Diabetes Melitus Tipe 2
Published on May 17, 2026
Risk Factors
Age > 45, BMI ≥ 23 kg/m² (Asian cutoff), first-degree relative with DM, sedentary lifestyle, history of gestational DM, delivery of baby > 4 kg, hypertension (≥140/90), HDL < 35 mg/dL, triglycerides > 250 mg/dL, PCOS, acanthosis nigricans, prediabetes, history of cardiovascular disease
Etiology
Progressive insulin resistance with eventual beta-cell secretory failure; driven by obesity-related chronic inflammation, lipotoxicity, and glucotoxicity
Presentation
Often asymptomatic and found on screening. Classic triad of polyuria, polydipsia, polyphagia with weight loss (the "3P + weight loss"). Fatigue, blurred vision, recurrent infections (UTI, candidiasis, skin infections), slow wound healing
Classic Exam
Obesity (especially central/visceral), acanthosis nigricans (velvety hyperpigmented skin at neck/axillae), peripheral neuropathy on monofilament testing, signs of diabetic foot (ulcers, calluses, deformity), hypertension, xanthelasma/xanthoma if concurrent dyslipidemia
Diagnostics
Fasting plasma glucose (FPG) ≥ 126 mg/dL, 2-hour OGTT ≥ 200 mg/dL, HbA1c ≥ 6.5%, or random glucose ≥ 200 mg/dL with classic symptoms. Prediabetes: FPG 100-125, 2h OGTT 140-199, HbA1c 5.7-6.4%
Management
Lifestyle modification (medical nutrition therapy + 150 min/week aerobic exercise) initiated simultaneously with pharmacotherapy. Metformin is the first-line oral agent. SGLT-2 inhibitors or GLP-1 receptor agonists are preferred add-on agents in patients with atherosclerotic cardiovascular disease (ASCVD), heart failure, or chronic kidney disease. Insulin initiation when HbA1c > 9% with metabolic decompensation, or when dual/triple oral therapy fails
Keywords
"Acanthosis nigricans," "insulin resistance," "metabolic syndrome," "polyuria/polydipsia/polyphagia," "HbA1c > 6.5%," "fasting glucose ≥ 126," "metformin first-line," "gradual onset," "obese adult"
01Pathophysiology
Type 2 diabetes mellitus is fundamentally a disease of two concurrent defects: insulin resistance in peripheral tissues and progressive beta-cell dysfunction in the pancreas. Understanding this dual defect is the key to understanding everything about DM type 2, from its presentation to its pharmacotherapy.
In early disease, skeletal muscle, adipose tissue, and the liver become resistant to the effects of insulin. In skeletal muscle, glucose transporter 4 (GLUT-4) translocation to the cell membrane is impaired, so glucose uptake drops. In the liver, insulin no longer adequately suppresses gluconeogenesis and glycogenolysis, meaning the liver continues to dump glucose into the bloodstream even when serum glucose is already elevated. This is why fasting hyperglycemia occurs and is the rationale behind metformin's primary mechanism of reducing hepatic glucose output.
Initially, the beta cells of the pancreas compensate by secreting more insulin (compensatory hyperinsulinemia). Over months to years, however, chronic exposure to elevated glucose levels (glucotoxicity) and elevated free fatty acids (lipotoxicity) leads to oxidative stress and endoplasmic reticulum stress in the beta cells, causing progressive beta-cell apoptosis. This is why DM type 2 is a progressive disease: what begins as a state of hyperinsulinemia with insulin resistance eventually transitions into relative and then absolute insulin deficiency. This progression explains why many patients who initially respond to oral agents eventually require insulin therapy.
The incretin effect is also impaired. In healthy individuals, oral glucose intake stimulates gut enteroendocrine cells (K cells in the duodenum and L cells in the ileum/colon) to release GIP and GLP-1, which potentiate insulin secretion in a glucose-dependent manner. In DM type 2, the insulinotropic response to GIP is blunted, and GLP-1 levels may be reduced. This forms the pharmacologic rationale for DPP-4 inhibitors (which prevent GLP-1 degradation) and GLP-1 receptor agonists.
Clinically, the symptoms directly mirror the pathophysiology: when blood glucose exceeds the renal threshold (~180 mg/dL), glucose spills into the urine (glucosuria), pulling water osmotically and causing polyuria and compensatory polydipsia. Because glucose cannot enter cells efficiently, the body perceives starvation despite hyperglycemia, triggering polyphagia. In severe cases, lipolysis and proteolysis occur, leading to weight loss and muscle wasting. This is why a vignette describing an overweight, middle-aged patient with "increased thirst, frequent urination, and a darkened neck crease" is almost certainly pointing you toward DM type 2.
02Classification and Diagnostic Criteria
Classification of Diabetes Mellitus
Type | Key Features |
|---|---|
DM Type 1 | Autoimmune or idiopathic beta-cell destruction leading to absolute insulin deficiency. Typically younger onset. Requires insulin from diagnosis |
DM Type 2 | Insulin resistance with progressive secretory failure. Accounts for 90-95% of all diabetes. Typically associated with obesity and sedentary lifestyle. Can occur at any age |
Gestational DM | Diagnosed in the 2nd or 3rd trimester of pregnancy, not pre-existing DM |
Other types | Monogenic (MODY), diseases of exocrine pancreas (pancreatitis, cystic fibrosis), endocrinopathies (Cushing, acromegaly, pheochromocytoma), drug-induced (glucocorticoids, antiretrovirals, post-transplant) |
Diagnostic Criteria for DM Type 2
Fasting plasma glucose
Diabetes
≥ 126 mg/dL
Prediabetes
100-125 mg/dL (IFG)
Normal
< 100 mg/dL
2-hour OGTT (75 g load)
Diabetes
≥ 200 mg/dL
Prediabetes
140-199 mg/dL (IGT)
Normal
< 140 mg/dL
HbA1c
Diabetes
≥ 6.5%
Prediabetes
5.7-6.4%
Normal
< 5.7%
Random plasma glucose
Diabetes
≥ 200 mg/dL + classic symptoms
Prediabetes
N/A
Normal
N/A
Test | Diabetes | Prediabetes | Normal |
|---|---|---|---|
Fasting plasma glucose | ≥ 126 mg/dL | 100-125 mg/dL (IFG) | < 100 mg/dL |
2-hour OGTT (75 g load) | ≥ 200 mg/dL | 140-199 mg/dL (IGT) | < 140 mg/dL |
HbA1c | ≥ 6.5% | 5.7-6.4% | < 5.7% |
Random plasma glucose | ≥ 200 mg/dL + classic symptoms | N/A | N/A |
A single random glucose ≥ 200 mg/dL requires classic symptoms to diagnose DM on its own. Without symptoms, the result must be confirmed by a repeat test on a different day or by a second abnormal test on the same day.
Prediabetes Subtypes
Impaired Fasting Glucose (IFG/GPT)
Fasting Glucose
100-125 mg/dL
2-hr OGTT
< 140 mg/dL
Impaired Glucose Tolerance (IGT/TGT)
Fasting Glucose
Normal or mildly elevated
2-hr OGTT
140-199 mg/dL
Combined IFG + IGT
Fasting Glucose
100-125 mg/dL
2-hr OGTT
140-199 mg/dL
Subtype | Fasting Glucose | 2-hr OGTT |
|---|---|---|
Impaired Fasting Glucose (IFG/GPT) | 100-125 mg/dL | < 140 mg/dL |
Impaired Glucose Tolerance (IGT/TGT) | Normal or mildly elevated | 140-199 mg/dL |
Combined IFG + IGT | 100-125 mg/dL | 140-199 mg/dL |
Prediabetes reflects beta-cell compensation failure in the setting of insulin resistance. These patients should be rescreened annually.
03Diagnostic Workup
Fasting plasma glucose
Role
Best initial screening test
Key Detail
≥ 126 mg/dL diagnostic; enzymatic assay on venous plasma preferred
HbA1c
Role
Best for monitoring and also acceptable for diagnosis
Key Detail
≥ 6.5%; must be NGSP-certified and DCCT-standardized. Unreliable in hemoglobinopathies, anemia, CKD, recent transfusion
2-hr OGTT (75 g)
Role
Most sensitive for detecting impaired glucose tolerance
Key Detail
≥ 200 mg/dL diagnostic. 3-day unrestricted carbohydrate diet before; 8-hr fast required
Random plasma glucose
Role
Used when patient is symptomatic
Key Detail
≥ 200 mg/dL + symptoms (polyuria, polydipsia, weight loss)
Lipid panel (fasting)
Role
Screen for comorbid dyslipidemia
Key Detail
Check total cholesterol, LDL, HDL, triglycerides at diagnosis
Renal function
Role
Screen for diabetic nephropathy
Key Detail
Serum creatinine, BUN, eGFR, urine albumin-to-creatinine ratio (UACR)
Liver function
Role
Baseline before metformin/TZD; screen for fatty liver
Key Detail
AST, ALT, albumin, globulin
ECG
Role
Screen for silent ischemia
Key Detail
At diagnosis for all DM type 2 patients
Fundoscopy / fundus photo
Role
Screen for diabetic retinopathy
Key Detail
At diagnosis, then annually
Monofilament (10 g) + tuning fork (128 Hz)
Role
Screen for peripheral neuropathy
Key Detail
At diagnosis, then at least annually
Ankle-Brachial Index (ABI)
Role
Screen for peripheral arterial disease
Key Detail
At diagnosis for lower extremity assessment
Test | Role | Key Detail |
|---|---|---|
Fasting plasma glucose | Best initial screening test | ≥ 126 mg/dL diagnostic; enzymatic assay on venous plasma preferred |
HbA1c | Best for monitoring and also acceptable for diagnosis | ≥ 6.5%; must be NGSP-certified and DCCT-standardized. Unreliable in hemoglobinopathies, anemia, CKD, recent transfusion |
2-hr OGTT (75 g) | Most sensitive for detecting impaired glucose tolerance | ≥ 200 mg/dL diagnostic. 3-day unrestricted carbohydrate diet before; 8-hr fast required |
Random plasma glucose | Used when patient is symptomatic | ≥ 200 mg/dL + symptoms (polyuria, polydipsia, weight loss) |
Lipid panel (fasting) | Screen for comorbid dyslipidemia | Check total cholesterol, LDL, HDL, triglycerides at diagnosis |
Renal function | Screen for diabetic nephropathy | Serum creatinine, BUN, eGFR, urine albumin-to-creatinine ratio (UACR) |
Liver function | Baseline before metformin/TZD; screen for fatty liver | AST, ALT, albumin, globulin |
ECG | Screen for silent ischemia | At diagnosis for all DM type 2 patients |
Fundoscopy / fundus photo | Screen for diabetic retinopathy | At diagnosis, then annually |
Monofilament (10 g) + tuning fork (128 Hz) | Screen for peripheral neuropathy | At diagnosis, then at least annually |
Ankle-Brachial Index (ABI) | Screen for peripheral arterial disease | At diagnosis for lower extremity assessment |
The best initial test for screening DM type 2 in at-risk populations is the fasting plasma glucose (FPG) because it is simple, inexpensive, widely available, and has well-established cutoffs. The test requires at least 8 hours of fasting.
The most accurate confirmatory and long-term monitoring test is HbA1c. This glycated hemoglobin measurement reflects average blood glucose over the preceding 2-3 months (the lifespan of an erythrocyte). It does not require fasting, making it convenient. However, the exam will test you on its limitations: HbA1c is unreliable in patients with hemoglobinopathies (sickle cell disease, thalassemia), recent blood transfusion, iron deficiency anemia, chronic kidney disease (especially end-stage), hemolytic anemia, or conditions affecting red blood cell turnover. For these patients, use fructosamine or glycated albumin (GA), which reflect glycemic control over the preceding 2-3 weeks.
The OGTT is the most sensitive test for detecting early glucose intolerance (IGT) that the FPG or HbA1c might miss. The 2026 Indonesian guideline specifies a standardized procedure: 3 days of unrestricted carbohydrate intake beforehand, fasting for at least 8 hours, then ingestion of 75 g glucose dissolved in 250 mL water over 5 minutes, with plasma glucose measured at 2 hours.
Once diabetes is diagnosed, the next step is screening for complications at the initial visit. This includes a fasting lipid panel, renal function tests, urine albumin quantification, ECG, chest X-ray, fundoscopy, body composition analysis, and neurological screening with Michigan Neuropathy Score. This baseline workup is critical because DM type 2 may have been present for years before clinical diagnosis, and complications may already be established at the time of presentation.
04Management and Treatment
Oral Antihyperglycemic Agents
Metformin
Mechanism
Decreases hepatic glucose production, improves peripheral insulin sensitivity
HbA1c Reduction
1.0-1.3%
Key Side Effects
GI disturbance (nausea, diarrhea), B12 deficiency (long-term), lactic acidosis (rare)
Renal Adjustment
Dose reduce: eGFR 30-45 → 500 mg/day; contraindicated if eGFR < 30
Sulfonylurea (glimepiride, gliclazide)
Mechanism
Stimulates pancreatic insulin secretion via SUR/KATP channels
HbA1c Reduction
0.4-1.2%
Key Side Effects
Hypoglycemia, weight gain
Renal Adjustment
Dose adjustment at CKD stage 3; caution with hepatic disease
TZD (pioglitazone)
Mechanism
PPAR-gamma agonist; improves insulin sensitivity in muscle, fat, liver
HbA1c Reduction
0.5-1.4%
Key Side Effects
Edema, weight gain, fractures (distal limbs), bladder cancer risk
Renal Adjustment
Avoid in NYHA class III-IV heart failure
DPP-4 inhibitor (sitagliptin, vildagliptin, linagliptin)
Mechanism
Inhibits DPP-4 enzyme, raises endogenous GLP-1/GIP levels
HbA1c Reduction
0.5-0.9%
Key Side Effects
Pancreatitis (rare), nasopharyngitis
Renal Adjustment
Dose adjustment required (except linagliptin)
SGLT-2 inhibitor (empagliflozin, dapagliflozin)
Mechanism
Blocks glucose reabsorption at proximal tubule, promotes glucosuria
HbA1c Reduction
0.5-0.9%
Key Side Effects
UTI, genital mycotic infections, euglycemic DKA, volume depletion
Renal Adjustment
Avoid if eGFR < 45 (for glycemic benefit); cardiovascular/renal benefit may persist at lower eGFR
Alpha-glucosidase inhibitor (acarbose)
Mechanism
Delays intestinal carbohydrate absorption
HbA1c Reduction
0.5-0.8%
Key Side Effects
Flatulence, bloating, diarrhea
Renal Adjustment
Discontinue if eGFR < 30
Drug Class | Mechanism | HbA1c Reduction | Key Side Effects | Renal Adjustment |
|---|---|---|---|---|
Metformin | Decreases hepatic glucose production, improves peripheral insulin sensitivity | 1.0-1.3% | GI disturbance (nausea, diarrhea), B12 deficiency (long-term), lactic acidosis (rare) | Dose reduce: eGFR 30-45 → 500 mg/day; contraindicated if eGFR < 30 |
Sulfonylurea (glimepiride, gliclazide) | Stimulates pancreatic insulin secretion via SUR/KATP channels | 0.4-1.2% | Hypoglycemia, weight gain | Dose adjustment at CKD stage 3; caution with hepatic disease |
TZD (pioglitazone) | PPAR-gamma agonist; improves insulin sensitivity in muscle, fat, liver | 0.5-1.4% | Edema, weight gain, fractures (distal limbs), bladder cancer risk | Avoid in NYHA class III-IV heart failure |
DPP-4 inhibitor (sitagliptin, vildagliptin, linagliptin) | Inhibits DPP-4 enzyme, raises endogenous GLP-1/GIP levels | 0.5-0.9% | Pancreatitis (rare), nasopharyngitis | Dose adjustment required (except linagliptin) |
SGLT-2 inhibitor (empagliflozin, dapagliflozin) | Blocks glucose reabsorption at proximal tubule, promotes glucosuria | 0.5-0.9% | UTI, genital mycotic infections, euglycemic DKA, volume depletion | Avoid if eGFR < 45 (for glycemic benefit); cardiovascular/renal benefit may persist at lower eGFR |
Alpha-glucosidase inhibitor (acarbose) | Delays intestinal carbohydrate absorption | 0.5-0.8% | Flatulence, bloating, diarrhea | Discontinue if eGFR < 30 |
Injectable Agents
GLP-1 receptor agonists (liraglutide, dulaglutide, semaglutide)
Mechanism
Enhances insulin secretion (glucose-dependent), suppresses glucagon, delays gastric emptying, promotes satiety
HbA1c Reduction
0.8-2.0%
Key Notes
Weight loss 1-4 kg; cardiovascular and renal benefit. Contraindicated in personal/family history of medullary thyroid carcinoma or MEN2. Avoid if eGFR < 30. Pancreatitis risk
Basal insulin (glargine, detemir, degludec)
Mechanism
Suppresses hepatic glucose output, covers fasting hyperglycemia
HbA1c Reduction
Dose-dependent
Key Notes
Start at 10 U/day or 0.2 U/kg; titrate by 2-4 U every 3-5 days targeting FPG < 130 mg/dL
Prandial insulin (lispro, aspart, glulisine)
Mechanism
Covers postprandial glucose excursion
HbA1c Reduction
Dose-dependent
Key Notes
Start at 4 U or 10% of basal dose before the largest meal; titrate by 1-2 U every 3-4 days
Premixed / Co-formulation insulin (IDegLira, IGlarLixi)
Mechanism
Combined basal coverage + incretin or basal + prandial
HbA1c Reduction
Dose-dependent
Key Notes
Fixed-ratio combinations reduce injection burden; lower hypoglycemia risk than basal-bolus alone
Agent | Mechanism | HbA1c Reduction | Key Notes |
|---|---|---|---|
GLP-1 receptor agonists (liraglutide, dulaglutide, semaglutide) | Enhances insulin secretion (glucose-dependent), suppresses glucagon, delays gastric emptying, promotes satiety | 0.8-2.0% | Weight loss 1-4 kg; cardiovascular and renal benefit. Contraindicated in personal/family history of medullary thyroid carcinoma or MEN2. Avoid if eGFR < 30. Pancreatitis risk |
Basal insulin (glargine, detemir, degludec) | Suppresses hepatic glucose output, covers fasting hyperglycemia | Dose-dependent | Start at 10 U/day or 0.2 U/kg; titrate by 2-4 U every 3-5 days targeting FPG < 130 mg/dL |
Prandial insulin (lispro, aspart, glulisine) | Covers postprandial glucose excursion | Dose-dependent | Start at 4 U or 10% of basal dose before the largest meal; titrate by 1-2 U every 3-4 days |
Premixed / Co-formulation insulin (IDegLira, IGlarLixi) | Combined basal coverage + incretin or basal + prandial | Dose-dependent | Fixed-ratio combinations reduce injection burden; lower hypoglycemia risk than basal-bolus alone |
Step-by-Step Management Algorithm
The 2026 Indonesian guideline uses the following decision architecture based on HbA1c at the time of diagnosis:
Step 1: HbA1c < 7.5% at diagnosis Start lifestyle modification (medical nutrition therapy + exercise) simultaneously with monotherapy (metformin is first-line). Re-evaluate in 3 months.
Step 2: HbA1c ≥ 7.5%, or monotherapy fails at 3 months (HbA1c still ≥ 7%) Escalate to dual therapy: metformin + a second agent with a different mechanism. The choice of second agent depends on comorbidities:
ASCVD or high ASCVD risk → SGLT-2 inhibitor or GLP-1 RA
Heart failure or CKD → SGLT-2 inhibitor preferred (if eGFR adequate); GLP-1 RA if SGLT-2i contraindicated
Cost constraint, no cardiovascular comorbidity → sulfonylurea (modern generation with lower hypoglycemia risk), TZD, or acarbose
Weight concern → DPP-4 inhibitor, SGLT-2 inhibitor, or GLP-1 RA (weight-neutral or weight-reducing)
Step 3: Dual therapy fails at 3 months Escalate to triple oral therapy (three agents with different mechanisms) or add injectable therapy.
Step 4: HbA1c > 9% without metabolic decompensation Can initiate dual or triple combination therapy from the start.
Step 5: HbA1c > 9% WITH metabolic decompensation (rapid weight loss, ketonuria, catabolic state) Insulin is mandatory from the outset, combined with oral agents.
Step 6: Triple therapy failure Proceed to insulin intensification. Begin with basal insulin at bedtime (10 U, around 22:00). If fasting glucose reaches target (< 130 mg/dL) but HbA1c remains above target, add prandial insulin or a GLP-1 RA to cover postprandial excursions.
Treatment Targets
Parameter | Target |
|---|---|
HbA1c | < 7% (individualized) |
Fasting / pre-meal capillary glucose | 80-130 mg/dL |
Post-prandial capillary glucose (1-2 hr) | < 180 mg/dL |
Blood pressure | < 140/90 mmHg (general); < 130/80 if 10-year ASCVD risk > 15% |
LDL cholesterol | < 100 mg/dL (without ASCVD); < 70 mg/dL (with ASCVD) |
HDL cholesterol | > 40 mg/dL (men); > 50 mg/dL (women) |
Triglycerides | < 150 mg/dL |
BMI | 18.5-22.9 kg/m² |
Metformin Dose Adjustment by Renal Function
eGFR (mL/min/1.73 m²) | Maximum Daily Dose |
|---|---|
60-90 | 2000 mg/day |
45-60 | 1000 mg/day |
30-45 | 500 mg/day |
< 30 | Contraindicated |
Medical Nutrition Therapy
The guideline stresses that there is no single ideal macronutrient ratio; dietary planning must be individualized. Key numbers:
Total calories: 25-30 kcal/kg/day (low activity), 30-35 (moderate), 35-40 (high). Alternatively, use the Harris-Benedict equation corrected for activity and stress.
Carbohydrate: minimum 130 g/day (to meet brain glucose needs), 45-65% of total energy. Favor low glycemic index, high fiber sources. Limit simple sugars to < 5% of carbohydrate intake.
Protein: 1.0-1.2 g/kg/day (10-20% of total energy). Do not exceed 2 g/kg/day.
Fat: < 30% of total energy. SAFA < 7%, MUFA 12-15%, PUFA ≤ 10%. Cholesterol < 300 mg/day (< 200 mg/day if LDL > 100).
Sodium: ≤ 1500 mg/day.
Fiber: 14 g per 1000 kcal (about 20-35 g/day).
For weight loss: reduce total energy by 500-750 kcal/day from baseline, aiming for ≥ 5% weight loss, which produces clinically meaningful improvements in insulin sensitivity, HbA1c (0.3-2.0% reduction), lipid profile, and blood pressure.
Comorbidity-Directed Pharmacotherapy
ASCVD (coronary, stroke, PAD)
Preferred Add-On to Metformin
SGLT-2 inhibitor or GLP-1 RA
Why
Proven cardiovascular outcome benefit in CVOT trials
Heart failure
Preferred Add-On to Metformin
SGLT-2 inhibitor
Why
Reduces HF hospitalization and CKD progression. Avoid saxagliptin (worsens HF). Avoid TZD (fluid retention)
CKD
Preferred Add-On to Metformin
SGLT-2 inhibitor (if eGFR adequate) or GLP-1 RA
Why
Slows CKD progression, reduces cardiovascular events
Obesity
Preferred Add-On to Metformin
GLP-1 RA or SGLT-2 inhibitor
Why
Weight reduction 1-4 kg (GLP-1 RA) or 0.7-3.5 kg (SGLT-2i)
High hypoglycemia risk
Preferred Add-On to Metformin
DPP-4 inhibitor, SGLT-2 inhibitor, GLP-1 RA, or TZD
Why
All have low intrinsic hypoglycemia risk
Cost constraint
Preferred Add-On to Metformin
Sulfonylurea (modern generation) or TZD or acarbose
Why
Affordable and widely available
Comorbidity | Preferred Add-On to Metformin | Why |
|---|---|---|
ASCVD (coronary, stroke, PAD) | SGLT-2 inhibitor or GLP-1 RA | Proven cardiovascular outcome benefit in CVOT trials |
Heart failure | SGLT-2 inhibitor | Reduces HF hospitalization and CKD progression. Avoid saxagliptin (worsens HF). Avoid TZD (fluid retention) |
CKD | SGLT-2 inhibitor (if eGFR adequate) or GLP-1 RA | Slows CKD progression, reduces cardiovascular events |
Obesity | GLP-1 RA or SGLT-2 inhibitor | Weight reduction 1-4 kg (GLP-1 RA) or 0.7-3.5 kg (SGLT-2i) |
High hypoglycemia risk | DPP-4 inhibitor, SGLT-2 inhibitor, GLP-1 RA, or TZD | All have low intrinsic hypoglycemia risk |
Cost constraint | Sulfonylurea (modern generation) or TZD or acarbose | Affordable and widely available |
05Acute Complications
Complication | Key Features |
|---|---|
Diabetic Ketoacidosis (DKA) | Glucose 300-600 mg/dL, positive plasma ketones, metabolic acidosis, increased anion gap, osmolarity 300-320 mOsm/mL. Treat with IV fluids (NaCl 0.9%), insulin drip, potassium correction. Hold insulin if K+ < 3.3 mmol/L until corrected |
Hyperosmolar Hyperglycemic State (HHS) | Glucose 600-1200 mg/dL, no significant acidosis, no or minimal ketones, osmolarity 330-380 mOsm/mL, anion gap normal or mildly increased. Very high mortality. Aggressive fluid resuscitation is the cornerstone |
Hypoglycemia | Glucose < 70 mg/dL. Adrenergic symptoms (tremor, palpitations, diaphoresis, hunger) and neuroglycopenic symptoms (confusion, dizziness, loss of consciousness). Treat with 15-20 g oral glucose if conscious; 40% dextrose IV if unconscious. Recheck glucose every 15 minutes. Most commonly caused by sulfonylureas and insulin. Monitor for 24-72 hours with sulfonylurea-induced hypoglycemia |
06Chronic Complications
Macrovascular
Complication
Coronary artery disease, stroke, peripheral arterial disease
Screening / Notes
Claudication, ABI at diagnosis, ECG. Aspirin 75-162 mg/day for secondary prevention or primary prevention if age ≥ 50 with additional risk factors
Microvascular
Complication
Diabetic retinopathy
Screening / Notes
Fundoscopy at diagnosis, then annually. Good glycemic and BP control slows progression
Microvascular
Complication
Diabetic nephropathy
Screening / Notes
UACR + eGFR at diagnosis, then annually. ACE inhibitor or ARB is first-line antihypertensive if albuminuria present
Microvascular
Complication
Diabetic neuropathy
Screening / Notes
Monofilament 10 g + tuning fork 128 Hz at diagnosis, then annually. Symptomatic treatment: gabapentin, pregabalin, or tricyclic antidepressants
Diabetic foot
Complication
Neuropathic and/or ischemic ulceration
Screening / Notes
Comprehensive foot exam annually. Foot care education from diagnosis
Category | Complication | Screening / Notes |
|---|---|---|
Macrovascular | Coronary artery disease, stroke, peripheral arterial disease | Claudication, ABI at diagnosis, ECG. Aspirin 75-162 mg/day for secondary prevention or primary prevention if age ≥ 50 with additional risk factors |
Microvascular | Diabetic retinopathy | Fundoscopy at diagnosis, then annually. Good glycemic and BP control slows progression |
Diabetic nephropathy | UACR + eGFR at diagnosis, then annually. ACE inhibitor or ARB is first-line antihypertensive if albuminuria present | |
Diabetic neuropathy | Monofilament 10 g + tuning fork 128 Hz at diagnosis, then annually. Symptomatic treatment: gabapentin, pregabalin, or tricyclic antidepressants | |
Diabetic foot | Neuropathic and/or ischemic ulceration | Comprehensive foot exam annually. Foot care education from diagnosis |
07Differential Diagnosis and Distractors
DM Type 1
Why It Looks Similar
Also presents with polyuria, polydipsia, weight loss, hyperglycemia
Key Discriminator
Type 1: typically younger, lean, rapid onset, prone to DKA at presentation, positive anti-GAD/anti-islet cell antibodies, absolute insulin deficiency requiring insulin from day 1. Type 2: older, obese, gradual onset, strong family history, insulin resistance features (acanthosis nigricans), often asymptomatic at diagnosis
LADA (Latent Autoimmune Diabetes of Adults)
Why It Looks Similar
Adult-onset autoimmune diabetes; initial response to oral agents
Key Discriminator
Positive autoantibodies (anti-GAD). Progressive beta-cell failure faster than typical type 2. Consider LADA if a lean adult with DM type 2 fails oral therapy within 1-2 years
MODY (Maturity-Onset Diabetes of the Young)
Why It Looks Similar
Young patient with mild hyperglycemia and strong family history
Key Discriminator
Autosomal dominant inheritance across 3 generations. Negative autoantibodies. Genetic testing confirms. Different subtypes respond to different therapies (e.g., MODY 3 responds to SU)
Cushing syndrome
Why It Looks Similar
Hyperglycemia, obesity, hypertension, dyslipidemia
Key Discriminator
Look for truncal obesity with thin extremities, moon facies, purple striae, proximal muscle weakness, easy bruising. Elevated midnight cortisol or failed dexamethasone suppression test
Acromegaly
Why It Looks Similar
Hyperglycemia and insulin resistance
Key Discriminator
Coarsened facial features, enlarged hands/feet, macroglossia, visual field defects. Elevated IGF-1, GH not suppressed on OGTT
Pheochromocytoma
Why It Looks Similar
Episodic hyperglycemia, hypertension, diaphoresis
Key Discriminator
Paroxysmal symptoms (headache, palpitations, sweating), elevated plasma/urine metanephrines and catecholamines
Drug-induced hyperglycemia
Why It Looks Similar
Hyperglycemia in a patient on glucocorticoids, thiazides, atypical antipsychotics, ARVs (protease inhibitors, NRTIs)
Key Discriminator
Temporal relationship between drug initiation and glucose elevation. Resolves or improves with drug discontinuation or substitution
Hemochromatosis
Why It Looks Similar
"Bronze diabetes": skin hyperpigmentation + diabetes + liver disease
Key Discriminator
Elevated ferritin, increased transferrin saturation, liver biopsy with iron deposition. Genetic testing for HFE mutations
Differential | Why It Looks Similar | Key Discriminator |
|---|---|---|
DM Type 1 | Also presents with polyuria, polydipsia, weight loss, hyperglycemia | Type 1: typically younger, lean, rapid onset, prone to DKA at presentation, positive anti-GAD/anti-islet cell antibodies, absolute insulin deficiency requiring insulin from day 1. Type 2: older, obese, gradual onset, strong family history, insulin resistance features (acanthosis nigricans), often asymptomatic at diagnosis |
LADA (Latent Autoimmune Diabetes of Adults) | Adult-onset autoimmune diabetes; initial response to oral agents | Positive autoantibodies (anti-GAD). Progressive beta-cell failure faster than typical type 2. Consider LADA if a lean adult with DM type 2 fails oral therapy within 1-2 years |
MODY (Maturity-Onset Diabetes of the Young) | Young patient with mild hyperglycemia and strong family history | Autosomal dominant inheritance across 3 generations. Negative autoantibodies. Genetic testing confirms. Different subtypes respond to different therapies (e.g., MODY 3 responds to SU) |
Cushing syndrome | Hyperglycemia, obesity, hypertension, dyslipidemia | Look for truncal obesity with thin extremities, moon facies, purple striae, proximal muscle weakness, easy bruising. Elevated midnight cortisol or failed dexamethasone suppression test |
Acromegaly | Hyperglycemia and insulin resistance | Coarsened facial features, enlarged hands/feet, macroglossia, visual field defects. Elevated IGF-1, GH not suppressed on OGTT |
Pheochromocytoma | Episodic hyperglycemia, hypertension, diaphoresis | Paroxysmal symptoms (headache, palpitations, sweating), elevated plasma/urine metanephrines and catecholamines |
Drug-induced hyperglycemia | Hyperglycemia in a patient on glucocorticoids, thiazides, atypical antipsychotics, ARVs (protease inhibitors, NRTIs) | Temporal relationship between drug initiation and glucose elevation. Resolves or improves with drug discontinuation or substitution |
Hemochromatosis | "Bronze diabetes": skin hyperpigmentation + diabetes + liver disease | Elevated ferritin, increased transferrin saturation, liver biopsy with iron deposition. Genetic testing for HFE mutations |
08Traps and High-Yield Pearls
The most common way students lose points on DM type 2 questions falls into several categories:
Trap 1: Choosing the wrong first-line drug. Metformin remains the first-line oral agent for nearly all patients with DM type 2. The only exceptions are when metformin is contraindicated (eGFR < 30, severe hepatic disease, conditions predisposing to lactic acidosis) or when the patient has established ASCVD, heart failure, or CKD that warrants prioritizing an SGLT-2 inhibitor or GLP-1 RA. Do not pick a sulfonylurea as first-line unless the question stem mentions cost as the dominant constraint.
Trap 2: Forgetting to initiate insulin when indicated. When HbA1c > 9% with metabolic decompensation (ketonuria, rapid weight loss, catabolic symptoms), the answer is always insulin, not oral therapy alone. Students who pick "add a second oral agent" in this scenario will get the question wrong.
Trap 3: Ignoring HbA1c limitations. The exam loves to present a patient with sickle cell trait, iron deficiency anemia, or end-stage renal disease and ask about glycemic monitoring. In these patients, HbA1c is unreliable. The correct answer is fructosamine or glycated albumin, which reflects control over the preceding 2-3 weeks.
Trap 4: Not adjusting metformin for renal function. The dose adjustment table for metformin by eGFR is a tested point. Metformin is contraindicated below eGFR 30, and the dose must be halved at eGFR 45-60. Students who miss this will fall for distractors about "lactic acidosis risk."
Trap 5: Missing the cardiovascular comorbidity question. When the question describes a DM type 2 patient with a history of MI, stroke, heart failure, or CKD, the test-writer is asking you to select an SGLT-2 inhibitor or GLP-1 RA as the add-on agent. Choosing a sulfonylurea or TZD in this scenario is the designed wrong answer.
Trap 6: Misclassifying prediabetes. Remember the distinction: IFG (impaired fasting glucose) is fasting 100-125 with normal 2-hr OGTT (< 140); IGT (impaired glucose tolerance) is 2-hr OGTT 140-199. The vignette might present one or the other and ask whether lifestyle modification alone is sufficient or whether metformin should be added (consider metformin for prediabetes only in high-risk patients: BMI ≥ 35, history of GDM, or rising HbA1c despite lifestyle changes).
Trap 7: Diagnosis using glucometer only. The guideline is clear: diagnosis cannot be made on the basis of glucosuria or capillary glucometer readings alone for initial diagnosis (capillary sampling can be used for screening, but enzymatic assay on venous plasma is the standard). However, glucometer is acceptable for ongoing self-monitoring of blood glucose (SMBG).
The core competency being tested in DM type 2 questions is your ability to match the treatment to the patient's cardiovascular and renal risk profile, to correctly escalate therapy based on HbA1c thresholds, and to recognize when insulin becomes non-negotiable.