Soner Cander

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.

Serum Levels of sRAGE Are Associated with Body Measurements, but Not Glycemic Parameters in Patients with Prediabetes.

BACKGROUND Our aim was to assess serum levels of the soluble receptor for advanced glycation end products (sRAGE) and to examine their association with anthropometric and metabolic parameters in patients with prediabetes and obese controls. METHODS The two study groups were composed of 42 patients with prediabetes and diabetic neuropathy and 42 age-, gender-, body weight (BW)-, and body mass index (BMI)-matched obese adults as the control group. Prediabetes was diagnosed by the following criteria issued by the American Diabetes Association: impaired fasting glucose [fasting plasma glucose (FPG) level of 100-125 mg/dL], impaired glucose tolerance (2 hr plasma glucose level of 140-199 mg/dL after a 75 grams oral glucose challenge), or a glycated hemoglobin (HbA1C) level of 5.7%-6.4%. RESULTS There were no differences between the groups in terms of age, gender distribution, BW, or BMI. Despite these similarities, patients with prediabetes had higher FPG, HbA1c, and 2-hr postchallenge glucose levels, higher systolic and diastolic blood pressure, and larger waist and hip circumferences compared with the obese controls. Lipid measurements, complete blood counts, kidney and liver function tests, high-sensitivity C-reactive protein, and sRAGE levels were similar between the two groups. We found significant negative correlations between sRAGE levels and BW, BMI, waist and hip circumferences, waist-to-hip ratios, and low-density lipoprotein (LDL) cholesterol levels. There were no significant correlations with other parameters, including demographic, metabolic, and blood pressure measurements. CONCLUSIONS In contrast to glycemic parameters, serum levels of sRAGE were negatively correlated with body measurements indicative of obesity in the prediabetic state. In addition, the negative correlation with LDL cholesterol levels suggests that sRAGE has a more robust association with metabolic syndrome than with prediabetes.

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.

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 cycline 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.

Evaluation of insulin resistance and plasma levels for visfatin and resistin in obese and non-obese patients with polycystic ovary syndrome

This study was designed to evaluate insulin resistance and plasma levels of visfatin and resistin in obese and non-obese patients with polycystic ovary syndrome (PCOS).A total of 37 premenopausal PCOS patients with (n = 18, mean (SD) age: 27.5 (5.7 years) or without obesity (n = 19, mean (SD) age: 23.7 (3.1) years) and healthy volunteers (n = 18, mean (SD) age:29.8 (4.1) years) were included in this study. Data on clinical characteristics, glycemic parameters and lipid parameters were recorded for each subject as were plasma visfatin and resistin levels. Mean (SD) HOMA-IR values were significantly higher in obese PCOS patients (3.4 (1.7)) compared with non-obese PCOS patients (2.0 (1.2), p<0.01) and controls (1.6 (0.8), p<0.01). No significant difference was noted between study groups in terms of plasma resistin (ng/mL) or visfatin (ng/mL) levels. There was no correlation between serum plasma visfatin (r = 0.127, p = 0.407) and resistin (r = -0.096, p = 0.544) levels and HOMA-IR. In conclusion, our findings revealed increased likelihood of metabolic and dyslipidemic manifestations in obese compared to non-obese PCOS patients, while no significant difference was noted in visfatin and resistin levels among PCOS patients in terms of co-morbid obesity and in comparison to controls.

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

Abstract 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.

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.

Prolactin levels and gender are associated with tumour behaviour in prolactinomas but Ki-67 index is not

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.

The Impact of Patient Education on Anthropometric, Lipidemic, and Glycemic Parameters Among Patients With Poorly Controlled Type II Diabetes Mellitus: A 3-Month Prospective Single-Center Turkish Study.

This study evaluated the impact of patient education on adherence to a diabetes care plan (e.g., anthropometric, lipidemic, and glycemic parameters) among adults with type II diabetes mellitus without adequate glycemic control. A total of 61 ambulatory adults with type II diabetes mellitus (mean age: 53.6 ± 8.2 years, 70.5% female) were evaluated for anthropometrics, duration of diabetes mellitus, type of anti-diabetic treatment, blood biochemistry, and glycemic parameters in this 3-month prospective observational single-center study. During the course of the study, participants demonstrated a significant decrease in body weight and fat percentage and HbA1c (p < .001 for each). None of the factors evaluated was a significant determinant for glycemic parameters. These findings revealed that adults with type II diabetes mellitus who received education on adherence to routine self-monitoring of blood glucose, standard diabetic diet, and an exercise program delivered by certified diabetes educators had better glycemic control and significant decrease in body weight and fat percentage over a 3-month monitoring period.