Kidney Week 2018: Does Diabetes Increase the Risk for Renal Tumorigenesis?
Posted: Wednesday, November 21, 2018
A preclinical study recently presented at the 2018 American Society of Nephrology Kidney Week (Abstract TH-PO895) found that prolonged exposure to hyperglycemia appears to be a risk factor for acceleration of kidney cancer. Samy L. Habib, PhD, of The University of Texas Health Science Center at San Antonio, and colleagues sought to determine the effect of diabetes on mice with renal tumors.
“Our data provided in vivo evidence of [the] role of diabetes in [accelerating] kidney tumorigenesis,” concluded the authors. “These data confirmed for the first time that diabetes is a major risk factor for increasing kidney cancer.”
The study assessed the tumorigenic outcomes in four models of mice: wildtype (WT), tuberous sclerosis complex (TSC)2+/-, db/db, and TSC2+/-dbdb+/-. The TSC2+/-dbdb model was developed by researchers by cross-breeding the TSC2+/- model, which is naturally heterozygous for a mutation in tumor suppression genes, and the db/dbdb model. When evaluated after an overnight fast, the blood glucose levels of WT and TSC2+/- models were normal (80–109 mg/dL), whereas db/db and TSC2+/-dbdb models were in the hyperglycemic range (405–510 mg/dL).
At 8 months of age, WT and db/db models showed no evidence of tumor, and no significant difference in the tumor size or number was noted between TSC2+/- and TSC2+/-dbdb models. At 10 months of age, all models underwent RNA sequencing on samples isolated from the kidney cortex. The results showed differences in downregulation and upregulation patterns of multiple genes among TSC2+/-, db/db, and TSC2+/-dbdb models compared with the WT model, indicating a significant effect on the regulation of tumorigenesis. These novel data showed that, at 10 months of age, diabetes increased kidney tumor size 4-fold and kidney tumor number 2-fold in the TSC2+/-dbdb model compared with the TSC2+/- model.