FTO is the strongest known genetic susceptibility locus for obesity. Experimental studies in animals suggest the potential roles of FTO in regulating food intake. The interactive relation among FTO variants, dietary intake and body mass index (BMI) is complex and results from previous often small-scale studies in humans are highly inconsistent. We performed large-scale analyses based on data from 177,330 adults (154 439 Whites, 5776 African Americans and 17 115 Asians) from 40 studies to examine: (i) the association between the FTO-rs9939609 variant (or a proxy single-nucleotide polymorphism) and total energy and macronutrient intake and (ii) the interaction between the FTO variant and dietary intake on BMI. The minor allele (A-allele) of the FTO-rs9939609 variant was associated with higher BMI in Whites (effect per allele = 0.34 [0.31, 0.37] kg/m(2), P = 1.9 × 10(-105)), and all participants (0.30 [0.30, 0.35] kg/m(2), P = 3.6 × 10(-107)). The BMI-increasing allele of the FTO variant showed a significant association with higher dietary protein intake (effect per allele = 0.08 [0.06, 0.10] %, P = 2.4 × 10(-16)), and relative weak associations with lower total energy intake (-6.4 [-10.1, -2.6] kcal/day, P = 0.001) and lower dietary carbohydrate intake (-0.07 [-0.11, -0.02] %, P = 0.004). The associations with protein (P = 7.5 × 10(-9)) and total energy (P = 0.002) were attenuated but remained significant after adjustment for BMI. We did not find significant interactions between the FTO variant and dietary intake of total energy, protein, carbohydrate or fat on BMI. Our findings suggest a positive association between the BMI-increasing allele of FTO variant and higher dietary protein intake and offer insight into potential link between FTO, dietary protein intake and adiposity.

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OBJECTIVETo test the hypothesis that type 2 diabetes is associated with greater decline in cognitive function in middle-aged individuals.RESEARCH DESIGN AND METHODSIn the Dutch prospective Doetinchem Cohort Study, cognitive functioning was measured twice within a 5-year time interval in 2,613 men and women. Participants were aged 43–70 years at baseline (1995–2002), and no one had a history of stroke. Change in scores on global cognitive function as well as on specific cognitive function domains (memory, speed of cognitive processes, and cognitive flexibility) were compared for respondents with and without type 2 diabetes (verified by the general practitioner or random plasma glucose levels ≥11.1 mmol/l).RESULTSAt the 5-year follow-up, the decline in global cognitive function in diabetic patients was 2.6 times greater than that in individuals without diabetes. For individuals aged ≥60 years, patients with incident and prevalent diabetes showed a 2.5 and 3.6 times greater decline, respectively, in cognitive flexibility than individuals without diabetes. For most cognitive domains, the magnitude of cognitive decline in patients with incident diabetes was intermediate between that of individuals without diabetes and that of patients with diabetes at baseline.CONCLUSIONSMiddle-aged individuals with type 2 diabetes showed a greater decline in cognitive function than middle-aged individuals without diabetes.

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