Assiamira Ferrara

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.

Recent data show that gestational diabetes mellitus (GDM) prevalence has increased by ∼10–100% in several race/ethnicity groups during the past 20 years. A true increase in the prevalence of GDM, aside from its adverse consequences for infants in the newborn period, might also reflect or contribute to the current patterns of increasing diabetes and obesity, especially in the offspring. Therefore, the public health aspects of increasing GDM need more attention. The frequency of GDM usually reflects the frequency of type 2 diabetes in the underlying population (1,2). Established risk factors for GDM are advanced maternal age, obesity, and family history of diabetes (3). Unquestionably, there are ethnic differences in the prevalence of GDM (4–15). In the U.S., Native Americans, Asians, Hispanics, and African-American women are at higher risk for GDM than non-Hispanic white women (4–6,8–11,13–15). In Australia, GDM prevalence was found to be higher in women whose country of birth was China or India than in women whose country of birth was in Europe or Northern Africa (7). GDM prevalence was also higher in Aboriginal women than in non-Aboriginal women (12). In Europe, GDM has been found to be more common among Asian women than among European women (16). The proportion of pregnancies complicated by GDM in Asian countries has been reported to be lower than the proportion observed in Asian women living in other continents (17). In India, GDM has been found to be more common in women living in urban areas than in women living in rural areas (18). The trend toward older maternal age (19), the epidemic of obesity (20) and diabetes (21), and the decrease in physical activity (22) and the adoption of modern lifestyles in developing countries (23) may all …

BACKGROUND: Glycemic control is associated with microvascular events, but its effect on the risk of heart failure is not well understood. We examined the association between hemoglobin (Hb) A(Ic) and the risk of heart failure hospitalization and/or death in a population-based sample of adult patients with diabetes and assessed whether this association differed by patient sex, heart failure pathogenesis, and hypertension status. METHODS AND RESULTS: A cohort design was used with baseline between January 1, 1995, and June 30, 1996, and follow-up through December 31, 1997 (median 2.2 years). Participants were 25 958 men and 22 900 women with (predominantly type 2) diabetes, >/=19 years old, with no known history of heart failure. There were a total of 935 events (516 among men; 419 among women). After adjustment for age, sex, race/ethnicity, education level, cigarette smoking, alcohol consumption, hypertension, obesity, use of beta-blockers and ACE inhibitors, type and duration of diabetes, and incidence of interim myocardial infarction, each 1% increase in Hb A(Ic) was associated with an 8% increased risk of heart failure (95% CI 5% to 12%). An Hb A(Ic) >/=10, relative to Hb A(Ic) <7, was associated with 1.56-fold (95% CI 1.26 to 1.93) greater risk of heart failure. Although the association was stronger in men than in women, no differences existed by heart failure pathogenesis or hypertension status. CONCLUSIONS: These results confirm previous evidence that poor glycemic control may be associated with an increased risk of heart failure among adult patients with diabetes.

OBJECTIVE: Some preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study examining the association between pioglitazone therapy and the risk of bladder cancer in patients with diabetes. RESEARCH DESIGN AND METHODS: This study includes 193,099 patients in the Kaiser Permanente Northern California diabetes registry who were ≥40 years of age between 1997 and 2002. Those with prior bladder cancer were excluded. Ever use of each diabetes medication (defined as two or more prescriptions within 6 months) was treated as a time-dependent variable. Cox regression-generated hazard ratios (HRs) compared pioglitazone use with nonpioglitazone use adjusted for age, sex, race/ethnicity, diabetes medications, A1C, heart failure, household income, renal function, other bladder conditions, and smoking. RESULTS: The group treated with pioglitazone comprised 30,173 patients. There were 90 cases of bladder cancer among pioglitazone users and 791 cases of bladder cancer among nonpioglitazone users. Overall, ever use of pioglitazone was not associated with risk of bladder cancer (HR 1.2 [95% CI 0.9-1.5]), with similar results in men and women (test for interaction P = 0.8). However, in the a priori category of >24 months of therapy, there was an increased risk (1.4 [1.03-2.0]). Ninety-five percent of cancers diagnosed among pioglitazone users were detected at early stage. CONCLUSIONS: In this cohort of patients with diabetes, short-term use of pioglitazone was not associated with an increased incidence of bladder cancer, but use for more than 2 years was weakly associated with increased risk.