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in category endocrinology

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1: METFORMIN USE IS ASSOCIATED WITH REDUCED MORTALITY IN A DIVERSE POPULATION WITH COVID-19 AND DIABETES
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Posted 31 Jul 2020

METFORMIN USE IS ASSOCIATED WITH REDUCED MORTALITY IN A DIVERSE POPULATION WITH COVID-19 AND DIABETES
5,970 downloads medRxiv endocrinology

Andrew Crouse, Tiffany Grimes, Peng Li, Matthew Might, Fernando Ovalle, Anath Shalev

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a growing pandemic with an increasing death toll that has been linked to various comorbidities as well as racial disparity. However, the specific characteristics of these at-risk populations are still not known and approaches to lower mortality are lacking. METHODS: We conducted a retrospective electronic health record data analysis of 25,326 subjects tested for COVID-19 between 2/25/20 and 6/22/20 at the University of Alabama at Birmingham Hospital, a tertiary health care center in the racially diverse Southern U.S. The primary outcome was mortality in COVID-19-positive subjects and the association with subject characteristics and comorbidities was analyzed using simple and multiple linear logistic regression. RESULTS: The odds ratio of contracting COVID-19 was disproportionately high in Blacks/African-Americans (OR 2.6; 95%CI 2.19-3.10; p<0.0001) and in subjects with obesity (OR 1.93; 95%CI 1.64-2.28; p<0.0001), hypertension (OR 2.46; 95%CI 2.07-2.93; p<0.0001), and diabetes (OR 2.11; 95%CI 1.78-2.48; p<0.0001). Diabetes was also associated with a dramatic increase in mortality (OR 3.62; 95%CI 2.11-6.2; p<0.0001) and emerged as an independent risk factor in this diverse population even after correcting for age, race, sex, obesity and hypertension. Interestingly, we found that metformin treatment was independently associated with a significant reduction in mortality in subjects with diabetes and COVID-19 (OR 0.33; 95%CI 0.13-0.84; p=0.0210). CONCLUSION: Thus, these results suggest that while diabetes is an independent risk factor for COVID-19-related mortality, this risk is dramatically reduced in subjects taking metformin, raising the possibility that metformin may provide a protective approach in this high risk population.

2: Predicting mortality attributable to SARS-CoV-2: A mechanistic score relating obesity and diabetes to COVID-19 outcomes in Mexico
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Posted 24 Apr 2020

Predicting mortality attributable to SARS-CoV-2: A mechanistic score relating obesity and diabetes to COVID-19 outcomes in Mexico
5,104 downloads medRxiv endocrinology

Omar Yaxmehen Bello-Chavolla, Jessica Paola Bahena-López, Neftali Eduardo Antonio-Villa, Arsenio Vargas-Vázquez, Armando González-Díaz, Alejandro Márquez-Salinas, Carlos A. Fermín-Martínez, Jose De Jesus Naveja Romero, Carlos A. Aguilar-Salinas

BACKGROUND: The SARS-CoV-2 outbreak poses challenge to healthcare systems due to high complication rates in patients with cardiometabolic diseases. Here, we identify risk factors and propose a clinical score to predict COVID-19 lethality, including specific factors for diabetes and obesity and its role in improving risk prediction. METHODS: We obtained data of confirmed and negative COVID-19 cases and their demographic and health characteristics from the General Directorate of Epidemiology of Mexican Ministry of Health. We investigated specific risk factors associated to COVID-19 positivity and mortality and explored the impact of diabetes and obesity on modifying COVID-19 related lethality. Finally, we built a clinical score to predict COVID-19 lethality. RESULTS: Among 71,103 subjects at April 27th, 2020, we observed 15,529 subjects with SARS-CoV-2 and 1,434 deaths. Risk factors for lethality in COVID-19 includes early-onset diabetes obesity, COPD, advanced age, immunosuppression, and CKD; we observed that obesity mediates 45.5% of the effect of diabetes on COVID-19 lethality. Early-onset diabetes conferred an increased risk of hospitalization and obesity conferred an increased risk for ICU admission and intubation. Our predictive score for COVID-19 lethality included age [&ge;]65 years, diabetes, early-onset diabetes, obesity, age <40 years, CKD, hypertension, pregnancy and immunosuppression and significantly discriminates lethal from non-lethal COVID-19 cases (c-statistic=0.830). RESULTS: Here, we propose a mechanistic approach to evaluate risk for complications and lethality attributable to COVID-19 considering the effect of obesity and diabetes in Mexico. Our score offers a clinical tool for quick determination of high-risk susceptibility patients in a first contact scenario.

3: Effects of hypertension, diabetes and coronary heart disease on COVID-19 diseases severity: a systematic review and meta-analysis
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Posted 30 Mar 2020

Effects of hypertension, diabetes and coronary heart disease on COVID-19 diseases severity: a systematic review and meta-analysis
4,155 downloads medRxiv endocrinology

Yingyu Chen, Xiao Gong, Lexun Wang, Jiao Guo

BackgroundCOVID-19 patients with chronic diseases such as hypertension, diabetes and coronary heart diseases is more likely to worsen, but with mixed results for COVID-19 severity. This meta-analysis is to analyze the correlation between hypertension, diabetes, coronary heart disease and COVID-19 disease severity. MethodsAvailable data from PubMed, Web of Science, China National Knowledge Infrastructure Database, WanFang Database and VIP Database, were analyzed using a fixed effects model meta-analysis to derive overall odds ratios (OR) with 95% CIs. Funnel plots and Beggs were used to assess publication bias. FindingsOf 182 articles found following our initial search, we assessed 34 full-text articles, of which 9 articles with 1936 COVID-19 patients met all selection criteria for our meta-analysis. No significant heterogeneity between studies. There were significant correlations between COVID-19 severity and hypertension [OR=2.3 [95% CI (1.76, 3.00), P<0.01], diabetes [OR=2.67, 95% CI (1.91, 3.74), P<0.01], coronary heart disease [OR=2.85 [95% CI (1.68, 4.84), P<0.01]. Most of the studies in the funnel plot are on the upper part and few on the base part, and are roughly symmetrical left and right. Beggs test: hypertension (Z=-0.1, P=1.0), diabetes (Z=0.73, P=0.466), coronary heart disease (Z=0.38, P=0.707), all found no publication bias. InterpretationHypertension, diabetes, and coronary heart disease can affect the severity of COVID-19. It may be related to the imbalance of angiotensin-converting enzyme 2 (ACE2) and the cytokine storm induced by Glucolipid metabolic disorders (GLMD). FundingNational Natural Science Foundation of China (No. 81830113, 81530102); Major basic and applied basic research projects of Guangdong Province of China (No. 2019B030302005); National key R & D plan "Research on modernization of traditional Chinese medicine" (No. 2018YFC1704200) and Natural Science Foundation of Guangdong Province (No. 2018A030313391)

4: Thyroid function abnormalities in COVID-19 patients
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Posted 16 Jun 2020

Thyroid function abnormalities in COVID-19 patients
2,445 downloads medRxiv endocrinology

Weibin Wang, Xingyun Su, Yongfeng Ding, Weina Fan, Junwei Su, Zhendong Chen, Hong Zhao, Kaijin Xu, Qin Ni, Xiaowei Xu, Yunqing Qiu, Lisong Teng

Background: The novel coronavirus COVID-19, has caused a worldwide pandemic, impairing several human organs and systems. Whether COVID-19 affects human thyroid function remains unknown. Methods: 84 hospitalized COVID-19 patients in the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou, China) were respectively enrolled in this study. In addition, 91 other patients with pneumonia and 807 healthy subjects were included as controls. Findings: We found that the levels of TT3 and TSH were lower in COVID-19 patients than control groups (p<0.001). Within the group of COVID-19 patients, 61.9% patients (52/84) presented with thyroid function abnormalities. We found a larger proportion of patients in severe condition exhibited thyroid dysfunction than mild/moderate cases (74.6% vs. 23.8%, p < 0.001). Patients with thyroid dysfunction tended to have increased interval time for negative conversion of viral nucleic acid (14.1 {+/-} 9.4 vs. 10.6 {+/-} 8.3 days, p = 0.088). To note, thyroid dysfunction was also associated with decreased lymphocytes (p < 0.001) and increased CRP (p = 0.002). In 7 patients with dynamic changes of thyroid function, we observed the levels of TT3 and TSH gradually increased and reached normal range without thyroid hormone replacement at Day 30 post-admission. The correlation between TT3 and TSH level seemed to be positive rather than negative in the early stage, and gradually turned to be negatively related over time. Interpretations: Thyroid function abnormalities are common in COVID-19 patients, especially in severe cases. This might be caused by virus attack and damage to the thyroid-pituitary axis. Therefore, more attention should be paid to thyroid function during treatment of COVID-19, and close follow-up is also needed after discharge.

5: Low serum 25-hydroxyvitamin D (25D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice.
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Posted 23 Jun 2020

Low serum 25-hydroxyvitamin D (25D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice.
2,213 downloads medRxiv endocrinology

Grigorios Panagiotou, Su Ann Tee, Yasir Ihsan, Waseem Athar, Gabriella Marchitelli, Donna Kelly, Christopher S. Boot, Nadia Stock, Jim Macfarlane, Adrian R. R. Martineau, Graham Paul Burns, Richard Quinton

Objectives: To audit implementation of a local protocol for the treatment of vitamin D deficiency (VDD) among patients hospitalized for Coronavirus Disease 2019 (COVID-19), including an assessment of the prevalence of VDD in these patients, and of potential associations with disease severity and fatality. Design: This was not a study or clinical trial, but rather a retrospective interim audit (Newcastle-upon-Tyne Hospitals Registration No. 10075) of a local clinical care pathway for hospitalized patients with COVID-19-related illness. The Information (Caldicott) Guardian permitted these data to be shared beyond the confines of our institution. Setting: A large tertiary academic NHS Foundation Trust in the North East of England, UK, providing care to COVID-19 patients. Participants: One hundred thirty-four hospitalized patients with documented COVID-19 infection. Main outcome measures: Adherence to local investigation and treatment protocol; prevalence of VDD, and relationship of baseline serum 25(OH)D with markers of COVID-19 severity and inpatient fatality versus recovery. Results: 55.8% of eligible patients received Colecalciferol replacement, albeit not always loaded as rapidly as our protocol suggested, and no cases of new hypercalcaemia occurred following treatment. Patients admitted to ITU were younger than those managed on medical wards (61.1 years +/- 11.8 vs. 76.4 years +/- 14.9, p<0.001), with greater prevalence of hypertension, and higher baseline respiratory rate, National Early Warning Score-2 and C-reactive protein level. While mean serum 25(OH)D levels were comparable [i.e. ITU: 33.5 nmol/L +/- 16.8 vs. Non-ITU: 48.1 nmol/L +/- 38.2, mean difference for Ln-transformed-25(OH)D: 0.14, 95% Confidence Interval (CI) (-0.15, 0.41), p=0.3], only 19% of ITU patients had 25(OH)D levels greater than 50 nmol/L vs. 39.1% of non-ITU patients (p=0.02). However, we found no association with fatality, potentially due to small sample size, limitations of no-trial data and, potentially, the prompt diagnosis and treatment of VDD. Conclusions: Subject to the inherent limitations of observational (non-trial) audit data, analysed retrospectively, we found that patients requiring ITU admission were more frequently vitamin D deficient than those managed on medical wards, despite being significantly younger. Larger prospective studies and/or clinical trials are needed to elucidate the role of vitamin D as a preventive and/or therapeutic strategy for mitigating the effects of COVID-19 infection in patients with VDD.

6: Vitamin D status and seroconversion for COVID-19 in UK healthcare workers who isolated for COVID-19 like symptoms during the 2020 pandemic.
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Posted 06 Oct 2020

Vitamin D status and seroconversion for COVID-19 in UK healthcare workers who isolated for COVID-19 like symptoms during the 2020 pandemic.
1,874 downloads medRxiv endocrinology

Aduragbemi A Faniyi, Sebastian T Lugg, Sian E Faustini, Craig Webster, Joanne E Duffy, Martin Hewison, Adrian Shields, Peter Nightingale, Alex G Richter, David R Thickett

BackgroundIt is clear that in UK healthcare workers, COVID-19 infections and deaths were more likely to be in staff who were of BAME origin. This has led to much speculation about the role of vitamin D in healthcare worker COVID-19 infections. We aimed to determine the prevalence of vitamin D deficiency in NHS staff who have isolated with symptoms suggestive of COVID-19 and relate this to vitamin D status. MethodsWe recruited NHS healthcare workers between 12th to 22nd May 2020 as part of the COVID-19 convalescent immunity study (COCO). We measured anti-SARS-Cov-2 antibodies using a combined IgG, IgA and IgM ELISA (The Binding Site). Vitamin D status was determined by measurement of serum 25(OH)D3 using the AB SCIEX Triple Quad 4500 mass spectrometry system. FindingsOf the 392 NHS healthcare workers, 214 (55%) had seroconverted for COVID-19. A total of 61 (15.6%) members of staff were vitamin D deficient (<30 nmol/l) with significantly more staff from BAME backgrounds or in a junior doctor role being deficient. Vitamin D levels were lower in those who were younger, had a higher BMI (>30 kg/m2), and were male. Multivariate analysis revealed that BAME and COVID-19 seroconversion were independent predictors of vitamin D deficiency. Staff who were vitamin D deficient were more likely to self-report symptoms of body aches and pains but importantly not the respiratory symptoms of cough and breathlessness. Vitamin D levels were lower in those COVID-19 positive staff who reported fever, but this did not reach statistical significance. Within the whole cohort there was an increase in seroconversion in staff with vitamin D deficiency compared to those without vitamin D deficiency (n=44/61, 72% vs n=170/331, 51%; p=0{middle dot}003); this was particularly marked in the proportion of BAME males who were vitamin D deficient compared to non-vitamin D deficient BAME males (n=17/18, 94% vs n=12/23, 52%; p=0{middle dot}005). Multivariate analysis revealed that vitamin D deficiency was an independent risk factor for seroconversion (OR 2{middle dot}6, 95%CI 1{middle dot}41-4{middle dot}80; p=0{middle dot}002). InterpretationIn those healthcare workers who have isolated due to symptoms of COVID-19, those of BAME ethnicity are at the highest risk of vitamin D deficiency. Vitamin D deficiency is a risk factor for COVID-19 seroconversion for NHS healthcare workers especially in BAME male staff. FundingThis study was funded internally by the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust and supported by the National Institute for Health Research (NIHR)/Wellcome Trust Birmingham Clinical Research Facility. AAF and DRT are funded by the Medical Research Council (MR/S002782/1). The Binding Site (Edgbaston, UK) have provided reagents and plates for the SARS-CoV-2 ELISA free of charge. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThe ongoing COVID-19 pandemic has raised several questions, one of which is whether individuals with vitamin D deficiency were at a greater risk of being infected or having a severe outcome if infected. Among UK healthcare workers, and indeed the general population, individuals of BAME ethnicity are disproportionately affected by COVID-19. It is well established that individuals of BAME ethnicity have a higher prevalence of vitamin D deficiency, but it is unknown if vitamin D deficiency among UK NHS workers was connected to the risk of COVID-19 infection. Our search of the literature revealed no previous studies have established the prevalence of vitamin D deficiency within a UK NHS trust. Unsurprisingly, there is also no evidence to suggest if vitamin D deficiency was connected to the risk of infection among UK healthcare workers. Added value of this studyIn this study of healthcare workers who had isolated for COVID-19 symptoms towards the end of UK surge within a large UK NHS trust, 15.6% were vitamin D deficient. Our data also reveal that healthcare workers of BAME ethnicity and those who had seroconverted for COVID-19 were more likely to be vitamin D deficient. Multivariate analysis also show that vitamin D deficiency was the only predictor of COVID-19 seroconversion. Vitamin D deficient healthcare workers that are BAME and male had a 94% seroconversion for COVID-19 compared to non-deficient BAME males suggesting they are more at risk of COVID-19 if vitamin D deficient. Implications of all the available evidenceThere is an increased risk of COVID-19 infection in healthcare workers with vitamin D deficiency. Our data adds to the emerging evidence from studies in the UK and across the globe that individuals with severe COVID-19 are more vitamin D deficient than those with mild disease. Finally, ours and the available evidence demonstrate vitamin D supplementation in individuals at risk of vitamin D deficiency or shown to be deficient may help alleviate the impact of COVID-19.

7: Blood glucose levels in elderly subjects with type 2 diabetes during COVID-19 outbreak: a retrospective study in a single center
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Posted 02 Apr 2020

Blood glucose levels in elderly subjects with type 2 diabetes during COVID-19 outbreak: a retrospective study in a single center
1,643 downloads medRxiv endocrinology

Ting Xue, Qianwen Li, Qiongyao Zhang, Wei Lin, Junping Wen, Li Li, Gang Chen

AimsIdeal glycemic control is of great importance for diabetic patients during public health emergencies of infectious diseases as long-term hyperglycemic are not only associated with chronic complications but also vital drivers of common and life-threatening infections. The present study was designed to investigate the changes of blood glucose levels in elderly subjects with type 2 diabetes(T2D) during COVID-19 outbreak. MethodsThis retrospective study focused on the T2D outpatients at Fujian Provincial Hospital aged 65 years old and above who received baseline test for fasting plasma glucose and/or glycated hemoglobin (HbA1c) between January 1, 2019 and March 8, 2019 and were followed up on fasting plasma glucose and/or HbA1c in the same period in 2020. The baseline and follow-up data were analyzed with the paired-samples T-test. ResultsA total of 135 elderly subjects with T2D with baseline and follow-up fasting plasma glucose and 50 elderly subjects with T2D with baseline and follow-up HbA1c were analyzed, respectively. The baseline and follow-up fasting plasma glucose were 7.08 {+/-} 1.80 and 7.48{+/-}2.14 mmol/L, respectively (P=0.008). The baseline and follow-up HbA1c were 7.2{+/-}1.7% and 7.4{+/-}1.8%, respectively (P=0.158). ConclusionsElderly subjects with T2D had higher fasting plasma glucose levels during COVID-19 outbreak. We should pay more attension to the management of diabetics during public health emergencies.

8: Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes
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Posted 14 Oct 2020

Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes
1,588 downloads medRxiv endocrinology

Robert Wagner, Martin Heni, Adam G. Tabak, Jürgen Machann, Fritz Schick, Elko Randrianarisoa, Martin Hrabě de Angelis, Andreas L. Birkenfeld, Norbert Stefan, Andreas Peter, Hans-Ulrich Häring, Andreas Fritsche

The state of intermediate hyperglycemia is indicative of elevated risk of developing type 2 diabetes1. However, the current definition of prediabetes neither reflects subphenotypes of pathophysiology of type 2 diabetes nor is it predictive of future metabolic trajectories. We used partitioning on variables derived from oral glucose tolerance tests, MRI measured body fat distribution, liver fat content, and genetic risk in a cohort of extensively phenotyped individuals who are at increased risk for type 2 diabetes2,3 to identify six distinct clusters of subphenotypes. Three of the identified subphenotypes have increased glycemia (clusters 3, 5 and 6), but only individuals in clusters 5 and 3 have immanent diabetes risks. By contrast, those in cluster 6 have moderate risk of type 2 diabetes, but an increased risk of kidney disease and all-cause mortality. Findings were replicated in an independent cohort using simple anthropomorphic and glycemic constructs4. This proof-of-concept study demonstrates that pathophysiological heterogeneity exists before diagnosis of type 2 diabetes and highlights a group of individuals who have an increased risk of complications without rapid progression to overt type 2 diabetes.

9: Short-term versus 6-week prednisone in the treatment of subacute thyroiditis: a randomized controlled trial
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Posted 20 Feb 2020

Short-term versus 6-week prednisone in the treatment of subacute thyroiditis: a randomized controlled trial
1,469 downloads medRxiv endocrinology

Lian Duan, Xiaoli Feng, Rui Zhang, Xiaojuan Tan, Xiaoyan Xiang, Rufei Shen, Hongting Zheng

BackgroundModerate-to-severe subacute thyroiditis is commonly treated with 6-8 weeks glucocorticoids; however, no studies have described short-term prednisone treatment for subacute thyroiditis. We evaluated the efficacy of this treatment for subacute thyroiditis. MethodsThis was a 24-week, prospective, single-blind, randomized controlled study. Patients aged 18-70 years with subacute thyroiditis were hospitalized from August 2013 to December 2014. Patients with moderate-to-severe symptoms were randomized to receive either 30 mg/d prednisone for 1 week and then switched to 1 week of nonsteroidal anti-inflammatory drugs or 6 weeks of prednisone. The primary endpoints were the differences in efficacy at the end of treatment between two groups. Secondary endpoints included differences between the two groups in parameters of side effects at withdrawal and thyroid function at weeks 6, 12, 24. ResultsOf 96 patients screened, 52 subjects were randomized and 50 completed the study. Efficacy and recurrence rates were not significantly different at withdrawal in both groups (P=0.65). Parathyroid hormone (28.8 vs 38.9 pg/ml, p=0.011) and mean systolic blood pressure (113.9 vs 122.4 mmHg, p=0.023) were significantly lower in the experimental group than in the control group at discontinuation. No significant differences were observed in other secondary endpoints at withdrawal and in thyroid function at the 6th, 12th and 24th week during the follow-up time between the two groups. ConclusionsFewer side effects of glucocorticoids and similar efficacy and recurrence rates were observed with short-term prednisone compared with those with 6-week treatment for subacute thyroiditis. Short-term prednisone with a better safety profile may be as one alternative strategy for ameliorating moderate-to-severe symptoms of subacute thyroiditis. Trial registrationTrial registration number NCT01837433. Registered with Clinicaltrials.gov on 23 April 2013

10: Impact of COVID-19 on diagnoses, monitoring and mortality in people with type 2 diabetes: a UK-wide cohort study involving 14 million people in primary care
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Posted 27 Oct 2020

Impact of COVID-19 on diagnoses, monitoring and mortality in people with type 2 diabetes: a UK-wide cohort study involving 14 million people in primary care
1,428 downloads medRxiv endocrinology

Matthew J Carr, Alison K. Wright, Lalantha Leelarathna, Hood Thabit, Nicola Milne, Naresh Kanumilli, Darren M. Ashcroft, Martin K Rutter

AIMSTo compare trends in diagnoses, monitoring and mortality in patients with type 2 diabetes, before and after the first COVID-19 peak. METHODSWe constructed a cohort of 25 million patients using electronic health records from 1831 UK general practices registered with the Clinical Practice Research Datalink (CPRD), including 14 million patients followed between March and December 2020. We compared trends using regression models and 10-year historical data. We extrapolated the number of missed/delayed diagnoses using UK Office for National Statistics data. RESULTSIn England, rates of new type 2 diabetes diagnoses were reduced by 70% (95% CI 68%-71%) in April 2020, with similar reductions in Northern Ireland, Scotland and Wales. Between March and December, we estimate that there were approximately 60,000 missed/delayed diagnoses across the UK. In April, rates of HbA1c testing were greatly reduced in England (reduction: 77% (95% CI 76%-78%)) with more marked reductions in the other UK nations (83% (83-84%)). Reduced rates of diagnosing and monitoring were particularly evident in older people, in males, and in those from deprived areas. In April, the mortality rate in England was more than 2-fold higher (112%) compared to prior trends, but was only 65% higher in Northern Ireland, Scotland and Wales. CONCLUSIONSAs engagement increases, healthcare services will need to manage the backlog and anticipate greater deterioration of glucose control due to delayed diagnoses and reduced monitoring in those with pre-existing diabetes. Older people, men, and those from deprived backgrounds will be groups to target for early intervention. RESEARCH IN CONTEXTO_ST_ABSWhat is already known about this subject?C_ST_ABSO_LIThe higher COVID-related death rate in people with diabetes has been well-documented C_LIO_LIA study involving the residents of Salford, UK showed 135 fewer diagnoses of type 2 diabetes than expected between March and May 2020, which amounted to a 49% reduction in activity C_LIO_LIThere is limited data on the impact of the COVID-19 pandemic on the diagnosis and monitoring of type 2 diabetes C_LI What is the key question?O_LIWhat has been the impact of the COVID-19 pandemic on the diagnosis and monitoring of type 2 diabetes across the UK? C_LI What are the new findings?O_LIAcross the UK, the rate of new type 2 diabetes diagnoses was reduced by up to 70% in April 2020 compared to 10-year historical trends C_LIO_LIBetween March and December 2020, it is estimated that 60,000 people have had a missed or delayed diagnosis C_LIO_LIThe frequency of HbA1c monitoring in type 2 diabetes was reduced by 77-83% in April 2020 and by 31-37% overall between March and December 2020 C_LI How might this impact on clinical practice in the foreseeable future?O_LIDuring this pandemic and associated lockdowns, effective public communications should ensure that patients remain engaged with diabetes services including HbA1c screening and monitoring C_LI

11: Severe obesity is associated with higher in-hospital mortality in a cohort of patientswith COVID-19 in the Bronx, New York
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Posted 09 May 2020

Severe obesity is associated with higher in-hospital mortality in a cohort of patientswith COVID-19 in the Bronx, New York
1,061 downloads medRxiv endocrinology

Leonidas Palaiodimos, Damianos G. Kokkinidis, Weijia Li, Dimitrios Karamanis, Jennifer Ognibene, Shitij Arora, William N. Southern, Christos S. Mantzoros

Background & Aims: New York is the current epicenter of Coronavirus disease 2019 (COVID-19) pandemic. The underrepresented minorities, where the prevalence of obesity is higher, appear to be affected disproportionately. Our objectives were to assess the characteristics and early outcomes of patients hospitalized with COVID-19 in the Bronx and investigate whether obesity is associated with worse outcomes. Methods: This retrospective study included the first 200 patients admitted to a tertiary medical center with COVID-19. The electronic medical records were reviewed at least three weeks after admission. The primary endpoint was in-hospital mortality. Results: 200 patients were included (female sex: 102, African American: 102). The median BMI was 30 kg/m2. The median age was 64 years. Hypertension (76%), hyperlipemia (46.2%), and diabetes (39.5%) were the three most common comorbidities. Fever (86%), cough (76.5%), and dyspnea (68%) were the three most common symptoms. 24% died during hospitalization (BMI <25 kg/m2: 31.6%, BMI 25-34 kg/m2: 17.2%, BMI[&ge;]35 kg/m2: 34.8%, p= 0.03). The multivariate analysis for mortality, demonstrates that BMI[&ge;]35 kg/m2 (OR: 3.78; 95% CI: 1.45 - 9.83; p=0.006), male sex (OR: 2.74; 95% CI: 1.25 - 5.98; p=0.011) and increasing age (OR: 1.73; 95% CI: 1.13 - 2.63; p=0.011) were independently associated with higher inhospital mortality. Similar results were obtained for the outcomes of increasing oxygen requirement and intubation. Conclusions: In this cohort of hospitalized patients with COVID-19 in a minority-predominant population, severe obesity, increasing age, and male sex were associated with higher in-hospital mortality and in general worse in-hospital outcomes.

12: A Pilot Study on the Effects of Medically Supervised, Water-Only Fasting and Refeeding on Cardiometabolic Risk
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Posted 12 Aug 2020

A Pilot Study on the Effects of Medically Supervised, Water-Only Fasting and Refeeding on Cardiometabolic Risk
1,020 downloads medRxiv endocrinology

Eugene L Scharf, Patricia Kolbe, Su-Yeon Hwang, Natasha Thompson, Mara Gilbert, Faye Alexandrakis, Matthieu Bonjour, Evelyn Zeiler, Toshia R Myers

The Fasting for Brain and Heart Health Study was a prospective, single-center, observational study examining the effects of medically supervised, water-only fasting followed by an exclusively whole-plant-food refeeding diet on accepted measures of cardiovascular risk and metabolic health. The study enrolled 48 overweight/obese, non-diabetic participants of which 26 completed the full study protocol. The participants fasted according to an established protocol at an independent medical center that reported mean fast and refeed lengths of 17 and 7 days, respectively. The primary endpoint was to describe mean glucose tolerance as indicated by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) scores at baseline, end-of-fast (EOF), and end-of-refeed (EOR) visits. Secondary endpoints were to describe the effects of fasting and refeeding on accepted markers of cardiovascular risk. Here we show that medically supervised, water-only fasting and/or whole-plant-food refeeding reduced resting systolic blood pressure (SBP), abdominal circumference, low-density lipoprotein (LDL), and high-sensitivity C-reactive protein (hsCRP) after refeeding. An increase in HOMA-IR scores at EOR was also observed.

13: The clinical outcomes and effectiveness of mHealth interventions for diabetes and hypertension: a systematic review and meta-analysis
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Posted 23 Feb 2020

The clinical outcomes and effectiveness of mHealth interventions for diabetes and hypertension: a systematic review and meta-analysis
1,004 downloads medRxiv endocrinology

Yaqian Mao, Wei Lin, Junping Weng, Gang Chen

BackgroundWith the development of technology, mobile health (mHealth) intervention has been proposed as a treatment strategy for chronic diseases that could improve the quality of chronic care and outcomes in some developed countries. However, the effectiveness of mHealth intervention in developing countries is not clear. PurposeA systematic review and meta-analysis was conducted to study the clinical outcomes and effectiveness of mHealth interventions for diabetes and hypertension in countries with different levels of economic development. MethodsPubmed, ResearchGate, Embase and Cochrane documents were searched by computer, and the retrieval period was from 2008 to June 2019. All studies were randomized controlled trials (RCTs) comparing mHealth treatments to other traditional treatments. Meta-analysis was conducted using stata software. Results51 RCTs (N=13,054 participants) were eligible for this systematic review and meta-analysis. Compared with the usual care, the mHealth interventions yielded significant mean differences in clinical outcomes, and had a positive effect on countries at different levels of economic development. It is reassuring that we found mHealth interventions combined with human intelligence could significantly improve clinical outcomes more than mHealth interventions alone [WMD (95%Cl)=-6.75 (-9.98, -3.52)] VS [WMD (95%Cl)=-2.53 (-4.99, -0.07)]. The main secondary outcomes showed that mHealth interventions could also improve quality of life, satisfaction and self-efficacy, etc. ConclusionThis review shown that mHealth interventions as a therapeutic strategy could improve the management of diabetes and hypertension in countries with different levels of economic development. O_TEXTBOXWhat is already known about this subject?O_LIWith the development of technology, mobile health (mHealth) intervention has been proposed as a treatment strategy for chronic diseases that could improve the quality of chronic care in some developed countries. C_LIO_LINowdays, there are many mHealth products on the market, whether these mHealth products can improve the patients clinical results or improve the quality of life are still lack of research. C_LI What are the new findings?O_LImHealth interventions as a therapeutic strategy could improve the management of diabetes and hypertension in countries with different levels of economic development. C_LIO_LImHealth interventions combined with human intelligence could significantly improve clinical outcomes more than mHealth interventions alone. C_LI How might these results change the focus of research or clinical practice?O_LImobile health (mHealth) intervention can as a treatment strategy for chronic diseases, especially in the undeveloped places. C_LIO_LImHealth intervention treatments combined with special staff management (pharmacist, dietitian, specialist nurse and sports trainer) had more effective than mHealth interventions alone. C_LI C_TEXTBOX

14: Effects of a DPP-4 inhibitor and RAS blockade on clinical outcomes of patients with diabetes and COVID-19
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Posted 23 May 2020

Effects of a DPP-4 inhibitor and RAS blockade on clinical outcomes of patients with diabetes and COVID-19
969 downloads medRxiv endocrinology

Sang Youl Rhee, Jeongwoo Lee, Hyewon Nam, Dae-Sung Kyoung, Dae Jung Kim

Background: Dipeptidyl peptidase-4 inhibitor (DPP-4i) and renin-angiotensin system (RAS) blockade are reported to affect the clinical course of coronavirus disease 2019 (COVID-19) in patients with diabetes mellitus (DM). However, the effectiveness of these drugs in large populations is unclear. Subjects and Methods: As of May 2020, data analysis was conducted on all subjects who could confirm their history of claims related to COVID-19 in the National Health Review and Assessment Service database in Korea. Using the COVID-19 and claims data of the past 5 years, we compared the short-term prognosis of COVID-19 infection according to the use of DPP-4i and RAS blockade. Results: Totally, data of 67850 subjects were accessible. Of these, 5080 were confirmed COVID-19. Among these, 832 subjects with DM were selected for analysis in this study. Among the subjects, 263 (31.6%) and 327 (39.3%) were DPP-4i and RAS blockade users, respectively. Thirty-four subjects (4.09%) received intensive care or died. The adjusted odds ratio for severe treatment among DPP-4i users was 0.362 [95% confidence interval (CI), 0.135-0.971], and that for RAS blockade users was 0.599 (95% CI, 0.251-1.431). No synergy was observed for subjects using both drugs. Conclusion: This population-based study suggests that DPP-4i is significantly associated with a better clinical outcome of patients with COVID-19. However, the effect of RAS blockade is not significant.

15: Prevalence of diabetic peripheral neuropathy in Africa: A systematic review and meta-analysis
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Posted 25 Sep 2019

Prevalence of diabetic peripheral neuropathy in Africa: A systematic review and meta-analysis
960 downloads medRxiv endocrinology

Wondimeneh Shibabaw Shiferaw, Tadesse Yirga, Yeshamble Work, Yared Asmare Aynalem

IntroductionDiabetes mellitus is a global health care problem and financially costly. Diabetic peripheral neuropathy is common and frequent cause of morbidity and disability. Despite its serious complications, limited evidence is available on the magnitude of diabetic peripheral neuropathy among patient with diabetes mellitus. Hence, the objective of this systematic review and meta-analysis was to estimate the pooled prevalence of diabetic peripheral neuropathy among patients with diabetes mellitus in Africa. MethodsPubMed, Scopus, Google Scholar, Africa journal online, WHO afro library and Cochrane review were systematically searched online to retrieve related articles. The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline was followed. Heterogeneity across the included studies was evaluated by inconsistency index (I2). Publication bias was examined by funnel plot and Eggers regression test. The random-effect model was fitted to estimate the pooled prevalence of diabetic peripheral neuropathy among diabetes mellitus patients. All statistical analysis was done using STATA version 14 software for windows. ResultsTwenty-three studies which comprises of 269,691 participants were included in the meta-analysis. The overall pooled prevalence of diabetic peripheral neuropathy was 46% (95% CI:36.21-55.78%). Based on the subgroup analysis, the highest magnitude of diabetic peripheral neuropathy was reported in West Africa 49.4% (95% CI: 32.74, 66.06). ConclusionThis study revealed that the overall prevalence of diabetic peripheral neuropathy is relatively high in Africa. Hence, diabetic peripheral neuropathy needs situation based intervention and preventive strategy depending on their country context. Furthermore, further meta-analysis study is needed to identify associated factors for the occurrence of diabetic peripheral neuropathy.

16: Prevalence of diabetic foot ulcer and its association with duration of illness and residence in Ethiopia: a systematic review and meta-analysis.
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Posted 13 Aug 2019

Prevalence of diabetic foot ulcer and its association with duration of illness and residence in Ethiopia: a systematic review and meta-analysis.
923 downloads medRxiv endocrinology

Henok Mulugeta, Fasil Wagnew, Haymanot Zeleke, Bekele Tesfaye, Haile Amha, Cheru Tesema Leshargie, Henok Biresaw, Getenet Dessie, Yihalem Abebe Belay, Tesfa Dejenie Habtewold

BackgroundDiabetic foot ulcer (DFU), devastating complications of diabetes mellitus, is a major public health problem, and one of the leading reasons for hospital admission, amputations, and even death among diabetic patients in Ethiopia. Despite its catastrophic health consequences, the national burden of diabetic foot ulcer remains unknown in Ethiopia. Hence, the objective of this systematic review and meta-analysis was to estimate the national prevalence of diabetic foot ulcer and investigate the association with duration of illness and patient residence among diabetic patients. MethodsWe searched PubMed, Google Scholar, Cochrane Library, CINAHL, EMBASE, and PsycINFO databases for studies of diabetic foot ulcers prevalence that published from conception up to June 30, 2019. Quality of each article was assessed using a modified version of the Newcastle-Ottawa Scale for cross-sectional studies. All statistical analyses were done using STATA version 14 software for Windows, and meta-analysis was carried out using a random-effects method. The pooled national prevalence of diabetic foot ulcers was presented using a forest plot. ResultsA total of 10 studies with 3,029 diabetic patients were included. The pooled national prevalence of diabetic foot ulcers among Ethiopian diabetic patients was 11.27% (95% CI 7.22, 15.31%, I2=94.6). Duration of illness (OR: 3.91, 95%CI 2.03, 7.52, I2=63.4%) and patients residence (OR: 3.40, 95%CI 2.09, 5.54, I2=0.0%) were significantly associated with a diabetic foot ulcer. ConclusionIn Ethiopia, at least one out of ten diabetic patients had diabetic foot ulcers. Healthcare policymakers (FMoH) need to improve the standard of diabetic care and should design effective preventive strategies to improve health care delivery for people with diabetes and reduce the risk of foot ulceration.

17: Extensive weight loss can reduce immune age by altering IgG N-glycosylation
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Posted 29 Apr 2020

Extensive weight loss can reduce immune age by altering IgG N-glycosylation
870 downloads medRxiv endocrinology

Valentina L Greto, Ana Cvetko, Tamara Štambuk, Niall J Dempster, Domagoj Kifer, Helena Deriš, Ana Cindrić, Frano Vučković, Mario Falchi, Richard S Gillies, Jeremy W Tomlinson, Olga Gornik, Bruno Sgromo, Timothy Spector, Cristina Menni, Alessandra Geremia, Carolina V Arancibia-Carcamo, Gordan Lauc

Obesity is a major global health problem and is associated with increased cardiometabolic morbidity and mortality. Protein glycosylation is a frequent posttranslational modification, highly responsive to numerous pathophysiological conditions and aging. The prospect of biological age reduction, by reverting glycosylation changes through metabolic intervention, opens many possibilities. We have investigated whether weight loss interventions affect inflammation- and aging-associated IgG glycosylation changes, in a longitudinal cohort of bariatric surgery patients. To support potential findings, BMI-related glycosylation changes were monitored in a longitudinal twins cohort. IgG N-glycans were chromatographically profiled in 37 obese patients, subjected to a low-calorie diet, followed by bariatric surgery, across multiple timepoints. Similarly, plasma-derived IgG N-glycan traits were longitudinally monitored in 1,680 participants from the TwinsUK cohort. Low-calorie diet induced a marked decrease in the levels of IgG N-glycans with bisecting GlcNAc, whose higher levels are usually associated with aging and inflammatory conditions. Bariatric surgery resulted in extensive alterations of the IgG glycome that accompanied progressive weight loss during a one-year follow-up. We observed a significant increase in digalactosylated and sialylated glycans, and a substantial decrease in agalactosylated and core fucosylated IgG glycans. In general, this IgG glycan profile is associated with younger biological age and reflects an enhanced anti-inflammatory IgG potential. Loss of BMI over a 20 year period in the TwinsUK cohort validated a weight loss-associated agalactosylation decrease and an increase in digalactosylation. Altogether, these findings highlight that weight loss substantially affects IgG N-glycosylation, resulting in reduced biological and immune age.

18: Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients
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Posted 28 May 2020

Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients
861 downloads medRxiv endocrinology

Leonidas Palaiodimos, Natalia Chamorro-Pareja, Dimitrios Karamanis, Weijia Li, Phaedon D Zavras, Priyanka Mathias, Damianos G. Kokkinidis

Background: Infectious diseases are more frequent and can be associated with worse outcomes in patients with diabetes. Our aim was to systematically review and synthesize with a meta-analysis the available observational studies reporting the effect of diabetes in mortality among hospitalized patients with COVID-19. Methods: Medline, Embase, Google Scholar, and medRxiv databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. In-hospital mortality was defined as the endpoint. Sensitivity, subgroup, and meta-regression analyses were performed. Results: 18,506 patients were included in this meta-analysis (3,713 diabetics and 14,793 non-diabetics). Patients with diabetes were associated with a higher risk of death compared to patients without diabetes (OR: 1.65; 95% CI: 1.35, 1.96; I2 77.4%). The heterogeneity was high. A study level meta-regression analysis was performed for all the important covariates and no significant interactions were found between the covariates and the outcome of mortality. Conclusion: This meta-analysis shows that that the likelihood of death is 65% higher in diabetic hospitalized patients with COVID-19 compared to non-diabetics. Further studies are needed to assess whether this association is independent or not, as well as to investigate to role of glucose control prior or during the disease.

19: Identifying subtypes of a stigmatized medical condition
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Posted 29 Aug 2019

Identifying subtypes of a stigmatized medical condition
810 downloads medRxiv endocrinology

Irene Gabashvili

BackgroundSome conditions - such as obesity, depression and functional odor disorders - come with a social stigma. Understanding the etiology of these conditions helps to avoid stereotypes and find remedies. One of the major obstacles facing researchers, especially for those studying socially distressing metabolic malodor, is the difficulty in assembling biologically homogenous study cohorts. ObjectiveThe aim of this study was to examine phenotypic variance, self-reported data and laboratory tests for the purpose of identifying clinically relevant and etiologically meaningful subtypes of idiopathic body odor and the "People are Allergic To Me" (PATM) syndrome. MethodsParticipants with undiagnosed body odor conditions enrolled to participate in this research study initiated by a healthcare charity MEBO Research and sponsored by Wishart Research group at the Metabolomics Innovation Centre, University of Alberta, Canada. Primary outcomes were differences in metabolite concentrations measured in urine, blood and breath of test and control groups. Principal component analyses and other statistical tests were carried out for these measurements. ResultsWhile neither of existing laboratory tests could reliably predict chronic malodor symptoms, several measurements distinguished phenotypes at a significance level less than 5%. Types of malodor can be differentiated by self-reported consumption of (or sensitivity to) added sugars (p<0.01), blood alcohols after glucose challenge (especially ethanol: p<0.0005), urinary excretion of phenylalanine, putrescine, and combinations of blood or urine metabolites. ConclusionsOur preliminary results suggest that malodor heterogeneity can be addressed by analyses of phenotypes based on patients dietary and olfactory observations. Our studies highlight the need for more trials. Future research focused on comprehensive metabolomics and microbiome sequencing will play an important role in the diagnosis and treatment of malodor. Trial RegistrationThe study discussed in the manuscript was registered as NCT02692495 at clinicaltrials.gov. The results were compared with our earlier study registered as NCT02683876.

20: Validation of multiplex steroid hormone measurements in prostate cancer using plasma for multimodality biomarker studies
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Posted 06 Aug 2020

Validation of multiplex steroid hormone measurements in prostate cancer using plasma for multimodality biomarker studies
803 downloads medRxiv endocrinology

Gido Snaterse, Lisanne F. van Dessel, Angela E Taylor, Jenny A Visser, Wiebke Arlt, Martijn P. Lolkema, Johannes Hofland

ABSTRACT Background Steroid hormones are essential signalling molecules in prostate cancer (PC). However, many studies focusing on liquid biomarkers fail to take the hormonal status of these patients into account. Steroid measurements are sensitive to bias caused by matrix effects, thus assessing potential matrix effects is an important step in combining circulating tumor DNA analysis with hormone status. Methods We investigated the accuracy of multi-steroid hormone profiling in mechanically-separated plasma (MSP) samples and in plasma from CellSave Preservative (CS) tubes, that are typically used to obtain ctDNA, compared to measurements in serum. We performed multiplex steroid profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in samples obtained from ten healthy controls and ten castration-resistant prostate cancer (CRPC) patients. Results Steroid measurements were comparable between MSP and serum. A small but consistent decrease of 8-21% compared to serum was observed when using CS plasma, which was considered to be within the acceptable margin. The minimal residual testosterone levels of CRPC patients could be sensitively quantified in both MSP and CS samples. Conclusions We validated the use of MSP and CS samples for multi-steroid profiling by LC-MS/MS. The optimised use of these samples in clinical trials will allow us to gain further insight into the steroid metabolism in PC patients.

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