Insulin resistance, lipid and fatty acid concentrations in 867 healthy Europeans

Background Insulin resistance, dyslipidaemia and abnormal nonesterified fat ty acid (NEFA) metabolism are features of the 'metabolic syndrome', but the mechanisms of these relationships are uncertain. Materials and methods We studied associations between insulin resistance an d lipoprotein concentrations by retrospective analysis of euglycaemic hyper insulinaemic clamp data from 867 normoglycaemic subjects in 21 European cen tres. Data on NEFA concentrations were available in a subgroup of 541 subje cts from 9 clinical centres. These subjects' characteristics do not vary si gnificantly from those of the whole cohort. Results After adjustment for the effects of age, sex, obesity and intercent re variability, regression analysis showed relationships between triglyceri des and markers of insulin sensitivity. There were significant correlations between triglycerides and fasting plasma glucose (P < 0.0001), fasting pla sma insulin (P < 0.0001) and mean glucose infusion rate at steady state (M- value, P < 0.0001). Indices of insulin resistance were related to NEFA conc entrations. Fasting NEFA were negatively correlated with the M-value (P < 0 .0001). Non-esterified fatty acids at steady state were positively correlat ed with fasting markers of insulin resistance: fasting plasma glucose (P < 0.05), fasting plasma insulin (P < 0.005) and negatively correlated with th e M-value (P < 0.0005). There were relationships between fasting concentrat ions of plasma lipids and of NEFAs. Non-esterified fatty acids at steady st ate correlated with fasting triglycerides (P < 0.0001), but not with any of the other plasma lipoprotein concentrations. The associations of fasting t riglycerides with the M-value and with NEFAs at steady state were independe nt of each other. All these associations were independent of obesity and ge ographical location Conclusion The results in this large cohort of healthy European subjects su ggest that triglyceride concentrations depend upon both insulin's gluco-reg ulation (estimated by glucose uptake) and antilipolytic insulin action (mea sured by NEFA levels) during an euglycaemic clamp.