Nerlich A G, Hagedorn H G, Böheim M, Schleicher E D
Institute for Pathology, Ludwig-Maximilians-Universität München, Germany.
In Vivo. 1998 Nov-Dec;12(6):667-70.
Contradictary results have been reported indicating both increased and reduced risks for malignancies in diabetic patients. This may possibly be due to difficulties in the clinical diagnosis of carcinomas and inaccuracies in the determination of diabetic conditions in the autopsy studies. Since glomerular microangiopathy is a typical feature of long-term diabetes, we performed a retrospective statistical analysis on 5000 consecutive, non-selected autopsy cases with particular reference to the presence/absence of microangiopathy in diabetic individuals. In our study group, we found a total incidence of 9.8% (n = 488) diabetic patients of which 213 (4.3%) had a histologically confirmed significant glomerulosclerosis and a total of 34% patients with verified carcinoma (n = 1699). The age- and sex ratios were matched between diabetic, non-diabetic and carcinoma patients. Systemic and coronary arteriosclerosis were significantly higher in diabetics than non-diabetics (p < 0.0001). Most interestingly, the rate of carcinomas in the diabetic group with nodular and diffuse glomerulosclerosis was 2.5- (p < 0.0001) and 1.9-fold (p < 0.0027), respectively, lower than in the non-diabetic group. In addition, the statistical evaluation showed in the glomerulosclerotic diabetic group significantly lower rates of metastasis. Our retrospective statistical analysis on an unselected series of autopsy cases thus provides evidence that diabetes mellitus with glomerulosclerosis is associated with a significantly lower frequency of carcinomas when compared to individuals without renal microangiopathy. Since TGF-beta is assumed to play a crucial role both in diabetes and carcinogenesis/tumor progression, our findings suggest an altered cell-matrix interaction in diabetes, possibly exerted by chronic TGF-beta overexpression.
已有相互矛盾的结果报道，提示糖尿病患者发生恶性肿瘤的风险既可能增加，也可能降低。这可能是由于临床诊断癌症存在困难，以及尸检研究中糖尿病病情判定不准确所致。由于肾小球微血管病变是长期糖尿病的典型特征，我们对5000例连续的、未经筛选的尸检病例进行了回顾性统计分析，特别关注糖尿病个体中微血管病变的有无。在我们的研究组中，共发现9.8%（n = 488）的糖尿病患者，其中213例（4.3%）经组织学证实有明显的肾小球硬化，共有34%的患者经证实患有癌症（n = 1699）。糖尿病患者、非糖尿病患者和癌症患者的年龄和性别比例相匹配。糖尿病患者的全身和冠状动脉硬化明显高于非糖尿病患者（p < 0.0001）。最有趣的是，伴有结节性和弥漫性肾小球硬化的糖尿病组癌症发生率分别比非糖尿病组低2.5倍（p < 0.0001）和1.9倍（p < 0.0027）。此外，统计评估显示肾小球硬化性糖尿病组的转移率明显较低。因此，我们对一系列未经筛选的尸检病例进行的回顾性统计分析提供了证据，表明与无肾微血管病变的个体相比，伴有肾小球硬化的糖尿病患者发生癌症的频率显著降低。由于假定TGF-β在糖尿病以及癌症发生/肿瘤进展中均起关键作用，我们的研究结果提示糖尿病中细胞与基质的相互作用发生改变，可能是由慢性TGF-β过表达所致。
