What is the recommended approach to evaluate insulin resistance in an overweight adult with risk factors (central obesity, family history of type 2 diabetes, hypertension, dyslipidemia, sedentary lifestyle, prior gestational diabetes) and how should it be managed?

Evaluating Insulin Resistance in High-Risk Adults

Screen this patient immediately using fasting plasma glucose, hemoglobin A1C, or a 75-gram oral glucose tolerance test—all three are equally appropriate and validated screening methods. 1, 2

Who Requires Screening

This patient meets multiple American Diabetes Association criteria for immediate testing:

• Overweight/obesity (BMI ≥25 kg/m² or ≥23 kg/m² for Asian Americans) 1
• Central obesity (clinical marker of insulin resistance) 1, 3
• First-degree family history of type 2 diabetes 1
• Hypertension (≥130/80 mmHg or on therapy) 1
• Dyslipidemia (HDL <35 mg/dL and/or triglycerides >250 mg/dL) 1
• Physical inactivity 1
• Prior gestational diabetes (requires testing every 1-3 years lifelong) 1

The presence of any two of these risk factors in an overweight adult mandates screening. 1

Diagnostic Testing Algorithm

Choose One of Three Equally Valid Tests:

Fasting Plasma Glucose (FPG):

• Prediabetes/insulin resistance: 100-125 mg/dL (5.6-6.9 mmol/L) 1, 2, 3
• Diabetes: ≥126 mg/dL 2
• Requires 8-hour fast 3, 4

Hemoglobin A1C:

• Prediabetes/insulin resistance: 5.7-6.4% (39-47 mmol/mol) 1, 2
• Diabetes: ≥6.5% 2
• No fasting required 1
• Stronger predictor of cardiovascular events than fasting glucose 1

75-gram Oral Glucose Tolerance Test (OGTT):

• Prediabetes/insulin resistance: 2-hour glucose 140-199 mg/dL (7.8-11.0 mmol/L) 1, 2, 3
• Diabetes: 2-hour glucose ≥200 mg/dL 2
• Patient must consume ≥150g carbohydrate daily for 3 days before testing 2

Additional Confirmatory Testing (Optional):

Fasting insulin levels can directly confirm insulin resistance:

• Normal: <15 mU/L 3, 4
• Borderline high: 15-20 mU/L 4
• High (confirms insulin resistance): >20 mU/L 4

Physical Examination Findings

Look specifically for these clinical markers of insulin resistance:

• Acanthosis nigricans (velvety hyperpigmentation in skin folds—pathognomonic for hyperinsulinemia) 1, 3, 4
• Central/visceral adiposity (waist circumference measurement) 3
• Skin tags 3

Risk Stratification for Intervention Intensity

Very high-risk patients requiring aggressive intervention include those with:

• A1C >6.0% (>42 mmol/mol) 1
• Both impaired fasting glucose and impaired glucose tolerance 1

These individuals have a 25-50% five-year risk of developing diabetes and a 20-fold increased relative risk compared to those with A1C 5.0%. 1

Management Approach

First-Line Treatment: Intensive Lifestyle Modification

Implement targeted weight loss combined with regular physical activity immediately—this is the primary intervention that reduces insulin resistance and can achieve diabetes remission. 2

Specific recommendations:

• Weight loss to achieve healthy body weight 2, 5
• 30 minutes of moderate-intensity physical activity daily 5
• Increased dietary fiber intake 5

Pharmacologic Management

Metformin is the preferred medication when lifestyle measures alone are insufficient. 2

Comorbidity Management

Aggressively control hypertension as part of comprehensive insulin resistance management. 2

Treat dyslipidemia according to standard lipid-lowering guidelines—this reduces cardiovascular events in insulin-resistant patients. 2

Follow-Up Testing Schedule

If initial tests are normal: Repeat screening every 3 years minimum 1, 2

If prediabetes is identified (IFG, IGT, or A1C 5.7-6.4%): Test annually 1, 2

If BMI is increasing or risk factors are worsening: Test more frequently than standard intervals 1, 2

Prior gestational diabetes: Test every 1-3 years lifelong 1

Critical Pitfalls to Avoid

Always perform testing in the fasting state (minimum 8 hours) to avoid postprandial variations that invalidate results. 3, 4

Normal glucose levels do not exclude insulin resistance—hyperinsulinemia can exist with euglycemia, so consider measuring fasting insulin if clinical suspicion remains high despite normal glucose. 3

Do not diagnose insulin resistance during acute illness—stress hyperglycemia temporarily mimics insulin resistance and should not be used for diagnosis. 4

Note all medications affecting glucose metabolism when interpreting results, as these can confound testing. 4

Population-Specific Considerations

Asian Americans have increased diabetes risk at lower BMI thresholds: Use BMI ≥23 kg/m² (not ≥25 kg/m²) as the screening threshold. 1, 3, 4

African Americans may have equivalent diabetes risk at BMI 26 kg/m² compared to BMI 30 kg/m² in non-Hispanic whites. 3