Serdar Guler

Insulin Resistance in Nonobese Patients with Polycystic Ovary Syndrome

Objectives: Most patients with polycystic ovary syndrome (PCOS) are obese and known to have insulin resistance. Obesity per se is a cause of insulin resistance. This study was performed to determine whether insulin resistance occurs in patients with PCOS in the absence of obesity and acanthosis nigricans. Method: For this purpose, an euglycemic hyperinsulinemic clamp study was performed in 12 nonobese patients with PCOS and in 10 healthy control subjects matched for age and weight. Results: The mean serum testosterone and luteinizing hormone (LH) levels were significantly elevated (4.09 ± 1.32 vs. 1.18 ± 0.53 pg/ml, p < 0.001, and 11.63 ± 5.37 vs. 4.98 ± 2.73 mIU/ml, p < 0.001, respectively), and the serum sex hormone binding globulin level was significantly reduced (40.96 ± 14.94 vs. 73.98 ± 30.40 nmol/l, p < 0.001) in patients with PCOS as compared with the values in control subjects. The mean serum insulin level was also elevated in patients with PCOS as compared with control subjects (32.33 ± 4.98 vs. 19.56 ± 2.21 µU/ml, p < 0.05). The insulin sensitivity was lower in patients with PCOS as compared with the control subjects (200 ± 27.8 vs. 427.8 ± 88.9 µmol kg–1min–1, p < 0.001). In patients with PCOS, the serum levels of free testosterone (r = –0.89, p < 0.001) and LH were inversely correlated with the insulin sensitivity (r = –0.63, p < 0.05). Serum follicle-stimulating hormone, prolactin, and dehydroepiandrosterone sulfate levels were similar in both groups. Conclusions: These results indicate that a significant degree of insulin resistance exists in nonobese patients with PCOS and that this insulin resistance is significantly related to serum LH and free testosterone levels. Thus, measures to decrease insulin resistance may have to be considered earlier to decrease the potential risks of developing diabetes mellitus and coronary artery disease at later ages of life in these patients.

Plasma Soluble Intercellular Adhesion Molecule 1 Levels Are Increased in Type 2 Diabetic Patients with Nephropathy

Background/Aim: Intercellular adhesion molecule 1 (ICAM-1) is a mediator in the recruitment of leukocytes in the glomerular cells. The role of ICAM-1 in diabetic complications is still a matter of debate. This study was performed to investigate the relation of plasma soluble ICAM-1 (sICAM-1) to nephropathy in patients with type 2 diabetes mellitus. Methods: Ninety-three patients (24 males and 69 females) with type 2 diabetes mellitus were included into the study. Fifty patients had nephropathy, and 43 were free from nephropathy. Fifty healthy subjects (14 males and 36 females) served as the control group (group 1). Twenty-five of the diabetic patients had microalbuminuria (group 2), 25 had macroalbuminuria (group 3), and 43 had neither micro- nor macroalbuminuria (group 4). The plasma sICAM-1 levels were measured in blood samples drawn after fasting. Results: The mean plasma sICAM-1 levels were not different in the 93 diabetic patients as compared with the healthy controls (392.7 ± 119.5 vs. 350.1 ± 90.2 ng/ml, p > 0.05). The mean sICAM-1 level was significantly higher in the diabetic patients with nephropathy than in those without nephropathy (430.3 ± 78.2 vs. 368.2 ± 122.5 ng/ml, p = 0.03) and in the controls (430.3 ± 78.2 vs. 350.1 ± 90.2 ng/ml, p = 0.016). The difference in sICAM-1 levels between groups 2 and 3 was not significant (p > 0.05). The plasma sICAM-1 levels were significantly higher in both groups 2 and 3 than in both groups 1 and 4 (434.5 ± 129.2 vs. 427.2 ± 113.7 ng/ml and 368.2 ± 122.5 vs. 350.1 ± 90.2 ng/ml, respectively). Conclusions: The plasma sICAM-1 levels in patients with type 2 diabetes mellitus are not significantly different from those in nondiabetic subjects. High levels of sICAM-1 suggest that sICAM-1 may play a role in the development of nephropathy in patients with type 2 diabetes mellitus.

Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria

OBJECT Acromegaly is a disease that has significant morbidity and mortality related to high levels of growth hormone (GH) and insulin-like growth factor-I (IGF-I), and is usually caused by pituitary adenomas. The goal in this study was to investigate the role of endoscopic transsphenoidal surgery and surgical experience in the treatment of GH adenoma cases in relation to surgical results and hormonal cure rates, and to perform a review of the literature. METHODS The authors present a retrospective analysis of 214 GH adenoma cases. Restoration of IGF-I levels to normal for age and sex, suppression of GH levels below 0.4 μg/L on the oral glucose tolerance test, and demonstration of the total removal of the tumor on MRI studies obtained after administration of contrast material at the 3-month postoperative follow-up visit were the criteria for cure. RESULTS In total 214 patients with a mean age of 41.9 ± 12 years (range 17-75 years) and a male/female ratio of 106/108 were enrolled in the study. Cure was achieved in 134 (62.6%) of 214 patients. One hundred sixty-nine patients were primary cases, and of these 109 (64.5%) were cured, whereas 61 patients were previously operated cases and of these 25 (41%) were cured. With a 51.1% decrease in the 1st month postoperatively, IGF-I levels were found to be predictive of cure (74.4% sensitivity and 73.7% specificity). Cut-off values for GH levels in predicting cure for the 1st day, 1st week, and 1st month postoperatively were 2.33, 2.05, and 2.25 μg/L, respectively. The cut-off value for surgical experience was 57 for primary surgeries (58.5% cure rate before this cut-off value compared with 72.6% after it; p = 0.025) and 108 for all operations (45.8% vs. 79.4%, p = 0.037). Although 28 patients were found to be in remission according to the criteria in 2000, they were not in remission according to the new consensus criteria. Nine of these cases (32.1%) had random GH levels < 1 μg/L at the 1-year follow-up. The 1-year IGF-I and GH levels in these 28 patients showed no significant difference when compared with the cases defined as cured according to the current criteria. CONCLUSIONS In acromegaly treatment, transsphenoidal endoscopic surgery performed by an expert senior surgeon and increased surgical experience are important for higher cure rates. Random GH levels < 2.33 μg/L after the 1st day postoperatively and a > 50% decrease in IGF-I levels after the 1st month postoperatively are predictive of cure. Moreover, there is no urgency for additional therapy in patients with GH levels of 0.4-1 μg/L and MRI sequences showing no tumor at the 3-month follow-up, because for these cases remission can be achieved at the 1-year follow-up.

The Value of Fine-Needle Aspiration Biopsy in Subcentimeter Thyroid Nodules

BACKGROUND The need to perform fine-needle aspiration biopsy (TFNAB) on subcentimeter thyroid nodules is less clear than for larger nodules. We compared the ultrasonographic features of thyroid nodules less than and greater than one centimeter and correlated this information with the cytological results for TFNAB and the final histopathological diagnosis in selected patients. METHODS We evaluated 520 thyroid nodules (247 subcentimeter [group 1], 273 supracentimeter [group 2]) in 426 patients. Ultrasonography-guided fine-needle aspiration biopsy was performed on all nodules. Surgery was recommended for patients with TFNAB results that were read as malignant or suspicious. The results of ultrasonography, TFNAB, and histopathology were compared between the groups. RESULTS Out of 426 patients, 337 had one nodule, 84 had two, and five had three. There was indeterminate cytology in 20 cases, 10 from each group. Inadequate cytology was obtained in 41/247 (16.6%) nodules in group 1 and 61/273 (22.3%) nodules in group 2, and the difference in rate was not significant (p = 0.067). The malignancy rate as determined by TFNAB was 4.9% in group 1 and 1.5% in group 2 (p < 0.025). In patients who underwent surgery for thyroid nodules the malignancy rate was 6% in group 1 and 2.9% in group 2 (p = 0.08). Hypoechoic pattern, microcalcification, and a long axis/short axis ratio (LA/SA) of < 1.5 were associated with malignancy in subcentimeter thyroid nodules (group 1), while only a hypoechoic pattern was associated with malignancy in supracentimeter thyroid nodules (group 2). CONCLUSIONS The incidence of cancer in thyroid nodules < 1 cm does not appear to be lower than in larger nodules and may even be higher. Physicians should consider obtaining biopsy samples from subcentimeter hypoechoic nodules that contain microcalcification and have a relatively round shape (LA/SA < 1.5).

Relation of Leptin and Tumor Necrosis Factor α to Body Weight Changes in Patients with Pulmonary Tuberculosis

In this study we investigated whether leptin and TNFα levels change with improvement in body weight with antituberculotic therapy in active tuberculosis patients. 30 patients (8 females and 22 males) with active pulmonary tuberculosis formed the patient group, and 25 sex- and age-matched healthy subjects (8 females and 17 males) served as the control group. Body weight, body mass index (BMI) and serum leptin and plasma TNFα levels are measured before and in the sixth month of therapy in all patients. Before the initiation of therapy, BMI of the patients was significantly lower than BMI of the controls (20.2 ± 1.6 vs. 25.2 ± 2.7 kg/m2, respectively; p < 0.05). After treatment, BMI of the patients increased significantly to 21.4 ± 1.9 kg/m2 (p < 0.05), but was still lower than that of the controls (p < 0.05). Pretreatment serum leptin (4.5 ± 0.9 vs. 2.1 ± 0.2 ng/ml, respectively; p < 0.05) and plasma TNFα (27.9 ± 3.4 vs. 23.9 ± 3.0 pg/ml, respectively; p < 0.05) levels of the patients were significantly higher than those of the controls. After treatment, serum leptin levels increased to 6.7 ± 2.2 ng/ml, but this rise was not statistically significant (p > 0.05). Treatment did not result in any significant change in TNFα levels, either. Δ leptin was highly related to Δ BMI in patients with tuberculosis (r = 0.68, p = 0.02). In the pretreatment period, there was a significant correlation between leptin and TNFα levels in the whole patient group (r = 0.78, p < 0.001), and in female (r = 0.74, p < 0.001) and male patients separately (r = 0.74, p = 0.035). In conclusion, leptin and TNFα may be responsible for the weight loss in pulmonary tuberculosis patients, but their levels do not change with improvement in body weight with antituberculotic treatment.

Compatibility of different methods for the measurement of visceral fat in different body mass index strata.

PURPOSE Obesity, particularly visceral obesity, is associated with increased risk of cardiovascular morbidity and mortality. Therefore, cardiovascular risk should be determined by evaluating visceral fat tissue not only in obese individuals but also in non-obese individuals. We aimed to evaluate the comparison of visceral fat tissue measurement methods with computed tomography (CT). MATERIALS AND METHODS One hundred four participants, 19 to 58 years of age (21 males, 83 females) were enrolled in this study. Participants underwent anthropometric evaluation, bioelectrical impedance analysis (BIA), ultrasonography (US), and CT examinations on the same day. RESULTS The mean body mass index (BMI) was 31.2 +/- 8.7 kg/m2 (73 individuals [70.2%] had BMI > or =30, and 31 individuals [29.8%] had BMI < 30). The non-obese group (BMI < 30) that showed the best correlation coefficient values were for visceral fat area (VFA) by BIA in all participants, males and women (r = 0.902, P < 0.001; r = 0.994, P < 0.001; r = 0.645, P = 0.01, respectively); in case of BMI > or =30 the best correlation coefficient values were for VFA by BIA (r = 0.774, P < 0.001) for all participants, and visceral fat thickness by US for males (r = 0.851, P < 0.001), and BMI (r = 0.786, P < 0.001) for females. Using multiple stepwise regression analysis, the methods best reflecting VFA by CT were as follows: In subjects with BMI < 25, BIA correlated best with CT measures of VFA; while in subjects with BMI > 30 waist-to-hip ratio showed the best correlation with CT measures of VFA. The method best reflecting VFA by CT was visceral thickness by US in males; and the method best reflecting VFA by CT in females was visceral thickness by US, BMI and waist circumference. CONCLUSION Anthropometric measurements and visceral fat tissue measurement methods such as US and BIA exhibit differences with respect to compliance with CT results in visceral fat tissue measurements by gender and BMI levels.

Skin findings in thyroid diseases

BACKGROUND In cases of thyroid diseases, many of the symptoms arise on the skin. In this study, we aimed to detect and compare the skin findings and accompanying dermatoses of patients with thyroid diseases. MATERIALS AND METHODS 220 patients with thyroid diseases, who did not have any medical cure, and 90 healthy individuals as a control group attended our study. All of the cases were examined, and the skin findings and/or dermatoses were recorded. The skin findings in the patients and the control group were compared statistically. RESULTS Among 220 cases, in 125 (56.8%) skin findings were detected. The most frequently observed skin findings were chronic urticaria (6.8%), vitiligo (6.8%), diffuse alopecia (6%), acne vulgaris (5%) and acne rosacea (3.6%). No significant difference was detected statistically between the patients and control group in terms of skin findings. When compared for the presence of each dermatosis, chronic urticaria, vitiligo and pruritus were found to be significantly higher in the patient group with thyroid diseases than in the control group. In terms of the presence of skin findings, no statistical difference was detected between autoimmune hyperthyroidism and non-autoimmune hyperthyroidism, between autoimmune hypothyroidism and non-autoimmune hypothyroidism, or between autoimmune euthyroidism and non-autoimmune euthyroidism. Chronic urticaria, vitiligo, and diffuse alopecia were found to be significantly higher in patients with autoimmune thyroid diseases than in the control group. Vitiligo and diffuse alopecia were found to be higher in autoimmune hyperthyroidism patients than in the control group. Vitiligo was found to be significantly higher in autoimmune hypothyroidism patients than in the control group. CONCLUSION To our knowledge, no report investigating the skin findings among thyroid diseases exists in literature. We believe this study would provide data for further studies.

Is insulin lispro safe in pregnant women : Does it cause any adverse outcomes on infants or mothers?

AIM To determine the rate of major congenital anomalies and complications retrospectively in offspring of women with diabetes mellitus treated insulin lispro. MATERIAL AND METHODS Twenty-seven patients had used insulin lispro (ILYS) and 59 patients had used regular human insulin (RHI) during the pregnancy period were evaluated. We also evaluated and analyzed the results of 53 of the 86 women who had gestational diabetes mellitus only. They were not using insulin aspart or insulin glarjine. We evaluated the birth weight, congenital anamolies, mode of delivery, abortus and stillbirth rates. RESULTS Mean HbA1c level was 6.27+2.23 for ILYS group and 7.07+2.09 for RHI group (p: 0.067). The duration of diabetes, gestational age, mode of delivery, type of diabetes, number of liveborn, stillbirth and miscarriages were not stastically different between all groups (p>0.05). Nine (15.25%) of 59 infants treated with RHI had congenital anomalies and one stillborn. The infants in ILYS-receiving group had no congenital anomalies but one pregnant (3.70%) had a stillborn. The difference in incidence of congenital anomalies between those using ILYS and RHI was not statistically significant (p: 0.157). There was also no difference in respect to congenital anomalies of gestational diabetic groups which used either ILYS or RHI. CONCLUSION Major congenital anomalies for offspring of mothers treated with ILYS are similar with RHI group. Although HbA1c levels were lower in ILYS group, all outcomes are similar with RHI. So ILYS is an alternative choice in treatment of pregnant women with DM.

Evaluation of Ovarian Reserve Based on Hormonal Parameters, Ovarian Volume, and Antral Follicle Count in Women with Type 2 Diabetes Mellitus

OBJECTIVE The aim of this study was to evaluate ovarian reserve of women with type 2 diabetes mellitus (T2DM). METHODOLOGY Eighty-nine women with T2DM and 73 healthy controls were enrolled and divided into three age groups [group 1 (20-29 yr), seven diabetics and 18 healthy controls; group 2 (30-39 yr): 35 diabetics and 35 healthy controls; and group 3 (40-49 yr): 47 diabetics and 20 healthy controls]. All participants were subjected to transvaginal ultrasonographic examination on the third day of their menstrual periods for the determination of ovarian volume and total antral follicle count (AFC). RESULTS A significant difference in mean FSH levels (international units per liter) was observed between women with diabetes and healthy controls in all age groups (group 1, 7.8 ± 0.9 vs. 5.0 ± 1.0; group 2, 8.2 ± 1.1 vs. 7.2 ± 1.8; group 3, 9.5 ± 3.2 vs. 6.4 ± 2.4; P < 0.001 for all). Similarly, mean AFC was significantly lower in patients with T2DM than in healthy controls in all age groups (group 1, 21.1 ± 4.8 vs. 25.0 ± 9.1; group 2, 10.4 ± 5.2 vs. 23.0 ± 9.5; group 3, 6.0 ± 3.5 vs. 21.7 ± 2.1; P < 0.001 for all). A statistically significant difference in total ovarian volume was only observed in group 1 (9.7 ± 3.0 in T2DM patients vs. 6.8 ± 2.7 in healthy controls; P = 0.002). AFC was found to be negatively correlated with FSH (r = -0.406, P < 0.001), age (r = -0.618, P < 0.001), glycolized hemoglobin (r = -0.505, P < 0.001), and fasting blood glucose (r = -0.687, P < 0.001). CONCLUSION In this pioneer study, the first to evaluate ovarian reserve in T2DM patients, we managed to demonstrate lower ovarian reserves in women with diabetes compared with healthy controls.

Gestational diabetes and subclinical inflammation: Evaluation of first year postpartum outcomes

AIM The aim of this study was to evaluate the relationship between sublinical inflammation and glycemic status in patients with gestational diabetes mellitus (GDM). METHODS Sixty-one patients with GDM and 40 healthy pregnant women were included in the study. Fasting blood glucose (FBG), insulin, high sensitivity C-reactive protein (hsCRP), lipid parameters and carotid artery intima-media thickness (CIMT) were measured. Fifty-five of the patients with GDM returned for a follow-up visit scheduled at 1-year post-partum. These patients were subjected to 75 g oral glucose tolerance test (OGTT) followed by an evaluation of metabolic and subclinical inflammatory parameters were evaluated. RESULTS The mean FBG, insulin, homeostasis model assessment insulin resistance (HOMA-IR), triglyceride (TG), hsCRP levels and CIMT in the women with GDM were significantly higher than those in the control group. C-reactive protein and CIMT were positively correlated with insulin, HOMA-IR, glucose value at the time of the OGTT 50, prepregnancy body mass index, TG and FBG. Multivariate logistic regression analysis on patients with sustained hyperglycemia one-year postpartum revealed elevated hsCRP levels to be independent risk factors for the development of dysglycemia. CONCLUSIONS Elevated hsCRP levels could be predictors of progression to T2DM later in life in patients with GDM.