Division of Renal Medicine, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Medical Department III, Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany.
Department of Diabetes and Endocrinology, Sheffield Teaching Hospitals, Sheffield.
Am J Kidney Dis. 2024 Jan;83(1):18-27. doi: 10.1053/j.ajkd.2023.05.010. Epub 2023 Aug 30.
RATIONALE & OBJECTIVE: Poor glycemic control may contribute to the high mortality rate in patients with type 2 diabetes receiving hemodialysis. Insulin type may influence glycemic control, and its choice may be an opportunity to improve outcomes. This study assessed whether treatment with analog insulin compared with human insulin is associated with different outcomes in people with type 2 diabetes and kidney failure receiving hemodialysis.
Retrospective cohort study.
SETTING & PARTICIPANTS: People in the Analyzing Data, Recognizing Excellence and Optimizing Outcomes (AROii) study with kidney failure commencing hemodialysis and type 2 diabetes being treated with insulin within 288 dialysis facilities between 2007 and 2009 across 7 European countries. Study participants were followed for 3 years. People with type 1 diabetes were excluded using an established administrative data algorithm.
Treatment with an insulin analog or human insulin.
All-cause mortality, major adverse cardiovascular events (MACE), all-cause hospitalization, and confirmed hypoglycemia (blood glucose<3.0mmol/L sampled during hemodialysis).
Inverse probability weighted Cox proportional hazards models to estimate hazard ratios for analog insulin compared with human insulin.
There were 713 insulin analog and 733 human insulin users. Significant variation in insulin type by country was observed. Comparing analog with human insulin at 3 years, the percentage of patients experiencing end points and adjusted hazard ratios (AHR) were 22.0% versus 31.4% (AHR, 0.808 [95% CI, 0.66-0.99], P=0.04) for all-cause mortality, 26.8% versus 35.9% (AHR, 0.817 [95% CI, 0.68-0.98], P=0.03) for MACE, and 58.2% versus 75.0% (AHR, 0.757 [95% CI, 0.67-0.86], P<0.001) for hospitalization. Hypoglycemia was comparable between insulin types at 14.1% versus 15.0% (AHR, 1.169 [95% CI, 0.80-1.72], P=0.4). Consistent strength and direction of the associations were observed across sensitivity analyses.
Residual confounding, lack of more detailed glycemia data.
In this large multinational cohort of people with type 2 diabetes and kidney failure receiving maintenance hemodialysis, treatment with analog insulins was associated with better clinical outcomes when compared with human insulin.
PLAIN-LANGUAGE SUMMARY: People with diabetes who are receiving dialysis for kidney failure are at high risk of cardiovascular disease and death. This study uses information from 1,446 people with kidney failure from 7 European countries who are receiving dialysis, have type 2 diabetes, and are prescribed either insulin identical to that made in the body (human insulin) or insulins with engineered extra features (insulin analog). After 3 years, fewer participants receiving analog insulins had died, had been admitted to the hospital, or had a cardiovascular event (heart attack, stroke, heart failure, or peripheral vascular disease). These findings suggest that analog insulins should be further explored as a treatment leading to better outcomes for people with diabetes on dialysis.
血糖控制不佳可能导致接受血液透析的 2 型糖尿病患者死亡率升高。胰岛素类型可能会影响血糖控制，其选择可能是改善预后的机会。本研究评估了与使用人胰岛素相比，2 型糖尿病和肾衰竭接受血液透析的患者使用胰岛素类似物治疗是否与不同的结局相关。
回顾性队列研究。
在 Analyzing Data, Recognizing Excellence and Optimizing Outcomes (AROii) 研究中，2007 年至 2009 年间，来自 7 个欧洲国家的 288 家透析中心中有 733 名患者开始接受血液透析，且正在接受胰岛素治疗，确诊患有 2 型糖尿病。研究参与者随访 3 年。使用既定的行政数据算法排除 1 型糖尿病患者。
使用胰岛素类似物或人胰岛素治疗。
全因死亡率、主要不良心血管事件（MACE）、全因住院和确认的低血糖症（血液葡萄糖<3.0mmol/L，在血液透析期间采样）。
使用逆概率加权 Cox 比例风险模型估计与使用人胰岛素相比，使用胰岛素类似物的风险比。
有 713 名胰岛素类似物和 733 名人胰岛素使用者。观察到各国之间胰岛素类型存在显著差异。在 3 年时，与使用人胰岛素相比，使用模拟胰岛素的患者出现终点的百分比和调整后的危险比（AHR）分别为 22.0%和 31.4%（AHR，0.808[95%CI，0.66-0.99]，P=0.04），全因死亡率为 26.8%和 35.9%（AHR，0.817[95%CI，0.68-0.98]，P=0.03），MACE 为 58.2%和 75.0%（AHR，0.757[95%CI，0.67-0.86]，P<0.001），住院率为 58.2%和 75.0%（AHR，0.757[95%CI，0.67-0.86]，P<0.001）。与使用人胰岛素相比，模拟胰岛素在 14.1%和 15.0%（AHR，1.169[95%CI，0.80-1.72]，P=0.4）时低血糖症的发生率相似。一致性和方向在敏感性分析中都观察到了关联的强度。
残留混杂，缺乏更详细的血糖数据。
在这项针对 7 个欧洲国家的 713 名患有 2 型糖尿病和肾衰竭并接受维持性血液透析的患者的大型多国队列研究中，与使用人胰岛素相比，使用胰岛素类似物治疗与更好的临床结局相关。
患有糖尿病且因肾衰竭接受透析治疗的患者，患心血管疾病和死亡的风险较高。这项研究使用了来自 7 个欧洲国家的 1446 名患有肾衰竭、2 型糖尿病且接受人胰岛素（与体内产生的胰岛素相同）或具有工程设计的额外特性的胰岛素（胰岛素类似物）治疗的患者的信息。3 年后，接受胰岛素类似物治疗的患者中死亡、住院或发生心血管事件（心脏病发作、中风、心力衰竭或外周血管疾病）的比例较低。这些发现表明，应进一步探索胰岛素类似物作为一种治疗方法，以改善接受透析治疗的糖尿病患者的预后。
