Stronger association between morning serum cortisol level and diurnal time in range in type 2 diabetes?

The hypothalamic-pituitary-adrenal axis is thought to play a vital role in glucose homeostasis and diabetes. This study investigated the association between morning serum cortisol and time in range (TIR), including daytime TIR, in type 2 diabetes (T2DM). 310 patients with T2DM had serum cortisol measured at 8 a.m. All participants underwent continuous glucose monitoring (CGM) for three consecutive days, then TIR and glycemic variability (GV) parameters were evaluated. Using 100 g standard steamed bread meal test, blood glucose, C peptide and insulin at different points were collected to assess insulin sensitivity and islet function. Patients with higher serum cortisol exhibited lower TIR and TITR (P < 0.001). Spearman correlation analysis showed that the negative correlation between cortisol and daytime TIR (r=-0.231, P < 0.001) was stronger than that of overnight TIR (r=-0.134, P = 0.028). Similarly, there existed a negative correlation between cortisol and pancreatic function indicators such as HOMA-β, insulinogenic index (IGI), area under the curve of C-peptide within half an hour (AUCCp0.5 h) and three hours (AUCCp3h) (r=-0.248, -0.176, -0.140, -0.185, respectively, P < 0.05). In contrast, cortisol was positively associated with TAR (r = 0.217, P < 0.001) and GV parameters including MBG, MAGE, LAGE, HBGI, MODD, ADDR (P of MAGE and MODD > 0.05). Multiple stepwise regression revealed that cortisol was an independent contributor of TIR, TITR and diurnal TIR, with diurnal TIR of stronger relevance. Morning serum cortisol is negatively correlated with TIR, especially diurnal TIR and positively associated with GV parameters. Inappropriate cortisol secretion may have an adverse influence on glucose homeostasis in T2DM.