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Diabetes Care 29:1337-1344, 2006
DOI: 10.2337/dc05-2565
© 2006 by the American Diabetes Association
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Pathophysiology/Complications
Original Article

Effect of Calorie Restriction With or Without Exercise on Insulin Sensitivity, ß-Cell Function, Fat Cell Size, and Ectopic Lipid in Overweight Subjects

D. Enette Larson-Meyer, PHD1, Leonie K. Heilbronn, PHD1, Leanne M. Redman, PHD1, Bradley R. Newcomer, PHD2, Madlyn I. Frisard, PHD1, Steve Anton, PHD1, Steven R. Smith, MD1, Anthony Alfonso, MAPLSTAT1, Eric Ravussin, PHD1 the Pennington CALERIE Team

1 Pennington Biomedical Research Center, Baton Rouge, Louisiana
2 Department of Critical and Diagnostic Care, University of Alabama at Birmingham, Birmingham, Alabama

Address correspondence and reprint requests to Eric Ravussin, PhD, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808. E-mail: ravusse{at}pbrc.edu

OBJECTIVE—The purpose of this article was to determine the relationships among total body fat, visceral adipose tissue (VAT), fat cell size (FCS), ectopic fat deposition in liver (intrahepatic lipid [IHL]) and muscle (intramyocellular lipid [IMCL]), and insulin sensitivity index (Si) in healthy overweight, glucose-tolerant subjects and the effects of calorie restriction by diet alone or in conjunction with exercise on these variables.

RESEARCH DESIGN AND METHODS—Forty-eight overweight volunteers were randomly assigned to four groups: control (100% of energy requirements), 25% calorie restriction (CR), 12.5% calorie restriction +12.5% energy expenditure through structured exercise (CREX), or 15% weight loss by a low-calorie diet followed by weight maintenance for 6 months (LCD). Weight, percent body fat, VAT, IMCL, IHL, FCS, and Si were assessed at baseline and month 6.

RESULTS—At baseline, FCS was related to VAT and IHL (P < 0.05) but not to IMCL. FCS was also the strongest determinant of Si (P < 0.01). Weight loss at month 6 was 1 ± 1% (control, mean ± SE), 10 ± 1% (CR), 10 ± 1% (CREX), and 14 ± 1% (LCD). VAT, FCS, percent body fat, and IHL were reduced in the three intervention groups (P < 0.01), but IMCL was unchanged. Si was increased at month 6 (P = 0.05) in the CREX (37 ± 18%) and LCD (70 ± 34%) groups (P < 0.05) and tended to increase in the CR group (40 ± 20%, P = 0.08). Together the improvements in Si were related to loss in weight, fat mass, and VAT, but not IHL, IMCL, or FCS.

CONCLUSIONS—Large adipocytes lead to lipid deposition in visceral and hepatic tissues, promoting insulin resistance. Calorie restriction by diet alone or with exercise reverses this trend.

Abbreviations: AIRg, acute insulin response to glucose • CALERIE, Comprehensive Assessment of the Long-term Effects of Reducing Intake of Energy • DSAT, deep subcutaneous abdominal adipose tissue • FCS, fat cell mass • IHL, intrahepatic lipid • IMCL, intramyocellular lipid • SAT, subcutaneous abdominal adipose tissue • VAT, visceral adipose tissue


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