NEJM: New-Onset Diabetes in Covid-19 #covid19rftlks

Rubino, F. et al. | June 12, 2020 | NEJM| DOI: 10.1056/NEJMc2018688

There is a bidirectional relationship between Covid-19 and diabetes. On the one hand, diabetes is associated with an increased risk of severe Covid-19. On the other hand, new-onset diabetes and severe metabolic complications of preexisting diabetes, including diabetic ketoacidosis and hyperosmolarity for which exceptionally high doses of insulin are warranted, have been observed in patients with Covid-19.1-3 These manifestations of diabetes pose challenges in clinical management and suggest a complex pathophysiology of Covid-19–related diabetes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19, binds to angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in key metabolic organs and tissues, including pancreatic beta cells, adipose tissue, the small intestine, and the kidneys.4 Thus, it is plausible that SARS-CoV-2 may cause pleiotropic alterations of glucose metabolism that could complicate the pathophysiology of preexisting diabetes or lead to new mechanisms of disease.

There are also several precedents for a viral cause of ketosis-prone diabetes, including other coronaviruses that bind to ACE2 receptors.5 Greater incidences of fasting glycemia and acute-onset diabetes have been reported among patients with SARS coronavirus 1 pneumonia than among those with non-SARS pneumonia.5

In the aggregate, these observations provide support for the hypothesis of a potential diabetogenic effect of Covid-19, beyond the well-recognized stress response associated with severe illness. However, whether the alterations of glucose metabolism that occur with a sudden onset in severe Covid-19 persist or remit when the infection resolves is unclear. How frequent is the phenomenon of new-onset diabetes, and is it classic type 1 or type 2 diabetes or a new type of diabetes? Do these patients remain at higher risk for diabetes or diabetic ketoacidosis? In patients with preexisting diabetes, does Covid-19 change the underlying pathophysiology and the natural history of the disease? Answering these questions in order to inform the immediate clinical care, follow-up, and monitoring of affected patients is a priority.

To address these issues, an international group of leading diabetes researchers participating in the CoviDIAB Project have established a global registry of patients with Covid-19–related diabetes (covidiab.e-dendrite.com. opens in new tab). The goal of the registry is to establish the extent and phenotype of new-onset diabetes that is defined by hyperglycemia, confirmed Covid-19, a negative history of diabetes, and a history of a normal glycated hemoglobin level. The registry, which will be expanded to include patients with preexisting diabetes who present with severe acute metabolic disturbance, may also be used to investigate the epidemiologic features and pathogenesis of Covid-19–related diabetes and to gain clues regarding appropriate care for patients during and after the course of Covid-19. Given the very short history of human infection with SARS-CoV-2, an understanding of how Covid-19–related diabetes develops, the natural history of this disease, and appropriate management will be helpful. The study of Covid-19–related diabetes may also uncover novel mechanisms of disease (Source: NEJM)

NHS study: “demonstrates that all types of diabetes are independently associated with a significant increased risk of in-hospital death with COVID-19”

NHS England | May 2020 | NHS expands offer of help to people with diabetes during coronavirus outbreak

NHS England have published the findings of new NHS research which looked at data from 263,830 patients registered with a a General Practice in England on February 19th 2020 with a recorded diagnosis of Type 1, and 2,864,670 patients with a diagnosis of Type 2 diabetes.

The population cohort study assessing risks of in-hospital death using Multivariate logistic regression to examine diabetes status, by type, and associations with in-hospital death, adjusting for demographic factors and comorbidities.

The world-leading studies reveal that people living with type 1 diabetes are at three and a half times the risk, and people living with type 2 are at double the risk of dying in hospital with the virus, compared to people without diabetes.

The strongest risk factor for dying with the virus is age, and people with type 1 diabetes are on average younger than people with type 2 diabetes.

Overall, 7,466 of those who died in hospitals in England had type 2 and 365 who died had type 1 diabetes, and the research suggests that the threat for those under 40 with type 1 or type 2 diabetes is very low, with no recorded deaths in those under 20.

It is thought that the risk to people with diabetes and the virus is in line with the extra risk seen in other infectious conditions such as pneumonia.

The study also shows that in people with both type 1 and type 2 diabetes, even when all other known factors are taken into account, higher blood glucose levels and obesity are linked to higher risk (Source: NHS England).

Abstract
Background
Although diabetes has been associated with COVID-19 mortality, the absolute and relative risks for Type 1 and Type 2 diabetes are unknown.
Methods
A population cohort study assessing risks of in-hospital death with COVID-19 between 1stMarch and 11th May 2020, including individuals registered with a General Practice in England and alive on February 19th 2020.
Multivariate logistic regression examined diabetes status, by type, and associations with in-hospital death, adjusting for demographic factors and comorbidities.
Findings
Of the 61,414,470 individuals registered, 263,830 (0∙4%) had a recorded diagnosis of Type 1 and 2,864,670 (4∙7%) of Type 2 diabetes. There were 23,804 COVID-19 related deaths. One third occurred in people with diabetes: 7,466 (31∙4%) with Type 2 and 365 (1∙5%) with Type 1 diabetes. Crude mortality rates per 100,000 persons over the 72 days for the overall population and for those with Type 1 and Type 2 diabetes were 38∙8
, 138∙3, and 260∙6 respectively. Adjusted for age, sex, deprivation, ethnicity and geographical region, people with Type 1 and Type 2 diabetes had 3∙50 and 2∙03 times the odds respectively of dying in hospital with COVID-19 compared to those without diabetes, attenuated to 2∙86 and 1∙81 respectively when also adjusted for previous hospital admissions with coronary heart disease, cerebrovascular disease or heart failure.
Interpretation
This nationwide analysis in England demonstrates that all types of diabetes are independently associated with a significant increased risk of in-hospital death with COVID-19.
Funding
NHS England & Improvement and Public Health England.


Research in context
Evidence before this study

From March 2020, we performed weekly searches of PubMed and MedRxiv using the terms COVID-19, SARSCoV-2, coronavirus,SARS virus and diabetes. Studies from China, Italy, the USA and the UK have suggested that people with diabetes have higher risks of more severe outcomes with COVID-19, including death. One population-based UK study reported a higher risk of COVID-19 related death in those with diabetes after
adjustment for demographic factors and other comorbidities. However, none of these studies have assessed differences in risk by type of diabetes.
Added value of this study
This is the largest COVID-19 related study, covering almost the entire population of England, and is the first study to investigate the relative and absolute risks of death in hospital with COVID-19 by type of diabetes, adjusting for key confounders. It demonstrates that one third of all deaths in-hospital with COVID-19 occur in people with diabetes. Adjusted for age, sex, deprivation, ethnicity and geographical region, people with Type 1
and Type 2 diabetes had 3.50 and 2.03 times the odds respectively of dying in hospital with COVID-19 compared to those without diabetes. These relative odds were attenuated to 2.86 and 1.81 respectively when also adjusted for previous hospital admissions with cardiovascular comorbidities.
Implications of all the available evidence
People with diabetes are at higher risk of COVID-19 related death, and those with Type 1 diabetes are at higher risk than those with Type2 diabetes. These insights are important in both understanding the pathophysiological mechanisms underlying the determinants of more severe outcomes with COVID-19, and in informing potential clinical and public health responses to the pandemic.

Read the full paper

In the news:

The Guardian Covid-19: people with type 1 diabetes more likely to die than those with type 2 – study

Metro Why are people with diabetes at higher risk of dying from coronavirus?

Rapid Review: Diabetic retinopathy screening during the COVID-19 pandemic #covid19rftlks

Ahmad, E., Davies, M.J. & Khunti, K. | Centre for Evidence-Based Medicine| May 2020 | Diabetic retinopathy screening during the COVID-19 pandemic

A new rapid review from tbeCentre for Evidence-Based Medicine considers the question

People with diabetes (PWD) are included in the group at increased risk of severe illness from coronavirus (COVID-19) and have been advised to observe stringent social distancing measures.(1)  This creates a difficult situation for PWD and their Health Care Providers (HCP) as PWD require an annual review including retinal screening as part of their screening for complications, which involves a physical visit to a community or hospital facility or an eye clinic.

  • How can we help stratify annual retinal screening programmes for people with diabetes (PWD) during the COVID-19 pandemic?
  • Can we do remote retinal review for PWD?
  • What can we do to control the risk factors for development or progression of diabetic retinopathy during the COVID-19 pandemic?
  • Is hydroxycholoroquine safe to use in individuals with diabetic retinopathy?

Rapid Review: Diabetic retinopathy screening during the COVID-19 pandemic

 

 

Should a chronic condition, such as type 1 diabetes, prevent regular exercise?

NICE |nd| Should a chronic condition, such as type 1 diabetes, prevent regular exercise?

In the latest episode of NICE’S podcast NICE Talks, the topic is whether a long term chronic condition such as type 1 diabetes should prevent regular exercise.

The hosts of the podcast speak with Chris Bright, a Welsh International Futsal player, who has lived with type 1 diabetes for 20 years; Professor Partha Kar a Consultant Endocrinologist at Portsmouth Hospitals NHS Trust and aNational Specialty Advisor, Diabetes, for NHS England; and chiropractor Peter Dixon, President of the Royal College of Chiropractors and NICE Fellow. They discuss the NICE recommendations on physical activity for those with type 1 diabetes, available from NICE.

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Listen via Soundcloud

Results of long-term study could help identify children at risk of future type 2 diabetes

University of Plymouth| January 2020 | Results of long-term study could help identify children at risk of future type 2 diabetes

University of Plymouth & Nestle researchers have identified biological and physiological factors which lead to the development of type 2 diabetes in adults. 

The EarlyBird cohort study followed 300 healthy children in Plymouth,  for 15 years to determine who would become at risk of developing type 2 diabetes, and why. The findings have been published in the journal Diabetes Care 

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Jon Pinkney, Professor of Endocrinology and Diabetes in the University of Plymouth’s Peninsula Medical School and Honorary Consultant Physician in Endocrinology and Diabetes at University Hospitals Plymouth NHS Trust said:

“The rapidly rising prevalence of type 2 diabetes is one of the biggest global health challenges, and there is an urgent need to develop effective strategies for early intervention and prevention.

“The research partnership between University of Plymouth and Nestlé has shown how the risks of future type 2 diabetes can be predicted in childhood. This opens up the possibility of individualised advice and early intervention to reduce the risks of future type 2 diabetes.” (Source: University of Plymouth)

The press release from University of Plymouth also provides more information on the EarlyBird study, available here 

The abstract is available from Diabetes Care but for the full contact the Library & Knowledge Service 

University of Plymouth Results of long-term study could help identify children at risk of future type 2 diabetes

Related:

Diabetes.co.uk Genetic link to identify children at risk of type 2 diabetes

National Diabetes Audit – Report 2: Complications and Mortality

This report from the National Audit of Diabetes covers complications arising from diabetes. Most cardiovascular and diabetes specific complications are covered.

Part a is divided into three main sections: cardiovascular complications, diabetes specific complications and mortality. Each section aims to address overall rates, time trends, geographical variation and hospital utilisation.

Part b investigates associations between patient characteristics and adverse outcomes. The impact of changes to lifestyle and treatment have been estimated for both the person with diabetes and diabetes services for the first time.

The reports can be downloaded here:

BMJ: Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: population based cohort study with 40 years of follow-up

BMJ | November 2019 | Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: population based cohort study with 40 years of follow-up| 67| l6398

A study that looked at the associations between maternal diabetes (diagnosed prior to or during pregnancy) and early onset cardiovascular disease (CVD) in offspring during their first four decades of life adds to the evidence around non-genetic intergenerational connections between maternal illness and risk factors for CVD among offspring. The experts who authored the study looked at data from more than 2 million births in Denmark between 1977 and 2016. 

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The findings from this population based study indicate that the children of mothers with diabetes, especially mothers with CVD history or diabetic complications, had increased rates of early-onset CVD throughout the early decades of life. If the associations are causal, then preventing and treating diabetes in women of childbearing age could have a significant impact on the reduction of CVD incidence in the next generation.

The authors argue that their findings highlight the importance of effective strategies for screening and preventing diabetes in women of childbearing age (Source: BMJ).

 

 

Read the full Opinion from BMJ

Yongfu, Y. et al | 2019|  Maternal diabetes during pregnancy and early onset of cardiovascular disease in offspring: population based cohort study with 40 years of follow-up|

Abstract

Objective To evaluate the associations between maternal diabetes diagnosed before or during pregnancy and early onset cardiovascular disease (CVD) in offspring during their first four decades of life.

Design Population based cohort study.

Setting Danish national health registries.

Participants All 2 432 000 liveborn children without congenital heart disease in Denmark during 1977-2016. Follow-up began at birth and continued until first time diagnosis of CVD, death, emigration, or 31 December 2016, whichever came first.

Exposures for observational studies Pregestational diabetes, including type 1 diabetes (n=22 055) and type 2 diabetes (n=6537), and gestational diabetes (n=26 272).

Main outcome measures The primary outcome was early onset CVD (excluding congenital heart diseases) defined by hospital diagnosis. Associations between maternal diabetes and risks of early onset CVD in offspring were studied. Cox regression was used to assess whether a maternal history of CVD or maternal diabetic complications affected these associations. Adjustments were made for calendar year, sex, singleton status, maternal factors (parity, age, smoking, education, cohabitation, residence at childbirth, history of CVD before childbirth), and paternal history of CVD before childbirth. The cumulative incidence was averaged across all individuals, and factors were adjusted while treating deaths from causes other than CVD as competing events.

 

Results During up to 40 years of follow-up, 1153 offspring of mothers with diabetes and 91 311 offspring of mothers who did not have diabetes were diagnosed with CVD. Offspring of mothers with diabetes had a 29% increased overall rate of early onset CVD ; cumulative incidence among offspring unexposed to maternal diabetes at 40 years of age 13.07%, difference in cumulative incidence between exposed and unexposed offspring 4.72% . The sibship design yielded results similar to those of the unpaired design based on the whole cohort. Both pregestational diabetes and gestational diabetes were associated with increased rates of CVD in offspring. We also observed varied increased rates of specific early onset CVDs, particularly heart failure, hypertensive disease, deep vein thrombosis, and pulmonary embolism. Increased rates of CVD were seen in different age groups from childhood to early adulthood until age 40 years. The increased rates were more pronounced among offspring of mothers with diabetic complications. A higher incidence of early onset CVD in offspring of mothers with diabetes and comorbid CVD was associated with the added influence of comorbid CVD but not due to the interaction between diabetes and CVD on the multiplicative scale.

 

Conclusions Children of mothers with diabetes, especially those mothers with a history of CVD or diabetic complications, have increased rates of early onset CVD from childhood to early adulthood. If maternal diabetes does have a causal association with increased CVD rate in offspring, the prevention, screening, and treatment of diabetes in women of childbearing age could help to reduce the risk of CVD in the next generation.

Offspring of mothers with diabetes, especially those mothers with a history of CVD or diabetic complications, have increased rates of early onset CVD from childhood to early adulthood

The article is available in full from The BMJ

Diabetes UK strategy 2020-2025

Diabetes UK has launched a new strategy called ‘A generation to end the harm: Diabetes UK Strategy 2020-2025’ coinciding with World Diabetes Day 2019 

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Image source: https://www.diabetes.org.uk/

There are an estimated 2.85 million people diagnosed with type 2 diabetes in England, and more than 850,000 living with the condition who do not know they have it because they have not yet been diagnosed − bringing the total up to 3.7 million.

The new strategy from Diabetes UK focuses on achieving five key outcomes by 2025:

  • more people with type 1, type 2 and all other forms of diabetes will benefit from new treatments that cure or prevent the condition
  • more people will be in remission from type 2 diabetes
  • more people will get the quality of care they need to manage their diabetes well
  • fewer people will get type 2 and gestational diabetes
  • more people will live better and more confident lives with diabetes, free from discrimination.

The charity said that more than half of all cases of type 2 diabetes could be prevented or delayed, and in turn, the risk of developing the related complications, by tackling overweight and obesity.

Full document: A generation to end the harm: Diabetes UK Strategy 2020-2025

See also: Obesity rate doubles over past 20 years | OnMedica

National Pregnancy in Diabetes Audit

National Pregnancy in Diabetes (NPID) audit report 2018 | The Healthcare Quality Improvement Partnership

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The National Pregnancy in Diabetes (NPID) audit measures the quality of antenatal care and pregnancy outcomes for women with pre-gestational diabetes.

This is the first year that a Quality Improvement Collaborative (QIC) has been incorporated into the NPID programme for 2018/19 with the aim of focusing on improvement activity.

Some of the key findings include:

  • Overall 7 out of 8 women were not well prepared for pregnancy
  • There has been an increase in the rate of admissions with hypoglycaemia for women with type 1 diabetes
  • Almost one in two babies had complications related to maternal diabetes which is mostly the result of large for gestational age (LGA) babies
  • Admissions to neonatal units are more common than in the general population.

Full report: National Pregnancy in Diabetes (NPID) Audit Report 2018

See also: NHS Digital resources

NHS spends around £3bn a year on ‘avoidable’ treatment for diabetes

ITV | September 2019 | NHS spends around £3bn a year on ‘avoidable’ treatment for diabetes

An analysis of hospital treatment in 2017/18 highlights that approximately £5.5bn each year is spent on treatment of diabetes, of this an estimated £3bn is on ‘potentially avoidable’ treatment. The authors of the research explain that this equates to around one-tenth of the NHS budget; compared to people without diabetes, the average annual cost of planned care was over twice as high for those with Type 2 diabetes and the average cost of emergency care was three times higher, once age was taken into account.

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Study author, Dr Adrian Heald from Salford Royal Hospital, said: “People with diabetes are admitted to hospital more often, especially as emergencies, and stay on average longer as inpatients.

“These increased hospital costs, 40% of which come from non-elective and emergency care, are three times higher than the current costs of diabetes medication.

“Improved management of diabetes by GPs and diabetes specialist care teams could improve the health of people with diabetes and substantially reduce the level of hospital care and costs.” (Source: ITV News)

The team’s finding will be presented this week at the European Association for the study of Diabetes (EASD)  annual meeting in Barcelona.

Read the full story from ITV News

See also:

BT NHS spends around £3bn a year on ‘avoidable’ treatment for diabetes