Patterns and preferences of antidiabetic drug use in Turkish patients with type 2 diabetes - A nationwide cross-sectional study (TEMD treatment study).

AIMS: The treatment preferences in type 2 diabetes (T2DM) are affected by multiple factors. This survey aims to find out the profiles of the utilization of antidiabetics and their determinants. METHODS: The nationwide, multicenter TEMD survey consecutively enrolled patients with T2DM (n = 4678). Medications including oral antidiabetics (OAD) and injectable regimens were recorded. Multiple injectable regimens with or without OADs were defined as complex treatments. RESULTS: A total of 4678 patients with T2DM (mean age: 58.5 ± 10.4 years, 59% female) were enrolled. More than half of patients (n = 2372; 50.7%) were using injectable regimens with or without OADs, and others (n = 2306, 49.3%) were using only OADs. The most common OADs were metformin (93.5%), secretagogues (40.1%), and DPP-4 inhibitors (37.2%). The rates of the use of basal, basal-bolus and premix insulin were 26.5%, 39.5% and 22.4%, respectively. Patients using OADs achieved better glycemia, blood pressure and weight control (p < 0.001 for all) but poorer LDL-C control (p < 0.001). The independent associates of complex treatments were diabetes duration, obesity, eGFR, glycated haemoglobin, macro and microvascular complications, education level, and self-reported hypoglycemia. CONCLUSION: This study is the first nationwide report to show that almost half of the patients with T2DM are using injectable regimens in Turkey.

Early retinal neurodegeneration in preclinical diabetic retinopathy: a multifactorial investigation.

BACKGROUND/OBJECTIVES: To investigate effects of microalbuminuria (MA), diabetes duration, glycosylated haemoglobin (HbA1c) level, hypertension (HT) and/or hyperlipidaemia (HL) coexistence on retinal layers in diabetic patients without diabetic retinopathy (DR) using spectral-domain optical coherence tomography (SD-OCT). SUBJECTS/METHODS: This cross-sectional study involved 95 (45 had MA and 50 had no MA) patients with type 2 diabetes mellitus (DM) without DR and 91 age- and gender-matched non-diabetic controls. Macular and peripapillary SD-OCT measurements (Heidelberg Engineering GmbH, Heidelberg, Germany), DM duration, HbA1c levels and presence of HT and/or HL were used for statistical analyses. RESULTS: The MA (+), MA (-) and control groups had similar age and gender distribution (p > 0.05). The differences in SD-OCT measurements among the MA (+), MA (-) and control groups were insignificant (p > 0.05). However, diabetic patients (n = 95) had significantly thinner inferior-temporal peripapillary retinal nerve fibre layer (RNFL) (p = 0.042) than in the controls (n = 91). Superior peripapillary RNFL was significantly thinner in patients with an HbA1c level > 7% (p = 0.049). However, 3 mm-nasal, temporal and superior perifoveal thicknesses were significantly lower in patients with DM duration over 10 years (p < 0.05). HT and/or HL coexistence did not lead a significant difference in SD-OCT parameters among the groups. CONCLUSIONS: In diabetic patients without DR, peripapillary inferior-temporal RNFL thinning might be an early sign of neuroretinal degeneration and it seems to be independent from vascular endothelial damage (MA). Poor metabolic control appears to lead superior peripapillary RNFL thinning, while perifoveal thicknesses tend to decrease with longer DM duration.

Effect of microalbuminuria on corneal endothelium in patients with diabetes without retinopathy.

BACKGROUND: The aim of this study was to investigate the effect of microalbuminuria on corneal endothelium in patients with diabetes without retinopathy. METHODS: This cross-sectional study comprised 100 patients with type 2 diabetes mellitus (DM) without diabetic retinopathy and 92 control subjects without diabetes. Forty-five patients had microalbuminuria and 55 subjects were microalbuminuria negative. Endothelial measurements were obtained using specular microscopy. Endothelial cell density, average area, co-efficient of variation, maximum area, minimum area, hexagonality and corneal thickness were compared between the groups on the basis of microalbuminuria, DM duration and medication, HbA1c , body mass index, serum lipid and protein profiles, hypertension and hyperlipidaemia diagnosis. RESULTS: There were no significant differences in age, gender, endothelial cell density, average area, co-efficients of variation, maximum area, minimum area, hexagonality or corneal thickness among the microalbuminuria positive, microalbuminuria negative and control groups (p > 0.05). However, microalbuminuria positive patients had lower high-density lipoprotein levels than the microalbuminuria negative patients (p = 0.042). DM and control groups showed similar endothelial measurements (p > 0.05). Patients with a HbA1c > 7 per cent (53 mmol/mol) had lower hexagonality value (p = 0.039) than in the subjects with a HbA1c ≤ 7 per cent. No significant differences were found in endothelial parameters when groups were compared based on DM duration, medication and co-morbidities. CONCLUSIONS: Microalbuminuria positive and negative patients with DM without retinopathy seem to have similar corneal endothelial measurements with controls. However, patients with a HbA1c > 7 per cent should be monitored for deterioration in corneal endothelial cell morphology even without diabetic retinopathy, which might be critical prior to anterior segment surgery.

Osteocalcin and epicardial adipose tissue in obesity: new hints for epicardial adipose tissue-bone crosstalk.

Objectives: Osteocalcin (OC) appears to be involved in the regulation of glucose and fat metabolism. We aimed to determine the association between OC and epicardial adipose tissue (EAT) in premenopausal obese women. Design: The study included 73 premenopausal obese women and 55 non-obese women. Echocardiographic examination was performed to measure EAT. Serum OC levels were measured by chemiluminescence immunoassay. Results: OC levels were significantly lower in obese women than controls (18.26 ± 5.27 vs. 22.53 ± 6.84 ng/ml, p < .001). EAT thickness was higher in obese women than controls (5.19 ± 0.73 vs. 3.25 ± 1.35 mm, p < .001). In obese women, OC was positively correlated with EAT thickness (p = .043; r = 0.326). There was no correlation in controls. Conclusions: Premenopausal obese women had lower OC levels and thicker EAT than controls. There was a weak positive correlation between OC and EAT in premenopausal obese women. This potential cross talk between bone metabolism and EAT could play a role in the development of atherosclerosis in obesity.

Predictive power of different obesity measures for the presence of diastolic dysfunction.

OBJECTIVE: Body mass index (BMI) and waist circumference (WC) as measures of obesity have some limitations. The aim of this study was to evaluate whether one measure could predict the presence of diastolic dysfunction (DD) more accurately than the other measures. METHODS: A total of 91 obese patients without any other risk factors for DD were prospectively enrolled. Echocardiographic examination was performed. DD was defined and categorized according to recent guidelines. The study participants were divided into 2 groups according to the presence of DD. Weight, height, and WC were measured; BMI and waist-to-hip ratio (WHR) were calculated; and a body shape index (ABSI) was calculated as WC/(BMI2/3height1/2). The associations between ABSI, BMI, WHR, and WC and the presence of DD were examined using logistic regression analyses. Analysis of covariance was used to examine the differences. RESULTS: WC and BMI were significantly greater in subjects with DD (p=0.049 and 0.051, respectively). A greater BMI, WC, and WHR increased the risk of the presence of DD (BMIDD: odds ratio [OR]=1.096, p=0.024; WC-DD: OR=1.059, p=0.007; WHR-DD: OR=2.363, p=0.007). After adjustment for age and sex, only BMI continued to be significantly associated with DD (p=0.031). ABSI was not associated with DD. CONCLUSION: After adjustment for age and sex, BMI was the only predictor of DD in obesity. Despite its limitations, BMI may still be a potentially more accurate measure of DD compared with other obesity measures.

The Association between Central Adiposity and Autonomic Dysfunction in Obesity.

OBJECTIVE: To determine the relationship between central adiposity parameters and autonomic nervous system (ANS) dysfunction. SUBJECTS AND METHODS: The study included 114 obese individuals without any cardiovascular risk factors. Weight (in kg), height (in m), and waist circumference (WC; in cm) were measured and body mass index was calculated. Echocardiographic examination was performed to measure left ventricular mass and epicardial fat thickness (EFT). All the participants underwent an exercise test and electrophysiological evaluation using electromyography. Heart rate recovery (HRR) at 1-5 min, R-R interval variation at rest and during hyperventilation, and sympathetic skin response were measured. Pearson's correlation analysis was used. Multiple linear regression analysis was used to identify the factors associated with autonomic dysfunction. RESULTS: The HRR at 1-5 min was negatively correlated with WC and age (WC-HRR1: r = -0.32; WC-HRR2: r = -0.31; WC-HRR3: r = -0.26; WC-HRR4: r = -0.23; WC-HRR5: r = -0.21; age-HRR2: r = -0.32; age-HRR3: r = -0.28; age-HRR4: r = -0.41; age-HRR5: r = -0.42). Age was the only independent predictor of reduced HRR at 1-5 min. In addition, WC predicted a reduced HRR at 3 min. There were no significant associations between central obesity and electrophysiological parameters. EFT was not associated with ANS dysfunction. CONCLUSION: In this study, central adiposity and aging were associated with ANS dysfunction in obese individuals. The WC could be a marker of ANS dysfunction in obese individuals without any cardiovascular risk factors. The HRR assessment at a later decay phase could be more valuable for evaluating ANS function than during early recovery.

Antidiabetic exendin-4 activates apoptotic pathway and inhibits growth of breast cancer cells.

Exendin-4 is a GLP-1 analog used for the treatment of type 2 diabetes mellitus in its synthetic form. As women with diabetes have higher breast cancer incidence and mortality, we examined the effect of the incretin drug exendin-4 on breast cancer cells. The aim of the study is to investigate anticancer mechanism of exendin-4 in MCF-7 breast cancer cells. Cytotoxic effects of exendin-4 were determined by XTT assay. IC50 dose in MCF-7 cells were detected as 5 µM at 48th hour. Gene messenger RNA (mRNA) expressions were evaluated by real-time PCR. According to results, caspase-9, Akt, and MMP2 expression was reduced in dose group cells, compared with the control group cells. p53, caspase-3, caspase-8, caspase-10, BID, DR4, DR5, FADD, TRADD, PARP, PTEN, PUMA, NOXA, APAF, TIMP1, and TIMP2 expression was increased in dose group cells, compared with the control group cells. Effects of exendin-4 on cell invasion, colony formation, and cell migration were detected by Matrigel chamber, colony formation assay, and wound-healing assay, respectively. To conclude, it is thought that exendin-4 demonstrates anticarcinogenesis activity by effecting apoptosis, invasion, migration, and colony formation in MCF-7 cells. Exendin-4 may be a therapeutic agent for treatment of breast cancer as single or in combination with other agents. More detailed researches are required to define the pathways of GLP-1 effect on breast cancer cells because of the molecular biology of breast cancer that involves a complex network of interconnected signaling pathways that have role in cell growth, survival, and cell invasion.

IGF-1 gene polymorphism in obese patients with insulin resistance.

IGFs (Insulin like growth factors) are important regulators of pancreatic beta cell development, growth and maintenance. Mutations in the IGF genes have been found to be associated with diabetes mellitus, myocardial infarction obesity. These associations could result from changes in insulin secretion. We aimed to investigate IGF-1 gene polymorphism in obese patients with insulin resistance. We included 100 obese patients with insulin resistance 30 healthy subjects to study. At baseline examinations, antropometric measurements were done. Genomic DNA from the patients and controls were prepared. Thyroid function tests and serum IGFBP3 levels were similar between patients and controls whereas IGF, GH levels were significantly lower in obese patients. We categorized the IGF-1 (CA)19 polymorphism area into 3 groups as lower than 192 bp (group 1), 192-194 bp (group 2), and higher than 194 bp(group 3). Group 3 was more frequent in both obese and control groups. IGF-1 levels were also significantly lower in obese group (138.51 +/- 49.3) in than controls (218.14 +/- 69.15). IGF-1 levels were significantly lower in obese patients. The most frequent IGF-1 gen polymorphism allel is >194 bp in both obese insulin resistant patients and controls. IGF-1 levels and the other biochemical and hormonal parameters were similar in different genotype groups. The cause of lower IGF-1 levels in obese patients might be different from IGF-1 gene polymorphism and it may be insulin resistance.

Successful treatment of visceral leishmaniasis with fluconazole and allopurinol in a patient with renal failure.

Standard treatments for visceral leishmaniasis (antimonials, amphotericin B and pentamidine) pose several problems. Failure of antimonials or severe toxicity is particularly troublesome in patients with renal insufficiency. We report a case of visceral leishmaniaisis and renal insufficiency successfully treated with fluconazole and allopurinol for 4 months.