, MBBS, DPhil, FRCP(c); for the SHARE Investigators Background-Body mass index (BMI) is widely used to assess risk for cardiovascular disease and type 2 diabetes. Cut points for the classification of obesity (BMI Ͼ30 kg/m 2 ) have been developed and validated among people of European descent. It is unknown whether these cut points are appropriate for non-European populations. We assessed the metabolic risk associated with BMI among South Asians, Chinese, Aboriginals, and Europeans. Methods and Results-We randomly sampled 1078 subjects from 4 ethnic groups (289 South Asians, 281 Chinese, 207Aboriginals, and 301 Europeans) from 4 regions in Canada. Principal components factor analysis was used to derive underlying latent or "hidden" factors associated with 14 clinical and biochemical cardiometabolic markers. Ethnicspecific BMI cut points were derived for 3 cardiometabolic factors. Three primary latent factors emerged that accounted for 56% of the variation in markers of glucose metabolism, lipid metabolism, and blood pressure. For a given BMI, elevated levels of glucose-and lipid-related factors were more likely to be present in South Asians, Chinese, and Aboriginals compared with Europeans, and elevated levels of the blood pressure-related factor were more likely to be present among Chinese compared with Europeans. The cut point to define obesity, as defined by distribution of glucose and lipid factors, is lower by Ϸ6 kg/m 2 among non-European groups compared with Europeans. Conclusions-Revisions may be warranted for BMI cut points to define obesity among South Asians, Chinese, and Aboriginals. Using these revised cut points would greatly increase the estimated burden of obesity-related metabolic disorders among non-European populations.

The utility of the disposition index as a measure of β-cell compensatory capacity rests on the established hyperbolic relationship between its component insulin secretion and sensitivity measures as derived from the intravenous glucose tolerance test (IVGTT). If one is to derive an analogous measure of β-cell compensation from the oral glucose tolerance test (OGTT), it is thus necessary to first establish the existence of this hyperbolic relationship between OGTT-based measures of insulin secretion and insulin sensitivity. In this context, we tested five OGTT-based measures of secretion (insulinogenic index, Stumvoll first phase, Stumvoll second phase, ratio of total area-underthe-insulin-curve to area-under-the-glucose-curve (AUC ins/gluc ), and incremental AUC ins/gluc ) with two measures of sensitivity (Matsuda index and 1/Homeostasis Model of Assessment for insulin resistance (HOMA-IR)). Using a model of log(secretion measure) = constant + β × log(sensitivity measure), a hyperbolic relationship can be established if β is approximately equal to −1, with 95% confidence interval (CI) excluding 0. In 277 women with normal glucose tolerance (NGT), the pairing of total AUC ins/gluc and Matsuda index was the only combination that satisfied these criteria (β = −0.99, 95% CI (−1.66, −0.33)). This pairing also satisfied hyperbolic criteria in 53 women with impaired glucose tolerance (IGT) (β = −1.02, (−1.72, −0.32)). In a separate data set, this pairing yielded distinct hyperbolae for NGT (n = 245) (β = −0.99, (−1.67, −0.32)), IGT (n = 116) (β = −1.18, (−1.84, −0.53)), and diabetes (n = 43) (β = −1.37, (−2.46, −0.29)). Moreover, the product of AUC ins/gluc and Matsuda index progressively decreased from NGT (212) to IGT (193) to diabetes (104) (P < 0.001), consistent with declining β-cell function. In summary, a hyperbolic relationship can be demonstrated between OGTT-derived AUC ins/gluc and Matsuda index across a range of glucose tolerance. Based on these findings, the product of these two indices emerges as a potential OGTT-based measure of β-cell function.