Human Nutrition & Exercise Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK.
The Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Oxford, UK.
Diabetologia. 2024 Jul;67(7):1413-1428. doi: 10.1007/s00125-024-06153-0. Epub 2024 Apr 25.
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 .
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 test and did not differ between control and type 1 diabetes groups. All participants completed 45 min of incline treadmill walking (60% ) 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 ( ) during exercise in health and type 1 diabetes.
Maximal aerobic capacity ( ) inversely correlated with HbA in the type 1 diabetes group (r=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) 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 ( ) 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.
目的/假设：我们的目的是描述 1 型糖尿病患者有氧运动的深入代谢反应和残余胰岛β细胞功能的影响。我们还旨在使用代谢组学来区分运动定义的最大有氧能力降低的 1 型糖尿病患者。
招募了 30 名患有 1 型糖尿病（≥3 年）的参与者和 30 名对照参与者。两组在年龄和性别上没有差异。在定量测定峰值刺激 C 肽后，将参与者分为无检测到（<3 pmol/l）、低（3-200 pmol/l）或高（>200 pmol/l）残余β细胞功能的患者。最大有氧能力通过 测试评估，1 型糖尿病组和对照组之间没有差异。所有参与者均完成 45 分钟倾斜跑步机步行（60% ），在运动前、运动后立即和 60 分钟恢复后采集静脉血。使用靶向代谢组学分析血清。使用多元统计分析代谢组学数据，以定义 1 型糖尿病患者运动的代谢表型。使用接收者操作特征（ROC）曲线确定健康和 1 型糖尿病患者运动期间最大有氧能力（ ）的循环代谢标志物。
最大有氧能力（ ）与 1 型糖尿病组的 HbA 呈负相关（r=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）区分了 1 型糖尿病患者。较高的血清酰基辅酶 A（AC）（AC C14:1，F 值=12.25，p=0.001345；AC C12，F 值=11.055，p=0.0018）是 1 型糖尿病患者运动代谢反应的独特标志。C 肽状态在运动期间对血清 AC 中的代谢反应有不同的影响（AC C18:1，杠杆率 0.066；平方预测误差 3.07）。休息时血清中苹果酸/丙酮酸的比值可诊断 1 型糖尿病患者的最大有氧能力（ ）（ROC 曲线 AUC 0.867[95%CI 0.716, 0.956]）。
结论/解释：血清代谢组学可区分高和低最大有氧能力，具有诊断潜力，可促进个体化医学方法来管理 1 型糖尿病患者的有氧运动和健身。
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