🩺 HKMLE Module 2: Diabetes Mellitus, Metabolic Syndrome, Obesity & Lipid Disorders

High-Yield Master Study Note

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📋 TABLE OF CONTENTS

1. Diagnostic Criteria for DM
2. Type 1 Diabetes Mellitus
3. Type 2 Diabetes Mellitus
4. DM Drug Therapy
5. Diabetic Complications
6. DKA vs HHS
7. Metabolic Syndrome
8. Obesity
9. Lipid Disorders
10. Notable Trials Table
11. Drug Traps Table
12. Master Mnemonics Table

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1. DIAGNOSTIC CRITERIA 🔴

WHO / ADA Diagnostic Criteria for Diabetes Mellitus

HbA1c reflects glycaemic control over the preceding 2–3 months. A cutoff of 6.5% was selected based on the glucose threshold above which diabetes-specific microvascular complications emerge. - GOLDMAN-CECIL MEDICINE

🇭🇰 Hong Kong Context

• HK Reference Framework recommends screening from age 45, every 1–3 years depending on risk factors (HKMJ 2020)
• DM is the 11th commonest cause of death in HK (CHP data)
• ~50% of T2DM patients in public hospitals achieved HbA1c <7% by 2015, up from 40% in 2010 (HA guidelines)
• Waist circumference cut-offs for Asian populations are lower than for Western populations (see Metabolic Syndrome section)

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2. TYPE 1 DM 🔴

Pathophysiology

• Autoimmune destruction of pancreatic β-cells → absolute insulin deficiency
• Autoantibodies: anti-GAD65, anti-IA-2, anti-insulin, anti-ZnT8

MNEMONIC: Type 1 DM Features - "ACID"

A – Autoimmune (anti-GAD65, anti-IA-2 antibodies)
C – C-peptide low/absent
I – Insulin required (absolute deficiency)
D – DKA prone

Clinical Features

• Classically young, lean patient
• Acute onset: polyuria, polydipsia, polyphagia, weight loss
• May present with DKA (13–80% of new T1DM presentations globally; more common in children <5 yr and low-resource settings)
• "Honeymoon phase" - temporary partial remission weeks-months after insulin initiation (do NOT stop insulin)
• LADA (Latent Autoimmune Diabetes in Adults) - insidious, may mimic T2DM initially

Treatment

• Insulin is mandatory - basal-bolus regimen preferred
  • Basal: glargine, detemir, degludec
  • Bolus (prandial): aspart, lispro, glulisine
• Carbohydrate counting + insulin dose adjustment
• Continuous glucose monitoring (CGM) improves time-in-range
• Target HbA1c: <7% (ADA), individualised

⚠️ HKMLE TRAP: Never use metformin, SGLT2i (alone), or sulfonylureas as primary therapy for T1DM. Insulin is the only essential therapy. SGLT2i have been used adjunctively in T1DM off-label but carry high euglycaemic DKA risk.

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3. TYPE 2 DM 🔴

Pathophysiology

• Dual defect: Insulin resistance + progressive β-cell failure
• Ominous Octet (DeFronzo): muscle resistance, hepatic glucose overproduction, impaired incretin effect, α-cell hyperglucagonaemia, renal glucose reabsorption ↑, brain insulin resistance, β-cell failure, intestinal glucose absorption ↑

MNEMONIC: T2DM Risk Factors - "FOAF HOPS"

F – Family history
O – Obesity (especially visceral)
A – Age >45
F – Female sex (gestational DM history)
H – Hypertension
O – OGTT impaired / prediabetes
P – PCOS
S – Sedentary lifestyle / South Asian / Southeast Asian ethnicity

Type 1 vs Type 2 DM Comparison 🔴

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4. DM DRUG THERAPY 🔴

Treatment Escalation Algorithm (T2DM)

STEP 1: Lifestyle modification (diet, exercise, weight loss)
   ↓ (HbA1c still ≥7%)
STEP 2: Metformin (first-line unless CKD G4-5 or contraindicated)
   ↓ (HbA1c still ≥7%)
STEP 3: Add second agent based on COMORBIDITY PROFILE:
   • ASCVD / High CV risk → ADD SGLT2i or GLP-1 RA
   • HF / CKD → PREFER SGLT2i (empagliflozin/dapagliflozin)
   • Obesity → PREFER GLP-1 RA (semaglutide, liraglutide) or SGLT2i
   • Cost constraint → Sulfonylurea or TZD
   ↓ (HbA1c still ≥7%)
STEP 4: Triple therapy or add insulin
   ↓ (HbA1c still ≥7%)
STEP 5: Intensify insulin (basal-bolus)

Drug Classes Summary

Insulin Types

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📌 QUICK SUMMARY: DM Drug Therapy

1. ✅ Metformin first line in T2DM unless eGFR <30 (hold if <45 for contrast or surgery)
2. ✅ SGLT2i/GLP-1 RA for patients with established ASCVD, HF, or CKD - regardless of HbA1c
3. ✅ Sulfonylureas cause weight gain and hypoglycaemia - avoid in frail/elderly
4. ✅ Tirzepatide (dual GIP/GLP-1) achieves the highest weight loss (~22% body weight in SURMOUNT trials)
5. ✅ Pioglitazone causes fluid retention - avoid in HF (NYHA III-IV)

⚠️ HKMLE TRAP: SGLT2i should be withheld 3 days before surgery and during illness/fasting (euglycaemic DKA risk). Blood glucose may be misleadingly normal in SGLT2i-associated DKA - check ketones directly. - GOLDMAN-CECIL MEDICINE

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5. DIABETIC COMPLICATIONS 🔴

MNEMONIC: Microvascular Complications - "RNF"

R – Retinopathy
N – Nephropathy
F – (Neuro)Foot / Neuropathy

Macrovascular Complications - "CAP"

C – Coronary artery disease (CAD)
A – Atherosclerotic stroke
P – Peripheral vascular disease (PVD)

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5a. Diabetic Retinopathy 🔴

• NPDR (mild-moderate): Optimise glucose, BP, lipids; Annual review
• Severe NPDR/PDR: Panretinal photocoagulation (PRP) or intravitreal anti-VEGF
• DMO: Intravitreal anti-VEGF (bevacizumab, ranibizumab) first-line; laser photocoagulation

⚠️ HKMLE TRAP: "Severe NPDR" means 4-2-1 rule, NOT neovascularisation. Neovascularisation = PDR. Don't confuse. The 4-2-1 rule = high risk for converting to PDR.

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5b. Diabetic Nephropathy 🔴

1. Tight glucose control (HbA1c <7%)
2. BP control: target <130/80 mmHg; ACE inhibitor or ARB first-line (reduce proteinuria)
3. SGLT2i (empagliflozin, dapagliflozin) - proven renoprotection independent of glucose
4. Avoid nephrotoxins (NSAIDs, contrast media without hydration)
5. Protein restriction (0.8 g/kg/day)

⚠️ HKMLE TRAP: In T1DM, nephropathy is almost always accompanied by retinopathy. If CKD without retinopathy in T1DM, think non-diabetic renal disease. In T2DM this co-occurrence is less reliable. - Harrison's Principles

⚠️ HKMLE TRAP: ACE inhibitors/ARBs are CONTRAINDICATED in pregnancy. Switch to methyldopa or labetalol for hypertensive diabetic pregnant women.

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5c. Diabetic Neuropathy 🟡

⚠️ HKMLE TRAP: Diabetic CN III palsy spares the pupil (ischaemic - parasympathetic fibres on outer CN III are preserved). Aneurysmal CN III compression (PComm aneurysm) causes pupil dilation. This distinction is a classic HKMLE exam point.

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5d. Diabetic Foot 🔴

MNEMONIC: Diabetic Foot Risk Factors - "INAPT"

I – Insensitivity (neuropathy)
N – Narrow vessels (peripheral vascular disease)
A – Abnormal biomechanics / deformity
P – Previous ulcer/amputation
T – Tight glucose control poor

• Grade 0: Podiatric care, footwear, education
• Grade 1–2: Debridement + offloading + wound care; antibiotics if infected
• Grade 3: IV antibiotics + urgent surgical debridement; MRI for osteomyelitis
• Grade 4–5: Vascular surgical assessment; amputation if non-viable

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Complication Screening Schedule 📌

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6. DKA vs HHS 🚨

MNEMONIC: DKA Diagnosis - "KASH"

K – Ketonaemia (blood ketones >3 mmol/L or urine ketones 2+)
A – Acidosis (pH <7.3, bicarbonate <18 mmol/L)
S – Serum glucose >11 mmol/L (note: euglycaemic DKA can occur, especially with SGLT2i)
H – High anion gap (>12 mmol/L)

DKA vs HHS Comparison Table 🔴

ROSEN's Emergency Medicine: "Features Distinguishing DKA Versus HHS" - DKA: T1DM, acidosis, glucose typically >250 mg/dL. HHS: T2DM elderly, no frank ketoacidosis, glucose >600 mg/dL, serum osmolality >350 mOsm/L, BUN invariably elevated.

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🚨 DKA Emergency Management (Step-by-Step)

• 0.9% NaCl: 1 L in first hour (or faster if shocked)
• Then 0.9% NaCl 500 mL/hr for next 2–4 hours
• Switch to 0.45% NaCl when corrected Na is normal
• Switch to 5% Dextrose + 0.45% NaCl when blood glucose falls to ≤14 mmol/L (250 mg/dL)

• K+ ≥5.5 mmol/L: Hold K+ replacement; start insulin; recheck in 1 hr
• K+ 3.5–5.5 mmol/L: Add 20–40 mEq/L KCl to IV fluids
• K+ <3.5 mmol/L: HOLD INSULIN - replace K+ first (40 mEq/hr IV); start insulin when K+ ≥3.5

• Only start after K+ ≥3.5 mmol/L
• Fixed rate IV insulin infusion: 0.1 units/kg/hr
• Target glucose fall: ~5.5 mmol/L/hr (~10%/hr)
• Do NOT stop insulin until ketones cleared and pH >7.3 - then overlap with SC insulin

• Only consider if pH <6.9 (50 mEq sodium bicarbonate in 200 mL water over 1 hr)

• The 6 I's: Infection, Insulin omission, Infarction (MI), Intoxication, Iatrogenic (steroids), Initial presentation

MNEMONIC: DKA Precipitants - "6 I's"

Infection | Insulin omission | Infarction (MI/CVA) | Intoxication | Iatrogenic (steroids, SGLT2i) | Initial presentation

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🚨 HHS Emergency Management

1. Fluids - larger volumes required (8–10 L deficit)
   • 0.9% NaCl initially; switch to 0.45% once euvolaemic
   • Add dextrose when glucose <14 mmol/L
   • Careful in elderly: risk of pulmonary oedema/CCF - may need haemodynamic monitoring
2. Insulin - Low dose or not initially required; fluids alone may reduce glucose significantly
   • If needed: 0.05–0.1 units/kg/hr (lower than DKA)
3. Anticoagulation - Consider prophylactic LMWH (high thrombosis risk due to hyperviscosity)
4. Monitor osmolality - Target reduction <3–8 mOsm/kg/hr (rapid correction → cerebral oedema)

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📌 QUICK SUMMARY: DKA vs HHS

1. ✅ DKA: pH <7.3, ketones present, glucose usually 14–28 mmol/L
2. ✅ HHS: No significant ketones, glucose >33.3 mmol/L, osmolality >320, obtunded
3. ✅ Always check K+ before starting insulin in DKA - hold insulin if K+ <3.5
4. ✅ HHS mortality (10–20%) > DKA mortality (~1–5%)
5. ✅ SGLT2i can cause euglycaemic DKA - glucose may be "normal" but check ketones!

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🚨 RED FLAGS - Diabetic Emergencies

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7. METABOLIC SYNDROME 🟡

Diagnostic Criteria (IDF / AHA-NHLBI Harmonised 2009)

MNEMONIC: Metabolic Syndrome - "WGBTH" ("We Get Big Then Hurt")

W – Waist circumference elevated
G – Glucose elevated
B – Blood pressure elevated
T – Triglycerides elevated
H – HDL low

Management

• Lifestyle: 5–7% weight loss reduces progression to T2DM by 58% (DPP Trial)
• Treat each component (antihypertensives, statins, metformin for prediabetes if high risk)

⚠️ HKMLE TRAP: For Asian populations (including Chinese HK patients), use lower waist thresholds (Men ≥90 cm, Women ≥80 cm) compared to Caucasian criteria. This is commonly tested.

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8. OBESITY 🟡

BMI Classification (WHO - but Asian thresholds differ!)

✅ Asian obesity BMI cut-off is ≥27.5 (vs ≥30 in Caucasians). Relevant for HK exams.

MNEMONIC: Obesity Complications - "DM CASH"

D – Diabetes (T2DM)
M – Metabolic syndrome
C – CVD / Coronary artery disease
A – Arthritis (osteoarthritis) / Apnoea (OSA)
S – Stroke / Steatohepatitis (NAFLD/NASH)
H – Hypertension / Hyperlipidaemia

Management Ladder

Pharmacotherapy for Obesity

Notable Trial - SELECT (2023) 🔴

• 20% ↓ MACE (CV death, non-fatal MI, non-fatal stroke)
• This was the first trial showing GLP-1 RA reduces CV events without requiring DM
• PMID: 37952131 (Lincoff et al., NEJM 2023)

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9. LIPID DISORDERS 🔴

Lipid Targets in DM

Goldman-Cecil: "Lowering LDL cholesterol levels with statin drugs is recommended to a target of less than 100 mg/dL (2.6 mmol/L) for most adults with diabetes and less than 70 mg/dL (1.8 mmol/L) for people with established cardiovascular disease."

Fredrickson Classification

Drugs for Dyslipidaemia

MNEMONIC: Statin High-Intensity vs Moderate

Atorvastatin 40–80 mg | Rosuvastatin 20–40 mg

⚠️ HKMLE TRAP: Gemfibrozil + statin = HIGH risk of myopathy/rhabdomyolysis. Fenofibrate has lower risk with statins. Prefer fenofibrate if combination needed.

MNEMONIC: Familial Hypercholesterolaemia - "TALL"

T – Tendon xanthomata (Achilles, extensor tendons)
A – Arcus cornealis (before age 45)
L – LDL >4.9 mmol/L
L – LDL receptor defect (autosomal dominant)

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📌 QUICK SUMMARY: Lipid Disorders

1. ✅ All DM patients with ASCVD: LDL <1.8 mmol/L (use high-intensity statin ± ezetimibe)
2. ✅ TG >5.6 mmol/L: Acute pancreatitis risk - fibrate + omega-3 first
3. ✅ FH: Consider PCSK9i if statin + ezetimibe cannot achieve target
4. ✅ Gemfibrozil + statin = dangerous combination (rhabdomyolysis)
5. ✅ Niacin ↑glucose - avoid in diabetics if possible

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10. NOTABLE TRIALS TABLE 🔴

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11. DRUG TRAPS TABLE ⚠️

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12. MASTER MNEMONICS TABLE 🔴

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PROGNOSIS MNEMONICS

T2DM Prognosis - "AHEAD" (worse prognosis if...)

A – Age of onset early (longer exposure to hyperglycaemia)
H – HbA1c persistently >9%
E – End-organ damage present (retinopathy, nephropathy)
A – ASCVD established
D – Duration of disease long

HHS Prognosis - "OLD TRAP"

O – Older age
L – Level of consciousness impaired
D – Delayed diagnosis
T – Thrombotic complications
R – Renal failure
A – Aspiration/infection
P – Pre-existing comorbidities

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BONUS: DIAGNOSTIC ALGORITHM 🔴

Patient with suspected DM (polyuria/polydipsia/weight loss/incidental hyperglycaemia)
              ↓
     SYMPTOMATIC?
    /            \
  YES              NO
   ↓               ↓
Single result    TWO separate abnormal results needed
≥11.1 mmol/L    (any 2 of: FPG, OGTT, HbA1c)
random glucose       ↓
   → CONFIRM    FPG ≥7.0 mmol/L
   DIAGNOSIS    HbA1c ≥6.5%
                OGTT 2hr ≥11.1 mmol/L
                    ↓
             CONFIRMED DM
                    ↓
         Is it T1DM or T2DM?
         (age, BMI, ketosis, antibodies, C-peptide)
              ↓                    ↓
           T1DM                  T2DM
      (Insulin mandatory)   (Metformin + lifestyle)

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ADDITIONAL HIGH-YIELD POINTS FOR HKMLE ❓

Commonly Tested Exam Facts

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SOURCES

• GOLDMAN-CECIL MEDICINE International Edition (Chapter 210 - Diabetes Mellitus)
• ROSEN's Emergency Medicine (Chapter 115 - Diabetic Emergencies)
• Harrison's Principles of Internal Medicine 22E (Chapters on DM, MetSyn, Lipids)
• Katzung's Basic and Clinical Pharmacology 16th Ed (Chapter on Antidiabetic drugs)
• Comprehensive Clinical Nephrology 7th Ed (DKA, Diabetic Nephropathy)
• EMPA-REG OUTCOME: Zinman et al., NEJM 2015 (PMID: 26378978)
• LEADER: Marso et al., NEJM 2016 (PMID: 27295427)
• DECLARE-TIMI 58: Wiviott et al., NEJM 2019 (PMID: 30415602)
• CANVAS: Neal et al., NEJM 2017 (PMID: 28605608)
• SELECT: Lincoff et al., NEJM 2023 (PMID: 37952131)
• SURMOUNT-CN: Zhao et al., JAMA 2024 (PMID: 38819983)
• HK Reference Framework for Diabetes Care (Primary Healthcare Office, HK Government)
• Centre for Health Protection (CHP), HK - DM Epidemiology Data 2024

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📌 Final Exam Tip: The HKMLE loves testing: (1) insulin-before-K+ in DKA, (2) Asian waist thresholds, (3) the SGLT2i euglycaemic DKA trap, (4) diabetic CN III pupil sparing, (5) T1DM retinopathy screen at 5 years vs T2DM at diagnosis, and (6) which drug to add first when a diabetic patient also has HF or CKD. Master these 6 areas and you will clear this module.Your complete Module 2 study note is above. Here's a quick orientation to what was added beyond your original request:

• Diagnostic algorithm flowchart (symptomatic vs asymptomatic path - commonly tested)
• Complication Screening Schedule table (T1DM vs T2DM timing - classic HKMLE trap)
• DKA step-by-step emergency management with exact thresholds (K+ <3.5 → hold insulin, glucose ≤14 → switch to dextrose)
• Wagner Classification for diabetic foot (grading tested frequently)
• Insulin types table (onset/peak/duration - required for prescribing questions)
• HHS Management as its own section separate from DKA comparison
• Fredrickson Classification for lipid disorders (phenotype typing)
• Commonly Tested Exam Facts Q&A table at the end (quick-fire revision format)
• SURMOUNT and SURMOUNT-CN (tirzepatide in Chinese adults - directly relevant to HK context)
• Asia-Pacific BMI thresholds (≥27.5 for obesity, not ≥30)
• Prognosis mnemonics for both T2DM and HHS

1. Hold insulin if K+ <3.5 in DKA
2. Asian waist circumference thresholds (Men ≥90, Women ≥80)
3. SGLT2i euglycaemic DKA (check ketones, not just glucose)
4. Diabetic CN III palsy spares the pupil (vs aneurysm which dilates it)
5. T2DM retinopathy screen at diagnosis (not 5 years after like T1DM)
6. Add SGLT2i/GLP-1 RA first when DM patient has HF or CKD, regardless of HbA1c