Using Cluster Analysis to Identify Metabolic Syndrome Components and Physical Fitness in Patients with Metabolic Syndrome.

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.

International Diabetes Federation Position Statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes.

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 (HbA1c) 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 HbA1c 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.

TASL Practice Guidance on the Clinical Assessment and Management of Patients with Nonalcoholic Fatty Liver Disease.

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.

Electrochemical skin conductances values and clinical factors affecting sudomotor dysfunction in patients with prediabetes, type 1 diabetes, and type 2 diabetes: A single center experience.

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.

Clinical characteristics of adult and paediatric patients with familial hypercholesterolemia: A real-life cross-sectional study from the Turkish National Database.

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.

Lactobacillus GG is associated with mucin genes expressions in type 2 diabetes mellitus: a randomized, placebo-controlled trial.

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 × 109 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.

Reduction in the Risk of Peripheral Neuropathy and Lower Decrease in Kidney Function with Metformin, Linagliptin or Their Fixed-Dose Combination Compared to Placebo in Prediabetes: A Randomized Controlled Trial.

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.

Estimates and Forecasts on the Burden of Prediabetes and Diabetes in Adult and Elderly Population in Turkiye.

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.

Telemedicine as a Motivational Tool to Optimize Metabolic Control in Patients with Diabetes in Turkey: A Prospective, Randomized, Controlled TeleDiab Trial.

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.

The Clinical Characteristics and Outcomes of COVID-19 Patients with Pre-Existing Thyroid Dysfunction: A Nationwide Study.

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.

Cytokine Profile in Patients With Maturity-onset Diabetes of the Young (MODY).

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-1ß (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-1ß (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-1ß, 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.

Precision Diagnosis of Maturity-Onset Diabetes of the Young with Next-Generation Sequencing: Findings from the MODY-IST Study in Adult Patients.

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.

Higher rate of COVID-19 mortality in patients with type 1 than type 2 diabetes: a nationwide study.

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.

Clinical Characteristics and Outcomes of COVID-19 Patients with Overweight and Obesity: Turkish Nationwide Cohort Study (TurCObesity).

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.

No association of Gaucher disease with COVID-19-related outcomes: a nationwide cohort study.

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.

Obstacles and expectations of rare disease patients and their families in Türkiye: ISTisNA project survey results.

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.

Lower COVID-19 Mortality in Patients with Type 2 Diabetes Mellitus Taking Dipeptidyl Peptidase-4 Inhibitors: Results from a Turkish Nationwide Study.

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.

Monogenic Childhood Diabetes: Dissecting Clinical Heterogeneity by Next-Generation Sequencing in Maturity-Onset Diabetes of the Young.

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 ß-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.