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Diabetes mellitus (DM) is an important health problem that should be treated efficiently because of its high prevalence and high morbidity and mortality due to its complications. In patients with DM, the application of a treatment which provides physiologic insulin secretion as such in healthy individuals is directly related with the prevention of diabetes complications. Insulin analogs, which were developed in recent years and shown to have pharmacokinetic and pharmacodynamic superiority to human insulin, have made it possible to obtain natural insulin pattern in the body. In addition to development of insulin analogs, introduction of insulin application method of “continuous subcutaneous insulin infusion” (insulin pump) has led a new era in the treatment of DM. In this review, treatment of type 1 and 2 DM patients with insulin analogs, particularly insulin aspart, applied with insulin pump was discussed in the light of the current literature.

Context: Although patients with acromegaly may have an increased risk of developing several types of cancers, the degree of risk for malignancy in these patients is unresolved. Objective: The present study aimed to investigate the potential genotoxic effects of acromegaly on the cell cycle in peripheral blood lymphocyte cultures. Design: This was a single center, crossover, case-control study conducted on the acromegalic patients in Turkey. Setting: The study was conducted in the outpatient clinic of a university hospital. Patients: Seventy-one consecutively screened acromegalic patients and 56 controls participated in the study. Intervention: Patients were included, regardless of the disease activity status and their treatment duration before the study. Main Outcome Measures: The primary end point was the frequency of micronucleus (MN) in the peripheral blood lymphocyte cultures, and the secondary end point was its clinical correlations. Results: The MN level was 3.82 ± 1.49 in the control group and 18.00 ± 6.13 in the acromegalic group (P < .01), whereas the nuclear division index (NDI) was 1.79 ± 0.12 in the control group and 1.68 ± 0.07 in the acromegalic group (P < .01). Neither MN nor NDI was correlated with age, GH, IGF-I, initial GH, initial IGF-I, duration of the remission period, and initial tumor size. Only the MN level was positively correlated with the duration of disease (r = 0.323, P = .014). Conclusion: Our results indicated that acromegalic patients had genotoxic damage at a substantial level, and there was a positive correlation between the duration of disease and genotoxicity level.

The prevalence of diabetes is increasing in elderly populations, and is thought to be an important risk factor for cognitive dysfunction in this age group.The study included 104 patients aged over 60 years who were followed-up for type 2 diabetes for at least 6 months, in addition to 44 controls. Glycemic parameters, microangiopathic complications, microalbumin elimination, and the Standardized Mini Mental State Examination (SMMSE) scores were used as indicators of cognitive function.The SMMSE scores of diabetic patients were significantly lower than the control group (p 0.05). The average SMMSE score for normoalbuminuric diabetic patients was 22.36 ± 4.66, compared with 22.61 ± 4.90 for the microalbuminuria patients (p = 0.84). A positive correlation was found between SMMSE scores and patients' hemoglobin values and education levels, whereas a negative correlation was noted between SMMSE scores and systolic and diastolic blood pressures and hemoglobin A1c levels (p 0.05). Patients with diabetic neuropathy, a microvascular complication of diabetes, were found to have significantly lower SMMSE scores (p = 0.011).Elderly diabetic patients showed decreased cognitive function compared to volunteers. No relationship was established between microalbuminuria and cognitive functions, although diabetic neuropathy was found to be related to decreased cognitive function.

Introduction: The objective of this study was to investigate the effects of some clinical and pathological features of prolactinomas on tumour behaviour. Material and methods: The study included 113 patients with prolactinoma (27 male, 86 female), with a mean age at diagnosis of 34.4 ± 10.0 years (40.3 ± 12.6 in males, 32.6 ± 8.3 in females). Patients were grouped as invasive or non-invasive according to radiological imaging findings. Ki-67 levels were evaluated if possible. Results: The mean adenoma size (longest dimension) was 38.6 ± 21.6 mm and 10.8 ± 9.4 mm in male and female patients. Pre-treatment serum levels of prolactin were defined as mean 1,926 ± 6,662 ng/mL in all, 124.8 ± 63.4 and 4,675 ± 10,049 ng/mL in the noninvasive and invasive groups (p < 0.05). A positive correlation was found between the serum levels of prolactin and tumour size. The rate of patients with Ki-67 ≥ 0.03 was 37.5% and 47.8% in the noninvasive and invasive groups. The reduction rates were 60.8% and 80.4% in tumour sizes and 81.1% and 93.8% in prolactin level in the noninvasive and invasive groups, respectively, (p < 0.05). Conclusions: We found a strong correlation between prolactin levels and invasiveness in male patients compared to females. Ki-67 index was not found to have a place in defining the prognosis.

Pituitary tumors usually originate as benign sporadic adenomas and develop into invasive and aggressive tumors such as prolactinomas, which are common functioning pituitary adenomas. The aim of the present study was to examine the association between the tumor behavior in prolactinomas and the p16(CDKN2A) gene polymorphism occurring at the 3′-untranslated region of exon 3 (C540G). A total of 104 patients with prolactinoma were included and assigned to two groups based on invasive vs. non-invasive tumor behavior. Ki67 indices were recorded according to histopathology results. Genotypic analysis of the p16(CDKN2A) C540G polymorphism was carried out using a modified polymerase chain reaction-restriction fragment length polymorphism assay. The corresponding frequencies for CC, CG and GG genotypes in non-invasive vs. invasive tumors were 61.5, 30.8, 7.7 and 64.1, 28.2, 7.7%, respectively (not significant). The observed CG genotype frequency was higher compared with previous studies. In addition, the patients with giant adenomas or a high Ki67 index had a higher frequency of the CG genotype as compared with the other subgroups, although the differences were not significant (46.2 and 42.9%, respectively). In conclusion, a higher frequency of the C540G CG genotype of the CDKN2A gene was found among patients with prolactinoma in comparison with previous studies. These frequencies were also higher in the subgroups with elevated Ki67 or giant adenomas. Further studies are required to improve the definition of the role of the CG genotype in the development and progression of tumors in prolactinomas.

Aims: To evaluate the potential of urinary miR-451 as a biomarker at different stages of diabetic nephropathy. Methods: A total of 45 subjects having stage 3 chronic kidney disease (n=15) or stage 5 chronic kidney disease (n=15) and 15 healthy volunteers were included. Data on patient demographics, laboratory findings [creatinine, estimated glomerular filtration rate, urinary protein excretion] target genes and functions of the selected MicroRNAs associated with diabetic nephropathy and fold differences in the level of MicroRNA expression in blood and urine and the correlation of urine and plasma MicroRNA expression with estimated glomerular filtration rate were recorded. Results: MiR-195 expression level among stage 3 chronic kidney disease patients was higher in plasma samples compared to the control group, while it was significantly lower in the urine samples (p=0.036). In the stage 5 chronic kidney disease patient group, while the expression level was significantly higher in the plasma samples (p=0.005), urine sample expression was lower but not significantly different than the control group. Compared to the controls, miR-451 expression level was higher in the plasma samples of stage 3 chronic kidney disease patients, but significantly lower in the urine samples (p=0.019). Among the stage 5 chronic kidney disease patients, there was significantly higher level of expression in plasma samples (p=0.007) and significantly lower expression in urine samples (p=0.022) than the control group. Conclusions: Our study is original with its investigation of MicroRNA expressions at different stages of chronic kidney disease. Especially the statistically significant changes in the expression of miR-195 and miR-451 make these MicroRNAs come forward as good noninvasive biomarker candidates.

ABS TRACT Objective: Pre o pe ra ti ve pre pa ra ti on of hyperth yro id pa ti ents is ex tre mely im por tant to avo id comp li ca ti ons du e to se ve re thyro to xi co sis during surgery. We in ves ti ga ted the ef fects of lu gol’s so lu ti on (LS) with or wit ho ut thi o na mi des in the ra pid pre pa ra ti on of the patients for thy ro id sur gery and com pa red the ef fect of LS in pa ti ents with Gra ves’ di se a se (GD) and to xic mul ti no du lar go i ter (TMNG). Material and Met hods: Da ta we re col lec ted ret ros pec ti vely from 44 pa ti ents with hyperth yro i dism who we re fol lo wed up in our cli nic. Twenty-two pa ti ents with GD, 19 pa ti ents with TMNG and three pa ti ents with so li tary to xic ade no ma we re en rol led in to the study. To res to re euth yro i dism be fo re sur gery, 27 pa ti ents we re tre a ted with LS (gro up 1) whi le 17 pa ti ents re ce i ved LS and thi o na mi des (gro up 2). Re sults: Me an da ily to tal do sa ge of LS and du ra ti on of tre at ment to res to re euth yro i dism we re not sta tis ti cally dif fe rent bet we en gro ups 1 and 2. When the two tre at ment gro ups we re com pa red, the re was no sig ni fi cant dif fe ren ce in ba se li ne pa ra me ters and per cen ta ge of chan ges of se rum fT4 and fT3 le vels. Du ra ti on of LS tre at ment and do sa ges of LS and thi o na mi des we re al so si mi lar in pa ti ents with GD and TMNG. Per cen ta ge of chan ges in se rum fT4 and fT3 le vels af ter LS tre at ment we re not sta tis ti cally dif fe rent in two gro ups of pa ti ents. All pa ti ents we re cli ni cally euth yro id be fo re sur gery. Conc lu si on: LS tre at ment, ei t her alo ne or to get her with an tith yro id drugs, is a sa fe and ef fec ti ve cho i ce for the ra pid pre pa ra ti on of hyperth yro id pa ti ents for thyro i dec tomy, in de pen dent from the eti o logy of hyper th yro i dism.

Objective: To evaluate the usage of duplex power Doppler ultrasound (PDUS) for the differentiation of benign and malignant thyroid nodules. Materials and Methods: We prospectively examined 77 thyroid nodules in 60 patients undergoing ultrasound-guided fine needle aspiration biopsy (FNAB). Each nodule was described according to size, inner structure, borders, parenchymal echogenicity, peripheral halo formation, and the presence of calcification (B-mode ultrasound findings). Vascularity as determined by PDUS imaging was defined as non-vascular, peripheral, central, or of mixed type. For each nodule, the pulsatility index (PI) and resistive index (RI) values were obtained. Results of FNAB and surgical pathological examination (if available) were used as a proof of final diagnosis to categorize all nodules as benign or malignant. A receiver operating characteristic (ROC) curve analysis was performed to establish cut-off, sensitivity, and specificity values associated with RI-PI values. Results: A significant relationship was observed between malignancy and irregular margins, microcalcifications, and hypoechogenicity on ultrasound examination (p < 0.05). The pattern of vascularity as determined by PDUS analysis was not a statistically significant criterion to suggest benign or malignant disease in this study (p > 0.05). The central, peripheral, and mean RI-PI values were higher in malignant nodules when compared to the other cytologies (p < 0.05). Conclusion: Vascularity is not a useful parameter for distinguishing malignant from benign thyroid nodules. However, RI and PI values are useful in distinguishing malignant from benign thyroid nodules.

Type 2 diabetes is an endocrine and metabolic disorder appearing with insulin resistance and impaired beta cell secretory function. Type 1 diabetes is characterized by the autoimmune destruction of pancreatic beta cells, which leads to absolute insulin deficiency. Diabetic ketoacidosis is considered a cardinal feature of type 1 diabetes. A number of studies have demonstrated that diabetic ketoacidosis also occurs in subjects with type 2 diabetes. Such patients are classified as idiopathic type 1 diabetes, type 1B diabetes, Flatbush diabetes or ketosis-prone type 2 diabetes. The aim of our study was to present two patients, who were diagnosed with ketosis-prone type 2 DM, as well as to discuss the subject in the light of the extant literature and to be able to make general recommendations. Turk Jem 2009; 13: 56-9

WOS: 000362601700003 Purpose: This open-label, single-arm, phase 4 study was designed to evaluate the efficacy of intensive insulin glargine titration in type 2 diabetes mellitus (T2DM) patients for 6 months to reach good glycaemic control. Material and Method: Two hundred-forty one insulin-naive T2DM patients were included. The primary efficacy variable was the glycaemic control (HbA1c level of

Bu çalışma, 26 Nisan 2003 tarihinde Lyon[Fransa]'da düzenlenen 6. European Congress of Endocrinology'de bildiri olarak sunulmuştur. To examine serum leptin concentrations in obese and lean patients with polycystic ovary syndrome (PCOS) to assess whether the changes in leptin levels are due to obesity or hormonal alterations. Controlled clinical study. Academic research environment. Obese and lean women with PCOS. Blood samples were collected before and after food consumption. Serum leptin and insulin levels. Serum leptin concentrations were significantly correlated with body mass index (r = 0.649) and also with HOMA (r = 0.535). However, after controlling for body mass index in a partial correlation analysis, no significant correlation was found between serum leptin levels and HOMA or hyperinsulinemia. While lean patients with PCOS had a significant correlation between leptin concentrations and obesity parameters, they did not show any significant correlation with insulin resistance parameters. Although leptin concentrations in women with PCOS correlate with insulin resistance/hyperinsulinemia, this is related only to obesity.

The objective of this study was to investigate the effects of some clinical and pathological features of prolactinomas on tumour behaviour.The study included 113 patients with prolactinoma (27 male, 86 female), with a mean age at diagnosis of 34.4 ± 10.0 years (40.3 ± 12.6 in males, 32.6 ± 8.3 in females). Patients were grouped as invasive or non-invasive according to radiological imaging findings. Ki-67 levels were evaluated if possible.The mean adenoma size (longest dimension) was 38.6 ± 21.6 mm and 10.8 ± 9.4 mm in male and female patients. Pre-treatment serum levels of prolactin were defined as mean 1,926 ± 6,662 ng/mL in all, 124.8 ± 63.4 and 4,675 ± 10,049 ng/mL in the noninvasive and invasive groups (p0.05). A positive correlation was found between the serum levels of prolactin and tumour size. The rate of patients with Ki-67 ≥ 0.03 was 37.5% and 47.8% in the noninvasive and invasive groups. The reduction rates were 60.8% and 80.4% in tumour sizes and 81.1% and 93.8% in prolactin level in the noninvasive and invasive groups, respectively, (p0.05).We found a strong correlation between prolactin levels and invasiveness in male patients compared to females. Ki-67 index was not found to have a place in defining the prognosis.

Pituitary apoplexy is a rare clinical syndrome characterized by sudden onset of headache and vomiting, accompanied by visual disturbance or ocular motility impairment and pituitary insufficiency. Pituitary apoplexy presenting with these symptoms is seen in approximately 3% of patients with surgically treated pituitary adenomas. In acromegalic patients, apoplexy can be related to some provocating factors and rarely may be spontaneous. We present the case of an acromegalic patient with spontaneous remission after apoplexy. A 39-year-old male patient had transsphenoidal microsurgery for acromegaly in 1994 but remission was not achieved. After a 10-year period without follow-up, he experienced severe headache, nausea, vomiting, photophobia, and visual disturbance in July 2005 and scheduled an appointment with an ophthalmologist. His complaints ceased spontaneously within weeks. In October 2005, sellar MRI examination revealed a 3x2.5 cm mass of adenomatous tissue with necrosis. On admission to our clinic in November 2005, visual acuity, visual fields, and ocular motility, were normal; but results of laboratory tests revealed panhypopituitarism. He was thought to have apoplexy of a growth hormone secreting tumor, and hormone replacement therapy was initiated for panhypopituitarism. Because his symptoms had regressed, surgery was not considered. On rare occasions, acromegaly spontaneously remits after apoplexy, resulting in improved control of the functional adenoma without surgical intervention. Turk Jem 2008; 12: 80-2

The objective of this study was to investigate the effect of G870A gene polymorphism of CCND1 on the formation and behavioral features of prolactinomas. One hundred and thirteen patients with prolactinoma and 108 age and gender matched control were included in the study. The patients were divided into two groups as noninvasive and invasive tumors. CCND1 G870A gene polymorphism was compared in patients/control and invasive/noninvasive groups. A and G allele frequencies were found as 41.7% and 58.3% in the controls, and 61.1% and 38.9% in the patients (p

Aim Sitagliptin is not associated with weight gain and has neutral effects on body weight. It is unclear whether sitagliptin treatment alters serum ghrelin levels in people with type 2 diabetes. Methods Forty-four subjects with type 2 diabetes were randomly assigned to receive sitagliptin or medical nutrition therapy (MNT) for 12 weeks. Changes in anthropometric variables, glycemic control, insulin resistance, lipid parameters, and total ghrelin levels were evaluated at baseline and following 12 weeks of treatment. Results Significant decreases in body weight and body mass index were observed over the entire study period in both treatment groups. Glycosylated hemoglobin and postprandial plasma glucose levels were statistically significant decreased in the groups receiving sitagliptin compared with baseline values ( p = 0.021 and p = 0.021, respectively), while they were unchanged in the groups receiving MNT. There was a significant decrease in total ghrelin in the groups receiving sitagliptin ( p = 0.04) compared with baseline values but not in the groups receiving MNT ( p = 0.46) at the end of the 12 weeks. Conclusions In this study of patients with type 2 diabetes, treatment with sitagliptin was associated with a significant decrease in serum ghrelin levels. These results suggest that the neutral effect of sitagliptin on weight might be associated with the suppression of fasting serum ghrelin levels.

The effects of Origanum onites on endothelial function and antioxidative status were investigated in 48 patients with mild hyperlipidaemia who required no drug therapy. All participants were given lifestyle and low-fat dietary advice, however 32 of the patients (study group) were also prescribed 25 ml of aqueous distillate of Origanum onites to be taken after each meal for 3 months. The remaining 16 patients were the control group. Various biochemical markers and endothelial function parameters were measured at baseline and after 3 months. A significantly greater increase in high density lipoprotein-cholesterol and significantly greater decreases in low density lipoprotein-cholesterol, apolipo-protein B, lipoprotein(a) and high-sensitivity C-reactive protein occurred in the study group compared with the control group over the 3-month study period. Paraoxonase and arylesterase activities, and flow- and nitroglycerine-mediated dilatation of the brachial artery showed significantly greater increases in the study group compared with the changes in the control group. In conclusion, consumption of Origanum onites distillate had beneficial effects on lipid profiles, antioxidant status and endothelial function in patients with mild hyperlipidaemia.

Tumour necrosis factor-alpha (TNF-alpha) has been suggested to play a key role in insulin resistance (IR) in obesity and may contribute to the development of type 2 diabetes mellitus. Recently, studies are focused on the effect of antihypertensive drugs on insulin sensitivity and cytokines. We undertook this study to evaluate the effect of amlodipine, a long-acting dihydropyridine calcium channel blocker treatment on TNF-alpha, homeostasis model assessment (HOMA) IR and leptin levels in obese hypertensive type 2 diabetic patients.Amlodipine 5-10 mg for 12 wk was given to type 2 diabetic patients in the amlodipine group. Pre- and post-treatment values of laboratory parameters in the amlodipine group were compared with those of normotensive nondiabetic obese controls. At baseline blood pressures (BP) and metabolic parameters were measured in all patients and repeated after 12 wk in the amlodipine group.Basal waist-to-hip ratio, systolic and diastolic BPs, fasting glucose, TNF-alpha and HOMAIR values of the amlodipine group were higher than the control group. No difference was detected in body mass index, fasting insulin, hemoglobin A1c and leptin values between groups. The systolic and diastolic BPs, fasting glucose, HOMA-IR and TNF-alpha values decreased significantly after the treatment. But, there was no correlation between percentage change in TNF-alpha and HOMA-IR.Besides reducing BP, amlodipine seemed to improve IR and decrease TNF-alpha levels. In this context, these properties may provide additional benefits of antihypertensive drug regimens chosen for this population, but larger group interventions are needed.

Corrigendum to “Effect of cyclin D1 (CCND1) gene polymorphism on tumor formation and behavior in patients with prolactinoma” [Gene 509 (2012) 158–163] Soner Cander ⁎, Erdinc Erturk , Mutlu Karkucak , Ozen Oz Gul , Orhan Gorukmez , Tahsin Yakut , Oguz Kaan Unal, Canan Ersoy , Ercan Tuncel , Sazi Imamoglu a a Uludag University, Medical School, Department of Endocrinology and Metabolism, Bursa, Turkey b Uludag University, Medical School, Department of Medical Genetic, Bursa, Turkey c Bursa Sevket Yilmaz Education and Research Hospital, Department of Endocrinology and Metabolism, Bursa, Turkey

Insulin resistance (IR) is the core problem in type 2 diabetes mellitus that may lead to cardiovascular morbidity and mortality. Hypertension commonly accompanies type 2 diabetes. Antihypertensive agents improving IR may reduce the risk of cardiovascular diseases. This study was conducted to assess the effect of trandolapril on IR, glucose and lipid metabolisms in hypertensive subjects with different degrees of IR and investigate the importance of IR level in angiotensin converting enzyme inhibitor response. The subjects were nondiabetic and type 2 diabetic hypertensive patients treated with trandolapril for 12 weeks. Blood pressures (BP) and metabolic parameters were measured in all patients at baseline and after 12 weeks of trandolapril treatment and compared. Trandolapril reduced BP similarly in nondiabetic and diabetic patients. Homeostasis model assessment insulin resistance (HOMA-IR), serum glucose and hemoglobin A1C (A1C) in diabetic patients were higher than nondiabetics. HOMAsignificantly after trandolapril in diabetics, while serum glucose, insulin and A1C remained unchanged. The posttreatment HOMA-IR values were comparable in both groups. Pretreatment HOMA-IR value was found to be associated with HOMA-IR response to trandolapril while changes in BMI, A1C and BPs were unrelated. The patients with a pretreatment HOMA-IR of >4.67 responded better. In conclusion, trandolapril improved insulin sensitivity better in type 2 diabetic hypertensive patients with higher degree of IR compared with the ones with low grade IR, being independent of its hemodynamic action, Insulin resistance (IR) is the core problem in type 2 diabetes mellitus that may lead to cardiovascular morbidity and mortality. Hypertension commonly accompanies type 2 diabetes. Antihypertensive agents improving IR may reduce the risk of cardiovascular diseases. This study was conducted to assess the effect of trandolapril on IR, glucose and lipid metabolisms in hypertensive subjects with different degrees of IR and investigate the importance of IR level in angiotensin converting enzyme inhibitor response. The subjects were nondiabetic and type 2 diabetic hypertensive patients treated with trandolapril for 12 weeks. Blood pressures (BP) and metabolic parameters were measured in all patients at baseline and after 12 weeks of trandolapril treatment and compared. Trandolapril reduced BP similarly in nondiabetic and diabetic patients. Homeostasis model assessment insulin resistance (HOMA-IR), serum glucose and hemoglobin A1C (A1C) in diabetic patients were higher than nondiabetics. HOMA-IR (from 9.0  1.0 to 6.6  0.7, p4.67 responded better. In conclusion, trandolapril improved insulin sensitivity better in type 2 diabetic hypertensive patients with higher degree of IR compared with the ones with low grade IR, being independent of its hemodynamic action.