Male patients with higher C-peptide have significantly positive hormone counterregulatory responses to hypoglycemia among patients with diabetes mellitus

Abstract

Abstract Purpose Hypoglycemia is a frequent complication of diabetes, hindering treatment efficacy and elevating mortality rates. Hypoglycemia prompts a counterregulatory response (CRR) striving to restore normoglycemia. Hormonal counterregulation is crucial in orchestrating this hypoglycemic response. Our study aimed to investigate the correlations between levels of pertinent counterregulatory hormones and diverse clinical parameters in both type 1 diabetes (T1DM) and type 2 diabetes (T2DM), and to compare these hormonal profiles between T1DM and T2DM. Methods This cross-sectional study aimed to identify the variables associated with levels of relevant counterregulatory hormones in hospitalized individuals diagnosed with T1DM (n = 71) and T2DM (n = 185), who experienced hypoglycemic episodes. This goal was achieved using separate univariate and multivariate linear regression analyses. The evaluated counterregulatory hormones included glucagon, growth hormone (GH), cortisol, and adrenocorticotropic hormone (ACTH), all measured during hypoglycemic episodes. Subsequently, the hormone levels were compared between patients diagnosed with T1DM and those with T2DM. Multiple imputation techniques were used to address missing data and rectify the dataset. Results Among patients with T2DM, multiple linear regression analysis revealed significant positive associations during hypoglycemia: fasting C-peptide levels were positively correlated with glucagon levels; male gender showed positive correlations with both GH and cortisol levels; hemoglobin A1c (HbA1c) had positive correlations with ACTH levels; and polyneuropathy exhibited positive correlations with ACTH levels. Among patients with T1DM, multiple linear regression analysis disclosed a substantial positive link between nephropathy and cortisol levels during hypoglycemia. After adjusting for confounding factors, there were no significant differences in counterregulatory hormone levels during hypoglycemia between patients with T1DM and T2DM. Conclusion In patients with T2DM, elevated fasting C-peptide levels were associated with increased glucagon responses, and male gender was associated with enhanced GH and cortisol responses to hypoglycemia. Furthermore, elevated HbA1c levels and polyneuropathy were correlated with an increased ACTH response to hypoglycemia. Nephropathy in patients with T1DM was found to be associated with an augmented cortisol response during hypoglycemia. No significant differences in counterregulatory hormone levels during hypoglycemia were observed between patients with T1DM and T2DM.