Tumour necrosis factor-alpha plasma level in patients with type 1 diabetesmellitus and its association with glycaemic control and cardiovascular risk factors

Objectives. Diabetic patients reveal a significant increase in their cardio vascular risk. Beside glycaemic control and management of established risk factors, determination of cytokines, like serum levels of tumour necrosis f actor-alpha (TNF-alpha), might offer a tool to determine patients at high r isk. The cytokine TNF-alpha reveals a complex relationship with diabetes. I t is involved in beta-cell damage leading to type 1 diabetes, causes insuli n resistance associated with obesity and is of influence in the formation o f atherosclerotic vascular lesions. We were interested in the possible asso ciation of this cytokine with metabolic control and cardiovascular risk fac tors in patients with type 1 diabetes. Design and Subjects. TNF-alpha plasma levels were determined in 44 outdoor patients (15 women, 29 men) with type 1 diabetes mellitus (mean duration 11 .2 +/- 8.7 years) and in 24 healthy controls by use of a solid phase enzyme amplified sensitivity immunoassay (TNF-alpha elisa, Biosource Fleurus, Bel gium). None of our study participants suffered from inflammatory or other c oncurrent diseases. Relationships between variables were evaluated by non-p arametric Spearman correlation coefficients. Results. TNF-alpha plasma levels were significantly higher in diabetic pati ents (19.3 +/- 7.5 pg mL(-1)) than in non-diabetic subjects (11.1 +/- 5.8 p g mL(-1); P < 0.023), and revealed a significant positive correlation with glycated haemoglobin (HbA(1c)) (r = 0.43; P < 0.004) and fructosamine (r = 0.31; P < 0.049) values, and a negative correlation with HDL cholesterol (r = -0.36; P < 0.018) and apoAI-levels (r = -0.37; P < 0.015). These relatio nships could be observed in patients with a duration of diabetes for more t han 5 years, as well as in patients with a shorter duration of diabetes. In the male group, TNF-alpha plasma levels revealed a significant positive correlation with plasma levels of thiobarbituric acid reacting substances ( r = 0.61; P < 0.001). Plasma levels of thiobarbituric acid reacting substan ces showed a positive correlation with the duration of diabetes (r = 0.58; P < 0.008), as well as with the serum levels of the vascular adhesion molec ules intercellular adhesion molecule (ICAM) (r = 0.34; P < 0.051) and vascu lar cell adhesion molecule (VCAM) (r = 0.30; P < 0.052). Conclusions. Our data indicate that TNF-alpha plasma levels are increased i n type 1 diabetes mellitus and reveal a significant association with metabo lic long-term control parameters, HbA(1c) and fructosamine for glycaemic co ntrol, and HDL cholesterol for triglyceride metabolism, as well with lipid peroxidation.