Department of Endocrinology and Nephrology, Nordsjællands Hospital, Hillerød, Capital Region of Denmark, Denmark.
Department of Clinical Medicine, University of Copenhagen Faculty of Health and Medical Sciences, Kobenhavn, Capital Region of Denmark, Denmark.
BMJ Open Diabetes Res Care. 2023 Jun;11(3). doi: 10.1136/bmjdrc-2023-003327.
Hypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to hypoglycemia. Limited data on metabolic adaptation to recurrent hypoglycemia are available. This study examined the acute metabolic responses to hypoglycemia and the effect of antecedent hypoglycemia on these responses in type 1 diabetes.
Twenty-one outpatients with type 1 diabetes with normal or impaired awareness of hypoglycemia participated in a study assessing the response to hypoglycemia on 2 consecutive days by a hyperinsulinemic glucose clamp. Participants underwent a period of normoglycemia and a period of hypoglycemia during the hyperinsulinemic glucose clamp. Plasma samples were taken during normoglycemia and at the beginning and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry.
In total, 68 metabolites were studied. On day 1, concentrations of the branched-chain amino acids, leucine (p=3.8×10) and isoleucine (p=2.2×10), decreased during hypoglycemia. On day 2, during hypoglycemia, five amino acids (including leucine and isoleucine) significantly decreased, and two fatty acids (tetradecanoic and oleic acids) significantly increased (p<0.05). Although more metabolites responded to hypoglycemia on day 2, the responses of the single metabolites were not statistically significant between the 2 days.
In individuals with type 1 diabetes, one episode of hypoglycemia decreases leucine and isoleucine concentrations. Antecedent hypoglycemia results in the decrement of five amino acids and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptation. However, more studies are needed to gain a comprehensive understanding of the consequences of these alterations.
NCT01337362.
低血糖是 1 型糖尿病患者达到推荐血糖目标的主要限制因素。反复发生低血糖会导致激素的代偿性和症状性反应减弱。关于反复发生低血糖的代谢适应的有限数据可用。本研究检查了 1 型糖尿病患者对低血糖的急性代谢反应以及先前低血糖对这些反应的影响。
21 名伴有或不伴有低血糖感知障碍的 1 型糖尿病门诊患者参与了一项研究，通过高胰岛素葡萄糖钳夹在连续两天评估低血糖反应。参与者经历了正常血糖期和高胰岛素葡萄糖钳夹期间的低血糖期。在正常血糖期和低血糖期开始和结束时采集血浆样本。使用全面二维气相色谱-飞行时间质谱对血浆样本进行代谢组学分析。
总共研究了 68 种代谢物。在第 1 天，支链氨基酸亮氨酸（p=3.8×10）和异亮氨酸（p=2.2×10）的浓度在低血糖期间降低。在第 2 天，在低血糖期间，五种氨基酸（包括亮氨酸和异亮氨酸）显著降低，两种脂肪酸（十四烷酸和油酸）显著增加（p<0.05）。尽管第 2 天有更多的代谢物对低血糖有反应，但两种情况下单个代谢物的反应没有统计学意义。
在 1 型糖尿病患者中，一次低血糖会降低亮氨酸和异亮氨酸的浓度。先前的低血糖导致五种氨基酸减少，两种脂肪酸增加，这表明两个低血糖事件之间存在变化，这可能表明存在一种适应。然而，还需要更多的研究来全面了解这些变化的后果。
NCT01337362。
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