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The Carbohydrate-Insulin Model of ObesityBeyond “Calories In, Calories Out”

Educational Objective
To review the association of a high-carbohydrate diet with postprandial hyperinsulinemia, deposition of calories in fat cells instead of oxidation in lean tissues, and predisposition to weight gain through increased hunger, slowing metabolic rate, or both.
1 Credit CME

Despite intensive research, the causes of the obesity epidemic remain incompletely understood and conventional calorie-restricted diets continue to lack long-term efficacy. According to the carbohydrate-insulin model (CIM) of obesity, recent increases in the consumption of processed, high–glycemic-load carbohydrates produce hormonal changes that promote calorie deposition in adipose tissue, exacerbate hunger, and lower energy expenditure. Basic and genetic research provides mechanistic evidence in support of the CIM. In animals, dietary composition has been clearly demonstrated to affect metabolism and body composition, independently of calorie intake, consistent with CIM predictions. Meta-analyses of behavioral trials report greater weight loss with reduced-glycemic load vs low-fat diets, though these studies characteristically suffer from poor long-term compliance. Feeding studies have lacked the rigor and duration to test the CIM, but the longest such studies tend to show metabolic advantages for low-glycemic load vs low-fat diets. Beyond the type and amount of carbohydrate consumed, the CIM provides a conceptual framework for understanding how many dietary and nondietary exposures might alter hormones, metabolism, and adipocyte biology in ways that could predispose to obesity. Pending definitive studies, the principles of a low-glycemic load diet offer a practical alternative to the conventional focus on dietary fat and calorie restriction.

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Article Information

Corresponding Author: David S. Ludwig, MD, PhD, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115 (

Accepted for Publication: May 7, 2018.

Published Online: July 2, 2018. doi:10.1001/jamainternmed.2018.2933

Author Contributions: Author Ludwig had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Ludwig.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Ludwig.

Critical revision of the manuscript for important intellectual content: All authors.

Administrative, technical, or material support: All authors.

Conflict of Interest Disclosures: Both authors received grants (to Boston Children’s Hospital) from the National Institutes of Health, Nutrition Science Initiative, the Laura and John Arnold Foundation and other philanthropic organizations unaffiliated with the food industry. Both authors have conducted research studies examining the carbohydrate-insulin model. Dr Ludwig received royalties for books on obesity and nutrition that recommend a low-glycemic load diet. Dr Ludwig is supported in part by award K24DK082730 from the National Institute of Diabetes and Digestive and Kidney Diseases. No other disclosures are reported.

Disclaimer: The content of this article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Diabetes and Digestive and Kidney Diseases or the National Institutes of Health.

Additional Contributions: We thank Dariush Mozaffarian, MD, PhD, Tufts University, for advice on an earlier version of this manuscript. He received no financial compensation.

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