Q1 LONG ANSWER 10M ★ High-yield

Classify insulin preparations. Describe the regimens, uses and adverse effects of insulin and the management of hypoglycaemia.

Pharmacology · 2nd Professional — Para-Clinical

Insulin Preparations

Type	Examples	Onset	Peak	Duration	Role
Rapid-acting analogues	LISPRO, aspart, glulisine	10–15 min	1 h	3–5 h	Given with the meal; the amino acid change prevents hexamer formation so absorption is fast
Short-acting (regular / soluble)	Human regular insulin	30 min	2–3 h	6–8 h	Given 30 min before food; the only insulin that may be given intravenously, hence its use in ketoacidosis
Intermediate (NPH / isophane)	Insulin with protamine and zinc	1–2 h	6–12 h	18–24 h	Basal cover; the peak causes nocturnal hypoglycaemia
Long-acting analogues	Glargine, detemir, degludec	1–2 h	Peakless — a flat profile	24 h (degludec >40 h)	Basal cover with much less nocturnal hypoglycaemia
Premixed	30/70, 25/75 biphasic	—	Two peaks	12–18 h	Twice-daily regimens; convenient but inflexible

Regimens

Basal-bolus (multiple daily injections) — a long-acting basal insulin once daily plus a rapid-acting bolus with each meal. The most physiological, the most flexible, and the standard in type 1 diabetes
Twice-daily premixed — simpler and fewer injections, but requires fixed meal times and doses; still widely used in India where cost and monitoring are constraints
Basal insulin added to oral agents — the usual first step when oral treatment fails in type 2 diabetes
Continuous subcutaneous infusion (insulin pump) — the closest approach to physiological delivery, increasingly combined with continuous glucose monitoring in closed-loop systems
Intravenous infusion of regular insulin — in ketoacidosis, hyperosmolar state, and perioperatively

CLINICAL PEARL

The whole design of insulin therapy is an attempt to reproduce two separate secretion patterns. The normal pancreas provides a low continuous basal output between meals, and a sharp prolactin-like bolus at each meal. Long-acting peakless analogues imitate the first; rapid analogues imitate the second. Every regimen is judged by how closely it approaches that pattern against how many injections the patient will actually take.

Uses

Type 1 diabetes — essential and lifelong; these patients die without it
Type 2 diabetes — where oral agents fail, in intercurrent illness, surgery, or with very high glucose at presentation
Diabetic ketoacidosis and hyperosmolar hyperglycaemic state — intravenous regular insulin
Gestational diabetes not controlled by diet; insulin does not cross the placenta
Hyperkalaemia — insulin with glucose drives potassium into cells; a temporising measure
Perioperative and critical care glycaemic control

Adverse Effects

Effect	Details
Hypoglycaemia — the most important	Autonomic warning first: sweating, tremor, palpitations, hunger, anxiety; then neuroglycopenic: confusion, slurred speech, odd behaviour, seizures, coma. Precipitated by a missed meal, extra exercise, alcohol, an excessive dose, renal impairment, or a wrong injection
Hypoglycaemia unawareness	Loss of the autonomic warning after repeated episodes or with beta-blockers, autonomic neuropathy or long duration — the patient goes straight to confusion and coma. Relieved by avoiding hypoglycaemia strictly for some weeks
Weight gain	Anabolic effect and reduced glycosuria
Lipodystrophy at injection sites	Lipohypertrophy from repeatedly injecting the same spot — absorption from such sites is erratic, causing unexplained swings. Prevented by rotating sites, and sites must be examined at every review
Allergy and local reactions	Now rare with human and analogue insulins
Insulin oedema and transient blurred vision	On starting or after rapid improvement in control
Hypokalaemia	Potassium shifts intracellularly — important during treatment of ketoacidosis

Management of Hypoglycaemia

Conscious and able to swallow — 15 to 20 g of rapid-acting glucose (glucose tablets, sugar, sweetened drink), repeated after 15 minutes if needed, then a longer-acting carbohydrate
Unconscious or unable to swallow — intravenous 25% dextrose, or glucagon intramuscularly where no vein is available (though glucagon fails in a patient with depleted liver glycogen, as in alcoholism or starvation)
Nothing by mouth in an unconscious patient — a real risk of aspiration, and a common error by relatives
Sulphonylurea-induced hypoglycaemia is prolonged and recurs; such patients need admission and a glucose infusion, not simply a sweet drink and discharge
Acarbose-treated patients must be given glucose, not sucrose, since acarbose blocks the enzyme that would split sucrose

The Somogyi and Dawn Phenomena

Feature	Somogyi phenomenon (rebound)	Dawn phenomenon
Mechanism	Nocturnal HYPOglycaemia triggers counter-regulatory hormones (glucagon, cortisol, growth hormone, catecholamines), causing rebound hyperglycaemia	The normal early-morning surge of growth hormone and cortisol raises glucose; no preceding hypoglycaemia
Glucose at 3 a.m.	Low	Normal or high
Morning glucose	High	High
Other clues	Night sweats, nightmares, morning headache	None
Correct action	Reduce the evening insulin, or add a bedtime snack — increasing it makes matters worse	Increase the evening basal insulin, or switch to a peakless analogue or a pump

The two present identically in the morning and require opposite treatment, which is why a 3 a.m. Glucose measurement (or continuous monitoring) is needed before adjusting the dose — raising insulin in a Somogyi patient deepens the nocturnal hypoglycaemia and worsens the rebound
Peakless long-acting analogues have made the Somogyi phenomenon much less common, since NPH insulin peaking at 2 to 3 a.m. Was its usual cause

Applied Aspects

Teach injection technique, site rotation and storage — insulin must be kept cool, which is a real difficulty in much of India where refrigeration is unreliable; unopened vials keep in an earthen pot with water in an emergency
Examine injection sites at every visit; lipohypertrophy is common, painless (which is why patients prefer those sites) and a frequent cause of unexplained instability
Every patient must carry glucose and identification, and family members must be taught to recognise and treat hypoglycaemia
Reduce insulin before unusual exercise and take extra carbohydrate; exercise increases insulin sensitivity for many hours afterwards
Never omit insulin in a type 1 patient who is not eating because of illness — basal insulin must continue or ketoacidosis follows; this "sick day rule" is among the most important things to teach
Beta-blockers mask hypoglycaemic warning and are used cautiously in insulin-treated patients, though cardioselective agents are acceptable where indicated
Insulin requirements fall in renal impairment, since the kidney degrades a substantial fraction; unexplained hypoglycaemia in a stable patient should prompt a check of renal function
Requirements rise in infection, pregnancy, surgery and with corticosteroids, and fall with exercise and weight loss
Check that the patient can actually see the syringe markings and manage the device; visual impairment from retinopathy and arthritis of the hands are common and frequently unaddressed causes of dosing error
Cost and cold storage are the practical limits in India, and analogue insulins are unaffordable for many; human insulin used properly achieves good control and remains appropriate

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