Objectives: Diabetic patients reveal a significant increase in their cardiovascular risk. Beside glycaemic control and management of established risk factors, determination of cytokines, like serum levels of tumour necrosis factor-alpha (TNF-alpha), might offer a tool to determine patients at high risk. The cytokine TNF-alpha reveals a complex relationship with diabetes. It is involved in beta-cell damage leading to type 1 diabetes, causes insulin resistance associated with obesity and is of influence in the formation of atherosclerotic vascular lesions. We were interested in the possible association of this cytokine with metabolic control and cardiovascular risk factors 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, Belgium). None of our study participants suffered from inflammatory or other concurrent diseases. Relationships between variables were evaluated by non-parametric Spearman correlation coefficients.
Results: TNF-alpha plasma levels were significantly higher in diabetic patients (19.3 +/- 7.5 pg mL-1) than in non-diabetic subjects (11.1 +/- 5.8 pg mL-1; P < 0. 023), and revealed a significant positive correlation with glycated haemoglobin (HbA1c) (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 relationships could be observed in patients with a duration of diabetes for more than 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 substances 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 molecules intercellular adhesion molecule (ICAM) (r = 0.34; P < 0.051) and vascular cell adhesion molecule (VCAM) (r = 0.30; P < 0.052).
Conclusions: Our data indicate that TNF-alpha plasma levels are increased in type 1 diabetes mellitus and reveal a significant association with metabolic long-term control parameters, HbA1c and fructosamine for glycaemic control, and HDL cholesterol for triglyceride metabolism, as well with lipid peroxidation.