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Objectives: To propose the grounds for "diabetic sarcopenia" as a new comorbidity of diabetes, and to establish a muscle screening algorithm proposal to facilitate its diagnosis and staging in clinical practice., Method: A qualitative expert opinion study was carried out using the nominal technique. A literature search was performed with the terms "screening" or "diagnostic criteria" and "muscle loss" or "sarcopenia" and "diabetes" that was sent to a multidisciplinary group of 7 experts who, in a face-to-face meeting, discussed various aspects of the screening algorithm., Results: The hallmark of diabetic sarcopenia (DS) is muscle mass atrophy characteristic of people with diabetes mellitus (DM) in contrast to the histological and physiological normality of muscle mass. The target population to be screened was defined as patients with DM with a SARC-F questionnaire > 4, glycosylated haemoglobin (HbA1C) ≥ 8.0%, more than 5 years since onset of DM, taking sulfonylureas, glinides and sodium/glucose cotransporter inhibitors (SGLT2), as well as presence of chronic complications of diabetes or clinical suspicion of sarcopenia. Diagnosis was based on the presence of criteria of low muscle strength (probable sarcopenia) and low muscle mass (confirmed sarcopenia) using methods available in any clinical consultation room, such as dynamometry, the chair stand test, and Body Mass Index (BMI)-adjusted calf circumference. DS was classified into 4 stages: Stage I corresponds to sarcopenic patients with no other diabetes complication, and Stage II corresponds to patients with some type of involvement. Within Stage II are three sublevels (a, b and c). Stage IIa refers to individuals with sarcopenic diabetes and some diabetes-specific impairment, IIb to sarcopenia with functional impairment, and IIc to sarcopenia with diabetes complications and changes in function measured using standard tests Conclusion: Diabetic sarcopenia has a significant impact on function and quality of life in people with type 2 diabetes mellitus (T2DM), and it is important to give it the same attention as all other traditionally described complications of T2DM. This document aims to establish the foundation for protocolising the screening and diagnosis of diabetic sarcopenia in a manner that is simple and accessible for all levels of healthcare., (© 2024. The Author(s).)

Context: The presence of metabolic dysfunction-associated steatotic liver disease (MASLD) in patients with diabetes mellitus (DM) is associated with a high risk of cardiovascular disease, but is often underdiagnosed., Objective: To develop machine learning (ML) models for risk assessment of MASLD occurrence in patients with DM., Methods: Feature selection determined the discriminative parameters, utilized to classify DM patients as those with and without MASLD. The performance of the multiple logistic regression model was quantified by sensitivity, specificity, and percentage of correctly classified patients, and receiver operating characteristic (ROC) curve analysis. Decision curve analysis (DCA) assessed the model's net benefit for alternative treatments., Results: We studied 2000 patients with DM (mean age 58.85 ± 17.37 years; 48% women). Eight parameters: age, body mass index, type of DM, alanine aminotransferase, aspartate aminotransferase, platelet count, hyperuricaemia, and treatment with metformin were identified as discriminative. The experiments for 1735 patients show that 744/991 (75.08%) and 586/744 (78.76%) patients with/without MASLD were correctly identified (sensitivity/specificity: 0.75/0.79). The area under ROC (AUC) was 0.84 (95% CI, 0.82-0.86), while DCA showed a higher clinical utility of the model, ranging from 30% to 84% threshold probability. Results for 265 test patients confirm the model's generalizability (sensitivity/specificity: 0.80/0.74; AUC: 0.81 [95% CI, 0.76-0.87]), whereas unsupervised clustering identified high-risk patients., Conclusion: A ML approach demonstrated high performance in identifying MASLD in patients with DM. This approach may facilitate better risk stratification and cardiovascular risk prevention strategies for high-risk patients with DM at risk of MASLD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Skin disorders are common in diabetes, affecting both patients with type 1 and type 2 diabetes. These cutaneous manifestations can be classified into three categories: dermatoses associated with the presence of diabetes, cutaneous complications of diabetes (acute and chronic) and dermatoses linked to antidiabetic treatments. These conditions vary considerably in terms of severity (from insignificant cosmetic problems to life-threatening) and prevalence (from relatively frequent to rare). Despite the high prevalence of diabetes and associated skin disorders, the dermatological manifestations of diabetes are generally neglected and often under-diagnosed. Failure to diagnose and treat skin disorders at an early stage can lead to clinical worsening, whereas early detection and treatment can reduce the risk of serious complications., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

1,5-Anhydroglucitol (1,5-AG) is sensitive to short-term glucose fluctuations and postprandial hyperglycemia, which has great potential in the clinical application of diabetes as a nontraditional blood glucose monitoring indicator. A large number of studies have found that 1,5-AG can be used to screen for diabetes, manage diabetes, and predict the perils of diabetes complications (diabetic nephropathy, diabetic cardiovascular disease, diabetic retinopathy, diabetic pregnancy complications, diabetic peripheral neuropathy, etc.). Additionally, 1,5-AG and β cells are also associated with each other. As a noninvasive blood glucose monitoring indicator, salivary 1,5-AG has much more benefit for clinical application; however, it cannot be ignored that its detection methods are not perfect. Thus, a considerable stack of research is still needed to establish an accurate and simple enzyme assay for the detection of salivary 1,5-AG. More clinical studies will also be required in the future to confirm the normal reference range of 1,5-AG and its role in diabetes complications to further enhance the blood glucose monitoring system for diabetes., 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 © 2024 Xu, Pan and Chen.)

Background: Novel biomarkers have been suggested for the diagnosis and prognosis of diabetes mellitus. The biomarker utility of netrin-1 in diabetes as an extracellular protein has been investigated. In this systematic review and meta-analysis, we reviewed the role of netrin-1 as a biomarker in prediabetes, diabetes, and complications of diabetes., Methods: PubMed, Embase, Scopus, and Web of Science were systematically searched for studies that measured circulatory and/or urinary netrin-1 levels in diabetes and compared them with non-diabetic patients or evaluated the prognostic role of this marker. Standardized mean difference (SMD) and 95% confidence interval (CI) were calculated using random-effect meta-analysis to compare netrin-1 levels between groups. The impact of mean age, male sex percentage, sample size, mean body mass index, and publication year on the overall heterogeneity was assessed using meta-regression., Results: Among 413 records from international databases, 19 original studies were included with 2061 cases (1137 diabetics, 196 prediabetics, and 728 healthy controls). Meta-analysis of eight studies measuring netrin-1 in patients with diabetes and comparing it with healthy controls showed no significant difference between the two groups (SMD 0.69, 95% CI -0.78 to 2.16, I 2  = 98%, p-value = 0.36). On the other hand, a meta-analysis of netrin-1 levels in patients with prediabetes in comparison with healthy controls revealed that they had lower levels (SMD -0.51, 95% CI -0.81 to -0.21, p-value < 0.01). Diabetic patients with microalbuminuria and macroalbuminuria had significantly higher circulatory netrin-1 levels compared to normoalbuminuric group SMD 1.18, 95% CI 0.83 to 1.53, p-value < 0.01 and SMD 1.67, 95% CI 0.76 to 2.58, p-value < 0.01, respectively). Moreover, no difference in urinary netrin-1 levels was found between micro-, macro-, and normoalbuminuric groups (p-value > 0.05)., Conclusion: Netrin-1 showed promising results as a biomarker in diabetes prognosis. However, more studies are required to confirm our findings, and higher sample size studies are needed to evaluate the diagnostic utility of this marker., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aims: Using machine learning algorithms and administrative data, we aimed to predict the risk of being diagnosed with several diabetes-related complications after one-, two- and three-year post-diabetes diagnosis., Methods: We used longitudinal data from administrative registers of 610,019 individuals in Catalonia with a diagnosis of diabetes and checked the presence of several complications after diabetes onset from 2013 to 2017: hypertension, renal failure, myocardial infarction, cardiovascular disease, retinopathy, congestive heart failure, cerebrovascular disease, peripheral vascular disease and stroke. Four different machine learning (ML) algorithms (logistic regression (LR), Decision tree (DT), Random Forest (RF), and Extreme Gradient Boosting (XGB)) will be used to assess their prediction performance and to evaluate the prediction accuracy of complications changes over the period considered., Results: 610,019 people with diabetes were included. After three years since diabetes diagnosis, the area under the curve values ranged from 60% (retinopathy) to 69% (congestive heart failure), whereas accuracy rates varied between 60% (retinopathy) to 75% (hypertension). RF was the most relevant technique for hypertension, myocardial and retinopathy, and LR for the rest of the comorbidities. The Shapley additive explanations values showed that age was associated with an elevated risk for all diabetes-related complications except retinopathy. Gender, other comorbidities, co-payment levels and age were the most relevant factors for comorbidity diagnosis prediction., Conclusions: Our ML models allow for the identification of individuals newly diagnosed with diabetes who are at increased risk of developing diabetes-related complications. The prediction performance varied across complications but within acceptable ranges as prediction tools., 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 © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Diabetic striatopathy (DS) is a rare and life-threatening mani- festation of diabetes. The disease commonly affects individuals of Asian descent, women and the elderly. DS is characterized by dyskinesias with basal ganglia hyperintensities on imaging. Despite being rare, prompt recognition of a hyperglycaemia- induced hemichorea-hemiballismus is essential because the symptoms are reversible with correction of hyperglycaemia. Diagnosis is based on blood analysis and neuroimaging findings. Laboratory tests reveal raised glycosylated haemoglobin (HbA1c) levels, which indicate poorly controlled diabetes. Neuroimaging provides suggestive findings of DS. It is usually associated with non-ketotic hyperglycaemia. We report a 50-year-old woman who presented with ketotic hyperglycaemia and left-sided hemichorea and partial seizures with secondary generalization.

The number of diabetic patients visiting stomatology for periodontal disease is increasing, and the symptoms are relatively severe, and often complications increase the complexity of periodontal treatment. This article briefly describes the research progress and clinical manifestations of the epidemiology and related pathological mechanisms of periodontitis with diabetes, focusing on the treatment and providing reference for stomatologists in the clinical diagnosis and treatment of patients with diabetic periodontitis.

Mucormycosis is an acute, life-threatening infection and isolated renal involvement is rare. Due to the angioinvasive nature of the disease, it is rapidly progressive and can be lethal if not managed expeditiously. In patients with underlying conditions of immunosuppression, diabetes mellitus, transplantation, COVID-19, intravenous drug and substance use and pyelonephritis, which is unable to be controlled via regular antibiotics, mucormycosis must be considered on the differential and antifungals must be empirically started. Most cases are often diagnosed on histopathology, which causes delayed treatment and resolution. We present a case of emphysematous pyelonephritis diagnosed on imaging and was later found to have mucormycosis on histopathological examination., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients with concurrent atrial fibrillation (AF) and diabetes mellitus (DM) [AF-DM] have a high risk of cardiovascular and diabetes-related complications, but are less engaged in a comprehensive treatment approach. We evaluated the association of early rhythm control (ERC), lifestyle modification (LSM), and a combination of ERC and LSM with cardiovascular or diabetes-related complication risk in patients with AF-DM (type 2)., Methods: From the National Health Information Database, 47,940 patients diagnosed with AF-DM in 2009-2016 were included. We defined ERC as rhythm control therapy within two years of AF diagnosis and LSM as adherence to ≥ 2 of the healthy behaviors among non-current smoking, non-drinking, and regular exercise. We compared the primary (ischemic stroke) and secondary (macro- and microvascular complications, glycemic emergency, and all-cause death) outcomes in four groups: non-ERC and non-LSM (group 1), LSM only (group 2), ERC only (group 3), and both ERC and LSM (group 4)., Results: Of total, 10,617 (22%), 26,730 (55.8%), 2,903 (6.1%), and 7,690 (16.0%) were classified into groups 1 to 4, in sequence. The mean duration from AF diagnosis to ERC was 25.6 ± 75.5 days. During 4.0 (interquartile range: 2.5-6.2) years' follow-up, groups 2 and 3 were associated with 23% and 33% lower risks of stroke than group 1, respectively. Group 4 was associated with the lowest risk of stroke: hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.51-0.67, p < 0.001. Regarding secondary outcomes, the lowest risks were also observed in group 4; macro- and microvascular complications, glycemic emergency, and all-cause death had HRs (95% CIs) of 0.63 (0.56-0.70), 0.88 (0.82-0.94), 0.72 (0.62-0.84), and 0.80 (0.73-0.87), respectively, all p < 0.001., Conclusions: For AF-DM patients, ERC and LSM exert a synergistic effect in preventing cardiovascular and diabetes-related complications with the greatest lowered risk of stroke. A comprehensive treatment approach should be pursued in AF-DM patients., (© 2023. The Author(s).)

Objective: To investigate the impact of metabolic status on choroidal thickness (ChT) in healthy subjects, patients with obesity, and type 2 diabetes., Design and Methods: Fasting blood glucose, insulin, insulin-like growth factor-1 (IGF-1), and ChT measured by optical coherence tomography were assessed in healthy normal-weight (n=17), obese participants (n=20), and obese participants with T2D (n=16)., Results: ChT increased in obese participants and obese participants with T2D as compared to healthy normal-weight participants (P<0.0001). A negative correlation was observed between IGF1 and ChT (r=-0.268, P=0.050) for all cohorts. Furthermore, body mass index (BMI; R 2 =0.209; P=0.002; beta=0.388) and model assessment-estimated insulin resistance (HOMA-IR; R 2 =0.074; P=0.015; beta=0.305) were independent variables of ChT, explaining 20.9 and 7.4% of its variance (both p<0.016), whereas age, sex, and IGF-1 were not significant confounders of ChT (p>0.975)., Conclusion: ChT is associated with metabolic characteristics, i. e., BMI and HOMA-IR. Due to the key role of choroidal function in retinal physiology, future studies are needed to evaluate whether metabolic traits, ChT, and potential metabolic eye complications are mechanistically linked., Competing Interests: S.M., B.W., R.C., A.K., A.J.P., M.S., N.K., A.S.S., E.P., H.J.G., and S.M.M. have nothing to disclose. One sentence summary This study investigated the impact of metabolic status on choroidal thickness in healthy subjects, patients with obesity, and those with type 2 diabetes and found that choroidal thickness is associated with metabolic characteristics, i. e. BMI and HOMA-IR., (Thieme. All rights reserved.)

Background: Cardiac autonomic neuropathy in population with diabetes mellitus (DM) is frequent and linked with high risk of cardiovascular mortality. However, studies on whether blood hemoglobin A1c (HbA1c) levels are related to adverse differences in heart rate variability (HRV) in individuals with DM are scarce., Aim: We aimed to investigate the association of blood HbA1c levels with adverse differences in HRV, which is an indicator of cardiac autonomic control, in adult individuals with and without DM., Methods: Data were collected from the Midlife in the United States (MIDUS) study, and 928 individuals were analyzed for the relationship between blood HbA1c levels and HRV through a cross-sectional analysis., Results: Participants with DM had significantly higher HRV than those without DM. The smooth curve suggested inverse relationships between blood HbA1c levels and HF- and LF-HRV seen in participants with DM but not in those without DM after controlling for all covariates (age, sex, BMI, smoking, number of drinking years and exercise). Furthermore, linear regression analysis demonstrated that elevated blood HbA1c levels did contribute to adverse differences in HF-HRV (Sβ= -0.118; 95% CI -0.208, -0.027; P=0.012) and LF-HRV (Sβ= -0.097; 95% CI -0.177, -0.017; P=0.019) after controlling for these covariates in participants with DM, while in participants without DM, blood HbA1c was not significantly related to adverse differences in HF-HRV (Sβ=0.095; 95% CI -0.059, 0.248; P=0.228) or LF-HRV (Sβ=0.043; 95% CI -0.103, 0.189; P=0.565). DM has a significant modifying effect on associations between blood HbA1c and adverse differences in HF-HRV (P for interaction=0.019) and LF-HRV (P for interaction=0.029)., Conclusions: We reported strong evidence that elevated blood levels of HbA1c were associated with adverse differences in HRV in the diabetic population but not in the nondiabetic population. This finding supported that long-term hyperglycemia is related to autonomic nerve injury in the diabetic population. Blood HbA1c might be a good indicator of cardiac autonomic neuropathy., 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 © 2022 Huang, Chen, Hu and Wan.)

Diabetes is prevalent in patients with coronary artery disease (CAD). Using the oral glucose tolerance test (OGTT), abnormal glucose regulation can be detected early in CAD patients without known diabetes. In the present study, we assessed the impact of abnormal glucose regulation on the long-term cardiovascular outcomes of patients with established CAD. Patients hospitalized for a scheduled angiography due to angina were enrolled in Taichung Veterans General Hospital. Fasting plasma glucose (FPG) and 2-hour postload glucose (2hPG) were assessed using the OGTT. Hemoglobin A1c (HbA1c) and other biochemical analyses were assessed using fasting blood samples. During a median follow-up period of 4.6 years, a composite of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke was recorded as the primary endpoint. In 682 enrolled patients who completed the follow-up, there were 16 myocardial infarction events, 12 stroke events, and 58 deaths as composite endpoints. According to FPG and 2hPG, patients with newly diagnosed diabetes had a 2-fold higher risk for the composite endpoint than those in the normal glucose group (hazard ratio [HR], 2.011; 95% confidence interval (CI), 1.101-3.673; P = .023); however, prediabetes was not significantly associated with the composite endpoint (HR, 1.452; 95% CI, 0.788-2.675; P = .232). On the other hand, patients with diabetes diagnosed by FPG and HbA1c did not have a significantly higher risk for the composite endpoint than those in the normal glucose group (HR, 1.321; 95% CI, 0.686-2.545; P = .405). A 2hPG ≥7.8 mmol/L was a significant predictor for the composite endpoint (odds ratio, 1.743; 95% CI, 1.060-2.863; P = .028) after adjusting for age, sex, and estimated glomerular filtration rate. Diabetes, but not prediabetes, detected via OGTT is associated with a significantly increased risk for the composite endpoint in patients with established CAD. The 2hPG provided a greater predictive power for the composite endpoint than fasting glucose and HbA1c., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: There are still not enough studies on the prediction of non-utilization of a complication test or a glycated hemoglobin test for preventing diabetes complications by using large-scale community-based big data. This study identified the ratio of not taking a diabetes complication test (fundus examination and microprotein urination test) among adult diabetic patients over 19 years using a national survey conducted in South Korea and developed a model for predicting the probability of not taking a diabetes complication test based on it., Methods: This study analyzed 25,811 subjects who responded that they had been diagnosed with diabetes by a doctor in the 2020 Community Health Survey. Outcome variables were defined as the utilization of the microprotein urination test and the fundus examination during the past year. This study developed a model for predicting the utilization of a diabetes complication test using logistic regression analysis and nomogram to understand the relationship of predictive factors on the utilization of a diabetes complication test., Results: The results of this study confirmed that age, education level, the recognition of own blood glucose level, current diabetes treatment, diabetes management education, not conducting the glycated hemoglobin test in the past year, smoking, single-person household, subjectively good health, and living in the rural area were independently related to the non-utilization of diabetes complication test after the COVID-19 pandemic., Conclusion: Additional longitudinal studies are required to confirm the causality of the non-utilization of diabetes complication screening tests., Competing Interests: The author declares 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 © 2022 Byeon.)

Background: There is a paucity of data on the coverage of diabetes mellitus (DM) complications screening in primary healthcare facilities in South Africa (SA). This study assesses the extent of screening for DM complications among individuals with type 2 DM attending primary health facilities in rural Eastern Cape (EC), SA., Methods: The study adopted a descriptive, cross-sectional design and obtained data from 372 individuals with type 2 diabetes attending six selected primary healthcare centres (PHCs) in two EC districts. Demographic and clinical data were obtained through questionnaire-based interviews and reviews of medical records. We assessed the extent of screening for estimated glomerular filtration rate (eGFR), fasting lipogram, eye examination, foot examination and glycated hemoglobin (HbA1c) in the past year., Results: Participants mean age was 62 (standard deviation [s.d.] ± 11) years, and their mean duration of diagnosis was 9 (s.d. ± 8) years. In the past year, HbA1c result was available for 71 (19.1%) of the participants; 60 (16.1%) had eGFR results, while only 33 (8.9%) had documented lipid results. In total, 52 (14.0%) had carried out eye examinations, while only 9 (2.3%) had undergone foot examinations in the past year. About two-thirds of the participants (59.9%) had not undergone any form of complication screening in the past year, and none had undergone the complete screening panel., Conclusion: The coverage of screening for DM complications was low across all indicators. Studies to understand barriers to and facilitators of DM complications screening at PHCs are required. Also, interventions to improve diabetes complication screening in the region are needed and should target the primary healthcare providers.

Objective: Diabetic complications have brought a tremendous burden for diabetic patients, but the problem of predicting diabetic complications is still unresolved. Our aim is to explore the relationship between hemoglobin A1C (HbA1c), insulin (INS), and glucose (GLU) and diabetic complications in combination with individual factors and to effectively predict multiple complications of diabetes., Methods: This was a real-world study. Data were collected from 40,913 participants with an average age of 48 years from the Department of Endocrinology of Ruijin Hospital in Shanghai. We proposed deep personal multitask prediction of diabetes complication with attentive interactions (DPMP-DC) to predict the five complication models of diabetes, including diabetic retinopathy, diabetic nephropathy, diabetic peripheral neuropathy, diabetic foot disease, and diabetic cardiovascular disease., Results: Our model has an accuracy rate of 88.01% for diabetic retinopathy, 89.58% for diabetic nephropathy, 85.77% for diabetic neuropathy, 80.56% for diabetic foot disease, and 82.48% for diabetic cardiovascular disease. The multitasking accuracy of multiple complications is 84.67%, and the missed diagnosis rate is 9.07%., Conclusion: We put forward the method of interactive integration with individual factors of patients for the first time in diabetic complications, which reflect the differences between individuals. Our multitask model using the hard sharing mechanism provides better prediction than prior single prediction models., Competing Interests: There are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Ming Zuo et al.)

Diabetes is an ambulatory care sensitive condition that quality of care can prevent complications development and hospitalization needs. However, diabetes patients with disability face greater challenges with receiving quality diabetes care than those without disabilities. This study examined diabetes-related avoidable hospitalizations (DRAH) focusing on the association with disability. We used nationally representative health insurance cohort data from 2002 to 2013. The study population is people who were newly diagnosed with type 2 diabetes. We measured the cumulated number of DRAH using the Prevention Quality Indicators (PQIs). The variables of interest were disability severity and type. We performed a recurrent events analysis using Cox proportional hazard regression model. Among 49,410 type 2 diabetes patients, 12,231 (24.8%) experienced DRAHs at least once during the follow-up period. Among the total population, 5924 (12.0%) diabetes patients were registered as disabled. The findings report that disability severity was significantly associated with higher risks for DRAH, where severely disabled diabetes patients showed the highest hazard ratio of 2.24 (95% CI 1.80-2.79). Among three DRAH indicators, severely disabled diabetes patients showed increased risks for long-term (AHR 2.21, 95% CI 1.89-2.60) and uncontrolled (AHR 2.28, 95% CI 1.80-2.88) DRAH. In addition, intellectual (AHR 5.52, 95% CI 3.78-8.05) and mental (AHR 3.97, 95% CI 2.29-6.89) disability showed higher risks than other types of disability. In conclusion, diabetes patients with disability are at higher risk for DRAH compared to those without disabilities, and those with intellectual and mental disabilities were more likely to experience DRAH compared to those with physical or other types of disability. These findings call for action to find the more appropriate interventions to improve targeted diabetes primary care for patients with disability. Further research is needed to better understand determinants of increasing risks of DRAH., (© 2022. The Author(s).)

Purpose: Diabetes is a growing health problem. The aim of this study was to capture time trends in mortality associated with diabetes., Methods: The mortality database of the Veneto region (Italy) includes both the underlying causes of death, and all the diseases mentioned in the death certificate. The annual percent change (APC) in age-standardized rates from 2008 to 2017 was computed by the Joinpoint Regression Program., Results: Overall 453,972 deaths (56,074 with mention of diabetes) were observed among subjects aged ≥ 40 years. Mortality rates declined for diabetes as the underlying cause of death and from diabetes-related circulatory diseases. The latter declined especially in females - 4.4 (CI 95% - 5.3/- 3.4), while in males the APC was - 2.8 (CI 95% - 4.0/- 1.6)., Conclusion: We observed a significant reduction in mortality during the period 2008-2017 in diabetes either as underlying cause of death or when all mentions of diabetes in the death certificate were considered., (© 2021. The Author(s).)

Background: Chronic kidney disease is often asymptomatic in its early stages but constitutes a severe burden for patients and causes major healthcare systems costs worldwide. While models for assessing the cost-effectiveness of screening were proposed in the past, they often presented only a limited view. This study aimed to develop a simulation-based German Albuminuria Screening Model (S-GASM) and present some initial applications., Methods: The model consists of an individual-based simulation of disease progression, considering age, gender, body mass index, systolic blood pressure, diabetes, albuminuria, glomerular filtration rate, and quality of life, furthermore, costs of testing, therapy, and renal replacement therapy with parameters based on published evidence. Selected screening scenarios were compared in a cost-effectiveness analysis., Results: Compared to no testing, a simulation of 10 million individuals with a current age distribution of the adult German population and a follow-up until death or the age of 90 shows that a testing of all individuals with diabetes every two years leads to a reduction of the lifetime prevalence of renal replacement therapy from 2.5% to 2.3%. The undiscounted costs of this intervention would be 1164.10 € / QALY (quality-adjusted life year). Considering saved costs for renal replacement therapy, the overall undiscounted costs would be-12581.95 € / QALY. Testing all individuals with diabetes or hypertension and screening the general population reduced the lifetime prevalence even further (to 2.2% and 1.8%, respectively). Both scenarios were cost-saving (undiscounted, - 7127.10 €/QALY and-5439.23 €/QALY)., Conclusions: The S-GASM can be used for the comparison of various albuminuria testing strategies. The exemplary analysis demonstrates cost savings through albuminuria testing for individuals with diabetes, diabetes or hypertension, and for population-wide screening., Competing Interests: The authors have declared that no competing interests exist.

Diabetes is a common condition that is increasing in incidence worldwide. Although the skin manifestations of this condition are well described, there is scant literature on the associated nail changes. In this review, we describe the various clinical features of nail changes associated with diabetes, which can be broadly divided into infections, vascular changes, neuropathic manifestations and miscellaneous changes, although there is overlap between them. There is no pathognomonic nail alteration, but it is important for clinicians to be aware of the potential nail manifestations in diabetes as they can facilitate investigations and thereby early diagnosis of diabetes, resulting in holistic management of the patient., (© 2021 British Association of Dermatologists.)

Prevalence of both type 1 and type 2 diabetes mellitus is growing worldwide and one major cause for morbidity and mortality. However, not every patient develops diabetes-related complications, but causes for the individual susceptibility are still not fully understood. As a platform to address this, we initiated the TUDID (TUebingen DIabetes Database) study, a prospective, monocentric, observational study that includes adults with diabetes mellitus who are treated in the inpatient clinic of a University Hospital in southern Germany. Besides a thorough clinical examination and extensive laboratory tests (with integrated biobanking), major study focuses are the kidneys, the eyes, the vasculature as well as cognition and mood where standardized investigations for early stages for diabetes complications are performed. Analyses of the data generated by this precise characterization of diabetes-related complications will contribute to our understanding of the development and course of such complications, and thus facilitate the implementation of tailored treatment options that can reduce the risk and severity of diabetes-related complications., Competing Interests: As of 01/2020, B.A. Jaghutriz is an employee of Eli Lilly and Company. Outside of the current work, R.W. reports lecture fees from Novo Nordisk and travel grants from Eli Lilly. Outside of the current work, M.H. reports research grants from Boehringer Ingelheim and Sanofi (both to the University Hospital of Tübingen) and lecture fees from Sanofi, Novo Nordisk, Eli Lilly and Merck Sharp & Dohme. Outside of the current work, A.F. reports lecture fees and advisory board membership from Sanofi, Novo Nordisk, Eli Lilly, AstraZeneca. Outside of the current work, N.S. was and presently is consulting and was and is a member of the speaker bureau of Allergan, AstraZeneca, Boehringer Ingelheim, Gilead, Genkyotex, Intercept Pharma, MSD, Novartis, Novo Nordisk, Pfizer and Sanofi. Furthermore, he conducted clinical trials with support from AstraZeneca, Boehringer Ingelheim, Sanofi, DSM Nutritional Products and Roche Diagnostics. Outside of the current work, A.B. received advisory board fees and fees for serving on a speakers bureau from Novo Nordisk, Eli Lilly, Merck Sharp & Dohme, Sanofi and Boehringer Ingelheim. None of the other authors report a conflict of interest., (Thieme. All rights reserved.)

Chronic diabetic complications affect multiple organs causing widespread organ damage. Although there are some commonalities, the phenotype of such changes show tissue specific variation. Given this, we examined whether differences in circular RNA (circRNA) mediated gene regulatory mechanisms contribute to changes in gene expression at the basal level and in diabetes. CircRNAs are single-stranded RNA with covalently closed loop structures and act as miRNA sponges, factors of RNA splicing, scaffolding for proteins, regulators of transcription, and modulators of the expression of parental genes, among other roles. We examined heart and retinal tissue from Streptozotocin-induced diabetic mice with established diabetes related tissue damage and tissue from non-diabetic controls. A custom array analysis was performed and the data were analysed. Two major circRNA mediated processes were uniquely upregulated in diabetic heart tissue, namely, positive regulation of endothelial cell migration and regulation of mitochondria: mitochondrial electron transport. In the retina, circRNAs regulating extracellular matrix protein production and endothelial to mesenchymal transition (EndMT) were found to be upregulated. The current study identified regulatory and potential pathogenetic roles of specific circRNA in diabetic retinopathy and cardiomyopathy. Understanding such novel mechanisms, may in the future, be useful to develop RNA based treatment strategies., (© 2021. The Author(s).)

Fibroblasts are the essential cell type of skin, highly involved in the wound regeneration process. In this study, we sought to screen out the novel genes which act important roles in diabetic fibroblasts through bioinformatic methods. A total of 811 and 490 differentially expressed genes (DEGs) between diabetic and normal fibroblasts were screened out in GSE49566 and GSE78891, respectively. Furthermore, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in type 2 diabetes were retrieved from miRWalk. Consequently, the integrated bioinformatic analyses revealed the shared KEGG pathways between DEG-identified and diabetes-related pathways were functionally enriched in the MAPK signaling pathway, and the MAPKAPK3, HSPA2, TGFBR1, and p53 signaling pathways were involved. Finally, ETV4 and NPE2 were identified as the targeted transcript factors of MAPKAPK3, HSPA2, and TGFBR1. Our findings may throw novel sight in elucidating the molecular mechanisms of fibroblast pathologies in patients with diabetic wounds and targeting new factors to advance diabetic wound treatment in clinic., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2021 Weirong Zhu et al.)

Background: Given the increasing prevalence of diabetes in low-income and middle-income countries (LMICs), we aimed to estimate the health and cost implications of achieving different targets for diagnosis, treatment, and control of diabetes and its associated cardiovascular risk factors among LMICs., Methods: We constructed a microsimulation model to estimate disability-adjusted life-years (DALYs) lost and health-care costs of diagnosis, treatment, and control of blood pressure, dyslipidaemia, and glycaemia among people with diabetes in LMICs. We used individual participant data-specifically from the subset of people who were defined as having any type of diabetes by WHO standards-from nationally representative, cross-sectional surveys (2006-18) spanning 15 world regions to estimate the baseline 10-year risk of atherosclerotic cardiovascular disease (defined as fatal and non-fatal myocardial infarction and stroke), heart failure (ejection fraction of <40%, with New York Heart Association class III or IV functional limitations), end-stage renal disease (defined as an estimated glomerular filtration rate <15 mL/min per 1·73 m 2 or needing dialysis or transplant), retinopathy with severe vision loss (<20/200 visual acuity as measured by the Snellen chart), and neuropathy with pressure sensation loss (assessed by the Semmes-Weinstein 5·07/10 g monofilament exam). We then used data from meta-analyses of randomised controlled trials to estimate the reduction in risk and the WHO OneHealth tool to estimate costs in reaching either 60% or 80% of diagnosis, treatment initiation, and control targets for blood pressure, dyslipidaemia, and glycaemia recommended by WHO guidelines. Costs were updated to 2020 International Dollars, and both costs and DALYs were computed over a 10-year policy planning time horizon at a 3% annual discount rate., Findings: We obtained data from 23 678 people with diabetes from 67 countries. The median estimated 10-year risk was 10·0% (IQR 4·0-18·0) for cardiovascular events, 7·8% (5·1-11·8) for neuropathy with pressure sensation loss, 7·2% (5·6-9·4) for end-stage renal disease, 6·0% (4·2-8·6) for retinopathy with severe vision loss, and 2·6% (1·2-5·3) for congestive heart failure. A target of 80% diagnosis, 80% treatment, and 80% control would be expected to reduce DALYs lost from diabetes complications from a median population-weighted loss to 1097 DALYs per 1000 population over 10 years (IQR 1051-1155), relative to a baseline of 1161 DALYs, primarily from reduced cardiovascular events (down from a median of 143 to 117 DALYs per 1000 population) due to blood pressure and statin treatment, with comparatively little effect from glycaemic control. The target of 80% diagnosis, 80% treatment, and 80% control would be expected to produce an overall incremental cost-effectiveness ratio of US$1362 per DALY averted (IQR 1304-1409), with the majority of decreased costs from reduced cardiovascular event management, counterbalanced by increased costs for blood pressure and statin treatment, producing an overall incremental cost-effectiveness ratio of $1362 per DALY averted (IQR 1304-1409)., Interpretation: Reducing complications from diabetes in LMICs is likely to require a focus on scaling up blood pressure and statin medication treatment initiation and blood pressure medication titration rather than focusing on increasing screening to increase diabetes diagnosis, or a glycaemic treatment and control among people with diabetes., Funding: None., Competing Interests: Declaration of interests SB reports grants from the US National Institutes of Health (NIH) and US Centers for Disease Control and Prevention; consulting fees from the Clinton Health Access Initiative and University of California San Francisco; patents pending for a multi-model patient outreach system; unpaid leadership roles at La Scuola International School and Columbia University Global Research Analytics for Population Health; and stock options at Collective Health, outside the submitted work. DF reports volunteer affiliations with Wuqu' Kawoq and GlucoSalud, outside the submitted work. RA reports contracts with Novo Nordisk, outside the submitted work. TB reports grants from the NIH–National Institute of Allergy and Infectious Diseases, NIH–National Institute on Aging, NIH, National Institute of Child Health and Human Development, Wellcome, Alexander von Humboldt Foundation, UNAIDS, German Research Foundation, European Union, German Federal Ministry of Education and Research, German Federal Ministry of Environment, Nature Conservation and Nuclear Safety, German Federal Ministry of Health, KfW, Else Kröner Foundation, African Academy of Science, European and Developing Countries Clinical Trials Partnership, and the Bill & Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Diabetes mellitus and the associated complications are metabolic diseases with high morbidity that result in poor quality of health and life. The lack of diagnostic methods for early detection results in patients losing the best treatment opportunity. Oral hypoglycemics and exogenous insulin replenishment are currently the most common therapeutic strategies, which only yield temporary glycemic control rather than curing the disease and its complications. Exosomes are nanoparticles containing bioactive molecules reflecting individual physiological status, regulating metabolism, and repairing damaged tissues. They function as biomarkers of diabetes mellitus and diabetic complications. Considering that exosomes are bioactive molecules, can be obtained from body fluid, and have cell-type specificity, in this review, we highlight the multifold effects of exosomes in the pathology and therapy of diabetes mellitus and diabetic complications., 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 © 2021 Sun, Tao, Wu, Zhang, Liu and Wang.)

Background: Diabetes Mellitus (DM) is a common metabolic disease associated with increased risk of mortality., Objective: The aim of this study was to examine predictors of mortality among patients with type 2 diabetes in the north of Jordan., Methods: Electronic data files for diabetes patients admitted between the period of 2014-2018 at a tertiary center in the north of Jordan were reviewed. Patient's characteristics, clinical and laboratory data, use of medications and mortality rate were collected., Results: Mean age of patients (n = 957) was 60.99 ± 0.37 (mean ± sem). Most of patients had multiple risk factors and underlying cardiovascular diseases (CVDs). Mortality rate was 10.1%. Univariate predictors of mortality included age, chronic kidney disease (CKD), acute kidney injury, hypertension, heart failure (HF), coronary artery disease, venous thromboembolism (VTE), stroke, atrial fibrillation (AF), and chronic obstructive pulmonary disease (COPD). As the number of CVDs increases, mortality rate also increases (Odd ratio 2.0, p < 0.0001). Use of insulin, aspirin, ACEi/ARBS, beta blockers, and diuretics were also associated with mortality. Fasting glucose and percentage of glycated hemoglobin were not associated with mortality. By multivariable logistic regression analysis adjusting for confounders and collinearity; age, HF, AF, COPD, VTE, and CKD were associated with mortality., Conclusion: Key risk factors of mortality are CVDs and CKD indicating that the primary step of management should focus on optimizing risk factors to prevent diabetes complications and death., (© 2021. The Author(s).)

Purpose: Individuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications., Methods: We prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia., Results: Among 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p = 0.001), fasting blood glucose (HR 4.32, p < 0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p = 0.010) or fasting blood glucose ≥7 mmol/L (HR 3.07, p = 0.015)., Conclusions: Thromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose in relation to the topic of this manuscript. The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. This work was funded by Program Project COVID-19 OSR-UniSR and COVID-2020-12371617Ministero della Salute., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: We purposed to investigate whether preoperative HbA1c level is associated with the severity of surgical treatment in diabetic hand infection cases., Materials and Methods: Between December 2015 and October 2018, 102 patients were surgically treated due to diabetic hand infection. Of the patients, 75 who met the criteria for diabetic hand infection were included in the study. The patients were divided into two groups: Group 1, < 8.5% HbA1c level (poorly controlled); and Group 2, 8.5% or higher HbA1c level (uncontrolled). Preoperative, intraoperative, and postoperative data were recorded. Drainage, VAC, ray/open amputation, and microsurgical reconstruction were performed according to the examination and clinical findings. p<0.05 was considered statistically significant., Results: The study groups consisted of 41 patients (5 female/36 male; median age 59 years, range 32-68) in Group 1 and 34 patients (6 female/28 male; median age 62 years, range 28-67) in Group 2. The mean follow-up period was 21.14±10.42 months in Group 1 and 16.70±10.19 months in Group 2, which were not significantly different (p>0.05). The most common microbiological pathogen was polymicrobial in both study groups (39% in Group 1 and 41.2% in Group 2). Drainage was the most common surgical procedure in both groups and there was no significant difference between the groups in terms of the surgical techniques that were used (p>0.05)., Conclusion: Although HbA1c level is an important biomarker for monitoring glycemia in diabetic patients, it is not associated with the severity of surgical treatment in diabetic hand infections., Competing Interests: No conflict of interest has been declared by the authors., (Thieme. All rights reserved.)

Aim: To investigate the epidemiology of S. aureus and MRSA nasal carriage among people with diabetes at the Korle Bu Teaching Hospital in Accra, including the prevalence, predictors of carriage, and antibiotic resistance., Methodology: This study was cross-sectional, involving 300 diabetes patients and 106 non-diabetic individuals. Swab specimens of the nares were obtained from the participants and bacteriologically-cultured. Identification and characterization of S. aureus and MRSA were based on standard bacteriological methods; antimicrobial susceptibility testing was by the Kirby-Bauer method., Results: The prevalence of staphylococcal carriage, the diabetes group relative to the non-diabetes group, were 31.0% and 10.4% (S. aureus), and 3.3% and 0.0% (MRSA). Presence of diabetes predisposed to S. aureus carriage, but not MRSA nor coagulase-negative staphylococci (CoNS) carriage (OR = 3.88; p < 0.0001). Colonization with CoNS was protective of S. aureus (OR = 0.039, p < 0.001) and MRSA (OR = 0.115, p = 0.043) colonization among the diabetics. The antimicrobial resistance patterns recorded among the S. aureus isolated from the diabetic individuals relative to the non-diabetics were as follows: penicillin (95% vs. 91%), tetracycline (37% vs. 27%), cotrimoxazole (30% vs. 36%), erythromycin (17% vs. 0%), norfloxacin (13% vs. 0%), clindamycin (12% vs. 0%), gentamicin (9% vs. 0%), fusidic acid (10% vs. 9%), linezolid (4% vs. 0%), and rifampicin (5% vs. 0%). The proportion of multidrug resistant S. aureus was 41% (n = 38) in the diabetes group and 0% in the non-diabetes group; this difference was statistically significant (p = 0.01)., Conclusions: The presence of diabetes predisposed the participants to S. aureus carriage by almost four folds, but not MRSA carriage. Colonization with CoNS was protective of S. aureus and MRSA carriage in the diabetes group. Finally, linezolid remains a good therapeutic agent for anti-MRSA therapy., Competing Interests: FCNK and M-MO are affiliated with FleRhoLife Research Consult, but this firm didnot provide financial support nor play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Aims: To evaluate calculated total plasma osmolality as a marker of outcome prediction, fluid and metabolic balance, thrombotic risk in severe COVID-19 patients., Methods: Retrospective data of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 175 patients, including diabetic subset: n = 102) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for calculated total osmolality, eGFR, and D-dimer, and their correlations were studied., Results: Among 175 severe COVID-19 patients, a significant association with mortality was seen with respect to calculated total osmolality (p < 0.001), eGFR (p < 0.001), and D-dimer (p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for total osmolality 299 mosm/kg (area under the curve (AUC)-0.773, odds ratio (OR)-1.09), eGFR 61.5 ml/min/m2 (AUC-0.789, OR-0.96), D-dimer 5.13 (AUC-0.814, OR-2.65) respectively. In diabetic subset, the cut-offs for total osmolality were 298 mosm/kg (AUC-0.794, OR-1.12), eGFR 44.9 ml/min/m2 (AUC-0.774, OR-0.96) and D-dimer 1.59 (AUC-0.769, OR-1.52) respectively., Conclusions: Applicable cut-offs for calculated total plasma osmolality, eGFR, and D-dimer predicts clinical outcome in severe COVID-19 with and without diabetes. Correlation studies validated calculated total osmolality as a marker of the combined effect of fluid and metabolic imbalance, compromised renal function and hypercoagulability., Competing Interests: Declaration of competing interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

People with diabetes require lifelong access to healthcare services to delay the onset of complications. Their disease management processes generate great volumes of data across several domains, from clinical to administrative. Difficulties in accessing and processing these data hinder their secondary use in an institutional setting, even for highly desirable applications, such as the prediction of cardiovascular disease, the main driver of excess mortality in diabetes. Hence, in the present work, we propose a deep learning model for the prediction of major adverse cardiovascular events (MACE), developed and validated using the administrative claims of 214,676 diabetic patients of the Veneto region, in North East Italy. Specifically, we use a year of pharmacy and hospitalisation claims, together with basic patient's information, to predict the 4P-MACE composite endpoint, i.e., the first occurrence of death, heart failure, myocardial infarction, or stroke, with a variable prediction horizon of 1 to 5 years. Adapting to the time-to-event nature of this task, we cast our problem as a multi-outcome (4P-MACE and components), multi-label (1 to 5 years) classification task with a custom loss to account for the effect of censoring. Our model, purposefully specified to minimise data preparation costs, exhibits satisfactory performance in predicting 4P-MACE at all prediction horizons: AUROC from 0.812 (C.I.: 0.797 - 0.827) to 0.792 (C.I.: 0.781 - 0.802); C-index from 0.802 (C.I.: 0.788 - 0.816) to 0.770 (C.I.: 0.761 - 0.779). Components' prediction performance is also adequate, ranging from death's 0.877 1-year AUROC to stroke's 0.689 5-year AUROC.

Aim: Different guidelines provide similar, but not identical, therapeutic targets for HbA1c in type 2 diabetes. These targets can also depend from the different pharmacological strategies adopted for intensifying glycemic control., Data Synthesis: This meta-analysis includes randomized trials adopting any pharmacological regimen for intensifying glycemic control in T2DM (versus standard of care/placebo), with a trial duration ≥2 years and a between-group HbA1c difference≥0.5%. The primary outcome was to assess the effects of the improvement of glycemic control on major cardiovascular events (MACE), ocular and renal complications, and severe hypoglycemia. Mantel-Haenszel odds ratios (MH-OR) with 95% Confidence Intervals were calculated for all the outcomes considered. We included 13 trials fulfilling the inclusion criteria. The improvement of glycemic control was associated with a lower risk of MACE (MH-OR:0.89 [95%CI 0.85-0.94]) and renal adverse events (MH-OR 0.73 [0.65-0.82]), but not all-cause mortality (MH-OR 0.95 [0.88-1.01]) and ocular adverse complications (MH-OR 0.94 [0.72-1.22]). For glucose-lowering drugs inducing hypoglycemia, a protective effect on the risk of microvascular complications, but not of MACE and all-cause mortality, was observed only for HbA1c ≤ 48 mmol/mol, but with higher risk of severe hypoglycaemia (MH-OR 2.72 [1.79-4.13]). Drugs not inducing hypoglycaemia were associated with a reduction of MACE, renal adverse events, and all-cause mortality, for HbA1c< 7% (no data for lower targets)., Conclusions: The present meta-analysis show that the improvement of glycemic control with drugs not inducing hypoglycemia is associated with a reduction in the risk of long-term chronic vascular and renal complications, and all-cause mortality., Competing Interests: Declaration of competing interest MM has received speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, and Sanofi; RC, BP, and GT has no relevant conflicts of interest to declare. EM has received consultancy fees from Merck and Novartis speaking fees from Astra Zeneca, Bristol Myers Squibb, Boehringer-Ingelheim, Eli-Lilly, Merck, Novo Nordisk, Sanofi, and Novartis and research grants from Merck, Novartis, and Takeda. All the authors approved the final version of this manuscript. Dr. Edoardo Mannucci is the person who takes full responsibility for the work as a whole, including the study design, access to data, and the decision to submit and publish the manuscript., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Introduction: Children, adolescents and young adults with Type 1 diabetes mellitus need to be screened for chronic complications and associated (autoimmune) diseases. There are no Dutch national guidelines for screening available but the International Society for Pediatric and Adolescent Diabetes (ISPAD) gives recommendations in its guidelines. The ISPAD guidelines from 2014 were updated in 2018., Objectives: The adherence of the Dutch pediatric diabetes clinics to the international guidelines as stated by the ISPAD., Methods: A questionnaire about screening method and frequency was send to all members of the Dutch national committee for pediatric diabetes. The screening policies of the pediatric diabetes clinics were compared to the ISPAD guidelines of 2014 and 2018., Results: Sixty-two percent of all diabetes clinics filled out the questionnaire. None of the diabetes clinics followed all recommendations of the ISPAD. The majority of the clinics had a higher frequency of screening, performed extra blood tests and did not personalize their policy to the individual patient. Approximately one third of the diabetes clinics still commenced screening for chronic complications at the age of 10 years, as recommended in the previous version of the ISPAD guideline., Conclusions: Dutch pediatric diabetes clinics screen their patients on chronic complications and associated conditions very differently and not according to the international (and most recent) guidelines. A more individualized approach with respect to the newest ISPAD guidelines will diminish the burden for the patient and medical costs as well., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Objective: Male sex is one of the determinants of severe coronavirus diseas-e-2019 (COVID-19). We aimed to characterize sex differences in severe outcomes in adults with diabetes hospitalized for COVID-19., Methods: We performed a sex-stratified analysis of clinical and biological features and outcomes (i.e. invasive mechanical ventilation (IMV), death, intensive care unit (ICU) admission and home discharge at day 7 (D7) or day 28 (D28)) in 2380 patients with diabetes hospitalized for COVID-19 and included in the nationwide CORONADO observational study (NCT04324736)., Results: The study population was predominantly male (63.5%). After multiple adjustments, female sex was negatively associated with the primary outcome (IMV and/or death, OR: 0.66 (0.49-0.88)), death (OR: 0.49 (0.30-0.79)) and ICU admission (OR: 0.57 (0.43-0.77)) at D7 but only with ICU admission (OR: 0.58 (0.43-0.77)) at D28. Older age and a history of microvascular complications were predictors of death at D28 in both sexes, while chronic obstructive pulmonary disease (COPD) was predictive of death in women only. At admission, C-reactive protein (CRP), aspartate amino transferase (AST) and estimated glomerular filtration rate (eGFR), according to the CKD-EPI formula predicted death in both sexes. Lymphocytopenia was an independent predictor of death in women only, while thrombocytopenia and elevated plasma glucose concentration were predictors of death in men only., Conclusions: In patients with diabetes admitted for COVID-19, female sex was associated with lower incidence of early severe outcomes, but did not influence the overall in-hospital mortality, suggesting that diabetes mitigates the female protection from COVID-19 severity. Sex-associated biological determinants may be useful to optimize COVID-19 prevention and management in women and men.

Aims/hypothesis: Diabetes has been identified as a risk factor for poor prognosis of coronavirus disease-2019 (COVID-19). The aim of this study is to identify high-risk phenotypes of diabetes associated with COVID-19 severity and death., Methods: This is the first edition of a living systematic review and meta-analysis on observational studies investigating phenotypes in individuals with diabetes and COVID-19-related death and severity. Four different databases were searched up to 10 October 2020. We used a random effects meta-analysis to calculate summary relative risks (SRR) with 95% CI. The certainty of evidence was evaluated by the GRADE tool., Results: A total of 22 articles, including 17,687 individuals, met our inclusion criteria. For COVID-19-related death among individuals with diabetes and COVID-19, there was high to moderate certainty of evidence for associations (SRR [95% CI]) between male sex (1.28 [1.02, 1.61], n = 10 studies), older age (>65 years: 3.49 [1.82, 6.69], n = 6 studies), pre-existing comorbidities (cardiovascular disease: 1.56 [1.09, 2.24], n = 8 studies; chronic kidney disease: 1.93 [1.28, 2.90], n = 6 studies; chronic obstructive pulmonary disease: 1.40 [1.21, 1.62], n = 5 studies), diabetes treatment (insulin use: 1.75 [1.01, 3.03], n = 5 studies; metformin use: 0.50 [0.28, 0.90], n = 4 studies) and blood glucose at admission (≥11 mmol/l: 8.60 [2.25, 32.83], n = 2 studies). Similar, but generally weaker and less precise associations were observed between risk phenotypes of diabetes and severity of COVID-19., Conclusions/interpretation: Individuals with a more severe course of diabetes have a poorer prognosis of COVID-19 compared with individuals with a milder course of disease. To further strengthen the evidence, more studies on this topic that account for potential confounders are warranted., Registration: PROSPERO registration ID CRD42020193692.

Context: Emphysematous pyelonephritis (EPN) is a dangerous necrotizing infection of the kidney involving the diabetics with a high case fatality rate. Recent medical literature has shown shifting of treatment strategy from conventional radical approach to minimally invasive approach., Aims: The aim of our study was to assess the role of minimally invasive stepwise decompression techniques in the management of EPN and preservation of the renal unit., Settings and Design: : This was a retrospective observational study conducted from June 2017 to April 2020 at a tertiary care centre., Material and Methods: We reviewed the hospital online records of 18 patients diagnosed with EPN for patient demographics, clinical profiles, co-morbidities, laboratory and, radiological investigations, surgical interventions performed and the outcomes. The severity of EPN was graded as per the Huang classification. Patients underwent surgical interventions as per the treatment protocol and response was assessed., Statistical Analysis Used: Descriptive statistics was applied., Results: Diabetes mellitus was present in 15 (83.3%) patients along with urinary tract obstruction in 8 (44.4%) patients. Flank pain (77.7%) was the most common presenting clinical feature while Escherichia coli (55.5%) were the most common causative organism. Most patients (50%) had Type- II EPN, all of which were managed successfully by minimally invasive procedures. In total seventeen patients (94.4%) responded well while one patient (5.5%) underwent nephrectomy with no mortality., Conclusions: Renal salvage in EPN requires multidisciplinary approach including the initial medical management followed by properly selected stepwise decompressive surgical techniques. Conservative management and decompression techniques have shown to improve patient's outcome, reducing the traditional morbidity associated with nephrectomy., Competing Interests: None

Introduction: Severe COVID-19 illness in adults has been linked to underlying medical conditions. This study identified frequent underlying conditions and their attributable risk of severe COVID-19 illness., Methods: We used data from more than 800 US hospitals in the Premier Healthcare Database Special COVID-19 Release (PHD-SR) to describe hospitalized patients aged 18 years or older with COVID-19 from March 2020 through March 2021. We used multivariable generalized linear models to estimate adjusted risk of intensive care unit admission, invasive mechanical ventilation, and death associated with frequent conditions and total number of conditions., Results: Among 4,899,447 hospitalized adults in PHD-SR, 540,667 (11.0%) were patients with COVID-19, of whom 94.9% had at least 1 underlying medical condition. Essential hypertension (50.4%), disorders of lipid metabolism (49.4%), and obesity (33.0%) were the most common. The strongest risk factors for death were obesity (adjusted risk ratio [aRR] = 1.30; 95% CI, 1.27-1.33), anxiety and fear-related disorders (aRR = 1.28; 95% CI, 1.25-1.31), and diabetes with complication (aRR = 1.26; 95% CI, 1.24-1.28), as well as the total number of conditions, with aRRs of death ranging from 1.53 (95% CI, 1.41-1.67) for patients with 1 condition to 3.82 (95% CI, 3.45-4.23) for patients with more than 10 conditions (compared with patients with no conditions)., Conclusion: Certain underlying conditions and the number of conditions were associated with severe COVID-19 illness. Hypertension and disorders of lipid metabolism were the most frequent, whereas obesity, diabetes with complication, and anxiety disorders were the strongest risk factors for severe COVID-19 illness. Careful evaluation and management of underlying conditions among patients with COVID-19 can help stratify risk for severe illness.

Background: Erectile dysfunction is an inability to initiate and have a persistent erection firm enough to have satisfying sexual intercourse. The prevalence of erectile dysfunction in diabetic men is considerably high, but it is often underdiagnosed and under-managed., Objective: This study aimed to determine erectile dysfunction and associated factors among diabetic patients at, Hawassa, Southern, Ethiopia., Methods: The institution-based cross-sectional study was conducted on 352 adult male diabetic patients randomly selected from Adare general and Hawassa comprehensive specialized hospitals using a simple random sampling technique. The number of patients to be selected from each hospital was proportionally assigned based on the total population of diabetes mellitus patients following chronic care during the study period. The descriptive statistics and multiple logistic regressions (bivariate and multivariate analysis) were carried out., Result: The prevalence of erectile dysfunction was 72.2% (95%CI, 1.76-3.68). After adjusting all factors, old age, diabetes duration, drinking alcohol, and poor glycemic control had shown significant association with erectile dysfunction., Conclusion: The occurrence of erectile dysfunction in this study community is very high. Drinking alcohol, poor glycemic control, age, and duration of diabetes were predictors of erectile dysfunction in this study area. Assessment and management of erectile dysfunction in the diabetic clinic should be part of routine medical care during follow-up visits with diabetic patients. Healthcare providers should emphasize screening and treating older patients and those who have had a diabetes diagnosis for a longer duration.

Aims/introduction: As estimated glomerular filtration rate (eGFR) progression might correlate with cardiovascular prognosis, the correlation between 1-year decline in eGFR and cardiovascular incidences and renal outcome was investigated., Materials and Methods: The 1-year percentage decline in eGFR at the first observation year was calculated in a cohort of the standard versus intEnsive statin therapy for hypercholesteroleMic Patients with diAbetic retinopaTHY (EMPATHY) trial participants. The primary end-point was the composite cardiovascular end-point including the renal end-point. The associations between the incidence of each end-point and clinical markers were analyzed using the Cox proportional hazards regression model., Results: A total of 4,461 patients were analyzed. The mean observation period was 765.3 ± 363.1 days. The best cut-off value of 1-year eGFR decline was 0.099 in the first year for renal end-point prediction by receiver operating characteristic curve analysis. The area under the curve of the model including the 1-year eGFR decline of the first year was significantly larger than the model without it (0.943, 95% confidence interval 0.915-0.971 to 0.967, 95% confidence interval 0.950-0.983, P = 0.019). Primary end-point incidences and the renal end-point were much higher in rapid eGFR decliners compared with non-decliners (P < 0.0001). The cardiovascular end-point incidence, except for the renal end-point, was not different between the groups. According to Cox regression analysis, 1-year eGFR decline during the first year was a significant risk factor for the end-points, including the renal end-point, independent of albuminuria and eGFR at baseline., Conclusions: The 1-year eGFR decline rate provided useful information for cardiovascular end-point predictions, including the renal end-point, in addition to the conventional risk factors., (© 2020 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

The number of patients with diabetes with a risk of cardiovascular diseases (CVDs) is increasing worldwide, leading to a higher demand for evaluating atherosclerosis. Recently, the mean platelet volume (MPV) available from complete blood count is gaining attention as a marker of underlying atherosclerotic lesions. In the current study, we examined whether MPV can predict carotid atherosclerosis in patients with diabetes at an intermediate or high risk for CVD. A total of 224 patients with diabetes aged 36-85 years who underwent carotid ultrasound examination were assessed. The risk of CVD was evaluated using the Suita score. The greatest carotid intima-media thickness (IMT) in each common carotid artery (CCA Max-IMT), carotid bulb, internal carotid artery, or external carotid artery (Total Max-IMT) was measured. Subsequently, the relationship between MPV and IMT was analyzed. Patients were divided into three groups according to their MPV values (<9.5 fl, tertile 1; 9.5-10.2 fl, tertile 2; and >10.2 fl, tertile 3). A correlation was observed between MPV and platelet count (P < 0.001), platelet distribution width (P < 0.001), and glycated hemoglobin (P = 0.04); however, multivariate logistic regression analyses demonstrated no relationship between MPV and CCA Max-IMT [odds ratio, 0.89 (0.60-1.29), P = 0.54] or Total Max-IMT [odds ratio, 0.87 (0.61-1.24), P = 0.45]. MPV did not correlate with carotid artery thickness. Therefore, it is difficult to determine the significance of MPV in atherosclerotic conditions from this study., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The finding that high-dose dexamethasone improves survival in those requiring critical care due to COVID-19 will mean much greater usage of glucocorticoids in the subsequent waves of coronavirus infection. Furthermore, the consistent finding of adverse outcomes from COVID-19 in individuals with obesity, hypertension and diabetes has focussed attention on the metabolic dysfunction that may arise with critical illness. The SARS coronavirus itself may promote relative insulin deficiency, ketogenesis and hyperglycaemia in susceptible individuals. In conjunction with prolonged critical care, these components will promote a catabolic state. Insulin infusion is the mainstay of therapy for treatment of hyperglycaemia in acute illness but what is the effect of insulin on the admixture of glucocorticoids and COVID-19? This article reviews the evidence for the effect of insulin on clinical outcomes and intermediary metabolism in critical illness., 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 © 2021 Whyte, Vas and Umpleby.)

The relationship between COVID-19 and diabetes mellitus is complicated and bidirectional. On the one hand, diabetes mellitus is considered one of the most important risk factors for a severe course of COVID-19. Several factors that are often present in diabetes mellitus are likely to contribute to this risk, such as older age, a proinflammatory and hypercoagulable state, hyperglycemia and underlying comorbidities (hypertension, cardiovascular disease, chronic kidney disease and obesity). On the other hand, a severe COVID-19 infection, and its treatment with steroids, can have a specific negative impact on diabetes itself, leading to worsening of hyperglycemia through increased insulin resistance and reduced β-cell secretory function. Worsening hyperglycemia can, in turn, adversely affect the course of COVID-19. Although more knowledge gradually surfaces as the pandemic progresses, challenges in understanding the interrelationship between COVID-19 and diabetes remain., 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 © 2021 Landstra and de Koning.)

Background: Diabetes is a well-known risk factor for tuberculosis and poorly glycemic control may increase the risk of tuberculosis. We performed a meta-analysis to explore the association of glycemic control in diabetic patients and their tuberculosis prevalence., Methods: We included observational studies that investigated the prevalence of tuberculosis associated with glycemic control. The markers of glycated hemoglobin A1c (HbA1c) and fasting plasma glucose were used to evaluate the exposure of interest in the study. We searched related articles in PubMed, EMBASE and Web of Science through 14 December 2019. The Newcastle-Ottawa scale was used to assess the risk of bias of included studies., Results: Seventeen studies (four cohort studies, five case-control studies and eight cross-sectional studies) were included, involving 1,027,074 participants. The meta-analysis found the pooled odds ratio of prevalent tuberculosis increased a 2.05-fold (95%CI: 1.65, 2.55) for the patients with HbA1c ≥7.0% compared to those with HbA1c concentration < 7.0%. Furthermore, we found the mean of HbA1c was higher in the diabetes mellitus with tuberculosis group than the diabetes-only group (P = 0.002). In the sensitivity analysis, the finding remains consistent., Conclusion: Our study provides the evidence that poorly controlled diabetes in diabetics may be associated with increased prevalence of tuberculosis. More efforts should focus on screening tuberculosis in uncontrolled diabetes.

Introduction: Severe hypertriglyceridemia (HTG) is a rare complication of insulin resistance. Its presentation with diabetic ketoacidosis (DKA) has been reported in a few cases, where most patients have type-1 diabetes mellitus (DM). Our case represents a unique presentation of DKA associated with severe HTG above 10,000 mg/dL in an adult with type-2 DM., Patient Concerns and Diagnosis: Case Report: A 51-year-old man with no prior illnesses presented to the emergency department with abdominal pain and nausea. He was found to have DKA with a blood glucose level of 337 mg/dL, pH of 7.17, beta-hydroxybutyrate of 7.93 mmol/L, and anion gap of 20 mmol/L. His triglyceride levels were >10,000 mg/dL. His serum was found to be lipemic. Computerized tomography scan of the abdomen demonstrated mild acute pancreatitis. Negative GAD65 antibodies supported the diagnosis of type-2 DM., Interventions and Outcomes: Endocrinology was consulted and one cycle of albumin-bound plasmapheresis was administered. This therapy significantly improved his HTG. DKA gradually resolved with insulin therapy as well. He was discharged home with endocrinology follow-up., Conclusion: This unique case highlights an uncommon but critical consequence of uncontrolled DM. It brings forth the possibility of severe HTG presenting as a complication of uncontrolled type-2 DM. Severe HTG commonly presents with acute pancreatitis, which can be debilitating if not managed promptly. Most patients with this presentation are managed with insulin infusion. The use of plasmapheresis for management of severe HTG has not been well studied. Our case supports the use of plasmapheresis as an effective and rapid treatment for severe HTG., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Early diagnosis for the diabetes complications is clinically demanding with great significancy. Regarding the complexity of diabetes complications, we applied a multi-label classification (MLC) model to predict four diabetic complications simultaneously using data in the modern electronic health records (EHRs), and leveraged the correlations between the complications to further improve the prediction accuracy., Methods: We obtained the demographic characteristics and laboratory data from the EHRs for patients admitted to Changzhou No. 2 People's Hospital, the affiliated hospital of Nanjing Medical University in China from May 2013 to June 2020. The data included 93 biochemical indicators and 9,765 patients. We used the Pearson correlation coefficient (PCC) to analyze the correlations between different diabetic complications from a statistical perspective. We used an MLC model, based on the Random Forest (RF) technique, to leverage these correlations and predict four complications simultaneously. We explored four different MLC models; a Label Power Set (LP), Classifier Chains (CC), Ensemble Classifier Chains (ECC), and Calibrated Label Ranking (CLR). We used traditional Binary Relevance (BR) as a comparison. We used 11 different performance metrics and the area under the receiver operating characteristic curve (AUROC) to evaluate these models. We analyzed the weights of the learned model and illustrated (1) the top 10 key indicators of different complications and (2) the correlations between different diabetic complications., Results: The MLC models including CC, ECC and CLR outperformed the traditional BR method in most performance metrics; the ECC models performed the best in Hamming loss (0.1760), Accuracy (0.7020), F1&#95;Score (0.7855), Precision (0.8649), F1&#95;micro (0.8078), F1&#95;macro (0.7773), Recall&#95;micro (0.8631), Recall&#95;macro (0.8009), and AUROC (0.8231). The two diabetic complication correlation matrices drawn from the PCC analysis and the MLC models were consistent with each other and indicated that the complications correlated to different extents. The top 10 key indicators given by the model are valuable in medical application., Conclusions: Our MLC model can effectively utilize the potential correlation between different diabetic complications to further improve the prediction accuracy. This model should be explored further in other complex diseases with multiple complications.

The purpose of our research is to explore whether vitamin D levels were associated with the rupture of intracranial aneurysms. In this retrospective study, 105 patients diagnosed with ruptured intracranial aneurysms (RIAs) and 185 patients diagnosed with unruptured intracranial aneurysms (UIAs) at The First Affiliated Hospital of Zhengzhou University were recruited from September 2019 to September 2020. Patients' demographic and clinical information, including vitamin D levels, were recorded and compared. Univariate analysis showed that patients with UIAs had higher vitamin D levels than RIAs (p = 0.019). In addition, there were significant differences in aneurysm location (p < 0.001), aspirin use (p = 0.001), and comorbid diabetes mellitus (p = 0.037) between patients with UIAs and RIAs. Binary logistic regression analysis showed that the level of vitamin D was independently associated with RIAs [odds ratio (OR) 0.960; 95% confidence intervals (CI), 0.926-0.996, p = 0.028].

Background: Lactobacillus is a genus of Gram-positive non-spore-forming rods usually found in the microbiota of the oral cavity, gastrointestinal tract, and female genitourinary tract. Also, they are commonly used in the food industry as supplements and probiotics. Lactobacilli are normally considered non-pathogenic to the human body, however, under certain circumstances such as immunosuppression, they can cause severe infections, with only a few cases of bacteremia, infective endocarditis, pneumonia, meningitis, and intra-abdominal infections reported. Among these presentations, a pyogenic liver abscess is rather rare., Case Presentation: We describe the case of a 59-year-old man with a history of diabetes mellitus and multiple abdominal surgeries with the latest being in 2014 presenting with bacteremia and multiple large pyogenic liver abscesses due to Lactobacillus gasseri, which did not appear to be related to the use of probiotics or immunosuppression., Conclusions: Given the high prevalence of diabetes mellitus and the increased use of probiotics, it is expected that in the future we will see an increase in infections caused by Lactobacilli. Medical management with antibiotics and percutaneous drainage were successful strategies for the treatment of this unusual case of pyogenic liver abscesses and bacteremia caused by Lactobacillus gasseri.