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Aims: Bidirectional detrimental relationships between COVID-19 infection and diabetes have been described globally. However, new-onset diabetes in adults and its follow-up during the pandemic have not been sufficiently investigated. In this study, new-onset autoimmune and type 2 diabetes cases during the pandemic were compared to those before the pandemic, and the clinical course of new-onset diabetes during the pandemic was examined., Methods: In this single-center retrospective cohort study, clinical and laboratory characteristics of new-onset diabetes patients before the pandemic (n = 161) and during the pandemic (n = 144) were evaluated between March 2018 and March 2022., Results: A 1.85-fold increase in new-onset adult diabetes cases was observed during the pandemic compared to pre-pandemic period (p = 0.010), while the proportion of autoimmune and type 2 diabetes (T2D) did not change. During the pandemic, there was a 6.2-fold increase in autoimmune diabetes presented with DKA (p = 0.003). Insulin was preferred 1.7 times more frequently as initial treatment during the pandemic (p = 0.014), and mean HbA1c (p = 0.003) and C-peptide (p = 0.010) were higher. Clinical and laboratory data did not differ between PCR (+) and PCR (-) patients. At one-year follow-up, while only HbA1c decreased in the autoimmune diabetes; in T2D group fasting glucose, HbA1c, C-peptide, and lipid profile were significantly improved., Conclusions: The pandemic led to increased new-onset adult diabetes presented with DKA. However, clinical and laboratory features were similar between PCR positive and negative cases. PCR-confirmed COVID-19 may not adversely affect the medium-term clinical course of new diabetes in adults., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest relevant to the content of this article. No external funding was received for the conduct of this study or the preparation of this manuscript. The authors have no financial relationships with any organizations that might have an interest in the submitted work, and no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Purpose:   Familial hypercholesterolemia (FH) is a genetic disorder associated with extremely high levels of low-density lipoprotein cholesterol (LDL-C) and increased incidence of cardiovascular disease. We aimed to evaluate the efficacy and long-term outcomes of lipoprotein apheresis (LA) in the treatment of FH., Methods:   Cardiovascular events that occurred before and after LA treatment were evaluated by reviewing previous medical records of patients with FH., Results:   Thirteen patients (female/male: 8/5) were included in this study. The mean Dutch score was 20±4. All patients were treated with a combination of statin and ezetimibe. Before the onset of LA, 8 patients had a history of coronary artery disease, and the median age at onset of cardiovascular disease (CVD) in these patients was 24 years. At the initiation of LA, the median age was 22 years and the mean LDL-C level was 410±130 mg/dL. The mean duration of LA treatment was 13.9±6.9 years. The mean LDL-C levels before and after the latest three LA treatments were 267±63.4 and 71.5±23.4 mg/dL, respectively. The mean reduction in LDL-C levels after LA was 73±8.2%. De novo cardiovascular events occurred in 10 patients during LA treatment; six of these patients had a known history of CVD before LA. Eight of these patients underwent invasive procedures for therapeutic purposes and the total number of procedures was 12., Conclusion:   LA is an effective method of reducing LDL-C levels and an additional treatment option that may slow disease progression in patients with FH who are at high risk of cardiovascular events., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Aims: The objective of this study was to evaluate the associations of several genetic variants of peroxisome proliferator-activated receptors (PPARs) on clinical and laboratory parameters in patients with maturity-onset diabetes of the young (MODY), and possible contribution to heterogeneity of the disease., Methods: The study groups comprised patients with MODY (genetically confirmed (n = 28), clinically relevant but genetically unconfirmed; MODYX (n = 56)), type 2 diabetes mellitus (T2DM; n = 94) and healthy controls (n = 153). PPARA-L162V-(rs1800206), PPARG-C161T-(rs3856806), P12A-(rs1801282), and PPARB/D + 294 T/C-(rs2016520) polymorphisms were genotyped by real-time-PCR., Results: The results demonstrated that the frequencies of PPARA-LL162 (p = 0.002), PPARG-CC161 (p = 0.002), and PPARG-ProPro (p = 0.012) genotypes were significantly higher in the MODY group compared to the controls. Furthermore, total-MODY and MODYX groups had a higher frequency of PPARA-LL162 genotype than T2DM (p = 0.005 and p = 0.006, respectively). The frequency of the PPARB/D + 294 T allele was significantly higher in individuals with T2DM than in genetically-determined MODY group (p = 0.019). The PPARA-LL162 genotype was associated with early-onset diabetes in total-MODY (p = 0.022) and T2DM (p < 0.05) groups., Conclusions: The association of PPARA-L162V polymorphism with early-onset diabetes in both T2DM and MODY is a noteworthy finding. Considering these results, we suggested that genetic polymorphisms in PPAR isoforms may contribute to the clinical and metabolic heterogeneity of MODY., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Metabolic syndrome (MetS) comprises a cluster of cardiovascular risk factors. Physical inactivity and reduced physical fitness are associated with one or more components of MetS. However, MetS has many components, and the unclear relationship between the components and physical fitness parameters can provide a plain and straightforward understanding of the clustering method. Aim: To identify the relationship between physical fitness parameters, physical activity levels, and components of MetS using hierarchical cluster analysis. Methods: One hundred twenty-one patients (mean age = 51.4 ± 7.1/years, F:90, M:31) who were diagnosed as having MetS according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria were included in the study. Fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) were analyzed. Systolic and diastolic blood pressures, (SBP and DBP), were evaluated. Body composition (waist and hip circumference, (WC and HC), waist-to-hip ratio (WHR), body mass index (BMI), percent body fat, and visceral fat), upper and lower extremity muscle strength (dynamometer), and functional exercise capacity [6-minute walk test (6MWT)] were assessed as physical fitness parameters. Physical activity levels were assessed using a pedometer and number of steps (NS) was determined. Results: Of the patients, 45.5% were diagnosed as having MetS based on four components. The dendrogram consisted of two main clusters and four subclusters. The main cluster I composed of BMI, HC, WC, visceral fat, HDL-C, percent fat, SBP, DBP, and percent quadriceps. The main cluster II comprised FPG, TG, WHR, handgrip strength, 6MWT, and NS. Conclusion: MetS components clustered with different physical fitness parameters. The clusters in the dendrogram can provide substantial implications for heterogeneous MetS components and physical fitness parameters. Future studies are needed to elucidate the effectiveness of dendrogram-derived exercise programs in MetS.

Many individuals with intermediate hyperglycaemia (IH), including impaired fasting glycaemia (IFG) and impaired glucose tolerance (IGT), as presently defined, will progress to type 2 diabetes (T2D). There is confirmatory evidence that T2D can be prevented by lifestyle modification and/or medications, in people with IGT diagnosed by 2-h plasma glucose (PG) during a 75-gram oral glucose tolerance test (OGTT). Over the last 40 years, a wealth of epidemiological data has confirmed the superior value of 1-h plasma glucose (PG) over fasting PG (FPG), glycated haemoglobin (HbA 1c ) and 2-h PG in populations of different ethnicity, sex and age in predicting diabetes and associated complications including death. Given the relentlessly rising prevalence of diabetes, a more sensitive, practical method is needed to detect people with IH and T2D for early prevention or treatment in the often lengthy trajectory to T2D and its complications. The International Diabetes Federation (IDF) Position Statement reviews findings that the 1-h post-load PG ≥ 155 mg/dL (8.6 mmol/L) in people with normal glucose tolerance (NGT) during an OGTT is highly predictive for detecting progression to T2D, micro- and macrovascular complications, obstructive sleep apnoea, cystic fibrosis-related diabetes mellitus, metabolic dysfunction-associated steatotic liver disease, and mortality in individuals with risk factors. The 1-h PG of 209 mg/dL (11.6 mmol/L) is also diagnostic of T2D. Importantly, the 1-h PG cut points for diagnosing IH and T2D can be detected earlier than the recommended 2-h PG thresholds. Taken together, the 1-h PG provides an opportunity to avoid misclassification of glycaemic status if FPG or HbA 1c alone are used. The 1-h PG also allows early detection of high-risk people for intervention to prevent progression to T2D which will benefit the sizeable and growing population of individuals at increased risk of T2D. Using a 1-h OGTT, subsequent to screening with a non-laboratory diabetes risk tool, and intervening early will favourably impact the global diabetes epidemic. Health services should consider developing a policy for screening for IH based on local human and technical resources. People with a 1-h PG ≥ 155 mg/dL (8.6 mmol/L) are considered to have IH and should be prescribed lifestyle intervention and referred to a diabetes prevention program. People with a 1-h PG ≥ 209 mg/dL (11.6 mmol/L) are considered to have T2D and should have a repeat test to confirm the diagnosis of T2D and then referred for further evaluation and treatment. The substantive data presented in the Position Statement provides strong evidence for redefining current diagnostic criteria for IH and T2D by adding the 1-h PG., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Objective: Adipose tissue is the largest endocrine organ in the human body, and as its mass changes, the serum levels of the molecules it secretes also change. Visceral adipose tissue index (VAI) is a simple surrogate marker of visceral adipose tissue dysfunction. This study evaluated the effects of changes in fat mass on adipocytokine behavior and VAI in patients with anorexia nervosa (AN) and extreme obesity (EO)., Patients and Methods: The study group consisted of three subgroups: Group 1, patients with EO who were candidates for obesity surgery with BMI≥50 kg/m2 (n=20). Group 2, newly diagnosed patients with AN (n=12). Group 3 controls with BMI 20-25 kg/m2 (n=20). The AN and EO groups were followed until at least a 10% weight change before and after the intervention., Results: Prior to the intervention, EO patients exhibited the lowest levels of apelin, omentin, and adiponectin, while AN patients demonstrated the highest levels of these markers. Leptin and IL-6 were elevated in EO and reduced in AN patients. After treatment, all adipokines and VAI increased in AN patients, and omentin, adiponectin, and IL-6 increased in EO patients, while apelin, leptin, and VAI decreased. The change in each adipocytokine (∆) was positively correlated with the other adipocytokines (p<0.050) and negatively correlated with metabolic and VAI changes (p<0.050). The regression analysis determined that the following variables were associated with the change in adipose tissue mass: Δapelin (OR: 1.061; p=0.028) and Δadiponectin (OR: 1.057; p=0.036)., Conclusions: In individuals with pathological adipocyte mass, the change in adipocytokine levels in response to weight change is not as expected. The fact that these changes are not seen in the early period of the weight intervention treatment indicates that these patients have compensatory physiological mechanisms to protect them. In addition, using VAI instead of BMI, whose reliability is increasingly questioned because it does not reflect body fat mass, can be considered an alternative. However, there may be modeling errors in the early stages of weight change and in AN and EO patients where metabolic parameters reach extreme values. Therefore, it should be tested in studies where larger patient groups are followed for a more extended period.

Background and Aim: Sudomotor dysfunction is linked to small fibers damage. We investigated sudomotor dysfunction in a large group of participants with diabetes, prediabetes, and nondiabetic healthy subjects. This study aimed to complete knowledge on sudomotor dysfunction in this population, especially regarding the threshold values for the electrochemical skin conductance (ESC) and factors affecting it., Materials and Methods: A total of 690 volunteers in four groups were included in the study (type 1 [T1DG]: n = 80, 61.3% women; type 2 diabetes [T2DG]: n = 438, 63.5% women; prediabetes [Pre-DG]: n = 88, 80.7% women; healthy control [HC-G]: n = 84, 67.5% women). All subjects were investigated for clinical diabetic peripheral polyneuropathy and sudomotor dysfunction. The characteristics of participants obtained from outpatient records were evaluated. We used the Sudoscan device to measure ESC which was normalized for BMI, to improve the discriminative capability of the method., Results: Diabetic polyneuropathy was found in 17.5% of T1DG, 27.4% of T1DG, and 10.2% of Pre-DG. The mean ESC/BMI was lower in subgroups with diabetic polyneuropathy than those without. Mean ESC/BMI was lowest in T2DG and highest in HC-G but comparable in T1DG and Pre-DG. We accepted the "mean ESC/BMI-1 SD" in the HC-G as the threshold for sudomotor dysfunction. Accordingly, the prevalence of sudomotor dysfunction was 18.8%, 44.3%, 59.1%, and 15% in T1DG, T2DG, Pre-DG, and HC-G, respectively. In T2DG, sudomotor dysfunction was found in 66.7% of persons with retinopathy, of which 56.3% had clinical diabetic polyneuropathy. The prevalence of sudomotor dysfunction in subjects with peripheral artery disease, chronic kidney disease, cardiovascular disease, and hypertension was 46.7%, 47.4%, 43.4%, and 50%, respectively, and 42.9%, 38.9%, 45.5%, and 37.3% of whom in the same order detected with clinical diabetic polyneuropathy. Considering the entire group, a logistic regression model demonstrated that the variables associated with SMD were: retinopathy (OR: 2.969; 95% CI: 1.723, 5.114), female gender (OR: 1.952; 95% CI: 1.287, 2.962), and e-GFR (OR: 0.989; 95% CI: 0.981, 0.998). Since the rate of complications was very low in T1DG, excluding this group, a new model similarly revealed that retinopathy and female gender were associated with SMD, however, the association with e-GFR was disappeared., Conclusion: The prevalence of sudomotor dysfunction is high when established peripheral polyneuropathy was present in diabetes. Even though, sudomotor dysfunction can also occur before clinical polyneuropathy in both types of diabetes (T1DG: 18.8%, T2DG 44.3%), prediabetes (59.1%), and nondiabetic healthy subjects (15%). The variables associated with sudomotor dysfunction were retinopathy and female sex. Normalization of ESC for BMI would be a beneficial approach. However, before this method is included in the routine screening programs for diabetic polyneuropathy, large-scale and prospective studies are required to reach a consensus on the pathological threshold values., Competing Interests: Declaration of Competing Interest The authors: B.F.C., S.C., C.I., E.B., H.I., and I.S. declared that they have no conflict of interest. J-H.C. was former Medical Director of IMPETO Medical between 2010 and 2021., (Copyright © 2023 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Purpose: Recent studies indicate that dysbiosis of gut microbiota and low-grade inflammation are important pathogenic determinants of type two diabetes mellitus (T2DM). The aim of this study is to investigate the effects of Lactobacillus GG on glycemic control, lipid profile, inflammatory parameters, and some gene expression levels in individuals with T2DM., Methods: In a randomized, placebo-controlled trial, 34 women, aged 30-60 years with T2DM consumed daily probiotics or placebo for 8 weeks. The probiotic group consumed 10 × 10 9 Cfu/day Lactobacillus rhamnosus GG ATCC 53,103 (LGG), approved by the TR Ministry of Food, Agriculture, and Livestock. Anthropometric measurements, food diary, fasting blood, and fecal samples were taken at baseline and post-treatment., Results: Fasting blood glucose was significantly decreased in probiotic (p = 0.049) and placebo (p = 0.028), but there was no difference between the groups. In the probiotic group, no significant difference was observed in HbA1c, fructosamine, lipid profile, and inflammatory variables compared to baseline. In this group, with LGG supplementation, mucin 2 and 3A (MUC2 and MUC3A) gene expressions increased more than ninefolds (p = 0.046 and p = 0.008, respectively) at post-treatment. Meanwhile, there was no significant change in any of the gene expressions in the placebo group. There was no significant difference in energy, protein, dietary fiber, and cholesterol intakes between placebo and probiotic groups during the study. However, daily fat intake (p = 0.003), body weight (p = 0.014), and body fat (p = 0.015) in the probiotic group were significantly decreased., Conclusion: In this study, the effects of a single probiotic strain were investigated for 8 weeks. At the end of the study, although there was no finding that clearly reflected on the glycemic parameters of T2DM, its beneficial effects on the expression of mucin genes, which are responsible for weight loss and protection of intestinal barrier functions, cannot be denied. Further studies are needed to reveal the importance of these findings., Clinical Trial Registration: ID: NCT05066152, October 4, 2021 retrospectively registered in ClinicalTrials.gov PRS web site., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Aims: Familial hypercholesterolemia (FH) is the most common cause of premature atherosclerotic cardiovascular disease (ASCVD). Türkiye is among the countries with the highest rate of ASCVD. However, no population-based study has been published so far on the prevalence of FH, demographic and clinical characteristics, burden of ASCVD, treatment compliance, and attainment of low-density lipoprotein cholesterol (LDL-C) targets., Methods: We performed a study using the Turkish Ministry of Health's national electronic health records involving 83,063,515 citizens as of December 2021 dating back 2016. Adults fulfilling the diagnostic criteria of definite or probable FH according to the Dutch Lipid Network Criteria (DLNC), and children and adolescents fulfilling the criteria of probable FH according to the European Atherosclerosis Society (EAS) Consensus Panel report formed the study population (n = 157,790). The primary endpoint was the prevalence of FH., Results: Probable or definite FH was detected in 0.63% (1 in 158) of the adults and 0.61% (1 in 164) of the total population. The proportion of adults with LDL-C levels >4.9 mmol/L (190 mg/dL) was 4.56% (1 in 22). The prevalence of FH among children and adolescents was 0.37% (1 in 270). Less than one-third of the children and adolescents, and two-thirds of young adults (aged 18-29) with FH were already diagnosed with dyslipidaemia. The proportion of adults and children and adolescents on lipid-lowering treatment (LLT) was 32.1% and 1.5%, respectively. The overall discontinuation rate of LLT was 65.8% among adults and 77.9% among children and adolescents. Almost no subjects on LLT were found to attain the target LDL-C levels., Conclusions: This nationwide study showed a very high prevalence of FH in Türkiye. Patients with FH are diagnosed late and treated sub-optimally. Whether these findings may explain the high rates of premature ASCVD in Türkiye needs further investigation. These results denote the urgent need for country-wide initiatives for early diagnosis and effective management of FH patients., Competing Interests: Declaration of competing interest The authors written below declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Telemedicine is a follow-up system that can improve the quality of management and cost-effectiveness of rapidly increasing diabetes patients. Methods: Two hundred adult patients with diabetes were enrolled in this prospective, randomized study. Consecutive patients were divided equally into two groups. Both groups received routine care visits quarterly. TeleDiab group also sent self-monitoring of blood glucose data and received short message service over the transmission system for 12 months. After the study was completed, all patients continued their routine care visits, and their data were evaluated for another 12 months. Six years after the initial study, patients were contacted by phone during the Covid-19 lockdown, and their status was assessed. Results: At the end of the study, glycemic control, kidney function, and lipid parameters of the TeleDiab group were statistically significantly better than the Usual Care group. There was no significant change in the weights of the patients. It was observed that this state of wellbeing continued both at the end of the second year and during the Covid-19 lockdown. Individuals with type 2 diabetes were found to benefit more from telemedicine. Discussion: It has been beneficial to guide patients with applications such as TeleDiab in diseases such as diabetes that require lifelong follow-up. On the other hand, the importance of telemedicine programs in the management of chronic diseases in the current pandemic conditions has come to the fore even more. Telemedicine is an effective motivational tool to ensure optimal control not only of glycemic but also of kidney and lipid parameters.

Nonalcoholic fatty liver disease (NAFLD) is a multisystem disease and is significantly associated with obesity, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular disease. NAFLD has become the most prevalent chronic liver disease in Western countries, and the proportion of NAFLD-related cirrhosis among patients on liver transplantation waiting lists has increased. In light of the accumulated data about NAFLD, and to provide a common approach with multi-disciplines dealing with the subject, it has become necessary to create new guidance for diagnosing and treating NAFLD. This guidance was prepared following an interdisciplinary study under the leadership of the Turkish Association for the Study of the Liver (TASL), Fatty Liver Special Interest Group. This new TASL Guidance is a practical application guide on NAFLD and was prepared to standardize the clinical approach to diagnosing and treating NAFLD patients. This guidance reflects many advances in the field of NAFLD. The proposals in this guidance are meant to aid decision-making in clinical practice. The guidance is primarily intended for gastroenterology, endocrinology, metabolism diseases, cardiology, internal medicine, pediatric specialists, and family medicine specialists., Competing Interests: The authors have no conflict of interest to declare., (© Copyright 2023 by Hepatology Forum.)

Objective: To compare the effect of glucose-lowering drugs on peripheral nerve and kidney function in prediabetes., Methods: Multicenter, randomized, placebo-controlled trial in 658 adults with prediabetes treated for 1 year with metformin, linagliptin, their combination or placebo. Endpoints are small fiber peripheral neuropathy (SFPN) risk estimated by foot electrochemical skin conductance (FESC < 70 μSiemens) and estimated glomerular filtration rate (eGFR)., Results: Compared to the placebo, the proportion of SFPN was reduced by 25.1% (95% CI:16.3-33.9) with metformin alone, by 17.3% (95% CI 7.4-27.2) with linagliptin alone, and by 19.5% (95% CI 10.1-29.0) with the combination linagliptin/metformin ( p < 0.0001 for all comparisons). eGFR remained +3.3 mL/min (95% CI: 0.38-6.22) higher with the combination linagliptin/metformin than with the placebo ( p = 0.03). Fasting plasma glucose (FPG) decreased more with metformin monotherapy -0.3 mmol/L (95%CI: -0.48; 0.12, p = 0.0009) and with the combination metformin/linagliptin -0.2 mmol/L (95% CI: -0.37; -0.03) than with the placebo ( p = 0.0219). Body weight (BW) decreased by -2.0 kg (95% CI: -5.65; -1.65, p = 0.0006) with metformin monotherapy, and by -1.9 kg (95% CI: -3.02; -0.97) with the combination metformin/linagliptin as compared to the placebo ( p = 0.0002)., Conclusions: in people with prediabetes, a 1 year treatment with metformin and linagliptin, combined or in monotherapy, was associated with a lower risk of SFPN, and with a lower decrease in eGFR, than treatment with placebo.

Aims: Diabetes mellitus is a chronic disease that limits the quality and duration of life. We aimed to estimate the impact of demographic change on the burden of prediabetes and diabetes between 2010 and 2021, and the projections to 2030 and 2045 in Turkiye., Materials and Methods: Prediabetes and diabetes estimates were calculated by direct standardization method using age- and sex-specific prevalence data from the previous 'Turkish Epidemiology Survey of Diabetes, Hypertension, Obesity and Endocrine Disease' (TURDEP-II) as reference. The 2010-2021 population demographics were obtained from TurkStat. Comparative age-adjusted diabetes prevalence was estimated using the standard population models of world and Europe., Results: Estimates depicted that the population (20-84 years) of any degree of glucose intolerance in Turkiye increased by over 5.7 million (diabetes: 2.4 million and prediabetes: 3.3 million) from 2010 to 2021. While the increase in prediabetes and diabetes prevalence was 24.3% and 35.2% in overall population, corresponding increase were 46.5% and 51.3% in the elderly. Estimated prevalence of prediabetes and diabetes in 2021 was significantly higher in women than in men (prediabetes: 32.6% vs. 25.2%; diabetes: 17.1% vs. 14.2%). The comparative age-adjusted diabetes prevalence to the European population model was higher than that of the world population model (19.4% vs. 15.0%). According to the projections the prevalence of diabetes will reach 17.5% in 2030 and 19.2% in 2045., Conclusion: Assuming age- and sex-specific diabetes prevalence of TURDEP-II survey remained constant, this study revealed that the number of people with diabetes in the general population (particularly in the elderly) in the last 11 years in Turkiye has increased in parallel with the population growth and aging; it will continue to grow over the coming decades. This means the burden of diabetes on the social, economic and health services will remain to increase. The fact suggests that there is an urgent need for re-organization of care as well as to develop and implement a country-specific prevention program to reduce this burden., (© 2023. Springer Nature B.V.)

Rare disease patients constitute a significant part of the healthcare system of all countries. However, the information on the experiences during disease processes and daily life of rare disease patients is still limited. So far, there is a small number of studies conducted in Türkiye, and they mainly cover specific issues like education or anxiety. Here we present a comprehensive survey analysis conducted among the patients and their families within the scope of the Istanbul Solution Platform for Undiagnosed and Rare Diseases-ISTisNA project. A total of 498 individuals responded to the survey, and 58% of the participants answered all questions. The majority of the patients were in the age range of 1-10 years (44.7%), and 91% of all the patients had a precise diagnosis. The diagnosis rate in the first 6 months was 69%, and almost 10% of the patients remained undiagnosed. The mothers were the primary caregivers (72%). Nearly 30% of the caregivers had to quit their jobs and 25% of the patients (0-18 years) had to leave school. Accessing physicians with relevant specialization and reaching treatments/medications/supplements were the two main obstacles the participants mentioned, with a frequency of 81% and 73%, respectively. Around 50% of participants noted that they commonly faced difficulties at work/school and in their social lives. The highest expectation or priority was the establishment of rare disease-specific diagnosis and treatment centers, accurate and detailed information on diseases in the Turkish language, and easy access to physicians, treatments, and supportive therapies. To the best of our knowledge, this is the most comprehensive survey conducted on the rare disease community in Türkiye. These results show that regardless of the country, the individuals affected by rare diseases and their families have similar problems and expectations. On the other hand, regional and country-specific issues are still in the line to be solved. These studies can provide a deeper insight into rare diseases and guide the activities of Türkiye's national rare disease action plan., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hatirnaz Ng, Sahin, Erbilgin, Ozdemir, Yucesan, Erturk, Yemenici, Akgun Dogan, Ugur Iseri, Satman, Alanay and Ozbek.)

To which extent the pre-existing hypothyroidism or hyperthyroidism has an impact on coronavirus infection 2019 (COVID-19) outcomes remains unclear. The objective of this study was to evaluate COVID-19 morbidity and mortality in patients with pre-existing thyroid dysfunction. A retrospective cohort of patients with a polymerase chain reaction (PCR)-confirmed COVID-19 infection (n=14 966) from March 11 to May 30, 2020, was established using the database of the Turkish Ministry of Health. We compared the morbidity and mortality rates of COVID-19 patients with pre-existing hypothyroidism (n=8813) and hyperthyroidism (n=1822) to those patients with normal thyroid function (n=4331). Univariate and multivariate regression analyses were performed to identify the factors associated with mortality. Mortality rates were higher in patients with hyperthyroidism (7.7%) and hypothyroidism (4.4%) than those with normal thyroid function (3.4%) (p<0.001 and p=0.008, respectively). Pre-existing hyperthyroidism was significantly associated with an increased risk of mortality (OR 1.54; 95% CI, 1.02-2.33; p=0.042) along with advanced age, male gender, lymphopenia and chronic kidney disease (p<0.001 for all). Although a potential trend was noted, the association between pre-existing hypothyroidism and mortality was not significant (OR 1.36; 95% CI, 0.99-1.86; p=0.055). In conclusion, this study showed an association between pre-existing hyperthyroidism with higher COVID-19 mortality. A potential trend towards increased mortality was also observed for hypothyroidism. The risk was more pronounced in patients with hyperthyroidism., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Background/aim: High-sensitivity C-reactive protein (hs-CRP) is used in the differential diagnosis of maturity-onset diabetes of the young (MODY)-3, but other inflammatory markers have not been investigated in MODY patients. We aimed to compare the serum levels of anti-inflammatory and proinflammatory cytokines between MODY patients and healthy subjects and show the inflammatory features in MODY subtypes., Patients and Methods: Thirty patients with clinically suspected MODY and 34 healthy controls were included in this study. Next-generation sequencing (NGS) was used for the molecular diagnosis of MODY subtypes. Serum levels of cytokines were measured using a multiplexed cytokine assay and hs-CRP concentration was determined by the immunoturbidimetric assay., Results: The hs-CRP levels were higher in both NGS-confirmed (MODY, n=17) (p=0.009) and NGS-unconfirmed (non-MODY, n=13) patients (p<0.001) than those in controls. However, IL-1β (p=0.001), IL-6 (p=0.018), IL-31 (p=0.003), TNF-α (p<0.001), and sCD40L (p=0.007) levels of MODY patients and IL-1β (p=0.002), IL-31 (p<0.001), IL-22 (p=0.018), and sCD40L (p=0.039) levels of non-MODY patients were lower than those of controls. While hs-CRP levels were lower in MODY3 patients than non-MODY3 patients (p=0.009), IL-17A (p=0.006) and IL-23 (p=0.016) levels for the first time in this study were found to be higher in patients with MODY3 than in patients with other MODY subtypes (p<0.05)., Conclusion: MODY patients had lower serum levels of the proinflammatory cytokines IL-1β, IL-6, TNF-α, IL-31, and sCD40L compared to healthy controls. High IL-17A and IL-23 levels along with low hs-CRP levels may be potential markers to distinguish MODY3 from other MODY subtypes., (Copyright © 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Maturity-onset diabetes of the young (MODY) is a highly heterogeneous group of monogenic and nonautoimmune diseases. Misdiagnosis of MODY is a widespread problem and about 5% of patients with type 2 diabetes mellitus and nearly 10% with type 1 diabetes mellitus may actually have MODY. Using next-generation DNA sequencing (NGS) to facilitate accurate diagnosis of MODY, this study investigated mutations in 13 MODY genes ( HNF4A , GCK , HNF1A , PDX1 , HNF1B , NEUROD1 , KLF11 , CEL , PAX4 , INS , BLK , ABCC8 , and KCNJ11 ). In addition, we comprehensively investigated the clinical phenotypic effects of the genetic variations identified. Fifty-one adult patients with suspected MODY and 64 healthy controls participated in the study. We identified 7 novel and 10 known missense mutations localized in PDX1 , HNF1B , KLF11 , CEL , BLK , and ABCC8 genes in 29.4% of the patient sample. Importantly, we report several mutations that were classified as "deleterious" as well as those predicted as "benign." Notably, the ABCC8 p.R1103Q, ABCC8 p.V421I, CEL I336T, CEL p.N493H, BLK p.L503P, HNF1B p.S362P, and PDX1 p.E69A mutations were identified for the first time as causative variants for MODY. More aggressive clinical features were observed in three patients with double- and triple-heterozygosity of PDX1 - KLF11 (p.E69A/p.S182R), CEL - ABCC8 - KCNJ11 (p.I336, p.G157R/p.R1103Q/p.A157A), and HNF1B - KLF11 (p.S362P/p.P261L). Interestingly, the clinical effects of the BLK mutations appear to be exacerbated in the presence of obesity. In conclusion, NGS analyses of the adult patients with suspected MODY appear to be informative in a clinical context. These findings warrant further clinical diagnostic research and development in different world populations suffering from diabetes with genetic underpinnings.

Background: It is well documented that patients with chronic metabolic diseases, such as diabetes and obesity, are adversely affected by the COVID-19 pandemic. However, when the subject is rare metabolic diseases, there are not enough data in the literature., Aim: To investigate the course of COVID-19 among patients with Gaucher disease (GD), the most common lysosomal storage disease., Methods: Based on the National Health System data, a retrospective cohort of patients with confirmed (polymerase chain reactionpositive) COVID-19 infection (n = 149 618) was investigated. The adverse outcomes between patients with GD (n = 39) and those without GD (n = 149 579) were compared with crude and propensity score-matched (PSM) groups. The outcomes were hospitalisation, the composite of intensive care unit (ICU) admission and/or mechanical ventilation and mortality., Results: The patients with GD were significantly older and had a higher frequency of hypertension (HT), Type 2 diabetes mellitus (T2DM), dyslipidaemia, asthma or chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, heart failure and cancer. Although hospitalisation rates in Gaucher patients were found to be higher in crude analyses, the PSM models (model 1, age and gender matched; model 2, matched for age, gender, HT, T2DM and cancer) revealed no difference for the outcomes between patients with GD and the general population. According to multivariate regression analyses, having a diagnosis of GD was not a significant predictor for hospitalisation (P = 0.241), ICU admission/mechanical ventilation (P = 0.403) or mortality (P = 0.231)., Conclusion: According to our national data, SARS-CoV-2 infection in patients with GD does not have a more severe course than the normal population., (© 2021 Royal Australasian College of Physicians.)

Purpose: While obesity is related to more severe outcomes of coronavirus disease 2019 (COVID-19), factors leading to poor prognosis still remain unclear. The present study evaluated the outcomes of COVID-19 patients who were overweight or obese and variables associated with severe disease in a large group of consecutive cases., Methods: A nationwide retrospective cohort study was performed using the Turkish National Healthcare Database. Demographic characteristics, laboratory tests, comorbidities, and medications of patients registered between March 11 and May 30, 2020, were recorded., Results: A total of 14, 625 patients (median age:42, IQR:26 years; female 57.4%) with normal weight (34.7%), overweight (35.6%), and obesity (29.7%) were included. Hospitalization, ICU admission, intubation/mechanical ventilation, pulmonary involvement, and mortality were significantly higher in patients who were overweight or obese. In adjusted analyses, both overweight (OR, 95% CI: 1.82, 1.04-3.21; p=0.037) and obesity (OR, 95% CI: 2.69, 1.02-1.05; p<0.001) were associated with a higher intubation/mechanical ventilation rate but only obesity was associated with increased mortality (OR, 95% CI: 2.56, 1.40-4.67; p=0.002). Old age, male gender, chronic kidney disease, and high C reactive protein levels were independently associated with COVID-19 mortality in overweight or obese patients., Conclusions: COVID-19 patients who were overweight or obese were more likely to have adverse outcomes but only obesity was a predictor of mortality. Such patients should receive urgent medical attention and active management, especially the elderly, men, and people with chronic kidney disease., Competing Interests: The authors have no potential conflicts of interest to disclose., (Thieme. All rights reserved.)

This study was performed to evaluate whether the use of drugs in the treatment of osteoporosis in women is associated with COVID-19 outcomes. The results showed that the risk of hospitalization, intensive care unit admission, and mortality was not altered in individuals taking anti-osteoporosis drugs, suggesting no safety issues during a COVID-19 infection., Introduction: Whether patients with COVID-19 receiving anti-osteoporosis drugs have lower risk of worse outcomes has not been reported yet. The aim of this study was to evaluate the association of anti-osteoporosis drug use with COVID-19 outcomes in women., Methods: Data obtained from a nationwide, multicenter, retrospective cohort of patients diagnosed with COVID-19 from March 11th to May 30th, 2020 was retrieved from the Turkish Ministry of Health Database. Women 50 years or older with confirmed COVID-19 who were receiving anti-osteoporosis drugs were compared with a 1:1 propensity score-matched COVID-19 positive women who were not receiving these drugs. The primary outcomes were hospitalization, ICU (intensive care unit) admission, and mortality., Results: A total of 1997 women on anti-osteoporosis drugs and 1997 control patients were analyzed. In the treatment group, 1787 (89.5%) women were receiving bisphosphonates, 197 (9.9%) denosumab, and 17 (0.9%) teriparatide for the last 12 months. Hospitalization and mortality rates were similar between the treatment and control groups. ICU admission rate was lower in the treatment group (23.0% vs 27.0%, p = 0.013). However, multivariate analysis showed that anti-osteoporosis drug use was not an independent associate of any outcome. Hospitalization, ICU admission, and mortality rates were similar among bisphosphonate, denosumab, or teriparatide users., Conclusion: Results of this nationwide study showed that preexisting use of anti-osteoporosis drugs in women did not alter the COVID-19-related risk of hospitalization, ICU admission, and mortality. These results do not suggest discontinuation of these drugs during a COVID-19 infection., (© 2021. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Introduction: COVID-19 disease has a worse prognosis in patients with diabetes, but comparative data about the course of COVID-19 in patients with type 1 (T1DM) and type 2 diabetes (T2DM) are lacking. The purpose of this study was to find out the relative clinical severity and mortality of COVID-19 patients with T1DM and T2DM., Material and Methods: A nationwide retrospective cohort of patients with confirmed (PCR positive) COVID-19 infection (n = 149,671) was investigated. After exclusion of individuals with unspecified diabetes status, the adverse outcomes between patients with T1DM (n = 163), T2DM (n = 33,478) and those without diabetes (n = 115,108) were compared by using the propensity score matching method. The outcomes were hospitalization, the composite of intensive care unit (ICU) admission and/or mechanical ventilation, and mortality., Results: The patients with T1DM had higher mortality than the age- and gender-matched patients with T2DM (n = 489) and those without diabetes (n = 489) (p < 0.001). After further adjustment for the HbA1c, and microvascular and macrovascular complications, the odds of mortality (OR: 3.35, 95% CI: 1.41-7.96, p = 0.006) and ICU admission and/or mechanical ventilation (OR: 2.95, 95% CI: 1.28-6.77, p = 0.011) were significantly higher in patients with T1DM compared to those with T2DM. Older age (OR: 1.06, 95% CI: 1.01-1.12, p = 0.028) and lymphopaenia (OR: 5.13, 95% CI: 1.04-25.5, p = 0.045) were independently associated with mortality in patients with T1DM., Conclusions: Patients with T1DM had worse prognosis of COVID-19 compared to T2DM patients or those without diabetes. These cases should be cared for diligently until more data become available about the causes of increased COVID-19 mortality in T1DM.

Background: Vaccination against influenza and pneumococcus is effective in reducing morbidity and mortality in patients with diabetes., Aim: To investigate the prevalence of influenza and pneumococcal vaccinations and to search for the independent associates of vaccination in Turkish patients with diabetes., Methods: In this cross-sectional, nationwide, multicenter study, adult patients with type 1 diabetes (T1DM) ( n = 454) and type 2 diabetes (T2DM) ( n = 4721), who were under follow-up for at least a year in the outpatient clinics, were consecutively enrolled. Sociodemographic, clinical, and laboratory parameters of patients were recorded. Vaccination histories were documented according to the self-statements of the patients., Results: Patients with T1DM and T2DM had similar vaccination rates for influenza (23.6% vs 21.2%; P = 0.240) and pneumococcus (8% vs 7%; P = 0.451) vaccinations. Longer diabetes duration and older age were the common independent associates of having vaccination for both types of diabetes patients. Higher education level, using statin treatment, and having optimal hemoglobin A1c levels were the common independent associates of influenza and pneumococcal vaccination in patients with T2DM., Conclusion: TEMD Vaccination Study shows that patients with T1DM and T2DM had very low influenza and pneumococcal vaccination rates in Turkey. The lower rates of vaccination in certain populations urges the necessity of nationwide vaccination strategies targeting these populations., Competing Interests: Conflict-of-interest statement: There is no conflict of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: To investigate the effect of preexisting treatment with dipeptidyl peptidase-4 inhibitors (DPP-4is) on COVID-19-related hospitalization and mortality in patients with type 2 diabetes mellitus (T2DM)., Methods: A multicenter, retrospective cohort study was conducted using patient data extracted from the Turkish National Electronic Database. All patients who tested positive for COVID-19 (PCR test) between 11 March through to 30 May 2020 were screened for eligibility (n = 149,671). Following exclusion of patients based on pre-determined inclusion criteria, patients with T2DM using a DPP-4i or glucose-lowering medications other than a DPP-4i were compared for mortality and hospitalization. The propensity score method was used to match age, gender, micro- and macrovascular complications, and medications in the two groups. Independent associates of mortality were analyzed using multivariable analysis on the whole T2DM population., Results: A total of 33,478 patients with T2DM who tested postive for COVID-19 who met the inclusion criteria were included in the analysis. Median (interquartile range) age was 54 (22) years and 42.4% were male. Of these, 9100 patients using DPP-4is (n = 4550) or other glucose-lowering drugs (n = 4550) were matched in two groups. After matching, analysis revealed a lower mortality in the DPP-4i group (9.5 vs. 11.8%; p < 0.001). In the multivariable model, the use of DPP-4is (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.35-0.91; p = 0.02) was associated with lower mortality in the whole sample, while age, male gender, computed tomography finding of COVID-19, obesity, low glomerular filtration rate, and an insulin-based regimen also predicted increased risk of death. There was no association between the preexisting treatment with DPP-4is and COVID-19-related hospitalization in the matched analysis or multivariate model. The rate of admission to the intensive care unit and/or mechanical ventilation favored the DPP-4i group (21.7 vs. 25.2%; p = 0.001), although this association became saturated in the multivariate analysis (OR 0.65, 95% CI 0.39-1.08; p = 0.099)., Conclusions: The results of this study demonstrate an association between DDP-4i use and reduced mortality in people with T2DM who tested PCR positive for COVID-19., (© 2021. The Author(s).)

Background: There are scarce published data in differentiated thyroid cancer patients about new coronavirus disease 2019 (COVID-19) disease outcomes and mortality. Here, we evaluated COVID-19 infection outcomes and mortality in thyroid cancer patients with COVID-19 infection., Design and Methods: We included a cohort of patients with thyroid cancer with PCR-confirmed COVID-19 disease from 11 March to 30 May 2020 from the Turkish Ministry of Health database in our nationwide, retrospective study. We compared the mortality and morbidity of COVID patients with or without thyroid cancer. Univariate and multivariate analyses were used to assess the independent factors for mortality, length of hospital stay and intensive care unit (ICU) admission and mechanical ventilation. We also analysed the effect of radioiodine treatment on severity and death rate of COVID-19 disease., Results: We evaluated 388 COVID-19 patients with thyroid cancer [median age: 54 years, interquartile range (IQR) 18 years, males: 23%] and age and gender-matched 388 COVID-19 patients without thyroid cancer. Patients with thyroid cancer had a similar mortality ratio compared with the non-cancer group. Among patients with thyroid cancer, age, presence of diabetes mellitus, asthma/COPD, heart failure, chronic kidney disease, prior coronary artery disease, RAS blocker usage and low lymphocyte count were associated with mortality. Radioactive iodine (RAI) treatment and cumulative radioactive iodine dosage did not negatively affect the severity and mortality of COVID-19 disease in our patient group., Conclusions: Our study indicated that history of thyroid cancer did not have an increased risk of mortality or morbidity in COVID-19 disease. Besides, RAI therapy history and doses of radioactive iodine did not affect mortality or outcome., (© 2021 John Wiley & Sons Ltd.)

Purpose: New coronavirus disease 2019 (COVID-19) has a worse prognosis in patients with diabetes. However, there are insufficient data about the effect of hyperglycemia on COVID-19 prognosis in non-diabetic patients. This study aimed to investigate the relationship between random blood glucose levels measured at the time of diagnosis and prognosis of COVID-19 disease in non-diabetic patients., Methods: A nationwide retrospective cohort of non-diabetic patients with confirmed COVID-19 infection from 11 March to 30 May 2020 in the Turkish Ministry of Health database was investigated. The patients were stratified into three groups according to blood glucose levels which were <100 mg/dL in group-1, in the range of 100-139 mg/dl in group-2, and the range of 140-199 mg/dl in group-3. Clinical characteristics and outcomes were compared among the groups. The primary outcome was mortality., Results: A total of 12,817 non-diabetic patients (median age [IQR]: 44 [25] years, females: 50.9%) were included. Patients in group-2 (5%) and group-3 (14%) had higher mortality rates than patients in group-1 (2.1%). The rates of hospitalization, hospital stays longer than 8 days, intensive care unit (ICU) admission, ICU stay more than 6 days, and mechanical ventilation were also significantly higher in group-3 patients. Likewise, glucose levels in the range of 140-199 mg/dL were an independent associate of mortality and composite of ICU admission and/or mechanical ventilation., Conclusion: Hyperglycemia at the time of COVID-19 diagnosis is associated with poor prognosis in non-diabetic patients. Clinicians should be more careful in the treatment of non-diabetic COVID-19 patients with hyperglycemia.

Diabetes is a common disorder with a heterogeneous clinical presentation and an enormous burden on health care worldwide. About 1-6% of patients with diabetes suffer from maturity-onset diabetes of the young (MODY), the most common form of monogenic diabetes with autosomal dominant inheritance. MODY is genetically and clinically heterogeneous and caused by genetic variations in pancreatic β-cell development and insulin secretion. We report here new findings from targeted next-generation sequencing (NGS) of 13 MODY-related genes. A sample of 22 unrelated pediatric patients with MODY and 13 unrelated healthy controls were recruited from a Turkish population. Targeted NGS was performed with Miseq 4000 (Illumina) to identify genetic variations in 13 MODY-related genes: HNF4A , GCK , HNF1A , PDX1 , HNF1B , NEUROD1 , KLF11 , CEL , PAX4 , INS , BLK , ABCC8 , and KCNJ11 . The NGS data were analyzed adhering to the Genome Analysis ToolKit (GATK) best practices pipeline, and variant filtering and annotation were performed. In the patient sample, we identified 43 MODY-specific genetic variations that were not present in the control group, including 11 missense mutations and 4 synonymous mutations. Importantly, and to the best of our knowledge, the missense mutations NEUROD1 p.D202E, KFL11 p.R461Q, BLK p.G248R, and KCNJ11 p.S385F were first associated with MODY in the present study. These findings contribute to the worldwide knowledge base on MODY and molecular correlates of clinical heterogeneity in monogenic childhood diabetes. Further comparative population genetics and functional genomics studies are called for, with an eye to discovery of novel diagnostics and personalized medicine in MODY. Because MODY is often misdiagnosed as type 1 or type 2 diabetes mellitus, advances in MODY diagnostics with NGS stand to benefit diabetes overall clinical care as well.

Background: Coronavirus disease 2019 (COVID-19) has been reported to be associated with a more severe course in patients with type 2 diabetes mellitus (T2DM). However, severe adverse outcomes are not recorded in all patients. In this study, we assessed disease outcomes in patients with and without T2DM hospitalized for COVID-19., Methods: A nationwide retrospective cohort of patients with T2DM hospitalized with confirmed COVID-19 infection from 11 March to 30 May 2020 in the Turkish Ministry of Health database was investigated. Multivariate modeling was used to assess the independent predictors of demographic and clinical characteristics with mortality, length of hospital stay, and intensive care unit (ICU) admission and/or mechanical ventilation., Results: A total of 18 426 inpatients (median age [interquartile range, IQR]: 61 [17] years; males: 43.3%) were investigated. Patients with T2DM (n = 9213) were compared with a group without diabetes (n = 9213) that were matched using the propensity scores for age and gender. Compared with the group without T2DM, 30-day mortality following hospitalization was higher in patients with T2DM (13.6% vs 8.7%; hazard ratio 1.75; 95% CI, 1.58-1.93; P < .001). The independent associates of mortality were older age, male gender, obesity, insulin treatment, low lymphocyte count, and pulmonary involvement on admission. Older age, low lymphocyte values, and pulmonary involvement at baseline were independently associated with longer hospital stay and/or ICU admission., Conclusions: The current study from the Turkish national health care database showed that patients with T2DM hospitalized for COVID-19 are at increased risk of mortality, longer hospital stay, and ICU admission., (© 2021 Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Aims: Type 2 diabetes mellitus (T2DM) is a risk factor for severe COVID-19. Our aim was to compare the clinical outcomes of patients with and without T2DM during the first hit of COVID-19 in Istanbul., Methods: A retrospective population-based study was conducted including all consecutive adult symptomatic COVID-19 cases. Patients were confirmed with rt-PCR; treated and monitored in accordance with standard protocols. The primary endpoints were hospitalization and 30-day mortality., Results: Of the 93,571 patients, 22.6% had T2DM, with older age and higher BMI. Propensity Score matched evaluation resulted in significantly higher rates of hospitalization (1.5-fold), 30-day mortality (1.6-fold), and pneumonia (1.4-fold). They revealed more severe laboratory deviations, comorbidities, and frequent drug usage than the Non-DM group. In T2DM age, pneumonia, hypertension, obesity, and insulin-based therapies were associated with an increased likelihood of hospitalization; whereas age, male gender, lymphopenia, obesity, and insulin treatment were considerably associated with higher odds of death., Conclusions: COVID-19 patients with T2DM had worse clinical outcomes with higher hospitalization and 30-day mortality rates than those without diabetes. Compared to most territories of the world, COVID-19 mortality was much lower in Istanbul, which may be associated with accessible healthcare provision and the younger structure of the population., (Copyright © 2021 Elsevier B.V. All rights reserved.)

This study was designed to determine the protective effect of kefir on the oxidative damage, as well as histological and biochemical changes that occur in the kidney tissues of experimental diabetic rats. Forty rats were allocated into four groups as "healthy saline" (SF), "healthy kefir" (KF), and the same groups with experimentally induced diabetes (DSF and DKF). Diabetes was induced by administering 65 mg/kg single-dose streptozotocin. Oral kefir was given 10 ml/kg/day for 35 days to the rats in the groups KF and DKF. The same amount of saline was given to the groups SF and DSF. On the 36th day of the study, blood glucose, urea, and creatinine were measured besides glucose, creatinine, microalbuminuria, and sodium in the urine. Additionally, histological examination was performed on the kidney tissues. Blood glucose, creatinine, and urea levels were significantly lower in the DKF group compared with those of the DSF group (p < 0.001). Also, the creatinine level was significantly decreased (p < 0.001), and microalbuminuria was increased (p < 0.001) in the DKF group compared with that of the DSF group. Histologically, intermittent expansion in the renal glomeruli, reduction of cast formation in the tubules, and improvement in the renal epithelial tissues of the DKF group were observed. Kefir decreased the damage caused by diabetes. These results indicate that kefir supplementation may contribute to better control of oxidative stress, which is related to the improvement of renal functions, suggesting its use to slow down the progression of diabetic nephropathy.

Background: The present survey aimed to find out the demographical and clinical characteristics of patients with hypertension in a population with type 2 diabetes mellitus (T2DM) in Turkey., Methods: Patients with T2DM who were followed-up in tertiary endocrine units for at least last one year were recruited. Demographic, clinical and biochemical data of the patients were collected. Hypertension was defined as taking anti-hypertensive medications or having office arterial blood pressure (ABP) ≥140/90 mmHg or home ABP ≥ 130/80 mmHg., Results: A total of 4756 (58.9% women) diabetic patients were evaluated. The percentage of patients with hypertension was 67.5% (n = 3212). Although 87.4% (n = 2808) of hypertensive patients were under treatment, blood pressure was on target in 52.7% (n = 1479) of patients. Hypertension proportions were higher in woman (p = 0.001), older, more obese, and those who had longer diabetes duration, lower education levels, higher frequency of hypoglycemic events (all p < 0.001) and higher triglyceride levels (p = 0.003). LDL cholesterol level and the percentage of smokers were lower in hypertensive group than in non-hypertensive group (both p < 0.001). The percentage of macro and microvascular complications was higher in the hypertensive group than in the normotensive one (both p < 0.001). In multivariate logistic regression analysis, being a woman (OR: 1.26, 95% CI: 1.04-1.51, p = 0.016), smoking (OR: 1.38, 95% CI: 1.05-1.80, p = 0.020), regular physical activity (OR: 1.24, 95% CI: 1.01-1.53, p = 0.039) and the presence of macrovascular complications (OR: 1.38 95% CI: 1.15-1.65, p = 0.001) were the significant predictors of good ABP regulation. The ratios of masked and white coat hypertension were 41.2% and 5.7%, respectively., Conclusion: Our findings indicate that two-thirds (67.5%) of adult patients with T2DM have hypertension. Co-existence of hypertension increases the frequency of macro and microvascular diabetic complications in these patients. Despite the critical role of hypertension in morbidity and mortality, only half of the patients have favorable ABP levels. Masked hypertension seems to be another important issue in this population., (Copyright © 2020 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Purpose: Following Roux-en-Y gastric bypass (RYGB), positive alterations are observed in gut microbiota and intestinal peptides. Previous studies demonstrated similar alterations observed in cases when pre-probiotics are used without surgery. The aim of this trial was to evaluate the effectiveness of early use of pre-probiotics after RYGB., Material and Methods: The operation and follow-up of the patients were performed at Istanbul University Medical Faculty. Thirty-two patients who had undergone RYGB were randomized to pre-probiotic group (PreProBG, n = 16; 200 g/day yogurt plus 10 g/day inulin+oligofructose) and probiotic group (ProBG, n = 16; 200 g/day yogurt only) for 6 months. Blood samples (glucose, insulin, A1c, GLP-1, PYY), anthropometric measurements, and appetite ratings have been evaluated at baseline and 3 (m3) and 6 (m6) months after RYGB., Results: Initial anthropometric measurements and appetite ratings decreased significantly after surgery and there were no significant differences between the groups. The decrease of area under the curve(insulin) was less and has a positive correlation with the changes in anthropometric measurements in PreProBG. GLP-1 and PYY which increased dramatically after surgery in all patients were higher in PreProBG. But this increase had a negative correlation with the changes in anthropometric measurements during the study., Conclusion: Increased insulin, GLP-1, and PYY secretion was more enhanced by pre-probiotic use in early postoperative period. But this increase not only in anthropometric measurements but also in appetite ratings affects negatively, contrary to expectations. In summary, it should be investigated with new studies that use of pre-probiotics in the late postoperative period may be more effective in patients with weak insulin and incretin response and therefore insufficient weight loss. Trial Registration clinicaltrials.gov Identifier: NCT03517345.

Background: The nuclear receptors Rev-erb alpha and Rev-erb beta are transcription factors that regulate the function of genes in glucose and lipid metabolism, and they also form a link between circadian rhythm and metabolism. We evaluated the variations in Rev-erb alpha and Rev-erb beta genes together with biochemical parameters as risk factors in type 2 diabetic (T2DM) patients., Methods: Molecular analyses of Rev-erb alpha and Rev-erb beta genes were performed on genomic DNA by using next-generation sequencing in 42 T2DM patients (21 obese and 21 non-obese) and 66 healthy controls., Results: We found 26 rare mutations in the study groups, including 13 missense mutations, 9 silent mutations, 3 5'UTR variations, and a 3'UTR variation, of which 9 were novel variations (5 missense and 3 silent and 1 5'UTR). Six common variations were also found in the Rev-erb genes; Rev-erb beta Chr3:24003765 A > G, Rev-erb beta rs924403442 (Chr3:24006717) G > T, Rev-erb alpha Chr17:38253751 T > C, Rev-erb alpha rs72836608 C > A, Rev-erb alpha rs2314339 C > T and Rev-erb alpha rs2102928 C > T. Of these, Rev-erb beta Chr3:24003765 A > G was a novel missense mutation (p.Q197R), while others were identified as intronic variants. T2DM patients with Rev-erb beta rs924403442 T allele had lower body surface area (BSA) than noncarriers (GG genotype) (p = 0.039). Rev-erb alpha rs72836608 A allele and Rev-erb alpha rs2314339 CC genotype were associated with decreased serum HDL-cholesterol levels in T2DM patients (p = 0.025 and p = 0.027, respectively). In our study, different effects of Rev-erbs polymorphisms were found according to gender and presence of obesity. Rev-erb alpha rs72836608 (C > A) and rs2314339 (C > T) and Rev-erb alpha rs2102928 (C > T) were associated with low HDL-C levels in male T2DM patients. In female patients, Rev-erb alpha rs2102928 (C > T) was associated with high microalbuminuria and Rev-erb beta rs9244403442 G > T was associated with low HDL and high BSA values. In addition, Rev-erb alpha Chr17: 38,253,751 (T > C), rs72836608 (C > A), and rs2314339 (C > T) and Rev-erb beta Chr3:24003765 (A > G) were associated with increased serum GGT levels in obese T2DM patients. In non-obese patients, Rev-erbs SNPs had no effect on serum GGT levels., Conclusion: Our findings indicate that variations in the Rev-erb alpha and Rev-erb beta genes can affect metabolic changes in T2DM and these effects may vary depending on gender and obesity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Attaining acceptable levels of LDL Cholesterol (LDL-C) significantly improves cardiovascular (CV) outcomes in patients with type 2 diabetes mellitus (T2DM). The LDL-C target attainment and the characteristics of patients attaining these targets were investigated in this study. Furthermore, the reasons for not choosing statins and the physicians' attitudes on the treatment of diabetic dyslipidemia were also examined., Methods: A nationwide, cross-sectional survey was conducted in tertiary centers for diabetes management. Adult patients with T2DM, who were under follow-up for at least a year in outpatient clinics, were consecutively enrolled for the study. LDL-C goals were defined as below 70 mg/dL for patients with macrovascular complications or diabetic nephropathy, and below 100 mg/dL for other patients. Data about lipid-lowering medications were self-reported., Results: A total of 4504 patients (female: 58.6%) were enrolled for the study. The mean HbA1c and diabetes duration was 7.73 ± 1.74% and 10.9 ± 7.5 years, respectively. The need for statin treatment was 94.9% (n = 4262); however, only 42.4% (n = 1807) of these patients were under treatment, and only 24.8% (n = 448) of these patients achieved LDL-C targets. The main reason for statin discontinuation was negative media coverage (87.5%), while only a minority of patients (12.5%) mentioned side effects. Physicians initiated lipid-lowering therapy in only 20.3% of patients with high LDL-C levels. It was observed that the female gender was a significant independent predictor of not attaining LDL-C goals (OR: 0.70, 95% CI: 0.59-0.83)., Conclusions: Less than 50 % of patients with T2DM who need statins were under treatment, and only a quarter of them attained their LDL-C targets. There exists a significant gap between the guideline recommendations and the real-world evidence in the treatment of dyslipidemia in T2DM.

Purpose: To improve prescribing in older adults, criterion sets have been introduced from different countries. While current criterion sets are useful to some extent, they do not meet the need in some European countries. Turkish inappropriate medication use in the elderly (TIME) criteria was planned to meet this need., Methods: In phase 1, the user friendly sets: STOPP/START version2 and CRIME criteria were combined. National experts composed of geriatricians and non-geriatricians were invited to review and comment. In phase 2, thorough literature review was performed and reference-based revisions, omissions, and additions were made. Explanatory additions were added to some criteria to improve application in practice. In phase 3, all working group members reviewed the criteria/explanations and agreed on the final content., Results: Phase 1 was performed by 49 expert academicians between May and October 2016. Phase 2 was performed by 23 working group academicians between October 2016 and November 2018 and included face-to-face interviews between at least two geriatrician members and one criterion-related specialist. Phase 3 was completed between November 2018-March 2019 with review and approval of all criteria by working group academicians. As a result, 55 criteria were added, 17 criteria were removed, and 60 criteria were modified from the first draft. A total of 153 TIME criteria composed of 112 TIME-to-STOP and 41 TIME-to-START criteria were introduced., Conclusion: TIME criteria is an update screening tool that differs from the current useful tools by the interactive study of experts from geriatrics and non-geriatrics, inclusion of practical explanations for some criteria and by its eastern European origin. TIME study respectfully acknowledges its roots from STOPP/START and CRIME criteria. Studies are needed whether it would lead improvements in older adults' health.

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.)

Aims: Turkey has the highest prevalence of diabetes in Europe. It is therefore essential to know the overall cardiovascular risk and reveal the predictors of metabolic control in Turkish adults with diabetes mellitus., Methods: A nationwide, multicenter survey consecutively enrolled patients who were under follow up for at least a year. Optimal control was defined as HbA1c < 7%, home arterial blood pressure (ABP) < 135/85 mmHg, or LDL-C < 100 mg/dL. Achieving all parameters indicated triple metabolic control., Results: HbA1c levels of patients (n = 5211) were 8.6 ± 1.9% (71 ± 22 mmol/mol) and 7.7 ± 1.7% (61 ± 19 mmol/mol), in Type 1 and Type 2 diabetes, respectively. Glycemic control was achieved in 15.3% and 40.2%, and triple metabolic control was achieved in 5.5% and 10.1%, respectively. Only 1.5% of patients met all the criteria of being non-obese, non-smoker, exercising, and under triple metabolic control. Low education level was a significant predictor of poor glycemic control in both groups., Conclusions: Few patients with Type 2, and even fewer with Type 1 diabetes have optimal metabolic control in Turkey. TEMD study will provide evidence-based information to policy makers to focus more on the quality and sustainability of diabetes care in order to reduce the national burden of the disease., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.)