History of bariatric surgery and COVID-19 outcomes in patients with type 2 diabetes: Results from the CORONADO study.

OBJECTIVE: This study assessed the impact of a history of metabolic and bariatric surgery (MBS) on the clinical outcomes in patients with type 2 diabetes (T2D) and severe obesity hospitalized for COVID-19. METHODS: In this post hoc analysis from the nationwide observational CORONADO (Coronavirus SARS-CoV2 and Diabetes Outcomes) study, patients with T2D and a history of MBS were matched with patients without MBS for age, sex, and BMI either at the time of MBS or on admission for COVID-19. The composite primary outcome (CPO) combined invasive mechanical ventilation and/or death within 7 and 28 days following admission. RESULTS: Out of 2,398 CORONADO participants, 20 had a history of MBS. When matching for BMI at the time of MBS and after adjustment for diabetes duration, the CPO occurred less frequently within 7 days (3 vs. 17 events, OR: 0.15 [0.01 to 0.94], p = 0.03) and 28 days (3 vs. 19 events, OR: 0.11 [0.01 to 0.71], p = 0.02) in patients with MBS (n = 16) vs. controls (n = 44). There was no difference in CPO rate between patients with MBS and controls when matching for BMI on admission. CONCLUSIONS: These data are reassuring regarding COVID-19 prognosis in patients with diabetes and a history of MBS compared with those without MBS.

Diabetes Increases Severe COVID-19 Outcomes Primarily in Younger Adults.

CONTEXT: Diabetes is reported as a risk factor for severe coronavirus disease 2019 (COVID-19), but whether this risk is similar in all categories of age remains unclear. OBJECTIVE: To investigate the risk of severe COVID-19 outcomes in hospitalized patients with and without diabetes according to age categories. DESIGN SETTING AND PARTICIPANTS: We conducted a retrospective observational cohort study of 6314 consecutive patients hospitalized for COVID-19 between February and 30 June 2020 in the Paris metropolitan area, France; follow-up was recorded until 30 September 2020. MAIN OUTCOME MEASURE(S): The main outcome was a composite outcome of mortality and orotracheal intubation in subjects with diabetes compared with subjects without diabetes, after adjustment for confounding variables and according to age categories. RESULTS: Diabetes was recorded in 39% of subjects. Main outcome was higher in patients with diabetes, independently of confounding variables (hazard ratio [HR] 1.13 [1.03-1.24]) and increased with age in individuals without diabetes, from 23% for those <50 to 35% for those >80 years but reached a plateau after 70 years in those with diabetes. In direct comparison between patients with and without diabetes, diabetes-associated risk was inversely proportional to age, highest in <50 years and similar after 70 years. Similarly, mortality was higher in patients with diabetes (26%) than in those without diabetes (22%, P < 0.001), but adjusted HR for diabetes was significant only in patients younger than age 50 years (HR 1.81 [1.14-2.87]). CONCLUSIONS: Diabetes should be considered as an independent risk factor for the severity of COVID-19 in young adults more so than in older adults, especially for individuals younger than 70 years.

The COVID-19 lockdown as an opportunity to change lifestyle and body weight in people with overweight/obesity and diabetes: Results from the national French COVIDIAB cohort.

BACKGROUND AND AIMS: To analyze lifestyle habits and weight evolution during the COVID-19 pandemic-associated lockdown, in diabetes and overweight/obesity patients (body mass index (BMI) [25-29.9] and ≥30 kg/m2, respectively). METHODS AND RESULTS: We collected information on participants' characteristics and behavior regarding lifestyle before and during the lockdown, through the CoviDIAB web application, which is available freely for people with diabetes in France. We stratified the cohort according to BMI (≥25 kg/m2vs < 25 kg/m2) and examined the determinants of weight loss (WL), WL > 1 kg vs no-WL) in participants with a BMI ≥25 kg/m2, in both univariate and multivariate analyses. Of the 5280 participants (mean age, 52.5 years; men, 49%; diabetes, 100% by design), 69.5% were overweight or obese (mean BMI, 28.6 kg/m2 (6.1)). During the lockdown, patients often quit or decreased smoking; overweight/obese participants increased alcohol consumption less frequently as compared with normal BMI patients. In addition, overweight/obese patients were more likely to improve other healthy behaviors on a larger scale than patients with normal BMI: increased intake of fruits and vegetables, reduction of snacks intake, and reduction of total dietary intake. WL was observed in 18.9% of people with a BMI ≥25 kg/m2, whereas 28.6% of them gained weight. Lifestyle favorable changes characterized patients with WL. CONCLUSIONS: A significant proportion of overweight/obese patients with diabetes seized the opportunity of lockdown to improve their lifestyle and to lose weight. Identifying those people may help clinicians to personalize practical advice in the case of a recurrent lockdown.

Predictors of hospital discharge and mortality in patients with diabetes and COVID-19: updated results from the nationwide CORONADO study.

AIMS/HYPOTHESIS: This is an update of the results from the previous report of the CORONADO (Coronavirus SARS-CoV-2 and Diabetes Outcomes) study, which aims to describe the outcomes and prognostic factors in patients with diabetes hospitalised for coronavirus disease-2019 (COVID-19). METHODS: The CORONADO initiative is a French nationwide multicentre study of patients with diabetes hospitalised for COVID-19 with a 28-day follow-up. The patients were screened after hospital admission from 10 March to 10 April 2020. We mainly focused on hospital discharge and death within 28 days. RESULTS: We included 2796 participants: 63.7% men, mean age 69.7 ± 13.2 years, median BMI (25th-75th percentile) 28.4 (25.0-32.4) kg/m2. Microvascular and macrovascular diabetic complications were found in 44.2% and 38.6% of participants, respectively. Within 28 days, 1404 (50.2%; 95% CI 48.3%, 52.1%) were discharged from hospital with a median duration of hospital stay of 9 (5-14) days, while 577 participants died (20.6%; 95% CI 19.2%, 22.2%). In multivariable models, younger age, routine metformin therapy and longer symptom duration on admission were positively associated with discharge. History of microvascular complications, anticoagulant routine therapy, dyspnoea on admission, and higher aspartate aminotransferase, white cell count and C-reactive protein levels were associated with a reduced chance of discharge. Factors associated with death within 28 days mirrored those associated with discharge, and also included routine treatment by insulin and statin as deleterious factors. CONCLUSIONS/INTERPRETATION: In patients with diabetes hospitalised for COVID-19, we established prognostic factors for hospital discharge and death that could help clinicians in this pandemic period. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT04324736.

Use of dipeptidyl peptidase-4 inhibitors and prognosis of COVID-19 in hospitalized patients with type 2 diabetes: A propensity score analysis from the CORONADO study.

AIM: To investigate the association between routine use of dipeptidyl peptidase-4 (DPP-4) inhibitors and the severity of coronavirus disease 2019 (COVID-19) infection in patient with type 2 diabetes in a large multicentric study. MATERIALS AND METHODS: This study was a secondary analysis of the CORONADO study on 2449 patients with type 2 diabetes (T2D) hospitalized for COVID-19 in 68 French centres. The composite primary endpoint combined tracheal intubation for mechanical ventilation and death within 7 days of admission. Stabilized weights were computed for patients based on propensity score (DPP-4 inhibitors users vs. non-users) and were used in multivariable logistic regression models to estimate the average treatment effect in the treated as inverse probability of treatment weighting (IPTW). RESULTS: Five hundred and ninety-six participants were under DPP-4 inhibitors before admission to hospital (24.3%). The primary outcome occurred at similar rates in users and non-users of DPP-4 inhibitors (27.7% vs. 28.6%; p = .68). In propensity analysis, the IPTW-adjusted models showed no significant association between the use of DPP-4 inhibitors and the primary outcome by Day 7 (OR [95% CI]: 0.95 [0.77-1.17]) or Day 28 (OR [95% CI]: 0.96 [0.78-1.17]). Similar neutral findings were found between use of DPP-4 inhibitors and the risk of tracheal intubation and death. CONCLUSIONS: These data support the safety of DPP-4 inhibitors for diabetes management during the COVID-19 pandemic and they should not be discontinued.

Association of diabetes and outcomes in patients with COVID-19: Propensity score-matched analyses from a French retrospective cohort.

BACKGROUND: Our study aimed to compare the clinical outcomes of patients with and without diabetes admitted to hospital with COVID-19. METHODS: This retrospective multicentre cohort study comprised 24 tertiary medical centres in France, and included 2851 patients (675 with diabetes) hospitalized for COVID-19 between 26 February and 20 April 2020. A propensity score-matching (PSM) method (1:1 matching including patients' characteristics, medical history, vital statistics and laboratory results) was used to compare patients with and without diabetes (n = 603 per group). The primary outcome was admission to an intensive care unit (ICU) and/or in-hospital death. RESULTS: After PSM, all baseline characteristics were well balanced between those with and without diabetes: mean age was 71.2 years; 61.8% were male; and mean BMI was 29 kg/m2. A history of cardiovascular, chronic kidney and chronic obstructive pulmonary diseases were found in 32.8%, 22.1% and 6.4% of participants, respectively. The risk of experiencing the primary outcome was similar in patients with or without diabetes [hazard ratio (HR): 1.16, 95% confidence interval (CI): 0.95-1.41; P = 0.14], and was 1.29 (95% CI: 0.97-1.69) for in-hospital death, 1.26 (95% CI: 0.9-1.72) for death with no transfer to an ICU and 1.14 (95% CI: 0.88-1.47) with transfer to an ICU. CONCLUSION: In this retrospective study cohort of patients hospitalized for COVID-19, diabetes was not significantly associated with a higher risk of severe outcomes after PSM. TRIAL REGISTRATION NUMBER: NCT04344327.

Stay-at-Home Orders During the COVID-19 Pandemic, an Opportunity to Improve Glucose Control Through Behavioral Changes in Type 1 Diabetes.

OBJECTIVE: To investigate the impact of coronavirus disease 2019 lockdown on glycemic control and associated factors in people living with type 1 diabetes. RESEARCH DESIGN AND METHODS: An observational evaluation from a self-reported questionnaire on behavioral changes and glycemic information from flash glucose monitoring (FGM) during the lockdown in 1,378 individuals living with type 1 diabetes who used a French dedicated nationwide web application (CoviDIAB). RESULTS: The main outcome was the change of the mean glucose level 2 months before and 1 month after the lockdown. We found that mean glucose improved from 9.1 ± 1.7 mmol/L to 8.7 ± 1.7 mmol/L (P < 0.001). Factors associated with better glycemic control were a decrease of alcohol consumption (odds ratio [OR] 1.75 [95% CI 1.04-2.94]), an increase in the frequency of FGM scans (OR 1.48 [1.04-2.10]) and in the number of hypoglycemia events (OR 1.67 [1.13-2.46]), and an easier diabetes control perception (OR 1.71 [1.18-2.49]). CONCLUSIONS: Our findings suggest that lockdown has a positive impact on glycemic control in people with type 1 diabetes.

Metformin use is associated with a reduced risk of mortality in patients with diabetes hospitalised for COVID-19.

AIMS: Metformin exerts anti-inflammatory and immunosuppressive effects. We addressed the impact of prior metformin use on prognosis in patients with type 2 diabetes hospitalised for COVID-19. METHODS: CORONADO is a nationwide observational study that included patients with diabetes hospitalised for COVID-19 between March 10 and April 10, 2020 in 68 French centres. The primary outcome combined tracheal intubation and/or death within 7 days of admission. A Kaplan-Meier survival curve was reported for death up to day 28. The association between metformin use and outcomes was then estimated in a logistic regression analysis after applying a propensity score inverse probability of treatment weighting approach. RESULTS: Among the 2449 patients included, 1496 were metformin users and 953 were not. Compared with non-users, metformin users were younger with a lower prevalence of diabetic complications, but had more severe features of COVID-19 on admission. The primary endpoint occurred in 28.0% of metformin users (vs 29.0% in non-users, P = 0.6134) on day 7 and in 32.6% (vs 38.7%, P = 0.0023) on day 28. The mortality rate was lower in metformin users on day 7 (8.2 vs 16.1%, P < 0.0001) and on day 28 (16.0 vs 28.6%, P < 0.0001). After propensity score weighting was applied, the odds ratios for primary outcome and death (OR [95%CI], metformin users vs non-users) were 0.838 [0.649-1.082] and 0.688 [0.470-1.007] on day 7, then 0.783 [0.615-0.996] and 0.710 [0.537-0.938] on day 28, respectively. CONCLUSION: Metformin use appeared to be associated with a lower risk of death in patients with diabetes hospitalised for COVID-19.

Monocytopenia, monocyte morphological anomalies and hyperinflammation characterise severe COVID-19 in type 2 diabetes.

Early in the COVID-19 pandemic, type 2 diabetes (T2D) was marked as a risk factor for severe disease and mortality. Inflammation is central to the aetiology of both conditions where variations in immune responses can mitigate or aggravate disease course. Identifying at-risk groups based on immunoinflammatory signatures is valuable in directing personalised care and developing potential targets for precision therapy. This observational study characterised immunophenotypic variation associated with COVID-19 severity in T2D. Broad-spectrum immunophenotyping quantified 15 leucocyte populations in peripheral circulation from a cohort of 45 hospitalised COVID-19 patients with and without T2D. Lymphocytopenia and specific loss of cytotoxic CD8+ lymphocytes were associated with severe COVID-19 and requirement for intensive care in both non-diabetic and T2D patients. A morphological anomaly of increased monocyte size and monocytopenia restricted to classical CD14Hi CD16- monocytes was specifically associated with severe COVID-19 in patients with T2D requiring intensive care. Increased expression of inflammatory markers reminiscent of the type 1 interferon pathway (IL6, IL8, CCL2, INFB1) underlaid the immunophenotype associated with T2D. These immunophenotypic and hyperinflammatory changes may contribute to increased voracity of COVID-19 in T2D. These findings allow precise identification of T2D patients with severe COVID-19 as well as provide evidence that the type 1 interferon pathway may be an actionable therapeutic target for future studies.

Correction to: Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.

The authors regret a mistake in Table 1.

Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters.

Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events.

Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study.

AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736.