Approach Considerations

Evaluate patients for comorbid conditions; this is generally feasible on an outpatient basis. Admission for laboratory studies and treatment of acute complications may be warranted for patients whose conditions require urgent or emergent intervention. The metabolic syndrome requires aggressive control of cardiovascular and metabolic risk factors. Tailor therapy for optimal benefits.

Weight reduction improves insulin sensitivity in cases of obesity and in most of the obesity-related insulin-resistant states. Restriction of caloric intake is indicated. Dietary indiscretion, such as consumption of a diet high in cholesterol and sodium, should be avoided. Alcohol use should be limited. Smoking cessation is indicated.^{[64, 65]}

Patiends should avoid physical inactivity.^[66]Exercise improves insulin sensitivity via the following^{[67, 68]}:

Increased oxidative enzymes
Increased GLUT-4
Increased capillarity
Reduced central adiposity

In patients with insulin resistance, diligent monitoring of metabolic profile, general status, medications, and side effects is indicated. Transfer may be indicated for diagnostic evaluation and for the treatment of major primary conditions and complications.

Consultation with an endocrinologist is indicated in insulin resistance. Referral to a medical weight management program is usually needed. Consultation with a cardiologist is also usually indicated. Other specialists, such as a dermatologist, gynecologist, cardiothoracic surgeon, and ophthalmologist, may need to be consulted based on the nature of the disease and the prevailing pathology.

Pharmacologic Therapy

Medications that reduce insulin resistance (insulin-sensitizing and antihyperglycemic effects) include metformin and the thiazolidinediones.^[11]

Metformin is a biguanide; it reduces hepatic glucose output and increases the uptake in the peripheral tissues (muscle and adipocytes). Metformin is a major drug in the treatment of patients who are obese and have type 2 diabetes. The drug enhances weight reduction and improves lipid profile and vascular integrity.^[69]

Long-term follow-up data from the Diabetes Prevention Program (DPP)/DPP Outcomes Study (DPPOS) found metformin is associated with vitamin B12 deficiency, and routine measurement of vitamin B12 should be considered in patients receiving metaformin.^[70]

Thiazolidinediones lower plasma insulin levels and treat type 2 diabetes associated with insulin resistance.^{[71, 72, 73]} In a multicenter, double-blind trial of 3876 insulin-resistant patients who had had a recent ischemic stroke or transient ischemic attack (TIA), those receiveing pioglitazone (45 mg daily) had a reduced the risk of stroke, myocardial infarction, and diabetes compared to those receiving placebo. However, pioglitazone increased the risk for weight gain, edema, and fracture.^[74]

Successful treatment of severe type B insulin resistance has been reported with rituximab, cyclophosphamide, and prednisone following failure of immunosuppressive therapy and plasmapheresis to control glucose levels or reduce insulin dosage.^[75]

Surgical Treatment of Underlying Causes

Improvement in insulin resistance occurs after bariatric surgery, such as gastric banding, sleeve gastrectomy, and gastric bypass, when carried out in carefully selected morbidly obese patients.^[76]Bariatric surgery may be appropriate for patients with a body mass index (BMI) greater than 40 kg/m² or greater than 35 kg/m² in combination with high-risk comorbidities. It is the most effective treatment for obesity that is currently available, but it is reserved for patients who are unable to attain weight reduction after attempting noninvasive or less intense options. In severe cardiovascular disease, procedures such as coronary artery bypass graft and peripheral vascular surgery may be necessary.

Cosmetic and palliative treatments may be indicated in the treatment of many patients with insulin resistance syndrome, depending on the type and severity of physical anomalies (eg, epilation and electrolysis for hirsutism in patients with PCOS).

Guidelines

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