Okuma Hideyuki, Tsutsumi Takahiro, Ichijo Masashi, Kobayashi Tetsuro, Tsuchiya Kyoichiro
Department of Diabetes and Endocrinology, Graduate School of Interdisciplinary Research, Faculty of Medicine, University of Yamanashi, Yamanashi, JPN.
Department of Endocrinology and Metabolism, Toranomon Hospital, Tokyo, JPN.
Cureus. 2024 Oct 8;16(10):e71055. doi: 10.7759/cureus.71055. eCollection 2024 Oct.
Introduction The duration of diabetes mellitus (DM), blood pro-inflammatory markers, and dipeptidyl peptidase 4 (DPP4) activity are known predictors of diabetic kidney disease (DKD) progression in acute-onset type 1 DM (AT1DM) and type 2 DM. However, predictors of DKD progression in slowly progressive type 1 insulin-dependent DM (SPIDDM) have been less frequently studied. Patients and methods This retrospective cohort study included 60 patients with SPIDDM (definite) (26 men/34 women). We utilized Cox proportional hazard analyses to determine whether characteristics and laboratory findings at the time of the SPIDDM diagnosis were associated with subsequent DKD progression. The urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) at the last outpatient clinic visit served as indicators of renal function. Also, to compare blood markers in patients with SPIDDM, we included 21 patients diagnosed with AT1DM at the same department during the same period and 50 healthy adult volunteers. Results In patients with SPIDDM (definite), the multivariate Cox proportional hazard analysis revealed that the body mass index (BMI), high-sensitivity C-reactive protein (hs-CRP) levels at diagnosis, and the duration of DM prior to SPIDDM diagnosis were associated with the new onset of albuminuria and systolic blood pressure (SBP) at diagnosis, and the duration of DM prior to SPIDDM diagnosis was associated with a decline in eGFR to less than 60 ml/min/1.73 m². Additionally, serum hs-CRP levels were significantly higher in the SPIDDM (definite) group compared to both the AT1DM patients and healthy controls, suggesting a higher inflammatory state in patients with SPIDDM at the time of diagnosis. In patients with SPIDDM (definite) who were not treated with a DPP4 inhibitor, plasma DPP4 activity was associated with the new onset of albuminuria. Conclusions BMI, SBP, hs-CRP levels, DPP4 activity at SPIDDM diagnosis, and the duration of DM prior to SPIDDM diagnosis are associated with subsequent progression of DKD in SPIDDM. Also, we found that the patients with SPIDDM are often already being treated as DM for a long period of time at the time of diagnosis, which may be linked to their already high inflammatory status at the time of SPIDDM diagnosis and contribute to DKD progression. These findings underscore the importance of early diagnosis and management in preventing DKD progression in this population.
引言 糖尿病（DM）病程、血液促炎标志物及二肽基肽酶4（DPP4）活性是急性起病1型糖尿病（AT1DM）和2型糖尿病中糖尿病肾病（DKD）进展的已知预测指标。然而，缓慢进展1型胰岛素依赖型糖尿病（SPIDDM）中DKD进展的预测指标较少受到研究。
患者与方法 这项回顾性队列研究纳入了60例确诊的SPIDDM患者（26例男性/34例女性）。我们采用Cox比例风险分析来确定SPIDDM诊断时的特征和实验室检查结果是否与随后的DKD进展相关。最后一次门诊就诊时的尿白蛋白与肌酐比值（UACR）和估计肾小球滤过率（eGFR）作为肾功能指标。此外，为比较SPIDDM患者的血液标志物，我们纳入了同期在同一科室确诊的21例AT1DM患者和50名健康成年志愿者。
结果 在确诊的SPIDDM患者中，多变量Cox比例风险分析显示，体重指数（BMI）、诊断时的高敏C反应蛋白（hs-CRP）水平以及SPIDDM诊断前的DM病程与蛋白尿的新发和诊断时的收缩压（SBP）相关，且SPIDDM诊断前的DM病程与eGFR降至低于60 ml/min/1.73 m²相关。此外，与AT1DM患者和健康对照相比，确诊的SPIDDM组血清hs-CRP水平显著更高，提示SPIDDM患者在诊断时炎症状态更高。在未接受DPP4抑制剂治疗的确诊SPIDDM患者中，血浆DPP4活性与蛋白尿的新发相关。
结论 SPIDDM诊断时的BMI、SBP、hs-CRP水平、DPP4活性以及SPIDDM诊断前的DM病程与SPIDDM中随后的DKD进展相关。此外，我们发现SPIDDM患者在诊断时往往已经接受了很长时间的糖尿病治疗，这可能与其在SPIDDM诊断时已经较高的炎症状态有关，并促进DKD进展。这些发现强调了早期诊断和管理对预防该人群DKD进展的重要性。
