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A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
Manning, AK, Hivert, MF, Scott, RA, Grimsby, JL, Bouatia-Naji, N, Chen, H, Rybin, D, Liu, CT, Bielak, LF, Prokopenko, I, et al
Nature genetics. 2012;(6):659-69
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Abstract
Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
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Weight fluctuations and risk for metabolic syndrome in an adult cohort.
Vergnaud, AC, Bertrais, S, Oppert, JM, Maillard-Teyssier, L, Galan, P, Hercberg, S, Czernichow, S
International journal of obesity (2005). 2008;(2):315-21
Abstract
OBJECTIVE Weight gain is a risk factor for metabolic syndrome (MS). However, it is not known whether weight fluctuations (WF) have a deleterious effect upon MS risk. In the present study, we investigated this association in subjects participating in the SU.VI.MAX cohort. METHODS MS status was assessed at baseline (1994/1995) and at the end of follow-up (2001/2002) using the National Cholesterol Education Program-Adult Treatment Panel III criteria. WF were estimated with four weight measures during follow-up. Odds ratio (OR, 95% confidence interval (CI)) for incident MS cases was evaluated according to four WF groups (no WF and tertiles of WF) in 3553 middle-aged subjects. RESULTS The OR (95% CI) for MS was 2.06 (1.20-3.52) for the third WF tertile compared to the first tertile. This association was independent of confounding variables, especially relative weight change during follow-up. Subjects without WF had a 2.72-fold increase (1.64-4.53) for MS risk compared to the first tertile of WF. For MS components taken separately, similar associations were found for raised blood pressure, low high-density lipoprotein-cholesterol and increased waist circumference. CONCLUSION Our results showed that WF was an independent risk factor for MS after 7 years of follow-up. Moreover, subjects without WF were also at risk for MS, due to the highest weight gain during follow-up. These results support the benefits of weight stability and emphasize the importance of weight gain prevention starting from early adulthood.
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Blood lipid and lipoprotein levels: relationships with educational level and region of residence in the French SU.VI.MAX study.
Bruckert, E, Czernichow, S, Bertrais, S, Paillard, F, Tichet, J, Galan, P, Castetbon, K, Hercberg, S
Preventive medicine. 2005;(6):803-11
Abstract
BACKGROUND Blood lipid profile of French men and women obtained from the general population is not well known. Furthermore, the association between these lipids, as a function of other potential risk factors for cardiovascular disease, and sociodemographic factors such as age, educational level, and region of residence is not well studied in large samples in Europe. METHODS Data on French healthy volunteers, aged between 40 and 65 years for men (n = 5141) and 35 and 65 years for women (n = 7876) were obtained from the "Supplementation en Vitamines et Mineraux Antioxydants" (SU.VI.MAX) study, a primary prevention trial. Baseline blood samples were collected in 1994-1995 and analyzed for cholesterol, triglyceride, apolipoproteins (apo)-B and -A1. The results were analyzed separately for men and women as a function of age, educational level, and area of residence. RESULTS Overall, blood lipid levels for men and women did not differ significantly from those reported in other Western industrialized countries. Except for triglyceride in men, all blood lipids were statistically different among ages. In women, cholesterol, apo-A1, and apo-B showed a significant decrease with educational level. Statistical differences were found in both genders between blood lipids and lipoproteins among regions of residence. CONCLUSIONS Even if differences between region of residence were found in blood lipid levels, this cannot explain the North-East to South gradient in the prevalence of cardiovascular disease in France nor differences between France and other industrialized Western countries.