The formulae for calculating the sample size required to study the interaction between a continuous exposure and a genetic factor on a continuous outcome variable in the face of measurement error will be of considerable utility in designing studies with appropriate power. These calculations suggest that smaller studies with repeated and more precise measurement of the exposure and outcome will be as powerful as studies even 20 times bigger, which necessarily employ less precise measures because of their size. Even though the cost of genotyping is falling, the magnitude of the effect of measurement error on the power to detect interaction on continuous traits suggests that investment in studies with better measurement may be a more appropriate strategy than attempting to deal with error by increasing sample sizes.

The Isle of Ely Diabetes Project is a prospective population-based study of the aetiology and pathogenesis of Type 2 diabetes mellitus. Between 1990 and 1992, 1156 subjects aged between 40 and 65 years underwent a standard 75 g oral glucose tolerance test (OGTT). A total of 1122 individuals who were not known to have diabetes completed the test and were classified according to WHO criteria; 51 subjects (4.5%) had previously undiagnosed diabetes and 188 (16.7%) had impaired glucose tolerance. The subjects with newly diagnosed glucose intolerance were significantly older, more obese, and shorter than those with normal glucose tolerance. Blood pressure, cholesterol, triglyceride, and LDL-cholesterol concentrations were elevated and HDL-cholesterol levels were lower among those with abnormal rather than normal glucose tolerance. In multiple regression analyses stratified by gender and including age, body mass index, and the waist-hip ratio as covariates, there were significant differences between those with normal and abnormal glucose intolerance in blood pressure, triglyceride, and HDL-cholesterol, but not total or LDL-cholesterol. In both male and female subjects, height had a significant independent negative association with the plasma glucose at 120 min after administration of oral glucose (standardized beta coefficient = -0.12, p < 0.01).

OBJECTIVE:To explore the association between measures of insulin resistance with objectively assessed physical activity. DESIGN: School-based, cross-sectional study. SUBJECTS: A randomly selected sample of 589 children (310 girls, 279 boys, mean (standard deviations, s.d.) age ¼ 9.7 (0.44) y, weight ¼ 33.6 (6.4) kg, height ¼ 1.39 (0.06) m) from Denmark. METHODS: Fasting blood samples were analysed for serum insulin and glucose. Physical activity was measured with the uniaxial Computer Science and Applications (CSA) model 7164 accelerometer, worn for at least 3 days (Z10 h day À1 ). Adiposity was assessed by the sum of four skinfolds. Multiple linear regression were performed to model insulin and glucose from average CSA output, adjusted for age, gender, puberty, ethnicity, birth weight, parental smoking, socioeconomic group, and CSA unit. In addition, we adjusted for skinfold thickness. RESULTS: Mean fasting serum glucose ranged from 4.1 to 6.5 mmol l À1 with a mean (s.d.) of 5.1 (0.37) mmol l À1 . Fasting insulin was negatively correlated with CSA output on levels of adjustment. Fasting glucose was not significantly associated with physical activity. However, in girls both indices of insulin resistance were significantly related to activity, whereas in boys none of the associations were significant. CONCLUSION: Physical activity is inversely associated with fasting insulin in the nondiabetic range of fasting glucose. The relationship was stronger for insulin than for glucose, indicating compensatory action by the b cells. Our data emphasise the importance of physical activity in children for the maintenance of metabolic control.

Aims/hypothesis We sought to determine the effect of an aerobic exercise intervention on clustered metabolic risk and related outcomes in healthy older adults in a singlecentre, explanatory randomised controlled trial. Methods Participants from the Hertfordshire Cohort Study (born 1931-1939) were randomly assigned to 36 supervised 1 h sessions on a cycle ergometer over 12 weeks or to a non-intervention control group. Randomisation and group allocation were conducted by the study co-ordinator, using a software programme. Those with prevalent diabetes, unstable ischaemic heart disease or poor mobility were excluded. All data were collected at our clinical research facility in Cambridge. Components of the metabolic syndrome were used to derive a standardised composite metabolic risk score (zMS) as the primary outcome. Trial status: closed to follow-up. Results We randomised 100 participants (50 to the intervention, 50 to the control group). Mean age was 71.4 (range 67.4-76.3) years. Overall, 96% of participants attended for follow-up measures. There were no serious adverse events. Using an intention-to-treat analysis, we saw a nonsignificant reduction in zMS in the exercise group compared with controls (0.07 [95% CI −0.03, 0.17], p=0.19). However, the exercise group had significantly decreased weight, waist circumference and intrahepatic lipid, with increased aerobic fitness and a 68% reduction in prevalence of abnormal glucose metabolism ], p=0.035) compared with controls. Results were similar in per-protocol analyses. Conclusions/interpretation Enrolment in a supervised aerobic exercise intervention led to weight loss, increased fitness and improvements in some but not all metabolic outcomes. In appropriately screened older individuals, such interventions appear to be safe.