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Sex-specific interactions between the IRS1 polymorphism and intakes of carbohydrates and fat on incident type 2 diabetes.

  • Ulrika Ericson
  • Gull Rukh
  • Ivana Stojkovic
  • Emily Sonestedt
  • Bo Gullberg
  • Elisabet Wirfält
  • Peter Wallström
  • Marju Orho-Melander
Publishing year: 2012-12-05
Language: English
Publication/Series: The American journal of clinical nutrition
Document type: Journal article
Publisher: American Society for Clinical Nutrition

Abstract english

BACKGROUND: The minor T allele of rs2943641 near the gene encoding for insulin receptor substrate 1 (IRS1) has been associated with decreased risk of type 2 diabetes (T2D) and adiposity in genome-wide association studies. Dietary intake can influence the regulation of IRS1, and studies have indicated sex-specific associations between IRS1 and adiposity. OBJECTIVE: The objective was to examine the interaction between IRS1 rs2943641 and macronutrient intakes on incident T2D and percentage body fat in the Malmö Diet and Cancer cohort. DESIGN: The study included 15,227 women and 9614 men aged 45-74 y without prevalent diabetes. Dietary data were collected with a modified diet history method. During 12 y follow-up, 1567 incident T2D cases were identified. RESULTS: The T allele was associated with lower incidence of T2D (P-trend = 0.003) and, in men, with higher percentage body fat (P-trend = 0.00002). We observed 3-way interactions between sex, rs2943641, and carbohydrate intake (P = 0.01) as well as between sex, rs2943641, and fat intake (P = 0.01) on incident T2D. Among women, the T allele was associated with decreased risk only in the lower tertiles of carbohydrate intake (P-trend = 0.01, P-interaction = 0.01). In contrast, among men, the T allele was associated with decreased risk in the lowest tertile of fat intake (P-trend = 0.01, P-interaction = 0.02). No interaction was observed between macronutrient intakes and rs2943641 on percentage body fat. CONCLUSIONS: Our results indicate that IRS1 rs2943641 interacts with carbohydrate and fat intakes on incident T2D in a sex-specific fashion. A protective association between the rs2943641 T allele and T2D was restricted to women with low carbohydrate intake and to men with low fat intake.


  • Nutrition and Dietetics


  • Nutrition Epidemiology
  • Diabetes - Cardiovascular Disease
  • ISSN: 1938-3207
Emily Sonestedt
E-mail: emily [dot] sonestedt [at] med [dot] lu [dot] se

Associate senior lecturer

Nutrition Epidemiology

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+46 73 700 71 45


Jan Waldenströms gata 35, CRC 60:13, Malmö


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