Background: Type 2 diabetes mellitus (T2DM) is a chronic disease that is characterized by impaired glucose metabolism and insulin resistance. The objectives of the study were to evaluate the pattern of leptin receptor gene polymorphism Gln223Arg in T2DM and to identify its association with the serum leptin and insulin levels as well as with insulin resistance in diabetes. Methods: In this cross-sectional study, genotyping of leptin receptor was done for Gln223Arg alleles by PCR-restriction fragment length polymorphism in 39 patients with type 2 diabetes. Serum leptin and insulin levels were assayed using enzyme linked sorbent assay in 39 cases and 45 nondiabetic controls. Insulin resistance was calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) formula. Statistical analysis was performed with Graph pad Instat version 3. Results: Hardy–Weinberg Equilibrium for the leptin receptor (LEPR) gene variants showed that alleles were in equilibrium. Leptin levels were insignificantly low in patients with diabetes compared to those in controls. Women in the control group showed significantly higher leptin levels (p < 0.05) compared with men. There was a significant difference in the serum insulin levels and insulin resistance (HOMA-IR) among patients with different genotypes (p = 0.04 and p = 0.0378, respectively). Conclusion: Leptin receptor gene polymorphism affected glucose metabolism by altering insulin resistance and pancreatic beta cells. Thus, single-nucleotide polymorphism of LEPR may affect the pathogenesis of T2DM.
Background: Diabetes mellitus is a metabolic disorder characterized by hyperglycemia due to defects in insulin secretion, insulin action, or both. Chronic hyperglycemia induces reactive oxygen species and increases oxidative stress. Human serum paraoxonase-1 (PON-1) is an enzyme synthesized in the liver, and it is an antioxidant enzyme with a beneficial role in fighting oxidative stress. The objective of the study was to compare PON-1 activity in type 2 diabetes mellitus (T2DM) and nondiabetics, as well as to find the association between PON-1 activity and different insulin resistance (IR) models in diabetics. Methods: The cross-sectional study recruited 100 diabetic and 100 age and gender-matched controls. Fasting blood glucose, insulin, and C-peptide, were assayed. PON-1 activity was measured by the spectrophotometric method. Various insulin resistance models based on insulin and C-peptide were constructed using appropriate formulae. Receiver operating characteristic was constructed to find if PON-1 can be a good marker for diabetes. Results: PON-1 activity was found to be significantly higher (p < 0.0001) in diabetics compared to controls. Highly significant hyperinsulinemia (p < 0.0001) was noted in diabetics. C-peptide levels were significantly lower in cases (p = 0.0215) as compared to controls. Homeostasis model assessment (HOMA)-IR C was insignificantly higher in cases. HOMA B cell, HOMA 1% B cell, and C-peptide-based IR (CIR) were significantly lower in cases (p < 0.0001 and p = 0.002), respectively, as compared to controls. An odds ratio of 3.15 was obtained, which suggests that the risk of T2DM is 3 times higher in subjects with elevated PON-1 levels. Chi-square showed a significant association (p = 0.0001) between DM and PON-1 levels; the chi-square statistic value (with Yates correction) was 14.49. Correlation data showed that PON-1 activity had a significant negative correlation with quantitative insulin sensitivity check index (r = −0.265, p = 0.019). A significant negative correlation (r = −0.22, p = 0.016) was also seen between PON-1 and CIR (HOMA-IR C). There was no significant correlation seen between PON-1 and other IR models. Conclusion: It can be concluded from our study that PON-1 activity is elevated in T2DM patients, which can be a beneficial marker.
Learning process can’t be made simple unless one is wakeful/attentive/aware of present situations. Worldwide, it is known fact that behavioral modulating actions of Caffeine is used in many common beverages, likewise modafinil appears to promote a possible facilitatory effect on cognitive function perhaps that is the primary reason why is it is been used in narcolepsy, obstructive sleep apnea, shiftwork and Jet lag syndrome. The rationale for conducting this animal experiment was to exploit/evaluate the vigilance promoting pharmacological actions of modafinil and compare with caffeine and rivastigmine. It promising agent for various indications like cognitive dysfunctional disorders, chronic alcoholism, attention-deficit hyperactivity disorder and schizophrenia. Two drugs modafinil 75mg/kg and caffeine 10mg/kg were used as test drugs and rivastigmine 5mg/kg as standard cognition enhancing and scopolamine 0.5mg/kg to induce amnesia in Wistar albino rats. Three different experimental models were used to screen the memory enhancing activities. The ability of the rats to retain chronic and working memory were screened by standard experiments like T-Maze and passive avoidance respectively. Morris water and T-Maze were used to test navigation and spatial task memory enhancing activities respectively. Total 72 rats were used in the study, 4 groups in each model, and 6 rats in each group. The obtained data were denoted as mean values and statistically analyzed by One-way ANOVA using SPSS 20.0 software. Both the test drugs and rivastigmine treated rats exhibited significant anti- amnesic activities among all three models compared to control (P<0.05). In passive avoidance, rivastigmine ranked maximum in memory retention abilities (17.83), whereas in modafinil treated rats showed similar results however; the rank of increased latency time (15.33 s) was not comparable with caffeine (13.17 s). In T-maze, the no. of mean correct spontaneous and rewarded alternations exhibited by caffeine and modafinil treated rats were 16.50±0.50 and 15.83±0.60 respectively and were comparable to the rivastigmine treated rats. In Morris water maze test, all three drugs caffeine, modafinil and rivastigmine treated group showed significant difference compared to the control. However, caffeine treated rats exhibited statistically significant (P<0.01) least escape latency time at probe trial compared to other groups and rats treated with modafinil showed maximum time in the probe quadrant by 27.37 s. The total amount of time spent in the probe quadrant and escape latency in caffeine and modafinil treated rats were comparable to rivastigmine treated rats.
Introduction: Leptin is an adipokine hormone that regulates insulin sensitivity and lipid profile, which may contribute to complications like gestational diabetes.The goal of the study was to examine if there was a link between the leptin (LEP)/leptin receptor (LEPR) gene polymorphism and insulin resistance in pregnant women, and to determine the extent to which the leptin gene polymorphism could cause insulin resistance.. Methods: 208 pregnant women participated in this cross-sectional study of which 74 were insulin resistant cases and 134 were insulin sensitive controls. The study was carried out from December 2018 to December 2020 at a charitable hospital in Mangalore, Karnataka, India. Genotyping of leptin and its receptor gene were carried out using the Polymerase Chain Reaction- Restriction fragment Length Polymorphism (PCR-RFLP) method. Serum levels of leptin, insulin, and C peptide were assayed using Enzyme Linked Immuno Sorbent Assay (ELISA) and lipid profile by automated chemistry analyzer. Statistical analysis was carried out using SPSS 23. Results: Insignificant association was observed between leptin receptor gene polymorphisms and insulin resistance, and leptin gene and insulin resistant women. There was no significant difference in the serum leptin levels among the cases and control (61.62±29.23 and 59.88±22.25). However, fasting blood sugar, insulin, C peptide, Triglycerides (TG), and very low-density Lipoprotein (VLDL) levels were significantly higher in cases as compared to controls (p=0.0068, p<0.0001, p<0.0001 and 0.01 respectively). Homeostatic Model Assessment for Insulin Resistance (HOMA IR) was greater in subjects with homozygous dominant, 'GG' of LEPR (p=0.0409) and hyperinsulinemia (p=0.023) as compared to other genotypes. However, hyperglycaemia was observed in subjects with homozygous dominant, ‘AA’ of leptin gene (p=0.0173). Conclusion: No significant association was found between leptin and leptin receptor gene polymorphisms with insulin resistance in pregnancy. However, genotyping of these genes may be useful in predicting insulin resistance and gestational diabetes in pregnancy.
Pediatric epilepsy comprises chronic neurological disorders characterized by recurrent seizures. Sodium valproate is one of the common antiseizure medications used for treatment. Glucuronide conjugation is the major metabolic pathway of sodium valproate, carried out by the enzyme uridine 5′-diphosphate (UDP) glucuronosyl transferase (UGT) whose gene polymorphisms may alter the clinical outcome. The objective of this study was to assess the association between UGT1A6 genetic polymorphism and clinical outcome in terms of efficacy and tolerability in pediatric epileptic patients on sodium valproate monotherapy. Pediatric epileptic patients (n=65) aged 2-18 years receiving sodium valproate monotherapy for the past one month were included. Genetic polymorphism patterns of UGT1A6 (T19G, A541G, A552C) were evaluated by PCR-RFLP. Clinical outcome was seizure control during the 6 months observation period. Tolerability was measured by estimating the hepatic, renal, and other lab parameters. Out of 65 patients, TT (40%), TG (57%), and GG (3%) patterns were observed in UGT1A6 (T19G) gene, AA (51%), AG (40%), and GG (9%) in (A541G) gene, and AA (43%), AC (43%), and CC (14%) in (A552C) gene. No statistical difference in clinical outcome was found for different UGT1A6 genetic polymorphism patterns. We concluded that different patterns of UGT1A6 genetic polymorphism were not associated with the clinical outcome of sodium valproate in terms of efficacy and tolerability. Sodium valproate was well-tolerated among pediatric patients with epilepsy and can be used as an effective antiseizure medication.
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