Type 1 Diabetes Mellitus


  • Systemic disorder characterised by a lack of insulin due to destruction of β-islet cells
  • It accounts for around 15% of all cases of diabetes mellitus and around 90% of DM in children/young adults


  • Genetic factors account for up to a third of type 1 DM (polygenic).
    • In particular HLA-DR3 and DR4, HLA-DQA1 and DQB1
    • Family history, however, is relatively rare
  • T-cell mediated autoimmune destruction of the insulin-secreting β-islet cells of the pancreas.
  • Causes a progressive loss of β-cell function over months-years
    • Inflammatory process (insulitis)- involving activated macrophages, helper cytotoxic and suppressor T lymphocytes, natural killer cells and B lymphocytes.
    • Initial (and even later) stage disease is patchy, with inflammation of specific areas surrounded by otherwise normal tissue.  Symptoms only manifest once 80-90% of the β-islet cells are destroyed, once inflammation has spread throughout the pancreas.
    • ONLY β-cells are affected (α/γ cells remain unaffected)
  • Because the final stages of the pathogenesis (i.e. global destruction of the islet cells due to both autoimmune destruction and glucose toxicity) is quite rapid, features of the disease tend to appear subacutely-acutely with features of hypoinsulinaemia (see below)


  • Hyperglycaemia leads to
    • Glycosuria and dehydration
      • Fatigue, polyuria, nocturia, thirst, polydipsia, susceptibility to UTIs
    • Lipolysis and proteolysis
      • Weight loss
    • Persistently very high blood glucose levels may also present with diabetic ketoacidosis (may be an emergency presentation or not)
  • Symptoms usually develop over several weeks


  • Urine testing
    • Often used to screen patients in whom there is a clinical suspicion
      • Dipstick urinalysis for glucose and ketones
        • Note that there are other causes of glycosuria (e.g. pregnancy, drugs (antibiotics))
        • Ketonuria, particularly in children and in association with glycosuria, warrants an urgent referral to the diabetic clinic for quick diagnosis and management/long-term treatment
      • Proteinuria may indicate development of diabetic nephropathy
  • Blood
    • Glucose
      • Diabetes may be diagnosed with a blood glucose level of ≥11.1mmol/l (random or 2hrs after a 75g glucose load) or a fasting glucose of ≥7mmol/l if the patient is symptomatic
        • If the patient is asymptomatic, two tests on separate occasions are required
      • NB Pre-diabetes is defined as
        • Impaired fasting glucose i.e. fasting glucose ≥6mmol/l (<7mmol/l) (without raised glucose post-75mg load)
        • Impaired glucose tolerance i.e. fasting glucose <7mmol/l and 2hr glucose after 75mg load is 7.8-11.1mmol/l
    • Ketones (β-OHB)
      • <0.6mmol/l- normal- no action required
      • 0.6-1.5mmol/l- suggests metabolic control may be deteriorating- continue to monitor and seek medical advice if sustained/progressive
      • 1.5-3mmol/l- With high blood glucose (>10mmol/l), there is a significant risk of DKA- seek medical advice
      • >3mmol/l- Severe ketosis; with raised blood glucose, high risk of DKA- seek urgent medical help
    • Glycated haemoglobin (measures glycaemic control averaged over weeks/months- roughly a rise of 1% = 2mmol/l of blood glucose)
      • An HbA1c of >48mmol/mol (or 6.5%) is suggestive of diabetes
      • Target HbA1c is usually <53mmol/mol (<7%)
      • NB HbA1c may not be accurate in patients with haemoglobinopathies; haemolytic anaemia; iron deficient anaemia; children; HIV; chronic kidney disease
    • Autoantibodies are not routinely measured


  • Insulin treatment is required for all patients with T1DM to prevent DKA and the associated mortality
  • There are several types of insulins
    • Rapid-acting insulin analogues e.g. Insulin aspart, lispro and glulisine (onset of action ~15mins, peak at 1 hour and last 3-4 hours)- commonly used around meals to buffer the increase in glucose
    • Soluble (short-acting) insulin (onset 30 mins; peak at 2-3 hours and last ~8 hours)- ideally should be injected 30 mins before meals
    • Intermediate-acting (isophane) insulin (onset 2-4 hours, peak at 6-7 hours and lasts 20 hours)- used most commonly in twice daily regimens.  Can come ready mixed with shorter acting insulins.
    • Long-acting insulin analogues e.g. glargine/detemir (onset 1-3 hours, then plateau and last for 20-24 hours)- used once or twice daily to achieve steady state constant insulin (resembles physiological state)
  • There are different regimes of insulin treatment.  The two most commonly used in T1DM are
    • Twice daily regime (two administrations of a mix of intermediate and short acting insulins at a ratio of 2:1- 2/3rds of the total dose given in the morning and the remainder before the evening meal)
    • Basal-bolus regime (single dose of long-acting insulin accompanied by boluses of rapid acting insulins at meal times)
      • Suitable for well-motivated individuals with a good understanding of the disease and need for insulin.
  • Where appropriate, patients may be given BM kits for measuring blood sugar
    • Aim for pre-prandial BM of 4-7mmol/l and post-prandial BM of <9mmol/l

See also Complications of Diabetes


Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )

Connecting to %s

%d bloggers like this: