Aim: Pioglitazone, an agonist of peroxisome proliferator-activated receptor gamma, showed various anti-atherosclerotic effects on type 2 diabetic patients. This retrospective study was done to ascertain which risk factor(s) associate with anti-atherosclerotic effects of pioglitazone.
Methods: We enrolled 160 diabetic patients treated through diet only and 62 treated with pioglitazone and annually evaluated carotid maximum (MaxIMT) and averaged intima-media thickness (AveIMT) for 2 years. We analyzed the relation of 99 single-nucleotide polymorphisms (SNP) as well as conventional risk factors with the progression or regression of carotid atherosclerosis.
Results: The D allele of the angiotensin-converting enzyme (ACE) gene and 677 allele of the methylene-tetrahydrofolate reductase (MTHFR) gene showed a significant association with increases in MaxIMT among the diabetic subjects treated through diet only. The pioglitazone-treated carriers of the D allele showed an attenuation of MaxIMT as compared with the diet-treated carriers. The pioglitazone-treated carriers of the 677T allele carriers showed a significant attenuation of MaxIMT compared with the diet-treated carriers.
Conclusions: Pioglitazone may exert anti-atherosclerotic effects on type 2 diabetics carrying the ACE gene's D allele and/or MTHFR gene's 677T allele, who showed a progression of carotid atherosclerosis without the drug.