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.

Methods

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.

Results

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.

Trial registration

ClinicalTrials.gov NCT05095259

Graphical Abstract

中文翻译：

---

肾上腺素输注对 1 型糖尿病患者和健康个体的代谢影响

目标/假设

由于胰高血糖素反应早期丧失，肾上腺素是 1 型糖尿病的主要反调节激素。由于反调节失败而导致肾上腺素对低血糖的反应减弱在 1 型糖尿病中很常见，并且可能是由于反复发生低血糖而引起的，然而，肾上腺素的代谢作用受到的研究较少，并且关于肾上腺素敏感性的证据也相互矛盾在 1 型糖尿病中。因此，我们的目的是研究对肾上腺素的代谢反应，并探讨它是否会因先前暴露于低血糖而改变。

方法

18 名患有 1 型糖尿病的参与者和 9 名健康参与者在高胰岛素-正常血糖钳夹期间接受了三步上升肾上腺素输注。使用研究日前一周获得的连续血糖监测数据来评估低血糖暴露的程度。

结果

虽然 1 型糖尿病患者和健康参与者在钳夹期间的葡萄糖反应相似，但 NEFA 和甘油的血浆浓度仅在 1 型糖尿病组中增加 ( p <0.001)。代谢组学显示最常见的 NEFA 有所增加 ( p <0.01)。 1 型糖尿病参与者和健康参与者之间的其他代谢反应通常相似。暴露于低血糖与 NEFA 反应呈负相关；然而，这在统计上并不显着。

结论/解释

总之，与健康参与者相比，1 型糖尿病患者通过动员血浆中丰富的 NEFA，对肾上腺素的脂解作用增加，而其他代谢反应相似。这可能表明 1 型糖尿病中对肾上腺素的代谢敏感性以特定途径的方式发生改变。

试用注册

临床试验.gov NCT05095259

图形概要