Tang Yaling, Ang Lynn, Jaiswal Mamta, Dillon Brendan R, Esfandiari Nazanene H, Shah Hetal S, Spino Cathie, Plunkett Cindy, Perkins Bruce A, Pop-Busui Rodica, Doria Alessandro
Research Division, Joslin Diabetes Center, Boston, MA.
Department of Medicine, Harvard Medical School, Boston, MA.
Diabetes. 2024 May 1;73(5):751-762. doi: 10.2337/db23-0247.
Results of previous studies have suggested that cardiovascular autonomic neuropathy (CAN) may predict rapid kidney function decline among people with diabetes. We analyzed the association between baseline CAN and subsequent glomerular filtration rate (GFR) decline among individuals with type 1 diabetes (T1D) from the Preventing Early Renal Loss in Diabetes (PERL) study (N = 469) and with type 2 diabetes (T2D) from Action to Control Cardiovascular Risk in Diabetes (ACCORD) (N = 7,973). Baseline CAN was ascertained with electrocardiogram-derived heart rate variability indices. Its association with GFR slopes, rapid kidney function decline (GFR loss of ≥5 mL/min/1.73 m2/year), and ≥40% GFR loss was evaluated by linear mixed-effects, logistic, and Cox regression, respectively. Participants with CAN experienced more rapid GFR decline, by an excess 1.15 mL/min/1.73 m2/year (95% CI -1.93 to -0.37; P = 4.0 × 10-3) in PERL and 0.34 mL/min/1.73 m2/year (95% CI -0.49 to -0.19; P = 6.3 × 10-6) in ACCORD. This translated to 2.11 (95% CI 1.23-3.63; P = 6.9 × 10-3) and 1.39 (95% CI 1.20-1.61; P = 1.1 × 10-5) odds ratios of rapid kidney function decline in PERL and ACCORD, respectively. Baseline CAN was also associated with a greater risk of ≥40% GFR loss events during follow-up (hazard ratio 2.60 [95% CI 1.15-5.45], P = 0.02, in PERL and hazard ratio 1.54 [95% CI 1.28-1.84], P = 3.8 × 10-6, in ACCORD). These associations remained significant after adjustment for potential confounders, including baseline GFR and albuminuria. Our findings indicate that CAN is a strong, independent predictor of rapid kidney function decline in both T1D and T2D. Further studies of the link between these two complications may help with development of new therapies to prevent kidney function decline in patients with diabetes.
以往研究结果表明，心血管自主神经病变（CAN）可能预示糖尿病患者肾功能快速下降。我们分析了糖尿病早期肾脏损失预防（PERL）研究中1型糖尿病（T1D）患者（N = 469）以及糖尿病心血管风险控制行动（ACCORD）研究中2型糖尿病（T2D）患者（N = 7973）的基线CAN与随后肾小球滤过率（GFR）下降之间的关联。通过心电图衍生的心率变异性指标确定基线CAN。分别采用线性混合效应、逻辑回归和Cox回归评估其与GFR斜率、肾功能快速下降（GFR损失≥5 mL/min/1.73 m²/年）以及GFR损失≥40%之间的关联。在PERL研究中，患有CAN的参与者GFR下降更快，每年额外下降1.15 mL/min/1.73 m²（95% CI -1.93至-0.37；P = 4.0×10⁻³）；在ACCORD研究中为每年0.34 mL/min/1.73 m²（95% CI -0.49至-0.19；P = 6.3×10⁻⁶）。这转化为PERL研究和ACCORD研究中肾功能快速下降的优势比分别为2.11（95% CI 1.23 - 3.63；P = 6.9×10⁻³）和1.39（95% CI 1.20 - 1.61；P = 1.1×10⁻⁵）。基线CAN还与随访期间GFR损失≥40%事件的更大风险相关（PERL研究中风险比为2.60 [95% CI 1.15 - 5.45]，P = 0.02；ACCORD研究中风险比为1.54 [95% CI 1.28 - 1.84]，P = 3.8×10⁻⁶）。在对包括基线GFR和蛋白尿在内的潜在混杂因素进行调整后，这些关联仍然显著。我们的研究结果表明，CAN是T1D和T2D患者肾功能快速下降的一个强有力的独立预测因素。对这两种并发症之间联系的进一步研究可能有助于开发新的疗法来预防糖尿病患者的肾功能下降。
