Retrospective Evaluation of Bone Metastases in Patients With Thyroid Malignancy: A Single-Center Experience.

Background Thyroid cancer is one of the five most common cancers causing bone metastasis. If there is an increase in serum thyroglobulin-antithyroglobulin levels in differentiated thyroid cancer or calcitonin levels in medullary thyroid cancer, patients should be evaluated for recurrence and distant metastasis. The skeleton is the second most common site of distant metastasis in thyroid cancer after the lung. Bone metastases cause pain, fractures, and spinal cord compression, severely reducing the quality of life. They are associated with poor prognosis. Bone metastases severely reduce the quality of life. This study aimed to retrospectively evaluate the diagnosis and follow-up of patients with thyroid cancer with bone metastases diagnosed at our center. Methodology A total of 1,390 patients diagnosed with thyroid malignancy at our center between 2010 and 2023 were reviewed retrospectively. The study included 27 patients with differentiated and medullary thyroid cancer who had bone metastases. Results Of 27 patients, 19 (70.4%) had differentiated and eight (29.6%) had medullary thyroid cancer. Papillary thyroid cancer constituted 22.2% (n = 6) and follicular thyroid cancer constituted 14.8% (n = 4) of the cases. Papillary carcinoma follicular variant, oncocytic, and poorly differentiated thyroid cancer were diagnosed with similar frequency, each accounting for 11.1% (n = 3). It was found that vertebrae were most commonly involved, followed by the pelvis, sternum, costae, femur and patella, shoulder and humerus, cranium, and scapula. The five-year survival rate was 72%, and the 10-year survival rate was 53%. Conclusions The number of patients with papillary cancer was the highest, but the rate of bone metastases was the lowest in this group. The highest rate of bone metastases was found in patients with poorly differentiated, oncocytic, medullary, follicular, and papillary cancer, respectively. The results obtained in this study reveal the necessity and importance of bone metastasis evaluation in patients with thyroid cancer.

Central venous sampling and magnetic resonance imaging in the diagnosis of ACTH-dependent Cushing's syndrome.

OBJECTIVES: Central venous sampling (CVS) with corticotropin-releasing hormone (CRH) stimulation is a crucial technique in evaluating adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome (CS). We evaluated central venous sampling (CVS) and magnetic resonance imaging (MRI) findings in predicting the localization and lateralization of pituitary microadenomas. METHODS: We analyzed 29 patients with CS who underwent CVS with CRH stimulation and examined with MRI retrospectively. Catheterization to central sinuses was successfully performed in 26 patients. Three patients with variant anatomy or inability to cannulate were diagnosed with CD after examination of pathology. RESULTS: After CVS, among 26 patients, 23 patients were determined to have CD (88.4%) and 2 (7.7%) patients were diagnosed with ectopic ACTH syndrome. One patient was diagnosed with CD postoperatively. While the sensitivity of the CVS was 95.6%, sensitivity of the preoperative pituitary MRI was lower (69.5%). Also, the negative predictive value ratio was higher in CVS than in MRI (66% versus 22%). Diagnostic accuracy in the lateralization of the tumor was high as in CVS as in MRI (76.4% versus 73.9%). CONCLUSION: Central venous sampling with higher sensitivity in the localization of pituitary microadenoma, also has approximately similar diagnostic accuracy in lateralizing the tumor with MRI.

Comparison of the effects of medical and surgical treatments in giant prolactinoma: a single-center experience.

PURPOSE: Giant prolactinomas, which have extremely large sizes and high prolactin (PRL) values, are rarely seen. Although medical therapy is effective, surgical treatment is more frequently applied due to slightly lower response rates and compression symptoms. This study aimed to compare the medical and surgical treatment results in giant prolactinomas. METHODS: Thirty-nine patients who were followed up in our center for giant prolactinoma were included in the study, and the response rates of the patients were evaluated after the medical and surgical treatments. The treatment responses were compared in terms of tumor volume, PRL level, visual field, and pituitary function. RESULTS: The outcomes of the 66 treatment periods (medical n = 42; surgical n = 24) in 39 patients (mean age, 47.2 years; men, 89.7%) were evaluated. The most common presentations were hypogonadism and visual defects. The mean longest tumor diameter at diagnosis was 52.2 ± 11.8 mm, and the median PRL levels were 5000 ng/mL. PRL level normalization was achieved in 69% with medical therapy, and a curative response was obtained in only two patients with surgery. Tumor volume reduction was 67% (no cure) in the medical and 75% (13% cure) in the surgical groups (p = 0.39). Improvement of visual field was 70.8% in the medical and 84.2% in the surgical group (p = 0.12). CONCLUSION: In our study, it was observed that medical therapy was effective and safe in patients with giant prolactinomas. The use of surgical treatment should be limited to prolactinomas with compression or post-resistance to medical treatment in serious cases.

Is laparoscopic adrenalectomy for pheochromocytoma safe and effective in geriatric patients?

OBJECTIVES: The study aimed to assess the haemodynamic changes of laparoscopic adrenalectomy (LA) in geriatric patients with pheochromocytoma (PHEO). To the best of our knowledge, this is the first study to evaluate the haemodynamic outcomes of LA in this patient population. METHODS: Data of 350 patients who underwent single-side transperitoneal LA between 2000 and 2020 were reviewed retrospectively. Patients with a histopathological diagnosis of PHEO were included in the study and classified into two groups according to their ages at the date of surgery. Patients older than 65 years were accepted as elderly according to the World Health Organisation (WHO) recommendations. RESULTS: A total of 54 patients underwent LA for PHEO. Fifteen patients were enrolled in the elderly and 39 in the young groups. There were no significant differences in terms of the operation site (0.564), tumour size (0.878), perioperative results such as mean anaesthesia; operation times, blood loss and haemodynamic changes. There were no significant differences in mean hospitalisation and intensive care unit times. One patient in both groups had grade 1 complication according to Clavien Dindo classification (prolonged ileus, managed with medical treatment and transfusion during surgery, respectively). CONCLUSION: Young and elderly patients had similar outcomes in terms of haemodynamic changes that occurred with LA. LA in elderly patients with PHEO is as safe and effective as in younger patients.

Effect of Parathyroidectomy Timing in Kidney Transplant Recipients on Graft Function.

OBJECTIVES: Persistent hyperparathyroidism can have a deleterious effect on graft function in kidney transplant recipients, although serum calcium, phosphorus, and parathyroid hormone levels tend to normalize after successful transplant. Parathyroidectomy can result in sustained amelioration of persistent hyperparathyroidism despite graft failure risk and unfavorable graft outcomes. Data on this issue are limited and conflicting. Here, we evaluated the effects of parathyroidectomy on graft function in kidney transplant recipients. MATERIALS AND METHODS: This retrospective study included 249 adult kidney transplant recipients (121 deceased-donor/128 living-donor; 142 males/107 females; mean age of 39.3 ± 11.6 y; mean follow-up of 46.5 ± 23.5 mo). Participants were grouped as those without (n = 222), those with pretransplant (n = 12), and those with posttransplant (n = 15) parathyroidectomy. Graft outcomes and serum calcium, phosphorus, and parathyroid hormone levels were studied. RESULTS: Serum calcium levels at baseline and at 1, 3, 6, and 12 months and parathyroid hormone levels at baseline and at 6 and 12 months were higher and serum phosphorus levels at 3, 6, and 12 months were lower in the posttransplant parathyroidectomy group versus the other groups (P < .001). We observed no significant differences between groups regarding serum calcium, phosphorus, and parathyroid hormone levels at last visit. Estimated glomerular filtration rates at 3, 6, and 12 months and at last visit in the pretransplant parathyroidectomy group were higher than in those without parathyroidectomy (P < .05) and higher at 6 and 12 months than in the posttransplant parathyroidectomy group (P < .05). No significant differences regarding graft loss and patient mortality were observed among the 3 groups (P > .05). CONCLUSIONS: Parathyroidectomy resulted in sustained decreased levels of serum calcium and parathyroid hormone. We observed no graft failure risk associated with parathyroidectomy in our study. Parathyroidectomy before transplant is advantageous with better graft function.

Mental status and physical activity in patients with homozygous familial hypercholesterolemia: A subgroup analysis of a nationwide survey (A-HIT1 registry).

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening disease due to high serum low-density lipoprotein (LDL) cholesterol levels. LDL cholesterol-lowering interventions are fundamental for patients with HoFH. OBJECTIVE: It was aimed to investigate the association between the mental status of patients with HoFH and healthy lifestyle behaviors. METHODS: This subgroup analysis of the A-HIT1 population included the data of patients aged ≥18 years with a clinical diagnosis of HoFH undergoing therapeutic LDL apheresis. Besides the demographic and clinical characteristics of patients, healthy lifestyle behaviors were assessed, and psychiatric symptoms were screened by Symptom Check List (SCL-90-R). RESULTS: The highest percentage for pathology was observed in dimensions of obsessive-compulsive, somatization, interpersonal sensitivity, and depression in SCL-90-R. Patients with any cardiovascular condition have more psychiatric symptoms in different fields of SCL-90-R. The outcomes of the correlative analysis indicated that lower the age of the first coronary event better the psychiatric status, probably denoting a better adaptation to disease and its treatment. Among 68 patients, 36 patients were not exercising regularly. Patients with regular physical activity had significantly lower scores in most dimensions of SCL-90-R and there was no association between regular physical activity and other investigated variables. The strongest predictor of regular exercising was global severity index of SCL-90-R. CONCLUSION: In the HoFH population, there was a high prevalence of mental disturbances. Better psychiatric status was associated with regular exercising. Therefore, assessing the mental status of patients with HoFH and referring patients in need, to a psychiatrist, may improve the outcome of patients.

Evaluation of upper gastrointestinal system in acromegaly.

PURPOSE: Acromegaly causes multiple comorbidities, including gastrointestinal disorders. The present study evaluated the frequency of hiatal hernia and other upper gastrointestinal pathologies in patients with acromegaly, given that visceromegaly and reduced nitric oxide levels in acromegaly may impact diaphragm and lower esophageal sphincter function and thus possibly the development of hiatal hernia. METHODS: Thirty-nine acromegaly patients followed our center for the previous 6months were recruited. Upper gastrointestinal endoscopy was performed once in all patients to evaluate hiatal hernia, esophagitis, gastroduodenitis and ulcer. RESULTS: Twenty-three patients were male and 16 female. Upper gastrointestinal endoscopy found hiatal hernia, esophagitis and gastroduodenitis or gastric ulcer in 3 (7.6%), 2 (1.7%) and 31 (79.4%) patients, respectively. Pathologic examination of gastric antrum biopsy found intestinal metaplasia in 12 (30.7%) patients, and Helicobacter pylori was positive in 13 (33.3%). There were no significant correlations between age, gender, disease duration or preoperative adenoma size on the one hand and hiatal hernia or other endoscopic findings on the other. Similarly, neither surgical success nor recurrence was associated with endoscopic findings. CONCLUSIONS: The study showed that prevalence of gastritis, duodenitis, peptic ulcer and intestinal metaplasia is higher and prevalence of hiatal hernia lower in acromegaly patients than in the healthy population. Various unknown disease-related pathophysiological conditions may play a role; there is a need for further studies.

Clinical management, psychosocial characteristics, and quality of life in patients with homozygous familial hypercholesterolemia undergoing LDL-apheresis in Turkey: Results of a nationwide survey (A-HIT1 registry).

BACKGROUND: Homozygous familial hypercholesterolemia (HoFH) is a rare, life-threatening inherited disease leading to early-onset atherosclerosis and associated morbidity. Because of its rarity, longitudinal data on the management of HoFH in the real world are lacking, particularly on the impact the condition has on quality of life (QoL), including the impact of the extracorporeal lipid removal procedure apheresis (LA). METHODS: The A-HIT1 study included 88 patients with HoFH aged ≥12 years receiving regular LA in 19 centers in Turkey. Demographic and disease characteristics data were obtained. For patients aged ≥18 years, additional data on psychosocial status were obtained via the SF-36 score, the Hospital Anxiety and Depression Scale, and a HoFH-specific questionnaire. RESULTS: There was no standardized approach to therapy between centers. Mean (±SD) frequency of LA sessions was every 19.9 (±14) days, with only 11.6% receiving LA weekly, and 85% of patients were not willing to increase LA frequency. The most common concerns of patients were disease prognosis (31%), and physical, aesthetic, and psychological problems (27.5%, 15.9%, and 11.6%, respectively). Lower age at diagnosis was associated with better QoL, lower anxiety, improved functioning, and greater emotional well-being compared to later diagnosis. CONCLUSIONS: These findings demonstrate that adult patients with HoFH undergoing LA, experience significant impairment of QoL with an increased risk of depression. From patients' point of view, LA is time-consuming, uncomfortable, and difficult to cope with. The speed of diagnosis and referral has a considerable impact on patient well-being.

Cytokine signal suppressor (SOCS) 1-1478 CA/del gene polymorphism in Turkish patients with polycystic ovary syndrome.

Eighty-four subjects, premenopausal female patients (n = 42, mean (SD) age: 26.4 (4.2) years) diagnosed with polycystic ovary syndrome (PCOS) and age-matched healthy volunteers (n = 42, mean (SD) age: 27.6(3.4) years), were included in this study. Data on physical examination, anthropometric measurements and blood biochemistry analysis were recorded for each subject along with analysis for SOCS1-1478 CA/del polymorphism by polymerase chain reaction-restriction fragment length polymorphism. The relation of SOCS1-1478 CA/del polymorphism to PCOS status and insulin resistance was analysed via logistic regression analysis. Mean (SD) levels for BMI (28.5(6.5) vs.22.5 (4.9) kg/m2, p < .001), HOMA-IR (3.1(1.8) vs.1.5 (1.0), p < .001), LDL-cholesterol (115.9(32.7) vs.100.7 (27.3)mg/dL, p = .03) and triglyceride (113.8(64.9) vs.83.3(36.3)mg/dL, p = .017) were significantly higher in patients. Groups were similar in terms of SOCS1-1478 CA/del polymorphism. No significant relation of this polymorphism was noted to PCOS and HOMA-IR. Our findings revealed no difference between groups in terms of the rate of SOCS1-1478 CA/del polymorphism, and no significant relation of this polymorphism to insulin resistance and PCOS status. Impact statement Polycystic ovary syndrome (PCOS), the most common cause of anovulation and the most commonly encountered form of female endocrine disease. SOCS proteins have been suggested to play a fundamental role in the negative feedback regulation of the JAK-STAT pathway, which is the major signalling pathway involved in a wide range of physiologic and pathologic processes, including inflammatory diseases, malignancies and immune disorders. Pathways involving the induction of suppression of SOCS proteins were also shown likely to be involved in mediating cytokine-induced insulin resistance. The present study was designed to determine the frequency of SOCS1-1478 CA/del gene polymorphism in patients with PCOS in relation to healthy controls and insulin resistance. Our findings revealed significantly higher rates of insulin resistance, obesity and dyslipidaemia in Turkish patients with PCOS compared with age-matched healthy controls, while no difference between study groups in terms of the rate of SOCS1-1478 CA/del polymorphism along with no significant relation of SOCS1-1478 CA/del polymorphism to insulin resistance and PCOS status. Future larger scale studies with the application of standardised diagnostic methods and criteria, and of state-of-the-art modern techniques including genomics, proteomics and pharmacogenetics would provide better understanding of the association between PCOS and genomic variants.

Assessing the Impact of Insulin Glargine and Detemir Treatment to Serum Total IGF1 Levels in the Insulin-Naive Type 2 Diabetic Patients.

AIM: The mitogenic potential of analog insulins due to their different insulin-like growth factor-1 (IGF1) receptor affinity is a situation that causes concern related to cancer risk. We aimed to examine the changes in the serum IGF1 levels formed by insulin glargine and detemir in the insulin-naive type 2 diabetic patients. METHODS: The serum total IGF1 levels of the 62 insulin-naive type 2 diabetic patients were studied before and after 12 weeks of the started treatment with basal insulin analogs. Twenty-two and twenty patients (Group I and II) using the single-dose and double-dose insulin detemir and twenty patients (Group III) using insulin glargine were evaluated. RESULTS: In Group I and Group II, the average 8.5% and 0.1% increases and in the Group III, 6.5% decreases were determined in the IGF1 values. The IGF1 changes were significant in the men but not in the women. CONCLUSION: In our study, it was determined that the insulin glargine depressed the serum IGF1 levels much more when compared to the insulin detemir. This result can be evaluated as the in vivo reflection of the in vitro findings related to the fact that the IGF1 receptor affinity of the glargine is higher.

Changes in the management of type 2 diabetic patients in family medicine practices in the Bursa region.

AIM: The aim of the study was to investigate the treatment and monitoring patterns of type 2 diabetes patients in the Bursa region over the last 5 years since the implementation of family practice in Turkey in 2010. METHODS: A total of 216 volunteer family doctors working in family health centers took part in this study. The records of 44,819 diabetic patients who visited these doctors between January 1, 2010 and December 31, 2014 were inspected retrospectively. Apart from the identity of the patients, morphometric data, including the type of medication used for diabetes and the HbA1C, serum creatinine and LDL cholesterol values, were recorded. RESULTS: A total of 38.9% (17,416 patients) of the patients in the study were male and 61.1% (27,403 patients) were female. The average age was 59.7 years with a range of 13.2 years. Although the patients' average body mass index (BMI) did not change over the 5years monitoring, average blood pressure (BP), and serum creatinine and LDL cholesterol levels decreased significantly. The hemoglobin A1c levels were significantly lower after 2010 compared to the 2010 data. Upon examining the medication prescribed for the patients, we determined that the use of metformin and insulin increased, whereas the prescription of thiazolidinedione (glitazone) decreased. There was a significant increase in the amount of patient data recorded over the last 5 years. CONCLUSIONS: Despite the increased level of data entry in these patients with type 2 diabetes, the surveillance of diabetes parameters according to treatment guidelines remains suboptimal. There continues to be a need to engage family practitioners on ongoing education and practice enhancement programs.

Effect of Rosiglitazone and Insulin Combination Therapy on Inflammation Parameters and Adipocytokine Levels in Patients with Type 1 DM.

AIM: To investigate the efficacy of combined therapy of insulin and rosiglitazone on metabolic and inflammatory parameters, insulin sensitivity, and adipocytokine levels in patients with type 1 diabetes mellitus (type 1 DM). MATERIAL AND METHODS: A total of 61 adults with type 1 DM were randomly and prospectively assigned in open-label fashion to take insulin and rosiglitazone 4 mg/day (n = 30) or insulin alone (n = 31) for a period of 18 weeks while undergoing insulin therapy without acute metabolic complications. RESULTS: Combination therapy did not significantly improve metabolic and inflammatory parameters, insulin sensitivity, and adiponectin levels. While leptin and resistin levels decreased in both groups (group 1: resistin 6.96 ± 3.06 to 4.99 ± 2.64, P = 0.006; leptin 25.8 ± 17.6 to 20.1 ± 12.55, P = 0.006; group 2: resistin 7.16 ± 2.30 to 5.57 ± 2.48, P = 0.031; leptin 16.72 ± 16.1 to 14.0 ± 13.4, P = 0.007) Hgb and fibrinogen levels decreased only in group 1 (Hgb 13.72 ± 1.98 to 13.16 ± 1.98, P = 0.015, and fibrinogen 4.00 ± 1.08 to 3.46 ± 0.90, P = 0.002). Patients in both groups showed weight gain and the incidence of hypoglycemia was not lower. DISCUSSION: The diverse favorable effects of TZDs were not fully experienced in patients with type 1 DM. These results are suggesting that insulin sensitizing and anti-inflammatory characteristics of TZDs were likely to be more pronounced in patients who were not totally devoid of endogenous insulin secretion.

Relationship between glycemic control, microalbuminuria and cognitive functions in elderly type 2 diabetic patients.

AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Prevalence and correlates of erectile dysfunction in type 2 diabetes mellitus: a cross-sectional single-center study among Turkish patients.

OBJECTIVE: The aim of this study was to evaluate prevalence of erectile dysfunction (ED) in patients with type 2 diabetes mellitus (T2DM) in relation to vascular and neurogenic correlates. METHODS: A total of 116 males including T2DM patients [n=68; mean age, 56.7 (5.8) years] and age-matched healthy controls [n=48; mean age, 57.0 (6.6) years] were included in this cross-sectional single-center study. Data on anthropometrics, blood biochemistry, concomitant hypertension, hyperlipidemia, and coronary artery disease (CAD) were recorded in each subject along with measurement of carotid artery intima media thickness (CIMT) and evaluation of erectile dysfunction (ED) via International Index of Erectile Function (IIEF-5) Questionnaire. A univariate analysis was performed to determine the relationship of cardiovascular risk factors and diabetes-related complications to ED. RESULTS: Patient and control groups were similar in terms of percentage patients with hyperlipidemia (51.5% and 39.6%, respectively) and CAD (33.8% and 22.9%, respectively), whereas concomitant hypertension was more common (P=0.05) and CIMT values were significantly higher (P=0.020) in patients with T2DM compared with controls. Polyneuropathy was noted in 46.2% of patients, nephropathy in 30.8%, and retinopathy in 33.8%. ED scores were significantly lower in patients than controls [14.3 (7.3) vs. 18.2 (6.3), P=0.004] with a significantly higher percentage of patients than controls in the category of severe dysfunction (29.4 vs. 10.4%, P=0.014). Univariate analysis revealed that diabetic polyneuropathy was the only factor to be associated with higher likelihood (93.3% in the presence and 60.0% in the absence of neuropathy) and severity (43.3% in the presence and 14.3% in the absence of neuropathy) of ED (P=0.004). CONCLUSION: Findings from the present cross-sectional single-center study revealed the prevalence of ED to be considerably higher in patients with T2DM than age-matched healthy controls, with identification of diabetic polyneuropathy as the only risk factor associated with higher likelihood and more severe forms of ED.

Comparison of efficacy and safety of once- versus twice-daily insulin detemir added on to oral antidiabetics in insulin-naive type 2 diabetes patients: 24-week, crossover, treat to target trial in a single center.

AIM: To compare once- versus twice-daily insulin detemir added on OADS therapy in insulin-naive type 2 diabetes patients in terms of efficacy and safety. METHODS: An open-label study performed at a single center, comprised a randomized, crossover 24 week with insulin-naive type 2 diabetes patients. Insulin detemir was initiated with mean 0.12 U/kg in all patients (Group I once-daily, Group II twice-daily) and titrated for 24 week. RESULTS: A total of 50 patients completed the study (Group I n:25, Group II n:25). With use of once- and twice-daily insulin, HbA1c values were decreased by 1.8% (±2.0) and 1.5% (±1.4) within the first 12 weeks (p<0.01), whereas increased by 0.21% (±0.7) and 0.14% (±0.8) in the second 12 weeks (p>0.05). The increases in the insulin doses were found as 0.22 U/kg and 0.35 U/kg with once- and twice-daily insulin use, respectively (p:0.04). Although minor hypoglycemic events were similar in both groups in the first 12 weeks, 2-fold increase was found in the patients shifting from once- to twice-daily dose. Within the first and second periods, the body weight of the patients was observed an increase of 0.4 and 1.6 kg with once-daily dose, whereas a decrease of 0.1 and 2.1 kg in the twice-daily dose, in the same period. CONCLUSION: Once-daily use of insulin detemir up to 0.4 U/kg was found to have similar efficacy and safety as twice-daily use. Twice dose use of insulin did not provide a prominent glycemic control advantage on 1.5-fold higher use of insulin.

Comparative genotoxic and cytotoxic effects of the oral antidiabetic drugs sitagliptin, rosiglitazone, and pioglitazone in patients with type-2 diabetes: a cross-sectional, observational pilot study.

This cross-sectional, observational pilot study was designed to investigate the frequency of different endpoints of genotoxicity (sister-chromatid exchange, total chromosome aberrations, and micronucleus formation) and cytotoxicity (mitotic index, replication index, and nuclear division index) in the peripheral lymphocytes of patients with type-2 diabetes treated with different oral anti-diabetic agents for 6 months. A total of 104 patients who met the American Diabetes Association criteria for type-2 diabetes were enrolled in the study. Of the 104 patients, 33 were being treated with sitagliptin (100mg/day), 25 with pioglitazone (30mg/day), 22 with rosiglitazone (4mg/day), and 24 with medical nutrition therapy (control group). The results for all the genotoxicity endpoints were significantly different across the four study groups. Post hoc analysis revealed that the genotoxicity observed in the sitagliptin group was significantly higher than that observed in the medical nutrition therapy group, but lower than that occurring in subjects who received thiazolidinediones. All of the three cytotoxicity endpoints were significantly lower in patients treated by oral anti-diabetic agents compared with those who received medical nutrition therapy. However, the three indexes did not differ significantly in the sitagliptin, rosiglitazone, and pioglitazone groups. Taken together, these pilot data indicate that sitagliptin and thiazolidinediones may exert genotoxic and cytotoxic effects in patients with type-2 diabetes. Further investigations are necessary to clarify the possible long-term differences between oral anti-diabetic drugs in terms of genotoxicity and cytotoxicity, and how these can modulate the risk of developing diabetic complications in general and cancer in particular.

Effect of cyclin [corrected] D1 (CCND1) gene polymorphism on tumor formation and behavior in patients with prolactinoma.

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<0.01). Rates of G/G, G/A and A/A genotypes were found as 11.8%, 55.9% and 32.4% in the noninvasive group, and 15.6%, 44.4% and 40.0% in the invasive group, respectively. Differences between patient and control groups were significant but were not between invasive and noninvasive groups in terms of the allele frequencies and genotype distribution. Mean tumor size and serum levels of prolactin at the time of diagnosis and change in these values after the treatment were not found statistically significant in genotype subgroups. CCND1 G870A gene polymorphism may be an important factor in the early stages of the tumor formation. However, it did not affect the features of the tumor.

Comparative effects of pioglitazone and rosiglitazone on plasma levels of soluble receptor for advanced glycation end products in type 2 diabetes mellitus patients.

Low levels of soluble receptor for advanced glycation end products (sRAGE) have been associated with the occurrence of vascular complications in patients with type 2 diabetes mellitus. Preliminary evidence has suggested that thiazolidinediones have the ability to modulate circulating levels of this molecule in the hyperglycemic milieu. The aim of this pilot study was to assess the differential effect of 2 different thiazolidinediones-pioglitazone and rosiglitazone-on plasma levels of sRAGE in type 2 diabetes mellitus patients. Sixty type 2 diabetes mellitus subjects were randomly assigned to receive pioglitazone (30 mg/d, n = 19), rosiglitazone (4 mg/d, n = 20), or placebo (medical nutrition therapy, n = 21) for 12 weeks. Changes in plasma glucose, glycosylated hemoglobin, insulin resistance (homeostasis model assessment), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and sRAGE were evaluated at baseline and after 12 weeks. At 12 weeks, the pioglitazone (P < .001) group had a significant increase from baseline in sRAGE values that was not seen in the medical nutrition therapy and rosiglitazone groups. We conclude that, in type 2 diabetes mellitus patients, pioglitazone-but not rosiglitazone-significantly raised sRAGE, which may contribute to its antiatherogenic effects.

Evaluation of chromosome aberrations, sister chromatid exchange and micronuclei in patients with type-1 diabetes mellitus.

Oxidative stress-induced DNA damage seems to play a role in the pathogenesis of type-1 diabetes mellitus and its complications. Several in vitro assays have been used to measure the DNA damage produced by oxidative stress. In the present study, we aimed to investigate the frequency of sister chromatid exchange (SCE), chromosomal aberrations (CA) and micronuclei (MN) in type-1 diabetes mellitus patients compared with healthy controls. SCE, CA and MN tests were carried out with the blood-cell cultures from 35 type-1 diabetic patients and 15 healthy, age- and sex-matched control subjects. The mean age of the type-1 diabetic patients was 31.89 +/- 10.01 years, with a mean duration of the diabetes of 7.8 +/- 6.02 years. The mean level of HbA1c of the type-1 diabetic patients was 8.37+/-1.36%. Only three (8.5%) patients with type-1 diabetes mellitus had an HbA1c level below 7%. Patients with type-1 diabetes mellitus showed a higher frequency of SCE compared with controls (5.44 +/- 1.47 and 2.54 +/- 0.82, respectively, p < 0.001), but there was no significant correlation between the duration of diabetes, HbA1c and SCE. No significant difference was found in CA or MN frequency in type-1 diabetic patients compared with controls. In conclusion, these results suggest that type-1 diabetes mellitus is a condition with genomic instability characterized by an increased level of SCE. Hyperglycemia-induced oxidative stress may be the underlying factor of the increased SCE frequency.