Yan Xia,1,* Hong-jing Chen,1,* Reng-na Yan,2 Xiao-wei Zhu,1 Han Zhao,1 Bo Ding,2 Yun Hu1,2 

1Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, People’s Republic of China; 2Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Yun Hu, Department of Endocrinology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, No. 299 Qingyang Road, Wuxi, 214023, People’s Republic of China, Email huyunwuxi@163.com Bo Ding, Department of Endocrinology, Nanjing First Hospital, Nanjing Medical University, No. 32 Gongqingtuan Road, Nanjing, 210012, People’s Republic of China, Email dingbonanjing@sina.com

Purpose: The mechanism of the dawn phenomenon remains poorly understood, and no targeted therapies are currently available. Emerging evidence suggests thyroid dysfunction may contribute to dawn phenomenon by modulating hepatic glucose output, insulin sensitivity, and β-cell function. This study utilized continuous glucose monitoring (CGM) to identify patients with type 2 diabetes exhibiting dawn phenomenon and to investigate its association with thyroid feedback efficiency.
Patients and Methods: This study included patients with type 2 diabetes. All patients underwent CGM before any adjustments to their glucose-lowering therapy. The dawn phenomenon was determined if the elevation of blood glucose from 3 AM to 7 AM was more than 1.11 mmol/L. Clinical data, including medications, diabetic complications and comorbidities, biochemical markers, hemoglobin A1c (HbA1c), beta-cell function, and thyroid function, were recorded.
Results: A total of 524 patients were included, of whom 265 (50.6%) exhibited the dawn phenomenon. A control group of 216 patients was matched based on HbA1c levels from those without dawn phenomenon using propensity score matching. The standard deviation of blood glucose (SDBG) (2.26 vs 1.78, P=0.001) and coefficient of variation (CV) (22.86 vs 16.97, P< 0.001) were significantly higher in the dawn phenomenon group compared to the non-dawn phenomenon group. Thyroid feedback quantile-based index (TFQI) of free thyroxine (FT4) was negatively correlated with the elevation of blood glucose from 3 AM to 7 AM (BG 3– 7) (r=− 0.211, P=0.002). Low-density lipoprotein (LDL) showed a positive correlation with fasting blood glucose (r=0.242, P=0.001) and BG 3– 7 (r=0.123, P=0.083). Regression analysis indicated that TFQI of free triiodothyronine (FT3) (β=− 2.399, P< 0.001) and LDL (β=0.550, P=0.004) were independent predictors of BG 3– 7.
Conclusion: The dawn phenomenon significantly correlates with glycemic fluctuation severity and TFQI. These findings indicate the relationship between thyroid hormones and glucose regulation, providing new insights into the mechanism of the dawn phenomenon.

Keywords: diabetes, dawn phenomenon, blood glucose variability, thyroid hormones