Diabetes Mellitus Type 1

Type 1 diabetes mellitus (T1DM) is an organ-specific autoimmune disease resulting in destruction of the pancreatic beta cells and absolute insulin deficiency. Without insulin, glucose cannot enter most cells, and unregulated lipolysis and gluconeogenesis produce a metabolic crisis.

The pathophysiology involves T-cell-mediated autoimmune destruction of beta cells in the islets of Langerhans. Susceptibility is conferred by HLA class II alleles, particularly HLA-DR3 and HLA-DR4 haplotypes, which present self-antigens to autoreactive T cells. Autoantibodies — including anti-glutamic acid decarboxylase (GAD65), anti-islet antigen 2 (IA-2), anti-insulin (IAA), and anti-zinc transporter 8 (ZnT8) — are detectable years before clinical onset and are used for screening in first-degree relatives.

Clinical onset is typically abrupt, with symptoms of hyperglycaemia: polyuria, polydipsia, weight loss, and fatigue. Approximately 30% of new T1DM diagnoses present in diabetic ketoacidosis (DKA). DKA occurs because absolute insulin deficiency leads to uncontrolled lipolysis (fatty acids → ketone bodies: beta-hydroxybutyrate, acetoacetate), producing an elevated anion gap metabolic acidosis. Diagnostic criteria for DKA include blood glucose > 11 mmol/L (or known diabetes), blood or urine ketones ≥ 2+ (or blood ketones ≥ 3 mmol/L), and venous pH < 7.3 (or bicarbonate < 15 mmol/L). The anion gap = Na⁺ − (Cl⁻ + HCO₃⁻); normal < 12; elevated in DKA, lactic acidosis, uraemia, and toxic ingestions.

DKA management follows a structured approach: IV fluid resuscitation (0.9% NaCl initially), fixed-rate insulin infusion (typically 0.1 units/kg/h), potassium replacement (hypokalaemia is common once insulin drives K+ intracellularly — critical to avoid cardiac arrhythmias), glucose monitoring, and close monitoring of ketones and blood gases. Dextrose is added when blood glucose falls below 14 mmol/L to allow continuation of insulin until ketosis resolves.

Hypoglycaemia (blood glucose < 4 mmol/L in T1DM) is the most frequent acute complication. Whipple's triad: symptoms of hypoglycaemia + low blood glucose measurement + resolution with glucose administration. Counterregulatory hormones (glucagon, adrenaline, cortisol, growth hormone) normally restore euglycaemia, but patients with T1DM lose glucagon response within 5 years, making them dependent on adrenaline. Hypoglycaemia unawareness — loss of adrenergic symptoms — is a serious complication. Glucagon emergency kits are available for third-party administration.

In New Zealand, insulin types available and funded by Pharmac include: long-acting (basal) insulin — insulin glargine (Lantus) and insulin detemir (Levemir); short-acting (bolus) insulin — insulin aspart (NovoRapid) and insulin lispro (Humalog). Continuous glucose monitoring (CGM) systems (e.g., Dexterity/FreeStyle Libre) are increasingly used to improve glycaemic control and detect hypoglycaemia, with Pharmac funding criteria applying.