Heterogeneity in the prevalence of risk factors for cardiovascular disease and type 2 diabetes mellitus in obese individuals - Effect of differences in insulin sensitivity

Background: The possibility that substantial heterogeneity in metabolic abnormalities exists in moderately obese individuals has not been emphasized in studies of the effect of obesity on morbidity and mortality. We tested the hypothesis that risk factors for type 2 diabetes mellitus and cardiovascular disease vary dramatically in moderately obese individuals as a function of differences in a specific measure of insulin sensitivity. Methods: Participants included 211 apparently healthy, obese (body mass index [calculated as weight in kilograms divided by height in meters squared], 30.0-34.9) volunteers for weight loss studies. Main outcome measures included insulin-mediated glucose uptake as quantified by the insulin suppression test and metabolic variables known to increase the risk for type 2 diabetes and cardiovascular disease. Results: Insulin sensitivity varied 6-fold. When compared with the most insulin-sensitive third, the most insulin-resistant third of the population had significantly higher (P<.001) systolic and diastolic blood pressure (139 +/- 20 vs 123 +/- 18 mm Hg, and 83 +/- 3 vs 75 +/- 10 mm. Hg, respectively), higher fasting and 2-hour oral glucose load concentrations (103 +/- 11 vs 95 +/- 11 mg/dL [5.7 +/- 0.6 vs 5.3 +/- 0.6 mmol/L], and 139 +/- 30 vs 104 +/- 19 mg/dL [7.7 +/- 1.7 vs 5.8 +/- 1.1 mmol/L], respectively), higher plasma triglyceride concentrations (198 +/- 105 vs 114 +/- 51 mg/dL [2.2 +/- 1.2 vs 1.3 +/- 0.6 mmol/L]), lower plasma high-density lipoprotein cholesterol concentrations (41 +/- 9 vs 50 +/- 13 mg/dL [1.1 +/- 0.2 vs 1.3 +/- 0.3 mmol/L]), and more prevalent impaired glucose tolerance (47% vs 2%). Conclusions: The magnitude of risk factors for type 2 diabetes and cardiovascular disease varies markedly in moderately obese individuals as a function of differences in degree of insulin sensitivity. Because not all moderately obese individuals are at similar risk for developing type 2 diabetes and cardiovascular disease, intensive therapeutic interventions should be addressed to the insulin-resistant subset of this population.