Mechanisms through which diabetes mellitus influences renal cell carcinoma development and treatment: A review of the literature

Int J Mol Med. 2016 Dec;38(6):1887-1894. doi: 10.3892/ijmm.2016.2776. Epub 2016 Oct 17.

Abstract

Renal cell carcinoma (RCC) comprises 2‑3% of all malignant tumors in adults. Many studies have established the key roles of smoking, hypertension and other components of metabolic syndrome in the occurrence of RCC. Diabetes mellitus (DM), one of the main consequences of metabolic syndrome, appears much more often in patients with RCC. The prognosis for patients suffering from both diabetes and RCC is worse than for those with kidney cancer only. Diabetes is linked to higher rate of recurrence and a greater number of distant metastases. These factors contribute to a reduction in overall survival (OS) and cause‑specific survival (CSS). Diabetes can also occur as a paraneoplastic syndrome. Tyrosine kinase inhibitors (TKIs), which are agents used in the therapy of metastatic RCC, may have unexpected effects when administered to patients with diabetes. Studies and case reports have shown that they influence blood glucose levels (BGLs) in diabetic patients, sometimes causing dangerous episodes of hypoglycemia. Hyperinsulinemia and hyperglycemia can be considered independent carcinogenic factors, as they increase the amount of pro‑inflammatory cytokines, reactive oxygen species and lipid peroxidation. TKIs have yet to be re‑evaluated as to their safety of use in patients with diabetes.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Renal Cell / epidemiology
  • Carcinoma, Renal Cell / etiology*
  • Carcinoma, Renal Cell / therapy*
  • Diabetes Complications / epidemiology*
  • Diabetes Mellitus / epidemiology*
  • Endoplasmic Reticulum Stress
  • Humans
  • Insulin Resistance
  • Kidney Neoplasms / epidemiology
  • Kidney Neoplasms / etiology*
  • Kidney Neoplasms / therapy*
  • Obesity / complications
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Risk
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors