Morocutti A, Earle K A, Rodemann H P, Viberti G C
Unit for Metabolic Medicine, UMDS, London, UK.
Diabetologia. 1997 Feb;40(2):244-6. doi: 10.1007/s001250050670.
The rate of development and progression of renal disease varies greatly in insulin-dependent diabetic (IDDM) patients. The cellular and molecular reasons for this difference are largely unknown but could be related to early cell differentiation, a phenomenon recently reported in IDDM patients with nephropathy. In this study we compared cell differentiation and cell volume between IDDM patients with and without nephropathy and investigated the cell ageing characteristics in relation to the rate of evolution of renal disease in the IDDM patients with diabetic nephropathy. Cell volume was larger and the percentage of post-mitotic fibrocytes was higher in skin fibroblasts derived from IDDM patients with diabetic nephropathy compared to those from IDDM patients without kidney disease (mean +/- SD in arbitrary units 817.3 +/- 25.7 vs 760 +/- 32.8; p = 0.005; and mean +/- SD % 33.6 +/- 11.8 vs 20.8 +/- 10; p = 0.02 respectively). Analysis of the interaction of the time to proteinuria (TTP) and the rate of change of glomerular filtration rate (GFR) with glycaemic control, arterial blood pressure and cell volume and the state of cell differentiation showed that glycated haemoglobin and the percentage of post-mitotic fibrocytes were negatively correlated to TTP (r = -0.68; p = 0.008; r = 0.52; p = 0.05 respectively) and positively associated with the rate of change of GFR (r = 0.76; p = 0.03; r = 0.56; p = 0.037 respectively). Cell volume was negatively correlated to TTP (r = -0.53; p = 0.05). Diastolic blood pressure was also related to the rate of GFR change (r = 0.56; p = 0.039). In a multiple linear regression analysis glycated haemoglobin maintained its significance independent relationship with TTP at the 1% level, while the strength of the association between the percentage of post-mitotic cells and cell volume was reduced to the 11 and 9% level, respectively. Cultured skin fibroblasts from IDDM patients with nephropathy show signs of early differentiation. Glycaemic control is a key factor in the rate of onset of proteinuria and different rates of cell ageing appear to contribute to the rate of development and progression of diabetic nephropathy. Their interaction may be responsible for the severity of renal involvement in susceptible IDDM patients.
胰岛素依赖型糖尿病（IDDM）患者中肾病的发展和进展速度差异很大。造成这种差异的细胞和分子原因在很大程度上尚不清楚，但可能与早期细胞分化有关，这是最近在患有肾病的IDDM患者中报道的一种现象。在本研究中，我们比较了有和没有肾病的IDDM患者之间的细胞分化和细胞体积，并研究了与糖尿病肾病IDDM患者肾病进展速度相关的细胞衰老特征。与无肾脏疾病的IDDM患者相比，患有糖尿病肾病的IDDM患者皮肤成纤维细胞的细胞体积更大，有丝分裂后纤维细胞的百分比更高（以任意单位计，平均值±标准差分别为817.3±25.7和760±32.8；p = 0.005；平均值±标准差百分比分别为33.6±11.8和20.8±10；p = 0.02）。对出现蛋白尿的时间（TTP）和肾小球滤过率（GFR）变化率与血糖控制、动脉血压、细胞体积及细胞分化状态之间相互作用的分析表明，糖化血红蛋白和有丝分裂后纤维细胞的百分比与TTP呈负相关（r分别为 -0.68；p = 0.008；r = 0.52；p = 0.05），与GFR变化率呈正相关（r分别为0.76；p = 0.03；r = 0.56；p = 0.037）。细胞体积与TTP呈负相关（r = -0.53；p = 0.05）。舒张压也与GFR变化率有关（r = 0.56；p = 0.039）。在多元线性回归分析中，糖化血红蛋白在1%水平上与TTP保持显著独立关系，而有丝分裂后细胞百分比与细胞体积之间关联的强度分别降至11%和9%水平。患有肾病的IDDM患者培养的皮肤成纤维细胞显示出早期分化的迹象。血糖控制是蛋白尿发作速度的关键因素，不同的细胞衰老速度似乎对糖尿病肾病的发展和进展速度有影响。它们之间的相互作用可能是导致易感IDDM患者肾脏受累严重程度的原因。
