Diabetes

This is a condition which results from a lack of, or reduced effectiveness of endogenous insulin. There are two main types of diabetes mellitus, as well as some other rarer causes.

• Type 1 Diabetes

This is insulin deficiency due to an autoimmune destruction of pancreatic B-cells

– T lymphocytes attack islets, with autoantibodies against insulin present

– It is associated with HLA-DR3 and HLA-DR4

– The disease usually manifests in adolescence, sometimes after a viral infection.

Symptoms: Hyperglycemia – low insulin leads to decreased glucose uptake by fat and muscle

– Weight loss, low muscle mass – unopposed glucagon leads to lipolysis and glycogenolysis

– Polyuria, polydipsia and glycosuria

Management:

1) Insulin therapy – twice-daily insulin detemir is the regime of choice (2x long-acting)

– 2nd line, once-daily insulin glargine or insulin detemir

2) Monitor HbA1c every 3-6months – target of <48mM

3) Self-monitoring glucose – test this 4 times/day, before and after each meal + before sleep

– More frequency monitoring in illness, sport, pregnancy and breastfeeding

– Target = 5-7mM (Waking)       4-7mM (before meals)

4) Metformin – consider adding if BMI > 25kg/m²

5) Glucagon kit – given to all patients in case of hypoglycaemic crisis

There are several complications which are associated with Type 1 diabetes, which can be life threatening:

• Diabetic ketoacidosis

This is an emergency which is characterized by severe hyperglycaemia and severe acidosis, seen in diabetes.

– Due to the body being in starvation like state and excessive ketone body production.

Management – Use the ABC approach

i) Start fluid infusion 1L 0.9% saline

ii) Add insulin – IV infusion at 0.1 unit/kg/hour

– If on insulin, continue long-acting insulin, stop short-acting

iii) Monitor blood glucose and ketones hourly

iv) Dextrose solution – once [glucose] < 15mM, add 5% dextrose to prevent hypoglycaemia

v) Monitor Potassium – insulin forces K⁺ into cells, so give potassium to reduce hypokalaemia

Complications:

– Arrhythmias secondary to hyperkalaemia/iatrogenic hypokalaemia

– Cerebral oedema –> seen more in children/young adults, occurs 4-12 hours usually after treatment

–> Gives headache, confusion, visual disturbances due to raised ICP

• Impaired Hypoglycaemia Awareness

Long standing hyperglycaemia can lead to neuropathy of the autonomic nervous system.

– This is the leading cause of impaired hypoglycaemic awareness in diabetic patients

– Awareness is also reduced by usage of b-blockers

• Type 2 diabetes

This is end-organ insulin resistance which is the most common form of diabetes.

– Arises in middle aged, obese adults due to decreased number insulin receptors.

– Later insulin deficiency develops due to b-cells exhaustion

Causes: Obesity, lack of excessive + alcohol excess

– Stronger genetic influence than type 1 – high in Asians, men and the elderly

Symptoms: Initially clinically silent, but then similar symptoms to Type 1 in later disease

Diagnosis:

The diagnosis of diabetes mellitus can be made using plasma glucose or a HbA1c sample[1].

– Plasma glucose or HbA1c must show evidence of diabetes of two separate occasions if asymptomatic:

3) If HbA1c rises >58mM

– Add sulphonylurea or DPP–4 inhibitor

      or Thiazolidinedione or SGLT-2 inhibitor

4) If HbA1c stays >58mM

– Add 3rd drug (metformin + 2 of previous)

5) If not effective/tolerated and BMI>35 kg/m²

– Try metformin + Sulphonylurea + GLP1 mimic

6) If still not controlled –> commence insulin therapy (but continue metformin)

In addition to Type 1 and 2 diabetes, there are a few variant types of diabetes.

• Latent autoimmune diabetes of adults (LADA) – a form of type 1 DM, but with slower progression to insulin dependence in later life.

• Maturity Onset Diabetes of the Young – autosomal dominant mutation in HNF1A gene

– Leads to poor production of insulin, causing T2DM symptoms in much younger patients

Treatment – Sulphonylureas

• Gestational diabetes – transitory form caused by pregnancy associated hormonal changes

• Prediabetes – Used for patients who do not meet the criteria but are likely to develop condition soon

– HbA1c of 42-47mmol/mol or Fasting Glucose of 6.1-69mM

• Secondary diabetes – this can be due to conditions that affect blood glucose and/or insulin:

– Pancreatitis – damage to insulin producing cells.

– Hyperthyroidism – thyroid hormone excess

– Acromegaly – GH excess                                              – Cushing’s disease – cortisol excess