Type 1 diabetes mellitus

Question 1

What are the ambiguities in classification of diabetes mellitus?

Answer 1

Autoimmune ‘type 1’ diabetes leading to insulin deficiency can present >decades of life = latent autoimmune diabetes in adults (LADA).
T2DM may present in childhood.
Diabetic ketoacidosis is a feature of T2DM.
Monogenic diabetes can present phenotypically as type 1 or 2 diabetes (e.g. MODY, mitochondrial diabetes).
Diabetes may present following pancreatic damage or other endocrine disease.

Question 2

What is the current classification of diabetes mellitus based on aetiology?

Answer 2

Type 1: environmental trigger and genetic influences lead to autoimmune destruction of islet cells, insulin deficiency and hyperglycaemia.
Type 2: strong genetic influence and association with obesity lead to insulin resistance and hyperglycaemia.

Question 3

Why is the immune basis of T1DM important?

Answer 3

Increased prevalence of other autoimmune disease.
Risk of autoimmunity in relatives.
More complete destruction of beta cells.
Auto-antibodies can be useful clinically.
Immune modulation offers the possibility of novel treatments.

Question 4

What haplotypes produce significant genetic susceptibility to T1DM?

Answer 4

HLA-DR3 and HLA-DR4.

Question 5

What are the markers that can be measured for T1DM?

Answer 5

Islet cell antibodies (ICA)- grp O human pancreas.
Insulin antibodies (IAA).
Glutamic acid decarboxylase (GADA)- widespread neurotransmitter.
Insulinoma-associated-2 autoantibodies (IA-2A)-receptor like family.

Question 6

What are the symptoms of T1DM?

Answer 6

Polyuria.
Nocturia.
Polydipsia.
Blurring of vision.
'Thrush'.
Weight loss.
Fatigue.

Question 7

What are the signs of T1DM?

Answer 7

Dehydration.
Cachexia.
Hyperventilation.
Smell of ketones.
Glycosuria.
Ketonuria.

Question 8

What are the aims of treatment of T1DM?

Answer 8

Reduce early mortality.
Avoid acute metabolic decompensation.
Need exogenous insulin to preserve life.
Ketones define insulin deficiency.
Prevent long term complications: retinopathy, nephropathy, neuropathy, vascular disease.

Question 9

What is the recommended diet for type 1 diabetics?

Answer 9

Reduce calories as fat.
Reduce calories as refined carbohydrate.
Increase calories as complex carbohydrates.
Increase soluble fibre.
Balance distribution of food over course of day with regular meals and snacks.

Question 10

How do insulin levels change in a non-diabetic subject throughout the day?

Answer 10

Over night, low basal amount of insulin produced.

Insulin produced to normalise glucose level after a meal- peaks, then returns to basal level.

Question 11

What are the different types of insulin treatment available to patients with T1DM?

Answer 11

With meals: short acting, human insulin, insulin analogue (lisper, aspart, glulisine).
Background: long acting, non-c bound to zinc or protamine, insulin analogue (glargine, determir, degludec).
Genetic engineering to alter absorption, distribution, metabolism and excretion.

Question 12

What is the insulin pump?

Answer 12

Continuous insulin delivery.
Pre-programmed basal rates and bolus for meals.
Does not measure glucose, no completion of feedback loop.
Meant to mimic insulin profile of non-diabetic subject.

Question 13

What is the purpose of capillary monitoring in type 1 diabetics?

Answer 13

Measures capillary glucose levels through finger pricks- depends on tissue perfusion (e.g. temperature), can have continuous glucose monitor instead.

Question 14

How is HbA1c used to measure blood glucose?

Answer 14

Glucose reacts with red cells- irreversible, non-covalent.
Measures level of glucose.
Depends on lifespan of red cell (120 days), rate of glycation (faster in some individuals), haemoglobinopathy, renal failure, etc.
Glucose levels over 3 month period, measured through blood test. Measure of long-term glycaemic control.
More glucose = higher HbA1c.

Question 15

Give examples of acute complications of T1DM.

Answer 15

Ketoacidosis.
Hyperglycaemia: reduced tissue glucose utilisation, increased hepatic glucose production.
Metabolic acidosis: circulating acetoacetate and hydroxybutyrate, osmotic dehydration and poor tissue perfusion.

Question 16

What are the effects of hypoglycaemia in diabetic patients?

Answer 16

Most mental processes impaired at <3mmol/L.
Consciousness impaired at <2mmol/L.
Severe hypoglycaemia may contribute to arrhythmia and sudden death,
May have long-term effects on the brain.
Recurrent hypos result in loss of warnings- ‘hypoglycaemia unawareness’.

Question 17

What is severe hypoglycaemia?

Answer 17

Any hypo requiring help of another person to treat.

Question 18

What is severe hypoglycaemia?

Answer 18

Any hypo requiring help of another person to treat.

Question 19

Who may be affected by hypoglycaemia?

Answer 19

Main risk factor is quality of glycaemic control.

More frequent in patients with low HbA1c.

Question 20

When do hypoglycaemic attacks tend to occur?

Answer 20

Can occur at any time but often a clear pattern.
Pre-lunch hypos common.
Nocturnal hypos very common and often not recognised.

Question 21

Why do hypoglycaemic attacks occur?

Answer 21

Unaccustomed exercise.
Missed meals.
Inadequate snacks.
Alcohol.
Inappropriate insulin regime.

Question 22

What are the symptoms and signs of hypoglycaemia due to increased autonomic activation?

Answer 22

Palpitations and tachycardia.
Tremor.
Sweating.
Pallor/ cold extremities.
Anxiety.

Question 23

What are the symptoms and signs of hypoglycaemia due to impaired CNS function?

Answer 23

Drowsiness.
Confusion.
Altered behaviour.
Focal neurology.
Coma.

Question 24

How is hypoglycaemia treated?

Answer 24

Oral: feed the patient!
Glucose- rapidly absorbed as solution or tablets.
Complex carbohydrates- to maintain blood glucose after initial treatment.

Parenteral: give if consciousness impaired.
IV dextrose, e.g. 10% glucose infusion.
1mg glucagon IM.
Avoid concentrated solutions if possible (e.g. 50% glucose).