Aims/hypothesis

Our aim was to characterise the in-depth metabolic response to aerobic exercise and the impact of residual pancreatic beta cell function in type 1 diabetes. We also aimed to use the metabolome to distinguish individuals with type 1 diabetes with reduced maximal aerobic capacity in exercise defined by \(\dot{V}{\text{O}}_{\text{2peak}}\).

Methods

Thirty participants with type 1 diabetes (≥3 years duration) and 30 control participants were recruited. Groups did not differ in age or sex. After quantification of peak stimulated C-peptide, participants were categorised into those with undetectable (<3 pmol/l), low (3–200 pmol/l) or high (>200 pmol/l) residual beta cell function. Maximal aerobic capacity was assessed by \(\dot{V}{\text{O}}_{\text{2peak}}\) test and did not differ between control and type 1 diabetes groups. All participants completed 45 min of incline treadmill walking (60% \(\dot{V}{\text{O}}_{\text{2peak}}\)) with venous blood taken prior to exercise, immediately post exercise and after 60 min recovery. Serum was analysed using targeted metabolomics. Metabolomic data were analysed by multivariate statistics to define the metabolic phenotype of exercise in type 1 diabetes. Receiver operating characteristic (ROC) curves were used to identify circulating metabolomic markers of maximal aerobic capacity (\(\dot{V}{\text{O}}_{\text{2peak}}\)) during exercise in health and type 1 diabetes.

Results

Maximal aerobic capacity (\(\dot{V}{\text{O}}_{\text{2peak}}\)) inversely correlated with HbA_1c in the type 1 diabetes group (r²=0.17, p=0.024). Higher resting serum tricarboxylic acid cycle metabolites malic acid (fold change 1.4, p=0.001) and lactate (fold change 1.22, p=1.23×10⁻⁵) differentiated people with type 1 diabetes. Higher serum acylcarnitines (AC) (AC C14:1, F value=12.25, p=0.001345; AC C12, F value=11.055, p=0.0018) were unique to the metabolic response to exercise in people with type 1 diabetes. C-peptide status differentially affected metabolic responses in serum ACs during exercise (AC C18:1, leverage 0.066; squared prediction error 3.07). The malic acid/pyruvate ratio in rested serum was diagnostic for maximal aerobic capacity (\(\dot{V}{\text{O}}_{\text{2peak}}\)) in people with type 1 diabetes (ROC curve AUC 0.867 [95% CI 0.716, 0.956]).

Conclusions/interpretation

The serum metabolome distinguishes high and low maximal aerobic capacity and has diagnostic potential for facilitating personalised medicine approaches to manage aerobic exercise and fitness in type 1 diabetes.

Graphical Abstract

中文翻译：

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代谢组作为 1 型糖尿病运动期间最大有氧能力的诊断

目标/假设

我们的目的是表征有氧运动的深入代谢反应以及残余胰腺 β 细胞功能对 1 型糖尿病的影响。我们还旨在利用代谢组来区分运动中最大有氧能力降低的 1 型糖尿病患者，定义为\(\dot{V}{\text{O}}_{\text{2peak}}\)。

方法

招募了 30 名患有 1 型糖尿病（病程≥3 年）的参与者和 30 名对照参与者。各组在年龄或性别上没有差异。对峰值刺激的 C 肽进行定量后，参与者被分为残留 β 细胞功能不可检测（<3 pmol/l）、低（3-200 pmol/l）或高（>200 pmol/l）的人群。最大有氧能力通过\(\dot{V}{\text{O}}_{\text{2peak}}\)测试进行评估，并且在对照组和 1 型糖尿病组之间没有差异。所有参与者完成 45 分钟的倾斜跑步机行走（60% \(\dot{V}{\text{O}}_{\text{2peak}}\)），并在运动前、运动后立即和运动后采集静脉血60 分钟恢复。使用靶向代谢组学分析血清。通过多变量统计分析代谢组数据，以确定 1 型糖尿病运动的代谢表型。接受者操作特征（ROC）曲线用于识别健康和类型运动期间最大有氧能力（ \(\dot{V}{\text{O}}_{\text{2peak}}\) ）的循环代谢组标记物1 糖尿病。

结果

1 型糖尿病组中最大有氧能力 ( \(\dot{V}{\text{O}}_{\text{2peak}}\) ) 与 HbA _1c呈负相关( r ² =0.17, p =0.024) 。较高的静息血清三羧酸循环代谢物苹果酸（倍数变化1.4，p = 0.001）和乳酸（倍数变化1.22，p = 1.23×10 ^-5）使1型糖尿病患者得以区分。较高的血清酰基肉碱 (AC)（AC C14:1，F值=12.25，p =0.001345；AC C12，F值=11.055，p =0.0018）是 1 型糖尿病患者对运动的代谢反应所特有的。 C 肽状态对运动期间血清 AC 的代谢反应有不同影响（AC C18：1，杠杆 0.066；平方预测误差 3.07）。静息血清中的苹果酸/丙酮酸比率可诊断1 型糖尿病患者的最大有氧能力 ( \(\dot{V}{\text{O}}_{\text{2peak}}\) ）（ROC 曲线AUC 0.867 [95% CI 0.716，0.956]）。

结论/解释

血清代谢组可区分最大有氧能力的高低，并具有促进个性化医疗方法管理 1 型糖尿病有氧运动和健身的诊断潜力。

图形概要