1.
Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians.
Li, H, Kilpeläinen, TO, Liu, C, Zhu, J, Liu, Y, Hu, C, Yang, Z, Zhang, W, Bao, W, Cha, S, et al
Diabetologia. 2012;(4):981-95
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Abstract
AIMS/HYPOTHESIS FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. METHODS All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. RESULTS The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. CONCLUSIONS/INTERPRETATION FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
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Dietary carbohydrates, physical inactivity, obesity, and the 'metabolic syndrome' as predictors of coronary heart disease.
Liu, S, Manson, JE
Current opinion in lipidology. 2001;(4):395-404
Abstract
Several decades of epidemiological and clinical research have identified physical inactivity, excessive calorie consumption, and excess weight as common risk factors for both type 2 diabetes mellitus and coronary heart disease. This trio forms the environmental substrate for a now well-recognized metabolic phenotype called the insulin resistance syndrome. Recent data suggest that a high intake of rapidly absorbed carbohydrates, which is characterized by a high glycemic load (a measure of carbohydrate quality and quantity), may increase the risk of coronary heart disease by aggravating glucose intolerance and dyslipidemia. These data also suggest that individuals who are obese and insulin resistant are particularly prone to the adverse effects of a high dietary glycemic load. In addition, data continue to accumulate suggesting the important beneficial effects of physical activity, even at moderate levels, and weight reduction on improving insulin sensitivity and reducing the risk of coronary heart disease. Future metabolic studies should continue to quantify the physiological impact of different foods on serum glucose and insulin, and such information should routinely be incorporated into large-scale and long-term prospective studies, in which the possible interaction effects between diet and other metabolic determinants such as physical activity and obesity can be examined. Until more definitive data are available, replacing refined grain products and potatoes with minimally processed plant-based foods such as whole grains, fruits, and vegetables, and reducing the intake of high glycemic load beverages may offer a simple strategy for reducing the incidence of coronary heart disease.