Peking University Clinical Research Institute, Peking University First Hospital, Beijing, People's Republic of China; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Department of Pharmacy, Peking University Third Hospital, Beijing, People's Republic of China.
Am J Kidney Dis. 2023 Sep;82(3):267-278. doi: 10.1053/j.ajkd.2023.03.007. Epub 2023 May 13.
RATIONALE & OBJECTIVE: To characterize associations between long-term visit-to-visit variability of hemoglobin A (HbA) and risk of adverse kidney outcomes in patients with diabetes.
Observational study.
SETTING & PARTICIPANTS: 93,598 adults with diabetes undergoing routine care in Stockholm, Sweden.
Categories of baseline and time-varying HbA variability score (HVS, the percentage of total HbA measures that vary by>0.5% [5.5mmol/mol] during a 3-year window): 0-20%, 21%-40%, 41%-60%, 61%-80%, and 81%-100%, with 0-20% as the reference group.
Chronic kidney disease (CKD) progression (composite of>50% estimated glomerular filtration rate [eGFR] decline and kidney failure), acute kidney disease (AKI by clinical diagnosis or transient creatinine elevations according to KDIGO criteria), and worsening of albuminuria.
Multivariable Cox proportional hazards regression.
Compared with persons showing low HbA variability (HVS 0-20%), any increase in variability was associated with a higher risk of adverse kidney outcomes beyond mean HbA. For example, for patients with a baseline HbA variability of 81%-100%, the adjusted HR was 1.6 (95% CI, 1.47-1.74) for CKD progression, 1.23 [1.16-1.3] for AKI, and 1.28 [1.21-1.36] for worsening of albuminuria. The results were consistent across subgroups (diabetes subtypes, baseline eGFR, or albuminuria categories), in time-varying analyses and in sensitivity analyses including time-weighted average HbA or alternative metrics of variability.
Observational study, limitations of claims data, lack of information on diet, body mass index, medication changes, and diabetes duration.
Higher long-term visit-to-visit HbA variability is consistently associated with the risks of CKD progression, AKI, and worsening of albuminuria.
PLAIN-LANGUAGE SUMMARY: The evidence for current guideline recommendations derives from clinical trials that focus on a single HbA as the definitive measure of efficacy of an intervention. However, long-term visit-to-visit fluctuations of HbA may provide additional value in the prediction of future kidney complications. We evaluated the long-term fluctuations in glycemic control in almost 100,000 persons with diabetes undergoing routine care in Stockholm, Sweden. We observed that higher long-term HbA fluctuation is consistently associated with the risks of chronic kidney disease progression, worsening of albuminuria and acute kidney injury. This finding supports a role for long-term glycemic variability in the development of kidney complications and illustrates the potential usefulness of this metric for risk stratification at the bedside beyond a single HbA test.
本研究旨在描述血红蛋白 A（HbA）长期随访间变异性与糖尿病患者不良肾脏结局风险之间的关联。
观察性研究。
在瑞典斯德哥尔摩接受常规治疗的 93598 名糖尿病患者。
基线和时变 HbA 变异评分（HVS，HbA 测量值在 3 年窗口期内变化>0.5%[5.5mmol/mol]的总 HbA 测量值的百分比）的类别：0-20%、21%-40%、41%-60%、61%-80%和 81%-100%，以 0-20%作为参考组。
慢性肾脏病（CKD）进展（估算肾小球滤过率[eGFR]下降>50%和肾衰竭的复合终点）、急性肾损伤（AKI 根据临床诊断或 KDIGO 标准的短暂肌酐升高）和白蛋白尿恶化。
多变量 Cox 比例风险回归。
与 HbA 变异性较低的患者（HVS 0-20%）相比，HbA 变异性的任何增加都与平均 HbA 以外的不良肾脏结局风险增加相关。例如，基线 HbA 变异性为 81%-100%的患者，CKD 进展的调整 HR 为 1.6（95%CI，1.47-1.74），AKI 为 1.23（1.16-1.3），白蛋白尿恶化的为 1.28（1.21-1.36）。结果在亚组（糖尿病亚型、基线 eGFR 或白蛋白尿类别）、时变分析以及包括时间加权平均 HbA 或变异性替代指标的敏感性分析中均一致。
观察性研究、索赔数据的局限性、缺乏有关饮食、体重指数、药物变化和糖尿病病程的信息。
HbA 的长期随访间变异性越高，与 CKD 进展、AKI 和白蛋白尿恶化的风险呈正相关。
目前指南推荐的证据来源于侧重于单一 HbA 作为干预疗效的明确衡量标准的临床试验。然而，HbA 的长期随访间波动可能在预测未来肾脏并发症方面提供额外的价值。我们评估了近 100000 名在瑞典斯德哥尔摩接受常规治疗的糖尿病患者的长期血糖控制波动情况。我们观察到，HbA 的长期波动与慢性肾脏病进展、白蛋白尿恶化和急性肾损伤的风险呈正相关。这一发现支持长期血糖变异性在肾脏并发症发展中的作用，并说明了该指标在床边除了单次 HbA 测试之外进行风险分层的潜在有用性。
