Even Short-Term Telmisartan Treatment Ameliorated Insulin Resistance But Had No Influence on Serum Adiponectin and Tumor Necrosis Factor-Alpha Levels in Hypertensive Patients with Metabolic Syndrome.

BACKGROUND: We investigated the effect of short-term telmisartan usage in addition to lifestyle changes such as diet and exercise on insulin resistance, lipid metabolism, and serum adiponectin and tumor necrosis factor-alpha (TNF-α) levels in hypertensive patients with metabolic syndrome (MetS). METHODS: A total of 36 hypertensive patients with MetS were randomized to telmisartan and control groups in an open-labeled prospective study. RESULTS: There were significant decreases in anthropometric variables of patients according to baseline measurements in both groups at the end of the study. Serum insulin level and insulin resistance assessed by homeostasis model assessment-insulin resistance were decreased significantly in the telmisartan group (P = 0.040 and P = 0.034, respectively) compared with the controls, while there was no statistically significant change in the lipid profiles of the two groups. Serum adiponectin level was increased by 19.1% ± 41.7% in the telmisartan group, but intergroup analysis revealed no significant change. There was also no significant change in serum TNF-α level in either group. CONCLUSION: It has been observed that even short-term telmisartan treatment had favorable effects on insulin resistance and glucose metabolism compared with lifestyle changes alone. The fundamental effect of telmisartan treatment on insulin resistance renders it a good therapeutic option for hypertensive patients with MetS.

Sexual dysfunction in female patients with type 2 diabetes mellitus: a cross-sectional single-centre study among Turkish patients.

The aim of the study was to assess the prevalence of female sexual function and related factors in Turkish women with type 2 diabetes mellitus (T2DM). A total of 93 female patients diagnosed with T2DM (age 48.0 ± 7.2 years (Mean ± SD) were included. Data on age, diabetes age, HbA1c level, educational level, diabetes treatment, diabetes-related complications, co-morbid disorders and concomitant medications were recorded, as were the scores obtained using a Female Sexual Function Index (FSFI) questionnaire. Sexual dysfunction was noted in 55.9% of patients including problems related to desire (60.2%), arousal (52.7%), lubrication (55.9%), orgasm (51.6%) and satisfaction (58.1%) as well as pain during sexual intercourse (54.8%). Total scores were correlated negatively to age (r= -0.329, p = 0.001) and duration of diabetes (r= -0.246, p = 0.018), while significantly higher in patients with than without hypertension (19.6 vs. 22.4, p = 0.012) and with than without insulin therapy (20.0 vs. 23.7, p = 0.050). Our findings indicate the adverse effects of T2DM on sexual function in 55.9% of women in all domains of sexual response cycle, although this seems to be associated with older age, longer duration of diabetes, insulin and antidepressant therapy, presence of hypertension as well as end-organ complications of neuropathy and coronary artery disease (CAD).

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.

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.

Association between p16(CDKN2A) C540G polymorphism and tumor behavior in prolactinoma: A single-center study.

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.

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.

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.

Ultrasound biomicroscopic evaluation of anterior segment cysts as a risk factor for ocular hypertension and closure angle glaucoma.

AIM: To investigate the relationship between the ultrasound biomicroscopic (UBM) features of anterior-segment cysts (ASCs) and increased intraocular pressure (IOP) as a risk factor for closed-angle glaucoma (CAG). METHODS: Totally 24 eyes with recently diagnosed ASCs were divided into two groups. First group with ASC and ocular normotension (n=13), second group with ASC and ocular hypertension (n=11). An ophthalmologic examination, including tonometry, slit-lamp biomicroscopy (SLBM), gonioscopy, fundoscopy, pentacam, and UBM, was performed. The features of the ASCs were compared with the IOP. RESULTS: ASCs were accurately diagnosed and delineated in 24 eyes using UBM. IOP was elevated in those ASCs with a secondary aetiology (P=0.027), iridociliary location (P=0.006), deformed shape (P=0.013), increased size (P=0.001) and elongated pupillary aperture (P=0.009). However, the count (P=0.343) of ASCs, anterior chamber depth (ACD; P=0.22) and axial lenght (AL; P=0.31) were not associated with ocular hypertension. Correlations were found between the IOP and ASC size (r=-0.712; P=0.003), anterior chamber angle (ACA; r=-0.985; P<0.001), angle opening area (AOA; r=0.885; P<0.001), angulation of iris (r=-0.776, P<0.001), and affected iris quadrant (r =-0.655, P=0.002). CONCLUSION: Ocular hypertension in some eyes with ASC might be associated with various mechanisms, including secondary aetiology, iridociliary location, deformed shape, increased size and elongated pupill, which can be determined by UBM.

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.

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.

Vitamin D receptor gene BsmI, FokI, ApaI, TaqI polymorphisms and bone mineral density in a group of Turkish type 1 diabetic patients.

Previous studies have suggested an influence of vitamin D receptor alleles on bone metabolism and on susceptibility to type 1 diabetes mellitus in different ethnic populations. We aimed to investigate the distribution of vitamin D receptor (VDR) alleles in relation to biochemical bone turnover parameters and bone densitometry measurements in a group of Turkish type 1 diabetic patients. One hundred and seventeen patients (M/F 57/60, 27.6 ± 7.3 y duration of diabetes 8.1 ± 6.3 y) and 134 healthy controls (M/F 61/73, 26.2 ± 5.3 y) were included in the study. Bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry (DEXA). The vitamin D receptor gene (VDR) polymorphisms FokI, Bsm1, Apa1, and Taq1 were examined using a PCR-based restriction analysis. Serum levels of calcium, phosphor osteocalcin, intact parathyroid hormone, and C telopeptide were measured. Vitamin D receptor Bsm1 Fok1, Apa1, and Taq1 genotype distributions were not different between patient with diabetes and control groups. BMD was 0.77 ± 0.2 g/cm(2) vs. 0.97 ± 0.2 g/cm(2) (P = 0.0001) for the femur, 1.0 ± 0.1 g/cm(2) vs. 1.13 ± 0.1 g/cm(2) (P = 0.001) for type 1 diabetic patients and controls. Bone turnover markers were significantly lower in type 1 diabetic group. BMD measurements and bone metabolic markers were not different between the genotypes in either the patient with diabetes or the controls. The VDR gene polymorphisms, Bsm1, Fok 1, Apa1, and Taq1 showed no influence on bone metabolism in our group of type 1 diabetic patients.

Role of duplex power Doppler ultrasound in differentiation between malignant and benign thyroid nodules.

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.

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.

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.

Comparison of composite whole body insulin sensitivity index derived from mixed meal test and oral glucose tolerance test in insulin resistant obese subjects.

Apart from fasting blood glucose (FBG) and insulin (FBI), oral glucose tolerance test (OGTT) is also used in calculating insulin sensitivity. During OGTT, insulin secretion may not reflect normal physiological insulin secretion. Based on this idea, hepatic and whole body insulin sensitivity rates were tested during OGTT and mixed meal test (MMT) in obese subjects. Thirty-one women with Quantitative Insulin Sensitivity Check Index (QUICKI) values below 0.350 and body mass index (BMI) >or=30 were included into the study. OGTT with 75-g glucose and MMT 300 kcal were applied to all cases. Data obtained from OGTT and MMT were used in the assessment of insulin sensitivity with Hemostasis of Model Assessment-Insulin Resistance (HOMA-IR) and Matsuda's Composite Whole Body Insulin Sensitivity Index (Matsuda's ISI). Mean BMI, FBG, and FBI were 36.8 +/- 3.9 kg/m(2), 100.5 +/- 0.10 mg/dl, 16.2 +/- 5.3 microg/ml, respectively. QUICKI was 0.31 +/- 0.01 and HOMA-IR was 3.71 +/- 0.88. Matsuda's ISI derived from OGTT was 6.96 +/- 3.35 and from MMT was 11.32 +/- 6.61. In analysis, it was demonstrated that there was a correlation between HOMA-IR, QUICKI, and Matsuda's ISIs derived from OGTT and MMT. Comparing the time periods separately, it was detected that despite similar increment in insulin levels, glucose levels were higher in OGTT than MMT at 15 and 30 min. Consequently, Matsuda's ISI was demonstrated to be effectively used with the data of MMT, as used with OGTT. Moreover, MMT was shown to be in parallel to physiologic insulin secretion and reflect pancreatic functions better compared to OGTT.

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.

Arterial elasticity and plasma levels of adiponectin and leptin in type 2 diabetic patients treated with thiazolidinediones.

BACKGROUND: Thiazolidinediones (TZDs) improve peripheral insulin sensitivity, but the effect on arterial stiffness is less clear. The aim of the present study was to assess the differential effect of pioglitazone or rosiglitazone on arterial stiffness and plasma levels of adiponectin and leptin in patients with type 2 diabetes mellitus. METHODS: Thirty-five type 2 diabetic subjects were randomly assigned to receive pioglitazone (30 mg/day; n = 14), rosiglitazone (4 mg/day; n = 11), or placebo (medical nutrition therapy; n = 10) for 12 weeks. Changes in plasma glucose, glycosylated hemoglobin, insulin resistance (HOMA-IR), total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, adiponectin, and leptin were evaluated at baseline and after 12 weeks. In parallel, large arterial compliance (C1) and small arterial compliance (C2) were measured at baseline and at the end of treatment period. RESULTS: At 12 weeks, the rosiglitazone (P = 0.026) and pioglitazone (P = 0.004) groups had a significant increase from baseline in adiponectin that was not seen in the medical nutrition therapy group. No significant changes in plasma leptin and in C1 and C2 elasticity indexes were observed over the entire study period in any of the treatment groups. CONCLUSIONS: In this study of patients with type 2 diabetes, treatment with TZDs was associated with a significant improvement in adiponectin levels, although no significant effects were seen on leptin levels and arterial elasticity.

The effect of metformin treatment on VEGF and PAI-1 levels in obese type 2 diabetic patients.

The aim of the study was to evaluate the effect of metformin on markers of endothelial function, vascular inflammation and factors of thrombosis in obese type 2 diabetic patients. Twenty-four type 2 diabetic patients (15 female, 9 male) previously under medical nutrition treatment (MNT)+regular exercise programme (REP) without chronic micro or macrovascular complications with the mean age of 50.5+/-1.5 years, diabetes duration of 17.9+/-6.3 months and body mass index (BMI) of 31.7+/-0.8 kg/m(2) were enrolled in the study. In the first 4 weeks, all the patients continued MNT+REP. In the following 12 weeks, metformin (mean daily dosage of 1381+/-85 mg) was added. After the first period with MNT+REP, BMI, waist circumference, fat percentage, blood pressure and HDL cholesterol decreased significantly. After metformin addition, there was a significant decrement in BMI, waist circumference, fat percentage, fasting and postprandial plasma glucose, hemoglobin A1C, plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF) and increment in beta cell reserve values of the patients. Our results indicated that, metformin addition had beneficial effect on VEGF and PAI-1 levels in obese type 2 diabetic patients under MNT+REP, independent from its' favourable effects on BMI and glycemic control.