Genetic polymorphisms influencing response to lithium in early-onset Bipolar disorder from south India.

OBJECTIVES: Early-onset Bipolar disorder (EOBD), has a more malignant course with high recurrence risk and there is a need for population-specific pharmaco-genomic study. METHODS: This study is a prospective and retrospective observational study. Both newly diagnosed patients and those on follow-up with a diagnosis of bipolar I disorder with onset before 18 years of age and on lithium prophylaxis as part of treatment-as-usual were recruited for the study. Response to treatment was assessed at the end of two years follow up using ALDA scale. Ten single nucleotide polymorphisms associated with treatment response based on previous studies were chosen for analysis. RESULTS: Of 162 who had EOBD, sixty-four fulfilled inclusion criteria and fifty-seven completed the study. TT and TG genotypes of rs75222709 on AL157359.3 gene were found to be significantly different between non-responders(N = 43) and healthy controls (N = 220). The frequency of the GA genotype of the single nucleotide polymorphism rs17204573 of the RORA (Retinoic Acid related orphan receptor alpha) gene was significantly lower among subjects (27.3%, N = 54) as compared to controls (42.9%, OR:0.5, CI: 0.26-0.96, p value 0.035). However, the significance of both disappeared after Bonferroni correction. Among clinical factors female gender was significantly associated with lithium non-response. CONCLUSION: Although conducting pharmaco-genomic studies with large sample size is a challenge for low and middle-income countries, future studies can help improve the long-term outcome of youth with EOBD.

Association of genetic polymorphisms in vitamin D receptor (ApaI, TaqI and FokI) with vitamin D and glycemic status in type 2 diabetes patients from Southern India.

OBJECTIVES: To evaluate the association of VDR polymorphisms (FokI, TaqI and ApaI) with vitamin D levels and glycemic status in type 2 diabetes patients from Southern India. METHODS: In this observational study, genotype frequencies and vitamin D levels of 200 cases (type 2 diabetes patients) were compared with 300 controls (unrelated anonymised stored samples of healthy volunteers) from south India. Serum 25 (OH) D levels were measured by immunoassay technique, glycated hemoglobin (HbA1c) was measured using HPLC and genotyping of VDR polymorphisms were carried out using Real time Polymerase Chain Reaction (RT PCR). RESULTS: About 69.2% of type 2 diabetes patients were found to have vitamin D deficiency. FokI polymorphism showed variations in serum 25 (OH) D levels, with AA and AG genotypes having significantly lower serum 25 (OH) D levels as compared to GG [13.24 (8.4) ng/ml, 15.02 (7.07) ng/ml and 20.67 (13.64) ng/ml respectively]. There was no difference in HbA1c levels with respect to the vitamin D levels and VDR polymorphisms. CONCLUSIONS: AA and AG genotypes of FokI polymorphisms are associated with low serum 25 (OH) D levels. However there was no association between VDR polymorphisms and glycemic status in south Indian type 2 diabetes patients.

Association of genetic polymorphisms in vitamin D receptor (ApaI, TaqI and FokI) with vitamin D and glycemic status in type 2 diabetes patients from Southern India.

OBJECTIVES: To evaluate the association of VDR polymorphisms (FokI, TaqI and ApaI) with vitamin D levels and glycemic status in type 2 diabetes patients from Southern India. METHODS: In this observational study, genotype frequencies and vitamin D levels of 200 cases (type 2 diabetes patients) were compared with 300 controls (unrelated anonymised stored samples of healthy volunteers) from south India. Serum 25 (OH) D levels were measured by immunoassay technique, glycated hemoglobin (HbA1c) was measured using HPLC and genotyping of VDR polymorphisms were carried out using Real time Polymerase Chain Reaction (RT PCR). RESULTS: About 69.2% of type 2 diabetes patients were found to have vitamin D deficiency. FokI polymorphism showed variations in serum 25 (OH) D levels, with AA and AG genotypes having significantly lower serum 25 (OH) D levels as compared to GG [13.24 (8.4) ng/ml, 15.02 (7.07) ng/ml and 20.67 (13.64) ng/ml respectively]. There was no difference in HbA1c levels with respect to the vitamin D levels and VDR polymorphisms. CONCLUSIONS: AA and AG genotypes of FokI polymorphisms are associated with low serum 25 (OH) D levels. However there was no association between VDR polymorphisms and glycemic status in south Indian type 2 diabetes patients.

Effect of Curcuma longa on vascular function in native Tamilians with type 2 diabetes mellitus: A randomized, double-blind, parallel arm, placebo-controlled trial.

Diabetes mellitus is characterized by increased central arterial stiffness and endothelial dysfunction leading to increased risk of cardiovascular complications. The aim of this study is to evaluate the effect of Curcuma longa on arterial stiffness and endothelial dysfunction in patients with type 2 diabetes mellitus. This randomized controlled trial was conducted in 136 patients of type 2 diabetes. Among them, 114 completed at least one follow-up visit and included for data analysis. Arterial stiffness parameters were measured at baseline and every month for 3 months and endothelial dysfunction markers at baseline and after 3 months of treatment with C. longa or placebo. These parameters were compared between the two groups. Both C. longa and placebo groups were comparable at baseline. After 3 months of treatment, C. longa produced significant reduction from baseline in carotid-femoral pulse wave velocity (p = .002), left brachial-ankle pulse wave velocity (p = .001), aortic augmentation pressure (p = .007), aortic augmentation index (p = .007), and aortic augmentation index at heart rate 75 (p = .018) as compared with the placebo group. Three months treatment with C. longa significantly decreases arterial stiffness as compared with placebo in type 2 diabetes mellitus patients.

Effect of metformin on exercise capacity: A meta-analysis.

AIMS: To evaluate the effect of metformin on various parameters of exercise capacity [oxygen consumption (VO2), peak oxygen consumption (VO2peak), heart rate (HR), exercise test duration, respiratory exchange ratio (RER), rating of perceived exertion (RPE), lactate and ventilatory anaerobic threshold (VAT)]. METHODS: Studies reporting change in VO2 or VO2peak after metformin administration were included. Subgroup analyses were performed as applicable. Mean difference with 95% CIs were pooled using random-effects model [RevMan (v5.3)]. RESULTS: There were no changes in VO2 and VO2peak in the overall population [VO2: n = 388, mean difference: -0.12 ml/kg/min, 95% CI: -0.74, 0.51, p = 0.71 (i2 = 0%, p = 0.99); VO2peak: n = 345, mean difference: 0.41 ml/kg/min, 95% CI: -0.51, 1.33, p = 0.38 (i2 = 0%, p = 0.89)], healthy volunteers and patients (type 2 diabetes mellitus, insulin resistance, impaired glucose tolerance/impaired fasting glucose and metabolic syndrome). For patients with insulin resistance, there was a decrease in VO2peak, but not VO2. In the overall population, there was a significant decrease in HR and RER, a significant increase in RPE, and no changes in exercise test duration and VAT. In addition, there was an increased VAT in the healthy volunteers. CONCLUSIONS: In the overall population, metformin did not affect VO2, VO2peak, exercise test duration and VAT, although it significantly decreased HR, RER and increased RPE.