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Introduction: Targeting better glycated hemoglobin (HbA1c) and blood pressure (BP) goals may endanger older adults with type 2 diabetes mellitus (T2DM). Overtreatment of T2DM and hypertension is a trending issue, although undertreatment is still common. We investigated the rates and predictors of overtreatment and undertreatment of glycemia and BP in older adults with T2DM and physicians' attitudes to deintensify or intensify treatment., Methods: Data from older adults (≥ 65 years) enrolled in a large nationwide T2DM survey in 2017 across Turkey were analyzed. Overtreatment of glycemia was defined as HbA1c < 6.5% plus the use of ≥ 2 oral antihyperglycemics or insulin, and BP overtreatment was defined as systolic BP (SBP) < 120 mmHg or diastolic BP (DBP) < 65 mmHg plus the use of ≥ 2 drugs. Undertreatment of glycemia was defined as HbA1c > 9%, and BP undertreatment was defined as SBP > 150 mmHg or DBP > 90 mmHg. Deintensification or intensification rates were calculated according to treatment modification initiated by the treating physician(s)., Results: The rate of overtreatment in the glycemia group (n = 1264) was 9.8% (n = 124) and that in the BP group (n = 1052) was 7.3% (n = 77), whereas the rate of undertreatment was 14.2% (n = 180) and 15.2% (n = 160), respectively. In the adjusted model, use of oral secretagogues (sulfonylureas or glinides) (odds ratio [OR] 1.94, 95% confidence interval [CI] 1.2-3.1) and follow-up at a private clinic (OR 1.81, 95% CI 1.0-3.3) were predictors of glycemia overtreatment. BP overtreatment was independently associated with the use insulin-based diabetes therapies (OR 1.86, 95% CI 1.14-3.04). There was no independent association of BP undertreatment to the study confounders. The deintensification and intensification rates were 25 and 75.6%, respectively, for glycemia and 10.9 and 9.2%, respectively, for BP., Conclusions: The results show that one in ten older adults with T2DM are overtreated while one in four require modification of their current antihyperglycemic and antihypertensive treatments. Physicians are eager to intensify medications while they largely ignore deintensification in diabetes management. These results warrant enforced measures to improve the care of older adults with T2DM., Trial Registration: ClinicalTrials.gov identifier, NCT03455101.

Objectives: To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes., Methods: Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial., Participants: Males and females aged 45-74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey., Intervention: Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function., Results: One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%., Conclusions: ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with pre-diabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes., Registration: - ClinicalTrials.Gov Identifier: NCT03222765 - EUDRACT Registry Number: 2013-000418-39., Competing Interests: the authors received funding from Merck Serono GmbH and Boehringer Ingelheim. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.

Introduction: Gastroesophageal reflux disease (GERD) is more frequent in patients with diabetes mellitus (DM).The aim of the present study was to evaluate gastroesophageal reflux (GER) in asymptomatic patients with DM using 24-h pH impedance., Materials and Methods: 19 healthy controls and 35 patients with DM without typical GERD symptoms were enrolled in the study. A 24-h pH-impedance study, esophageal manometry and gastroscopy were performed on all patients with DM. In the control group, an impedance study was performed on all subjects, and gastroscopy and esophageal manometry were performed on those who consented to the procedures. Patients with diabetes were categorized as obese [body mass index (BMI)>30 kg/m 2 ] or non-obese (BMI<30 kg/m 2 ) and both groups were compared with healthy controls., Results: The mean BMI was similar in the control group (27.3±2.6 kg/m 2 ) and the diabetic group (28.7±5 kg/m 2 ) (p>0.05).Erosive esophagitis was found in 7.5% of the DM group. Esophageal dysmotility was higher in diabetics compared to the control group (45.5 vs. 11%, p=0.04). Neuropathy was found to be an independent risk factor for dysmotility. The mean DeMeester score (DMS) (25.6±32.5 vs. 11.2±17, p=0.01) and bolus exposure time (2.1±1.3 vs.1.3±1.3 min, p=0.009) were higher in the DM group compared with the control group.The difference was mainly observed between obese diabetics and the control group (p<0.05). The mean DMS, pathologic acid reflux, and esophageal dysmotility rate were higher in patients without complications of DM (p<0.05). BMI was higher in these patients than in patients with complications., Conclusion: Acid reflux is common in patients with diabetes.GER is associated with the existence of obesity rather than hyperglycemia., Competing Interests: No conflict of interest has been declared by the authors., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: This study aimed (1) to compare physical activity (PA) indicators, metabolic biomarkers, and comorbidity, (2) to investigate the relationship between PA indicators and metabolic biomarkers, comorbidity and (3) to identify barriers to PA in patients with type 2 diabetes (T2DM) who are using oral hypoglycaemic agent (OHA) or combined OHA and insulin (OHAiN). Methods: Sixty-one patients were classified as patients using only OHA or combined OHAiN. Metabolic biomarkers (waist-to-hip ratio, body mass index (BMI), lipid profile, glycosylated haemoglobin (HbA1c), fasting blood glucose, comorbidity and PA indicators (self-reported PA, number of steps (NOS), 6-minute walking distance (6MWD)) were assessed. PA perceptions and reasons for inactivity were questioned. Results: The comorbidity ( p = .013), low-density lipoprotein-cholesterol ( p = .026), total cholesterol ( p = .008) and HbA1c ( p = .020) were higher and PA level was lower ( p = .007) in the OHAiN group. NOS was positively correlated with high-density lipoprotein-cholesterol ( p = .037) and negatively correlated with BMI ( p = .007). 6MWD was negatively correlated with BMI ( p = .014) and comorbidity ( p = .004) in the OHA group. BMI was a significant predictor of NOS (adjusted R 2  = 0.242) and comorbidity for 6MWD (adjusted R 2  = 0.250) in the OHA group. The majority of the patients (OHA = 34.3%, OHAiN = 42.3%) reported "lack of time" as the most common barrier to PA. Conclusions: This study showed that patients on OHAiN have lower PA levels, poorer metabolic profiles, and higher comorbidity rates than OHA users. PA indicators were related with some metabolic biomarkers and comorbidity in only OHA users. The most common reason for inactivity was "the lack of time" in both groups.

Branched chain amino acids (BCAA) are essential elements of the human diet, which display increased plasma levels in obesity and regained particular interest as potential biomarkers for development of diabetes. To define determinants of insulin resistance (IR) we investigated 73 genes involved in BCAA metabolism or regulation by fine-scale haplotype mapping in two European populations with metabolic syndrome. French and Romanians (n = 465) were genotyped for SNPs (Affymetrix) and enriched by imputation (BEAGLE 4.1) at 1000 genome project density. Initial association hits detected by sliding window were refined (HAPLOVIEW 3.1 and PHASE 2.1) and correlated to homeostasis model assessment (HOMAIR) index, in vivo insulin sensitivity (SI) and BCAA plasma levels (ANOVA). Four genomic regions were associated with IR located downstream of MUT, AACS, SLC6A15 and PRKCA genes (P between 9.3 and 3.7 x 10-5). Inferred haplotypes up to 13 SNPs length were associated with IR (e.g. MUT gene with P < 4.9 x 10-5; Bonferroni 1.3 x 10-3) and synergistic to HOMAIR. SNPs in the same regions were also associated with one order of magnitude lower P values (e.g. rs20167284 in the MUT gene with P < 1.27 x 10-4) and replicated in Mediterranean samples (n = 832). In French, influential haplotypes (OR > 2.0) were correlated with in vivo insulin sensitivity (1/SI) except for SLC6A15 gene. Association of these genes with BCAA levels was variable, but influential haplotypes confirmed implication of MUT from BCAA metabolism as well as a role of regulatory genes (AACS and PRKCA) and suggested potential changes in transcriptional activity. These data drive attention towards new regulatory regions involved in IR in relation with BCAA and show the ability of haplotypes in phased DNA to detect signals complimentary to SNPs, which may be useful in designing genetic markers for clinical applications in ethnic populations., Competing Interests: The authors have declared that no competing interests exist. We confirm that commercial affiliation of BC Platforms Ltd Oy, Espoo, Finland and Intactile Design SA, Montpellier, France does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Obesity is the main obstacle for metabolic control in patients with type 2 diabetes. Turkey has the highest prevalence of obesity and type 2 diabetes in Europe. The effect of obesity on the metabolic control, and the macro- and microvascular complications of patients are not apparent., Objectives: This nationwide survey aimed to investigate the prevalence of overweight and obesity among patients with type 2 diabetes and to search for the impact of obesity on the metabolic control of these patients. We also investigated the independent associates of obesity in patients with type 2 diabetes., Methods: We consecutively enrolled patients who were under follow-up for at least 1 year in 69 tertiary healthcare units in 37 cities. The demographic, anthropometric, and clinical data including medications were recorded. Patients were excluded if they were pregnant, younger than 18 years, had decompensated liver disease, psychiatric disorders interfering with cognition or compliance, had bariatric surgery, or were undergoing renal replacement therapy., Results: Only 10% of patients with type 2 diabetes (n = 4,648) had normal body mass indexes (BMI), while the others were affected by overweight (31%) or obesity (59%). Women had a significantly higher prevalence of obesity (53.4 vs. 40%) and severe obesity (16.6 vs. 3.3%). Significant associations were present between high BMI levels and lower education levels, intake of insulin, antihypertensives and statins, poor metabolic control, or the presence of microvascular complications. Age, gender, level of education, smoking, and physical inactivity were the independent associates of obesity in patients with type 2 diabetes., Conclusion: The TEMD Obesity Study shows that obesity is a major determinant of the poor metabolic control in patients with type 2 diabetes. These results underline the importance of prevention and management of obesity to improve health care in patients with type 2 diabetes. Also, the results point out the independent sociodemographic and clinical associates of obesity, which should be the prior targets to overcome, in the national fight with obesity., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Objective: Diabetes mellitus (DM) is a serious public health problem. Despite various epidemiological studies reporting prevalence of DM in Turkey, there is no meta-analysis or systematic review evaluating these studies as a whole and assessing temporal changes in the prevalence of DM. In this meta-analysis, the studies that have been conducted in the last 15 years and which provide information on the prevalence of DM in our country are examined., Methods: Epidemiological studies on cardiovascular risk factors in adult Turkish population that had been conducted within the last 15 years and having the capacity of either representating or potentially representing the country, were searched through Ovid, Medline and Web of Science Core Collection the Turkish Academic Network and Information Center (ULAKBIM) databases. Additionally, websites of Ministry of Health and related societies were investigated for additional studies. Random effects model was used in meta-analysis of low bias risk studies. Meta-regression was performed to evaluate the temporal change in DM prevalence., Results: There were 8 studies which provided information with regard to DM prevalence (n=84656). Four of these studies (n=56853) had low bias risk and four had high bias risk (n=27803). When compared with low bias risk studies, those with high bias risk had very large variation of DM prevalence (between 4% to 15%). Meta-analysis of the low bias risk group yielded a crude DM prevalence of 13.5% (95% CI: 11.6-15.5%) in the whole group, 14.2% (95% CI: 12.3-16.2%) in females, 12.6% (95% CI: 10.5-14.9%) in males. In meta-regression analysis of low bias risk group, mean age difference among the studies and the time period in which the study was undertaken were partially able to explain the inter-study heterogeneity (R2 values were 52% and 78%)., Conclusion: This meta-analysis shows that DM is a highly prevalent public health problem in our country. Contrary to studies, which compare the recent studies with previous ones and report an increasing prevalence of DM, the present meta-analysis-despite its limitations-provides findings that the temporal increase of DM prevalence is at least paused over time. This situation underlines the need for new studies.

Branched-chained amino acids (BCAA) are essential dietary components for humans and can act as potential biomarkers for diabetes development. To efficiently estimate dietary intake, we developed a BCAA database for 1331 food items found in the French Centre d'Information sur la Qualité des Aliments (CIQUAL) food table by compiling BCAA content from international tables, published measurements, or by food similarity as well as by calculating 267 items from Greek, Turkish, Romanian, and Moroccan mixed dishes. The database embedded in MEDIPAD software capable of registering 24 h of dietary recalls (24HDR) with clinical and genetic data was evaluated based on archived 24HDR of the Saint Pierre Institute (France) from 2957 subjects, which indicated a BCAA content up to 4.2 g/100 g of food and differences among normal weight and obese subjects across BCAA quartiles. We also evaluated the database of 119 interviews of Romanians, Turkish and Albanians in Greece (27⁻65 years) during the MEDIGENE program, which indicated mean BCAA intake of 13.84 and 12.91 g/day in males and females, respectively, comparable to other studies. The MEDIPAD is user-friendly, multilingual, and secure software and with the BCAA database is suitable for conducting nutritional assessment in the Mediterranean area with particular facilities for food administration., Competing Interests: The authors declare no conflict of interest.

Objectives: To compare the effects of Internet-based exercise on glycaemic control, blood lipids, body composition, physical activity level, functional capacity, and quality of life with supervised group exercise in patients with type 2 diabetes., Design: Single-blind, randomized controlled study., Setting: A Faculty of Health Sciences., Subjects: A total of 65 patients with type 2 diabetes (47 women, 18 men)., Intervention: Group A ( n = 22), control group - physical activity counselling once with a brochure. Group B ( n = 22), supervised group-based exercise, three days per week for eight weeks. Group C ( n = 21), Internet-based exercise following the same programme via a website., Main Measures: Primary outcomes - glycosylated haemoglobin, fasting blood glucose, high-density and low-density lipoprotein, triglyceride, and cholesterol. Secondary outcomes - waist and hip circumferences, body mass index, number of steps, six-minute walking test, and Euro-Quality of Life-5 Dimension., Results: After treatment, glycaemic control (mean change for Group B; Group C; -0.80%, -0.91%, P = 0.003), waist circumference (-4.23 cm, 5.64 cm, P = 0.006), and quality of life (0.26, 0.15, P = 0.013) significantly improved in both training groups compared with the control group. Fasting blood glucose (-46.86 mg/dL, P = 0.009) and hip circumference (-2.7 cm, P = 0.011) were significantly decreased in Group B and total cholesterol (-16.4 mg/dL, P = 0.028), six-minute walking distance (30.5 m, P = 0.01), and number of steps (1258.05, P = 0.023) significantly improved in Group C compared with control group. Group B and Group C changed with equal magnitude., Conclusion: In type 2 diabetes, supervised group-based and Internet-based exercise can improve equally glycaemic control, waist circumference, and quality of life, and both are better than simply counselling.

Introduction: Diabetes mellitus (DM) affects peripheral nerves inducing diabetic polyneuropathy (DPN). Mitochondrial dysfunction and oxidative stress are potential causes of DPN., Methods: Nerve conduction studies were performed in 20 type 2 DM patients (11 with DPN) and 15 healthy controls. Perception threshold values of cold, warm and vibration were measured by quantitative sensory testing. Variants of a superoxide dismutase 2 (SOD2) gene single nucleotide polymorphism (SNP) (rs5746136) were determined by polymerase chain reaction (PCR) and following NexteraXT DNA Library., Results: DPN patients showed significantly increased threshold values. DM patients without DPN and healthy controls showed comparable values. TT variant of the SOD2 SNP was more prevalent in DM and DPN patients. DM patients with the TT variant displayed increased perception threshold values., Conclusions: Quantitative sensory testing is not superior to standard nerve conduction studies in DPN. Carriers of SOD2 SNP manifested increased sensory threshold levels which is important in further corroborating the link between oxidative stress and DPN., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors.

Background: Although the number of antihyperglycemic agents has expanded significantly, sulfonylureas (in particular gliclazide) remain an important option because of a variety of patient and health system factors. The large, real world, observational, and international EASYDia trial evaluated the effectiveness of gliclazide modified release (MR) 60 mg in individuals with type 2 diabetes with a broad range of diabetes history, body mass index (BMI) and background antihyperglycemic treatment., Methods: A total of 7170 participants from eight countries, age ≥ 35 years with HbA1c ≥ 7.5% and not treated with insulin, were prescribed 30-120 mg of gliclazide MR 60 mg once daily. HbA1c goals were individualized and dosing uptitrated, as required, over the 6-month long study. In this post hoc subanalysis, efficacy endpoints were analyzed according to stratified baseline HbA1c levels, weight and glucose-lowering regimens. Episodes of hypoglycemia requiring assistance were documented., Results: At baseline, mean age was 58.9 years, HbA1c 8.8%, BMI 30.1 kg/m 2 , and diabetes duration 5.1 years. At study end, clinically significant HbA1c improvements (mean change - 1.78%) were noted across all baseline HbA1c strata (> 7.0 to ≤ 8.0%, > 8.0 to ≤ 9.0%, > 9.0 to ≤ 10.0%, and > 10.0%), BMI classifications (18.5 to < 25.0, 25.0 to < 30.0, and ≥ 30.0 kg/m 2 ), and regardless of the original diabetes treatment regimen ( P  < 0.001 in all cases). In contrast to the subgroups with BMI 25.0-30.0 and ≥ 30.0 kg/m 2 that registered weight losses of 0.9 and 2.2 kg, respectively ( P  < 0.001 vs. baseline weight); the BMI 18.5-24.9 kg/m 2 subgroup gained a mean 0.5 kg ( P  < 0.02 vs. baseline weight). Severe hypoglycemic events were rare (0.06%)., Conclusions: Progressive gliclazide MR 60 mg uptitration was well tolerated and lowered HbA1c across a broad range of HbA1c, BMI and background glucose-lowering therapy. Weight loss was noted when BMI was ≥ 25.0 kg/m 2 . Individuals with the highest baseline HbA1c and BMI experienced the greatest HbA1c and weight improvements. Trial registration ISRCTN Registry ISRCTN00943368 on 1st July 2011.

Introduction Genetic mutations such as C599T polymorphism in glutathione peroxidase [GPX1] gene and polymorphisms in potassium channel (KCNJ11) genes have recently been proposed in the etiopathogenesis of new onset diabetes mellitus after renal transplantation (NODAT). We aimed to examine the association of GPX1 and KCNJ11 polymorphisms in NODAT. Materials and Methods This is a monocenter case-control study with a total of 118 renal transplant recipients who were divided into 2 groups; NODAT and normal glucose tolerance. Relation of GPX1 and KCNJ11 polymorphisms were investigated between these groups. PCR-RFLP method was used for genotyping of polymorphisms in the GPX1 (rs1050450) and KCNJ11 (rs1805127) genes. Two alleles were visualized for each gene (C/T for GPX1 and A/G for KCNJ11). Results NODAT was correlated with age at transplantation (p<0.001, r=0.380), post-transplant systolic blood pressure (BP) (p=0.02, r=0.211), post-transplant non-HDL cholesterol levels (p=0.01, r=0.803), degree of weight change at the end of the first year (p=0.01, r=0.471), presence of pre-transplant hypertension (HT) (p=0.02, r=0.201), family history of diabetes (p=0.01, r=0.29) and dyslipidemia (p=0.012, r=0.362). GPX1 polymorphism of TT (mutant) allele was significantly more frequent in patients with NODAT (p<0.001, r=0.396) independent from other diabetogenic risk factors. KCNJ11 polymorphisms were similar in both groups and did not show any significant association with NODAT (p=0.10). Conclusions In addition to several diabetogenic risk factors, C599T polymorphisms in GPX1 gene might also contribute to the development of NODAT. Further studies on larger patient series are necessary in order to reach definitive suggestions., Competing Interests: Conflict of interest : All the authors confirm no conflict of interest, (© Georg Thieme Verlag KG Stuttgart · New York.)

Aims: To examine the prevalence of chronic kidney disease (CKD) and its associated factors in a multinational population with type 2 diabetes mellitus (T2DM) and prior cardiovascular disease (CVD)., Methods: The LEADER trial randomized 9340 participants-81.3% with prior CVD at baseline. CKD was defined as estimated GFR <60ml/min/1.73m 2 and/or an albumin-to-creatinine ratio ≥3.0mg/mmol., Results: At baseline, 51.9% of participants with prior CVD had CKD. CKD prevalence was highest in Asia (75.8%) and lowest in Europe (43.7%) and the Middle East (43.4%). Baseline factors associated with increased CKD prevalence included increased age, HbA 1c , diabetes duration, systolic blood pressure or triglyceride levels; greater number of antihypertensive medications; living in Asia, the Americas or Africa versus Europe; being male; and not receiving oral antidiabetic drugs (most receiving insulin), beta-blockers or ACE inhibitors. Factors associated with decreased CKD prevalence included increased diastolic blood pressure, no diuretic treatment and prior myocardial infarction, angina or stroke., Conclusions: CKD prevalence is high among patients with T2DM and prior CVD. Advanced age, long diabetes duration, poor glycemic control, comorbidities and medications used are associated with CKD. Our results strengthen the rationale for early screening and interventions for CKD in patients with T2DM and prior CVD., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: In Turkey, the prevalence of diabetes is high but the influenza vaccination coverage rate (VCR) is low (9.1% in 2014), despite vaccination being recommended and reimbursed. This study evaluated the cost-effectiveness of increasing the influenza VCR of adults with type 2 diabetes in Turkey to 20%., Methods: A decision-analytic model was adapted to Turkey using data derived from published sources. Direct medical costs and indirect costs due to productivity loss were included in the societal perspective. The time horizon was set at 1 year to reflect the seasonality of influenza., Results: Increasing the VCR for adults with type 2 diabetes to 20% is predicted to avert an additional 19,777 influenza cases, 2376 hospitalizations, and 236 deaths. Associated influenza costs avoided were estimated at more than 8.3 million Turkish Lira (TRY), while the cost of vaccination would be more than TRY 8.4 million. The incremental cost-effectiveness ratio was estimated at TRY 64/quality-adjusted life years, which is below the per capita gross domestic product of TRY 21,511 and therefore very cost-effective according to World Health Organization guidelines. Factors most influencing the incremental cost-effectiveness ratio were the excess hospitalization rate, inpatient cost, vaccine effectiveness against hospitalization, and influenza attack rate. Increasing the VCR to >20% was also estimated to be very cost-effective., Conclusions: Increasing the VCR for adults with type 2 diabetes in Turkey to ≥20% would be very cost-effective.

Objective: As glucagon-like peptide-1 receptor agonists lower blood pressure (BP) in type 2 diabetes mellitus (T2DM), we examined BP control in relation to targets set by international bodies prior to randomization in the Liraglutide Effect and Action in Diabetes: Evaluation of cardiovascular outcome Results (LEADER) trial., Methods: We analyzed baseline data from LEADER (NCT01179048), an ongoing phase 3B, randomized, double-blind, placebo-controlled cardiovascular outcomes trial examining the cardiovascular safety of the glucagon-like peptide-1 receptor agonist liraglutide in 9340 people with T2DM from 32 countries [age (all mean ± SD) 64 ± 7.2 years, BMI 32.5 ± 6.3 kg/m, duration of diabetes 12.7 ± 8.0 years], all of whom were at high risk for cardiovascular disease (CVD)., Results: A total of 81% (n = 7592) of participants had prior CVD and 90% (n = 8408) had a prior history of hypertension. Despite prescription of multiple antihypertensive agents at baseline, only 51% were treated to a target BP of less than 140/85 mmHg and only 26% to the recommended baseline BP target of less than 130/80 mmHg. In univariate analyses, those with prior CVD were prescribed more agents (P < 0.001) and had lower BP than those without (137 ± 18.8/78 ± 10.6 mmHg versus 140 ± 17.7/80 ± 9.9 mmHg; P < 0.001). In logistic regression analyses, residency in North America (64% treated to <140/85 mmHg; 38% treated to <130/80 mmHg) was the strongest predictor of BP control., Conclusion: These contemporary data confirm that BP remains insufficiently controlled in a large proportion of individuals with T2DM at high cardiovascular risk, particularly outside North America. Longitudinal data from the LEADER trial may provide further insights into BP control in relation to cardiovascular outcomes in this condition.

Background: Middle income countries are facing an epidemic of non-communicable diseases, especially coronary heart disease (CHD). We used a validated CHD mortality model (IMPACT) to explain recent trends in Tunisia, Syria, the occupied Palestinian territory (oPt) and Turkey., Methods: Data on populations, mortality, patient numbers, treatments and risk factor trends from national and local surveys in each country were collated over two time points (1995-97; 2006-09); integrated and analysed using the IMPACT model., Results: Risk factor trends: Smoking prevalence was high in men, persisting in Syria but decreasing in Tunisia, oPt and Turkey. BMI rose by 1-2 kg/m(2) and diabetes prevalence increased by 40%-50%. Mean systolic blood pressure and cholesterol levels increased in Tunisia and Syria. Mortality trends: Age-standardised CHD mortality rates rose by 20% in Tunisia and 62% in Syria. Much of this increase (79% and 72% respectively) was attributed to adverse trends in major risk factors, occurring despite some improvements in treatment uptake. CHD mortality rates fell by 17% in oPt and by 25% in Turkey, with risk factor changes accounting for around 46% and 30% of this reduction respectively. Increased uptake of community treatments (drug treatments for chronic angina, heart failure, hypertension and secondary prevention after a cardiac event) accounted for most of the remainder., Discussion: CHD death rates are rising in Tunisia and Syria, whilst oPt and Turkey demonstrate clear falls, reflecting improvements in major risk factors with contributions from medical treatments. However, smoking prevalence remains very high in men; obesity and diabetes levels are rising dramatically., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim: The 6-months titration profile of a new scored gliclazide modified release (MR) formulation (MR 60 mg) was explored in individuals with type 2 diabetes., Methods: This international study enrolled 7170 individuals, age ≥ 35 years with HbA1c ≥ 7.5% (59 mmol/mol) and not on insulin. Participants were started on 30-120 mg gliclazide MR 60 mg once daily as a first line (FIRST), add-on (ADD) or switch from a previous oral antihyperglycemic treatment strategy (SWITCH). Uptitration was capped at 120 mg., Results: Women comprised 58.5% of the cohort. Mean baseline age was 58.9 years, body mass index 30.1 kg/m(2) and diabetes duration 5.1 years. Mean baseline HbA1c for the FIRST (n=2023), ADD (n=3136) and SWITCH (n=1834) groups was 8.9% (74 mmol/mol), 8.8% (73 mmol/mol) and 8.8% (73 mmol/mol), respectively. Probability of reaching optimal dose at months 1, 2, 3 and 6 was 15%, 39%, 59% and 92%, respectively. Mean HbA1c changes from baseline to month 6 were FIRST: -1.98%, ADD: -1.74% and SWITCH: -1.61% (all p<0.01). Overall, 65.3% achieved HbA1c ≤ 7.0% (53 mmol/mol); average duration for achieving glucose control was 80.1 days. Mean weight loss ranged from -1.45 to -1.27 kg. Severe hypoglycemia was experienced by 0.06% of participants. Most (95.5%) indicated a greater likelihood of adherence with the gliclazide MR 60 mg regime relative to their previous therapy., Conclusions: In this large, real world study, progressive uptitration with gliclazide MR 60 mg once daily appears to be efficacious and safe in individuals with suboptimal glycemic control at various stages of the diabetes continuum., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c) have been used to diagnose new-onset diabetes mellitus (DM) in order to simplify the diagnostic tests compared with the 2-hour oral glucose tolerance test (OGTT; 2-hPG). We aimed to identify optimal cut-off points of high sensitive C-reactive protein (hs-CRP) in new-onset DM people based on FPG, 2-hPG, or HbA1c methods. Data derived from recent population-based survey in Turkey (TURDEP-II). The study included 26,499 adult people (63% women, response rate 85%). The mean serum concentration of hs-CRP in women was higher than in men (p < 0.001). The people with new-onset DM based on HbA1c had higher mean hs-CRP level than FPG based and 2-hPG based DM cases. In HbA1c, 2-hPG, and FPG based new-onset DM people, cut-off levels of hs-CRP in women were 2.9, 2.1, and 2.5 mg/L [27.5, 19.7, and 23.5 nmol/L] and corresponding values in men were 2.0, 1.8, and 1.8 mg/L (19.0, 16.9, and 16.9 nmol/L), respectively (sensitivity 60-65% and specificity 54-64%). Our results revealed that hs-CRP may not further strengthen the diagnosis of new-onset DM. Nevertheless, the highest hs-CRP level observed in new-onset DM people diagnosed with HbA1c criterion supports the general assumption that this method might recognize people in more advanced diabetic stage compared with other diagnostic methods.

Aim: Hypoglycemia can be a concern for patients with type 2 diabetes when fasting during Ramadan. In this analysis, we assessed the incidence of symptomatic hypoglycemic events in fasting patients treated with gliclazide or dipeptidyl peptidase-4 (DPP-4) inhibitors., Methods: A systematic literature review was performed to identify randomized clinical trials comparing the efficacy and safety of gliclazide with DPP-4 inhibitors when treating adults with type 2 diabetes fasting during Ramadan. The primary endpoint of all included studies was the incidence of symptomatic hypoglycemic events., Results: The pooled analysis included three randomized trials. There was no evidence of heterogeneity between the studies (I(2)=0%). There was no significant difference in the incidence of symptomatic hypoglycemic events in patients fasting during Ramadan treated with either a DPP-4 inhibitor or gliclazide (5.6% versus 7.2%, risk ratio 1.12, 95% CI 0.73-1.73, p=0.61)., Conclusion: Patients treated with either gliclazide or DPP-4 inhibitors while fasting during Ramadan have similarly low risks of experiencing symptomatic hypoglycemia. Gliclazide is an effective oral antidiabetic that may be suitable for the management of patients with type 2 diabetes during Ramadan. Individualized Ramadan-focused advice and evening intake of treatment may improve the management of patients with diabetes during Ramadan., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Our goal was to reduce the number of modifiable risk factors for cardiovascular disease (CVD) through providing lifestyle adjustment training and counseling to patients with type 2 diabetes. In this pre-post intervention study, 139 patients with diabetes were provided with training to reduce the modifiable risks of CVD. One hundred three patients attended the post-training evaluation. Two phone counseling sessions were provided with 1-month intervals. Consumption of red meat and processed food decreased and water consumption, carrying on the recommended diet, and the frequency of exercise increased (p = .000), A1C decreased (p = .05), and the use of aspirin increased (p = .03). Thus, a contribution to the reduction of CVD risk factors in patients with type 2 diabetes was achieved. The training program for reducing CVD risk factors in patients with type 2 diabetes was effective in improving nutrition and lifestyle behaviors and decreasing glycemic control., (© The Author(s) 2014.)

Background: The objective of this qualitative study on young adults with type 1 diabetes was to determine the factors associated with mismanagement of diabetes., Methods: In this qualitative study, a descriptive phenomenological and psychological method was followed. Purposeful sampling method was used in this study. 28 young adults aged 18-25 with type 1 diabetes (16 females, 12 males) with HbA1c levels >6.5% were interviewed in-depth. Each interview lasted 40-45 minutes. The recorded interviews were transcribed verbatim, examined line-by-line and coded using open coding techniques and managed by QSR NVivo 7. During the research period, Guba ve Lincolln criteria were used to ensure the accuracy and precision of the study findings., Results: The study identified seven themes which affect the diabetes management of the patients. These themes were negative emotions about the disease, difficulties arising from living condition, difficulties arising from the treatment treatment process, lack of social support, not solution oriented coping methods, concerns about the future and issues of developing knowledge and attitude regarding diabetes management., Conclusion: There are multiple factors affecting the management of diabetes in young adults with type 1 diabetes. Diabetes has a biopsychosocial impact on young adults' lives, developing a negative attitude toward their future and that of their family.

Purpose: To determine the cardiovascular risk factors according to the Framingham, PROCAM and SCORE models, to evaluate the 10-year cardiovascular disease (CVD) risk factors, and to compare the suitability of different models in Turkish Type 2 diabetes patients., Methods: Risk factors and the 10-year CVD risk in 265 patients were evaluated using three risk models. Measurements included blood pressure, weight, height, waist and hip circumferences. Cholesterol, triglycerides, fasting and postprandial plasma glucose and HbA1c were measured. Low-, moderate- and high-risk groups were determined according to the three risk calculations., Results: Hypertension, obesity and no exercise, dyslipidemia and high HbA1c in women, and excessive cigarette/alcohol consumption, increased weight, dyslipidemia and high HbA1c in men were crucial. Men were in the moderate-risk group according to three risk models. Women were in the medium-risk group according to the Framingham and PROCAM risks and in the low-risk group according to the SCORE., Conclusion: Results estimating the 10-year CVD according to the three risk models were inconsistent. More sensitive CVD risk calculators are needed. Discussion and practice implications: Our results could guide diabetes specialists in identifying gender-specific risks and designing preventive interventions.

Background: To estimate cardiovascular disease (CVD) mortality in relation to obesity and gender., Methods: Data from 11 prospective cohorts from four European countries including 23 629 men and 21 965 women, aged 24 to 99 years, with a median follow-up of 7.9 years were analyzed. Hazards ratios (HR) for CVD mortality in relation to baseline body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were estimated using Cox proportional hazards models with age as the timescale., Results: Men had higher CVD mortality than women in all four BMI categories (<25.0, 25.0-29.9, 30.0-34.9 and ≥35.0 kg/m(2)). Compared with the lowest BMI category in women, multivariable adjusted HRs (95% confidence intervals) for higher BMI categories are 1.0 (0.8-1.4), 1.6 (1.1-2.1) and 2.8 (2.0-3.8) in women and 2.8 (2.2-3.6), 3.1 (2.5-3.9), 3.8 (2.9-4.9) and 5.4 (3.8-7.7) in men, respectively. Similar findings were observed for abdominal obesity defined by WC, WHR or WHtR. The gender difference was slightly smaller in obese than in non-obese individuals; but the interaction was statistically significant only between gender and WC (p = 0.02), and WHtR (p = 0.01). None of the interaction terms was significant among non-diabetic individuals., Conclusions: Men had higher CVD mortality than women across categories of anthropometric measures of obesity. The gender difference was attenuated in obese individuals, which warrants further investigation.

The role for the novel treatment approach of sodium-glucose cotransporter-2 (SGLT-2) in type 2 diabetes is increasing. Structured self-monitoring of blood glucose (SMBG), based on a less intensive and a more intensive scheme, may contribute to an optimization of SGLT-2 inhibitor based treatment. The current expert recommendation suggests individualized approaches of SMBG, using simple and clinically applicable schemes. Potential benefits of SMBG in SGLT-2 inhibitor based treatment approaches are early assessment of treatment success or failure, timely modification of treatment, detection of hypoglycemic episodes, assessment of glucose excursions, and support of diabetes management and education. The length and frequency of SMBG should depend on the clinical setting and the quality of metabolic control., (© 2014 Diabetes Technology Society.)

We aimed to examine the effect of increased physician awareness on the rate and determinants of influenza and pneumococcal vaccinations in diabetic patients. Diabetic patients (n = 5682, mean [SD] age: 57.3 [11.6] years, 57% female) were enrolled by 44 physicians between Sept 2010 and Jan 2011. The physicians were initially questioned regarding vaccination practices, and then, they attended a training program. During the last five years, the physicians recommended influenza and pneumococcal vaccinations to 87.9% and 83.4% of the patients, respectively; however; only 27% of the patients received the influenza and 9.8% received the pneumococcal vaccines. One year after the training, the vaccination rates increased to 63.3% and 40.7%, respectively. The logistic regression models revealed that variables which increased the likelihood of having been vaccinated against influenza were: longer duration of diabetes, presence of hyperlipidemia and more use of concomitant medications whereas more use of anti-hyperglycemic medications was associated with increased odds of vaccination. On the other hand, older age, longer duration of diabetes and presence of a cardiovascular disease were variables which decreased the likelihood of having been vaccinated against pneumococcal disease during the past five years. However, during the study period, variables which decreased the odds of having been vaccinated included: older age and anti-hyperglycemic medications for influenza, and presence of hyperlipidemia and a family history of hypertension for pneumococcal disease. While variables which increased the likelihood of vaccination in the same period were: increased number of co-morbidities for influenza, and family history of diabetes for pneumococcal disease. We conclude that increased awareness of physicians may help improve vaccination rates against influenza and pneumococcal disease. However, diabetic patients with more severe health conditions are less likely to having been vaccinated. More structural/systematic vaccination programs are needed to increase the vaccination rates in patients with diabetes.

Background: Type 2 diabetes mellitus (T2DM) poses a significant burden on population well being and healthcare expenditure in Turkey, with disease prevalence continuing to increase. Insulin treatment is necessary for patients failing to achieve glycaemic control with lifestyle modification or oral antidiabetic drugs. While neutral protamin Hagedorn (NPH) insulin has been traditionally prescribed for insulin introduction, insulin glargine has been shown to reduce glycated hemoglobin (HbA1c) with a more favourable hypoglycaemic profile. Objective: To evaluate the cost-effectiveness of insulin glargine compared to NPH insulin in patients with T2DM in Turkey, from a Social Security Institution perspective. Methods: A previously published discrete event simulation model of T2DM progression was utilised to characterise the cost-effectiveness of insulin glargine in a Turkish population given the benefits observed in clinical practice. Improvements in glycaemic control have been incorporated using data from The Health Improvement Network (THIN) database in the United Kingdom, combined with meta-regression results describing the relationship between hypoglycaemia and glycaemic control. Outcomes were evaluated over a 40-year horizon, and costs and benefits discounted at an annual rate of 3.5%. Results are reported in Turksih lira (TL), 2012. Results: Over a lifetime, the Incremental Cost-effectiveness Ratio (ICER) of insulin glargine compared to NPH was 40,101 TL per Quality-adjusted Life Year (QALY). Almost 52 hypoglycaemic events per patient were avoided with the use of insulin glargine compared to NPH, at an incremental lifetime cost of 7,140 TL per patient. The cost-effectiveness of insulin glargine is reduced when modelling only those benefits considered in the trial setting, while the cost-effectiveness profile can be expected to further improve in patients with higher HbA1c levels at baseline. Conclusion: It is difficult to interpret the results of modelling as there is no official cost-effectiveness threshold in Turkey. However, the results may be evaluated using thresholds derived according to methodology proposed by the World Health Organisation (WHO). Insulin glargine is expected to be costeffective compared to NPH insulin, with an ICER below three times the estimated gross domestic product (GDP) per capita; 56,850 TL.

The increasing role for structured and personalized self-monitoring of blood glucose (SMBG) in management of type 2 diabetes has been underlined by randomized and prospective clinical trials. These include Structured Testing Program (or STeP), St. Carlos, Role of Self-Monitoring of Blood Glucose and Intensive Education in Patients with Type 2 Diabetes Not Receiving Insulin, and Retrolective Study Self-Monitoring of Blood Glucose and Outcome in Patients with Type 2 Diabetes (or ROSSO)-in-praxi follow-up. The evidence for the benefit of SMBG both in insulin-treated and non-insulin-treated patients with diabetes is also supported by published reviews, meta-analyses, and guidelines. A Cochrane review reported an overall effect of SMBG on glycemic control up to 6 months after initiation, which was considered to subside after 12 months. Particularly, the 12-month analysis has been criticized for the inclusion of a small number of studies and the conclusions drawn. The aim of this article is to review key publications on SMBG and also to put them into perspective with regard to results of the Cochrane review and current aspects of diabetes management., (© 2013 Diabetes Technology Society.)

There is concern about an emerging diabetes epidemic in Turkey. We aimed to determine the prevalence of diagnosed and undiagnosed diabetes, prediabetes and their 12-year trends and to identify risk factors for diabetes in the adult Turkish population. A cross-sectional, population-based survey, 'TURDEP-II' included 26,499 randomly sampled adults aged ≥ 20 years (response rate: 87 %). Fasting glucose and biochemical parameters were measured in all; then a OGTT was performed to identify diabetes and prediabetes in eligible participants. The prevalence of diabetes was 16.5 % (new 7.5 %), translating to 6.5 million adults with diabetes in Turkey. It was higher in women than men (p = 0.008). The age-standardized prevalence to the TURDEP-I population (performed in 1997-98) was 13.7 % (if same diagnostic definition was applied diabetes prevalence is calculated 11.4 %). The prevalence of isolated-IFG and impaired glucose tolerance (IGT), and combined prediabetes was 14.7, 7.9, and 8.2 %, respectively; and that of obesity 36 % and hypertension 31.4 %. Compared to TURDEP-I; the rate of increase for diabetes: 90 %, IGT: 106 %, obesity: 40 % and central obesity: 35 %, but hypertension decreased by 11 % during the last 12 years. In women age, waist, body mass index (BMI), hypertension, low education, and living environment; in men age, BMI, and hypertension were independently associated with an increased prevalence of diabetes. In women current smoking, and in men being single were associated with a reduced risk. These results from one of the largest nationally representative surveys carried out so far show that diabetes has rapidly become a major public health challenge in Turkey. The figures are alarming and underscore the urgent need for national programs to prevent diabetes, to manage the illness and thus prevent complications.

The role of glucagon-like peptide (GLP)-1-based treatment approaches for type 2 diabetes mellitus (T2DM) is increasing. Although self-monitoring of blood glucose (SMBG) has been performed in numerous studies on GLP-1 analogs and dipeptidyl peptidase-4 inhibitors, the potential role of SMBG in GLP-1-based treatment strategies has not been elaborated. The expert recommendation suggests individualized SMBG strategies in GLP-1-based treatment approaches and suggests simple and clinically applicable SMBG schemes. Potential benefits of SMBG in GLP-1-based treatment approaches are early assessment of treatment success or failure, timely modification of treatment, detection of hypoglycemic episodes, assessment of glucose excursions, and support of diabetes management and diabetes education. Its length and frequency should depend on the clinical setting and the quality of metabolic control. It is considered to play an important role for the optimization of diabetes management in T2DM patients treated with GLP-1-based approaches., (© 2012 Diabetes Technology Society.)

The present report aims mainly at a reevaluation of salivary glucose concentration and excretion in unstimulated and mechanically stimulated saliva in both normal and diabetic subjects. In normal subjects, a decrease in saliva glucose concentration, an increase in salivary flow, but an unchanged glucose excretion rate were recorded when comparing stimulated saliva to unstimulated saliva. In diabetic patients, an increase in salivary flow with unchanged salivary glucose concentration and glucose excretion rate were observed under the same experimental conditions. Salivary glucose concentration and excretion were much higher in diabetic patients than in control subjects, whether in unstimulated or stimulated saliva. No significant correlation between glycemia and either glucose concentration or glucose excretion rate was found in the diabetic patients, whether in unstimulated or stimulated saliva. In the latter patients, as compared to control subjects, the relative magnitude of the increase in saliva glucose concentration was comparable, however, to that of blood glucose concentration. The relationship between these two variables was also documented in normal subjects and diabetic patients undergoing an oral glucose tolerance test.

To examine the short- and long-term influences of the Marmara earthquake, which occurred on August 17, 1999 in Turkey, on glycemic control and quality of life (QOL), HbA1c, insulin requirement and QOL of 88 people with type 1 diabetes living in the quake zone were evaluated one year before (PreE), 3 months after (PostE) and one year after (FE) the earthquake. HbA1c levels and daily insulin requirements increased significantly at PostE (HbA1c from 7.4 +/- 1.3% to 8.5 +/- 1.8%, p<0.05; insulin from 0.58 +/- 0.2 IU/kg/day to 0.77 +/- 0.2 IU/kg/day, p<0.05). Mean total QOL scores at PostE were significantly lower than the scores obtained at PreE (62.7 +/- 17.3 vs 74.2 +/- 13.4, p<0.001). There were no significant differences between HbA1c levels and total QOL scores at PreE and FE. People with type 1 diabetes living in the same house after the earthquake and not having enough food supply were reported to have lower QOL than people moving to another house and having enough food supply after the earthquake (p = 0.014, p<0.0001, respectively). The Marmara Earthquake had a negative impact on the glycemic control and QOL of the subjects with type 1 diabetes for the short term but prequake scores might be achieved after a long period.

Objectives: To investigate for the first time the prevalence of diabetes and impaired glucose tolerance (IGT) nationwide in Turkey; to assess regional variations and relationships between glucose intolerance and lifestyle and physical risk factors., Research Design and Methods: The Turkish Diabetes Epidemiology Study (TURDEP) is a cross-sectional, population-based survey that included 24,788 subjects (age > or =20 years, women 55%, response 85%). Glucose tolerance was classified according to World Health Organization recommendations on the basis of 2-h blood glucose values., Results: Crude prevalence of diabetes was 7.2% (previously undiagnosed, 2.3%) and of IGT, 6.7% (age-standardized to world and European populations, 7.9 and 7.0%). Both were more frequent in women than men (P < 0.0001) and in those living in urban rather than rural communities (P < 0.001). Prevalence rates of hypertension and obesity were 29 and 22%, respectively. Both were more common among women than men (P < 0.0001). Prevalence of diabetes and IGT increased with rising BMI, waist-to-hip ratio (WHR), and waist girth (P < 0.0001). Multiple logistic regression analysis revealed that age, BMI, WHR, familial diabetes, and hypertension were independently associated with diabetes, age, BMI, WHR, familial diabetes, and hypertension with IGT (except for familial diabetes in women with IGT). Education was related to diabetes in men but was protective for diabetes and IGT in women. Socioeconomic status appeared to decrease the risk of IGT in men while it increased the risk in women. Smoking had a protective effect for IGT in both sexes., Conclusions: Diabetes and IGT are moderately common in Turkey by international standards. Associations with obesity and hypertension have been confirmed. Other lifestyle factors had a variable relationship with glucose tolerance.

Alstrom syndrome is a rare disorder characterized by early obesity, loss of central vision, diabetes mellitus, hearing loss and short stature. Previous studies, have reported no information regarding oral findings. This article describes oral findings in two cases of Alstrom syndrome. In both cases, gingivitis was present and also light yellow-brown discolored enamel bands were observed on the anterior teeth. This staining may have resulted from discoloration of the preexisting slight band-like enamel hypoplasia. The gingiva was examined histologically by light and transmission electron microscopy. Irregular thickness of the basal lamina and delamination of the myelin sheath were detected by transmission electron microscopy. There is no information about pathological odontogenesis in Alstrom syndrome in previous reports. Oral present findings may contribute further information about the clinical manifestations of Alstrom syndrome.

Aim: To compare the effect of acarbose and gliclazide on clinical findings, biochemical parameters and safety in type 2 diabetic patients insufficiently controlled with medical nutrition therapy (MNT)., Methods: Seventy-two patients (age 35-70 years, BMI < or = 35 kg/m2), who had not taken any oral antidiabetic drug previously, were randomised into two groups after a four-week placebo period, and treated for 24 weeks with acarbose (100 mg two to three times daily) and gliclazide (40-80 mg twice daily). The study was open and 57 patients (33 males and 24 females) completed it. MNT was provided for each patient based on personal requirements as defined by a dietitian. The effect of treatment was evaluated by fasting and postprandial (PP) metabolic parameters (blood glucose, insulin and C peptide levels), HbA1c and plasma lipid levels. In addition, side-effects were recorded and clinical examinations performed., Results: Both drugs were effective in reducing of HbA1c, fasting and PP blood glucose levels. However, PP serum insulin levels in the gliclazide group increased more than those in the group treated with acarbose (p = 0.007). Moreover, a small weight reduction was obtained with acarbose treatment but not with gliclazide. Lipid levels were favourably affected by both drugs. Total cholesterol levels decreased in both groups, the decrease only reaching significance in the acarbose group (p = 0.013). However, serum levels of LDL cholesterol decreased in both groups (acarbose and gliclazide, p = 0.033 and p = 0.023, respectively), but the ratio of HDL to LDL cholesterol increased in the acarbose group only (p = 0.045). Both treatments were generally well tolerated. Common complaints in the acarbose group were flatulence and meteorism (29.6%). However, 10.0% of the patients in the gliclazide group reported at least one mild hypoglycaemic episode., Conclusions: The results of the study demonstrate that acarbose and gliclazide were reasonably effective in improving metabolic control in patients insufficiently controlled with diet alone, and both treatments were well tolerated. Because of its effects on weight reduction and PP hyperinsulinaemia, acarbose may be preferred as a first-line drug, particularly in the treatment of overweight type 2 diabetic patients.

The primary objectives of this study were to assess the efficacy and safety of Lys(B28), Pro(B29) in the treatment of patients with diabetes mellitus and to compare Lys(B28), Pro(B29) to currently available regular insulin with respect to quality of life. This study was designed as an open-label, non-comparative one. The number of patients enrolled in the trial was 39. At Visit 1 (week 0), blood samples for fasting, 1- and 2-hour postprandial blood glucose, and HbA1c were taken. At Visit 2 (week 6) and Visit 3 (week 12), fasting, 1- and 2-hour postprandial blood glucose, and HbA1c levels were measured again. There was no significant change in HbA1c, fasting blood glucose and 1- and 2-hour postprandial blood glucose levels. The 1- and 2-hour postprandial blood glucose excursions decreased significantly from Visit 1 to Visit 3. There were no serious adverse events during the study. Half of the patients had less hypoglycemia with LysPro insulin, while 25% had an increase in episodes. Thirty percent of patients were more satisfied with LysPro insulin than with the short-acting insulin that they had previously used. In conclusion, LysPro therapy can be regarded as safe, since there were no unexpected adverse events and no changes in the usual physical parameters.

In this study we evaluated 31 insulin-dependent diabetes mellitus (IDDM) patients (ages 12.1 +/- 3.4 years, 18 males/13 females) who started on multiple subcutaneous insulin injections (MSII) within six weeks of diagnosis and achieved either complete (CR: no insulin requirement and near-normoglycemia for at least two weeks) or incomplete (ICR: minimum 50% decline in insulin requirement while maintaining near-normoglycemia for two weeks or more) remissions within the first 12 weeks of the MSII trial. Methylprednisolone pulse therapy (MP) was administered four times per day by i.v. bolus at a dose of 30 mg/kg (max. 1000 mg) on alternative days. Eleven patients did not accept "MP-pulse" therapy; therefore, we followed these cases (7 males/4 females) as the control group. During the first year of follow-up, 13 patients from the "MP pulse" group achieved CR (3 males/1 female) or ICR (5 males/4 females) in 3.5 to 14 months. Remission occurred in only two of the control group cases (1 male CR for 17 days and 1 female CR for 7 months). Of those with CR in the "MP-pulse" and control groups, all were greater than 12 years of age, and all but one in the "MP-pulse" group were males. The stimulation capacity of beta cells (as defined by percentage increase in serum C-peptide levels after glucagon injection) among CR cases was found to be higher than that of non-remitted (NR) cases (p < 0.05 at onset, p < 0.001 during MSII-induced remission and p < 0.05 at the end of the first year of follow-up). Although patients with CR or ICR had higher beta cell reserves than NR cases at onset, only CR cases could sustain this capacity during the MSII-induced remission phase and one year after "MP-pulse" therapy. From this preliminary study, we conclude that "MP-pulse" therapy, may lead to prolonged near-normal beta cell function or partly preserved residual beta cell reserve during the MSII-induced remission phase of IDDM, The beneficial effects of MP could be seen clearly in patients diagnosed during the late childhood years.

Sclerodactyly is a chronic skin disorder seen together with long-term degenerative microvascular complications of diabetes mellitus. In this study, the relationship between sclerodactyly and various clinical and laboratory characteristics of diabetes mellitus have been investigated. One hundred and forty-two diabetic patients (63 type 1 and 79 type 2) and 72 healthy controls were evaluated clinically. Among the 142 diabetic patients, skin biopsies were taken from 21; 38 underwent soft tissue X-ray examination and 78 underwent periungual capillaroscopy. Among the healthy controls those with sclerodactyly were on the average 12 years older than those without (T: 3.38; P < 0.01). On the other hand, among the patients with either type 1 or type 2 diabetes mellitus the ages were similar between those with and without sclerodactyly. There were no statistically significant differences in the prevalence of diabetic complications. The presence of complications, increased proximal nail fold capillarity, HbA1c levels, radiological and histopathological findings were not different among those patients who had or did not have sclerodactyly.