Q1 LONG ANSWER 10M ★ High-yield

Discuss the classification, pathogenesis, clinical features, diagnosis and management of diabetes mellitus.

General Medicine · Final Professional

Definition

Diabetes mellitus is a group of metabolic disorders characterised by chronic hyperglycaemia resulting from defects in insulin secretion, insulin action, or both, leading to long-term microvascular and macrovascular complications. India carries one of the largest diabetic populations in the world, with a distinct phenotype — onset a decade earlier, at a lower BMI, with greater central adiposity and insulin resistance than in Western populations.

Classification

Feature	Type 1	Type 2
Pathogenesis	Autoimmune beta-cell destruction — absolute insulin deficiency	Insulin resistance with progressive beta-cell failure
Age at onset	Usually childhood/adolescence	Usually > 40 years (falling in India)
Body habitus	Lean	Overweight, central obesity
Onset	Abrupt, weeks	Insidious, often asymptomatic for years
Ketosis	Prone — presents with DKA	Resistant; presents with HHS
Autoantibodies	Anti-GAD65, IA-2, ZnT8, islet cell	Absent
C-peptide	Low or absent	Normal or high (low late in disease)
Treatment	Insulin from diagnosis, lifelong	Lifestyle, oral agents, later insulin

Other types: gestational diabetes; MODY (autosomal dominant, young, non-obese, non-ketotic, often sulphonylurea-responsive); LADA (latent autoimmune diabetes in adults); secondary diabetes from pancreatic disease (fibrocalculous pancreatic diabetes is important in India), Cushing's syndrome, acromegaly, phaeochromocytoma, and drugs (corticosteroids, thiazides, antipsychotics, protease inhibitors).

Pathogenesis of Type 2 Diabetes — the "ominous Octet"

Eight mechanisms contribute, and each is a drug target: reduced insulin secretion (beta cell), increased glucagon (alpha cell), increased hepatic glucose production, decreased muscle glucose uptake, increased lipolysis (adipocyte), increased renal glucose reabsorption, decreased incretin effect (gut), and neurotransmitter dysfunction (brain).

Risk factors: family history, obesity (especially central obesity — waist circumference thresholds are lower for Indians: ≥ 90 cm men, ≥ 80 cm women), physical inactivity, dietary pattern, prior gestational diabetes, PCOS, and low birth weight (thrifty phenotype).

Clinical Features

Classic osmotic symptoms: polyuria, polydipsia, polyphagia with weight loss, nocturia, fatigue, blurred vision.
Infections: recurrent candidiasis, balanoposthitis, pruritus vulvae, boils, urinary tract infection, poorly healing wounds, and tuberculosis — a critical association in India.
Asymptomatic detection on routine testing is common in type 2.
Presenting with a complication — neuropathy, retinopathy, nephropathy, coronary disease or a diabetic foot ulcer — indicates that hyperglycaemia has been present for years.
Acanthosis nigricans and skin tags indicate insulin resistance.

Diagnosis

Test	Diabetes	Prediabetes
Fasting plasma glucose	≥ 126 mg/dL (8 h fast)	100–125 mg/dL (impaired fasting glucose)
2-h plasma glucose on 75 g OGTT	≥ 200 mg/dL	140–199 mg/dL (impaired glucose tolerance)
HbA1c	≥ 6.5%	5.7–6.4%
Random glucose with classic symptoms	≥ 200 mg/dL	—

In the absence of unequivocal hyperglycaemia, a diagnostic result must be confirmed by repeat testing. HbA1c is unreliable in anaemia, haemoglobinopathies, recent transfusion, pregnancy, and chronic kidney or liver disease — all common in India.

Management

1. Lifestyle — the foundation for every patient

Medical nutrition therapy with an individualised, culturally appropriate plan; at least 150 minutes of moderate aerobic activity weekly plus resistance training; weight loss of 5–10% substantially improves glycaemia; smoking cessation; alcohol moderation; and structured diabetes self-management education, including foot care and sick-day rules.

2. Pharmacological therapy in type 2

Metformin — first-line unless contraindicated. Reduces hepatic gluconeogenesis and improves insulin sensitivity; weight-neutral, no hypoglycaemia; adverse effects include gastrointestinal upset and vitamin B12 deficiency; withhold in renal impairment and before contrast studies because of lactic acidosis risk.
SGLT2 inhibitors (empagliflozin, dapagliflozin) — glycosuric; proven cardiovascular and renal benefit and reduction in heart failure hospitalisation; risks are genital mycotic infection, volume depletion and euglycaemic DKA.
GLP-1 receptor agonists (liraglutide, semaglutide, dulaglutide) — incretin-based; weight loss and cardiovascular benefit; nausea is the main limitation.
DPP-4 inhibitors (sitagliptin, vildagliptin) — weight-neutral, well tolerated, modest efficacy.
Sulphonylureas (glimepiride, gliclazide) — potent and cheap, widely used in India; cause hypoglycaemia and weight gain.
Pioglitazone — improves insulin sensitivity; causes weight gain, fluid retention and fracture risk; avoid in heart failure.
Insulin — for type 1 always; in type 2 for marked hyperglycaemia, symptoms, catabolism, pregnancy, intercurrent illness, surgery, or failure of oral agents. Regimens range from basal insulin added to oral agents, through premixed twice-daily, to basal-bolus.

Choice is increasingly driven by comorbidity rather than glucose alone: SGLT2 inhibitors for heart failure and chronic kidney disease, GLP-1 agonists for established atherosclerotic disease and obesity.

3. Glycaemic targets

Generally HbA1c below 7%, individualised — tighter in the young, newly diagnosed and otherwise healthy; more relaxed (7.5–8%) in the elderly, those with hypoglycaemia unawareness, limited life expectancy or advanced complications.

4. Comprehensive risk reduction — as important as glucose control

Blood pressure control (ACE inhibitor or ARB, particularly with albuminuria), statin therapy, antiplatelet therapy where indicated, annual retinal screening, annual urine albumin:creatinine ratio and eGFR, annual foot examination with monofilament testing, dental care, and vaccination.

CLINICAL PEARL

Screen every newly diagnosed diabetic in India for tuberculosis, and screen every tuberculosis patient for diabetes. Diabetes triples the risk of active TB, worsens treatment outcomes and increases relapse; the bidirectional screening policy is national programme guidance and a frequently examined point.

Complications

Acute: diabetic ketoacidosis, hyperglycaemic hyperosmolar state, hypoglycaemia, lactic acidosis.

Chronic microvascular: retinopathy, nephropathy, neuropathy.

Chronic macrovascular: coronary artery disease, stroke, peripheral arterial disease.

Others: diabetic foot, infections, autonomic neuropathy, cataract, dyslipidaemia, non-alcoholic fatty liver disease.

NEEDS VERIFICATION

Drug doses, HbA1c targets and the Indian waist circumference thresholds — confirm against current ADA/RSSDI standards of care before publication.

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