FTO, Type 2 Diabetes, and Weight Gain Throughout Adult Life

A Meta-Analysis of 41,504 Subjects From the Scandinavian HUNT, MDC, and MPP Studies

  1. Pål R. Njølstad1,14
  1. 1Department of Clinical Medicine, University of Bergen, Bergen, Norway
  2. 2Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
  3. 3Department of Clinical Sciences in Malmö, Nutrition Epidemiology, Lund University, Malmö, Sweden
  4. 4Department of Clinical Sciences in Malmö, Diabetes and Cardiovascular Disease–Genetic Epidemiology, Lund University, Malmö, Sweden
  5. 5Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, and Lund University Diabetes Centre, Malmö, Sweden
  6. 6Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway
  7. 7HUNT Research Centre, Department of Public Health and General Practice, Norwegian University of Science and Technology, Verdal, Norway
  8. 8Department of Internal Medicine, Levanger Hospital, Nord-Trøndelag Health Trust, Norway
  9. 9Department of Clinical Sciences, Division of Medicine, Lund University, Malmö, Sweden
  10. 10Department of Clinical Sciences, Hypertension and Cardiovascular Diseases, University Hospital Malmö, Lund University, Malmö, Sweden
  11. 11Department of Medicine, Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland
  12. 12Gade Institute, University of Bergen, Bergen, Norway
  13. 13Department of Pathology, Haukeland University Hospital, Bergen, Norway
  14. 14Department of Pediatrics, Haukeland University Hospital, Bergen, Norway
  1. Corresponding author: Pål R. Njølstad, pal.njolstad{at}uib.no.
  1. J.K.H. and S.J. contributed equally to this work.

  2. E.S. and A.J. contributed equally to this work.

Abstract

OBJECTIVE FTO is the most important polygene identified for obesity. We aimed to investigate whether a variant in FTO affects type 2 diabetes risk entirely through its effect on BMI and how FTO influences BMI across adult life span.

RESEARCH DESIGN AND METHODS Through regression models, we assessed the relationship between the FTO single nucleotide polymorphisms rs9939609, type 2 diabetes, and BMI across life span in subjects from the Norwegian population-based HUNT study using cross-sectional and longitudinal perspectives. For replication and meta-analysis, we used data from the Malmö Diet and Cancer (MDC) and Malmö Preventive Project (MPP) cohorts, comprising a total sample of 41,504 Scandinavians.

RESULTS The meta-analysis revealed a highly significant association for rs9939609 with both type 2 diabetes (OR 1.13; P = 4.5 × 10−8) and the risk to develop incident type 2 diabetes (OR 1.16; P = 3.2 × 10−8). The associations remained also after correction for BMI and other anthropometric measures. Furthermore, we confirmed the strong effect on BMI (0.28 kg/m2 per risk allele; P = 2.0 × 10−26), with no heterogeneity between different age-groups. We found no differences in change of BMI over time according to rs9939609 risk alleles, neither overall (∆BMI = 0.0 [−0.05, 0.05]) nor in any individual age stratum, indicating no further weight gain attributable to FTO genotype in adults.

CONCLUSIONS We have identified that a variant in FTO alters type 2 diabetes risk partly independent of its observed effect on BMI. The additional weight gain as a result of the FTO risk variant seems to occur before adulthood, and the BMI difference remains stable thereafter.

Footnotes

  • Received September 20, 2010.
  • Accepted February 17, 2011.

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  1. Diabetes vol. 60 no. 5 1637-1644
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