Suleyman Hilmi Ipekci

Increased pulse wave velocity and relationship with inflammation, insulin, and insulin resistance in inflammatory bowel disease.

Objective Both ulcerative colitis and Crohn’s disease are forms of inflammatory bowel disease (IBD), which is characterized by chronic, progressive inflammation of the gastrointestinal tract. Recent studies have shed new light on the importance of inflammation in the pathogenesis of arterial stiffness. Aim This study aimed to evaluate the relationship between pulse wave velocity (PWV) measurement and biochemical parameters in inactive and active IBD patients without cardiovascular risk factors and perform a comparison with the control group. Materials and methods We enrolled 102 IBD patients without cardiovascular risk factors and 74 matched controls, and evaluated each patient in active and inactive disease periods. All patients completed a standard questionnaire form and we assessed various laboratory parameters. We carried out vascular measurements using a Mobil-O-Graph 24-h pulse wave analysis monitor, an automatic oscillometric device. Results Although cardiovascular risk factors, such as total cholesterol and low-density lipoprotein cholesterol, were significantly lower (P<0.05) in IBD patients than the controls, 24 h, day and night PWV values, erythrocyte sedimentation rate, C-reactive protein, insulin, homeostasis model assessment of insulin resistance, and homocysteine were higher in patients with active and inactive IBD than the controls (P<0.05). Multiple linear regression analysis showed that PWV was correlated positively with age and duration of IBD. Conclusion This study showed increased PWV, homocysteine, erythrocyte sedimentation rate, C-reactive protein, insulin, and homeostasis model assessment of insulin resistance in patients with active and inactive IBD and provides evidence of the potential contribution of inflammation and inflammation-related factors toward arterial stiffening independent from conventional cardiovascular risk factors.

The Adiponectin variants contribute to the genetic background of type 2 diabetes in Turkish population

Adiponectin, an adipose tissue specific protein encoded by the Adiponectin gene, modulates insulin sensitivity and plays an important role in regulating energy homeostasis. Many studies have shown that single nucleotide polymorphisms (SNPs) in the Adiponectin gene are associated with low plasma adiponectin levels, insulin resistance and an increased risk of type 2 diabetes mellitus. The aim of the present study was to evaluate the contribution of the Adiponectin gene polymorphisms in genetic background of type 2 diabetes in a Turkish population. In total, 169 unrelated and non-obese diabetic patients and 119 age- and BMI-matched non-diabetic individuals with no family history of diabetes were enrolled in this study. We detected a significant association between type 2 diabetes and two SNPs: SNP -11391G>A, which is located in the promoter region of the Adiponectin gene, and SNP +276G>T, which is found in intron 2 of the gene (P<0.05). The silence SNP G15G (+45T>G) in exon 1 and SNP +349A>G in intron 2 also showed a weak association with type 2 diabetes (P=0.06 and P=0.07, respectively), while SNPs -3971A>G in intron 1 and Y111H, R112C and H241P in exon 3 showed no association (P>0.05). In conclusion, these findings suggest that Adiponectin gene polymorphisms might be effective on susceptibility for type 2 diabetes development which emerged from the interactions between multiple genes, variants and environmental factors.

Mean Platelet Volume Could be a Possible Biomarker for Papillary Thyroid Carcinomas

Thyroid cancer is the most prevalent endocrine cancer and is evident in nearly 5% of thyroid nodules. The correlation between mean platelet volume (MPV) and many other cancer types has been investigated previously. However, the correlation between papillary thyroid carcinoma (PTC) and MPV has not yet been studied in detail. The aim of this study was to examine whether MPV would be a useful inflammatory marker to differentiate PTC patients from cases of benign goiter and healthy controls. Preoperative MPV levels in patients with PTC were found to be significantly higher when compared with benign goiter patients and healthy controls ((respectively, 8.05 femtoliter (fl), 7.57 fl, 7.36 fl, p=0.001). After surgical treatment of PTC patients, a significant decrease in MPV levels was seen (8.05 fl versus 7.60 fl, p=0.005). ROC analysis suggested 7.81 as the cut-off value for MPV (AUC=0.729, sensitivity 60%, specificity 80%). In conclusion, maybe changes in MPV levels can be used as an easily available biomarker for monitoring the risk of PTC in patients with thyroid nodules, enabling early diagnosis of PTC.

IRS1 gene polymorphisms Gly972Arg and Ala513Pro are not associated with insulin resistance and type 2 diabetes risk in non-obese Turkish population.

Insulin receptor substrate 1 (IRS1), plays a critical role in insulin signaling and its control has an important place in the development of insulin resistance. The tyrosine phosphorylation of IRS1 serves as docking molecules for downstream effectors such as Phosphatidylinositol 3-kinase and phosphotyrosine phosphatase-2. We focused on the Gly972Arg and Ala513Pro variants of the IRS1 gene, since these specific allelic variants are located near the Tyr-Met-X-Met (YMXM) motifs around Tyr987 and Tyr612. Thus, we aimed to investigate the effects of Gly972Arg/Ala513Pro polymorphisms in IRS1 gene on development of insulin resistance and the risk of type 2 diabetes in a non-obese Turkish population. This work included 306 individuals comprising 178 subjects with type 2 diabetes and 128 healthy subjects matched for body mass index. Gly972Arg/Ala513Pro polymorphisms had no effect on type 2 diabetes risk and its phenotypes (P > 0.05). Although IRS1 gene and its variants are associated with type 2 diabetes and insulin resistance in several studies worldwide, our data showed that there is no association between Gly972Arg and Ala513Pro variants in IRS1 and disease in Turkish population.

Relationship between mean platelet volume and low-grade systemic coagulation with vitamin D deficiency in primary ovarian insufficiency

ObjectivePremature menopause in young women is associated with an increased incidence of cardiovascular disease. The present study was designed to determine vitamin D (vit D) and the coagulation parameters such as activated partial thromboplastin time (APTT), PT, D-dimer, white blood cell (WBC), and mean platelet volume (MPV) levels, in primary ovarian insufficiency (POI) patients and control women with a normal menstrual cycle.Materials and methodsA total of 43 patients with non-diabetic POI were studied in order to evaluate and compare with the control group comprising 33 women with a normal menstrual cycle.ResultsThere was no significant difference between the groups for age and body mass index (BMI). D-dimer, WBC, MPV, PT, total cholesterol, and LDL cholesterol were higher in women with POI. APTT levels were also increased but missed the significance in POI group. Women with POI had significantly lower serum vit D levels compared with healthy control group. FSH level was positively correlated with D-dimer, WBC, MPV, and negatively correlated to vit D and serum D vit level was inversely correlated with MPV, APTT, D-dimer, FSH levels in individual women.ConclusionsThe obtained results seem to indicate that POI patients had low-grade systemic coagulation and fibrinolytic activation as evidenced by elevated D-dimer, WBC, MPV, PT values potentially be used as indicators of risk factor for thrombosis and atherosclerosis in POI women. All of our patients with POI were deficient in vit D. These results also suggest that vit D deficiency plays important roles of POI women and associated with coagulation, independently from age and BMI.

Effects of Single Nucleotide Polymorphisms in KATP Channel Genes on Type 2 Diabetes in a Turkish Population

BACKGROUND AND AIMS ATP-sensitive potassium (K(ATP)) channels of pancreatic β-cells play a key role in glucose-stimulated insulin secretion mechanism. The Kir6.2 protein, forming the K(ATP) channel pore inwardly, and the SUR1 protein that surrounds it forming the outside part of the channel were encoded by ABCC8 and KCNJ11 genes, respectively. Recent studies reported that the single nucleotide polymorphisms (SNPs) established in these genes are associated with defects in insulin secretion and type 2 diabetes mellitus (T2DM). We aimed to investigate the allele profiles and the risk alleles of the ABCC8 and KCNJ11 genes and to highlight the associations with the disease in patients in Konya region of Turkey where T2DM is common. METHODS In this study, 169 patients with T2DM and 119 healthy controls were included. A total of 29 SNPs in ABCC8 and KCNJ11 genes were screened by PCR-SSCP technique and sequenced. Biochemical parameters and genotype-phenotype relationships were analyzed using variance analysis. RESULTS R1273R silent substitution in exon 31 and 16/-3t→c substitution in noncoding region of exon 16 of ABCC8 gene showed a significant association (OR 4.8 [95% CI 2.41-9.77], p <0.001 and OR 3.5 [95% CI 1.64-7.40], p <0.001 under dominant and recessive models, respectively). We detected a significant association between E/K heterozygote genotype and reduced plasma insulin level in patients with T2DM (p <0.05). CONCLUSIONS ABCC8 exons 16 and 31 variants increase susceptibility to T2DM and KCNJ11 E23K decreases insulin secretion in a Turkish population.

Risk factors for diabetes mellitus in women with primary ovarian insufficiency.

Primary ovarian insufficiency (POI) is not only a gynecological problem but also has serious effects on women’s health such as changes in hormone levels that can trigger fluctuations in blood sugar level and inflammation status. The present study was designed to determine vitamin D, copper, zinc, metabolic parameters [insulin, homeostasis model of assessment-insulin resistance (HOMA-IR)], inflammation parameters such as procalcitonin and high sensitivity C reactive protein (hs-CRP), and lipid profile in POI patients and control subjects with normal menstrual cycles. A total of 43 patients with nondiabetic POI were studied in order to evaluate and compare the findings with those of the control group, which comprised 33 women with normal menstrual cycles. The women with POI had higher levels of serum copper, serum insulin, glucose, LDL-cholesterol, total cholesterol, HOMA-IR, hs-CRP, and procalcitonin, whereas serum vitamin D and zinc levels were lower compared with the healthy control group. Follicle-stimulating hormone (FSH) levels were positively correlated with insulin, glucose, HOMA-IR, hs-CRP, procalcitonin, and copper and negatively correlated with vitamin D and zinc levels. In multivariate statistic analyses with body mass index and FSH as dependent variables, FSH was positively associated with copper and HOMA-IR negatively with vitamin D levels. The present study demonstrated that women with POI have traditional risk factors for diabetes mellitus, including lower levels of vitamin D, whereas higher levels of copper and HOMA-IR.

Effect of Aerobic Exercise Training on MDA and TNF-α Levels in Patients with Type 2 Diabetes Mellitus

Objective. Diabetes mellitus (DM) is associated with low-grade inflammation. The benefits of regular exercise for the DM are well established, whereas less is known about the impact of aerobic exercise on malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) in the DM. Methods. We randomised 64 participants, who do not exercise regularly, without any diabetic chronic complications in parallel to 12 weeks of aerobic exercise (three times per week, n = 31) and no exercise (control; n = 33). Plasma levels of soluble TNF-α and MDA levels were measured before-after physical training programme and control group. Results. Sixty-four patients with type 2 diabetes mellitus were analysed. When comparing the two groups of patients with age, gender, hemoglobin A1c (HbA1c) levels, lipid profile, waist circumference, body mass index (BMI) and class of treatment for diabetes were not different between groups. While soluble TNF-α remained essentially unaffected by physical training, plasma concentrations of MDA markedly decreased (P < 0.05); physical training also decreased body weight, waist circumference, and blood pressure (P < 0.05). Conclusion. Exercise training favorably affected body weight, waist circumference, and blood pressure. A three-weekly, 12-week, aerobic-training programme, without a concomitant weight loss diet, was associated with significant decrease in MDA levels in type 2 diabetic individuals.

Letrozole Induced Hypercalcemia in a Patient with Breast Cancer

Hypersecretion of PTHrP is a relatively common cause of malignancy-related hypercalcemia. However, there is only one case report of letrozole induced hypercalcemia. A 52-year-old female patient was referred to our clinic because of the recent discovery of hypercalcemia (11.0 mg/dL). The patient had a history of left breast carcinoma. She had started a course of letrozole (aromatase inhibitor; 2.5 mg dose/day) ten months earlier. Patients parathyroid hormone-related protein levels were normal and a bone scintigram revealed no evidence of skeletal metastasis. Other potential causes of high calcium levels were ruled out. We recognized that, when letrozole was taken at one dose daily (2.5 mg), she had recurrent hypercalcemia. Our experience suggests that letrozole may precipitate hypercalcemia in a patient with breast cancer.

Cornea in PCOS patients as a possible target of IGF-1 action and insulin resistance

ObjectivesPrevious studies suggest that serum IGF-1 is higher in women with polycystic ovary syndrome (PCOS). The ophthalmologic effects of IGF-1 excess have not yet been investigated in women with PCOS. The aim of the current study is to compare the corneal thickness of patients with PCOS and those of healthy subjects.MethodsForty three patients with PCOS and 30 age-matched and gender-matched healthy individuals were enrolled in this cross-sectional study. Central corneal thickness (CCT) was measured in patients with PCOS and in healthy individuals with an ultrasound pachymeter. IGF-1 values were also determined in the study group.ResultsWomen with PCOS had significantly higher levels of IGF-1 and homeostasis model assessment (HOMA-IR) levels than the control group. Right and left CCT measurements were higher in the PCOS group than in the control group. A positive correlation between IGF-1 and right and left CCT was identified in both groups. In multiple linear stepwise regression analyses, IGF-1 independently and positively associated with HOMA-IR in women with PCOS. A correlation between total testosterone and CCT was identified in the whole group. In multiple stepwise regression analyses, total testosterone independently and positively associated with left central corneal thickness in the whole group.ConclusionsThese findings indicate that PCOS has target organ effects on the eye. Consequently, it can change central corneal thickness. Higher IGF-1 levels seem to be the main causes of increased corneal thickness. Insulin resistance in PCOS is one of the underlying causes and promotes increase in IGF-1. We suggest a careful and detailed corneal evaluation in PCOS patients to prevent the potential risk of increased CCT, in addition to the already-known complications.