Devrim Tok Devrim Tok TIP FAKÜLTESİ CERRAHİ TIP BİLİMLERİ BÖLÜMÜ KADIN HASTALIKLARI VE DOĞUM ANABİLİM DALI
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PPAR-g2 Pro12Ala polymorphism is associated with weight gain in women with gestational diabetes mellitus

Tok, Devrim | Erdal, Mehmet Emin

Objective: The polymorphisms of peroxisome proliferator–activator receptor-g2 (PPAR-g2) have been suggested to affect glucose metabolism and weight gain. Both conditions show great variations during pregnancy that makes pregnancy a suitable condition to detect any metabolic abnormalities related to PPAR-g2 polymorphisms. The objective of this study is to investigate the prevalence and metabolic impacts of PPAR-g2 polymorphism in control pregnant women and in patients with gestational diabetes mellitus (GDM). Methods: In this case-control study, anthropometric and metabolic variables of 100 non-diabetic pregnant women and of 62 women who were diagnosed as having GDM according to 100 g oral glucose tolerance test (OGTT) were compared on the basis of PPAR-g2 polymorphism by univariate analysis of covariance. Results: There were no statistically significant differences in baseline characteristics and the mean 50 g glucose challenge test values of pregnant women in both groups on the basis of PPAR-g2 genotype, although patients with Pro12Ala polymorphism were significantly taller in GDM group. The Pro12Ala polymorphism had no effect on 100 g OGTT results of patients with GDM. However, patients with GDM who had Pro12Ala polymorphism gained significantly more weight during their pregnan...

Association of insulin receptor substrate-1 G972R variant with baseline characteristics of the patients with gestational diabetes mellitus

Tok, Devrim | Erdal, Mehmet Emin

Objective: Insulin receptor substrate-1 (IRS-1) expression and tyrosine phosphorylation is decreased during pregnancy. Pregnancy may be a suitable condition to detect any abnormalities related to IRS-1 polymorphisms. Therefore, we aimed to investigate the prevalence and metabolic impacts of IRS-1 G972R polymorphism in patients with gestational diabetes mellitus (GDM). Study design: Anthropometric and metabolic variables of 62 women who were diagnosed as having GDM according to 100 g oral glucose tolerance test were compared on the basis of IRS-1 polymorphism by univariate analysis of covariance. Results: Patients with IRS-1 G972R were more obese at the beginning of pregnancy, had higher serum fasting insulin and glucose levels. Weight gain during pregnancy and insulin and glucose levels after glucose ingestion was comparable between groups. Conclusion: IRS-1 G972R was associated with the baseline characteristics of the patients with GDM, and might be related to insulin resistance that is seen in obese patients with GDM.

Evaluation of glucose metabolism and reproductive hormones in polycystic ovary syndrome on the basis of peroxisome proliferator-activated receptor (PPAR)-g2 Pro12Ala genotype

Tok, Devrim | Erdal, Mehmet Emin

BACKGROUND: Peroxisome proliferator-activated receptor (PPAR)-g2 Pro12Ala polymorphism has been suggested as a protective factor for polycystic ovary syndrome (PCOS). In this study, we aimed to investigate metabolic features and reproductive hormones in women with PCOS and compare these features with control women on the basis of Pro12Ala genotype. METHODS: This study involved 60 randomly selected women with PCOS and 60 controls. Main outcome measures were anthropometric measures, variables of glucose metabolism and reproductive hormones. All the patients were genotyped for Pro12Ala variant of PPAR-g2 gene. RESULTS: Patients with Pro12Ala polymorphism were more obese in both groups. Furthermore, they had lower fasting insulin levels, were less insulin-resistant and were less glucose-intolerant as demonstrated by 2 h glucose concentrations. However, there was no difference in reproductive hormone levels on the basis of Pro12Ala genotype. CONCLUSIONS: Both control women and women with PCOS had significant differences in glucose metabolism on the basis of PPAR-g2 Pro12Ala polymorphism. Pro12Ala variant may break the process that leads to PCOS in susceptible women, instead of being a direct causal relationship between Pro12Ala polymorphism and PCOS.

Association of Gly972Arg variant of insulin receptor substrate-1 with metabolic features in women with polycystic ovary syndrome

Tok, Devrim | Erdal, Mehmet Emin

Objective: To examine the prevalence and the effects of Gly972Arg (G972A) variant of insulin receptor substrate-1 (IRS-1) in women with polycystic ovary syndrome (PCOS). Design: Controlled clinical study. Setting: An academic clinical research center. Patient(s): Sixty women with PCOS and 60 control women matched for age. Intervention(s): Biometric measures, metabolic and hormonal measures, genetic analyses. Main Outcome Measure(s): Serum androgens, glucose, and insulin were measured. Blood leukocytes were used for genetic analyses. Result(s): The G972A variant was encountered more often in women with PCOS. The G972A carriers were more obese than their counterparts, had higher fasting insulin levels, and were more insulin-resistant. However, androgen levels did not differ on the basis of IRS-1 genotype. Conclusion(s): We observed that the G972A variant of IRS-1 was more prevalent in women with PCOS, and that it had important metabolic effects without having a direct effect on the androgen levels. However, the G972A variant of IRS-1 may modulate reproduction by lowering sex hormone–binding globulin in both healthy women and women with PCOS.

The importance of IRS-1 Gly972Arg polymorphism in evaluating the response to metformin treatment in polycystic ovary syndrome

Tok, Devrim | Erdal, Mehmet Emin

BACKGROUND: Recent evidence suggests that one of the modes of action of metformin may be through phosphorylation of the insulin receptor and insulin receptor substrates. With this in mind, we supposed that the G972A variant of insulin receptor substrate-1 (IRS-1) may modulate the response to metformin treatment in women with polycystic ovary syndrome (PCOS). METHODS: This preliminary study involved 60 randomly selected women with PCOS. All patients received dietary instructions and metformin 500mg three times daily for 6 months. Main outcome measures were androgen levels, parameters of glucose and insulin metabolism and anthropometric variables. After a second evaluation of the patients at 6 months, they were genotyped for the Gly972Arg variant of the IRS-1 gene. RESULTS: Metformin had differential effects on fasting insulin levels, insulin resistance as demonstrated by homeostasis model assessment (HOMA), LH, total testosterone, dehydroepiandrosterone sulphate and free testosterone index on the basis of IRS genotype. The response to metformin therapy in other parameters was not different according to IRS genotype. CONCLUSION: There was a differential effect of metformin therapy in PCOS women on the basis of IRS genotype. This study may call attention to the importance of molecul...