Vulnerable Hours of the Day for Iatrogenic Hypoglycaemia

Background: Normal or near normal glucose to prevent and hopefully reverse diabetic complications is difficult to attain in the real world due to drug-induced hypoglycaemia. In this study, we explored possible existence of “hypoglycaemia-vulnerable hours of the day (HVHD)” in patients with diabetes. If such circadian preponderance exists for iatrogenic hypoglycaemia, utilization of this knowledge would be a great help in achieving optimal glycaemia without iatrogenic hypoglycaemia.<br><br>Methods: From all patients who visited the Critical Care and Emergency Centre of Aizawa Hospital between 2008 and 2019 (n=553 201), 421 patients with clinically suspected hypoglycaemia and using insulin or oral hypoglycaemic agents (OHA) for the treatment of type 2 diabetes were extracted. We further selected adults (over 20 years of age) with proven hypoglycaemia (plasma glucose &lt;70 mg/dL at the time of consultation). In 55 patients who visited emergency room twice or more the during the observation period due to hypoglycaemia, only the data at the initial visit was included to avoid self-intensification of HVHD. From that group of patients, those diagnosed as having liver cirrhosis, cancer and alcoholic abuse, and those needing cardiorespiratory resuscitation upon arrival were excluded. The data from 330 patients were analysed for HVHD including 164 insulin-users and 166 OHA-users. Cosinor analysis was employed for the identification of HVHD.<br><br>Findings: Based on the time of the day when patients visited the emergency room, HVHD were determined. Hypoglycaemia was observed as quadra-peaked (at 01:00h, 08:00h, 13:00h and 19:00h) in insulin-users and double-peaked (at 08:00h and 18:00h) in OHA-users.<br><br>Interpretation: Unique HVHD in insulin- and OHA-users found in patients with type 2 diabetes suggested an interaction between the disease pathophysiology and the drugs used. The data would be a platform for formulating methods to prevent and/or lessen iatrogenic hypoglycaemia.<br><br>Funding: None<br><br>Declaration of Interests: No funding was received by any of the authors. The authors declare no competing interests<br><br>Ethics Approval Statement: This study was approved by the Aizawa Hospital Clinical Research Ethics Review Committee (#2020-055). In addition, we obtained the consent of patients by opting out on our hospital website and hospital postings.