We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.

BackgroundLow total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably.ObjectivesWe aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components.Data sourcesTwo previously published meta-analyses including an updated systematic search in PubMed and EMBASE.Study Eligibility CriteriaCross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men.MethodsWe conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied.ResultsMen with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension.ConclusionsAssociations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.

Elevated WBC count, even within the normal range, is associated with both macro- and microvascular complications in type 2 diabetes. Chronic inflammation, as indicated by a higher WBC count, may play a linkage role in the development of macro- and microvascular complications in diabetes.

OBJECTIVE -Type 2 diabetes is the leading cause of end-stage renal disease worldwide. Aside from hyperglycemia and hypertension, other metabolic factors may determine renal outcome. We examined risk associations of metabolic syndrome with new onset of chronic kidney disease (CKD) in 5,829 Chinese patients with type 2 diabetes enrolled between 1995 and 2005.RESEARCH DESIGN AND METHODS -Metabolic syndrome was defined by National Cholesterol Education Program Adult Treatment Panel III criteria with the Asian definition of obesity. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease formula modified for the Chinese population. New onset of CKD was defined as eGFR Ͻ60 ml/min per 1.73 m 2 at the time of censor. Subjects with CKD at baseline were excluded from the analysis. RESULTS-After a median follow-up duration of 4.6 years (interquartile range: 1.9 -7.3 years), 741 patients developed CKD. The multivariable-adjusted hazard ratio (HR) of CKD was 1.31 (95% CI 1.12-1.54, P ϭ 0.001) for subjects with metabolic syndrome compared with those without metabolic syndrome. Relative to subjects with no other components of metabolic syndrome except for diabetes, those with two, three, four, and five metabolic syndrome components had HRs of an increased risk of CKD of 1.15 (0.83-1.60, P ϭ 0.407) 1.32 (0.94 -1.86, P ϭ 0.112), 1.64 (1.17-2.32, P ϭ 0.004), and 2.34 (1.54 -3.54, P Ͻ 0.001), respectively. The metabolic syndrome traits of central obesity, hypertriglyceridemia, hypertension, and low BMI were independent predictors for CKD.CONCLUSIONS -The presence of metabolic syndrome independently predicts the development of CKD in subjects with type 2 diabetes.

OBJECTIVEInsulin has mitogenic effects, although hyperglycemia may be a risk factor for cancer in type 2 diabetes. It remains uncertain whether use of insulin increases cancer risk because of its effect on cell growth and proliferation or decreases cancer risk because of its glucose-lowering effect.RESEARCH DESIGN AND METHODSA 1:2-matched new insulin user cohort on age (±3 years), smoking status, and likelihood of initiating insulin therapy (±0.05) was selected from a cohort of 4,623 Chinese patients with type 2 diabetes, free of cancer, and naive to insulin at enrollment. Stratified Cox regression analysis on the matched pairs was used to obtain hazard ratios (HRs) of insulin therapy and A1C for cancer risk. A structured adjustment scheme was used to adjust for covariates.RESULTSOf 973 new insulin users, 971 had matched nonusers (n = 1935). The cancer incidence in insulin nonusers was much higher than that in insulin users (49.2 vs. 10.2, per 1,000 person-years, P < 0.0001). After further adjustment for all other covariates with a P value less than 0.3 and nonlinear associations with cancer, A1C was associated with an increased cancer risk (HR per percentage 1.26, 95% CI 1.03–1.55), whereas use of insulin was associated with a decreased cancer risk (HR of insulin users vs. nonusers: 0.17, 0.09–0.32). Consistent results were found in analyses including all 973 insulin users and 3,650 nonusers.CONCLUSIONSIn Chinese patients with type 2 diabetes, hyperglycemia predicts cancer, whereas insulin usage was associated with a reduced cancer risk.

Objective To investigate the effects of compliance and periodic telephone counselling by a pharmacist on mortality in patients receiving polypharmacy. Design Two year randomised controlled trial. Setting Hospital medical clinic. Participants 502 of 1011 patients receiving five or more drugs for chronic disease found to be non-compliant at the screening visit were invited for randomisation to either the telephone counselling group (n = 219) or control group (n = 223) at enrolment 12-16 weeks later. Main outcome measures Primary outcome was all cause mortality in randomised patients. Associations between compliance and mortality in the entire cohort of 1011 patients were also examined. Patients were defined as compliant with a drug if they took 80-120% of the prescribed daily dose. To calculate a compliance score for the whole treatment regimen, the number of drugs that the patient was fully compliant with was divided by the total number of prescribed drugs and expressed as a percentage. Only patients who complied with all recommended drugs were considered compliant (100% score). Results 60 of the 502 eligible patients defaulted and only 442 patients were randomised. After two years, 31 (52%) of the defaulters had died, 38 (17%) of the control group had died, and 25 (11%) of the intervention group had died. After adjustment for confounders, telephone counselling was associated with a 41% reduction in the risk of death (relative risk 0.59, 95% confidence interval 0.35 to 0.97; P = 0.039). The number needed to treat to prevent one death at two years was 16. Other predictors included old age, living alone, rate of admission to hospital, compliance score, number of drugs for chronic disease, and non-treatment with lipid lowering drugs at screening visit. In the cohort of 1011 patients, the adjusted relative risk for death was 1.61 (1.05 to 2.48; P = 0.029) and 2.87 (1.80 to 2.57; P < 0.001) in patients with compliance scores of 34-66% and 0-33%, respectively, compared with those who had a compliance score of 67% or more. Conclusion In patients receiving polypharmacy, poor compliance was associated with increased mortality. Periodic telephone counselling by a pharmacist improved compliance and reduced mortality. Trial registration International Standard Randomised Controlled Trial Number Register: SRCTN48076318.

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Maternal gestational diabetes mellitus increases the offspring's cardiometabolic risk, and in utero hyperinsulinemia is an independent predictor of abnormal glucose tolerance in childhood.