Key Facts

Type 1 diabetes mellitus (T1DM) in children is caused by autoimmune destruction of insulin-producing beta cells in the pancreatic islets of Langerhans. It results in absolute insulin deficiency requiring exogenous insulin replacement. It is the most common endocrine disorder of childhood.

Epidemiology

UK incidence is approximately 28 per 100,000 children per year — among the highest worldwide. Prevalence is approximately 196 per 100,000 children under 15. Peak incidence is at 10-14 years (puberty) with a smaller peak at 5-7 years (school entry). Increasing incidence of approximately 3-4% per year over recent decades. Slight male predominance in post-pubertal presentation.

Aetiology

T1DM is an autoimmune condition with both genetic and environmental contributors:

• Genetic: HLA-DR3/DR4 and HLA-DQ2/DQ8 confer ~50% of genetic risk; concordance in identical twins is 30-50%
• Autoantibodies: Anti-GAD (glutamic acid decarboxylase), anti-IA2 (islet antigen 2), anti-insulin, anti-ZnT8 — present in >90% at diagnosis
• Environmental triggers: Enteroviral infections (Coxsackie B), early cow's milk exposure, vitamin D deficiency (all proposed but not proven)

Pathophysiology

Autoimmune T-cell-mediated destruction of pancreatic beta cells leads to progressive insulin deficiency. Clinical diabetes manifests when approximately 80-90% of beta cells are destroyed. Without insulin, glucose cannot enter cells → hyperglycaemia → osmotic diuresis (polyuria, polydipsia). Unopposed glucagon action and lipolysis → ketogenesis → DKA if untreated.

Classic Presentation

• Polyuria (including secondary nocturnal enuresis)
• Polydipsia
• Weight loss
• Fatigue, lethargy
• Symptoms typically over days to weeks

DKA Presentation (25-30% at diagnosis)

• Vomiting, abdominal pain
• Kussmaul breathing (deep, sighing respiration)
• Dehydration
• Drowsiness, confusion → coma
• Acetone (pear drops) smell on breath

Ongoing Monitoring Issues

• Hypoglycaemia (most common acute complication of insulin therapy)
• Diabetic ketoacidosis (intercurrent illness, insulin omission)
• Poor glycaemic control in adolescence

Red Flags

• Any child with unexplained weight loss, polyuria, polydipsia — check blood glucose immediately
• Reduced consciousness with hyperglycaemia — DKA emergency
• Recurrent DKA — consider insulin omission, safeguarding concerns, eating disorder
• Signs of cerebral oedema during DKA treatment: headache, bradycardia, altered consciousness, hypertension

Bedside

• Capillary blood glucose: Random glucose ≥11.1 mmol/L with symptoms = diagnostic
• Urine dipstick: Glycosuria, ketonuria
• Blood ketones: β-hydroxybutyrate >3 mmol/L with hyperglycaemia suggests DKA
• Blood gas: pH, bicarbonate — DKA: pH <7.3, HCO3 <15 mmol/L

Bloods

• HbA1c: Reflects glycaemic control over 2-3 months; diagnostic if ≥48 mmol/mol
• Autoantibodies: Anti-GAD, anti-IA2, anti-insulin (if <5 years), anti-ZnT8 — positive in >90% of T1DM
• C-peptide: Low/undetectable in established T1DM (reflects endogenous insulin production)
• TFTs: Screen for autoimmune thyroid disease (~20% develop thyroid autoantibodies)
• Coeliac screen (tTG-IgA): ~10% have coeliac autoantibodies; screen at diagnosis and periodically
• U&Es: Assess renal function and electrolytes (especially in DKA)
• Lipid profile: Annual screening from age 12

Imaging

• Not routinely required at diagnosis
• Retinal screening: Annual from age 12 years (or 5 years after diagnosis if earlier)

Special Tests

• Genetic testing: If atypical features (MODY suspected, diagnosis <6 months, negative autoantibodies)

Non-pharmacological

• Structured diabetes education: For child and family at diagnosis and ongoing (NICE NG18)
• Carbohydrate counting: Essential skill for flexible insulin dosing
• Regular exercise: Encouraged; adjust insulin and carbohydrate intake around activity
• Psychological support: Screen for diabetes distress, eating disorders, depression annually
• School management plan: Ensure school staff trained in hypoglycaemia management

Pharmacological

• Basal-bolus insulin (MDI): First-line regimen
  • Basal: Insulin detemir (Levemir) or insulin degludec (Tresiba) or insulin glargine (Lantus) OD-BD
  • Bolus: Rapid-acting insulin (insulin aspart/lispro/glulisine) with meals, dose adjusted by carbohydrate counting and correction factor
• Insulin pump (CSII): NICE NG18 recommends offering to all children; uses rapid-acting insulin only; improved HbA1c and reduced hypoglycaemia
• Closed-loop/hybrid systems: Automated insulin delivery combining pump with continuous glucose monitoring (CGM) — increasingly standard of care
• Continuous glucose monitoring: NICE recommends real-time CGM or intermittently scanned CGM (e.g., FreeStyle Libre) for all children with T1DM
• DKA management: IV 0.9% NaCl fluid resuscitation (10ml/kg bolus if shocked, then replace deficit over 48 hours), IV insulin 0.05-0.1 units/kg/hr (BSPED DKA guidelines), potassium replacement, monitor for cerebral oedema
• Hypoglycaemia treatment: Oral glucose (fast-acting carbohydrate), glucagon IM/SC 0.5mg (<8 years) or 1mg (≥8 years) if unconscious

Surgical/Interventional

• Islet cell transplantation: Experimental; not standard of care in children

Referral Criteria

• All newly diagnosed T1DM — immediate paediatric diabetes team referral
• Same-day assessment if DKA suspected
• Annual review with MDT: diabetologist, diabetes specialist nurse, dietitian, psychologist
• Transition to adult services at age 16-18 (NICE NG18)

• Life expectancy: Reduced by approximately 10-13 years compared to general population, though gap is narrowing with improved management
• DCCT/EDIC: Intensive insulin therapy reduced retinopathy by 76%, nephropathy by 50%, neuropathy by 60%
• DKA mortality: ~0.15-0.3% in children; cerebral oedema accounts for 60-90% of DKA-related deaths
• Microvascular complications: Rare before puberty; screening starts at age 12 or 5 years post-diagnosis
• HbA1c of <48 mmol/mol is associated with significantly lower complication rates
• Technology (CGM, pumps, closed-loop systems) has significantly improved outcomes in recent years

DKA Severity Classification (BSPED)

Insulin Types

NICE NG18 Key Recommendations