Aims/hypothesis. Several case-control studies have examined the association between the Gly972Arg variant in the IRS-1 gene and Type 2 diabetes, but most had limited power and results could therefore be conflicting. Methods. We systematically reviewed the literature by means of a meta-analysis and investigated sources of heterogeneity in results of different studies.Results. The summary risk ratio, based on 3408 cases and 5419 control cases from 27 studies, was 1.25 (95% CI 1.05-1.48). The results, however, differed according to the type of study, method of verifying non-diabetic status of the control subjects, and age of the case subjects. Population-based studies reported lower odds ratios than hospital-based studies (OR 0.98, 95% CI 0.74-1.30 vs OR 1.43, 95% CI 1.17-1.74). Also, the diagnostic test to exclude diabetes amongst control subjects interacted with the association between the IRS-1 Gly972Arg variant and Type 2 diabetes (p=0.03). Finally, the odds ratio reduced with increasing age (p=0.03). Conclusion/interpretation. Overall, carriers of the 972Arg variant of the IRS-1 gene are at a 25% increased risk of having Type 2 diabetes compared with non-carriers. The odds ratios are generally higher in hospital-based studies, including relatively young, symptomatic, cases. [Diabetologia (2003) 46:990-995]
For slightly obese subjects a moderate intake of fish oil does not have the same favourable effects on markers for a low-grade inflammatory state as weight reduction.
Overweight persons are at risk for cardiovascular diseases, which may relate to a disturbed endothelial function and pro-inflammatory serum profiles. Indeed, weight loss lowers cardiovascular disease risk, but weight maintenance is difficult. Therefore, dietary supplements such as fish oil, which improve endothelial function, are useful. In this study, we evaluated effects of fish oil and moderate weight loss in the same population. For this, 11 normolipidemic healthy, moderately obese men (BMI 30-35 kg/m2) received in random order 1.1 g/d eicosapentanoic acid (EPA) + docosahexanoic acid (DHA) or oleic acid (control) for 6 wk. In the 3rd period, 8 of the 11 subjects consumed low-energy diets (2 MJ/d) for 4 wk followed by 4 wk weight stabilization. Their body weight was reduced by 9.4 +/- 2.0 kg (P < 0.05). On the final day of all 3 periods, a postprandial test was conducted. Weight loss lowered fasting and postprandial plasma triacylglycerol (TG) responses (P < 0.001), whereas fish oil reduced only postprandial TG (P = 0.006). Fish oil did not affect soluble intercellular adhesion molecule (s-ICAM), whereas weight loss reduced fasting (P = 0.009) and postprandial s-ICAM responses (P < 0.001). Fasting s-ICAM and TG correlated (r = 0.68; P = 0.029), as did changes in fasting s-ICAM and TG during weight loss (r = 0.80; P = 0.029) and fish oil treatment (r = 0.76; P = 0.009). Fasting (P = 0.027) and postprandial (P < 0.001) serum C-reactive protein were lowered by weight loss. The postprandial monocyte chemoattractant protein-1 response was lowered by fish oil and after weight loss (P < 0.001). This indicates that 1.1 g/d EPA+DHA supplied for 6 wk, in contrast to approximately 10 kg weight loss, does not improve markers of endothelial function and inflammation.
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