Curtin Medical School, Curtin University, Perth, Western Australia, Australia.
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Br J Clin Pharmacol. 2022 Jun;88(6):2718-2726. doi: 10.1111/bcp.15182. Epub 2021 Dec 28.
To investigate the association between proton pump inhibitors (PPIs) and risk of incident diabetes in a follow-up study and to investigate its potential mechanisms.
A total of 9531 individuals without type 2 diabetes (T2DM) at baseline were included from the Rotterdam Study, a prospective population-based cohort of 14 926 individuals aged 45 years or older. During the study period (1 April 1997 to 1 January 2012) all incident cases of T2DM were enrolled. We used multivariable linear regression analysis to investigate the associations of baseline PPI use and various serum biomarkers (eg, serum magnesium, insulin-like growth factor 1) which might modify the association. Thereafter, we excluded prevalent PPI users and performed a Cox proportional hazard regression analysis to explore the time-varying effect of incident PPI use on T2DM during follow-up.
Baseline use of a PPI was associated with increased serum levels of fasting insulin (0.091 pmoL/L, 95% confidence interval [CI] 0.049, 0.133), homeostasis model assessment-insulin resistance (0.100, 95% CI 0.056, 0.145) and C-reactive protein (0.29 mg/L, 95% CI 0.198, 0.384), but decreased levels of magnesium (-0.009 mmol/L, 95% CI -0.014, -0.004) and IGF-1 (-0.805 nmoL/L, 95% CI -1.015, -0.595). After adjustment for risk factors such as physical activity and body mass index/waist-to-hip ratio, current use of PPI was associated with an increased risk of incident T2DM (hazard ratio [HR] 1.69, 95% CI 1.36-2.10). The effect was dose-dependent with the highest risk (HR 1.88, 95% CI 1.29-2.75) in those on more than one defined daily dose.
New users of PPIs during follow-up had a significantly higher dose-dependent risk of incident diabetes. We suggest vigilance regarding their potential adverse effect on glucose homeostasis.
在一项随访研究中，调查质子泵抑制剂（PPIs）与新发糖尿病风险之间的关联，并探讨其潜在机制。
本研究共纳入了来自鹿特丹研究的 9531 名基线时无 2 型糖尿病（T2DM）的个体，该研究是一项针对 14926 名年龄在 45 岁或以上的人群的前瞻性人群队列研究。在研究期间（1997 年 4 月 1 日至 2012 年 1 月 1 日），所有新发 T2DM 病例均被纳入。我们使用多变量线性回归分析来研究基线时使用 PPI 与各种血清生物标志物（如血清镁、胰岛素样生长因子 1）之间的关联，这些生物标志物可能会改变这种关联。此后，我们排除了现用 PPI 使用者，并进行了 Cox 比例风险回归分析，以探讨随访期间新发 PPI 使用对 T2DM 的时变影响。
基线时使用 PPI 与空腹胰岛素水平升高（0.091 pmol/L，95%置信区间 [CI] 0.049，0.133）、稳态模型评估胰岛素抵抗（0.100，95%CI 0.056，0.145）和 C 反应蛋白（0.29mg/L，95%CI 0.198，0.384）有关，但与镁（-0.009mmol/L，95%CI -0.014，-0.004）和 IGF-1（-0.805nmol/L，95%CI -1.015，-0.595）水平降低有关。在调整了体育活动和体重指数/腰臀比等风险因素后，目前使用 PPI 与新发 T2DM 的风险增加相关（风险比[HR] 1.69，95%CI 1.36-2.10）。这种效应呈剂量依赖性，在使用超过一种定义日剂量的患者中，风险最高（HR 1.88，95%CI 1.29-2.75）。
在随访期间新使用 PPI 的患者新发糖尿病的风险显著增加，且呈剂量依赖性。我们建议警惕 PPI 对葡萄糖稳态可能产生的不良影响。
