Chapter 19: Diabetes Mellitus

INTRODUCTION

• Diabetes mellitus (DM) is a group of metabolic disorders characterized by chronically elevated blood glucose (BG) and abnormal carbohydrate, fat, and protein metabolism. Without effective treatment, DM can lead to acute complications such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS). Chronic hyperglycemia can cause microvascular, macrovascular, and neuropathic complications.

PATHOPHYSIOLOGY

• Type 1 DM (5%–10% of cases) usually 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 disorder is believed to be initiated by exposure to an unknown environmental trigger in a genetically susceptible individual. 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) is also deficient in type 1 DM due to β-cell destruction. Amylin suppresses inappropriate glucagon secretion, slows gastric emptying, and causes central satiety.

  • ✔ After the initial diagnosis, a period of transient remission called the “honeymoon” phase may occur, during which insulin doses can be reduced or withdrawn before continued β-cell destruction requires lifelong insulin replacement therapy.

• Type 2 DM (90%–95% of cases) is characterized by multiple defects:

  • ✔ Impaired insulin secretion: β-cell mass and function are both reduced, and β-cell failure is progressive.

  • ✔ Reduced incretin effect: Normally, the gut incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are released and stimulate insulin secretion in response to a meal. Patients with type 2 DM have a reduced incretin effect due to decreased concentrations of or resistance to the effects of incretin hormones.

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

  • ✔ Excess glucagon secretion: This 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: This increases reabsorption of glucose by proximal renal tubular cells, which further contributes to hyperglycemia.

• Gestational diabetes (GDM) is DM that occurs in women during pregnancy.

• Less common causes of DM (1%–2%) include maturity onset diabetes of the young (MODY), genetic syndromes (eg, Down syndrome), endocrine disorders (eg, acromegaly, Cushing syndrome), pancreatic exocrine dysfunction, infections, and medications (eg, glucocorticoids, thiazides, niacin, atypical antipsychotics).

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

CLINICAL PRESENTATION

Type 1 Diabetes Mellitus

• Patients often have symptoms in the days or weeks preceding the diagnosis. The most common initial symptoms are polyuria, polydipsia, polyphagia, weight loss, fatigue, and lethargy.

• Individuals are often thin and are prone to develop DKA in the absence of an adequate insulin supply; many ...