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Physiology

Endocrine

Question 167 of 180

Which of the following is NOT a typical clinical feature of hypoglycaemia:

Answer:

Clinical features of hypoglycaemia:
  • Autonomic  symptoms
    • Sweating, feeling hot, anxiety/agitation, palpitations, shaking, paraesthesia, dizziness
  • Neuroglycopaenic symptoms
    • Weakness, blurred vision, difficulty speaking, poor concentration, poor coordination, drowsiness, confusion, seizures, coma
  • Other symptoms
    • Nausea, fatigue, hunger

Diabetes Mellitus

Diabetes mellitus is a metabolic disorder characterised by persistent hyperglycaemia which is a result of defects in insulin secretion, insulin action or both.

Classification

Diabetes mellitus is broadly classified as type 1 or type 2 (although rarer causes of diabetes exist):

  • Type 1 (5 - 10%)
    • Autoimmune destruction of beta-cells of the pancreas results in absolute insulin deficiency with patients requiring insulin to survive
    • In absence of insulin action in muscle and adipose tissue, glucose is not transported into cells by the GLUT4 transporter
  • Type 2 (90 - 95%)
    • Caused by both insulin resistance and a defect in insulin secretion as a result of beta-cell dysfunction
    • Insulin resistance occurs in skeletal muscle, adipose tissue and liver, resulting in reduced glucose uptake in skeletal muscle, impaired inhibition of hepatic glucose output and increased fatty acid production in adipose tissue, which stimulates gluconeogenesis and triglyceride synthesis
    • Risk factors include obesity, lack of physical activity, increasing age, dyslipidaemia, hypertension, certain ethnic groups, genetic predisposition

Clinical Features

T1DM:

  • Osmotic symptoms
    • Thirst, polydipsia, polyuria
    • Dehydration, hypovolaemia, drowsiness
    • Blurred vision
    • Cutaneous Candida infections
  • Catabolic symptoms
    • Muscle wasting, fatigue and weight loss
  • Diabetic ketoacidosis (approx 25% of children with T1DM present in DKA)
    • Aetiology
      • Impairment of glucose utilisation in the peripheral tissues leads to increased gluconeogenesis and glycogenolysis in the liver with consequent worsened hyperglycaemia.
      • Simultaneous counter-regulatory hormone hypersecretion (including cortisol, glucagon and catecholamines) in tandem with insulin deficiency causes release of free fatty acids into the circulation as a result of lipolysis in adipose tissue.
      • Free fatty acids undergo oxidation in the liver to produce ketone bodies and subsequent ketonaemia. As ketone bodies are weakly acidic, this causes increased plasma hydrogen ion concentrations and metabolic acidosis.
    • Characterised by the biochemical triad:
      • Hyperglycaemia (> 11 mmol/L)
      • Ketonaemia (> 3 mmol/L)
      • Acidosis (pH < 7.3 +/- HCO3 < 15 mmol/L)
    • Clinical features
      • Symptoms
        • Polyuria, polydipsia, thirst, lethargy, weight loss, nausea, vomiting, anorexia, abdominal pain, dehydration, headache, altered mental state
      • Signs
        • Dry mucous membranes, ketotic breath, tachycardia, hypotension, Kussmaul breathing, focal signs of precipitant e.g. infection
    • Management
      • Fluid replacement
      • Insulin (+ glucose)
      • Monitoring of [K+] (+/- replacement)
      • Treat underlying cause

T2DM:

  • One-third of cases are detected incidentally
  • Diagnosis is often delayed for many years and the patient can therefore present with complications from prolonged hyperglycaemia
  • Only about half of patients present with the classic symptoms of thirst, polydipsia, polyuria and tiredness secondary to hyperglycaemia, although these symptoms are less marked than in T1DM
  • Hyperglycaemic hyperosmolar state (up to 25% of patients with T2DM present as HHS)
    • Aetiology
      • Prolonged hyperglycaemia from insulin resistance or insulin deficiency results in an osmotic diuresis with renal sodium and potassium loss.
      • This results in extracellular volume depletion and dehydration, with a raised serum osmolality.
      • Ketosis/ketonaemia does not typically occur in HHS, because some insulin is still present and hyperosmolality can inhibit lipolysis.
    • Characterised by triad:
      • Hypovolaemia
      • Marked hyperglycaemia (> 30 mmol/L) without significant hyperketonaemia or acidosis
      • Osmolality > 320 mosmol/kg
    • Clinical features
      • Polydipsia, polyuria, impaired cognitive function, tachycardia, hypotension, seizures
    • Management
      • Treat underlying cause
      • Fluid replacement (+/- insulin)
      • Correct electrolyte imbalance
      • Treat with prophylactic anticoagulation

Diagnosis

  • Glucose concentration criteria:
    • In symptomatic individuals (e.g. thirst, polyuria, polydipsia and unexplained weight loss):
      • A random venous plasma glucose concentration ≥ 11.1 mmol/L OR
      • A fasting plasma glucose concentration ≥ 7.0 mmol/L OR
      • Two-hour plasma glucose concentration ≥ 11.1 mmol/L after 75g anhydrous glucose in an oral glucose tolerance test (OGTT)
    • In asymptomatic individual:
      • At least one of the above criteria fulfilled on two separate occasions
  • HbA1c criteria:
    • HbA1c ≥  48 mmol/mol (6.5%) confirmed with second sample unless individual is symptomatic with plasma glucose ≥ 11.1 mmol/L when confirmation is not needed
    • N.B. Not to use in children and young people, type 1 DM, symptom onset within 2 months, pregnancy, drugs causing hyperglycaemia (e.g. steroids) or blood conditions affecting Hb (e.g. haemolytic anaemia)

Complications

  • Macrovascular
    • Ischaemic heart disease
      • Angina, ACS
    • Cerebrovascular ischaemia
      • TIA, stroke
    • Peripheral vascular disease
      • Intermittent claudication, acute ischaemic limb, foot ulcer
  • Microvascular
    • Autonomic neuropathy
      • Resting tachycardia, postural hypotension, cardiac ischaemia, sudden cardiac death
      • Gastroparesis, constipation/diarrhoea, oesophageal dysmotility
      • Erectile dysfunction, neuropathic bladder
    • Mononeuropathies
      • Often cranial nerves III and VI, median, ulnar and radial nerves
    • Diabetic peripheral neuropathy
      • Glove and stocking distribution, foot ulceration
    • Diabetic nephropathy
      • CKD
    • Diabetic retinopathy
      • Blindness

Hypoglycaemia

Hypoglycaemia occurs when plasma glucose falls below 4 mmol/L. It commonly occurs as a result of insulin therapy; it can also occur with certain oral hypoglycaemic agents.

In individuals without diabetes, the normal response to hypoglycaemia comprises reduced insulin secretion from the pancreas and increased glucagon release. A number of counter-regulatory hormones, including noradrenaline, cortisol and growth hormone, are also released. In patients with diabetes, these responses are reduced, especially with recurrent hypoglycaemia and with increased duration of disease - this can result in hypoglycaemic unawareness.

Clinical features of hypoglycaemia:

  • Autonomic  symptoms
    • Sweating, feeling hot, anxiety/agitation, palpitations, shaking, paraesthesia, dizziness
  • Neuroglycopaenic symptoms
    • Weakness, blurred vision, difficulty speaking, poor concentration, poor coordination, drowsiness, confusion, seizures, coma
  • Other symptoms
    • Nausea, fatigue, hunger

Any suspected hypoglycaemia should be managed as an emergency, and treated immediately to return blood glucose to the normal range.

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  • Biochemistry
  • Blood Gases
  • Haematology
Biochemistry Normal Value
Sodium 135 – 145 mmol/l
Potassium 3.0 – 4.5 mmol/l
Urea 2.5 – 7.5 mmol/l
Glucose 3.5 – 5.0 mmol/l
Creatinine 35 – 135 μmol/l
Alanine Aminotransferase (ALT) 5 – 35 U/l
Gamma-glutamyl Transferase (GGT) < 65 U/l
Alkaline Phosphatase (ALP) 30 – 135 U/l
Aspartate Aminotransferase (AST) < 40 U/l
Total Protein 60 – 80 g/l
Albumin 35 – 50 g/l
Globulin 2.4 – 3.5 g/dl
Amylase < 70 U/l
Total Bilirubin 3 – 17 μmol/l
Calcium 2.1 – 2.5 mmol/l
Chloride 95 – 105 mmol/l
Phosphate 0.8 – 1.4 mmol/l
Haematology Normal Value
Haemoglobin 11.5 – 16.6 g/dl
White Blood Cells 4.0 – 11.0 x 109/l
Platelets 150 – 450 x 109/l
MCV 80 – 96 fl
MCHC 32 – 36 g/dl
Neutrophils 2.0 – 7.5 x 109/l
Lymphocytes 1.5 – 4.0 x 109/l
Monocytes 0.3 – 1.0 x 109/l
Eosinophils 0.1 – 0.5 x 109/l
Basophils < 0.2 x 109/l
Reticulocytes < 2%
Haematocrit 0.35 – 0.49
Red Cell Distribution Width 11 – 15%
Blood Gases Normal Value
pH 7.35 – 7.45
pO2 11 – 14 kPa
pCO2 4.5 – 6.0 kPa
Base Excess -2 – +2 mmol/l
Bicarbonate 24 – 30 mmol/l
Lactate < 2 mmol/l

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