The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of heritability. To test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole genome sequencing in 2,657 Europeans with and without diabetes, and exome sequencing in a total of 12,940 subjects from five ancestral groups. To increase statistical power, we expanded sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support a major role for lower-frequency variants in predisposition to type 2 diabetes.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS) including 26,488 cases and 83,964 controls of European, East Asian, South Asian, and Mexican and Mexican American ancestry. We observed significant excess in directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven novel T2D susceptibility loci. Furthermore, we observed considerable improvements in fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterisation of complex trait loci, and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

OBJECTIVE -The International Diabetes Mellitus Practice Study is a 5-year survey documenting changes in diabetes treatment practice in developing regions.RESEARCH DESIGN AND METHODS -Logistic regression analysis was used to identify factors for achieving A1C Ͻ7% in 11,799 patients (1,898 type 1 diabetic and 9,901 type 2 diabetic) recruited by 937 physicians from 17 countries in Eastern Europe (n ϭ 3,519), Asia (n ϭ 5,888), Latin America (n ϭ 2,116), and Africa (n ϭ 276).RESULTS -Twenty-two percent of type 1 diabetic and 36% of type 2 diabetic patients never had A1C measurements. In those with values for A1C, blood pressure, and LDL cholesterol, 7.5% of type 1 diabetic (n ϭ 696) and 3.6% of type 2 diabetic (n ϭ 3,896) patients attained all three recommended targets (blood pressure Ͻ130/80 mmHg, LDL cholesterol Ͻ100 mg/dl, and A1C Ͻ7%). Selfmonitoring of blood glucose was the only predictor for achieving the A1C goal in type 1 diabetes (odds ratios: Asia 2.24, Latin America 3.55, and Eastern Europe 2.42). In type 2 diabetes, short disease duration (Asia 0.97, Latin America 0.97, and Eastern Europe 0.82) and treatment with few oral glucose-lowering drugs (Asia 0.64, Latin America 0.76, and Eastern Europe 0.62) were predictors. Other region-specific factors included lack of microvascular complications and old age in Latin America and Asia; health insurance coverage and specialist care in Latin America; lack of obesity and self-adjustment of insulin dosages in Asia; and training by a diabetes educator, self-monitoring of blood glucose in patients who self-adjusted insulin, and lack of macrovascular complications in Eastern Europe.CONCLUSIONS -In developing countries, factors pertinent to patients, doctors, and health care systems all impact on glycemic control. Diabetes Care 32:227-233, 2009A lthough optimizing diabetes care reduces death and complication rates (1-3), multiple barriers hinder turning evidence into practice (4,5). Most diabetic patients reside in developing countries (6) where standardized data on quality of care is relatively scarce. The International Diabetes Management Practices Study (IDMPS) is an ongoing observational survey to collect, analyze, and disseminate data in a standardized manner. By documenting changes in practices over time in a broad range of health care settings, we aim to raise awareness and identify barriers to quality diabetes care. Other objectives include evaluation of clinical progress, levels of compliance, attainment of treatment targets, and rates of hospitalization and work absenteeism. This analysis of the first-year survey examines factors predictive of glycemic control.RESEARCH DESIGN AND METHODS -There are five waves in this 5-year study, each consisting of a 2-week cross-sectional and a 9-month longitudinal survey. A 3-month interval separates the end of the longitudinal survey and the start of the next wave. Study design and reporting format are in accordance with the recommended STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guideline...

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