Exercise training has greater effects on insulin sensitivity in daughters of patients with type 2 diabetes than in women with no family history of diabetes

Aims/hypothesis. Sedentary offspring of patients with type 2 diabetes are often more insulin-resistant than persons with no family history of diabetes, but when active or fit offspring of type 2 diabetic patients are compared with non-diabetic persons, differences in insulin resistance are less evident. This study aimed to determine the effects of an exercise training intervention on insulin sensitivity in both groups. Methods. Women offspring (n=34) of type 2 diabetic patients (offspring age 35.6+/-7.0 years, BMI 28.1+/-5.1 kg/m(2)) and 36 matched female controls (age 33.6+/-6.1 years, BMI 27.3+/-4.7 kg/m(2)) participated. Body composition, fitness and metabolic measurements were made at baseline and after a controlled 7 week exercise intervention. Results. At baseline, insulin sensitivity index (ISI) was 22% lower in offspring than controls (p < 0.05), despite similar body fat and maximal oxygen uptake ((V)over dotO(2max)) values in the two groups. ISI increased by 23% (p < 0.05) in offspring following the exercise intervention, compared with 7% (NS) in the controls. Increases in ((V)over dotO(2max))were similar in both groups (controls 12%, offspring 15%, p < 0.05 for both). Plasma leptin concentrations decreased significantly in the offspring (-24%, p < 0.01) but not in controls (0%, NS). Change in ISI correlated significantly with baseline ISI (r=-0.47, p < 0.0005) and change in leptin (r=-0.43, p < 0.0005). The latter relationship was not attenuated by adjustment for changes in body fat. Conclusions/interpretation. Offspring, but not controls, significantly increased ISI in response to an exercise intervention, indicating that insulin sensitivity is more highly modulated by physical activity in daughters of patients with type 2 diabetes than in women with no family history of the disease

Genome-wide significant association with seven novel multiple sclerosis risk loci

Objective A recent large-scale study in multiple sclerosis (MS) using the ImmunoChip platform reported on 11 loci that showed suggestive genetic association with MS. Additional data in sufficiently sized and independent data sets are needed to assess whether these loci represent genuine MS risk factors. Methods The lead SNPs of all 11 loci were genotyped in 10 796 MS cases and 10 793 controls from Germany, Spain, France, the Netherlands, Austria and Russia, that were independent from the previously reported cohorts. Association analyses were performed using logistic regression based on an additive model. Summary effect size estimates were calculated using fixed-effect meta-analysis. Results Seven of the 11 tested SNPs showed significant association with MS susceptibility in the 21 589 individuals analysed here. Meta-analysis across our and previously published MS case-control data (total sample size n=101 683) revealed novel genome-wide significant association with MS susceptibility (p<5x10(-8)) for all seven variants. This included SNPs in or near LOC100506457 (rs1534422, p=4.03x10(-12)), CD28 (rs6435203, p=1.35x10(-9)), LPP (rs4686953, p=3.35x10(-8)), ETS1 (rs3809006, p=7.74x10(-9)), DLEU1 (rs806349, p=8.14x10(-12)), LPIN3 (rs6072343, p=7.16x10(-12)) and IFNGR2 (rs9808753, p=4.40x10(-10)). Cis expression quantitative locus effects were observed in silico for rs6435203 on CD28 and for rs9808753 on several immunologically relevant genes in the IFNGR2 locus. Conclusions This study adds seven loci to the list of genuine MS genetic risk factors and further extends the list of established loci shared across autoimmune diseases