommon causes of diabetes (less than 5% of cases) include gestational diabetes mellitus (GDM), maturity onset diabetes of youth (MODY), endocrine disorders (eg, acromegaly, Cushing syndrome), pancreatic exocrine dysfunction, infections, and medications (eg, glucocorticoids, thiazides, niacin).

• Microvascular complications include retinopathy, neuropathy, and nephropathy. Macrovascular complications include coronary heart disease, stroke, and peripheral vascular disease.

CLINICAL PRESENTATION

TYPE 1 DIABETES MELLITUS

• The most common initial symptoms are polyuria, polydipsia, polyphagia, weight loss, and lethargy accompanied by hyperglycemia.

• Individuals are often thin and are prone to develop diabetic ketoacidosis if insulin is ...