AN OPEN PILOT STUDY TO EVALUATE THE EFFECTS OF METFORMIN AND LIFE STYLE

Background. The prevention of type 2 diabetes has great clinical importance. Many pharmacologic and non-pharmacologic methods are used to prevent type 2 DM. Metformin reduces the risk of developing diabetes in insulin resistant subjects. Oxidative stress plays pivotal roles in the pathogenesis and complications of diabetes mellitus. Paraoxonase 1 has antioxidant capacity.Objective. This study was planned to assess the effects of metformin and life style changes on paraoxonase activity and oxidative stress markers in premenopausal, obese, insulin resistant women.Design.Open-pilot clinical study.Subjects and methods. Thirty-two insulin resistant, premenopausal, obese women were enrolled into this clinical study. These women were treated by diet + exercise + metformin (1700 mg/d) for 6-month interval. All anthropometric characteristics, serum fasting and postprandial glucose, fasting insulin, paraoxonase, arylesterase, and malondialdehyde (MDA) levels and lipid sub-fractions were measured at the commencement and the finish of the study. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance.Results. Significantly reduced body weight, body mass index, waist circumference measurements, HOMA-IR and scrum fasting insulin, postprandial glucose, triglyceride, MDA levels and paraoxonase/high density lipoprotein cholesterol (HDL-C) ratio were observed at the end of the study compared with initial evaluations. Conversely, there were considerable increases in serum arylesterase and HDL-C levels following the treatment. Nevertheless, the increase in scrum PON-1 level was statistically insignificant. Arylesterase was inversely correlated with TC, LDL-C levels and HOMA-IR.Conclusions. Met formin treatment with intensive life-style modification may be appropriate management in premenopausal, obese, insulin resistant women who have increased propensity for the development of type 2 diabetes, although long-term, controlled studies are needed for evaluation in greater detail

Serum Fetuin-A levels, insulin resistance and oxidative stress in women with polycystic ovary syndrome.

This study was designed to determine serum Fetuin-A levels and establish whether serum Fetuin-A level is related with insulin resistance, oxidative stress, ovarian hyperandrogenism and dyslipidemia in women with polycystic ovary syndrome (PCOS). Twenty-two patients with PCOS and twenty-one healthy control women were evaluated in this controlled clinical study. Serum Fetuin-A, lipid fractions, glucose, insulin, malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD) and other hormone (gonadotropins, androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-R). The women with PCOS had significantly higher serum fasting glucose, insulin, luteinizing hormone (LH), MDA, Fetuin-A levels, and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), HOMA-IR than healthy women. However, sex hormone-binding globulin (SHBG) and GSH levels were significantly lower in patients with PCOS compared with controls. Fetuin-A was positively correlated with insulin, HOMA-IR and FAI. Multiple regression analysis revealed that FAI was strong predictor of serum Fetuin-A level. Serum Fetuin-A level was related with insulin resistance and ovarian hyperandrogenism in women with PCOS. These results suggest that Fetuin-A may have a role in triggering the processes leading to insulin resistance and androgen excess in PCOS

with polycystic ovary syndrome

This study was designed to determine serum Fetuin-A levels and establish whether serum Fetuin-A level is related with insulin resistance, oxidative stress, ovarian hyperandrogenism and dyslipidemia in women with polycystic ovary syndrome (PCOS). Twenty-two patients with PCOS and twenty-one healthy control women were evaluated in this controlled clinical study. Serum Fetuin-A, lipid fractions, glucose, insulin, malondialdehyde (MDA), myeloperoxidase (MPO), glutathione (GSH), superoxide dismutase (SOD) and other hormone (gonadotropins, androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-R). The women with PCOS had significantly higher serum fasting glucose, insulin, luteinizing hormone (LH), MDA, Fetuin-A levels, and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), HOMA-IR than healthy women. However, sex hormone-binding globulin (SHBG) and GSH levels were significantly lower in patients with PCOS compared with controls. Fetuin-A was positively correlated with insulin, HOMA-IR and FAI. Multiple regression analysis revealed that FAI was strong predictor of serum Fetuin-A level. Serum Fetuin-A level was related with insulin resistance and ovarian hyperandrogenism in women with PCOS. These results suggest that Fetuin-A may have a role in triggering the processes leading to insulin resistance and androgen excess in PCOS

syndrome

BACKGROUND: Carnitine plays essential roles in energy production, oxidative stress and glucose metabolism. This study was planned to determine serum total L-carnitine levels in non-obese women with polycystic ovary syndrome (PCOS). METHODS: There were 27 non-obese women with PCOS and 30 healthy, age- and body mass index (BMI) matched controls were evaluated in this controlled clinical study. Serum lipid sub-fractions, fasting glucose, insulin and other hormones (gonadotrophins, androgens) and total L-carnitine levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. RESULTS: The women with PCOS had significantly higher serum dehydroepiandrosterone sulfate, total testosterone, free androgen index (FAI), luteinizing hormone (LH), low-density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, fasting insulin levels and HOMA-IR measurement and LH/FSH ratios than healthy women. However, total L-carnitine and sex hormone-binding globulin (SHBG) levels were significantly lower in women with PCOS. L-Carnitine level was negatively correlated with FAI, but positively correlated with SHBG. Multiple regression analysis revealed that SHBG was a strong predictor of serum total L-carnitine level. CONCLUSIONS: Decreased total L-carnitine levels may be associated with hyperandrogenism and/or insulin resistance in non-obese women with PCOS. Long-term studies are needed to evaluate carnitine metabolism in PCOS, especially with regard to the molecular basis

Serum HLA-G levels in women with polycystic ovary syndrome

This study was designed to determine serum human leukocyte antigen-G (HLA-G) levels and establish whether serum HLA-G level is related with insulin resistance, oxidative stress, dyslipidemia and ovarian hyperandrogenism in women with polycystic ovary syndrome (PCOS). Twenty-five patients with PCOS and 23 healthy control women were evaluated in this study. Serum HLA-G, lipid fractions, glucose, insulin, malondialdehyde (MDA), glutathione (GSH), white blood cell (WBC), sex hormone-binding globulin (SHBG) and other hormone (gonadotropins and androgens) levels were measured. The estimate of insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Serum luteinizing hormone (LH), total testosterone, fasting insulin, WBC levels and LH/follicle-stimulating hormone (FSH) ratio, free androgen index (FAI) and HOMA-IR values were significantly higher in patients with PCOS compared with healthy women. However, the women with PCOS had considerably lower serum FSH, SHBG, MDA, GSH and HLA-G levels than healthy subjects. HLA-G was inversely related with HOMA-IR, FAI, LH/FSH ratio and WBC, but positively with high-density lipoprotein cholesterol. Decreased serum HLA-G level may be related with insulin resistance, ovarian hyperandrogenism and oxidative stress in women with PCOS. Nevertheless, the exact role of HLA-G in the pathogenesis of the disease remains to be elucidated

Effects of short-term transdermal hormone replacement therapy on glycaemic control, lipid metabolism, C-reactive protein and proteinuria in postmenopausal women with type 2 diabetes or hypertension.

BACKGROUND: The study was carried out to evaluate the effects of short-term transdermal hormone replacement therapy (HRT) on glycaemic control, lipid metabolism, C-reactive protein (CRP) and proteinuria in high-risk postmenopausal women. METHODS: A total of 20 well-controlled type 2 diabetic, hypertensive and 21 well-controlled glucose-tolerant, hypertensive postmenopausal women were prospectively enrolled. After 12 weeks of transdermal HRT, the changes in serum lipid sub-fractions, fasting glucose, fructosamine, glycated haemoglobin (HbA(1c)), CRP, creatinine, 24 h urine protein levels, creatinine clearance and blood pressure were evaluated. RESULTS: After 12 weeks of treatment, serum total-cholesterol and low-density cholesterols (LDL-cholesterol) appeared slightly reduced and serum triglyceride slightly elevated, although non-significantly so in both groups. The increase in HDL-cholesterol (P < 0.05) and reduction in very low density (VLDL)-cholesterol (P < 0.05) levels were significant in hypertensive patients. Elevation in the Apolipoprotein A1 (P < 0.05) and reduction in the Apolipoprotein B (P < 0.05) levels were statistically significant in all patients. HRT was associated with significant decreases in serum fasting glucose (P < 0.05) and fructosamine (P < 0.05) levels in diabetic patients. Serum HbA(1c), CRP, creatinine, 24 h urine protein levels, creatinine clearance and systolic and diastolic blood pressure did not change significantly in either group. CONCLUSIONS: There were no detrimental effects of transdermal HRT on lipid profile, glucose metabolism, CRP and urine protein levels in our well-controlled diabetic or hypertensive patients. A decision regarding HRT use should be taken on a case-by-case basis

Serum Caspase-1 levels in women with polycystic ovary syndrome.

OBJECTIVE: Caspase-1 is implicated in several important inflammatory diseases and controls adipocyte differentiation and insulin sensitivity. Interleukin-10 (IL-10) is an anti-inflammatory cytokine and plays an important role in chronic inflammatory conditions. This study was planned to determine if there is any relationship between Caspase-1 and IL-10 levels in women with PCOS. MATERIALS AND METHODS: Forty-two women with PCOS and thirty-seven healthy controls were evaluated in this controlled clinical study. Caspase-1 and IL-10 levels, serum lipid sub-fractions, fasting glucose, fasting insulin and other hormones (gonadotropins, androgens), malondialdehyde (MDA) and glutathione (GSH) levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. RESULTS: Free androgen index (FAI), HOMA-IR, MDA and Caspase-1 levels were significantly higher in subjects with PCOS. However, the women with PCOS had considerably lower GSH concentration levels than healthy subjects. Serum IL-10 levels were higher in study subjects than in controls, though it was statistically insignificant. Caspase-1 was positively associated with IL-10. CONCLUSION: These outcomes propose that Caspase-1 may have a role in triggering the processes leading to chronic low-grade inflammation in women with PCOS, independent of insulin resistance, androgen excess and oxidative stress. Nevertheless, the precise role of Caspase-1 in the pathogenesis of the disease remains to be elucidated

Serum total L-carnitine levels in non-obese women with polycystic ovary syndrome.

BACKGROUND: Carnitine plays essential roles in energy production, oxidative stress and glucose metabolism. This study was planned to determine serum total L-carnitine levels in non-obese women with polycystic ovary syndrome (PCOS). METHODS: There were 27 non-obese women with PCOS and 30 healthy, age- and body mass index (BMI) matched controls were evaluated in this controlled clinical study. Serum lipid sub-fractions, fasting glucose, insulin and other hormones (gonadotrophins, androgens) and total L-carnitine levels were measured. Homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. RESULTS: The women with PCOS had significantly higher serum dehydroepiandrosterone sulfate, total testosterone, free androgen index (FAI), luteinizing hormone (LH), low-density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, fasting insulin levels and HOMA-IR measurement and LH/FSH ratios than healthy women. However, total L-carnitine and sex hormone-binding globulin (SHBG) levels were significantly lower in women with PCOS. L-Carnitine level was negatively correlated with FAI, but positively correlated with SHBG. Multiple regression analysis revealed that SHBG was a strong predictor of serum total L-carnitine level. CONCLUSIONS: Decreased total L-carnitine levels may be associated with hyperandrogenism and/or insulin resistance in non-obese women with PCOS. Long-term studies are needed to evaluate carnitine metabolism in PCOS, especially with regard to the molecular basis