Stress hyperglycemia, Diabetes mellitus and COVID-19 infection: The impact on newly diagnosed type 1 diabetes.

Several recent studies have documented an increased incidence of newly diagnosed type 1 Diabetes (T1D) cases in children and adolescents during the COVID-19 pandemic and a more severe presentation at diabetes onset. In this descriptive study, we present the experience of the Diabetes Centre of the Division of Endocrinology, Diabetes, and Metabolism of the First Department of Pediatrics of the National and Kapodistrian University of Athens Medical School at "Aghia Sophia" Children's Hospital in Athens, Greece, concerning new cases of T1D diagnosis during the COVID-19 pandemic (March 2020- December 2021). Patients who had already been diagnosed with T1D and needed hospitalization due to poor control during the pandemic have been excluded from this study. Eighty- three children and adolescents with a mean age of 8,5 ± 4.02 years were admitted to the hospital due to newly diagnosed T1D during this 22 months' period in comparison to 34 new cases in the previous year. All patients admitted during the pandemic with a new diagnosis of T1D, presented in their majority with DKA (Ph: 7.2) representing an increase of new severe cases in comparison to previous years (Ph 7.2 versus 7.3, p value: 0.021, in the previous year), [p-value: 0.027]. 49 cases presented with DKA, of which 24 were characterized moderate and 14 severe DKA (28.9% and 16,9%, respectively), while 5 patients newly diagnosed, needed to be admitted to the ICU to recover from severe acidosis. Whether a previous COVID- 19 infection could have been the triggering factor is not supported by the SARS-Cov2 specific antibodies analysis in our cohort of patients. As far as HbA1c is concerned there was no statistically significant difference between the pre COVID-19 year and the years of the pandemic (11.6% versus 11.9%, p- value: 0.461). Triglycerides values were significantly higher in patients with new onset T1D during COVID-19 years compared to those before the pandemic (p value= 0.032). Additionally, there is a statistically significant correlation between Ph and Triglycerides for the whole period 2020-2021 (p-value<0.001), while this correlation is not significant for the year 2019. More large- scale studies are required to confirm these observations.

Absolute Hyperglycemia versus Stress Hyperglycemia Ratio for the Prognosis of Hospitalized Patients with COVID-19 in the First Months of the Pandemic: A Retrospective Study.

Diabetes is a risk factor for greater severity of coronavirus disease 2019 (COVID-19). The stress hyperglycemia ratio (SHR) is an independent predictor of critical illness, and it is reported to have a stronger association than absolute hyperglycemia. The aim of this study was to assess the relationship of absolute hyperglycemia and SHR with the severity of COVID-19, since there are no studies investigating SHR in patients with COVID-19. We conducted a retrospective observational study on hospitalized patients with COVID-19 in the first months of the pandemic, regarding absolute hyperglycemia, SHR, and severity outcomes. Of the 374 patients, 28.1% had a previous diagnosis of type 2 diabetes. Absolute hyperglycemia (64.8% versus 22.7%; p < 0.01) and SHR [1.1 (IQR 0.9-1.3) versus 1.0 (IQR 0.9-1.2); p < 0.001] showed a statistically significant association with previous diabetes. Absolute hyperglycemia showed a significant association with clinical severity of COVID-19 (79.0% versus 62.7%; p < 0.001), need for oxygen therapy (74.8% versus 54.4%; p < 0.001), invasive mechanical ventilation (28.6% versus 11.6%; p < 0.001), and intensive care unit (30.3% versus 14.9%; p = 0.002), but not with mortality; by contrast, there was no statistically significant association between SHR and all these parameters. Our results are in agreement with the literature regarding the impact of absolute hyperglycemia on COVID-19 severity outcomes, while SHR was not a significant marker. We therefore suggest that SHR should not be evaluated in all patients admitted in the hospital for COVID-19, and we encourage the standard measures at admission of blood glucose and HbA1c levels.

Glycemic Gap Predicts Mortality in a Large Multicenter Cohort Hospitalized with COVID-19.

PURPOSE: Diabetes or hyperglycemia at admission are established risk factors for adverse outcomes during hospitalization for COVID-19, but the impact of prior glycemic control is not clear. METHODS: We examined the relationship between clinical predictors including acute and chronic glycemia and clinical outcomes including ICU admission, mechanical ventilation (MV), and mortality among 1,786 individuals with diabetes or hyperglycemia (glucose > 10 mmol/l twice in 24 hrs.) admitted from March 2020 through February 2021 with COVID-19 infection at 5 university hospitals in the eastern U.S. RESULTS: The cohort was 51.3% male, 53.3% White, 18.8% Black, 29.0% Hispanic, with age = 65.6 ± 14.4 yrs., BMI = 31.5 ± 7.9 kg/m2, glucose = 12.0 ± 7.5 mmol/l [216 ± 135 mg/dl], and HbA1c = 8.07 ± 2.25%. During hospitalization, 38.9% were admitted to the ICU, 22.9% received MV, and 10.6% died. Age (p < 0.001) and admission glucose (p = 0.014) but not HbA1c were associated with increased risk of mortality. Glycemic gap, defined as admission glucose minus estimated average glucose based on HbA1c, was a stronger predictor of mortality than either admission glucose or HbA1c alone (OR = 1.040 [95% CI: 1.019, 1.061] per mmol/l, p < 0.001). In an adjusted multivariable model, glycemic gap, age, BMI, and diabetic ketoacidosis on admission were associated with increased mortality, while higher eGFR and use of any diabetes medication were associated with lower mortality (p < 0.001). CONCLUSIONS: Relative hyperglycemia, as measured by the admission glycemic gap, is an important marker of mortality risk in COVID-19.

Relationship between cytokine release and stress hyperglycemia in patients hospitalized with COVID-19 infection.

Introduction: Stress hyperglycemia is a frequent finding in patients with COVID-19 infection and could affect the outcome of disease. Cytokines released in response to infection could have adverse effects on insulin sensitivity and pancreatic beta-cell function. The aim of the study was to examine the relationships of stress hyperglycemia with cytokines and clinical outcomes in hospitalized patients with COVID-19. Methods: In a cross-sectional analysis of 150 patients hospitalized for COVID-19 infection who were included in the GIRA-COVID database, we identified patients with stress hyperglycemia by calculation of the Stress Hyperglycemia Ratio (SHR) and use of a cut-off of 1.14. Plasma levels of cytokines principally involved in COVID-19 infection-related cytokine storm were measured. Outcome variables were use of mechanical ventilation and death within 60 days from hospital admission. Results: Patients with SHR > 1.14 had significantly higher plasma insulin, HOMA-index, and levels of interleukin-10 (IL-10), interleukin-10/tumor necrosis factor-a ratio (IL-10/TNF-α), and CXC motif chemokine ligand 10 (CXCL10) than patients with SHR ≤ 1.14. IL-10, IL-10/TNF-α ratio, CXCL10, and IFN-γ were significantly and directly related with SHR in univariate analysis and multivariate logistic regression models showed that IL-10, IL-10/TNF-α ratio, and CXCL10 were independently associated with SHR>1.14. In a multivariate logistic model, stress hyperglycemia predicted use of mechanical ventilation (OR 2.453; CI 1.078-6.012) and death (OR 2.281; CI 1.049-7.369) independently of diabetes and other major confounders. Conclusions: In patients hospitalized for COVID-19 infection, stress hyperglycemia is associated with worse clinical outcomes and is independently related to levels of cytokines that might impair glucose homeostasis.

Stress Hyperglycemia Ratio as a Prognostic Marker in Diabetic Patients Hospitalized with COVID-19.

Evidence is conflicting about the diabetes characteristics associated with worse outcome among hospitalized COVID-19 patients. We aimed to assess the role of stress hyperglycemia ratio (SHR) as a prognostic marker among them. In our retrospective cohort study, patients were stratified according to SHR, admission glucose, and glycated hemoglobin tertiles. The primary outcome was a composite endpoint of invasive mechanical ventilation, intensive care unit admission, and in-hospital mortality. The study included 395 patients with a mean age of 59 years, and 50.1% were males. Patients in the third tertile of SHR developed more primary events, and the difference was significant compared to the first tertile (p = 0.038) and close to significance compared to the second tertile (p = 0.054). There was no significant difference in the outcomes across admission glucose and glycated hemoglobin tertiles. A higher SHR tertile was an independent risk factor for the primary outcome (OR, 1.364; 95% CI: 1.014-1.836; p = 0.040) after adjustment for other covariables. In hospitalized COVID-19 diabetic patients, SHR third tertile was significantly associated with worse outcome and death. SHR can be a better prognostic marker compared to admission glucose and glycated hemoglobin. A higher SHR was an independent risk factor for worse outcome and in-hospital mortality.

Stress hyperglycemia ratio, rather than admission blood glucose, predicts in-hospital mortality and adverse outcomes in moderate-to severe COVID-19 patients, irrespective of pre-existing glycemic status.

AIM: To compare admission-blood-glucose (ABG) or stress-hyperglycemia-ratio (SHR) performs better in predicting mortality and worse outcomes in COVID-19 patients with (DM) and without known Type 2 Diabetes Mellitus (UDM). METHODS: ABG and SHR were tested for 451 patients with moderate-severe COVID-19 infection [DM = 216,47.9%; pre-diabetes = 48,10.6%, UDM = 187,41.4%],who were followed-up to look for in-hospital-mortality (primary outcome) and secondary outcomes (ICU stay or mechanical ventilation, hospital-acquired-sepsis and multiple organ dysfunction syndrome [MODS]). Those with and without SHR ≥ 1.14 were compared; logistic regression was done to identify predictors of outcomes, with subgroup analysis based on pre-existing DM status and COVID-19 severity. RESULTS: Those who died (n = 131) or developed ≥ 1 secondary outcomes (n = 218) had higher prevalence of SHR ≥ 1.14, ABG ≥ 180 mg/dl and higher median SHR (pall < 0.01). Those with SHR ≥ 1.14 had higher mortality (53.7%), higher incidence of ≥ 1 secondary outcomes (71.3%) irrespective of pre-existing diabetes status. SHR ≥ 1.14, but not ABG ≥ 180 was an independent predictor of mortality in the whole group (OR: 7.81,4.07-14.98), as also the DM (OR:10.51,4.34-25.45) and UDM (5.40 (1.57-18.55) subgroups. SHR ≥ 1.14 [OR: 4.41 (2.49-7.84)] but not ABG ≥ 180 could independently predict secondary outcomes AUROC of SHR in predicting mortality was significantly higher than ABG in all subgroups. CONCLUSION: SHR better predicts mortality and adverse outcomes than ABG in patients with COVID-19, irrespective of pre-existing chronic glycemic status.

Newly diagnosed diabetes vs. pre-existing diabetes upon admission for COVID-19: Associated factors, short-term outcomes, and long-term glycemic phenotypes.

AIMS: High rates of newly diagnosed diabetes mellitus (NDDM) have been reported in association with coronavirus disease-2019 (COVID-19). Factors associated with NDDM and long-term glycemic outcomes are not known. METHODS: Retrospective review of individuals admitted with COVID-19 and diabetes mellitus (DM; based on labs, diagnoses, outpatient insulin use, or severe inpatient hyperglycemia) between March and September 2020, with follow-up through July 2021. RESULTS: Of 1902 individuals admitted with COVID-19, 594 (31.2%) had DM; 77 (13.0%) of these had NDDM. Compared to pre-existing DM, NDDM was more common in younger patients and less common in those of non-Hispanic White race/ethnicity. Glycemic parameters were lower and inflammatory markers higher in patients with NDDM. In adjusted models, NDDM was associated with lower insulin requirements, longer length of stay, and intensive care unit admission but not death. Of 64 survivors with NDDM, 36 (56.3%) continued to have DM, 26 (40.6%) regressed to normoglycemia or pre-diabetes, and 2 were unable to be classified at a median follow-up of 323 days. CONCLUSIONS: Diabetes diagnosed at COVID-19 presentation is associated with lower glucose but higher inflammatory markers and ICU admission, suggesting stress hyperglycemia as a major physiologic mechanism. Approximately half of such individuals experience regression of DM.

Stress Hyperglycemia Ratio may Portend Poor Outcomes in COVID-19.

Magoon R, Jose J. Stress Hyperglycemia Ratio may Portend Poor Outcomes in COVID-19. Indian J Crit Care Med 2021;25(11):1329.