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Increased frequency of micronuclei in diabetes mellitus patients using pioglitazone and glimepiride in combination

Noor Ahmad Shaik1, Jilani Purusottapatnam Shaik, Sharique Ali

  • 1Department of Genetics, Osmania University, Hyderabad, India.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|September 28, 2010
PubMed

Insights

Long-term use of pioglitazone and glimepiride in type 2 diabetes mellitus (T2DM) patients showed a higher frequency of micronuclei, indicating genotoxicity. This suggests the micronuclei assay can monitor drug-induced genotoxicity in T2DM patients.

Area of Science:

  • Biomarkers and Toxicology
  • Genetics and Molecular Biology
  • Pharmacology and Therapeutics

Background:

  • Micronuclei frequency is a key biomarker for assessing xenobiotic-induced genotoxicity.
  • Previous studies in rats suggested potential genotoxicity of pioglitazone and glimepiride.
  • Limited data exists on the genotoxicity of combined pioglitazone and glimepiride use in type 2 diabetes mellitus (T2DM) patients.

Purpose of the Study:

  • To evaluate and compare the frequency of micronuclei in T2DM patients undergoing long-term combination therapy with pioglitazone and glimepiride versus healthy controls.
  • To determine if combined pioglitazone and glimepiride treatment influences genotoxicity as indicated by micronuclei frequency.

Main Methods:

  • A case-control study involving 127 T2DM patients on pioglitazone and glimepiride for over 5 years and 140 age-matched healthy controls.
  • Exfoliated oral mucosal cells were collected and analyzed for micronuclei using the Feulgen/Fast-Green staining method.
  • Demographic and lifestyle factors were assessed for their association with micronuclei frequency.

Main Results:

  • T2DM patients on long-term combination therapy exhibited a significantly higher frequency of micronuclei compared to the control group (p<0.001).
  • Factors like gender, diet, living area, and occupation did not show a significant association with micronuclei frequency variations.
  • The study identified a significant genotoxic effect associated with the combined use of pioglitazone and glimepiride in T2DM patients.

Conclusions:

  • Long-term combined therapy with pioglitazone and glimepiride in T2DM patients is associated with increased genotoxicity.
  • The micronuclei assay is a valuable tool for monitoring drug-induced genotoxicity in patients on long-term antihyperglycemic therapy.
  • Further research may be warranted to explore the clinical implications of this observed genotoxicity.

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