Ilhan Yetkin

Circulating concentrations of adiponectin and tumor necrosis factor-α in gestational diabetes mellitus

Adiponectin and tumor necrosis factor-α (TNF-α) have been implicated in insulin resistance and diabetes mellitus (DM). In the present study we investigated levels of adiponectin and TNF-α and their relationships with each other and metabolic factors in women with gestational DM (GDM). Thirty-four pregnant women with GDM and 31 pregnant women with normal glucose tolerance (NGT) were included in the study. Plasma adiponectin levels were lower in GDM than in NGT (36.9 ± 6.7 vs. 61.3 ± 13.0 ng/ml, p = 0.028). Serum TNF-α levels were increased in GDM compared with NGT (20.5 ± 2.4 vs. 14.0 ± 1.5 pg/ml, p = 0.042). After adjustment for pre-pregnancy and current body mass index (BMI), adiponectin levels correlated negatively with insulin resistance by homeostasis model assessment-insulin resistance (HOMA-IR) and 0-h and 1-h glucose both at glucose challenge test and oral glucose tolerance test in GDM. Adiponectin levels were correlated only with very low-density lipoprotein cholesterol and triglyceride levels in NGT. TNF-α levels were correlated with glycated hemoglobin in GDM. There was a significant positive correlation between TNF-α levels and pre-pregnancy and current BMI in GDM as well as NGT. HOMA-IR for adiponectin and pre-pregnancy BMI for TNF-α remained as significant determinants in multiple regression analyses. In conclusion, these data suggest that reduced adiponectin and increased TNF-α may be involved in the pathogenesis of GDM.

Risk factors for cardiovascular disease in patients with subclinical hypothyroidism

IntroductionThe relationship between subclinical hypothyroidism (SCH) and cardiovascular disease is not fully understood. We investigated risk factors for cardiovascular disease (lipid profile, lipoproteins, insulin resistance, C-reactive protein [CRP] homocysteine [Hcy] and fibrinogen levels) and their relationships with thyroid hormones in SCH patients and controls.MethodsThirty-eight SCH patients and 44 controls were enrolled in this study. No patients had any substantial confounding medical conditions (including diabetes mellitus or coronary heart disease) or were taking thyroidrelated medication.ResultsSerum total cholesterol (P<0.05), low-density lipoprotein cholesterol (P<0.05) and triglycerides (P<0.001) were higher in patients with SCH than in controls. Serum lipoprotein(a) (Lp[a]) levels were higher in SCH subjects but this difference did not reach statistical significance (P=0.07). No significant differences were noted in CRP, Hcy, fibrinogen, high-density lipoprotein cholesterol, apolipoprotein A-1, apolipoprotein B (Apo B) or insulin resistance between patients with SCH and controls (in all cases, P>0.05). Free triiodothyronine (FT3) negatively correlated with Apo B (r=.0.46, P=0.005) and Lp(a) (r=.0.31, P=0.03) in patients with SCH and negatively correlated with Lp(a) (r=.0.30, P=0.04) in controls. All of these parameters were comparable between patients with thyroid-stimulating hormone (TSH) >10 μIU/ml and TSH <10 μIU/ml (in SCH patients, P>0.05).ConclusionOur results suggest that SCH is associated with some lipid and lipoprotein abnormalities. Our results also suggest that this association does not depend on the subject’s TSH level.

Serum IL-18 levels in patients with type 1 diabetes : Relations to metabolic control and microvascular complications

The study was designed to examine serum IL-18 level and its relation to metabolic control parameters and microvascular complications in type 1 diabetes mellitus (DM). Sixty two patients with type 1 DM and 30 healthy individuals were enrolled in the study. Serum IL-18 levels of patients with type 1 DM were significantly increased compared to controls (293.4+/-133.4 vs 211.2+/-63.9 pg/ml, P=0.003). Patients with poor glycemic control had higher levels of IL-18 than patients with well glycemic control (329.9+/-141.0 vs 226.3+/-89.6 pg/ml, P=0.02). There was no significant difference between the serum IL-18 levels of patients with microvascular complications and those of patients without microvascular complications (307.6+/-127.6 vs 293.2+/-145.6 pg/ml, P>0.05). IL-18 correlated positively with HbA(1c) (r=0.32, P=0.01) and postprandial blood glucose (PPBG) (r=0.26, P=0.02); and negatively with HDL-cholesterol (HDL-C) (r=-0.38, P=0.007). By linear regression analysis, PPBG was determined as the most explanatory parameter for the alterations in serum IL-18 levels (P=0.02). High levels of IL-18 in patients with type 1 DM is related to short and long term glycemic control and HDL-C levels but not to microvascular complications.

The effect of blood glucose regulation on retinal nerve fiber layer thickness in diabetic patients.

Purpose: To evaluate the effect of blood glucose (BG) regulation on the retinal nerve fiber layer (RNFL) in diabetic patients by using a scanning laser polarimeter (NFA-GDx). Methods: We prospectively assessed RNFL thickness in diabetic patients and an age-matched control group. Patients without diabetic retinopathy, with BG >250 mg/dl, HbA1c >8%, fructosamine >285 µmol/l and triglyceride >200 mg/dl were included in the study. RNFL assessment was performed before and after metabolic regulation of diabetes. Symmetry, superior maximum, ellipse modulation and the average thickness variables of NFA-GDx were used for the assessment. Mann-Whitney U and Wilcoxon tests were used for the statistical analysis. Results: A total of 40 diabetic patients were included in the study and a repeat RNFL examination could be performed in 22 of them following regulation of BG levels. None of the GDx variables were significantly different between pre- and postregulation measurements (p > 0.05, Wilcoxon test). The mean superior maximum, ellipse modulation and average thickness values of the diabetic group were significantly lower than the control group (p < 0.05, Mann-Whitney U-test). Conclusions: Poor metabolic control of diabetes mellitus adversely affects the thickness of RNFL and this effect does not seem to be acute since it was not reversed by short-term BG regulation. This issue needs to be kept in mind when assessing glaucomatous progress in diabetic patients.

PON1 55 and 192 Gene Polymorphisms in Type 2 Diabetes Mellitus Patients in a Turkish Population

Diabetes mellitus is a multifactorial metabolic disease, caused by the complete or relative absence of insulin hormone, which results in the deterioration of carbohydrate, protein, and lipid metabolism. The PON1 55 and 192 polymorphisms have been reported to be associated with type 2 diabetes and its complications. In this study, the involvement of the PON1 55 and 192 polymorphisms and paraoxonase enzyme activity in diabetic complications was assessed. The MM and QQ genotypes were the most frequent in complications of type 2 diabetes in both of the polymorphisms. PON enzyme activity was lower in the type 2 diabetes group with respect to the control group. Regarding both genotypes and enzyme activity, correlations were found between the PON1 55 and 192 genotypes and diabetic complications. This study thus helps to outline a genotype–phenotype relation for the PON1 gene in a Turkish population.

Increased Colonic Intraepithelial Lymphocytes in Patients With Hashimoto's Thyroiditis

Background Hashimotos thyroiditis is an autoimmune thyroid disorder. Lymphocytic colitis and collagenous colitis are characterized by diarrhea with normal endoscopic findings. Autoimmune disorders are common in Hashimotos thyroiditis and lymphocytic colitis. The aim of this study was to investigate the incidence of lymphocytic colitis in patients with Hashimotos thyroiditis. Study Fifty patients with well-documented Hashimotos thyroiditis were included. Twenty patients with nonulcer dyspepsia served as a control group. Five of 50 patients with Hashimotos thyroiditis reported intermittent diarrhea, whereas no patients had diarrhea in the control group. All patients and the control group underwent total colonoscopy, and multiple colonoscopic biopsies were performed. Results We found that 40% (20 of 50) of Patients with Hashimotos thyroiditis had histologic findings consistent with lymphocytic colitis, and one patient in the control group had lymphocytic colitis (p < 0.01). The mean number of intraepithelial lymphocytes was 34.4/100 epithelial cells in these 20 patients, whereas the mean number of intraepithelial lymphocytes was 12.3/100 epithelial cells in the other 30 patients with Hashimotos thyroiditis (p < 0.05). Conclusions There was a higher incidence of histologic findings of lymphocytic colitis in patients with Hashimotos thyroiditis, although most of the patients were clinically asymptomatic. This finding suggests that lymphocytic colitis may have an asymptomatic clinical course and should encourage further clinical investigations to better anticipate the relationship between autoimmune disorders.

Reduced Serum Acylated Ghrelin Levels in Patients with Hyperthyroidism

Background and Objective: Recent studies have revealed that circulating ghrelin levels seem to play a role in energy homeostasis. The effect of hyperthyroidism on ghrelin levels is not fully known. Methods: Serum levels of ghrelin and its relationship with insulin resistance were evaluated in 48 patients with hyperthyroidism and 43 euthyroid healthy controls. Thyroid hormones, insulin, glucose, ghrelin levels and lipid parameters were measured in all subjects. Insulin sensitivity was determined using the homeostasis model assessment. Results: Serum ghrelin levels were significantly decreased in hyperthyroid patients than in controls (32.5 ± 23.3 vs. 54.1 ± 35.5 pg/ml, p < 0.001). Circulating ghrelin levels significantly correlated with age (r = –0.26, p = 0.01), fasting glucose (r = –0.21, p = 0.01), free triiodothyronine (r = –0.18, p = 0.04), free thyroxine (r = –0.23, p = 0.02) and thyroid stimulating hormone (r = 0.21, p = 0.04), but not with blood pressure, body mass index, lipid parameters, insulin and homeostasis model assessment (p > 0.05). Multiple regression analysis revealed glucose level to be the most important predictor of circulating ghrelin level. Conclusion: These results indicate that hyperthyroidism has effect on serum ghrelin levels. Further studies are needed for the exact mechanism.

Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma gene in first-degree relatives of subjects with polycystic ovary syndrome.

Aim. This study was designed to examine the relationship between the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-γ (PPAR-γ) gene and insulin resistance (IR) in first-degree relatives of subjects with polycystic ovary syndrome (PCOS). Materials and methods. One hundred and twenty family members of 55 patients with PCOS and 80 unrelated healthy control subjects without a family history of diabetes or PCOS were studied. IR was assessed by homeostatic model assessment (HOMA-IR) and area under the curve (AUC) for insulin during an oral glucose tolerance test in subjects with normal glucose tolerance and controls. Genetic analysis of the PPAR-γ gene Pro12Ala polymorphism was performed by restriction fragment length polymorphism. Results. Fasting insulin, HOMA-IR and AUC insulin were significantly higher in first-degree relatives of PCOS subjects than in controls. A significantly different allele distribution of the Pro12Ala polymorphism of PPAR-γ was observed between the two groups, with the frequency of the variant Ala isoform being significantly reduced in the first-degree relatives of PCOS subjects (10.8%, 13 subjects) compared with the control group (22.5%, 18 subjects). All Pro12Ala polymorphisms of the PPAR-γ gene were heterozygous. Compared with first-degree relatives of PCOS subjects with the Pro12Pro polymorphism of PPAR-γ, first-degree relatives of PCOS subjects with the Pro12Ala polymorphism had low fasting insulin, HOMA-IR and AUC insulin levels. The combined prevalence rate for impaired glucose tolerance, impaired fasting glucose and diabetes was 40% (16 subjects) in mothers and 52% (20 subjects) in fathers of PCOS women. Conclusion. Our findings suggest that Pro12Ala PPAR-γ gene polymorphism may be protective against IR and might prevent the development of diabetes mellitus in the first-degree relatives of subjects with PCOS.

Changes in intraocular pressure and corneal and retinal nerve fiber layer thicknesses in hypothyroidism

Purpose To evaluate the changes in intraocular pressure (IOP), corneal thickness (CT), and retinal nerve fiber layer thickness (RNFLT) in patients with hypothyroidism before and after treatment. Methods A complete ophthalmic examination including visual acuity, IOP, anterior segment, and fundus examination together with CT and RNFLT measurements were performed for each patient with newly diagnosed hypothyroidism, at the initial diagnosis and the third and ninth months of the L-thyroxine treatment. Wilcoxon signed rank test and Spearmans correlation test were used for statistical evaluation of the results. Results A total of 56 eyes of 28 patients were included in the study. The mean IOP and CT values were found to decrease with medical treatment (p=0.000). There was no significant change in any of the RNFLT parameters measured with scanning laser Polarimeter after L-thyroxine treatment (Wilcoxon, p>0.05). The change in IOP levels was not correlated with the change in thyroid hormone levels (Spearmans correlation test, p>0.05). The mean increase in serum free T3 and serum free T4 levels and the mean decrease in serum TSH levels at the ninth month of the therapy were found to be correlated with the decrease in CT in the left eyes (Spearmans correlation test, R>0.4 and p<0.05). Conclusions Hypothyroidism seems to cause a reversible increase in CT and IOP. IOP changes may be secondary to CT changes. RNFLT parameters measured with scanning laser Polarimeter do not seem to be affected by hypothyroidism. When the CT is taken into account and the IOPs corrected for CT, the prevalence of glaucoma in hypothyroidism may not be as high as previously reported. This issue should be taken into account while assessing glaucoma in patients with hypothyroidism.

Relationship between serum osteoprotegerin, glycemic control, renal function and markers of atherosclerosis in type 2 diabetes

Abstract We aimed to investigate the relationship between serum osteoprotegerin (OPG) level and glycemic control, lipids, renal function, microalbuminuria, insulin resistance and markers of atherosclerosis including C-reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate (ESR) in patients with type 2 diabetes mellitus (DM). A total of 166 patients (99 women and 67 men) with type 2 DM were recruited in the study. Serum OPG level was higher in poorly controlled diabetic patients (HbA1c ≥ 7%) than in well-controlled diabetic patients (HbA1c < 7%) [4.0 (3.6–5.0) and 3.5 (2.9–4.4) pmol/L, p = 0.02]. There was no difference between the patients with and without microalbuminuria with respect to OPG levels (p > 0.05). LogOPG was correlated with age (r = 0.47, p = 0.0001). After adjustment for age, sex and BMI, logOPG correlated positively with fasting blood glucose (FBG) (r = 0.28, p = 0.001), prandial blood glucose (PBG) (r = 0.22, p = 0.009), glycated hemoglobin (HbA1c) (r = 0.26, p = 0.002), logHOMA-IR (r = 0.30, p = 0.006), fibrinogen (r = 0.17, p = 0.04), mean albumin excretion rate (MAER) (r = 0.20, p = 0.01) and negatively with creatinine clearance (r = − 0.20, p = 0.01). Regression analysis revealed that logOPG was independently associated with age (p = 0.0001), HbA1c (p = 0.01) and MAER (p = 0.02) (r2 = 0.25). In conclusion; we found that serum OPG levels are increased in poorly controlled type 2 DM and associated with age, glycemic control and microalbuminuria.