Controlling Blood Glucose

3.11.05

Physiological control
• Postprandial increased insulin - glycogen/amino acid/fatty acid synthesis.
• Between meals - glycogenolysis, gluconeogenesis, fatty acid breakdown etc.

Insulin
• Peptide.
• Secreted from β cells of pancreas in response to rise in blood glucose.
• Drive glucose into cells (with K+) - lowers blood glucose.
• Promotes glycogenesis, fatty acid formation, amino acid synthesis - anabolic effects.
• Acts at specific receptors.

Diabetes mellitus
Type I
• Destruction of islets of Langerhans (why? Infection? Autoimmunity?)
• Lack of insulin.
• No glucose entring cells - hyperglycaemia, polyuria, polydipsia, dehydration.
• Fat breakdown increased - weight loss - incomplete, so free fatty acids.
• Ketoacidosis.
• Death.
• Onset occurs at less than 40 years of age.
• Normal/wasted appearance.
• Low/absent insuling.
• Abrupt onset symptoms.

Type II
• Peripheral insulin resistance.
• Less peripheral glucose absorption.
• Insulin levels often high.
• Pulyuria, polydipsia (dehydration).
• Fatigue, infections.
• No ketoacidosis.
• FHx.
• Onset occurs at more than 40 years of age.
• Obesity.
• Normal/increased insulin.
• Gradual onset symptoms.
• Hyper-osmolar coma in elderly sufferers.

Epidemiology
• Type I
-Younger patients.
-Less common.
-Often no family history.
-0.1-0.5%.
• Type II - older patients; very common and becoming more so - 1-4% adults.

Treatment - Type I
• Acutely.
• Rehydrate.
• Insulin.
• Correct acidosis?
• Chronically - insulin, diet.

Treatment - Type II
• Diet.
• Oral agents.
• Insulin.
• Often progressive disease.

Complications of diabetes mellitus:
• Glysylation of proteins (and other problems) leads to complications.
-Angiopathy - macrovascular, microvascular.
-Neuropathy.
-Nephropathy.
-Retinopathy.
• Occur in both forms (no such thing as "mild diabetes").
• Needs prophylaxis and treatment.

Insulin
• Stimulates β2 adrenoreceptors in pancreatic β cells - stimulates conversion of PRO-INSULIN to INSULIN (a and b chain) and C-PEPTIDE.
• Inactive if given orally.
• Given parenterally - subcutaneous, inter-muscular, intravenous.
• Wide variety of preparations.
• Source: bovine (3 amino acids' difference), porcine (1 amino acid).
• Human (90%).
-Chemically modified porcine or genetically engineered.

Duration of action:
• Soluble insulin - short, 0.5-1 hours.
• Insulin complexes - isophane/proteamine.
-Slow relase of insulin over several hours.
• Insulin analogues.
-Short-acting insulin lispro.
-Long-acting - insulin glargine.

Adverse effects of insulin (affect both Types I and II):
• Hypoglycaemia
-Sympathetic over-activity leads to tachycardia, sweats, tremor, palpitations.
-Neuroglycopenia leads to visual disturbance, drowsiness, aggression, coma.
-30% diabetics lose adrenergic symptoms of hypoglycaemia during 15-20 years of insulin therapy.
• Allergy?
-Antibodies - resistance.
• Local problems - lipodystrophy.

Oral hypoglycaemics (Type II):
• Sulphonylureas
-Gliclazide and many others.
-Stimulate insulin release from pancreas.
-Increase insulin sensitivity.
-Hypoglaycaemia.