Shimanoe Chisato, Matsumoto Akiko, Nishida Yuichiro, Furukawa Takuma, Sogawa Rintaro, Horita Mikako, Nanri Hinako, Higaki Yasuki, Tanaka Keitaro, Hara Megumi
Department of Pharmacy, Saga University Hospital, Saga, Japan.
Department of Social Medicine, Faculty of Medicine, Saga University, Saga, Japan.
Hypertens Res. 2025 Jun 27. doi: 10.1038/s41440-025-02271-3.
The incidence of hypertension and Type 2 diabetes mellitus (T2DM) is increasing, and their coexistence significantly increases the risk of cardiovascular diseases, stroke, nephropathy, retinopathy, and mortality. Mineralocorticoid receptor activity, primarily regulated by aldosterone, can be beneficially modulated by mineralocorticoid receptor antagonists, especially in patients with mineralocorticoid receptor-associated hypertension, which often occurs with obesity and T2DM. Thus, markers of mineralocorticoid receptor activation, such as 11β-hydroxysteroid dehydrogenase, may help identify patients who may not benefit from standard hypertension treatments. This study investigated the effects of the cortisol-to-cortisone ratio, a marker of 11β-hydroxysteroid dehydrogenase activity, on the relationship between T2DM and hypertension. Using a cross-sectional design, 6931 individuals aged 45-74 years from the Japan Multi-Institutional Collaborative Cohort Study were analyzed. Cortisol and cortisone levels in spot urine samples were measured using liquid chromatography-mass spectrometry. Hypertension (N = 3141) was observed among those who were older; male; current smokers; current drinkers; had T2DM, hyperlipidemia, high BMI; and low perceived stress, physical activity, and eGFR. Multiple logistic regression analysis was performed, and T2DM was associated with hypertension (odds ratio, 1.37; 95% CI, 1.14-1.66). This association varied with cortisol-to-cortisone ratio level and was more evident in participants with a higher odds ratio (2.01; 95% CI, 1.39-2.91; P = 0.040). These epidemiologic findings suggest that mineralocorticoid receptor activity and 11β-hydroxysteroid dehydrogenase regulation may play a role in hypertension among patients with T2DM, highlighting the potential for targeted treatments based on the cortisol-to-cortisone ratio.
高血压和2型糖尿病（T2DM）的发病率正在上升，二者并存会显著增加心血管疾病、中风、肾病、视网膜病变及死亡风险。盐皮质激素受体活性主要受醛固酮调节，盐皮质激素受体拮抗剂可对其进行有益调节，尤其是在与肥胖和T2DM常伴发的盐皮质激素受体相关高血压患者中。因此，盐皮质激素受体激活标志物，如11β-羟类固醇脱氢酶，可能有助于识别那些可能无法从标准高血压治疗中获益的患者。本研究调查了作为11β-羟类固醇脱氢酶活性标志物的皮质醇与可的松比值对T2DM与高血压之间关系的影响。采用横断面设计，对来自日本多机构合作队列研究的6931名45 - 74岁个体进行了分析。采用液相色谱 - 质谱法测量随机尿样中的皮质醇和可的松水平。在年龄较大、男性、当前吸烟者、当前饮酒者、患有T2DM、高脂血症、高体重指数以及低感知压力、低体力活动和低估算肾小球滤过率的人群中观察到高血压（N = 3141）。进行了多因素逻辑回归分析，T2DM与高血压相关（比值比，1.37；95%置信区间，1.14 - 1.66）。这种关联随皮质醇与可的松比值水平而变化，在比值比更高的参与者中更明显（2.01；95%置信区间，1.39 - 2.91；P = 0.040）。这些流行病学研究结果表明，盐皮质激素受体活性和11β-羟类固醇脱氢酶调节可能在T2DM患者的高血压中起作用，突出了基于皮质醇与可的松比值进行靶向治疗的潜力。
