Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: a Systematic Review of Reviews #Covid19RftLks

Hartmann-Boyce, J. et al | 2021| Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: a Systematic Review of Reviews | Diabetes Care | dc210930 |  DOI: 10.2337/dc21-0930

In this review of reviews, the reviewers set out to synthesize the evidence regarding the extent to which people with diabetes (PWD) are at increased risk of SARS-CoV-2 infection and/or from suffering its complications, including associated mortality. In particular, we set out to analyze evidence on the following questions:

  1. Is diabetes associated with increased risk of acquiring SARS-CoV-2?
  2. Is diabetes associated with hospitalization with COVID-19?
  3. Is diabetes associated with the severity (including intensive care unit [ICU] admission, death, and
    other composite measures of severity) of COVID-19 outcomes?
  4. Are there differences in outcomes of SARS-CoV-2 infection within the population of PWD?

They report that their overview of reviews provides consistent evidence from multiple metaanalyses that diabetes is a risk factor for severe disease and death from COVID-19.


Background This review was commissioned by the World Health Organization and presents a summary of the latest research evidence on the impact of coronavirus disease 2019 (COVID-19) on people with diabetes (PWD).

Purpose To review the evidence regarding the extent to which PWD are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and/or of suffering its complications, including associated mortality.

Data Sources We searched the Cochrane COVID-19 Study Register, Embase, MEDLINE, and LitCOVID on 3 December 2020.

Study Selection Systematic reviews synthesizing data on PWD exposed to SARS-CoV-2 infection, reporting data on confirmed SARS-CoV-2 infection, admission to hospital and/or to intensive care unit (ICU) with COVID-19, and death with COVID-19 were used.

Data Extraction One reviewer appraised and extracted data; data were checked by a second.

Data Synthesis Data from 112 systematic reviews were narratively synthesized and displayed using effect direction plots. Reviews provided consistent evidence that diabetes is a risk factor for severe disease and death from COVID-19. Fewer data were available on ICU admission, but where available, these data also signaled increased risk. Within PWD, higher blood glucose levels both prior to and during COVID-19 illness were associated with worse COVID-19 outcomes. Type 1 diabetes was associated with worse outcomes than type 2 diabetes. There were no appropriate data for discerning whether diabetes was a risk factor for acquiring SARS-CoV-2 infection.

Limitations Due to the nature of the review questions, the majority of data contributing to included reviews come from retrospective observational studies. Reviews varied in the extent to which they assessed risk of bias.

Conclusions There are no data on whether diabetes predisposes to infection with SARS-CoV-2. Data consistently show that diabetes increases risk of severe COVID-19. As both diabetes and worse COVID-19 outcomes are associated with socioeconomic disadvantage, their intersection warrants particular attention.

Risks of and From SARS-CoV-2 Infection and COVID-19 in People With Diabetes: a Systematic Review of Reviews

Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis #Covid19RftLks

Kan, C. et al | 2021| Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis| Frontiers in Endocrinology | https://doi.org/10.3389/fendo.2021.708494

The reviewers of this systematic review and meta-analysis investigate the associations of antidiabetic agents with mortality in patients with type 2 diabetes mellitus (T2DM) who have COVID-19. The authors conclude that metformin and sulfonylurea treatments could be associated with reduced mortality risk, while insulin treatment could be associated with enhanced mortality risk, in patients with T2DM who had COVID-19. However, DPP-4 inhibitor treatment could not be associated with mortality risk in these patients. The results of this meta-analysis should be interpreted carefully because of the limitations of included studies, although the effects of sulfonylurea and DPP-4 inhibitors should be more fully evaluated in subsequent studies. Further larger trials should also be done to confirm these results and especially other diabetes drugs including SGLT2 inhibitors and DPP-4 inhibitors (Source: Kan et al, 2021).

Aims: We conducted a systematic review and meta-analysis to assess various antidiabetic agents’ association with mortality in patients with type 2 diabetes (T2DM) who have coronavirus disease 2019 (COVID-19).

Methods: We performed comprehensive literature retrieval from the date of inception until February 2, 2021, in medical databases (PubMed, Web of Science, Embase, and Cochrane Library), regarding mortality outcomes in patients with T2DM who have COVID-19. Pooled OR and 95 per cent CI data were used to assess relationships between antidiabetic agents and mortality.

Results: Eighteen studies with 17,338 patients were included in the meta-analysis. Metformin (pooled OR, 0.69; P equal to 0.001) and sulfonylurea (pooled OR, 0.80; P equal to 0.016) were associated with lower mortality risk in patients with T2DM who had COVID-19. However, patients with T2DM who had COVID-19 and received insulin exhibited greater mortality (pooled OR, 2.20; P equal to 0.002). Mortality did not significantly differ (pooled OR, 0.72; P equal to 0.057) between DPP-4 inhibitor users and non-users.

Conclusions: Metformin and sulfonylurea could be associated with reduced mortality risk in patients with T2DM who have COVID-19. Furthermore, insulin use could be associated with greater mortality, while DPP-4 inhibitor use could not be. The effects of antidiabetic agents in patients with T2DM who have COVID-19 require further exploration.

Systematic Review Registration: PROSPERO (identifier, CRD42021242898).

Mortality Risk of Antidiabetic Agents for Type 2 Diabetes With COVID-19: A Systematic Review and Meta-Analysis [pdf]

National Pregnancy in Diabetes Audit Report 2020

Health Quality Improvement Partnership | October 2021 | National Pregnancy in Diabetes Audit Report 2021

The National Pregnancy in Diabetes Audit measures the quality of antenatal care and pregnancy outcomes for women with pre-gestational diabetes. HQIP has published its report for 2020.

Key findings from the audit report:

There are now more pregnancies in women with type 2 diabetes, than in women with type 1 diabetes (54 per cent of diabetes’ pregnancies, compared to 47 per cent in 2014).

Women with type 2 diabetes face additional healthcare inequalities and are frequently not prepared for pregnancy (reduced use of insulin and folic acid before pregnancy), and

Despite the additional challenges of supporting women with diabetes during the COVID-19 pandemic, pregnancy outcomes are comparable in 2019 and 2020.

Image source: HQIP The first mage shows a sonographer, ultrasound and an expectant couple. The second shows a pregnant women preparing a selection of healthy foods

The report makes three recommendations

  1. Dedicated pre-pregnancy co-ordinators focused on enhanced provision of contraception and support for pregnancy preparation are recommended to improve glycaemic management and 5mg folic acid supplementation before pregnancy, especially in women with type 1 and type 2 diabetes, living in the most deprived regions.
  2. We found fewer preterm births, large for gestational age (LGA) birthweight, neonatal care admissions and perinatal deaths in women with HbA1c less than 43mmol/mol from 24 weeks gestation, both in the current 2019-2020 and recent datasets*. NICE guidelines [NG3 Diabetes in pregnancy: management from preconception to the postnatal period], recommend use of continuous glucose monitoring (CGM) in type 1 diabetes. Data are now needed to evaluate whether Libre or CGM use will improve glucose levels, target HbA1c attainment and neonatal health outcomes in pregnant women with type 2 diabetes.
  3. Access to structured education, weight management and diabetes prevention programmes for women (Source: HQIP).

National Pregnancy in Diabetes (NPID) Audit Report 2020

Diabetes checks: delays in treatment are reduced when support staff assess eye images

NIHR | October 2021 | Diabetes checks: delays in treatment are reduced when support staff assess eye images

This NIHR Alert explains the findings of a piece of research that suggests that support staff could be trained to read images of the back of the eye (retina) almost as well as ophthalmologists. 

People living with diabetes need regular eye examinations to prevent serious problems with their vision. A shortage of eye specialists (ophthalmologists) is leading to delays in appointments. New research suggests that support staff could be trained to read images of the back of the eye (retina) almost as well as ophthalmologists. 

Most of the support staff in the study were specialist photographers who normally take images of the retina (ophthalmic photographers). The research suggests that they could be trained as ophthalmic graders and take on a new role in the NHS. They could increase capacity and reduce delays in people’s eye assessments (Source: NIHR)

The NIHR Alert can be read in full from the National Institute for Health Research


The increasing diabetes prevalence and advent of new treatments for its major visual-threatening complications (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]), which require frequent life-long follow-up, have increased hospital demands markedly. Subsequent delays in patient’s evaluation and treatment are causing sight loss. Strategies to increase capacity are needed urgently. The retinopathy (EMERALD) study tested diagnostic accuracy, acceptability, and costs of a new health care pathway for people with previously treated DME or PDR.


Prospective, multicenter, case-referent, cross-sectional, diagnostic accuracy study undertaken in 13 hospitals in the United Kingdom.


Adults with type 1 or 2 diabetes previously successfully treated DME or PDR who, at the time of enrollment, had active or inactive disease.


A new health care pathway entailing multimodal imaging (spectral-domain OCT for DME, and 7-field Early Treatment Diabetic Retinopathy Study [ETDRS] and ultra-widefield [UWF] fundus images for PDR) interpreted by trained nonmedical staff (ophthalmic graders) to detect reactivation of disease was compared with the current standard care (face-to-face examination by ophthalmologists).

Main Outcome Measures

Primary outcome: sensitivity of the new pathway. Secondary outcomes: specificity; agreement between pathways; costs; acceptability; proportions requiring subsequent ophthalmologist assessment, unable to undergo imaging, and with inadequate images or indeterminate findings.


The new pathway showed sensitivity of 97 per cent and specificity of 31 per cent to detect DME. For PDR, sensitivity and specificity using 7-field ETDRS images or UWF images, respectively) were comparable. For detection of high-risk PDR, sensitivity and specificity were higher when using UWF images, respectively, for UWF versus 80 per cent and 40 per cent , respectively, for 7-field ETDRS images). Participants preferred ophthalmologists’ assessments; in their absence, they preferred immediate feedback by graders, maintaining periodic ophthalmologist evaluations. When compared with the current standard of care, the new pathway could save £1 390 per 100 DME visits and between £461 and £1189 per 100 PDR visits.


The new pathway has acceptable sensitivity and would release resources. Users’ suggestions should guide implementation.

Evaluation of a New Model of Care for People with Complications of Diabetic Retinopathy [primary paper]

Metformin for pregnancy and beyond: the pros and cons

Newman, C. & Dunne, F. P. | 2021| Metformin for pregnancy and beyond: the pros and cons | Diabetic Medicine | https://doi.org/10.1111/dme.14700

The authors of this review set out to review the benefits and potential pitfalls of metformin use in pregnancy. To this end they conducted a literature search of web-based databases (including PubMed, CENTRAL via the Cochrane Library and EMBASE) using identified search terms. They read the full texts of any relevant texts published in English and searched clinicaltrials.gov for relevant unpublished trials. The team included randomised controlled trials (RCTs), cluster RCTs, pilot and feasibility studies in our review. They excluded conference abstracts, case reports and case series. Observational data which were deemed to be of high quality were also considered. Additionally, the researchers searched bibliographies for all relevant publications to identify other studies.

In this paper they report their findings that metformin has many maternal advantages when taken during and after pregnancy, including reduced maternal GWG, PTD and insulin requirements, a reduction in operative delivery and possible reduction in hypertensive disorders and future type 2 diabetes. Some benefits are even greater for women with a BMI more than or equal to 30 kg/m2 (Source: Newman & Dunne, 2021).


Context and Aim

Metformin has been used in pregnancy since the 1970s. It is cheap, widely available and is acceptable to women. Despite its increasing use, controversy remains surrounding its benefits and risks. Metformin effectively reduces hyperglycaemia for the mother during pregnancy and it reduces rates of macrosomia and neonatal hypoglycaemia. However, concern exists surrounding an increase in the rate of SGA births and obesity in childhood. We aim to review the evidence and expert opinion behind metformin in pregnancy through to the post-partum period.


We performed a literature review of relevant studies from online databases using a combination of keywords. We also searched the references of retrieved articles for pertinent studies.


There is strong evidence that metformin is safe in early pregnancy with no risk of congenital malformations. If used throughout pregnancy, it is likely to lead to reduced maternal weight gain and reduced insulin dose in women with type 2 diabetes. In infants, metformin reduces hypoglycaemia and macrosomia but may increase the rate of infants born SGA. There is some evidence of an increased risk of obesity and altered fat distribution in offspring. Metformin appears well tolerated in pregnancy and is more acceptable to women than insulin therapy.


Due to increasing rates of maternal obesity, GDM and type 2 diabetes, metformin use in pregnancy is increasing. Overall, it appears safe and effective but further research is needed to examine mechanisms linking metformin to obesity reported during childhood in some follow-up studies.

  • Metformin has been used outside of pregnancy for decades and has multiple benefits in pregnancy including reduced weight gain and a potential decrease in pre-eclampsia (PET).
  • However, some clinicians have concerns regarding its use due to increased rates of small for gestational age (SGA) births and adiposity in infants exposed to metformin.
  • With the rising rates of obesity and gestational diabetes (GDM), cheap, acceptable and effective treatments for hyperglycaemia are needed.
  • This study follows the use of metformin from the pre-conception to the post-partum period and examines the evidence for and against its use.

The primary paper is available from the journal Diabetic Medicine

COVID-19, Hyperglycemia, and New-Onset Diabetes #Covid19RftLks

Khunti, K., Del Prato, S., Mathieu, C., Kahn, S.E., Gabbay R. A. & Buse, J.B. | 2021| COVID-19, Hyperglycemia, and
New-Onset Diabetes | Diabetes Care | https://doi.org/10.2337/dc21-1318

This review looks at Covid-19, hyperglycemia and new-onset diabetes. The authors reports that recently published studies suggest that COVID-19 is associated with new-onset diabetes; therefore, there is potential to identify and manage these people early, with the aim of improving long-term outcomes.


Certain chronic comorbidities, including diabetes, are highly prevalent in people with coronavirus disease 2019 (COVID-19) and are associated with an increased risk of severe COVID-19 and mortality. Mild glucose elevations are also common in COVID-19 patients and associated with worse outcomes even in people without diabetes. Several studies have recently reported new-onset diabetes associated with COVID-19. The phenomenon of new-onset diabetes following admission to the hospital has been observed previously with other viral infections and acute illnesses. The precise mechanisms for new-onset diabetes in people with COVID-19 are not known, but it is likely that a number of complex interrelated processes are involved, including previously undiagnosed diabetes, stress hyperglycemia, steroid-induced hyperglycemia, and direct or indirect effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the β-cell. There is an urgent need for research to help guide management pathways for these patients. In view of increased mortality in people with new-onset diabetes, hospital protocols should include efforts to recognize and manage acute hyperglycemia, including diabetic ketoacidosis, in people admitted to the hospital. Whether new-onset diabetes is likely to remain permanent is not known, as the long-term follow-up of these patients is limited. Prospective studies of metabolism in the setting of postacute COVID-19 will be required to understand the etiology, prognosis, and treatment opportunities.

COVID-19, Hyperglycemia, and New-Onset Diabetes [primary paper]