Renin-Angiotensin-Aldosterone System, Glucose Metabolism and Incident Type 2 Diabetes Mellitus: MESA.
Renin-Angiotensin-Aldosterone System, Glucose Metabolism and Incident Type 2 Diabetes Mellitus: MESA.
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DOI：
10.1161/jaha.118.009890
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发表时间：
2018-09-04
影响因子：
5.4
通讯作者：
Golden SH
中科院分区：
文献类型：
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作者：
Joseph JJ;Echouffo Tcheugui JB;Effoe VS;Hsueh WA;Allison MA;Golden SH
机理研究表明，醛固酮损害葡萄糖代谢。我们在梅萨（动脉粥样硬化的多种族研究）前瞻性队列研究中调查了醛固酮和血浆肾素活性与空腹血糖、胰岛素抵抗（IR）、β细胞功能的横截面相关性，以及与成人糖尿病事件的纵向相关性。IR（HOMA 2-IR）和HOMA 2-β的稳态模型评估分别用于估计IR和β细胞功能。糖尿病事件定义为随访时空腹血糖≥126 mg/dL或使用降糖药物。采用线性回归分析醛固酮与空腹血糖、HOMA 2-IR和HOMA 2-β的横截面相关性;采用考克斯回归分析估计糖尿病事件的风险比（HR），并进行多变量校正。在1570例成人中，10.5年内发生了116例糖尿病事件（44%为非西班牙裔白色人，13%为华裔美国人，19%为黑人，24%为西班牙裔美国人，平均年龄64±10岁，51%为女性）。log‐醛固酮增加100%与空腹血糖升高2.6 mg/dL、HOMA 2 ‐IR升高15%和HOMA 2 ‐β升高6%相关（P<0.01）。log-醛固酮增加1-SD与糖尿病发病风险增加44%相关（P<0.01），在华裔美国人中观察到最大增加142%（P<0.01）（与其他种族相比，相互作用P =0.09）。对数血浆肾素活性存在类似的横截面结果，但在完全校正后，对数血浆肾素活性与糖尿病事件无关。醛固酮与葡萄糖稳态和糖尿病风险相关，在华裔美国人和黑人中具有分级相关性，表明醛固酮的多效性作用可能代表糖尿病发病机制的可改变机制，具有潜在的种族/民族差异。
Mechanistic studies suggest that aldosterone impairs glucose metabolism. We investigated the cross‐sectional associations of aldosterone and plasma renin activity with fasting plasma glucose, insulin resistance (IR), β‐cell function, and longitudinal association with incident diabetes mellitus among adults in MESA (the multiethnic study of atherosclerosis) prospective cohort study. Homeostatic model assessment of IR (HOMA2‐IR) and HOMA2‐β were used to estimate IR and β‐cell function, respectively. Incident diabetes mellitus was defined as fasting plasma glucose ≥126 mg/dL or anti‐diabetic medication use at follow‐up. Linear regression was used to examine cross‐sectional associations of aldosterone with fasting plasma glucose, HOMA2‐IR and HOMA2‐β; Cox regression was used to estimate hazard ratios (HR) for incident diabetes mellitus with multivariable adjustment. There were 116 cases of incident diabetes mellitus over 10.5 years among 1570 adults (44% non‐Hispanic white, 13% Chinese American, 19% Black, 24% Hispanic American, mean age 64±10 years, 51% female). A 100% increase in log‐aldosterone was associated with a 2.6 mg/dL higher fasting plasma glucose, 15% higher HOMA2‐IR and 6% higher HOMA2‐β (P<0.01). A 1‐SD increase in log‐aldosterone was associated with a 44% higher risk of incident diabetes mellitus (P<0.01) with the greatest increase of 142% (P<0.01) observed in Chinese Americans (P for interaction=0.09 versus other ethnicities). Similar cross‐sectional findings for log‐plasma renin activity existed, but log‐plasma renin activity was not associated with incident diabetes mellitus after full adjustment. Aldosterone is associated with glucose homeostasis and diabetes mellitus risk with graded associations among Chinese Americans and blacks, suggesting that pleiotropic effects of aldosterone may represent a modifiable mechanism in diabetes mellitus pathogenesis with potential racial/ethnic variation.