Effect of saroglitazar in South Indian patients with diabetic dyslipidemia uncontrolled on a moderate-intensity statin and the association of PPAR α and γ gene polymorphisms with its response

Background: Diabetic dyslipidemia is associated with atherosclerosis risk factors and cardiovascular disease. Saroglitazar is a dual PPAR α and γ agonist approved initially for diabetic dyslipidemia and later for managing non-alcoholic steatohepatitis and hyperglycemia in T2DM. This study was conducted to estimate the association of studied PPAR α and γ gene polymorphisms among patients with diabetic dyslipidemia at baseline and with triglyceride response to saroglitazar administration. Methods: A total of 54 diabetic dyslipidemia patients who are not controlled i.e., triglycerides (TG)>200 mg/dl with moderate intensity of atorvastatin (≥10 mg) were recruited to the study. All the patients were given saroglitazar 4 mg once daily for 12 weeks. PPARα single nucleotide polymorphisms (SNPs) rs1800206, rs4253778, rs135542 and those of PPARγ gene rs3856806, rs10865710, rs1805192 were genotyped by real-time PCR. Results: 54 patients (67% female) with a mean age of 48.01±6.73 years were given saroglitazar 4 mg once daily for 12 weeks. There was a significant decrease in TG (36.9%) from baseline of 292.33±83.81mg/dl (mean±SD) to 184.46±95.90 mg/dl (<0.001) and in HbA1c (0.66%) from baseline of 8.5% to 7.8% (<0.001). PPAR α and PPAR γ gene variants did not show any association with TG lowering response. Conclusions: Saroglitazar 4mg once daily effectively decreases the TG, non-HDL-C levels, and HbA1c with no major adverse events, and TG lowering response is not associated with the studied polymorphisms.

Peroxisome proliferator-activated receptor α and γ gene polymorphisms among South Indian patients with diabetic dyslipidaemia

Background: Peroxisome proliferator-activated receptors (PPAR) α and γ genes play an important role in dyslipidaemia of T2DM. Aims: To estimate the frequency distribution of PPAR α and γ gene polymorphisms in South Indian T2DM patients with dyslipidaemia compared to healthy controls. Normative frequencies of SNPs were established and compared with data for 1000 genome populations. Methods: Eligible 382 cases and 336 age and sex-matched controls were enrolled. Six SNPs in PPARα [rs1800206 C>G (Leu162Val), rs4253778 G>C, rs135542 T>C] and PPARγ [rs3856806 (C>T), rs10865710 (C>G), rs1805192 C>G (Pro12Ala)] genes were selected for genotyping. Results: The allele and gene frequencies did not significantly differ between the diabetic dyslipidaemia cases and healthy controls. However, they were significantly different from that of 1000 genome populations except for rs1800206 C>G (Leu162Val) and rs1805192 C>G (Pro12Ala). Conclusion: The studied polymorphisms in PPARα and PPARγ genes are not associated with diabetic dyslipidaemia among South Indian patients

A novel human donor cornea preservation cocktail incorporating a thermo-reversible gelation polymer (TGP), enhancing the corneal endothelial cell density maintenance and explant culture of corneal limbal cells

Abstract Purpose McCarey-Kaufman’s (MK) medium and Optisol-GS medium are the most commonly employed media for human donor corneal preservation. In this study, we evaluated the preservation efficacy of discarded human donor corneas using a Thermo-reversible gelation polymer (TGP) added to these two media. Methods Thirteen human corneal buttons collected from deceased donors, which were otherwise discarded due to low endothelial cell density (ECD) were used. They were stored in four groups: MK medium, MK medium with TGP, Optisol-GS and Optisol-GS with TGP at 4 °C for 96 h. Slit lamp examination and specular microscopy were performed. Corneal limbal tissues from these corneas were then cultured using explant methodology one with and the other without TGP scaffold, for 21 days. Results MK + TGP and Optisol-GS + TGP preserved corneas better than without TGP, which was observed by maintenance of ECD which was significantly higher in Optisol-GS + TGP than MK + TGP (p-value = 0.000478) and corneal thickness remaining the same for 96 h. Viable corneal epithelial cells could be grown from the corneas stored only in MK + TGP and Optisol-GS + TGP. During culture, the TGP scaffold helped maintain the native epithelial phenotype and progenitor/stem cell growth was confirmed by RT-PCR characterization. Conclusion TGP reconstituted with MK and Optisol—GS media yields better preservation of human corneal buttons in terms of relatively higher ECD maintenance and better in vitro culture outcome of corneal limbal tissue. This method has the potential to become a standard donor corneal transportation-preservation methodology and it can also be extended to other tissue or organ transportation upon further validation. </jats:sec