What we know so far
Diabetes (together with hypertension and ischaemic heart disease) is one of the conditions that is notably associated with poorer outcomes in individuals with COVID-19. This was initially highlighted in research from China and corroborated with further data from Italy.
One of the first papers by Wu et al.1 looked at case fatality rates and noted that those with diabetes had a higher rate of 7.3% compared to the overall rate of 2.3%. Further reviews of Chinese patient data from both intensive care and non-intensive care, looking at metabolic disease, noted a diabetes prevalence of 9.7% of patients.2 The authors also noted a two-fold increase in those with diabetes in patients with severe disease (i.e. admitted to intensive care units). Similarly, data from Italy noted that 31.3% of deceased patients with COVID-19 had diabetes.3
It is difficult to conclude anything substantive regarding risk of COVID-19 infections and diabetes for a number of reasons. The studies from China do not differentiate between diabetes type, although the Italian ICU data specifically state type 2 diabetes. Additionally, there are not data looking at HbA1c, glycaemic control (prior or during admission) or the medication patients were on. Given the age of the population reviewed and the associations with multimorbidity in older individuals, as well as the background diabetes prevalence in the population in those countries, the presence of diabetes could be merely an association rather than a true risk factor. Data do tend to suggest that those with diabetes are at higher risk of severity once they have COVID-19 (requiring intensive care support) but, again, further data specifically looking at diabetes subgroups and populations is necessary to confirm that suggestion.
ACE2 and COVID-19 infection susceptibility
There has been a lot of discussion around ACE2 receptors and whether variations in the expression of ACE2 in those with diabetes (and those on angiotensin-converting enzyme [ACE] inhibitors) may increase the susceptibility to COVID-19. This is purely theoretical and, in fact, conflicting discussions have even argued that ACE2 expression may be reduced thereby being protective in such groups. This has also been considered as one of the possible reasons why those from BAME (Black, Asian and minority ethnic) populations may be more at risk from the infection as there may be a variable ACE2 expression in different ethnicities. Currently there is no strong evidence for this although it is an interesting theory.
Regardless of whether diabetes is a risk factor or not, it is clear that those with diabetes are specifically considered to reduce risks of COVID-19 infection.
Diabetes – to shield or distance?
It is important to note that diabetes, itself, is not on the list of conditions from Public Health England that require shielding. It is, however, sensible to advise those with diabetes of the importance of standard social distancing measures and of the importance of optimising their blood sugars from a general health point of view. This would include advice on maintaining regular exercise given the potential limitation in these times.
Diabetes medications in COVID-19 patients
An area of importance are awareness of sick day rules specifically with regards to metformin, ACE inhibitors and SGLT2 inhibitors as well as more frequent blood sugar monitoring in those acutely unwell.
Not only will COVID-19 infection affect appetite and fluid intake (as well as increased loss from pyrexia) but it has been associated with gastrointestinal (GI) disturbances which can further worsen dehydration risk. Additionally SGLT2 inhibitors not only put patients at risk of dehydration but also diabetic ketoacidosis (DKA) risk (which can be euglycaemic). Hence anyone with an intercurrent illness is advised to withhold SGLT2 inhibitors to reduce this risk. For further detailed advice for SGLT2 inhibitors and those with type 2 diabetes see reference 4.
It is important to also be aware that a small number of patients with type 1 diabetes may also be on SGLT2 inhibitors and this will need to be reviewed with the specialist diabetes teams as many are advocating withholding SGLT2 inhibitors in this group for the current situation. Whilst hyperperglycaemia is common in intercurrent illness, conversely, it is important to consider older frail patients with diabetes who may also be at higher risk of hypoglycaemia if their appetite is affected and they are on medications that can increase their risk (sulphonylureas, insulins).
Specific guidance for the front door regarding those admitted with diabetes and COVID-19 infection has been created by a specialist inpatient response team and the Association of British Clinical Diabetologists.5 This highlights the risks of hyperglycaemia and ketosis in those admitted with diabetes and COVID-19 including anecdotal cases of increased insulin resistance, unusual DKA/Hyperosmolar Hyperglycaemic State (DKA/HHS) episodes and variations in fluid requirements (not forgetting that certain ongoing trials include a dexamethasone arm that may affect glycaemic control).
Amar Puttanna
Consultant Diabetologist
Good Hope Hospital
University Hospitals Birmingham NHS Foundation Trust
Sutton Coldfield
COVID-19 Bulletin 1:
COVID-19 and care of the elderly
COVID-19 and heart failure
COVID-19 and primary care
COVID-19 in cancer patients
COVID-19 and cardiovascular disease
COVID-19 and respiratory medicine
Round up of COVID-19 e-learning, apps and websites
References
- Wu Z, McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72,314 cases from the Chinese Center for Disease Control and Prevention. JAMA (published online 24 February 2020). https://doi.org/10.1001/jama.2020.2648
- Li B, Yang J, Zhao F et al. Prevalence and impact of cardiovascular metabolic diseases on COVID-19 in China. Clin Res Cardiol (published online 11 March 2020). https://doi.org/10.1007/s00392-020-01626-9
- https://www.epicentro.iss.it/coronavirus/bollettino/Report-COVID-2019_26_marzo_eng.pdf
- https://abcd.care/sites/abcd.care/files/site_uploads/Resources/Position-Papers/SGLT2-inhibitors-ABCD.pdf
- https://abcd.care/sites/abcd.care/files/site_uploads/COvID_Front_Door_v1.0.pdf
