Postprandial dyslipidemia in obesity & insulin resistance and type 2 diabetes

Background: Obesity and insulin resistance, increasingly prevalent in adolescents, commonly associates with postprandial dyslipidemia, an independent predictor of cardiovascular disease risk. Postprandially gut peptides, glucagon-like peptide 1 (GLP-1) and GLP-2, modulate intestinal dietary fat absorption and triglyceride-rich lipoprotein (TRL) output. Bile acids are also postprandial factors implicated in lowering lipemia. We hypothesize that the postprandial response of GLP-1, GLP-2, and bile acids to a high-fat meal is impaired in obese, insulin resistant adolescents and associates with postprandial dyslipidemia.Methods: Normal weight (n=15), obese insulin sensitive (n=20), and obese insulin resistant (n=10) adolescents underwent an oral fat tolerance test (83% kcal from fat) with blood collected at 0, 1, 2, 4, and 6 hours. The lipoprotein phenotype was obtained by nuclear magnetic resonance spectroscopy, GLP-1 and GLP-2 were measured by ELISA and the bile acid profile was quantified by mass spectrometry. Continuous variables, including area under the curve (AUC) and incremental AUC (iAUC), were compared by one-way analysis of variance (ANOVA) or Kruskal-Wallis. Postprandial differences were also compared by two-way mixed ANOVA.Results: Obese, insulin resistant adolescents exhibited dyslipidemia, particularly reduced high-density lipoprotein particle size and exaggerated postprandial intestinally-derived large TRLs. Postprandial plasma levels of GLP-1 and GLP-2 were blunted in obese, insulin resistant subjects and inversely correlated with postprandial dyslipidemia. However, fasting GLP-1 and GLP-2 directly correlated with postprandial dyslipidemia, suggesting a compensatory increase in fasting secretion. Postprandial, but not fasting, total bile acids were diminished in obese adolescents and inversely correlated with insulin resistance and postprandial dyslipidemia. Specifically, postprandial lithocholic acid was reduced, a potent stimulator of GLP-1 secretion.Conclusion: Postprandial GLP-1, GLP-2, and bile acids were blunted in response to a high-fat meal in obese, insulin resistant adolescents. However, it remains unknown if these postprandial metabolic changes are a cause or consequence of impaired glucose and lipid metabolism in an obese state.