Department of Clinical Therapeutics, National and Kapodistrian University of Athens Medical School, Athens, Greece.
Hypertens Res. 2023 Jun;46(6):1516-1524. doi: 10.1038/s41440-023-01192-3. Epub 2023 Jan 23.
The causative associations between glycemia and early alterations in renal and vascular function remain unclear. To examine the interplay among glycemia, renal function, and markers of subclinical atherosclerosis in apparently healthy subjects. Nondiabetic (30-60 years old) individuals (n = 205) without chronic kidney disease or cardiovascular disease were consecutively recruited from a cardiovascular prevention clinic. All subjects underwent arterial stiffness assessment by measuring the carotid-femoral pulse wave velocity (cfPWV). Glomerular filtration rate (GFR) was estimated by CKD-EPI equation. Study procedures were identical in the two visits (median follow-up 66 months). We employed structural equation modeling (SEM) analysis to investigate the directionality of associations. Baseline fasting plasma glucose (FPG) was independently and inversely associated with GFR (p = 0.008). GFR was significantly associated with cfPWV (p < 0.001) at baseline. By SEM analysis decreasing baseline GFR directly correlated with increasing cfPWV (p = 0.003) whereas FPG correlated with cfPWV indirectly through GFR (mediation) (P = 0.032). FPG did not mediate the effect of GFR on cfPWV (P = 0.768). SEM analysis of longitudinal data revealed bidirectional correlations between changes in FPG and GFR (P < 0.001). Alterations in GFR were directly related to changes in cfPWV (p < 0.001) whereas FPG only indirectly correlated with cfPWV through GFR changes (P = 0.002). In apparently healthy nondiabetic subjects, the association between baseline or longitudinal glycemia levels and arterial stiffening was indirect, consistently mediated by renal function status. These findings provide the first clinical evidence supporting the directionality between kidney function and glycemia in nondiabetic subjects leading to vascular dysfunction. In apparently healthy nondiabetic subjects, without cardiovascular disease or chronic kidney disease, the association between baseline or longitudinal glycemia levels and arterial stiffening was indirect, consistently mediated by renal function status.
血糖与早期肾功能和血管功能改变之间的因果关系尚不清楚。为了研究血糖、肾功能和亚临床动脉粥样硬化标志物在看似健康的个体中的相互作用。从心血管预防诊所连续招募了 205 名无慢性肾脏病或心血管疾病的非糖尿病（30-60 岁）个体。所有受试者均通过测量颈股脉搏波速度（cfPWV）评估动脉僵硬度。通过 CKD-EPI 方程估计肾小球滤过率（GFR）。两次就诊的研究程序相同（中位随访 66 个月）。我们采用结构方程模型（SEM）分析来研究关联的方向性。空腹血糖（FPG）与 GFR 呈独立负相关（p=0.008）。GFR 与基线时的 cfPWV 显著相关（p<0.001）。通过 SEM 分析，基线时 GFR 的降低与 cfPWV 的增加直接相关（p=0.003），而 FPG 通过 GFR（中介）与 cfPWV 间接相关（P=0.032）。FPG 不能介导 GFR 对 cfPWV 的影响（P=0.768）。纵向数据分析的 SEM 显示 FPG 和 GFR 之间的变化呈双向相关（P<0.001）。GFR 的变化与 cfPWV 的变化直接相关（p<0.001），而 FPG 仅通过 GFR 变化与 cfPWV 间接相关（P=0.002）。在看似健康的非糖尿病个体中，基线或纵向血糖水平与动脉僵硬之间的关联是间接的，始终由肾功能状态介导。这些发现为肾功能和血糖在非糖尿病个体中导致血管功能障碍的方向提供了首例临床证据。在没有心血管疾病或慢性肾脏病的看似健康的非糖尿病个体中，基线或纵向血糖水平与动脉僵硬之间的关联是间接的，始终由肾功能状态介导。
