Cortisol as a Predictor of Nocturnal Hypoglycemia in Insulin-Treated Diabetes: A Cross-Sectional Study

Introduction: Nocturnal hypoglycemia (NH) is a major clinical concern in insulin-treated diabetes due to blunted autonomic responses and reduced awareness of hypoglycemia during sleep. We investigated the association between NH and early morning fasting cortisol levels in this population. Methods: This case-control study included 30 insulin-treated adults with type 1 diabetes (n = 22) or advanced type 2 diabetes (n = 8) and depleted endogenous insulin secretion. Glucose profiles were assessed using intermittently scanned continuous glucose monitoring. NH was defined as glucose levels <70 mg/dL between 00:00 and 06:00. Fasting-morning serum cortisol, plasma glucagon, and serum C-peptide levels were also measured. The clinical and biochemical parameters were compared between patients with and without NH. Results: NH occurred in 15 of 30 patients (50.0%), including three (10.0%) with level 2 hypoglycemia (<54 mg/dL). There were no significant differences between the groups in terms of age, diabetes type, disease duration, HbA1c level, body mass index (BMI), insulin dose, or C-peptide level. However, fasting cortisol levels were significantly lower in patients with NH. Logistic regression analysis showed that lower cortisol levels were independently associated with NH (odds ratio: 0.708; 95% confidence interval: 0.52-0.97; p < 0.05). Receiver operating characteristic curve analysis identified a cortisol threshold of 10.7 μg/dL for predicting NH (area under the curve = 0.79, sensitivity = 0.73, specificity = 0.80). Conclusions: Lower early morning cortisol levels may serve as an independent risk factor for NH in patients with insulin-treated diabetes. Cortisol measurements may help identify individuals at risk of asymptomatic NH.