Erdinc Erturk

The effect of vitamin D replacement therapy on insulin resistance and androgen levels in women with polycystic ovary syndrome

Insulin resistance (IR) is one of the common features of the polycystic ovary syndrome (PCOS), and recent studies indicate the possible role of vitamin D in the pathogenesis of IR and glucose metabolism. Aim of this study was aimed to determine the effect of vitamin D replacement therapy on glucose metabolism, insulin, and androgen levels in obese, insulin-resistant women with PCOS. Eleven women with PCOS were included in the study. Mean age of the patients was 23.6±5.7 yr, body mass index 33.9±5.1 kg/m2. Six patients (54.5%) had acantosis nigricans and 10 (90.9%) oligoamenorrhea. The mean Ferriman Gallwey score was 14.1 ±4.6. Only 2 women were within the normal limits of vitamin D levels as >20 ng/ml. Three weeks after the administration of the single dose of 300,000 units of vitamin D3 orally, 25-hydroxyvitamin D3 significantly increased from 16.9±16 ng/ml to 37.1 ±14.6 ng/ml (p: 0.027) and only 2 women were detected to have vitamin D3 levels <20 ng/ml. Although glucose and insulin levels were decreased non-significantly, homeostasis model assesment (HOMA)-IR significantly decreased from 4.41 ±1.38 to 3.67±1.48 (p: 0.043). No significant alterations were witnessed at the levels of DHEAS, total and free testosterone, androstenedione. No correlation was found between vitamin D with HOMA and other hormonal parameters. In conclusion, women with PCOS have mostly insufficient vitamin D levels, and vitamin D replacement therapy may have a benefical effect on IR in obese women with PCOS.

Effect of rosiglitazone, metformin and medical nutrition treatment on arterial stiffness, serum MMP-9 and MCP-1 levels in drug naive type 2 diabetic patients.

The aim of the study was to evaluate the long-term effect of rosiglitazone and metformin monotherapy with medical nutrition treatment (MNT) and of MNT alone on arterial stiffness, serum monocyte chemoattractant protein (MCP)-1 and matrix metalloproteinase (MMP)-9 in drug naive patients with type 2 diabetes mellitus. Fifty type 2 diabetic patients were randomized to receive rosiglitazone 4 mg/day (n=19) or metformin 850 mg/day (n=16) with MNT or MNT alone (n=15), for 52 weeks. Arterial stiffness was assessed by using large and small artery elasticity index (SAEI and LAEI, respectively). SAEI, LAEI, serum MCP-1 and MMP-9 levels were measured at baseline and following 52 weeks of treatment. SAEI was improved only in the rosiglitazone group, and the difference was still statistically significant when the three groups were compared (p=0.024). There were no differences in LAEI in inter- and intragroup comparisons at the end of the study. Serum MMP-9 levels were decreased in the metformin (-13.5+/-34.8%, p=0.02) and rosiglitazone (-27.2+/-51.0%, p=0.023) groups compared with baseline values, whereas no significant change was seen in serum MCP-1 levels. These results suggest that rosiglitazone monotherapy has favorable effects on arterial stiffness compared with metformin monotherapy independent of glycemic control.

Effect of levothyroxine treatment on QT dispersion in patients with subclinical hypothyroidism.

OBJECTIVE To examine the effect of levothyroxine treatment in patients with subclinical hypothyroidism on electrocardiographic variables, especially on ventricular repolarization-related factors. METHODS Sixteen women (mean age, 48.2 years) with subclinical hypothyroidism were treated with levothyroxine for 16 weeks. All standard 12-lead electrocardiographic recordings were scanned and transferred to a computer, and the QT intervals were measured on 300 times magnified recordings. QT dispersion, which reflects the heterogeneity of the ventricular repolarization, was calculated by the difference between the QT maximum and the QT minimum. RESULTS We found that, after 16 weeks of levothyroxine treatment, the QT interval decreased from 387.2 +/- 10.8 ms to 345.6 +/- 13.0 ms (P<0.0001). The study patients exhibited a significant reduction of QT dispersion from 46.5 +/- 5.3 ms to 30.7 +/- 5.8 ms (P<0.0001). On linear regression analysis, a positive relationship was found between QT dispersion and logarithmic serum TSH levels (r = 0.492; P<0.0001). CONCLUSION We conclude that serum TSH concentration has a role in ventricular inhomogeneity and, therefore, that subclinical hypothyroidism may predispose to ventricular arrhythmias. A large-scale, multicenter, randomized trial should be undertaken to address the benefit-to-risk ratio of levothyroxine treatment on cardiac inhomogeneity in patients with subclinical hypothyroidism.

Metacarpal brown tumor in secondary hyperparathyroidism due to vitamin-D deficiency. A case report.

B rown tumors are locally destructive bone lesions caused by rapid osteoclastic bone resorption due to severe hyperparathyroidism1. For years, brown tumors have been considered to be characteristic of primary hyperparathyroidism. However, brown tumors also have been reported to occur in patients with severe hyperparathyroidism secondary to chronic renal failure2-4, especially those on long-term hemo-dialysis. Hypocalcemia, hyperphosphatemia, and vitamin-D deficiency are the basic characteristics of chronic renal failure associated with secondary hyperparathyroidism. Fig. 1 Photograph of the lesion at presentation. The appearance of brown tumor lesions in a patient with secondary hyperparathyroidism due to malabsorption has been reported5; but, to our knowledge, there are no reported cases of a patient in whom brown tumor developed secondary to osteomalacia due to inadequate sunlight exposure and dietary vitamin-D deficiency. Our patient was informed that data concerning the case would be submitted for publication. A twenty-eight-year-old woman who had been in purdah (no skin exposed in public except the hands and face) since she was thirteen years old presented with a 4 × 3-cm painful mass in the region of the fourth metacarpal of the right hand without redness or warmth (Fig. 1). Her hand movement was extremely restricted. Radiographs revealed an expansile lytic lesion …

Total and acylated ghrelin levels in type 2 diabetic patients: similar levels observed after treatment with metformin, pioglitazone or diet therapy.

Ghrelin, a potent gut-brain orexigenic peptide, has a role in stimulation of food intake and long-term regulation of body weight. Metformin and pioglitazone treatment have different effects on body weight. This discrepancy might be related with the effect of these two drugs on plasma ghrelin levels. We investigated the effect of these two drugs on post-prandial acylated and total ghrelin levels in patients with type 2 diabetes. Eleven patients treated with diet, 12 patients treated with 850 mg/day metformin monotherapy and 12 patients treated with 30 mg/day pioglitazone monotherapy for at least 6 months were enrolled in the study. Plasma acylated and total ghrelin levels were investigated at baseline and at the 60 (th), 120 (th), 180 (th), 240 (th) minutes after a mixed meal test. There were no differences between groups in any of baseline metabolic and anthropometric parameters, including acylated and total ghrelin levels. Acylated and total ghrelin concentrations were suppressed similarly after food consumption, and we could not determine any significant difference between the groups at any time interval. A prolonged postprandial suppression of acylated ghrelin concentrations was observed in the pioglitazone treatment group compared with baseline values. In conclusion, total and acylated ghrelin levels after a mixed meal test were similar in type 2 diabetic patients treated with metformin, pioglitazone or diet therapy alone. These results suggest that changes in body weight during metformin and pioglitazone treatment are not associated with plasma ghrelin levels.

Puberty, stress, and sudden death

In September, 2008, a 22-year-old man was referred for investigation of delayed puberty. He was thin (BMI 17·1 kg/m²) but had no history of anorexia nervosa. Neurological examination and sense of smell were normal; testes volumes were 2 mL and 3 mL [normal, 15–25 mL]. Concentrations of gonadotropins were not elevated (FSH 4·1 IU/L [normal 1·3–13·5], LH 0·77 IU/L [1·2–10]) and testosterone was 0·9 nmol/L [9–30], consistent with a central form of hypogonadism; prolactin concentration was normal. During a gonadotropin stimulation test, he became weak and dizzy; blood pressure was 90/40 mm Hg, sodium119 mmol/L, and potassium 5·4 mmol/L. At this time, we noticed that he was pigmented, and on further questioning we found that he had had previous episodes of weakness, especially during concurrent illnesses. We suspected adrenal insuffi ciency and treated him with intravenous hydrocortisone, which led to a rapid improvement in symptoms. Basal cortisol con centration before treatment was 290 nmol/L (180–500), but corticotropin was 297 pmol/L (0–11) (fi gure). On more detailed questioning we found that his older brother had presented at 18 years of age with features of hypogonadism that had been treated with testosterone. He also had a normal basal cortisol concentration, but a poor response to co-syntropin stimulation on two occasions, and slightly raised concentrations of corticotropin (20–47 pmol/L; fi gure). Although further review of adrenal function had been planned, our patient’s brother died suddenly during intensive physical activity.Impaired puberty in males can be due to testicular failure (hypergonadotropic hypogonadism) or to a central cause that aff ects pulsatile LH and FSH release (hypogonadotropic hypogonadism). The presence of adrenal insuffi ciency and central hypogonadism could refl ect a multiple pituitary defi ciency aff ecting both corticotropin and gonadotropin

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.

The investigation of the efficacy of insulin glargine on glycemic control when combined with either repaglinide or acarbose in obese Type 2 diabetic patients

Combinations of insulin and oral antidiabetic drugs (OAD) are often prescribed instead of insulin alone. In this study, the effects of insulin glargine (IG) in combination with repaglinide or acarbose on glycemic parameters were investigated. Obese Type 2 diabetic patients with fasting blood glucose (FBG) levels ≥ mmol/l and hemoglobin glycated (A1C) ≥9% under maximal OAD combination therapy were enrolled. Previous therapies were discontinued, and patients were randomized into 2 groups. The combinations of IG and repaglinide were administered to group 1, and of IG and acarbose to group 2 for 13 weeks. Twenty patients in group 1 and 18 patients in group 2 completed the study. A1C levels were significantly decreased from 10.9±1.4% to 7.7±1.1% in group 1 and 11.0±1.4% to 8.1±1.4% in group 2. FBG levels were significantly decreased from 11.9±2.7 to 7.1 ±2.3 mmol/l in group 1 and 11.1 ±2.5 to 6.8±1.4 mmol/l in group 2. Post-prandial glucose levels were significantly decreased from 15.3±3.8 to 10.3±3.0 mmol/l in group 1 and 14.0±3.1 to 8.9±2.2 mmol/l in group 2. Intergroup comparisons indicated no significant differences. More weight gain was detected in group 1, compared to the baseline. Syptomatic hypoglycemia incidence was similar in both groups. Severe hypoglycemic attacks were seen in two patients in group 1. Flatulance incidence was higher in acarbose group. Conclusively, repaglinide and acarbose were equally effective when combined with IG for obese Type 2 diabetic patients controlled inadequately with OAD alone. Furthermore, acarbose seems to have advantages over repaglinide concerning weight gain and severe hypoglycemic attacks.

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.

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.