Investigation of genotoxicity in acromegaly from peripheral blood lymphocyte cultures using a micronucleus assay.

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.

Evaluation of the ovarian reserve function in patients with metabolic syndrome in relation to healthy controls and different age groups.

OBJECTIVE: To evaluate the ovarian reserve function in female patients with metabolic syndrome (MetS). METHODS: This study evaluated 136 subjects, 67 with MetS and 69 controls. Subjects were divided into three age groups. Group I included 49 subjects aged 20-29 years, 22 with MetS and 27 controls; group II included 45 subjects aged 30-39 years, 22 with MetS and 23 controls; and group III included 42 subjects aged 40-49 years, 23 with MetS and 19 controls. Demographic characteristics, anthropometrics, blood biochemistry, and gonadotrophic hormones were compared as total ovarian volume and antral follicle count on ovarian transvaginal ultrasonography. RESULTS: Serum levels of FSH, LH, E2 and progesterone were similar in the MetS and control groups, while testosterone levels were significantly higher in MetS patients than controls, both in the overall population (p = 0.024) and in those aged 20-29 years (p = 0.018). Total ovarian volume was significantly lower in MetS patients than controls, in both the overall population (p = 0.003) and those aged 20-29 years (p = 0.018), while antral follicle counts were similar. Ovarian volume correlated positively with antral follicle count (AFC) (r = 0.37; p < 0.001) and negatively with age (r = 0.34; p < 0.001) and FSH concentration (r = 0.21; p = 0.013). AFC was negatively correlated with age (r = 0.36; p < 0.001). CONCLUSION: Ovarian reserve function is significantly lower in MetS patients than in healthy control subjects, particularly in women aged 20-29 years.

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.

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.

A rare cause of hypoglycemia in a type 2 diabetic patient: insulinoma.

Recurrent episodes of hypoglycemia in patients with diabetes are often associated with the ongoing treatment regimen. However, despite changes in treatment modalities, assessment of the causes of hypoglycemia in nondiabetic patients in the presence of severe and recurrent hypoglycemia is very important. The treatment that had been provided for 6 years in a 67-year-old female patient with type 2 diabetes mellitus was discontinued due to hypoglycemic episodes that presented for the previous 2 years. The patient experienced persistent hypoglycemia after cessation of the treatment and was hospitalized for further examination. Spontaneous hypoglycemia with a final diagnosis of insulinoma was established following histopathologic evaluation and was relieved postoperation. Insulinoma is rarely encountered as a cause of hypoglycemia in patients with type 2 diabetes. Insulin-secreting tumors should be considered where hypoglycemic episodes occur despite discontinuation of insulin and other antidiabetic treatment with endogenous hyperinsulinemia being noncompliant with the blood glycemic levels.

Effect of sitagliptin monotherapy on serum total ghrelin levels in people with type 2 diabetes.

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.