Metformin and carbohydrate-modified diet: a novel obesity treatment protocol: preliminary findings from a case series of nondiabetic women with midlife weight gain and hyperinsulinemia.

The authors conducted a retrospective analysis of a new obesity treatment protocol, metformin and hypocaloric, carbohydrate-modified diet, in high-risk, nondiabetic hyperinsulinemic women with progressive midlife weight gain (refractory to diet and exercise). Thirty consecutive nondiabetic women with glucose-mediated area-under-the-curve (AUC) insulin elevations (>or=100 microU/mL) in two body mass index (BMI) categories (group I: 25 to 32.9 kg/m(2) and group II: 33 to 41.7 kg/m(2)) participated in a 1-year treatment program of metformin (mean daily doses of 1,500 mg/day [group I] and 2,000 mg/day [group II]) and carbohydrate-modified dietary regimens. Follow-up body weight (at 3, 6, and 12 months), percentage of patients meeting goal weight attainment (10% reduction in body weight or BMI normalization), and fasting insulin levels (as available) are reported in 26 women (18/18 in group I and 8/12 in group II) who returned for one or more follow-up visits. Significant weight loss was observed at 3, 6, and 12 months in both group I (3.47 [SE 0.68], 6.41 [0.72], and 8.06 [0.96] kg, P < 0.0001) and group II (4.4 [0.8], 9.7 [2.3], 15.1 [3.3], P = 0.001, 0.004, 0.011). Twenty-five of 26 (96%) patients lost >or=5% of their body weight at 6 months and 21/26 (81%) patients lost >or=10% of their body weight at 12 months. Posttreatment fasting insulin decrement (-35.5 [8.2]%) was the most significant predictor of 1-year weight loss (R(2)=0.656, regression coefficient = 0.810, P = 0.005). Following completion of the 1-year intervention study, weight stabilization (within 1 kg) was observed at a 6-month surveillance in 8/9 patients who attained goal weight and continued metformin without additional nutritional counseling, in contrast to weight gain (>or=4 kg or 50% of lost weight) in 5/6 patients who discontinued metformin. The authors concluded that metformin and carbohydrate-modified hypocaloric diet could be an effective novel treatment for long-term weight management in nondiabetic, hyperinsulinemic women.

New perspectives on diagnosis and treatment of obesity.

The alarming increase in the prevalence of obesity in the past decade, as demonstrated by ongoing systematic population-based studies, and increased recognition of the adverse health consequences associated with excess body weight have generated widespread interest in the management of obesity. After an extensive review, the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health issued a consensus statement with comprehensive clinical treatment guidelines in 1998 that is relevant to cardiologists as well as primary care physicians. A new focus on obesity research has advanced our understanding of the complexity of this disorder and provided new molecular targets for intervention, including beta(3)-adrenergic receptor agonists, leptin analogues, and uncoupling proteins (UCPs) that stimulate energy expenditure. Two newly available pharmacotherapeutic agents approved by the United States Food and Drug Administration (FDA) and increasing acceptance of bariatric surgery for specific categories of obese patients have expanded current therapeutic options for the management of obesity. Nonetheless, the cornerstone of lifetime weight regulation and the prevention and treatment of obesity inevitably will remain lifestyle modification and long-term vigilance.

Insulin like growth factor-binding protein-1 as a marker for hyperinsulinemia in obese menopausal women.

Hyperinsulinemia, a manifestation of insulin resistance, precursor of non-insulin dependent diabetes mellitus (NIDDM) and the hallmark of Syndrome X was assessed in 27 obese post-menopausal women. Insulin-like growth factor binding protein-1 (IGFBP-1), which had been shown previously to correlate inversely with insulin in animal and human studies, was evaluated as a diagnostic marker for abnormal glucose stimulated area under the curve (AUC) insulin (defined a priori as > or = 100 microU/ml). We performed analysis of variance and logistic regression to assess IGFBP-1 and other study covariates, including body mass index, blood pressure, lipids and measures of glucose and insulin in hyperinsulinemic vs. normal women and evaluated performance characteristics (sensitivity, specificity, positive and negative predictive values and accuracy rates). The mean IGFBP-1 was 6.1 ng/ml (95% confidence interval (CI) 3.1 to 8.9) for the hyper-insulinemic women compared to 33.5 ng/ml (CI 15.8 to 51.2) for normal women (P = .0027). At a cutoff point of 15ng/ml, which was selected to correspond to the lower 95% confidence limit for the normal study population, IGFBP-1 was abnormal in all 13 women with hyperinsulinemia and 4 women with normal insulin levels (sensitivity 100%, specificity 69%; positive predictive value 76%, negative predictive value 100%, diagnostic accuracy rate 85%). Logistic regression models indicated that, of all study covariates, IGFBP-1 was the best predictor variable for AUC-insulin as a binary dependent variable. These results suggest that IGFBP-1 may be a simple serum marker for hyperinsulinemia in a subpopulation of obese menopausal women.