Alqallaf Alrataj, Swan Patrick, Docherty Neil G
Diabetes Complications Research Centre, Conway Institute of Biomolecular and Biomedical Research, School of Medicine, University College Dublin, Dublin, Ireland.
Expert Rev Endocrinol Metab. 2022 Nov;17(6):523-532. doi: 10.1080/17446651.2022.2131534. Epub 2022 Oct 6.
A bidirectional association exists between insulin resistance (IR) and chronic kidney disease (CKD) in Type 2 Diabetes Mellitus (T2DM). Baseline measures of IR are predictive of CKD progression, and uremia in progressive CKD is itself, in turn, associated with a worsening of IR. Pre-clinical research reveals that intrinsic IR in glomerular podocytes and the renal tubule may serve as a pathogenic driver of CKD in T2DM.
The present manuscript takes as its point of departure, the recently identified prognostic utility of severe insulin resistance as a predictor of CKD in T2DM. Findings from a series of studies describing the association of IR with pathological alterations in both established, and less commonly assessed dynamic measures of renal impairment are discussed. Drawing upon the pre-clinical mechanistic evidence base, the cellular and molecular basis of intrinsic renal IR as a promoter of CKD is considered.
Measurement of insulin sensitivity may add value to profiling of renal risk in T2DM. Rational selection of therapeutic strategies targeting the enhancement of insulin sensitivity merits special attention regarding the personalized management of CKD in insulin resistance predominant T2DM.
在2型糖尿病（T2DM）中，胰岛素抵抗（IR）与慢性肾脏病（CKD）之间存在双向关联。IR的基线测量可预测CKD的进展，而进展性CKD中的尿毒症本身又与IR的恶化相关。临床前研究表明，肾小球足细胞和肾小管中的内在IR可能是T2DM中CKD的致病驱动因素。
本手稿以最近确定的严重胰岛素抵抗作为T2DM中CKD预测指标的预后效用为出发点。讨论了一系列研究的结果，这些研究描述了IR与已确定的以及较少评估的肾功能损害动态指标的病理改变之间的关联。基于临床前机制证据，探讨了肾脏内在IR作为CKD促进因素的细胞和分子基础。
胰岛素敏感性的测量可能会为T2DM患者的肾脏风险评估增加价值。在以胰岛素抵抗为主的T2DM患者的CKD个性化管理中，合理选择旨在增强胰岛素敏感性的治疗策略值得特别关注。
