Diabetes

Overview – Diabetes

Diabetes mellitus is a chronic metabolic disorder characterised by elevated blood glucose levels (hyperglycaemia) due to impaired insulin secretion, insulin action, or both. It is a leading cause of morbidity and mortality worldwide due to its acute metabolic derangements and long-term microvascular and macrovascular complications. This article covers the physiology of insulin and glucagon, types of diabetes, diagnostic criteria, presentations, treatment options, and complications.

Physiology of Insulin & Glucagon

Insulin

Released in response to:

• ↑ Blood glucose
• ↑ Blood amino acids

Stimulates:

• Glucose uptake (muscle, adipose)
• Lipid synthesis/storage
• Protein synthesis

Inhibits:

• Ketogenesis
• Macromolecular breakdown

Glucagon

Released in response to:

• ↓ Blood glucose
• ↓ Blood amino acids (e.g. fasting)

Stimulates:

• Glycogenolysis
• Gluconeogenesis
• Lipolysis
• Ketogenesis

Inhibits:

• Storage/synthesis of macromolecules

Diagnostic Criteria (The “7–11 Rule”)

• Fasting BSL ≥ 7.0 mmol/L
• Random BSL > 11.1 mmol/L
• OGTT (2hr post-load) > 11.1 mmol/L
• HbA1c used for monitoring, not diagnosis
• Type 1 diabetes:
  • • Anti-GAD, Anti-Islet Cell Antibodies

Types of Diabetes

Type 1 Diabetes Mellitus

• Aetiology: Autoimmune β-cell destruction
• Onset: Juvenile, rapid
• Diagnosis: + Anti-GAD, Anti-ICA, Insulin Autoantibodies
• Clinical Features:
  • Polyuria, polydipsia, weight loss
  • Ketonuria → DKA risk
• Treatment: Exogenous insulin
• Complications: DKA

LADA (Latent Autoimmune Diabetes of Adults)

• Aetiology: Delayed-onset autoimmune
• Presentation: Slim adults, positive autoantibodies
• Complications: DKA, HONK
• Treatment: Insulin

Type 2 Diabetes Mellitus

• Aetiology: Insulin resistance ± β-cell dysfunction
• Onset: Adults, insidious
• Risk Factor: Obesity (especially central)
• Metabolic Syndrome:
  • ↑FFA, glucose, insulin, BP
  • ↓HDL
• Diagnosis: OGTT >11 mmol/L, random BSL >11
• Treatment:
  1. Lifestyle
  2. Oral agents (Metformin, Sulfonylureas, Incretins)
  3. Insulin
• Complications: HONK, macro/microvascular

MODY (Maturity Onset Diabetes of the Young)

• Aetiology: Monogenic (Autosomal Dominant)
• Clinical Features: Young, non-obese, strong family history
• Treatment: Oral hypoglycaemics → insulin

Initial & Emergency Presentation

• Classic symptoms: PPP (Polyuria, Polydipsia, Polyphagia)
• Weight loss, fatigue, recurrent infections
• Emergency presentations:
  • DKA (Type 1)
  • HONK (Type 2)
  • Hypoglycaemia

Acute Complications

Diabetic Ketoacidosis (DKA)

• Cause: Insulin deficiency (often missed dose)
• Triad:
  • Hyperglycaemia
  • Metabolic acidosis
  • Ketonuria
• Symptoms: Vomiting, Kussmaul breathing, acetone breath
• Treatment: IV fluids, insulin, monitor K+
• Complications: Severe dehydration, arrhythmias

Hyperosmolar Non-Ketotic Coma (HONC)

• Cause: Type 2 DM + stressor
• Features:
  • Very high BSL
  • No ketosis
  • Dehydration, confusion
• Treatment: IV fluids, insulin, electrolyte replacement

Hypoglycaemia

• BSL < 3.5 mmol/L
• Symptoms:
  • Adrenergic: Sweating, tremor, palpitations
  • Neuroglycopenic: Confusion, seizures, coma
• Treatment: Oral/IV glucose or IM glucagon

Chronic Complications

Microvascular

• Retinopathy → blindness
• Nephropathy → ESRD
• Neuropathy → foot ulcers, Charcot joints

Macrovascular

• MI
• Stroke
• Peripheral vascular disease

Pathogenic Mechanisms

Polyol Pathway

• Glucose → sorbitol → fructose
• Sorbitol accumulation → osmotic stress

Advanced Glycation End-products (AGEs)

• Non-enzymatic glycation of proteins → vessel damage
• ↓NO availability → impaired vasodilation
• ↑Matrix deposition, inflammation

Oxidative Stress

• Hyperglycaemia → ↑ROS
• Promotes endothelial dysfunction

Summary – Diabetes

Diabetes mellitus encompasses a group of metabolic diseases defined by chronic hyperglycaemia due to insulin deficiency, resistance, or both. It manifests acutely as DKA or HONK and has long-term complications affecting vascular, renal, and nervous systems. Timely diagnosis, lifestyle management, and glycaemic control are crucial. For more, visit our Endocrine Overview page.