Primary Unresponsiveness to Pioglitazone is not Related to PPAR-ϒ and Its Co-activator Gene Exon SNP Markers
Prashant Mathur
Department of Clinical Pharmacy, Division of Pharmaceutical Sciences, SGRRITS, Dehradun, Uttarakhand-248001, India.
Poonam Punjabi
Department of Physiology, S. M. S. Medical College, Jaipur, Rajasthan, 302004, India.
Soiya Lalwani
Department of Bioinformatics, Birla Institute of Scientific Research, Statue Circle, Jaipur, Rajasthan, 302001, India.
M. Krishna Mohan
Department of Biotechnology, Birla Institute of Scientific Research, Statue Circle, Jaipur, Rajasthan, 302001, India.
Mukul Mathur
Department of Pharmacology, S. M. S. Medical College, Jaipur, Rajasthan, 302004, India.
Sandeep K. Mathur *
Department of Endocrinology, S. M. S. Medical College, Jaipur, Rajasthan, India.
*Author to whom correspondence should be addressed.
Abstract
The objective of this prospective observational study was to assess inter-individual variations in lipid and glycemic response to pioglitazone (30 mg OD) and their predictors in newly diagnosed T2DM patients. Out of 104 patients recruited, 88 completed 12 weeks follow up and were included in the final analysis. The patient characterstics studied were: BMI, W: H ratio, HbA1c, fasting and post meal glucose, lipid profile, HOMA-R, HOMA- beta and high resolution melting curve analysis (HRM) of PCR amplified DNA fragments flanking SNP markers of PPAR- γ and its co-activator gene. The mean decrease in HbA1c observed was 2.61% with wide inter-individual variation (coefficient of variance 66.44%, 95.75%, and 75.22% respectively for FPG, 2 hours PPG and HbA1c). Positive association between decrease in glycemic parameters and baseline HOMA- β, FPG, PPG HbA1c1 was observed. This finding suggest better glycemic response could be expected in those with higher beta cell function and severe hyperglycemia. Though lipid parameters improved significantly, they did not show any association with baseline characteristics studied as well as change in glycemic parameters. Eighteen (20.45%) patients were primary non-responder for glycemic, lipid and weight changes. This unresponsive could not be predicted on the basis of clinical and genetic parameters studied.
Keywords: Pioglitazone 1, Type 2 diabetes mellitus 2, glycemic response 3, PPAR-ϒ and is co-activator gene 4, Exon SNP markers 5, primary un-responsiveness 6.