Dexamethasone Increases Diabetes Complications but Still Saves Lives

via MedScape | 12 November 2021 | Dexamethasone Increases Diabetes Complications but Still Saves Lives

Research presented earlier this month at The Society for Endocrinology’s annual conference, SfE BES 2021, suggests that  when dexamethasone is prescribed to hospitalised COVID-19 patients with diabetes may increase their risk of developing steroid-induced dysglycaemia but it does not prevent them from experiencing the life-saving benefits of the drug, suggests a real-world UK analysis.

Data on more than 2250 patients treated in the first and second waves of the pandemic showed that, in patients with diabetes, dexamethasone increased the risk of dysglycaemia more than 20-fold.

However, patients with dexamethasone-associated complications did not have an increased risk of death, and overall the drug was shown to reduce the risk of admission to intensive care or death within 30 days of admission by 56 per cent (Source: MedScape).

The full news story is available from MedScape

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.

Abstract

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]

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.

Abstract

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]

Insulin Treatment May Increase Adverse Outcomes in Patients With COVID-19 and Diabetes: A Systematic Review and Meta-Analysis

Yang, Y.,  Zixin, C. & Zhang, J. | 2021| Insulin Treatment May Increase Adverse Outcomes in Patients With COVID-19 and Diabetes: A Systematic Review and Meta-Analysis | Frontiers in Endocrinology | https://doi.org/10.3389/fendo.2021.696087

The reviewers invovlved in this analysis, conducted a systematic review and meta-analysis to determine the association between insulin injection and the outcomes of COVID-19 to provide certain clinical information for patients with Covid-19 and diabetes. They recognise that while their findings may provide evidence of the adverse effect of insulin treatment among patients with COVID-19 and diabetes, especially among those with type 2 diabetes (T2DM), as the subjects in most included studies suffered from T2DM. However, considering the limited number of studies concerning type 1 diabetes (T1DM) in our meta-analysis, the association between insulin treatment and adverse outcomes in patients with COVID-19 and T1DM are needed to be investigated in more large-scale clinical studies (Source: Yang, Zixin & Zhang, 2021).

Background and Objective: 

Recently, insulin treatment has been found to be associated with increased mortality and other adverse outcomes in patients with coronavirus disease 2019 (COVID-19) and diabetes, but the results remain unclear and controversial, therefore, we conducted this meta-analysis.

Methods: 

Four databases, namely, PubMed, Web of Science, EMBASE and the Cochrane Library, were used to identify all studies concerning insulin treatment and the adverse effects of COVID-19, including mortality, incidence of severe/critical complications, in-hospital admission and hospitalization time. To assess publication bias, funnel plots, Begg’s tests and Egger’s tests were used. The odds ratios (ORs) with 95% confidence intervals (CIs) were used to access the effect of insulin therapy on mortality, severe/critical complications and in-hospital admission. The association between insulin treatment and hospitalization time was calculated by the standardized mean difference (SMD) with 95% CIs.

Results: 

Eighteen articles, involving a total of 12277 patients with COVID-19 and diabetes were included. Insulin treatment was significantly associated with an increased risk of mortality (OR=2.10; 95% CI, 1.51-2.93) and incidence of severe/critical COVID-19 complications (OR=2.56; 95% CI, 1.18-5.55). Moreover, insulin therapy may increase in-hospital admission in patients with COVID-19 and diabetes (OR=1.31; 95% CI, 1.06-1.61). However, there was no significant difference in the hospitalization time according to insulin treatment (SMD=0.21 95% CI, -0.02-0.45).

Conclusions: 

Insulin treatment may increase mortality and severe/critical complications in patients with COVID-19 and diabetes, but more large-scale studies are needed to confirm and explore the exact mechanism.

Insulin Treatment May Increase Adverse Outcomes in Patients With COVID-19 and Diabetes: A Systematic Review and Meta-Analysis [primary paper]

Temporal trends in emergency admissions for diabetic ketoacidosis in people with diabetes in England before and during the COVID-19 pandemic #Covid19RftLks

Misra, S. et al | 2021| Temporal trends in emergency admissions for diabetic ketoacidosis in people with diabetes in England before and during the COVID-19 pandemic | The Lancet Diabetes & Endocrinology | https://doi.org/10.1016/S2213-8587(21)00208-4

The authors of this population study set out to examine DKA presentations during the COVID-19 pandemic to: determine whether numbers of DKA admissions had increased during the first wave, after the first wave, and during the second wave of the pandemic, compared with in preceding years; analyse the demographic characteristics associated with a presentation of DKA in those with pre-existing type 1 and type 2 diabetes and those with a new presentation of diabetes compared with in preceding years; and compare DKA admissions between the first wave, post-first wave, and second wave of the pandemic.

In this analysis of the largest analysis to date of diabetic ketoacidosis (DKA) cases in a complete national dataset; the authors of this paper found a rise in all hospital admissions with DKA during the first wave, post-first wave, and second wave of the COVID-19 pandemic in England, compared with mean numbers for matched time periods over the preceding 3 years. The significant increases in DKA admissions in people with type 2 diabetes and people with newly diagnosed diabetes were offset by a concurrent significant reduction in people with type 1 diabetes presenting with DKA. These trends by diabetes type held true during the first wave, when testing for COVID-19 was restricted; post-first wave, when COVID-19 cases were very low; and second wave, when universal testing was available (Source: Misra et al, 2021).

Temporal trends in emergency admissions for diabetic ketoacidosis in people with diabetes in England before and during the COVID-19 pandemic: a population-based study [primary apper]

COVID-19 and peripheral arterial complications in people with diabetes and hypertension: A systematic review #Covid19RftLks

Rastogi, A., Dogra, H. & Jude, E.B | 2021| COVID-19 and peripheral arterial complications in people with diabetes and hypertension: A systematic review| Diabetes Metab Syndr| | 15 | 5 | 102204. doi: 10.1016/j.dsx.2021.102204. Epub ahead of print. PMID: 34303918; PMCID: PMC8266514.

COVID-19 is a unique thrombo-inflammatory condition and patients with background diabetes or hypertension are more susceptible for lower limb complications due to peripheral arterial disease presenting as gangrene. The authors conducted a systematic review of the reported cases of peripheral gangrene in COVID-19 patients, co-existing comorbidities, specific treatment given, and outcomes of limb amputations or death.

COVID-19 and peripheral arterial complications in people with diabetes and hypertension: A systematic review [primary paper]

Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial

Kosiborod, M.N. et al | 2021 | Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial | The Lancet Diabetes & Endocrinology | DOI:https://doi.org/10.1016/S2213-8587(21)00180-7

The DARE-19 trial has evaluated the efficacy and safety of dapagliflozin in patients who had at least one cardiometabolic risk factor, such as hypertension and type 2 diabetes among others, and who were hospitalised with COVID-19.

At screening, 636 patients (50·9 per cent ) had type 2 diabetes. The prespecified subgroup analyses for the primary outcome of prevention and recovery are shown in, and were generally consistent with the main findings, including in patients with and without diabetes, although there was heterogeneity noted by sex. Diabetic ketoacidosis was reported in two patients in the dapagliflozin group both of whom had type 2 diabetes at baseline; these events were non-severe and resolved after study medication discontinuation.

To the authors’ knowledge, DARE-19 is the first, large randomised controlled trial to evaluate efficacy and safety of SGLT2 inhibitors in patients hospitalised with COVID-19 and has implications for clinical practice and future research. Dapagliflozin did not significantly reduce the proportion of patients with organ dysfunction or death or who experienced improved recovery. Although we observed numerically fewer events of organ dysfunction or death in patients who received dapagliflozin as compared with placebo, this difference was not statistically significant, and might not be generalisable to other populations. Importantly, dapagliflozin was well tolerated in one of the highest risk (with respect to organ failure and death) patient populations ever to be treated with SGLT2 inhibitors.


Implications of all the available evidence

Their study shows that dapagliflozin was well tolerated, with no new safety concerns identified in this acutely ill patient population. Therefore, for patients already receiving SGLT2 inhibitors before a COVID-19 diagnosis, our findings support continuation of this treatment, as long as patients are monitored. Because SGLT2 inhibitors do not have a direct anti-viral effect on SARS-CoV2, our findings (although not conclusive) suggest a need for future trials to determine whether dapagliflozin might provide organ protection in non-COVID-19 hospitalised patients at high risk for progressing to critical illness (Source: Kosiborod et al, 2021).

Primary paper Dapagliflozin in patients with cardiometabolic risk factors hospitalised with COVID-19 (DARE-19): a randomised, double-blind, placebo-controlled, phase 3 trial

Diabetes, Obesity, COVID-19, Insulin, and Other Antidiabetes Drugs #Covid19RftLks

 Dandona, P. & Ghanim, H. | 2021 | Diabetes, Obesity, COVID-19, Insulin, and Other Antidiabetes Drugs | Diabetes Care |   dci210003; DOI: 10.2337/dci21-0003

This review published in the journal Diabetes Care aims to explain some of the processes involved in chronic inflammation and identifies potential strategies to combat them.

Paper available from Diabetes Care