| Whole body insulin resistance appears to precede many of the metabolic abnormalities that are involved in the progression toward type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, hypertension, cardiovascular disease and some cancers. The overall objective of this project was to characterize modifiable correlates and sequelae that are associated with insulin sensitivity in humans.; In Study 1, we determined whether differences in insulin sensitivity persist between nonobese, nondiabetic Mexican American (MA) (n = 13; 27.0 ± 2.0 yrs; BMI = 23.0 ± 0.7) and Non-Hispanic White (NHW) (n = 13; 24.8 ± 1.5 yrs; BMI = 22.8 ± 0.6) males and females after accounting for effects of exercise, adiposity, dietary intake and skeletal muscle insulin signaling protein abundance. Significant differences in insulin sensitivity, estimated by the homeostatic model assessment of insulin resistance, between MA and NHW persisted (1.53 ± 0.22 vs. 0.87 ± 0.16, p < 0.05, respectively) after accounting for effects of acute and chronic exercise, and adiposity. Protein levels of IRβ, PI3K p85, Akt1, Akt2 and GLUT4 were not different between the two groups. Differences in HOMA-IR scores lost significance after accounting for percent intake of palmitic acid, palmitoleic acid and skeletal muscle protein abundance of IRβ. Our results suggest that differences in insulin sensitivity between nonobese, nondiabetic MA and NHW are not due to differences in level of cardiorespiratory fitness or adiposity, however dietary intake and key insulin signaling protein levels could contribute to these ethnic differences.; In Study 2, we determined whether the TNF-α system accounted for differences in insulin sensitivity between MA (n = 13; 27.0 ± 2.0 yrs; BMI = 23.0 ± 0.7) and NHW (n = 13; 24.8 ± 1.5 yrs; BMI = 22.8 ± 0.6) subjects. MA were less insulin sensitive compared to NHW, while circulating levels of TNF-α were higher (3.11 ± 0.38 vs. 2.10 ± 0.24 pg/ml, p < 0.05) and sTNFR2 (13)23.52 ± 84.73 vs. 1924.65 ± 127.36 pg/ml, p < 0.05) were significantly lower among MA subjects. TNFα, sTNFR1 and sTNFR2 were not related to estimates of insulin sensitivity or abdominal fat patterning when the two groups were analyzed in aggregate. These data indicate that although circulating levels of TNFα and sTNFR2 are different between nonobese, nondiabetic MA and NHW, they do not account for the observed differences in insulin sensitivity.; In Study 3, we determined the relationship between various estimates of insulin sensitivity, LDL size and oxidized LDL in a group of overweight, nondiabetic males (N = 34, BMI 25–35 kg/m2, 50–75y). Estimates of insulin sensitivity were inversely related to LDL size (r = .41, P < 0.05), although these relationships were largely mediated by VLDL triglyceride and HDL cholesterol concentrations. Estimates of insulin sensitivity were not related to plasma oxidized LDL concentrations. Furthermore, LDL size was not significantly associated with oxidized LDL. In this homogeneous group of overweight, nondiabetic men, estimates of insulin sensitivity are not independent markers of atherogenic small, dense and oxidized LDL. |
