Mehmet Bastemir

SHBG levels correlate with insulin resistance in postmenopausal women

BACKGROUND Overweight or central obesity is generally associated with increases in fasting insulin levels, insulin resistance, and glucose intolerance and has been identified as a target for new therapeutic strategies, including early change in lifestyle. Early biochemical markers for identifying at-risk patients will be useful for prevention studies. The aim of this study is to investigate whether or not SHBG level is a useful index of hyperinsulinemia and/or insulin resistance in pre- and postmenopausal obese women. At the same time, the relationship between SHBG concentrations and features of the metabolic syndrome were evaluated. METHODS 229 women were eligible for this study. MetS was defined by using a modification of the ATP III guidelines. All patients were euthyroid, obese and overweight, 25 to 69 years of age. Subjects were divided into groups of premenopausal women (n=125) and postmenopausal women (n=104). Various fatness and fat distribution parameters, SHBG, sex hormones, FSH, LH, thyroid hormones, serum levels of fasting and postprandial glucose, lipid profile, uric acid and serum insulin, and blood pressure were measured. RESULTS No significant difference was found in mean SHBG levels between pre- and postmenopausal obese women in this study (p=0.866). In premenopausal obese women, SHBG correlated negatively with BMI, waist circumference, fasting glucose, uric acid levels and FAI. In postmenopausal obese women, SHBG correlated negatively with fasting glucose, postprandial plasma glucose, fasting insulin, HOMA-IR and FAI and positively with HDL. SHBG had a significant inverse association with MetS parameters only in postmenopausal women, also after adjusting for BMI, age and estradiol. CONCLUSIONS Obesity may influence the levels of endogenous sex steroid, especially after menopause. SHBG concentrations are correlated with features of the metabolic syndrome, particularly in postmenopausal obese women. These results suggest that SHBG may be an index of insulin resistance in postmenopausal obese women.

Prevalence and risk factors for methicillin-resistant Staphylococcus aureus colonization in a diabetic outpatient population: A prospective cohort study

BACKGROUND Diabetes mellitus is a risk factor for methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection. We attempted to determine the prevalence and risk factors for MRSA colonization in a population of outpatients with diabetes. METHODS This prospective cohort study enrolled patients with diabetes. Anterior nares cultures were obtained from patients with diabetes admitted to outpatient endocrinology and metabolism clinics, and risk factors for MRSA colonization were analyzed. RESULTS Out of the 304 patients evaluated, 127 (41.9%) were colonized with S aureus and 30 (9.9%) were colonized with MRSA. Overall, 23.6% of all S aureus isolates were MRSA. In multivariate analysis, factors independently associated with an increased risk of MRSA colonization included the presence of connective tissue disease (odds ratio, 7.075; 95% confidence interval, 2.157-23.209; P = .001) and insulin therapy (odds ratio, 3.910; 95% confidence interval, 1.652-9.251; P = .002). CONCLUSIONS The prevalence of MRSA colonization in our sample of diabetic outpatients was 9.9%. Independent risk factors for MRSA colonization were the presence of connective tissue disease and insulin use. A better understanding of the epidemiology and risk factors for nasal MRSA colonization in the persons with diabetes may have significant implications for the treatment and prevention of MRSA infections.

Angiotensin-converting enzyme gene polymorphism in overweight and obese Turkish patients with insulin resistance.

The aim of this study was to analyze the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in obese Turkish patients with insulin resistance (IR). Sixty-two obese Turkish patients with IR were enrolled in this study. One hundred healthy people without IR were recruited as the control group. ACE amplification was performed by polymerase chain reaction. The frequency of the DD genotype was significantly higher in obese patients with IR than in control subjects. Of sixty-two patients, 1 (1.6%) had an II genotype, 22 (35.5%) had an ID genotype, and 39 (62.9%) had a DD genotype. The frequency of the I allele in the patient group was significantly lower than in controls. We found that the frequency of the DD genotype was higher in obese Turkish patients with IR. ACE gene I/D polymorphism may be associated with obesity in the Turkish population.

Insulin-like growth factor-I gene and insulin-like growth factor binding protein-3 polymorphism in patients with thyroid dysfunction.

BACKGROUND AND AIMS Thyroid hormones have important roles in normal growth and skeletal muscle development. IGF-I is one of the most important growth factors and is needed for the proliferation and development of thyroid cells. It stimulates fibroblasts, follicular and endothelia cells in thyroid gland. It has been shown that thyroid hormones play an important role in the regulation of IGF-I and IGFBP-3. In this study we proposed that IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphism may affect thyroid functions. For this purpose, frequency of IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphism in hypo- and hyperthyroid patients and possible role of these polymorphism in thyroid functions were investigated. METHODS This study was performed on 37 volunteer hyperthyroid and 76 hypothyroid patients as well as with 50 healthy subjects as controls. DNA isolation was applied in peripheral blood samples obtained from patients and controls. Required areas were amplified with PCR by using proper primers belonging to these gene areas from the isolated DNA samples. The products were evaluated with visualization by UV gel documentation system. RESULTS Frequency of IGF-I (CA)(19) gene polymorphism among hypothyroidism patients, hyperthyroidism patients and controls were statistically significant (chi(2) = 11.55, df = 4, p = 0.021). Genotypic variations between hyper- and hypothyroid patients were significant (chi(2) = 11.39, df = 2, p = 0.003), whereas there was no difference in IGF-I (CA)(19) gene polymorphism between the patients and controls. Differences in the IGFBP-3-202 A/C gene polymorphism between controls and hypo- as well as hyperthyroid patients were not significant. But IGFBP-3-202 A/C gene polymorphism genotype frequencies showed a significant difference between hypo- and hyperthyroid patients (chi(2) = 6.24, df = 2, p = 0.044). CONCLUSIONS These findings suggests that IGF-I (CA)(19) and IGFBP-3-202 A/C gene polymorphisms may be a risk factor for hypothyroidism.

ASSOCIATIONS BETWEEN SEX HORMONE BINDING GLOBULIN AND METABOLIC SYNDROME PARAMETERS IN PREMENOPAUSAL OBESE WOMEN

BACKGROUND AND AIMS The aim of this study was to determine sex hormone binding globulin (SHBG) concentrations in premenopausal obese women and to evaluate the relationships between sex hormones and features of the metabolic syndrome (MetS). SETTINGS AND DESIGN Retrospective cross-sectional analysis was carried out on 350 obese patients aged 25 to 69 years referred to the Department of Endocrinology, Pamukkale University in 2002-2003. MATERIALS AND METHODS 125 premenopausal euthyroid patients were eligible for this study. Subjects were divided into two groups according to the body mass index (BMI): Group I, women with BMI 2 (n = 17) and Group II,, women with BMI > or = 30 kg/m 2 (n = 108). Median SHBG concentration of Group I was 50.1 nmol/L. Group II was divided into two subgroups according to the median SHBG concentration of Group I: subjects with high SHBG levels (SHBG concentration > or = median level of the control group, i.e > or = 50.1 nmol/L) and subjects with low SHBG levels ( RESULTS No significant difference was found in mean age between the low and high SHBG groups. The low SHBG group was significantly heavier, and with higher waist circumference than the high SHBG group. In the low SHBG group, fasting glucose, postprandial glucose and gamma glutamyl transferase (GGT) and free androgen index (FAI) were significantly higher. Lipid profile, blood pressure, uric acid, insulin and HOMA were found similar between two groups. Linear regression analyses revealed that body mass index and FAI were significant, being independent predictors of SHBG concentrations in premenopausal women. (r = 0.365, r square = 0.134). CONCLUSIONS It is concluded that low SHBG concentrations may indicate visceral obesity and glucose intolerance in premenopausal women.

The PPAR-Gamma Activator Rosiglitazone Fails to Lower Plasma Growth Hormone and Insulin-Like Growth Factor-1 Levels in Patients with Acromegaly

Background/Aim: Despite combined therapy consisting of surgery, external X-ray, and medical therapy, a significant number of acromegaly patients continue to have uncontrolled growth hormone (GH) secretion and active disease. These patients, particularly those with large or invasive tumors, require additional therapy to decrease their GH levels. Our aim was to investigate whether patients with documented GH-secreting pituitary adenomas leading to acromegaly would respond with attenuation of GH and insulin-like growth factor-1 (IGF-1) levels after treatment with a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist. Methods: We conducted prospective analyses in the Endocrinology Clinic of the Pamukkale University. Acromegaly patients who had active disease participated in two admissions: before and after 6 weeks of daily treatment with 8 mg of oral rosiglitazone. Four male and 3 female patients have completed the study. Basal and nadir GH levels during an oral glucose tolerance test were determined, and the IGF-1 and IGF-binding protein-3 levels were also measured both before and 6 weeks after the rosiglitazone treatment. Results: Treatment with rosigitazone did not reduce basal and nadir GH levels during the oral glucose tolerance test and the IGF-1 levels in the patient population as a whole (p > 0.05). Conclusions: The PPAR-γ activator rosiglitazone, used at maximum approved dosage, did not reduce plasma GH and IGF-1 levels in patients with acromegaly. Further studies with higher doses and longer duration of PPAR-γ agonist administration would be required to determine its usefulness in the treatment in this group of patients.

Effect of insulin sensitivity on SHBG levels in premenopausal versus postmenopausal obese women

This study was performed to evaluate the impact of insulin sensitivity on sex hormone-binding globulin (SHBG) and sex steroids in premenopausal and postmenopausal euthyroid obese women. A total of 227 women were eligible for this study. All were euthyroid, obese, and overweight; ages ranged from 25 to 69 years. Women were divided into premenopausal (n=151) and postmenopausal (n=76) groups. SHBG, sex steroids, thyrotropin, fasting and postprandial glucose, lipid profile, uric acid, serum insulin, and blood pressure were measured. No significant difference was found in mean SHBG levels between premenopausal and postmenopausal women. The investigators observed that during transition from premenopause to postmenopause, SHBG levels increased in insulin-sensitive women in the postmenopausal group; however, SHBG levels decreased in insulinresistant women. It was concluded that SHBG blood concentration factors are likely to change during transition from premenopause to postmenopause. The positive effect of estradiol on SHBG levels is probably stronger in premenopausal women than in postmenopausal women. It has been noted that after menopause, the impact of insulin resistance on SHBG level seems more important than the effect of estradiol.

Interaction of Plasma Homocysteine and Thyroid Hormone Concentrations in the Pathogenesis of the Slow Coronary Flow Phenomenon

Background and Objective: The slow coronary flow (SCF) phenomenon is an angiographic observation and a well-recognized clinical entity characterized by delayed opacification of vessels in a normal coronary angiogram due to reasons yet unclear. Thyroid hormones exert significant effects on plasma homocysteine (Hcy) levels and microvascular resistance. Recently, several investigators have consistently reported that elevation of the plasma Hcy level can severely disturb vascular endothelial function and play a role in the pathogenesis of SCF. Accordingly, we investigated the levels of plasma Hcy and thyroid hormones and their relationship in patients with SCF. Method: Forty-four patients with angiographically proven SCF (Group I) (mean age 55.5 ± 10.4 years, 26 males) and 44 cases with normal coronary flow (NCF) pattern (Group II) (mean age 53.9 ± 11 years, 22 males) with similar risk profiles were enrolled in the study. Coronary flow patterns of the cases were determined by the thrombolysis in myocardial infarction (TIMI) frame count method. The coronary TIMI frame counts were calculated separately for each coronary artery and their average was determined as the mean TIMI frame count for each subject. Serum levels of free tri-iodothyronine (fT3), free thyroxine (fT4), thyroid stimulating hormone (TSH) and Hcy were measured. Patients with thyroid disease or on medications with a potential to affect thyroid functions were excluded. Results: There were no statistically significant differences between the groups concerning the demographic characteristics and major cardiovascular risk factors. Mean TIMI frame counts of SCF and NCF groups were 45.9 ± 12 and 23.3 ± 3.7, respectively. fT4 (ng/dl) and TSH (µIU/ml) levels of the two groups were similar (p > 0.05). The level of fT3, the active metabolite of the thyroid hormone family, was dramatically reduced in the SCF group when compared to the NCF group (2.3 ± 0.2 vs. 3.0 ± 0.3, p = 0.0001, respectively). Plasma Hcy levels of patients with SCF were found to be significantly higher than controls (12.2 ± 4.9 vs. 8.5 ± 2.9, p = 0.0001, respectively). Correlation analysis showed a significant negative correlation between the plasma fT3 and Hcy levels and the mean TIMI frame counts (r = –0.31, p = 0.003 vs. r = –0.66, p = 0.0001). Moreover, there was a significant positive correlation between the plasma Hcy levels and the mean TIMI frame counts (r = 0.58, p = 0.0001). Also, fT3 was the only significant determinant of the variance of Hcy in multiple regression analysis (r = –0.30, p = 0.005). Conclusion: fT3 levels were decreased and plasma Hcy levels were increased significantly in patients with SCF as compared to controls. This finding suggests that thyroid hormones and/or (?) a possible disturbance in their metabolism may be responsible for the elevated levels of plasma Hcy in patients with SCF and may play a role in the pathogenesis of the SCF phenomenon.

P-glycoprotein polymorphism in hypo- and hyper-thyroidism patients

P-glycoprotein (Pgp) is encoded by the multidrug resistance gene (MDR1) in humans and is the product of MDR1. It is expressed in various tissues and is related to drug distribution in intestinal erythrocytes, capillary endotel of brain, proximal tubules cells of kidneys and liver canalicular cells. Expression of Pgp is affected by Pgp polymorphism, and exon 26 C3435T polymorphism is the most common one. It has been thought that expression of Pgp is high in C-allele subjects and this situation is responsible for the resistance against some drugs and substances. Pgp may have a role in the distribution of thyroid hormones, drugs used for hypo- and hyperthyroidism and the resistance occurred. For this purpose possible relationship between T and C alleles and frequency of Pgp polymorphism as well as thyroid hormone distribution in patients with hypo- and hyperthyroidism was investigated. Thirty five hyperthyroidism patients diagnosed as Graves’ disease, 78 hypothyroidism patients diagnosed as Hashimoto’s thyroiditis and 100 healthy volunteers were included in the study. According to the results obtained no statistically significant difference was found in Pgp C3435T polymorphism between hypo- and hyperthyroidism patients. In addition, the serum free T3 levels of hyperthyroidism patients with C alleles was higher than those of subjects with T alleles. No statistically significant difference was seen in the CC, CT and TT genotype frequencies between the patients and control groups. In conclusion, it seems that Pgp polymorphism is not a predictor factor for the occurrence of hypo- and hyperthyroidism. There is a significant relationship between Pgp and the elevated serum free T3 levels of hyperthyroidism patients, and further research will help understand this situation.

GH/IGF‐1 axis in patients with subclinical hypothyroidism

Introduction Changes in thyroid status have a major effect on the GH/IGF-1 axis. Subclinical hypothyroidism occurs in 4%–10% of the general population, and is especially prevalent in elderly women. The natural history of subclinical hypothyroidism is variable; thyroid function normalizes spontaneously in some subjects, whereas it progresses to overt hypothyroidism in others. Potential risks of subclinical hypothyroidism include progression to overt hypothyroidism, dyslipidaemia, cardiovascular complications, and neurological and neuropsychiatric effects. To the best of our knowledge, there are no data about the possible influences of subclinical hypothyroidism on the GH/IGF-1 axis. Our aim was to evaluate serum concentrations of GH, IGF-1 and IGFBP-3 in patients with subclinical hypothyroidism before and after normalization of thyroid function.