Mustafa Sait Gonen

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.

Is there a link between premature ovarian failure and serum concentrations of vitamin D, zinc, and copper?

ObjectiveThe risk of primary ovarian insufficiency (POI) increases in association with autoimmune conditions. Adequate intake of vitamin D (vit D) and trace elements is required for the immune system to function efficiently. The aim of this study was to evaluate vit D, zinc, and copper blood levels in women with POI who had given birth to at least one child and in women with normal menstrual cycles. MethodsThis was a cross-sectional, case-control study involving 63 participants divided into two groups: the study group, which is composed of 35 women with POI, and the control group, which is composed of 28 women with normal menstrual cycles. Serum concentrations of zinc, vit D, and copper were determined for each participant. ResultsWomen with POI had significantly higher serum copper levels and copper-to-zinc ratio but significantly lower serum vit D and zinc levels when compared with the healthy control group. Serum follicle-stimulating hormone levels were inversely correlated with zinc and vit D levels and positively correlated with the copper-to-zinc ratio and copper levels. Vit D levels were inversely correlated with follicle-stimulating hormone levels, copper-to-zinc ratio, and copper levels and positively correlated with zinc levels. ConclusionsMost women with POI are deficient in vit D. Zinc, copper, and vit D seem to correlate with hormonal status in the participants. The present study may generate hypotheses for future studies that will investigate the possible mechanisms behind alterations in trace elements and vit D deficiency in women with POI and whether these changes could be used to screen for the risk of developing POI.

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.

Is There Any Relationship between Metabolic Parameters and Left Ventricular Functions in Type 2 Diabetic Patients without Evident Heart Disease

Background: The aim of the present study was to evaluate left ventricle (LV) systolic and diastolic function, using tissue Doppler echocardiography (TDE) and color M‐mode flow propagation velocity, in relation to blood glucose status in normotensive patients with type 2 diabetes mellitus (T2DM) who had no clinical evidence of heart disease. Methods: Seventy‐two patients with T2DM (mean age 49.1 ± 9.8 years) without symptoms, signs or history of heart disease and hypertension, and 50 ages matched healthy controls (mean age 46.1 ± 9.8 years) had echocardiography. Systolic and diastolic LV functions were detected by using conventional echocardiography, TDE and mitral color M‐mode flow propagation velocity (VE). Fasting blood glucose level (FBG) after 8 hours since eating a meal, postprandial blood glucose level (PPG), and HbA1C level were determined. The association of FBG, PPG and HbA1C with the echocardiographic parameters was investigated. Results: It was detected that although systolic functions of two groups were similar, diastolic functions were significantly impaired in diabetics. No relation of FBG and PPG with systolic and diastolic functions was determined. However, HbA1C was found to be related to diastolic parameters such as E/A, Em/Am, VE and E/VE (β=−0.314, P = < 0.05; β=–0.230, P < 0.05; β=–0.602, P < 0.001, β= 0.387, P < 0.005, respectively). In addition to HbA1C, LV, diastolic functions were also correlated with age and diabetes duration. Conclusion: Diastolic LV dysfunction may develop even in absence of ischemia, hypertension, and LVH in T2DM. FBG and PPG have no effect on LV functions, but HbA1C levels may affect diastolic parameters.

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.

Ocular changes in primary hypothyroidism

BackgroundTo determine the ocular changes related to hypothyrodism in newly diagnosed patients without orbitopathy.FindingsThirty-three patients diagnosed to have primary overt hypothyroidism were enrolled in the study. All subjects were assigned to underwent central corneal thickness (CCT), anterior chamber volume, depth and angle measurements with the Scheimpflug camera (Pentacam, Oculus) and cup to disc ratio (C/D), mean retinal thickness and mean retinal nerve fiber layer (RNFL) thickness measurements with optical coherence tomography (OCT) in addition to ophthalmological examination preceeding the replacement therapy and at the 1st, 3rd and 6th months of treatment.The mean age of the patients included in the study were 40.58 ± 1.32 years. The thyroid hormone levels return to normal levels in all patients during the follow-up period, however the mean intraocular pressure (IOP) revealed no significant change. The mean CCT was 538.05 ± 3.85 μ initially and demonstrated no statistically significant change as the anterior chamber volume, depth and angle measurements did. The mean C/D ratio was 0.29 ± 0.03 and the mean retinal thickness was 255.83 ± 19.49 μ initially and the treatment did not give rise to any significant change. The mean RNFL thickness was also stable during the control visits, so no statistically significant change was encountered.ConclusionsNeither hypothyroidism, nor its replacement therapy gave rise to any change of IOP, CCT, anterior chamber parameters, RNFL, retinal thickness and C/D ratio.

Blink Reflex Alterations in Diabetic Patients with or without Polyneuropathy

The main aim of this study is to evaluate the role of blink reflex for early diagnosis of cranial neuropathy in diabetic patients with or without polneuropathy. Ninety-five diabetic patients were included in the present study for the evaluation of blink reflex. The diabetic patients were divided into two groups according to having diabetic neuropathy or not. Both R1, R2i and R2c latencies in all diabetic patients with or without polyneuropathy were prolonged relative to controls and the differences were statistically significant (p < .001). R1 latencies in diabetic patients with polyneuropathy were prolonged relative to diabetic patients without polyneuropathy and the differences were statistically significant (p < .001). These findings presumably reflect that facial nerve is severly involved in diabetic polyneuropathy. Finally blink reflex is of value in detection of clinically silent intraaxial brainstem functional abnormalities or extraaxial lesions in diabetic patients before peripheral neuropathy.

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.

Multiorgan dysfunction accompanied with metimazole and thyroid storm.

A 41-year-old man with a history of hyperthyroidism had been treated with methimazole and propranolol for the past 2 months. He developed multiorgan dysfunction with acute liver failure, severe lactic acidosis, disseminated intravascular coagulation, heart failure and acute pulmonary edema with rapid deterioration of renal function. The patient had no history of alcoholism, drug abuse, blood transfusion, or exposure to hepatitis A, B, or C. Extrahepatic obstruction was ruled out with an abdominal ultrasonogram. Serologic studies and immunologic tests were negative. This case illustrates the sudden and abrupt deterioration of multiorgan dysfunction due to antithyroid drug administration and thyroid storm. The thyroid storm score of Burch and Wartofsky was 90/140. The multiorgan dysfunction was reversed by discontinuation of the methimazole and treat with hemodialysis, steroids, cholestyramine, nonselective beta-blocker, fresh frozen plasma infusion and supportive management in the intensive care unit. The patient was discharged from the hospital with normal coagulation parameters, renal and liver function tests.