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Aims/hypothesis: South Asians are up to four times more likely to develop type 2 diabetes than white Europeans. It is postulated that the higher prevalence results from greater genetic risk. To evaluate this hypothesis, we: (1) systematically reviewed the literature for single nucleotide polymorphisms (SNPs) predisposing to type 2 diabetes in South Asians; (2) compared risk estimates, risk alleles and risk allele frequencies of predisposing SNPs between South Asians and white Europeans; and (3) tested the association of novel SNPs discovered from South Asians in white Europeans., Methods: MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and the Cochrane registry were searched for studies of genetic variants associated with type 2 diabetes in South Asians. Meta-analysis estimates for common and novel bi-allelic SNPs in South Asians were compared with white Europeans from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium. The population burden from predisposing SNPs was assessed using a genotype score., Results: Twenty-four SNPs from 21 loci were associated with type 2 diabetes in South Asians after meta-analysis. The majority of SNPs increase odds of the disorder by 15-35% per risk allele. No substantial differences appear to exist in risk estimates between South Asians and white Europeans from SNPs common to both groups, and the population burden also does not differ. Eight of the 24 are novel SNPs discovered from South Asian genome-wide association studies, some of which show nominal associations with type 2 diabetes in white Europeans., Conclusions/interpretation: Based on current literature there is no strong evidence to indicate that South Asians possess a greater genetic risk of type 2 diabetes than white Europeans.

Aims: In an international prospective cohort study we assessed the relationship between glucose levels and incident cardiovascular events and death., Methods and Results: 18,990 men and women were screened for entry into the DREAM clinical trial from 21 different countries. All had clinical and biochemical information collected at baseline, including an oral glucose tolerance test (OGTT), and were prospectively followed over a median (IQR) of 3.5 (3.0-4.0) years for incident cardiovascular (CV) events including coronary artery disease (CAD), stroke, congestive heart failure (CHF) requiring hospitalization, and death. After OGTT screening, 8000 subjects were classified as normoglycaemic, 8427 had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and 2563 subjects had newly diagnosed type 2 diabetes mellitus (DM). There were incident events in 491 individuals: 282 CAD, 54 strokes, 19 CHF, and 164 died. The annualized CV or death event rate was 0.79/100 person-years in the overall cohort, 0.51/100 person-years in normoglycaemics, 0.92/100 person-years among subjects with IFG and/or IGT at baseline, and 1.27/100 person-years among those with DM (p for trend <0.0001). Among all subjects, a 1 mmol/l increase in fasting plasma glucose (FPG) or a 2.52 mmol/l increase in the 2-h post-OGTT glucose was associated with a hazard ratio increase in the risk of CV events or death of 1.17 (95% CI 1.13-1.22)., Conclusions: In this large multiethnic cohort, the risk of CV events or death increased progressively among individuals who were normoglycaemic, IFG or IGT, and newly diagnosed diabetics. A 1 mmol/l increase in FPG was associated with a 17% increase in the risk of future CV events or death. Therapeutic or behavioural interventions designed to either prevent glucose levels from rising, or lower glucose among individuals with dysglycaemia should be evaluated.

Objective: Identifying individuals who have elevated glucose concentrations is important for clinicians so that preventive strategies can be invoked, and it is useful for researchers who study associations between elevated glucose and adverse health outcomes. These methods should be applicable worldwide across different ethnic groups. Therefore, the objective of our analysis was to determine whether using the fasting glucose and HbA(1c) together could improve the classification of individuals with impaired glucose tolerance and diabetes in a multiethnic cohort randomly assembled in Canada., Research Design and Methods: We determined the optimum diagnostic criteria to identify people with abnormal glucose tolerance using fasting plasma glucose, 2-h post-glucose load plasma glucose, and HbA(1c) in 936 Canadians of South Asian, Chinese, and European descent., Results: The sensitivity of the American Diabetes Association (ADA) criteria to diagnose diabetes compared with the World Health Organization definitions was poor at 48.3% (95% confidence interval [CI] 35.7-61.0). Using a receiver operator characteristic curve, the optimum combined cut-point using fasting glucose and HbA(1c) to diagnose diabetes was a fasting glucose > or =5.7 mmol/l and an HbA(1c) > or =5.9%. These cut-points were associated with a sensitivity and specificity of 71.7% (60.3-83.1) and 95.0% (93.5-96.4), respectively, a positive likelihood ratio (LR) of 14.3 (9.6-19.0), and a negative LR of 0.3 (0.2-0.4). Significant ethnic variation in the sensitivity and specificity of this approach was observed: 47.4% (24.9-69.8) and 97.6% (95.9-99.4) among Europeans, 78.6% (57.1-100) and 95.9% (93.6-98.2) among Chinese, and 85.2% (71.8-98.6) and 91.3% (88.1-94.6) among South Asians, respectively. Participants with impaired glucose tolerance could not be identified reliably using the fasting glucose or HbA(1c) alone or in combination., Conclusions: The sensitivity of the ADA criteria to diagnose diabetes is low, and there is substantial variation between ethnic groups. Fasting glucose and HbA(1c) may be used together to improve the identification of individuals who have diabetes, allowing clinicians to streamline the use of the oral glucose tolerance test.

Objective: Raised glucose levels extending from normal into the diabetic range (dysglycemia) are an emerging risk factor for clinical cardiovascular events. The relationship between dysglycemia and atherosclerosis (AS) in the general population and in different ethnic groups remains controversial., Research Design and Methods: Glucose tolerance, HbA1c, other metabolic risk factors for AS, and carotid mean maximal intimal media thickness were assessed in a random sample of 979 Canadians of South Asian, Chinese, and European descent., Results: The age and sex-adjusted intimal medial thickness increased 0.026 mm for every 0.9% increase in HbA1c in all participants (P < 0.0001) and in those of South Asian (P = 0.018), Chinese (P = 0.002), and European (P < 0.0001) descent. This progressive curvilinear relationship was most apparent at HbA1c levels >5.7%. The HbA1c-AS relationship persisted after adjustment for ethnicity, age, sex, diabetes status, abdominal obesity, insulin resistance, insulin secretion, fasting free fatty acids, blood pressure, and/or dyslipidemia (P < 0.004). Both diabetes (P = 0.002) and HbA1c (P < 0.0001) were determinants of the intimal medial thickness when included in separate statistical models. When included together in a single model, HbA1c (P < 0.0001) but not diabetes (P = 0.6) was a significant determinant., Conclusions: The degree of AS is related to the level of HbA1c irrespective of diabetes status and independent of abdominal obesity and other markers of the metabolic syndrome. This progressive relationship between HbA1c and AS was observed within different ethnic groups.

The Study of Health Assessment and Risk in Ethnic groups (SHARE) is a study to determine the risk factors for atherosclerosis among three ethnic populations in Canada. Three hundred and thirty South Asian Canadian, 320 Chinese Canadian and 320 European Canadian men and women between 35 and 75 years of age are being randomly sampled from communities in Hamilton and Toronto, Ontario and Edmonton, Alberta for assessment of conventional (i.e., smoking, dyslipidemia, diabetes and hypertension) and emerging (i.e., candidate genes for atherosclerosis, homocysteine, fibrinolytic parameters, neurohormones, glucose intolerance, markers of infection, socioeconomic status, psychosocial status and diet) cardiovascular disease risk factors. Subclinical atherosclerosis is measured by quantitative B-mode ultrasonography of the carotid arteries, and other objective measures of vascular disease are a 12-lead electrocardiogram, a two-dimensional echocardiogram, ankle to arm blood pressure ratio and urine microalbumin concentration. The relationship between the conventional and emerging risk factors, and atherosclerosis, vascular disease and markers of end-organ damage will be evaluated between and within ethnic groups.