1. ^*Department of Medicine, Denver, Colorado
2. ^†Department of Pediatrics, Denver, Colorado
3. ^‡Department of Adult General Clinical Research Center, Denver, Colorado
4. ^§Center for Human Nutrition, University of Colorado Health Sciences Center, Denver, Colorado
5. ^¶Research Service of the Denver Veterans Administration Medical Center, Denver, Colorado
6. ^**Departments of Medical Genetics, Department of Medical Biochemistry, Gothenburg University, Goteborg, Sweden

Correspondence: Boris Draznin, Veterans Administration Medical Center, (151) 1055 Clermont Street Denver, CO 80220. E-mail: Boris.Draznin@med.va.gov

These authors contributed equally to the design and implementation of this study.

^**The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7 June 2004; Accepted 20 January 2005.

Abstract

Objective: To determine whether macronutrient composition of a hypocaloric diet can enhance its effectiveness and whether insulin sensitivity (Si) affects the response to hypocaloric diets.

Research Methods and Procedures: Obese nondiabetic insulin-sensitive (fasting insulin < 10 U/mL; n = 12) and obese nondiabetic insulin-resistant (fasting insulin > 15 U/mL; n = 9) women (23 to 53 years old) were randomized to either a high carbohydrate (CHO) (HC)/low fat (LF) (60% CHO, 20% fat) or low CHO (LC)/high fat (HF) (40% CHO, 40% fat) hypocaloric diet. Primary outcome measures after a 16-week dietary intervention were: changes in body weight (BW), Si, resting metabolic rate, and fasting lipids.

Results: Insulin-sensitive women on the HC/LF diet lost 13.5 1.2% (p < 0.001) of their initial BW, whereas those on the LC/HF diet lost 6.8 1.2% (p < 0.001; p < 0.002 between the groups). In contrast, among the insulin-resistant women, those on the LC/HF diet lost 13.4 1.3% (p < 0.001) of their initial BW as compared with 8.5 1.4% (p < 0.001) lost by those on the HC/LF diet (p < 0.04 between two groups). These differences could not be explained by changes in resting metabolic rate, activity, or intake. Overall, changes in Si were associated with the degree of weight loss (r = -0.57, p < 0.05).

Discussion: The state of Si determines the effectiveness of macronutrient composition of hypocaloric diets in obese women. For maximal benefit, the macronutrient composition of a hypocaloric diet may need to be adjusted to correspond to the state of Si.