Chronic inflammation contributes to cortisol-induced hyperglycemia: Findings from the KORA Age study

Aim: Although stress-induced increases in immune and endocrine responses have been implicated in glucose metabolism, the crosstalk between the two systems remains poorly understood. The study aimed to investigate the synergistic effect between Cortisol and inflammation on hyperglycemia in a representative sample of community-dwelling older people. Methods: The associations between Cortisol (salivary and serum), Interleukin-6 (IL-6) and glycated hemoglobin (HbAlc) were analyzed in a total sample of 394 men and 364 women (mean age = 75 ±6.3 years, 65-90 years). Using mediation analysis, we estimated the proportion explained by IL-6 on the relation between Cortisol levels and HbAlc. Results: Flatter diurnal Cortisol slope (DCS) was significantly associated with a 21% increase in IL-6 concentrations in the hyperglycemic state group compared with control subjects (P = .04). IL-6 significantly mediated the association between dysregulated Cortisol levels (i.e. flatter DCS and higher late-night salivary Cortisol) and elevated HbAlc. However, there was no significant indirect effect of Cortisol Awakening Response (CAR) through inflammation. Conclusion: In our sample, the relation between flatter diurnal Cortisol secretion patterns and hyperglycemia to a large extent was explained by IL-6 levels. The paradigm of subclinical inflammation-mediated Cortisol response on glucose metabolism could have widespread implications for understanding type 2 diabetes mellitus.