What are the actors for managing insulin resistance?

Management of Insulin Resistance

Begin with comprehensive lifestyle modifications including dietary changes, increased physical activity, and weight loss targeting 5-10% of body weight for overweight/obese individuals, followed by metformin as first-line pharmacological therapy if lifestyle changes are insufficient. 1

Lifestyle Interventions as Primary Treatment

Weight loss is the cornerstone of insulin resistance management. Structured programs emphasizing lifestyle changes with education, reduced energy and fat intake (≤30% of total energy), regular physical activity, and consistent participant contact can produce long-term weight loss of 5-7% of starting weight. 2 This modest weight loss significantly improves insulin sensitivity independent of the mechanism. 2

Exercise Prescription

The exercise regimen should be specific and quantified:

• Aerobic exercise: At least 150 minutes per week of moderate-intensity activity (50-70% of maximum heart rate), spread over at least 3 days with no more than 2 consecutive days without exercise. 2
• Resistance training: At least twice per week involving all major muscle groups, as progressive resistance exercise improves insulin sensitivity to the same or greater extent as aerobic exercise. 2
• Combined approach: Additive benefit occurs when aerobic and resistance training are performed together. 2

For children and adolescents with insulin resistance, encourage at least 60 minutes of physical activity daily. 2

Dietary Modifications

The DASH (Dietary Approaches to Stop Hypertension) diet framework should guide nutritional interventions: emphasize fruits, vegetables, low-fat dairy products, whole grains, poultry, fish, and nuts while reducing fats, red meat, sweets, and sugar-containing beverages. 2

Avoid low-carbohydrate diets restricting total carbohydrate to <130 g/day, as long-term effects are unknown and impact on cardiovascular risk profile is uncertain. 2 High total carbohydrate intake does not adversely affect insulin sensitivity compared with high-fat diets. 3

Chrononutrition strategies improve insulin responses: Consume most calories and carbohydrates at lunch time and early afternoon, avoid late evening dinner, and maintain consistent meal timing. 4 Meal sequence matters—consume vegetables/salads/soups first, followed by protein, then starchy foods to ameliorate glycemic and insulin responses. 4

Pharmacological Management

Metformin is the preferred first-line pharmacological agent for insulin resistance, particularly in patients with type 2 diabetes. 1 The American Diabetes Association strongly endorses this approach across multiple guidelines. 1

Metformin Dosing Strategy

Start at 500 mg daily with gradual titration, increasing by 500 mg every 1-2 weeks to minimize gastrointestinal side effects, targeting an ideal dose of 2000 mg daily in divided doses. 1 This slow titration is critical to avoid the most common side effect leading to discontinuation.

Alternative Pharmacological Agents

Thiazolidinediones (pioglitazone) directly decrease insulin resistance in peripheral tissues and liver by activating PPARγ nuclear receptors, resulting in increased insulin-dependent glucose disposal and decreased hepatic glucose output. 5 Unlike sulfonylureas, pioglitazone is not an insulin secretagogue and depends on the presence of insulin for its mechanism of action. 5

Pioglitazone improves lipid profiles with mean decreases in triglycerides (9-10%) and mean increases in HDL cholesterol (12-19%). 5 However, metformin remains preferred as first-line therapy per guideline recommendations. 1

Special Population Considerations

Patients with Severe Hyperglycemia

For patients presenting with significant hyperglycemic symptoms, markedly elevated plasma glucose, or HbA1c ≥10%, initiate insulin therapy from the outset rather than waiting for lifestyle modifications or oral agents to take effect. 1 This prevents further metabolic decompensation.

Older Adults (≥65-70 years)

Focus on drug safety when selecting treatments, prioritizing strategies that minimize hypoglycemia risk, heart failure, renal dysfunction, bone fractures, and drug-drug interactions. 1 Less stringent glycemic targets (HbA1c <7.5-8.0%) may be appropriate for elderly patients with long-standing or complicated disease. 1

Obese Patients

Intensive lifestyle intervention should be emphasized, and GLP-1 receptor agonists are particularly beneficial due to their association with weight reduction. 1 The combination of weight loss and improved insulin sensitivity creates a synergistic effect.

Pregnancy

Insulin is the preferred medication for treating hyperglycemia in pregnancy, with target fasting glucose <95 mg/dL and either one-hour postprandial <140 mg/dL or two-hour postprandial <120 mg/dL. 1 Oral agents should be avoided during pregnancy.

Monitoring and Follow-up

Monitor HbA1c every 3 months until target is achieved, then at least twice yearly. 1 Assess for improvement in markers of insulin resistance including fasting glucose, lipid profile (particularly triglycerides and HDL cholesterol), and blood pressure. 1

Comprehensive cardiovascular risk reduction must remain a major focus of therapy, as insulin resistance is strongly associated with cardiovascular disease, hypertension, and dyslipidemia. 1, 2

Common Pitfalls to Avoid

• Delaying pharmacological intervention: If lifestyle modifications alone are insufficient after 3-6 months, add metformin rather than continuing ineffective lifestyle-only approaches. 1
• Inadequate exercise intensity or duration: Ensure patients meet the 150 minutes per week threshold with proper intensity (50-70% maximum heart rate). 2
• Ignoring resistance training: Many patients focus solely on aerobic exercise, missing the equal or greater insulin sensitivity benefits of resistance training. 2
• Inappropriate exercise in complications: In proliferative diabetic retinopathy or severe non-proliferative diabetic retinopathy, vigorous aerobic or resistance exercise may trigger vitreous hemorrhage or retinal detachment. 2 In severe peripheral neuropathy, avoid treadmill, prolonged walking, jogging, and step exercises; recommend swimming, bicycling, rowing, and chair exercises instead. 2
• Neglecting cardiovascular risk assessment: Pre-exercise evaluation should assess for uncontrolled hypertension, severe autonomic neuropathy, severe peripheral neuropathy, history of foot lesions, and unstable proliferative retinopathy. 2