Diabetes Mellitus — Diagnosis, Complications and Management
Medicine — Endocrinology, NMC MBBS licence examination syllabus (Nepal Medical Council).
Diabetes mellitus: a vascular disease that happens to raise glucose
Nobody dies of a high blood sugar. They die of what it does to arteries.
Ask a student what diabetes is and you will usually be told it is a disease of high blood glucose. That is true, and it is the least useful true thing about it. Glucose is the marker. What actually harms the patient — what fills the wards, causes the amputations, the dialysis, the blindness and the heart attacks — is what chronic hyperglycaemia does to blood vessels over decades.
Holding that framing changes what you do. It explains why a patient with well-controlled glucose and untreated hypertension is badly managed. It explains why the statin often matters more than the third oral agent. And it explains the shape of every long-term management question you will be asked: the examiner wants to know whether you are treating a number or a patient's arteries.
🩺 Where this lives: A patient proud of an HbA1c that has come down from 75 to 52 mmol/mol, whose blood pressure is 158/94 and who is on no statin, has had the less important half of their diabetes treated. Most people with type 2 diabetes die of cardiovascular disease, not of hyperglycaemia — so the untreated blood pressure is the bigger threat sitting in plain sight on the same clinic letter.
Two diseases, one name
Type 1 and type 2 share a diagnostic threshold and almost nothing else. They differ in mechanism, in the patient, in the emergencies they produce, and in treatment.
The ketosis difference is the one worth understanding rather than memorising. Insulin is the hormone that suppresses lipolysis, and it takes very little of it to do so. A type 1 patient with no insulin at all cannot suppress fat breakdown, so free fatty acids flood the liver and become ketones — hence DKA. A type 2 patient retains some endogenous insulin, enough to hold lipolysis in check even when it is nowhere near enough to control glucose. That is why type 2 produces the hyperosmolar state rather than ketoacidosis.
Two other forms are worth recognising because they appear in questions:
🔍 The forms that do not fit the two-box model
GestationalHyperglycaemia first recognised in pregnancy, driven by placental hormones causing insulin resistance. Usually resolves after delivery, but it marks a substantially raised lifetime risk of type 2 — so these patients need follow-up, not discharge.
LADALatent autoimmune diabetes in adults: type 1 presenting slowly in an adult. Often misdiagnosed as type 2 until oral agents fail unusually fast. Autoantibodies and a low C-peptide give it away.
SecondaryPancreatic disease (chronic pancreatitis, cystic fibrosis, haemochromatosis), endocrine causes (Cushing's, acromegaly), or drugs — most commonly corticosteroids. Worth asking about, because the treatable cause is the answer.
How it presents
THE CLASSIC TRIAD — and the physiology behind it
POLYURIA
Glucose exceeds the renal reabsorption threshold
→ glucose in the tubule → osmotic diuresis
POLYDIPSIA
Water follows the glucose out → dehydration → thirst
WEIGHT LOSS
No insulin → cells cannot use glucose → the body
breaks down fat and muscle instead. Calories are
being lost in the urine as well.
Plus: fatigue, blurred vision (osmotic lens changes),
recurrent infections — thrush, skin, urinary.
TYPE 2 OFTEN HAS NO SYMPTOMS AT ALL
It is frequently found on screening, or at the point
where a COMPLICATION presents — which means the disease
has already been present for years.
Making the diagnosis
💡 Exam angle: the rule that catches people is repeat testing. In an asymptomatic patient a single abnormal result is not a diagnosis — it must be confirmed on a separate day, because a one-off value can reflect intercurrent illness or a laboratory artefact. But in a patient with classic symptoms, one diagnostic value is enough. Questions test this by describing either a routine screening result or an unwell patient with thirst and weight loss, and expecting different answers.
💡 Exam angle: HbA1c reflects average glycaemia over roughly 8–12 weeks, because it measures glycation of haemoglobin across the red cell lifespan. That is exactly why it is unreliable when the lifespan is abnormal — haemolysis and blood loss shorten it and give a falsely low value; iron deficiency can raise it. In those patients, and in pregnancy, use glucose-based testing instead. A question mentioning anaemia alongside an HbA1c is testing this.
What actually harms the patient
The split by vessel size is not academic taxonomy — it predicts which intervention helps which complication. Tight glucose control makes the biggest difference to microvascular disease. For macrovascular disease, blood pressure control and lipid management do more than glucose ever will.
🔍 The three microvascular complications, and what to do
RetinopathyProgresses from background changes (microaneurysms, dot-and-blot haemorrhages) through pre-proliferative to proliferative, where new vessels form and can bleed or detach the retina. It is asymptomatic until late, which is the entire argument for annual screening. Treatable when caught early.
NephropathyThe earliest sign is albuminuria, detected as a urine albumin:creatinine ratio long before the creatinine rises. Once detected, an ACE inhibitor or ARB slows progression — a rare instance of a cheap drug altering the natural history of a disease.
NeuropathyClassically distal, symmetrical, sensory, in a glove-and-stocking distribution — longest nerves affected first. Also autonomic: gastroparesis, postural hypotension, erectile dysfunction. The sensory loss is what makes the diabetic foot dangerous.
The diabetic foot deserves particular attention because it is where three complications converge: neuropathy means the patient does not feel the injury, ischaemia means it does not heal, and immune impairment means it becomes infected. A painless ulcer over a pressure point is the classic finding, and "painless" is the dangerous word — pain is what would otherwise have prompted the patient to act.
Managing type 2
THE MAJOR DRUG CLASSES
METFORMIN — biguanide, first-line
Reduces hepatic glucose output, improves insulin
sensitivity. Weight-neutral. No hypoglycaemia alone.
Adverse: GI upset (start low), B12 deficiency
long-term, rare lactic acidosis.
CAUTION in significant renal impairment; withhold
during acute illness and around contrast imaging.
SGLT2 INHIBITORS — "-gliflozins"
Block renal glucose reabsorption → glucose excreted.
Cardiovascular and RENAL protection beyond glucose
lowering — which is why they are chosen by comorbidity.
Adverse: genital thrush, urinary infection, volume
depletion, and EUGLYCAEMIC DKA (a real exam favourite).
GLP-1 AGONISTS — "-glutides", injectable
Enhance glucose-dependent insulin release, slow gastric
emptying, suppress appetite → notable WEIGHT LOSS.
Adverse: nausea, and a pancreatitis caution.
SULFONYLUREAS — gliclazide
Force insulin release from beta cells, independent of
glucose — hence HYPOGLYCAEMIA and weight gain.
Cheap and effective; the trade-off is the hypo risk.
DPP-4 INHIBITORS — "-gliptins"
Weight-neutral, well tolerated, modest effect.
INSULIN
Always the answer in type 1. In type 2 when other
agents no longer suffice.
💡 Exam angle: euglycaemic DKA with SGLT2 inhibitors is asked because it defeats the usual heuristic. These drugs dump glucose into the urine, so a patient can develop genuine ketoacidosis with a glucose that is normal or only mildly raised. If you screen for DKA by glucose alone you will miss it. Check ketones in any unwell patient on an SGLT2 inhibitor, whatever the glucose reads.
Hypoglycaemia — the risk of the treatment
💡 Exam angle: hypoglycaemia unawareness is the dangerous end-state. Repeated hypoglycaemia blunts the autonomic warning response, so the patient loses the early symptoms and drops straight to confusion or seizure without warning. It is a reason to relax glycaemic targets in that patient, not tighten them — a counter-intuitive answer that questions like to test. Note also the link back to beta-blockers: they mask the adrenergic warnings, but sweating is cholinergic and survives.
Clinical reasoning: four presentations
🔍 Case 1 — which type?
PresentationA 17-year-old with three weeks of thirst, polyuria and 6 kg unintentional weight loss. BMI 19. Glucose 24 mmol/L, ketones 3.1 mmol/L.
ReasoningSignificant ketosis means insulin is essentially absent, since even small amounts suppress lipolysis. This is type 1, and the ketones raise the immediate question of whether DKA is already established.
AnswerType 1 diabetes. Assess for DKA now (gas, ketones, electrolytes). Insulin is required and is not optional — no lifestyle trial, no metformin.
🔍 Case 2 — treating the wrong number
PresentationA 61-year-old with type 2 diabetes, HbA1c 54 mmol/mol on metformin. BP 156/92 on three readings. Total cholesterol 6.4. Not on a statin. He asks whether he should add a second diabetes drug.
The distractorThe question is framed around glucose, so a second agent feels like the answer.
ReasoningHis HbA1c is reasonable. His untreated hypertension and lipids are driving macrovascular risk, which is what is most likely to kill him. Glucose intensification would have far less impact than treating either.
AnswerTreat the blood pressure and start a statin. This is the "vascular disease that raises glucose" framing in action — and it is a common exam construction precisely because the reflex answer is wrong.
🔍 Case 3 — the painless ulcer
PresentationA 66-year-old with 14 years of type 2 diabetes has a 2 cm ulcer under the first metatarsal head. He cannot say when it started. It does not hurt. Foot warm, pulses present, monofilament sensation absent.
Key cluePainless, over a pressure point, with absent sensation — a neuropathic ulcer. Warm foot with present pulses argues against a primarily ischaemic one.
ReasoningSensory loss means repeated unnoticed trauma at a weight-bearing site. The absence of pain explains the delayed presentation and is itself the pathology.
AnswerNeuropathic foot ulcer. Needs urgent multidisciplinary foot care: pressure offloading, wound care, infection assessment including osteomyelitis, and vascular assessment. Screening and footwear education prevent the next one.
🔍 Case 4 — the normal glucose that is not reassuring
PresentationA 58-year-old with type 2 diabetes on metformin and empagliflozin presents with two days of vomiting and abdominal pain. Glucose 9.8 mmol/L. She is tachypnoeic.
TrapA glucose under 11 seems to rule out DKA.
ReasoningSGLT2 inhibitors excrete glucose renally, so the glucose can stay near normal while ketoacidosis develops — euglycaemic DKA. The tachypnoea is respiratory compensation for a metabolic acidosis.
AnswerCheck ketones and a blood gas regardless of the glucose. Treat as DKA if confirmed, and stop the SGLT2 inhibitor. Screening by glucose alone would have missed this.
Commonly confused
Confusion
The distinction
Why it matters
Type 1 vs type 2
Absent versus resisted insulin; ketosis-prone versus ketosis-resistant
Type 1 needs insulin immediately; a lifestyle trial would be dangerous.
Type 2 in a young person vs LADA
LADA has autoantibodies and a low C-peptide
Explains oral agents failing unusually fast.
HbA1c vs glucose
HbA1c averages 8–12 weeks; glucose is a moment
HbA1c is unreliable in anaemia, haemoglobinopathy and pregnancy.
Microvascular vs macrovascular
Glycaemia drives one; all risk factors drive the other
Determines whether tightening glucose or treating BP and lipids helps more.
Metformin causes no hypoglycaemia alone; sulfonylureas do
Governs the choice in patients who drive, fast, or live alone.
DKA vs euglycaemic DKA
SGLT2 inhibitors allow ketoacidosis at a normal glucose
Screening by glucose alone misses it.
Rapid revision
MUST-KNOW FACTS
1. Diabetes harms through VESSELS; glucose is the marker, not the disease.
2. Type 1 = autoimmune beta-cell destruction → no insulin → ketosis-prone.
3. Type 2 = insulin resistance + beta-cell decline → ketosis-resistant.
4. Insulin suppresses lipolysis — which is why residual insulin prevents DKA.
5. Fasting glucose ≥ 7.0 mmol/L is diagnostic.
6. 2-hour or random glucose ≥ 11.1 mmol/L is diagnostic.
7. HbA1c ≥ 48 mmol/mol (6.5%) is diagnostic.
8. Asymptomatic → REPEAT on a separate day. Symptomatic → one value suffices.
9. HbA1c reflects ~8–12 weeks; unreliable if red cell lifespan is abnormal.
10. Microvascular: retinopathy, nephropathy, neuropathy — glycaemia-driven.
11. Macrovascular: coronary, cerebrovascular, peripheral — all risk factors.
12. Most type 2 patients die of cardiovascular disease → statin and BP matter.
13. Retinopathy is asymptomatic until late → annual screening.
14. Nephropathy: albumin:creatinine ratio first, then ACE-I or ARB.
15. Neuropathy: glove-and-stocking, longest nerves first.
16. Diabetic foot = neuropathy + ischaemia + infection; painless is dangerous.
17. Metformin is first-line: weight-neutral, no hypoglycaemia alone.
18. SGLT2 inhibitors for cardiovascular disease, heart failure or CKD.
19. GLP-1 agonists cause weight loss; sulfonylureas cause weight gain and hypos.
20. Euglycaemic DKA — check ketones on SGLT2 inhibitors whatever the glucose.
21. Hypoglycaemia: conscious → oral carbohydrate; unconscious → IV glucose or IM glucagon.
22. Hypoglycaemia unawareness means RELAXING targets, not tightening them.
💡 Exam angle: the reliable threads are (a) type 1 versus type 2 from ketosis rather than age, (b) the diagnostic thresholds and the repeat-testing rule, (c) treating cardiovascular risk rather than only glucose, (d) recognising the neuropathic foot, and (e) euglycaemic DKA on SGLT2 inhibitors. Notice how many of these are cases where the obvious number misleads — that is the pattern worth carrying into the exam.
Syllabus points
Diabetes as a vascular disease: the framing that matters
Type 1 versus type 2: mechanism, patient and emergency
Why residual insulin prevents ketosis
Gestational, LADA and secondary diabetes
Clinical presentation and the physiology behind the triad
Diagnostic thresholds and the repeat-testing rule
HbA1c: what it measures and when it misleads
Microvascular complications and their screening
Macrovascular risk and why it dominates mortality
The diabetic foot
Stepwise management of type 2 and the drug classes
Hypoglycaemia, its treatment and unawareness
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