Abstract
IntroductionInsulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Here, the relationship of pioglitazone efficacy to single nucleotide polymorphisms (SNP) of the adiponectin gene, a critical gene directly regulated by the drug, was examined in a cohort of Chinese Han type 2 diabetic patients.MethodsEighty type 2 diabetic patients were treated with pioglitazone (15 mg/day) for 12 weeks without interruption of their current therapeutic regimen. Fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and glycated hemoglobin (HbA1c%) were collected both prior to and following pioglitazone treatment. Response to pioglitazone was defined as a decrease of at least 15% in HbA1c% levels. Three regions of the adiponectin gene containing SNPs (promoter, intron 2 and exon 2, and exon 3) were amplified and sequenced to determine genotype.ResultsSerum adiponectin levels were significantly increased (p<0.001) whereas fasting plasma glucose, fasting insulin, HOMA-IR, and HbA1c% values were significantly decreased relative to baseline measurements (p<0.001). Response of patients with TG and TT genotypes at rs2241766 (exon2; 52.9% vs. 12.7%, respectively p = 0.001) was statistically significant relative to all other patients. Amongst rs2241766 TG and TT patients, the mean decrease in HbA1c% levels was greater where the genotype was TG (1.15±0.80 vs. 0.52±0.64, p = 0.001).ConclusionsThe adiponectin gene polymorphism rs2241766 T/G is associated with pioglitazone efficacy in type 2 diabetic patients, and status of the polymorphism may be an important clinical factor to consider prior to pioglitazone treatment.
Highlights
Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients
Type 2 diabetes mellitus (T2DM) was diagnosed according to the World Health Organization criteria from 1999: (1) random plasma glucose$11.1 mmol/L, fasting plasma glucose (FPG) $7.0 mmol/L, or 2-hour oral glucose tolerance test result was $11.1 mmol/L; (2) symptomless: repeat the test a second time on a different day to confirm the diagnosis; (3) any stress that causes the level of blood glucose to temporarily rise was excluded
The primary measure of pioglitazone efficacy was that the change in serum ADIPOQ concentration significantly increased from 3.42 mg/l to 5.67 mg/l (p,0.001)
Summary
Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Alternative therapeutic strategies are necessary, as patients are known to develop resistance to treatment with insulin. Regulation of the gene is known to occur at least in part through the nuclear receptor transcription factor, peroxisome proliferator activated receptor c (PPARc) [3]. Pharmacological compounds, such as the thiazolidinediones (TDZ), that target PPARc activity have been exploited as insulin sensitizers, and are widely used for the treatment of insulin resistance in T2DM patients
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