Department of Endocrinology and Nephrology, Nordsjællands Hospital, Hillerød, Denmark.
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Diabetologia. 2024 Jun;67(6):1095-1106. doi: 10.1007/s00125-024-06116-5. Epub 2024 Mar 1.
AIMS/HYPOTHESIS: As a result of early loss of the glucagon response, adrenaline is the primary counter-regulatory hormone in type 1 diabetes. Diminished adrenaline responses to hypoglycaemia due to counter-regulatory failure are common in type 1 diabetes, and are probably induced by exposure to recurrent hypoglycaemia, however, the metabolic effects of adrenaline have received less research attention, and also there is conflicting evidence regarding adrenaline sensitivity in type 1 diabetes. Thus, we aimed to investigate the metabolic response to adrenaline and explore whether it is modified by prior exposure to hypoglycaemia.
Eighteen participants with type 1 diabetes and nine healthy participants underwent a three-step ascending adrenaline infusion during a hyperinsulinaemic-euglycaemic clamp. Continuous glucose monitoring data obtained during the week before the study day were used to assess the extent of hypoglycaemia exposure.
While glucose responses during the clamp were similar between people with type 1 diabetes and healthy participants, plasma concentrations of NEFAs and glycerol only increased in the group with type 1 diabetes (p<0.001). Metabolomics revealed an increase in the most common NEFAs (p<0.01). Other metabolic responses were generally similar between participants with type 1 diabetes and healthy participants. Exposure to hypoglycaemia was negatively associated with the NEFA response; however, this was not statistically significant.
CONCLUSIONS/INTERPRETATION: In conclusion, individuals with type 1 diabetes respond with increased lipolysis to adrenaline compared with healthy participants by mobilising the abundant NEFAs in plasma, whereas other metabolic responses were similar. This may suggest that the metabolic sensitivity to adrenaline is altered in a pathway-specific manner in type 1 diabetes.
ClinicalTrials.gov NCT05095259.
目的/假设：由于胰高血糖素反应的早期丧失，肾上腺素是 1 型糖尿病的主要代偿性激素。1 型糖尿病中常见由于代偿失败导致的低血糖时肾上腺素反应减弱，这可能是由于反复发生低血糖引起的，然而，肾上腺素的代谢作用受到的关注较少，并且关于 1 型糖尿病中肾上腺素敏感性也存在相互矛盾的证据。因此，我们旨在研究肾上腺素的代谢反应，并探讨其是否因先前暴露于低血糖而改变。
18 名 1 型糖尿病患者和 9 名健康参与者在高胰岛素-正常血糖钳夹期间进行了三步递增肾上腺素输注。在研究前一周获得的连续血糖监测数据用于评估低血糖暴露程度。
尽管 1 型糖尿病患者和健康参与者在钳夹期间的血糖反应相似，但只有 1 型糖尿病患者的血浆 NEFA 和甘油三酯浓度增加（p<0.001）。代谢组学显示最常见的 NEFA 增加（p<0.01）。其他代谢反应在 1 型糖尿病患者和健康参与者之间通常相似。低血糖暴露与 NEFA 反应呈负相关；然而，这并不具有统计学意义。
结论/解释：总之，与健康参与者相比，1 型糖尿病患者对肾上腺素的反应是通过动员丰富的血浆 NEFA 增加脂肪分解，而其他代谢反应相似。这可能表明，1 型糖尿病中肾上腺素的代谢敏感性以特定途径的方式发生改变。
ClinicalTrials.gov NCT05095259。
