Han Min-Min, Zhang Jia-Xin, Liu Zi-Ang, Xu Lin-Xin, Bai Tao, Xiang Chen-Yu, Zhang Jin, Lv Dong-Qing, Liu Yan-Fang, Wei Yan-Hong, Wu Bao-Feng, Zhang Yi, Liu Yun-Feng
Department of Endocrinology, First Hospital of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China.
The First Clinical Medical College of Shanxi Medical University, Taiyuan 030000, Shanxi Province, China.
World J Diabetes. 2023 Jul 15;14(7):1112-1125. doi: 10.4239/wjd.v14.i7.1112.
Commonly used glucocorticoids replacement regimens in patients with hypopituitarism have difficulty mimicking physiological cortisol rhythms and are usually accompanied by risks of over-treatment, with adverse effects on glucose metabolism. Disorders associated with glucose metabolism are established risk factors of cardiovascular events, one of the life-threatening ramifications.
To investigate the glycometabolism profile in patients with hypopituitarism receiving prednisone (Pred) replacement, and to clarify the impacts of different Pred doses on glycometabolism and consequent adverse cardiovascular outcomes.
Twenty patients with hypopituitarism receiving Pred replacement [patient group (PG)] and 20 normal controls (NCs) were recruited. A flash glucose monitoring system was used to record continuous glucose levels during the day, which provided information on glucose-target-rate, glucose variability (GV), period glucose level, and hypoglycemia occurrence at certain periods. Islet β-cell function was also assessed. Based on the administered Pred dose per day, the PG was then regrouped into Pred > 5 mg/d and Pred ≤ 5 mg/d subgroups. Comparative analysis was carried out between the PG and NCs.
Significantly altered glucose metabolism profiles were identified in the PG. This includes significant reductions in glucose-target-rate and nocturnal glucose level, along with elevations in GV, hypoglycemia occurrence and postprandial glucose level, when compared with those in NCs. Subgroup analysis indicated more significant glucose metabolism impairment in the Pred > 5 mg/d group, including significantly decreased glucose-target-rate and nocturnal glucose level, along with increased GV, hypoglycemia occurrence, and postprandial glucose level. With regard to islet β-cell function, PG showed significant difference in homeostasis model assessment (HOMA)-β compared with that of NCs; a notable difference in HOMA-β was identified in Pred > 5 mg/d group when compared with those of NCs; as for Pred ≤ 5 mg/d group, significant differences were found in HOMA-β, and fasting glucose/insulin ratio when compared with NCs.
Our results demonstrated that Pred replacement disrupted glycometabolic homeostasis in patients with hypopituitarism. A Pred dose of > 5 mg/d seemed to cause more adverse effects on glycometabolism than a dose of ≤ 5 mg/d. Comprehensive and accurate evaluation is necessary to consider a suitable Pred replacement regimen, wherein, flash glucose monitoring system is a kind of promising and reliable assessment device. The present data allows us to thoroughly examine our modern treatment standards, especially in difficult cases such as hormonal replacement mimicking delicate natural cycles, in conditions such as diabetes mellitus that are rapidly growing in worldwide prevalence.
垂体功能减退患者常用的糖皮质激素替代方案难以模拟生理皮质醇节律，且通常伴有过度治疗风险，对糖代谢有不良影响。糖代谢紊乱是心血管事件的既定危险因素，而心血管事件是危及生命的后果之一。
研究接受泼尼松（Pred）替代治疗的垂体功能减退患者的糖代谢情况，并阐明不同Pred剂量对糖代谢及随之而来的不良心血管结局的影响。
招募20例接受Pred替代治疗的垂体功能减退患者[患者组（PG）]和20例正常对照者（NCs）。使用动态血糖监测系统记录白天的连续血糖水平，该系统可提供血糖达标率、血糖变异性（GV）、特定时间段的血糖水平以及低血糖发生情况等信息。同时评估胰岛β细胞功能。根据每日Pred给药剂量，将PG再分为Pred>5mg/d和Pred≤5mg/d亚组。对PG和NCs进行比较分析。
PG患者的糖代谢情况有显著改变。与NCs相比，这包括血糖达标率和夜间血糖水平显著降低，同时GV、低血糖发生率和餐后血糖水平升高。亚组分析表明，Pred>5mg/d组的糖代谢损害更显著，包括血糖达标率和夜间血糖水平显著降低，以及GV升高、低血糖发生率增加和餐后血糖水平升高。关于胰岛β细胞功能，PG与NCs相比，稳态模型评估（HOMA）-β有显著差异；Pred>5mg/d组与NCs相比，HOMA-β有明显差异；对于Pred≤5mg/d组，与NCs相比，HOMA-β以及空腹血糖/胰岛素比值有显著差异。
我们的结果表明，Pred替代治疗破坏了垂体功能减退患者的糖代谢稳态。Pred剂量>5mg/d似乎比≤5mg/d的剂量对糖代谢产生更多不良影响。考虑合适的Pred替代方案时，需要进行全面准确的评估，其中动态血糖监测系统是一种有前景且可靠的评估工具。目前的数据使我们能够彻底审视我们的现代治疗标准，尤其是在诸如模拟微妙自然周期的激素替代等困难情况下，以及在全球患病率迅速上升的糖尿病等疾病中。
