DM Type- 1

 

• Pathophysiology

  Autoimmune cytotoxic T-cell destruction of pancreatic β-cells, leading to reduced insulin production.

• Risk factors

  • Family history and genetic factors including HLA-DR3 and DR4.
  • Association with other autoimmune diseases as part of polyglandular autoimmune syndrome type 2: pernicious anaemia, vitiligo, thyroid disease, Addison's.

• Investigations

  Following diagnosis of diabetes mellitus with venous glucose, diagnosis of type 1 is largely clinical:

  • Supportive features: ketosis, weight loss, age <50, BMI <25, personal or family history of autoimmune disease.
  • If typical clinical features are absent, consider checking GAD65 Ab (an islet cell Ab, 80% sensitive) and/or C-peptide (↓ in T1DM).

  Other investigations to perform in newly diagnosed patients:

  • Urine albumin for microalbuminuria.
  • HbA1c. Re-check every 3-6 months, aiming <48 mmol/mol (6.5%).
  • U&E
  • Test for other autoimmune diseases: coeliac, thyroid function.

• Insulin therapy

  Basics of subcutaneous insulin therapy:

  • Upon diagnosis of type 1 diabetes, same day referral to hospital diabetes team to initiate insulin.
  • Balance to strike between benefits of glucose control vs. risks of hypos and obesity.
  • Requires finger prick glucose testing to check control. Should be done at least 4 times per day e.g. before each meal and before bed. Aim for 5-7 mmol/L before breakfast and 4-7 mmol/L before other meals.
  • Vary insulin injection sites across outer thigh and abdomen.
  • All patients should be offered structured education programme in flexible insulin therapy (e.g. DAFNE, Dose Adjustment For Normal Eating).

  Classification

  Rapid-acting insulin analogues:

  • Lispro (aka Humalog), aspart (aka NovoRapid).
  • Onset in 5 minutes. Can be taken just before or even after meal. Peaks 1-2 hours, lasts 4 hours.

  Short-acting:

  • Human soluble insulin (HI): Humulin S, Actrapid.
  • Onset in 30 minutes. Take 20 mins before meal. Peaks 3 hours, lasts 8 hours.

  Intermediate-acting:

  • NPH insulin (Neutral Protamine Hagedorn): isophane, Insulatard, Humulin I.
  • 2 hour onset, peaks at 8 hours, lasts for 12-16 hours.

  Long-acting:

  • Glargine (Lantus), levemir (Detemir).
  • 1-2 hour onset, then constant up to 24 hours.

  Biphasic insulin:

  • Combination of NPH and short/rapid-acting.
  • Examples: Novomix 30 (30% aspart, 70% aspart protamine), Humalog Mix50 (50% lispro, 50% lispro protamine).

  Prescribing

  Dose:

  • Dose always starts low then titrated up based on glucose measurements.
  • Roughly, total daily dose of insulin (TDDI) is 0.5 units/kg/day in kids, and 0.3-0.5 units/kg/day in adults.
  • More required if ill.

  Avoiding prescribing errors, which can be fatal:

  • Use insulin syringe (marked with units), even for infusion.
  • Always write 'unit', not 'u'.
  • Use full correct name (usually brand name) including strength.

  Regimens

  Once daily regimen

  • Used in type 2 diabetes
  • Long or intermediate insulin at bedtime.

  Twice daily regimen

  • Used in type 1 or type 2 diabetes. Easy for kids, although they are increasingly being started on MDI.
  • Biphasic insulin pre-breakfast (⅔) + pre-dinner (⅓).
  • Side effects: nocturnal ↓glucose and morning ↑glucose.

  Basal-bolus insulin regime

  Aka multiple daily injections (MDI).

  Indications and method:

  • Standard for type 1 diabetes.
  • Bolus injections: 3 x rapid acting pre-meal.
  • Basal injections: 1 x long acting pre-bed (8-9 PM) or 2 x NPH (AM and PM).

  Calculating injection amount:

  • The amount for each bolus is the number of units required to cover the carbs to be eaten, plus the amount required to bring the blood glucose back down to 4-8 mmol/L.
  • The basal amount is TDDI÷2, and the other half should roughly be divided in 3 for the boluses.
  • CHO:insulin ratio: how many grams of carbs can be eaten with each unit of insulin. Calculation: 500÷TDDI.
  • Insulin sensitivity factor: how much blood glucose will come down with each unit of insulin. Calculation: 100÷TDDI.

  Continuous SC insulin infusion (SCII)

  • Aka insulin pump.
  • Continuous rapid-acting insulin, plus meal-time boluses activated by the patient.
  • Indications: MDI failed (e.g. severe hypos), HbA1c ≥69 mmol/mol despite high care, kids <12 years if MDI impractical.
  • Side effects: DKA risk if poorly used, expensive.

  Side effects

  • Hypoglycaemia, so patients must inform the DVLA. Must meet very strict requirements to apply for a HGV license.
  • Lipoatrophy where injecting. Vary site to reduce it, including abdo wall (quicker absorption) and thigh.