Study of tumor necrosis factor-alpha, leptin, plasminogen activator inhibitor-1 and oxidative stress in obese type 2 diabetic patients: Relation to insulin resistance

ABSTRACT

Great evidence indicates that some factors secreted by adipocytes are directly involved in the pathogenesis of obesity diabetes syndrome. This work was designed to study the role of tumor necrosis factor-alpha [TNF-alpha], leptin, plasminogen activator inhibitor-1 [PAI-1] and oxidative stress in relation to insulin resistance in obese type 2 diabetic patients. The study included 60 premenopausal women, classified into 4 groups; I] included 15 obese type 2 diabetics II] included 15 lean type 2 diabetics III] included 15 obese non diabetics and IV] included 15 lean non diabetics. All subjects were subjected to complete history taking, thorough clinical examination, anthropometric measurements and laboratory investigations including fasting and 2-hour post load glucose levels, fasting and 2-hour post load insulin levels, lipid profile, plasma TNF-alpha levels, leptin levels, PAI-1 levels and measurement of malondialdehyde [MDA] levels. The present study showed a significant positive correlation between leptin and body mass index [BMI], waist circumference, fasting insulin level and homeostasis model assessment insulin resistance index [HOMA IR], cholesterol and TNF-alpha. The statistical significance of association between leptin in one hand and waist circumference, HOMA, and cholesterol in the other hand was abolished when data were adjusted for BMI. The statistical significance between leptin and fasting insulin and TNF-alpha persisted after adjustment of data for BMI, indicating an independent association between leptin and both fasting insulin and TNF-alpha. There was an independent association between TNF-alpha and fasting glucose, 2-hour post load glucose, leptin and PAI-1. There was independent association between PAI-1 and fasting insulin, 2-hour post load insulin, triglycerides, high density lipoprotein-cholesterol [HDL-C] and TNF-alpha. MDA level was significantly higher in diabetic groups in comparison to the non-diabetic groups. However, there was no correlation between MDA and other parameters. We conclude that leptin, TNF-alpha, PAI-1 and increased oxidative stress may play a role in insulin resistance in obese type 2 diabetic patients