Metabolism: clinical and experimental
-
The aim of this cross-sectional study was to assess the association of insulin resistance (IR) with inflammatory molecules C-reactive protein (CRP), interleukin 6 (IL-6), vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemotactic protein 1 (MCP-1) in urban South Indian subjects. The following groups were selected from the population-based Chennai Urban Rural Epidemiology Study: group 1 composed of 50 healthy subjects with normal glucose tolerance without IR; group 2 consisted of 50 normal glucose-tolerant subjects with IR as defined by homeostasis model assessment of IR (HOMA-IR); group 3 consisted of 50 subjects with impaired glucose tolerance (IGT); and groups 4 and 5 each comprised 50 newly diagnosed and known type 2 diabetic subjects, respectively. The inclusion criteria included nonsmokers; normal resting 12-lead electrocardiogram; and absence of angina, myocardial infarction, or history of any known vascular, infectious, or inflammatory diseases, and not on statins or aspirin. ⋯ Monocyte chemotactic protein 1 did not show any correlation with HOMA-IR. Multiple linear regression analysis revealed CRP to be significantly associated with HOMA-IR (beta = .229; P < .001) and this was unaltered by the addition of waist and IL-6 into the model (beta = .158; P = .028). In conclusion, this study shows that in Asian Indians, inflammatory markers (CRP, IL-6, and VCAM-1) increase with increasing degrees of glucose intolerance.
-
Because hyperglycemia is a major detrimental factor in the prognosis of acute cardiovascular conditions such as acute myocardial infarction (AMI) and stroke, and because an acute glucose challenge in healthy subjects has been shown to induce oxidative stress in mononuclear cells (MNCs), we have now investigated whether glucose induces inflammatory stress at the cellular and molecular level. Glucose ingestion (75 g in 300 mL water) in healthy human subjects resulted in an increase in intranuclear nuclear factor kappaB (NF-kappaB) binding, the reduction of inhibitor kappaB alpha (IkappaBalpha) protein, and an increase in the activity of inhibitor kappaB kinase (IKK) and the expression of IKKalpha and IKKbeta, the enzymes that phosphorylate IkappaBalpha, in MNCs. ⋯ We conclude that glucose intake induces an immediate increase in intranuclear NF-kappaB binding, a fall in IkappaBalpha, an increase in IKKalpha, IKKbeta, IKK activity, and messenger RNA expression of TNF-alpha in MNCs in healthy subjects. These data are consistent with profound acute pro-inflammatory changes in MNCs after glucose intake.
-
Limited data are available on the association of insulin resistance, adipokines, and in vivo lipid peroxidation. We investigated the relationships between insulin resistance, adipokines (leptin, adiponectin, and resistin), and oxidative stress in nondiabetic, hypercholesterolemic patients. Seventy-six nondiabetic patients with hypercholesterolemia participated in this cross-sectional study. ⋯ Stepwise multiple linear regression analysis showed that leptin was associated with the urinary 8-epi-PGF(2alpha) excretion after adjusting for age, sex, body mass index, blood lipids, and HOMA-IR (P = .002). In conclusion, our results show that more insulin-resistant state of nondiabetic, hypercholesterolemic patients is associated with decreased adiponectin and increased leptin and urinary 8-epi-PGF(2alpha) levels, although no relationship with resistin was observed. Furthermore, serum leptin independently contributed to urinary 8-epi-PGF(2alpha) excretion.
-
Patients with diabetes mellitus have an increased risk of coronary artery diseases such as myocardial infarction. Sulfonylureas are used in the treatment of diabetes mellitus and have been linked with adverse cardiovascular effects due to an apparent effect on myocardial ischemic preconditioning. ⋯ Although the hypotheses were stimulated by animal studies and experimental studies using intermediate end points, data on the possible clinical implications in humans remain sparse. However, recent data seem reassuring.
-
Studies on fetal programming of adult diseases have highlighted the importance of maternal nutrition during pregnancy. Folic acid and long-chain essential polyunsaturated fatty acids (LC-PUFAs) have independent effects on fetal growth. However, folic acid effects may also involve alteration of LC-PUFA metabolism. ⋯ Docosahexaenoic acid levels in FAS/MP adult offspring were also lower (P<.05) when compared with the MP group. Plasma corticosterone concentrations were higher (P<.05) in male adult offspring from the FAS/MP group compared with control as well as the MP adult offspring. Results suggest that maternal folic acid supplementation at MP intake decreased brain docosahexaenoic acid levels probably involving corticosterone increase.