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

Summary, in English

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 Malmo Diet and Cancer (MDC) and Malmo 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 x 10(-8)) and the risk to develop incident type 2 diabetes (OR 1.16; P = 3.2 x 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/m(2) per risk allele; P = 2.0 x 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 (Delta 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. Diabetes 60:1637-1644, 2011

• Författare: Jens K. Hertel; Stefan Johansson; Emily Sonestedt; Anna Jonsson; Rolv T. Lie; Carl G. P. Platou; Peter Nilsson; Gull Rukh; Kristian Midthjell; Kristian Hveem; Olle Melander; Leif Groop; Valeriya Lyssenko; Anders Molven; Marju Orho-Melander; Pal R. Njolstad
• Avdelning/ar: Nutritionsepidemiologi; Translationell Muskel Forskning; Internmedicin - epidemiologi; Institutionen för kliniska vetenskaper, Malmö; EXODIAB: Excellence of Diabetes Research in Sweden; EpiHealth: Epidemiology for Health
• Publiceringsår: 2011
• Språk: Engelska
• Sidor: 1637-1644
• Publikation/Tidskrift/Serie: Diabetes
• Volym: 60
• Issue: 5
• Länkar: http://dx.doi.org/10.2337/db10-1340
• Dokumenttyp: Artikel i tidskrift
• Förlag: American Diabetes Association Inc.
• Ämne: Endocrinology and Diabetes
• Status: Published
• Forskningsgrupp: Nutrition Epidemiology; Genomics, Diabetes and Endocrinology; Internal Medicine - Epidemiology
• ISBN/ISSN/Övrigt: ISSN: 1939-327X