Diabetes & Regulation

Diabetes & Blood Glucose Regulation

Blood glucose is precisely regulated between 70–100 mg/dL in the fasting state. This is achieved through the coordinated actions of hormones, primarily insulin and glucagon, acting on liver, muscle, and adipose tissue.

Hormonal Control

  • Insulin (β-cells of islets of Langerhans): Anabolic hormone. Secreted in response to ↑blood glucose, GLP-1. Actions: ↑Glucose uptake (GLUT4 in muscle/fat), ↑Glycogenesis, ↑Glycolysis, ↑FA synthesis, ↑Protein synthesis; ↓Glycogenolysis, ↓Gluconeogenesis, ↓Lipolysis, ↓Ketogenesis.
  • Glucagon (α-cells): Catabolic hormone. Secreted in response to ↓blood glucose, amino acids. Actions: ↑Glycogenolysis (liver), ↑Gluconeogenesis, ↑Lipolysis, ↑Ketogenesis; ↓Glycolysis, ↓FA synthesis.
  • Cortisol: Raises blood glucose (induces gluconeogenic enzymes, stimulates lipolysis and proteolysis for substrates). Causes insulin resistance.
  • Epinephrine: Stress hormone; rapid glycogenolysis (liver and muscle), lipolysis.
  • Growth Hormone: Stimulates lipolysis; anti-insulin (diabetogenic in excess).

Diabetes Mellitus — Classification

  • Type 1 DM (Insulin-dependent): Autoimmune destruction of β-cells → absolute insulin deficiency. Prone to diabetic ketoacidosis. Treatment: Insulin replacement.
  • Type 2 DM (Non-insulin-dependent): Insulin resistance + relative insulin deficiency. Associated with obesity, aging. No ketoacidosis (some insulin present). Treatment: Lifestyle + Metformin/sulfonylureas/GLP-1 agonists; insulin if needed.
  • Gestational DM: Diagnosed in pregnancy; risk of macrosomia, neonatal hypoglycemia.
  • MODY: Maturity Onset Diabetes of the Young — monogenic, autosomal dominant.

Metabolic Changes in Diabetes

  • ↑Blood glucose → glycosuria (exceeded renal threshold ~180 mg/dL) → osmotic diuresis → polyuria, polydipsia
  • Lack of insulin → ↑Lipolysis → ↑FFA → ↑Ketogenesis (3 ketone bodies: Acetoacetate, β-Hydroxybutyrate, Acetone)
  • Ketoacidosis: Blood pH drops → Kussmaul breathing (rapid deep breathing to blow off CO₂)
  • Hyperglycemia → non-enzymatic glycosylation → HbA1c (3-month average glucose); AGEs cause vascular damage

Complications of Diabetes

  • Microvascular: Retinopathy, Nephropathy (Kimmelstiel-Wilson lesion), Neuropathy
  • Macrovascular: Accelerated atherosclerosis, MI, stroke, peripheral vascular disease
  • Sorbitol pathway: Excess glucose → sorbitol (aldose reductase) → cataracts, neuropathy in DM

HbA1c

Non-enzymatic glycosylation of Hb. Reflects average blood glucose over previous 2–3 months (RBC lifespan ~120 days). Normal <5.7%; Prediabetes 5.7–6.4%; Diabetes ≥6.5%.