Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ 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 ... Your MyAccess profile is currently affiliated with '[InstitutionA]' and is in the process of switching affiliations to '[InstitutionB]'. Please click ‘Continue’ to continue the affiliation switch, otherwise click ‘Cancel’ to cancel signing in. Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth