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Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths.
Grant, WB, Lahore, H, McDonnell, SL, Baggerly, CA, French, CB, Aliano, JL, Bhattoa, HP
Nutrients. 2020;12(4)
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This narrative review article looks at the role of Vitamin D in reducing the risk of respiratory tract infections, in relation to the incidence and prevalence of influenza and COVID-19. It also discusses how Vitamin D testing and optimisation with supplementation might be a simple measure to reduce risk. The authors site evidence supporting the possible role of Vitamin D: the fact that the outbreak occurred in winter when Vitamin D concentrations are lowest; vitamin D deficiency has been shown to contribute to acute respiratory distress; and case fatality rates increasing with age and incidence of underlying conditions, both of which are associated with lower Vitamin D concentrations. The authors goal is to raise Vitamin D concentrations to 100-150 nmol/l. Nutrition Practitioners wanting to support overall health and resilience to seasonal viral infections may want to consider testing and supplementing Vitamin D.
Abstract
The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40-60 ng/mL (100-150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.
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Association of Blood Glucose Control and Outcomes in Patients with COVID-19 and Pre-existing Type 2 Diabetes.
Zhu, L, She, ZG, Cheng, X, Qin, JJ, Zhang, XJ, Cai, J, Lei, F, Wang, H, Xie, J, Wang, W, et al
Cell metabolism. 2020;31(6):1068-1077.e3
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The novel coronavirus disease 2019 (COVID-19) is caused by infection from the newly emerged, highly contagious coronavirus SARS-CoV-2. The aim of this study was to analyse the association between plasma glucose levels and clinic outcomes in COVID-19 patients with type 2 diabetes (T2D). The study is a retrospective longitudinal, multi-centre study from a cohort of 7,337 COVID-19 cases enrolled among 19 hospitals. Results show that patients with pre-existing T2D received significantly more intensive integrated treatments to manage their symptoms of COVID-19 than the non-diabetic subjects. Furthermore, findings indicate that well-controlled blood glucose was associated with a markedly improved outcome of patients with COVID-19 and pre-existing T2D. Authors conclude that T2D is an important risk factor for COVID-19 progression and adverse endpoints, and well-controlled blood glucose is associated with a significant reduction in the composite adverse outcomes and death.
Abstract
Type 2 diabetes (T2D) is a major comorbidity of COVID-19. However, the impact of blood glucose (BG) control on the degree of required medical interventions and on mortality in patients with COVID-19 and T2D remains uncertain. Thus, we performed a retrospective, multi-centered study of 7,337 cases of COVID-19 in Hubei Province, China, among which 952 had pre-existing T2D. We found that subjects with T2D required more medical interventions and had a significantly higher mortality (7.8% versus 2.7%; adjusted hazard ratio [HR], 1.49) and multiple organ injury than the non-diabetic individuals. Further, we found that well-controlled BG (glycemic variability within 3.9 to 10.0 mmol/L) was associated with markedly lower mortality compared to individuals with poorly controlled BG (upper limit of glycemic variability exceeding 10.0 mmol/L) (adjusted HR, 0.14) during hospitalization. These findings provide clinical evidence correlating improved glycemic control with better outcomes in patients with COVID-19 and pre-existing T2D.
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Brown Adipose Crosstalk in Tissue Plasticity and Human Metabolism.
Scheele, C, Wolfrum, C
Endocrine reviews. 2020;41(1)
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Brown adipose tissue (BAT) is an important contributor to the regulation of metabolism via cellular communication with organs such as liver, muscle, gut and central nervous system. BAT is important for heat generation and is at high levels in human infants. Levels of activation of BAT decline as we age and it has been shown that the amount of BAT is smaller and its activity reduced in those with obesity and type 2 diabetes. To date, there is no answer to efficiently restore functional BAT in aging and obese subjects. This review looks at experiments done on the factors secreted from active BAT (batokines). The review aims to provide a structure for the processes and cell types involved in BAT and the recent findings of BAT whole-body communication are discussed. Altogether, these findings demonstrate that BAT has an adaptive capacity. Studying batokines, offers an alternative approach to identify novel drug targets for metabolic regulation.
Abstract
Infants rely on brown adipose tissue (BAT) as a primary source of thermogenesis. In some adult humans, residuals of brown adipose tissue are adjacent to the central nervous system and acute activation increases metabolic rate. Brown adipose tissue (BAT) recruitment occurs during cold acclimation and includes secretion of factors, known as batokines, which target several different cell types within BAT, and promote adipogenesis, angiogenesis, immune cell interactions, and neurite outgrowth. All these processes seem to act in concert to promote an adapted BAT. Recent studies have also provided exciting data on whole body metabolic regulation with a broad spectrum of mechanisms involving BAT crosstalk with liver, skeletal muscle, and gut as well as the central nervous system. These widespread interactions might reflect the property of BAT of switching between an active thermogenic state where energy is highly consumed and drained from the circulation, and the passive thermoneutral state, where energy consumption is turned off. (Endocrine Reviews 41: XXX - XXX, 2020).
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Targeting the Adipose Tissue in COVID-19.
Malavazos, AE, Corsi Romanelli, MM, Bandera, F, Iacobellis, G
Obesity (Silver Spring, Md.). 2020;28(7):1178-1179
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A UK study showed that 72% of COVID-19 patients in critical care units had either overweight or obesity, whilst studies in Italy have shown that 99% of deaths occurred in patients who had at least one underlying chronic condition, including obesity, diabetes and hypertension. As obesity is tightly connected with diabetes and other inflammatory conditions, it is difficult to separate the effects of the obesity per se, from other chronic conditions that are commonly associated with the obesity. The authors discuss possible molecular mechanisms by which the fat tissue itself may increase the risk of more severe COVID-19 disease, such as angiotensin converting enzyme 2 (ACE2) receptors and dipeptidyl peptidase 4 (two receptors which occur in fat tissue and may be entry points of the virus into the cell) and an imbalance between the secretion of anti‐ and proinflammatory compounds from visceral fat cells. The authors conclude that the role of the adipose (fat) tissue during infectious diseases, such as COVID‐19, could be important and note that this is a modifiable risk factor.
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The impact of educational attainment on cardiorespiratory fitness and metabolic syndrome in Korean adults.
Chang, M, Lee, HY, Seo, SM, Koh, YS, Park, HJ, Kim, PJ, Seung, KB
Medicine. 2020;99(17):e19865
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Lower socioeconomic status is associated with worse health outcomes, and in particular with cardiovascular disease and metabolic syndrome. This association is thought to be mediated through lifestyle factors such as physical activity, diet and smoking. Level of education is commonly used as an indicator for socioeconomic status. This Korean cross-sectional study, involving 988 healthy adults, evaluated the association between level of education (<12 years, 12-16 years, >16 years), cardiorespiratory fitness (CRF) and metabolic syndrome. People in the highest education group were more likely to be younger and male. There was no difference in the prevalence of metabolic syndrome, hypertension or diabetes mellitus between the three educational attainment groups, 36.1% overall had metabolic syndrome. There was also no difference in dyslipidaemia, physical activity or smoking status. Whilst BMI was similar in all groups, the higher the level of education, the lower the body fat and the higher lean mass and CRF were. Although education was not associated with metabolic syndrome, better CRF was associated with lower rates of metabolic syndrome. Limitations of the study as pointed out by the authors include the retrospective design and a potentially non-representative sample.
Abstract
The aim of this study was to evaluate the relationship between educational attainment and cardiorespiratory fitness (CRF) as a predictor of metabolic syndrome in a Korean population.In this single-center, retrospective cross-sectional study, 988 healthy adults (601 men and 387 women) who underwent regular health check-up in Seoul St. Mary's Hospital were analyzed. Educational attainment was categorized into 3 groups according to their final grade of educational course: middle or high school (≤12 years of education), college or university (12-16 years of education), and postgraduate (≥16 years of education). CRF was assessed by cardiopulmonary exercise testing, biceps strength, hand grip strength, bioelectrical impedance analysis, and echocardiography. Metabolic syndrome was diagnosed according to the 3rd report of the National Cholesterol Education Program.Among the subjects, 357 (36.1%) had metabolic syndrome. The postgraduate group had significantly higher peak oxygen consumption (VO2), biceps strength, hand grip strength, and peak expiratory flow than other groups (all P < .001). This group showed better left ventricular diastolic function, in terms of deceleration time of mitral inflow, maximal tricuspid valve regurgitation velocity, and left atrial volume index than other groups. Peak VO2 (%) was significantly correlated with all the parameters of metabolic syndrome, including insulin resistance (r = -0.106, P = .002), waist circumference (r = -0.387, P < .001), triglyceride (r = -0.109, P = .001), high density lipoprotein-cholesterol (r = 0.219, P < .001), systolic blood pressure (r = -0.143, P < .001), and diastolic blood pressure (r = -0.177, P < .001). And Peak VO2 (%) was found to be a predictor of metabolic syndrome (adjusted β = .988, P < .001). However, the level of education was not able to predict metabolic syndrome (postgraduate group; β = .955, P = .801).Although the postgraduate group had better CRF than other groups, the educational attainment could not exclusively predict metabolic syndrome in this study. Further research is needed to reveal the socioeconomic mechanism of developing metabolic syndrome.
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Physical activity can reduce the prevalence of gallstone disease among males: An observational study.
Kwon, OS, Kim, YK, Her, KH, Kim, HJ, Lee, SD
Medicine. 2020;99(26):e20763
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Gallstone disease (GD) is one of the most common digestive disorders and can cause acute abdominal pain, jaundice, and abnormal liver function due to stones deposited in the gallbladder or bile ducts. Metabolic syndrome is a known risk factor for GD and physical activity (PA) can reduce the incidence of metabolic syndrome. The aim of this observational study was to evaluate whether PA can reduce the risk of GD in a Korean population. 8908 subjects were included in this study, GD was diagnosed by ultrasound and PA was defined as moderate-intensity aerobic PA for at least 150 minutes, or vigorous-intensity activity for at least 75 minutes throughout the week. Participants underwent physical investigation and had blood samples taken to establish metabolic syndrome markers. In men, PA, old age and higher AST (aspartate aminotransferase, a liver enzyme) were independent risk factors for GD, whilst in women only a history of non-alcoholic fatty liver disease, but not PA, was independently associated with GD.
Abstract
Several previous studies have reported that physical activity (PA) levels can independently affect the prevalence of gallstone disease (GD) in Western countries. However, this association has not been reported in Eastern countries. Therefore, this study aimed to determine whether PA is an independent determinant of GD prevalence in a Korean population, according to the World Health Organizations Global Recommendations on PA for Health.A total of 8908 subjects who completed a questionnaire underwent medical examination and ultrasound scanning at the Health Promotion Center of the Jeju National University Hospital between January 2009 and December 2018. GD and fatty liver disease were diagnosed by abdominal ultrasound. Biochemical parameters and body mass index were determined, and metabolic syndrome status, age, and PA levels were extracted from medical records. Univariate and multivariate analyses were performed to identify independent factors affecting GD.The estimated rates of PA and GD among male subjects were 23.7% and 4.6%, whereas the rates among females were 18.4% and 4.2%, respectively. Multivariate analysis suggested that no PA, old age, and higher aspartate aminotransferase level in males and nonalcoholic fatty liver disease status in females were independent factors affecting GD.In our study, PA was associated with a reduction in GD among males but not females.
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A cross-sectional study: Associations between sarcopenia and clinical characteristics of patients with type 2 diabetes.
Cui, M, Gang, X, Wang, G, Xiao, X, Li, Z, Jiang, Z, Wang, G
Medicine. 2020;99(2):e18708
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Sarcopenia is characterised by the loss of muscle mass, decrease of muscle strength and decline of physical performance and is related to reduced physical ability, impaired cardiorespiratory function, disability and death in the elderly. Type 2 diabetics are at higher risk of developing sarcopenia. The aim of this cross-sectional study was to evaluate clinical characteristics of sarcopenia in elderly type 2 diabetics in the Northeast of China. 132 participants completed the study which was based on self-reported medical and lifestyle history, and clinical evaluations including measurements of weight, height and muscle strength, imaging to establish sarcopenia and blood tests. 28.8% of participants had sarcopenia. Age, increased truncal fat mass and increased free thyroxine increased the risk of sarcopenia, whilst regular exercise, being female, taking metformin, a higher body mass index and increased trunk skeletal mass were associated with a lower risk of sarcopenia. The authors point out that limitations include the small sample size and that, as this is a cross-sectional study, cause and effect cannot be established.
Abstract
Sarcopenia is a geriatric syndrome and it impairs physical function. Patients with type 2 diabetes mellitus (T2DM) are at a higher risk of sarcopenia. The purpose of this study is to explore characteristics of general information and metabolic factors of sarcopenia in patients with T2DM in the northeast of China, and provide information for the prevention and treatment of sarcopenia in clinical practice.Patients with T2DM aged ≥65 were recruited in Changchun from March 2017 to February 2018. Questionnaires of general information, physical examination, laboratory and imaging examination were conducted. The patients were assigned into sarcopenia group and non-sarcopenia group according to the diagnostic criteria proposed by Asian working group for sarcopenia (AWGS), and the differences between 2 groups were analyzed.A total of 132 participants were included in this study, of which, 38 (28.8%) were diagnosed with sarcopenia. 94 (71.2%) were with no sarcopenia. Logistic regression analysis showed that age (OR: 1.182, 95%CI: 1.038-1.346), trunk fat mass (TFM) (OR: 1.499, 95%CI: 1.146-1.960) and free thyroxine (FT4) (OR: 1.342, 95%CI: 1.102-1.635) were independent risk factors for sarcopenia. BMI (body mass index) (OR: 0.365, 95%CI: 0.236-0.661), exercise (OR: 0.016, 95%CI: 0.001-0.169), female (OR: 0.000, 95%CI: 0.00-0.012), metformin (OR: 0.159, 95%CI: 0.026-0.967) and TSM (trunk skeletal muscle mass) (OR: 0.395, 95%CI: 0.236-0.661) were protective factors for sarcopenia.Sarcopenia in patients with T2DM is associated with increased age, increased TFM and increased FT4 level. Regular exercise, female, metformin administrations, high BMI and increased TSM are associated with lower risk of sarcopenia.
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Play as a Method to Reduce Overweight and Obesity in Children: An RCT.
Sánchez-López, AM, Menor-Rodríguez, MJ, Sánchez-García, JC, Aguilar-Cordero, MJ
International journal of environmental research and public health. 2020;17(1)
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Obesity in children is increasing and is associated with an increased risk of ill health in adulthood. Both changes in dietary habits and a more sedentary lifestyle in children play an important role. The aim of this randomised study was to evaluate an intervention based on play on the body composition of overweight or obese children aged 8-12 years. The intervention consisted of physical activity based on play, with four 90 min sessions per week for nine months. Both the intervention and the control group received twice-monthly theoretical and practical nutritional advice, given to the children and their families. BMI, weight and body fat decreased in the intervention group and increased in the control group.
Abstract
BACKGROUND Overweight and obesity are the result of a complex interaction between genetic and environmental factors, which begins prenatally. AIM: To analyse an intervention based on play as a means of improving the body composition of children who are overweight or obese. METHODS The Kids-Play study is a randomized clinical trial (RCT) consisting of 49 children aged 8-12 years on a nine-month intervention programme based on physical activity, play and nutritional advice. Controls had another 49 children, who received only nutritional advice. RESULTS The play-based intervention achieved a moderate-vigorous level of physical activity in the study group of 81.18 min per day, while the corresponding level for the control group was only 37.34 min. At the start of the intervention, the children in the study group had an average body fat content of 41.66%, a level that decreased to 38.85% by the end of the programme. Among the control group, body fat increased from 38.83% to 41.4% during the same period. CONCLUSIONS The intervention programme considered, based on both play and nutritional recommendations, produced a decrease in body fat among children aged 8-12 years. However, the control group, which received only nutritional recommendations, experienced an increase in body weight.
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Effectiveness of an Interdisciplinary Program Performed on Obese People Regarding Nutritional Habits and Metabolic Comorbidity: A Randomized Controlled Clinical Trial.
Fernández-Ruiz, VE, Ramos-Morcillo, AJ, Solé-Agustí, M, Paniagua-Urbano, JA, Armero-Barranco, D
International journal of environmental research and public health. 2020;17(1)
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Obesity is a major health issue and research has shown that programs based on a number of different interventions, including diet, exercise and behavioural components, tend to be more successful than just focussing on one lifestyle habit. The aim of this randomised trial was to determine the effectiveness of a multidisciplinary program based on healthy eating, exercise, cognitive-behavioural therapy, and health education in improving metabolic abnormalities, body mass index (BMI), and nutritional habits among obese adults. The intervention group received monthly group education sessions, four weekly exercise sessions including stretching and moderate aerobic training, monthly cognitive behavioural therapy sessions and monthly clinical and nutritional assessments for 1 year. The control group received standard care. The intervention group lost an average of 2.6 and 2.7 BMI points at the end of the 12 month intervention and at a further 12 months follow-up, respectively, whilst the average BMI of the control group did not change significantly. At baseline hardly any of the participants were considered to have adequate dietary habits. After 12 and 24 months there was a significant improvement in dietary habits in the intervention group only, with an increased intake of fruit, vegetables and fortified foods and a decreased intake in sweets, fats and oils. Both groups saw decreases in blood pressure, but the intervention group improved significantly more than the control group. Other metabolic markers, including blood sugar and lipid metabolism and liver function tests only improved in the intervention group. The authors conclude that a multidisciplinary team supported by community resources and led by nurses is able to achieve significant improvements in dietary habits and health outcomes in obese adults.
Abstract
Obesity is an important public health problem. The combined use of different therapies performed by an interdisciplinary group can improve the management of this health issue. The main goal of this research is to determine the effectiveness of a multidisciplinary program based on healthy eating, exercise, cognitive-behavioral therapy, and health education in improving metabolic comorbidity, Body Mass Index (BMI), and nutritional habits among obese adults, at short (12 months) and long term (24 months). A randomized controlled clinical trial was conducted at a community care center between February 2014 and February 2016. A random sampling was done (299), total population (3262). A sample of 74 subjects diagnosed with obesity (experimental group, n = 37 and control group, n = 37) was conducted. Inclusion criteria: obese people (BMI: >30 kg/m2) with metabolic comorbidity and bad nutritional habits. Exclusion criteria: other comorbidities. A 12-month interdisciplinary program (with pre-test, 12 months and 24 months of follow-up) was applied. Intervention is based on healthy eating, exercise, and cognitive behavioral therapy. The intervention had a positive effect on nutritional habits (F2;144 = 115.305; p < 0.001). The experimental group increased fruit and vegetable intake (F2;144 = 39.604, p < 0.001), as well as fortified foods (F2;144 = 10,076, p < 0.001) and reduced fats, oils, and sweets F2;144 = 24,086, p < 0.001). In the experimental group, a BMI reduction of 2.6 to 24 months was observed. At follow-up, no participant had inadequate nutritional habits, compared to 35.1% of the control group (χ22 = 33,398; p < 0.001). There was also a positive response of metabolic comorbidities in the intervention group. The interdisciplinary program improved all participants' metabolic parameters, BMI, and nutritional habits while maintaining the long-term effects (24 months).
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Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study.
Holman, N, Knighton, P, Kar, P, O'Keefe, J, Curley, M, Weaver, A, Barron, E, Bakhai, C, Khunti, K, Wareham, NJ, et al
The lancet. Diabetes & endocrinology. 2020;8(10):823-833
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Diabetes, cardiovascular disease, and hypertension are the most common chronic conditions predisposing people to severe COVID-19 disease. The aim of this population-based cohort study, using data from 98% of general practices in England, was to investigate the associations between various risk factors, including poor blood sugar control, and COVID-19-related deaths in people with type 1 and type 2 diabetes. Between Feb 16 and May 11, 2020, 1604 people with type 1 diabetes and 36 291 people with type 2 diabetes died from all causes, of which almost 30% had COVID-19 listed on the death certificate, either a primary underlying or secondary cause of death. Male gender, age and being of Black or Asian ethnicity were associated with an increased mortality from COVID-19. Poor blood sugar control, as determined by HbA1C, prior to infection was strongly associated with COVID-19-related death, independent of other risk factors. Obesity (BMI of 30 or over) as well as being underweight were also significantly associated with COVID-19 mortality. The authors discuss that people with diabetes are at increased risk of many serious infections and that high blood glucose levels are known to impair immunity and may amplify the hyperimmune response associated with severe COVID-19.
Abstract
BACKGROUND Diabetes has been associated with increased COVID-19-related mortality, but the association between modifiable risk factors, including hyperglycaemia and obesity, and COVID-19-related mortality among people with diabetes is unclear. We assessed associations between risk factors and COVID-19-related mortality in people with type 1 and type 2 diabetes. METHODS We did a population-based cohort study of people with diagnosed diabetes who were registered with a general practice in England. National population data on people with type 1 and type 2 diabetes collated by the National Diabetes Audit were linked to mortality records collated by the Office for National Statistics from Jan 2, 2017, to May 11, 2020. We identified the weekly number of deaths in people with type 1 and type 2 diabetes during the first 19 weeks of 2020 and calculated the percentage change from the mean number of deaths for the corresponding weeks in 2017, 2018, and 2019. The associations between risk factors (including sex, age, ethnicity, socioeconomic deprivation, HbA1c, renal impairment [from estimated glomerular filtration rate (eGFR)], BMI, tobacco smoking status, and cardiovascular comorbidities) and COVID-19-related mortality (defined as International Classification of Diseases, version 10, code U07.1 or U07.2 as a primary or secondary cause of death) between Feb 16 and May 11, 2020, were investigated by use of Cox proportional hazards models. FINDINGS Weekly death registrations in the first 19 weeks of 2020 exceeded the corresponding 3-year weekly averages for 2017-19 by 672 (50·9%) in people with type 1 diabetes and 16 071 (64·3%) in people with type 2 diabetes. Between Feb 16 and May 11, 2020, among 264 390 people with type 1 diabetes and 2 874 020 people with type 2 diabetes, 1604 people with type 1 diabetes and 36 291 people with type 2 diabetes died from all causes. Of these total deaths, 464 in people with type 1 diabetes and 10 525 in people with type 2 diabetes were defined as COVID-19 related, of which 289 (62·3%) and 5833 (55·4%), respectively, occurred in people with a history of cardiovascular disease or with renal impairment (eGFR <60 mL/min per 1·73 m2). Male sex, older age, renal impairment, non-white ethnicity, socioeconomic deprivation, and previous stroke and heart failure were associated with increased COVID-19-related mortality in both type 1 and type 2 diabetes. Compared with people with an HbA1c of 48-53 mmol/mol (6·5-7·0%), people with an HbA1c of 86 mmol/mol (10·0%) or higher had increased COVID-19-related mortality (hazard ratio [HR] 2·23 [95% CI 1·50-3·30, p<0·0001] in type 1 diabetes and 1·61 [1·47-1·77, p<0·0001] in type 2 diabetes). In addition, in people with type 2 diabetes, COVID-19-related mortality was significantly higher in those with an HbA1c of 59 mmol/mol (7·6%) or higher than in those with an HbA1c of 48-53 mmol/mol (HR 1·22 [95% CI 1·15-1·30, p<0·0001] for 59-74 mmol/mol [7·6-8·9%] and 1·36 [1·24-1·50, p<0·0001] for 75-85 mmol/mol [9·0-9·9%]). The association between BMI and COVID-19-related mortality was U-shaped: in type 1 diabetes, compared with a BMI of 25·0-29·9 kg/m2, a BMI of less than 20·0 kg/m2 had an HR of 2·45 (95% CI 1·60-3·75, p<0·0001) and a BMI of 40·0 kg/m2 or higher had an HR of 2·33 (1·53-3·56, p<0·0001); the corresponding HRs for type 2 diabetes were 2·33 (2·11-2·56, p<0·0001) and 1·60 (1·47-1·75, p<0·0001). INTERPRETATION Deaths in people with type 1 and type 2 diabetes rose sharply during the initial COVID-19 pandemic in England. Increased COVID-19-related mortality was associated not only with cardiovascular and renal complications of diabetes but, independently, also with glycaemic control and BMI. FUNDING None.