OBJECTIVE Impaired insulin sensitivity is associated with hyperfiltration (i.e., elevated glomerular filtration rate [GFR]) in adolescents with type 2 diabetes (T2D) and adults with prediabetes. Yet, these relationships are based on studies that relied on estimated GFR (eGFR), estimates of insulin sensitivity, or both. We aimed to verify the relationship between insulin sensitivity and renal hemodynamic function by gold standard methods in adults with T2D. RESEARCH DESIGN AND METHODS Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp (M value) (glucose infusion rate in mg/kglean/min) and renal hemodynamic function by urinary inulin (GFR) and para-aminohippuric acid (effective renal plasma flow [ERPF]) clearances in participants with T2D without overt kidney disease. Filtration fraction (FF) (GFR/ERPF) was calculated. Relationships between insulin sensitivity and renal hemodynamic parameters were examined by multivariable linear regression. Renal hemodynamic parameters were examined across tertiles of M values. RESULTS We tested 44 adults with T2D, of whom 77% were male, with mean ± SD age 63 ± 7 years, BMI 31.2 ± 4.0 kg/m2, and HbA1c 7.4 ± 0.6%. Average GFR was 110 ± 26 mL/min, with an FF of 22.1 ± 2.8% and median 24-h urinary albumin excretion of 11.3 mg (interquartile range 5.8-17.0). Average M value was 5.6 ± 2.9 mg/kglean/min. Insulin sensitivity inversely correlated with GFR (r = -0.44, P < 0.01) and FF (r = -0.40, P < 0.01), and these associations remained significant after multivariable adjustments for age, sex, renin-angiotensin system inhibitor use, and HbA1c. In addition, GFR, FF, and urinary albumin excretion were highest in the participants in the lowest M value tertile. CONCLUSIONS For the first time, we demonstrate that impaired insulin sensitivity is associated with intrarenal hemodynamic dysfunction by gold standard techniques in adults with T2D treated with metformin monotherapy.

中文翻译：

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接受二甲双胍治疗的2型糖尿病和保留肾功能的成年人的胰岛素敏感性和肾血流动力学功能。

目的胰岛素敏感性受损与2型糖尿病（T2D）青少年和糖尿病前期成年人的超滤（即肾小球滤过率[GFR]升高）相关。但是，这些关系基于依赖于估计GFR（eGFR），胰岛素敏感性估计或两者的研究。我们旨在通过金标准方法验证成人T2D患者胰岛素敏感性与肾血液动力学功能之间的关系。研究设计和方法通过高胰岛素-正常血糖钳夹（M值）（以mg / kglean / min为单位的葡萄糖输注速率）评估胰岛素敏感性，并通过尿菊糖（GFR）和对氨基马尿酸（有效肾血浆流量[ERPF]评估肾血流动力学功能]）没有明显肾脏疾病的T2D参与者的清除率。计算过滤分数（FF）（GFR / ERPF）。通过多变量线性回归分析了胰岛素敏感性与肾血流动力学参数之间的关系。跨三分位数的M值检查肾血流动力学参数。结果我们测试了44位T2D成人，其中77％是男性，平均±SD年龄63±7岁，BMI 31.2±4.0 kg / m2，HbA1c 7.4±0.6％。平均GFR为110±26 mL / min，FF为22.1±2.8％，中位24小时尿白蛋白排泄为11.3 mg（四分位间距5.8-17.0）。平均M值为5.6±2.9 mg / kglean / min。胰岛素敏感性与GFR（r = -0.44，P <0.01）和FF（r = -0.40，P <0.01）成反比，并且在对年龄，性别，肾素-血管紧张素系统抑制剂的使用以及HbA1c。此外，GFR，FF，M值最低的三分位数中参与者的尿素和尿白蛋白排泄最高。结论我们首次证明，金标准技术在二甲双胍单药治疗的T2D成人中，胰岛素敏感性受损与肾内血流动力学功能障碍有关。