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📚 Diabetology - Complete Quiz Study Material

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1. CLASSIFICATION OF DIABETES MELLITUS

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2. DIAGNOSTIC CRITERIA (ADA)

Note: If no symptoms, FPG or OGTT must be confirmed by repeat testing on a separate day. Point-of-care (POCT) HbA1c is non-diagnostic.

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3. HbA1c - MONITORING & INTERPRETATION

• Reflects average blood glucose over the past 3 months (life of RBC)
• HbA1c 6% ≈ average BG of 130 mg/dL; each additional 1% ≈ +30 mg/dL
• Target for most patients: <7% (ADA); reduces microvascular complications significantly
• DCCT Trial: HbA1c <7% reduced retinopathy progression by 76%
• Unreliable in: sickle cell disease, spherocytosis, hemolytic anemias (abnormal RBC lifespan)
• UKPDS 35: Lower HbA1c directly associated with fewer macro- and microvascular complications

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4. ANTI-DIABETIC DRUGS (PHARMACOLOGY)

A. Biguanides - Metformin (First-line for T2DM)

• Mechanism: Activates AMP-activated protein kinase → inhibits hepatic gluconeogenesis; reduces hepatic glucose output
• Dose: Start 500 mg once daily with meal; titrate to max 2 g/day (given at least twice daily due to short t½)
• Advantages: Weight neutral, no hypoglycemia risk, cardioprotective
• Side effects: Nausea, diarrhea, crampy abdominal pain, metallic taste, dysgeusia
• Rare but serious: Lactic acidosis (almost exclusively in renal insufficiency)
• Contraindications: eGFR <30 mL/min, hepatic insufficiency, acidosis, severe hypoxemia, alcohol abuse, hold 48 hours after IV contrast

B. Sulfonylureas (Insulin Secretagogues)

• Mechanism: Bind sulfonylurea receptor (subunit of ATP-sensitive K⁺ channel) on β-cells → K⁺ channel closes → depolarization → Ca²⁺ influx → insulin exocytosis
• 1st generation: Chlorpropamide, tolbutamide, tolazamide, acetohexamide
• 2nd generation (higher potency, fewer interactions): Glipizide, glyburide, gliclazide, glimepiride
• Key risk: Hypoglycemia (especially glyburide in elderly/renal impairment)

C. Thiazolidinediones (Glitazones)

• Mechanism: Bind PPARγ (peroxisome proliferator-activated receptor gamma) → fibroblast differentiation to adipocytes → ↓ free fatty acids → improved peripheral insulin sensitivity
• Drugs: Pioglitazone, Rosiglitazone (replaced troglitazone due to hepatotoxicity)
• Side effects: Weight gain, fluid retention, increased risk of bone fractures (postmenopausal women, older males)
• Contraindicated: Active hepatocellular disease, heart failure

D. DPP-4 Inhibitors (Gliptins)

• Mechanism: Inhibit dipeptidyl peptidase-4 → prevent breakdown of endogenous GLP-1 → ↑ glucose-dependent insulin secretion
• Drugs: Sitagliptin, Saxagliptin, Alogliptin, Linagliptin
• Advantages: Weight neutral, low hypoglycemia risk
• Side effects: Upper respiratory infections, headache; saxagliptin associated with HF hospitalization

E. GLP-1 Receptor Agonists (Injectable)

• Mechanism: Structural analogs of GLP-1; resist DPP-4 breakdown → ↑ glucose-dependent insulin secretion, ↓ glucagon, improve satiety → weight loss
• Drugs: Liraglutide (once daily), Exenatide (twice daily or weekly extended release), Dulaglutide (weekly), Semaglutide (weekly injectable or daily oral)
• Advantages: Significant weight loss, CV benefit (liraglutide, semaglutide)
• Side effects: Nausea, vomiting, diarrhea, pancreatitis
• Contraindications: History of pancreatitis; history of medullary thyroid cancer or MEN2 (risk of C-cell tumors)
• Caution with renal impairment (especially exenatide - do not use if severe)

F. SGLT-2 Inhibitors (Gliflozins)

• Mechanism: Block sodium-glucose cotransporter 2 in the proximal renal tubule → ↑ urinary glucose excretion
• Drugs: Empagliflozin, Canagliflozin, Dapagliflozin
• Advantages: Weight loss, BP reduction, CV protection (empagliflozin, canagliflozin), renal protection - reduce progression of CKD (can initiate at eGFR ≥30)
• Side effects: Genital mycotic infections, UTIs, DKA risk, Fournier gangrene
• Avoid: eGFR <30 (reduced efficacy)

G. Alpha-Glucosidase Inhibitors

• Mechanism: Block alpha-glucosidase at brush border of intestine → slow carbohydrate absorption → reduce postprandial glucose spike
• Drugs: Acarbose, Miglitol
• Side effects: Flatulence, bloating, diarrhea

H. Insulin - Types and Kinetics

• Fastest absorption site: Abdomen > Arm > Buttock > Thigh
• Insulin duration is prolonged in renal failure

I. Amylin Analog

• Pramlintide: Blunts postprandial glucose; given as separate injection with meals; requires insulin dose reduction when starting

J. Dopamine Agonist

• Bromocriptine mesylate: Used for T2DM; mechanism of glucose lowering is unknown; do not use with dopamine antagonists

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5. CHRONIC COMPLICATIONS

Microvascular Complications (directly related to hyperglycemia)

A. Diabetic Retinopathy (DR)

• #5 cause of severe vision loss/blindness worldwide
• Classification:
  • Preproliferative: Microaneurysms, retinal infarcts, lipid exudates, cotton wool spots, microhemorrhages (with or without macular edema)
  • Proliferative: New vessel formation (especially near optic disc)
• Screening:
  • T1DM: Begin at puberty or 3-5 years after diagnosis, then annually
  • T2DM: At time of diagnosis, then annually
• Treatment:
  • First-line: Tight glycemic control + BP control (ACEi/ARB) + fenofibrate (if dyslipidemic)
  • Macular edema / proliferative DR: Anti-VEGF injections (better than laser for macular edema), or laser photocoagulation
  • Vitreous hemorrhage / retinal detachment: Vitrectomy

B. Diabetic Nephropathy

• Leading cause of ESRD in the United States
• Affects ~20-40% of both T1DM and T2DM patients
• Screening: Annual urine albumin-to-creatinine ratio (UACR)
  • T1DM: After >5 years of diagnosis
  • T2DM: Beginning at diagnosis
• Albuminuria: UACR ≥30 mg/g
• Annual serum creatinine + eGFR calculation
• Treatment:
  • ACEi or ARB = first-line antihypertensive (also reduce proteinuria)
  • SGLT-2 inhibitors (empagliflozin, canagliflozin) = reduce CKD progression regardless of HbA1c
  • Finerenone (nonsteroidal MRA) = reduces CKD progression with less hyperkalemia
  • BP target: <130/80 mmHg
  • Dietary protein: 0.8 g/kg/day

C. Diabetic Neuropathy

• Most common form: Distal symmetric polyneuropathy (stocking-glove pattern)
• Autonomic neuropathy manifestations and treatment:

• Foot ulcer management: Multidisciplinary - debridement, offloading, antibiotic coverage (Staph/Strep ± gram-negative/anaerobes for severe cases)

Macrovascular Complications

• Atherosclerosis of coronary, cerebral, and peripheral arteries
• DM is equivalent in CV risk to having had a prior MI
• Prevention: Statins, BP control (target <130/80), smoking cessation, antiplatelet therapy

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6. ACUTE COMPLICATIONS

Diabetic Ketoacidosis (DKA) - Primarily T1DM

• Triad: Hyperglycemia + Ketosis + Metabolic acidosis
• Precipitants: Infection, missed insulin, new-onset T1DM
• Labs: Glucose >250 mg/dL, pH <7.3, bicarbonate <18, ketonemia/ketonuria
• Treatment: Fluids (0.9% NaCl), insulin infusion, potassium replacement

Hyperosmolar Hyperglycemic State (HHS) - Primarily T2DM

• Severe hyperglycemia (>600 mg/dL), high osmolality (>320 mOsm/kg), minimal ketosis
• Usually elderly; precipitated by infection/dehydration
• Treatment: Aggressive fluid resuscitation, insulin, electrolyte correction

Hypoglycemia

• Threshold: Plasma glucose ≤70 mg/dL in diabetics
• Whipple triad (non-diabetics): Symptoms + low glucose + resolution with glucose
• Most common cause in diabetics: Excessive insulin or sulfonylurea dose
• Metformin, TZDs, DPP-4i, SGLT2i, GLP-1 RAs = low hypoglycemia risk (do not independently cause hypoglycemia)

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7. SCREENING & MONITORING

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8. HIGH-YIELD EXAM FACTS

1. DCCT Trial - Intensive glycemic control in T1DM reduced retinopathy by 76%, nephropathy by 50%
2. UKPDS - Every 1% reduction in HbA1c reduces microvascular risk by 37%
3. Metformin is first-line T2DM drug; do NOT use if eGFR <30
4. Sulfonylureas - most common drug class causing hypoglycemia
5. GLP-1 agonists + SGLT-2 inhibitors have proven cardiovascular and renal benefit beyond glucose lowering
6. HbA1c ≥6.5% = diagnostic for diabetes (lab test only, not POCT)
7. Acanthosis nigricans = cutaneous sign of insulin resistance
8. ACEi/ARB = first-line antihypertensive in diabetic nephropathy
9. Fastest insulin absorption: Abdomen
10. MEN2 or medullary thyroid cancer history = contraindication to GLP-1 agonists
11. Finerenone = nonsteroidal MRA that reduces CKD progression in T2DM with less hyperkalemia vs. spironolactone
12. HbA1c is unreliable in sickle cell disease, spherocytosis, hemolysis
13. Lente and Ultralente insulin are no longer available in the US
14. Diabetic nephropathy = leading cause of ESRD in the US
15. Diabetic retinopathy = 5th leading cause of blindness worldwide

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