Impaired glucose tolerance is associated with increased serum concentrations of interleukin 6 and co-regulated acute-phase proteins but not TNF-alpha or its receptors

Abstract

Aims/hypothesis: A population-based sample was studied to define immune abnormalities in individuals at risk of Type II (non-insulin-dependent) diabetes mellitus because of impaired glucose tolerance.

Methods: A total of 1653 individuals aged 55 to 74 years participated in a population based survey in Southern Germany (KORA Survey 2000). Those without a history of diabetes were subjected to an OGTT. Randomly selected subjects with IGT ( n=80) were compared with non-diabetic control subjects ( n=77) and patients with Type II diabetes ( n=152) of the same population-based sample after matching for age and sex. Immune parameters were analysed in serum with rigidly evaluated ELISA.

Results: Serum pro-inflammatory cytokine interleukin 6 (IL-6) concentrations were higher in subjects with IGT and Type II diabetes than in the control subjects (median 1.8 and 2.5 vs 0.8 pg/ml, p<0.0001). Soluble IL-6 receptors potentiate IL-6 bioactivity and their concentrations were mildly increased in Type II diabetes ( p<0.05). These immune changes seem relevant because IL-6 dependent acute-phase proteins C-reactive protein, serum amyloid A protein and fibrinogen were also increased in IGT and Type II diabetes. Circulating concentrations of TNF-alpha and its two receptors sTNF-R60 and sTNF-R80 were not increased in IGT subjects compared with the control subjects.

Conclusion/interpretation: Our study shows systemic up-regulation of selected inflammatory mediators in patients with Type II diabetes and IGT. The pattern observed is non-random and fits with an IL-6 associated rather than TNF-alpha associated response.