血浆中 ATP 酶抑制因子 1（IF1）水平与人类 2 型糖尿病风险相关：一项前瞻性队列研究。
Plasma level of ATPase inhibitory factor 1 (IF1) is associated with type 2 diabetes risk in humans: A prospective cohort study.
机构信息
Institut des Maladies Métaboliques et Cardiovasculaires, I2MC, Université de Toulouse, Inserm, Université Toulouse III - Paul Sabatier (UPS), UMR1297, Toulouse, France.
Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du Thorax, 44000 Nantes, France; Nantes Université, CHU Nantes, Pôle Hospitalo-Universitaire 11 : Santé Publique, Clinique des données, INSERM, CIC 1413, F-44000 Nantes, France.
出版信息
Diabetes Metab. 2023 Jan;49(1):101391. doi: 10.1016/j.diabet.2022.101391. Epub 2022 Sep 26.
AIM
Mitochondrial dysfunction is associated with the development of type 2 diabetes mellitus (T2DM). It is thus of clinical relevance to identify plasma biomarkers of mitochondrial dysfunction associated with the risk of T2DM. ATPase inhibitory factor 1 (IF1) endogenously inhibits mitochondrial ATP synthase activity. Here, we analyzed association of the plasma IF1 level with markers of glucose homeostasis and with the conversion to new-onset diabetes (NOD) in individuals with prediabetes.
METHODS
In the IT-DIAB prospective study, the baseline plasma level of IF1 was measured in 307 participants with prediabetes. The primary outcome was the incidence of NOD within five years of follow-up. Cross-sectional analysis of the IF1 level was also done in two independent interventional studies. Correlations between plasma IF1 and metabolic parameters at baseline were assessed by Spearman's correlation coefficients, and the association with the risk of NOD was determined using Cox proportional-hazards models.
RESULTS
In IT-DIAB, the mean IF1 plasma level was lower in participants who developed NOD than in those who did not (537 ± 248 versus 621 ± 313 ng/mL, P = 0.01). The plasma IF1 level negatively correlated with clinical variables associated with obesity and insulin resistance, including the body mass index (r = -0.20, P = 0.0005) and homeostasis model assessment of insulin resistance (HOMA-IR). (r = -0.37, P < 0.0001). Conversely, IF1 was positively associated with plasma markers of cardiometabolic health, such as HDL-C (r = 0.63, P < 0.0001) and apoA-I (r = 0.33, P < 0.0001). These correlations were confirmed in cross-sectional analyses. In IT-DIAB, the IF1 level was significantly associated with a lower risk of T2DM after adjustment for age, sex, and fasting plasma glucose (HR [95% CI] per 1 SD = 0.76 [0.62; 0.94], P = 0.012).
CONCLUSION
We identified for the first time the mitochondrial-related biomarker IF1 as being associated with the risk of T2DM.
目的
线粒体功能障碍与 2 型糖尿病（T2DM）的发生发展有关。因此，鉴定与 T2DM 风险相关的线粒体功能障碍的血浆生物标志物具有重要的临床意义。ATP 酶抑制因子 1（IF1）内源性地抑制线粒体 ATP 合酶的活性。在此，我们分析了 IF1 血浆水平与葡萄糖稳态标志物的相关性，并与 307 例有前驱糖尿病的个体中发生新诊断糖尿病（NOD）的转化率相关。
方法
在 IT-DIAB 前瞻性研究中，测量了 307 例前驱糖尿病患者的基线 IF1 血浆水平。主要结局为五年随访期间 NOD 的发生率。在两项独立的干预研究中还进行了 IF1 水平的横断面分析。采用 Spearman 相关系数评估 IF1 血浆水平与基线代谢参数之间的相关性，并采用 Cox 比例风险模型确定与 NOD 风险的相关性。
结果
在 IT-DIAB 中，发生 NOD 的参与者的 IF1 血浆水平低于未发生 NOD 的参与者（537±248 与 621±313ng/mL，P=0.01）。IF1 血浆水平与肥胖和胰岛素抵抗相关的临床变量呈负相关，包括体重指数（r=-0.20，P=0.0005）和稳态模型评估的胰岛素抵抗（HOMA-IR）（r=-0.37，P<0.0001）。相反，IF1 与心血管代谢健康的血浆标志物呈正相关，如高密度脂蛋白胆固醇（HDL-C）（r=0.63，P<0.0001）和载脂蛋白 A-I（apoA-I）（r=0.33，P<0.0001）。这些相关性在横断面分析中得到了证实。在 IT-DIAB 中，IF1 水平与调整年龄、性别和空腹血糖后 T2DM 的风险显著相关（每 1 SD 的 HR[95%CI]为 0.76[0.62；0.94]，P=0.012）。
结论
我们首次发现与线粒体相关的生物标志物 IF1 与 T2DM 的风险相关。
Zotero 插件