Impact of race/ethnicity on insulin resistance and hypertriglyceridaemia.

OBJECTIVE: Insulin sensitivity affects plasma triglyceride concentration and both differ by race/ethnicity. The purpose of this study was to provide a comprehensive assessment of the variation in insulin sensitivity and its relationship to hypertriglyceridaemia between five race/ethnic groups. RESEARCH DESIGN AND METHODS: In this cross-sectional study, clinical data for 1025 healthy non-Hispanic White, Hispanic White, East Asian, South Asian and African American individuals were analysed. Insulin-mediated glucose disposal (a direct measure of peripheral insulin sensitivity) was measured using the modified insulin suppression test. Statistical analysis was performed using analysis of co-variance. RESULTS: Of the study participants, 63% were non-Hispanic White, 9% were Hispanic White, 11% were East Asian, 11% were South Asian and 6% were African American. Overall, non-Hispanic Whites and African Americans displayed greater insulin sensitivity than East Asians and South Asians. Triglyceride concentration was positively associated with insulin resistance in all groups, including African Americans. Nevertheless, for any given level of insulin sensitivity, African Americans had the lowest triglyceride concentrations. CONCLUSION: Insulin sensitivity, as assessed by a direct measure of insulin-mediated glucose disposal, and its relationship to triglyceride concentration vary across five race/ethnic groups. Understanding these relationships is crucial for accurate cardiovascular risk stratification and prevention.

Evaluation of fasting plasma insulin concentration as an estimate of insulin action in nondiabetic individuals: comparison with the homeostasis model assessment of insulin resistance (HOMA-IR).

Insulin-mediated glucose disposal varies severalfold in apparently healthy individuals, and approximately one-third of the most insulin resistant of these individuals is at increased risk to develop various adverse clinical syndromes. Since direct measurements of insulin sensitivity are not practical in a clinical setting, several surrogate estimates of insulin action have been proposed, including fasting plasma insulin (FPI) concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) calculated by a formula employing fasting plasma glucose (FPG) and FPI concentrations. The objective of this study was to compare FPI as an estimate of insulin-mediated glucose disposal with values generated by HOMA-IR in 758 apparently healthy nondiabetic individuals. Measurements were made of FPG, FPI, triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) concentrations, and insulin-mediated glucose uptake was quantified by determining steady-state plasma glucose (SSPG) concentration during the insulin suppression test. FPI and HOMA-IR were highly correlated (r = 0.98, P < 0.001). The SSPG concentration also correlated to a similar degree (P < 0.001) with FPI (r = 0.60) and HOMA-IR (r = 0.64). Furthermore, the relationship between FPI and TG (r = 0.35) and HDL-C (r = -0.40) was comparable to that between HOMA-IR and TG (r = 0.39) and HDL-C (r = -0.41). In conclusion, FPI and HOMA-IR are highly correlated in nondiabetic individuals, with each estimate accounting for ~40% of the variability (variance) in a direct measure of insulin-mediated glucose disposal. Calculation of HOMA-IR does not provide a better surrogate estimate of insulin action, or of its associated dyslipidemia, than measurement of FPI.

Utility of homeostasis model assessment of beta-cell function in predicting diabetes in 12,924 healthy Koreans.

OBJECTIVE: It is unclear how well homeostasis model assessment of beta-cell function (HOMA-beta) predicts diabetes development beyond its components, especially glucose. RESEARCH DESIGN AND METHODS: We identified 12,924 nondiabetic Koreans who had fasting plasma glucose and insulin concentrations measured in 2003 and again in 2008. To minimize the impact of differences in baseline glucose concentration, individuals were divided into three glucose categories: normal fasting glucose (NFG, glucose <5.6 mmol/l), impaired fasting glucose (IFG-100) (5.6-6.0 mmol/l), and IFG-110 (6.1-6.9 mmol/l). RESULTS: Diabetes developed in 29% of individuals in the IFG-110 group, compared with 5% in IFG-100 and 0.3% in NFG groups. Within each glucose category, those who progressed to diabetes had higher baseline glucose concentrations (P < or = 0.04). Baseline HOMA-beta, however, was not lower but higher in individuals who developed diabetes in the NFG group (P = 0.009) and similar in the IFG-100 and IFG-110 groups. CONCLUSIONS: These data question the utility of using HOMA-beta to predict the development of diabetes.

Compensatory hyperinsulinemia and the development of an atherogenic lipoprotein profile: the price paid to maintain glucose homeostasis in insulin-resistant individuals.

The ability of insulin to stimulate glucose disposal varies sixfold to eightfold among apparently healthy individuals. The only way that insulin-resistant persons can prevent the development of type 2 diabetes is by secreting the increased amount of insulin that is necessary to compensate for the resistance to insulin action. The greater the magnitude of muscle and adipose tissue insulin resistance, the more insulin must be secreted to maintain normal or near-normal glucose tolerance. Although compensatory hyperinsulinemia may prevent the development of fasting hyperglycemia in insulin-resistant individuals, the price paid is the untoward physiologic effects of increased circulating insulin concentrations on tissues that retain normal insulin sensitivity. This article focused on the interplay between insulin resistance at the level of the muscle and adipose tissue and normal hepatic insulin sensitivity; this leads to the atherogenic lipoprotein profile that is characteristic of insulin-resistant individuals. It would be inappropriate to minimize the importance of differential insulin sensitivity in the genesis of the changes in lipoprotein metabolism that increase CVD risk in insulin-resistant persons. It would be equally remiss not to emphasize that differential tissue insulin resistance also is necessary to explain why insulin-resistant/hyperinsulinemic individuals are more likely to develop the clinical syndromes (with the exception of type 2 diabetes mellitus) that are listed in Box 1.