Type 1 Diabetes Mellitus

Type 1 diabetes is autoimmune destruction of pancreatic beta cells causing absolute insulin deficiency.

• Incidence is about 15 to 25 per 100,000 per year, with peaks in childhood and a second wave through adulthood, where 40% or more are diagnosed after age 20.
• Susceptibility is HLA DR3 DQ2 and DR4 DQ8 with environmental triggers (enterovirus).
• Autoantibodies: GAD65, IA-2, ZnT8, insulin. Staging: stage 1 (two or more antibodies, normoglycaemia), stage 2 (dysglycaemia), stage 3 (symptomatic).
• Associations: autoimmune thyroid disease, coeliac disease, Addison disease, pernicious anaemia, vitiligo.
• Acute complications: DKA, severe hypoglycaemia. Chronic: retinopathy, nephropathy, neuropathy, cardiovascular disease.

• Polyuria, polydipsia, weight loss, fatigue, blurred vision, often over weeks.
• DKA at presentation in 25 to 40%: vomiting, abdominal pain, Kussmaul breathing, dehydration, ketotic breath.
• Adults may have a slower onset and be misdiagnosed as type 2.
• Lean habitus is typical but obesity does not exclude.

• Glucose 200 mg/dL or more with symptoms, fasting 126 mg/dL or more, HbA1c 6.5% or more, or 2 hour OGTT 200 mg/dL or more.
• Ketones (blood beta hydroxybutyrate above 0.6 mmol/L), venous gas.
• Islet autoantibodies (GAD65 first); C peptide when type uncertain (below 0.2 nmol/L at 3 years supports absolute deficiency).
• Screen at diagnosis: TSH and TPO antibodies, coeliac serology (tTG IgA), lipids, urine albumin to creatinine ratio, retinal examination within 5 years.

• Basal bolus insulin or pump: total daily dose 0.5 to 1 unit/kg/day, about half basal (glargine U100 or degludec once daily, detemir) and half prandial (lispro, aspart, glulisine 1 unit per 10 to 15 g carbohydrate, correction 1 unit per 30 to 50 mg/dL above 150).
• Continuous glucose monitoring with automated insulin delivery. Targets: HbA1c below 7% (53 mmol/mol), time in range 70 to 180 mg/dL over 70%, time below 70 under 4%.
• Carbohydrate counting education, sick day rules (never omit basal insulin, check ketones when glucose above 250).
• Hypoglycaemia: 15 to 20 g fast carbohydrate, glucagon 1 mg IM or nasal 3 mg for severe episodes.
• Adjunct: pramlintide (selected), teplizumab 14 day infusion to delay stage 3 in stage 2 disease.
• Risk reduction: ACE inhibitor for albuminuria, statin from age 40, blood pressure below 130/80 mmHg.
• Annual screening for retinopathy, nephropathy, neuropathy, foot examination; thyroid and coeliac screening periodically.