Carbohydrate modified diet & insulin sensitizers reduce body weight & modulate metabolic syndrome measures in EMPOWIR (enhance the metabolic profile of women with insulin resistance): A randomized trial of normoglycemic women with midlife weight gain

Rationale: Progressive midlife weight gain is associated with multiple adverse health outcomes and may represent an early manifestation of insulin resistance in a distinct subset of women. Emerging data implicate hyperinsulinema as a proximate cause of weight gain and support strategies that attenuate insulin secretion. Objective: To assess a previously reported novel hypocaloric carbohydrate modified diet alone (D), and in combination with metformin (M) and metformin plus low-dose rosiglitazone (MR), in diverse women with midlife weight gain (defined as > 20lbs since the twenties), normal glucose tolerance, and hyperinsulinemia. Participants: 46 women, mean age 46.6±1.0, BMI 30.5±0.04 kg/m², 54.5% white, 22.7% black, 15.9% Hispanic, at 2 university medical centers. Methods: A dietary intervention designed to reduce insulin excursions was implemented in 4 weekly nutritional group workshops prior to randomization. Main Outcome Measure: Change in 6-month fasting insulin. Pre-specified secondary outcomes were changes in body weight, HOMA-IR, metabolic syndrome (MS) measures, leptin, and adiponectin. Results: Six-month fasting insulin declined significantly in the M group: 12.5 to 8.0 μU/ml, p = .026. Mean 6-month weight decreased significantly and comparably in D, M, and MR groups: 4.7, 5.4, and 5.5% (p's.049, .002, and.032). HOMA-IR decreased in M and MR groups (2.5 to 1.6 and 1.9 to 1.3, p's = .054, .013). Additional improvement in MS measures included reduced waist circumference in D and MR groups and increased HDL in the D and M groups. Notably, mean fasting leptin did not decline in a subset of subjects with weight loss (26.15±2.01 ng/ml to 25.99±2.61 ng/ml, p = .907. Adiponectin increased significantly in the MR group (11.1±1.0 to 18.5±7.4, p<.001) Study medications were well tolerated. Conclusions: These findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies. Trial Registration: ClinicalTrials.gov NCT00618072