WHAT IS DIABETES MELLITUS?

WHAT IS DIABETES MELLITUS?

  1. 1
    WHAT IS THE MEANING OF DIABETES MELLITUS?
    • Diabetes mellitus (DM) is a group of metabolic disorders characterised by hyperglycemia and abnormalities in carbohydrate, fat, and protein metabolism. It may result in chronic microvascular, macrovascular, and neuropathic complications.
  2. 2
    WHAT ARE THE CAUSES OF DIABETES MELLITUS?
    • Type 1 DM (5%–10% of cases) results from autoimmune destruction of pancreatic β-cells, leading to an 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, e.g., islet cell antibody, insulin antibodies). Amylin (a hormone secreted 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 characterised 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.
    • Metabolic syndrome involves multiple metabolic abnormalities and confers a higher risk of 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 (e.g., acromegaly, Cushing syndrome), pancreatic exocrine dysfunction, infections, and medications (e.g., glucocorticoids, thiazides, niacin).
    • Microvascular complications include retinopathy, neuropathy, and nephropathy. Macrovascular complications include coronary heart disease, stroke, and peripheral vascular disease.
  3. 3
    WHAT ARE THE SIGNS AND SYMPTOMS OF DIABETES MELLITUS?

    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 withheld or under conditions of severe stress.
    • Between 20% and 40% of patients present with diabetic ketoacidosis after several days of polyuria, polydipsia, polyphagia, and weight loss.

    TYPE 2 DIABETES MELLITUS

    • Patients are often asymptomatic and may be diagnosed secondary to unrelated blood testing.
    • Lethargy, polyuria, nocturia, and polydipsia can be present. Significant weight loss is less common; most patients are overweight or obese.
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