Patients with prediabetes are at greater risk of developing diabetes 5 months postacute SARS-CoV-2 infection: a retrospective cohort study.

INTRODUCTION: Patients with prediabetes who contract SARS-CoV-2 infection (COVID-19) could be at higher risk of developing frank diabetes compared those who do not. This study aims to investigate the incidence of new-onset diabetes in patients with prediabetes after COVID-19 and if it differs from those not infected. RESEARCH DESIGN AND METHODS: Using electronic medical record data, 42 877 patients with COVID-19, 3102 were identified as having a history of prediabetes in the Montefiore Health System, Bronx, New York. During the same time period, 34 786 individuals without COVID-19 with history of prediabetes were identified and 9306 were propensity matched as controls. SARS-CoV-2 infection status was determined by a real-time PCR test between March 11, 2020 and August 17, 2022. The primary outcomes were new-onset in-hospital diabetes mellitus (I-DM) and new-onset persistent diabetes mellitus (P-DM) at 5 months after SARS-CoV-2 infection. RESULTS: Compared with hospitalized patients without COVID-19 with history of prediabetes, hospitalized patients with COVID-19 with history of prediabetes had a higher incidence of I-DM (21.9% vs 6.02%, p<0.001) and of P-DM 5 months postinfection (14.75% vs 7.51%, p<0.001). Non-hospitalized patients with and without COVID-19 with history of prediabetes had similar incidence of P-DM (4.15% and 4.1%, p>0.05). Critical illness (HR 4.6 (95% CI 3.5 to 6.1), p<0.005), in-hospital steroid treatment (HR 2.88 (95% CI 2.2 to 3.8), p<0.005), SARS-CoV-2 infection status (HR 1.8 (95% CI 1.4 to 2.3), p<0.005), and hemoglobin A1c (HbA1c) (HR 1.7 (95% CI 1.6 to 1.8), p<0.005) were significant predictors of I-DM. I-DM (HR 23.2 (95% CI 16.1 to 33.4), p<0.005), critical illness (HR 2.4 (95% CI 1.6 to 3.8), p<0.005), and HbA1c (HR 1.3 (95% CI 1.1 to 1.4), p<0.005) were significant predictors of P-DM at follow-up. CONCLUSIONS: SARS-CoV-2 infection confers a higher risk for developing persistent diabetes 5 months post-COVID-19 in patients with prediabetes who were hospitalized for COVID-19 compared with COVID-19-negative counterparts with prediabetes. In-hospital diabetes, critical illness, and elevated HbA1c are risk factors for developing persistent diabetes. Patients with prediabetes with severe COVID-19 disease may need more diligent monitoring for developing P-DM postacute SARS-CoV-2 infection.

Dichotomising the risk of hyperglycaemia into diabetes and prediabetes may render a disservice to patient care.

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, accounting for one-third of global mortality. Prediabetes increases the risk of CVDs as well as several other conditions, yet people with prediabetes may not seek intervention, thinking that they do not have diabetes, as the risk of progression may have not been emphasised by the healthcare professional. Accumulating evidence indicates that hyperglycaemia represents a continuum of CVD risk and dichotomising the risk into type 2 diabetes and prediabetes may deter early clinical intervention. It is proffered that the term 'prediabetes' is a misnomer that may disguise a serious condition, fostering complacency and undermining its prognostic significance.

Prediabetes Induces More Severe Acute COVID-19 Associated With IL-6 Production Without Worsening Long-Term Symptoms.

Aims: Pre-existing conditions, such as age, hypertension, obesity, and diabetes, constitute known risk factors for severe COVID-19. However, the impact of prediabetes mellitus (PDM) on COVID-19 severity is less clear. This study aimed to evaluate the influence of PDM in the acute and long-term phases of COVID-19. Materials and methods: We compared inflammatory mediators, laboratory and clinical parameters and symptoms in COVID-19 patients with prediabetes (PDM) and without diabetes (NDM) during the acute phase of infection and at three months post-hospitalization. Results: Patients with PDM had longer hospital stays and required intensive care unit admission more frequently than NDM. Upon hospitalization, PDM patients exhibited higher serum levels of interleukin 6 (IL-6), which is related to reduced partial pressure of oxygen (PaO2) in arterial blood, oxygen saturation (SpO2) and increased COVID-19 severity. However, at three months after discharge, those with PDM did not exhibit significant alterations in laboratory parameters or residual symptoms; however, PDM was observed to influence the profile of reported symptoms. Conclusions: PDM seems to be associated with increased risk of severe COVID-19, as well as higher serum levels of IL-6, which may constitute a potential biomarker of severe COVID-19 risk in affected patients. Furthermore, while PDM correlated with more severe acute-phase COVID-19, no long-term worsening of sequelae was observed.

Prediabetes and COVID-19 severity, an underestimated risk factor: A systematic review and meta-analysis.

BACKGROUND AND AIMS: The novel coronavirus disease 2019 (COVID-19) has rapidly spread through the whole globe. Since the beginning of the outbreak, some individuals were more likely to manifest more severe outcomes. Diabetic patients were of that sort; however, the severity of COVID-19 in prediabetic ones remained less identified. This study aimed to systematically review and conduct a meta-analysis of the previously published observational studies investigating the severity of COVID-19 in prediabetic patients. METHODS: Medline/PubMed, Scopus, EMBASE, Web of Science, Cochrane library, and google scholar databases were queried to identify relevant studies concerning prediabetes and serious COVID-19 outcomes. The Newcastle-Ottawa scale was used to assess the quality of the included studies. Odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the likelihood of severe presentations in prediabetic patients. RESULTS: A total of 3027 patients were included in the meta-analysis. A random-effects model was used regarding the high heterogeneity (I2 = 55%). Prediabetes was significantly associated with adverse outcomes of COVID-19 with an OR of 2.58 (95%CI, 1.46-4.56). CONCLUSION: Prediabetes could act as a risk factor for the severity of COVID-19. Early detection of prediabetic patients might be helpful to adopt preventive and protective strategies to improve the prognosis of the infected individuals.

The Mechanisms of the Development of Atherosclerosis in Prediabetes.

Lifestyle changes, such as overeating and underexercising, can increase the risk of prediabetes. Diabetes is one of the leading causes of atherosclerosis, and recently it became clear that the pathophysiology of atherosclerosis progresses even before the onset of diabetic symptoms. In addition to changes in platelets and leukocytes in the hyperglycemic state and damage to vascular endothelial cells, extracellular vesicles and microRNAs were found to be involved in the progression of prediabetes atherosclerosis. This review discusses the cellular and molecular mechanisms of these processes, with an intention to enable a comprehensive understanding of the pathophysiology of prediabetes and atherosclerosis.

Impaired glucose metabolism in patients with diabetes, prediabetes, and obesity is associated with severe COVID-19.

BACKGROUND: Identification of risk factors of severe coronavirus disease 2019 (COVID-19) is critical for improving therapies and understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. We analyzed 184 patients hospitalized for COVID-19 in Livingston, New Jersey for clinical characteristics associated with severe disease. The majority of patients with COVID-19 had diabetes mellitus (DM) (62.0%), Pre-DM (23.9%) with elevated fasting blood glucose (FBG), or a body mass index >30 with normal hemoglobin A1c (HbA1C) (4.3%). SARS-CoV-2 infection was associated with new and persistent hyperglycemia in 29 patients, including several with normal HbA1C levels. Forty-four patients required intubation, which occurred significantly more often in patients with DM as compared with non-diabetics. Severe COVID-19 occurs in the presence of impaired glucose metabolism in patients, including those with DM, preDM, and obesity. COVID-19 is associated with elevated FBG and several patients presented with new onset DM or in DKA. The association of dysregulated glucose metabolism and severe COVID-19 suggests that SARS-CoV-2 pathogenesis involves a novel interplay with glucose metabolism. Exploration of pathways by which SARS-CoV-2 interacts glucose metabolism is critical for understanding disease pathogenesis and developing therapies.

Once-Weekly Semaglutide in Adults with Overweight or Obesity.

BACKGROUND: Obesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. METHODS: In this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions. RESULTS: The mean change in body weight from baseline to week 68 was -14.9% in the semaglutide group as compared with -2.4% with placebo, for an estimated treatment difference of -12.4 percentage points (95% confidence interval [CI], -13.4 to -11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was -15.3 kg in the semaglutide group as compared with -2.6 kg in the placebo group (estimated treatment difference, -12.7 kg; 95% CI, -13.7 to -11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]). CONCLUSIONS: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).

Diabetes, obesity and COVID-19: A complex interplay.

With the accumulation of observational data showing an association of metabolic co-morbidities with adverse outcomes from COVID-19, there is a need to disentangle the contributions of pre-existing macro- and microvascular disease, obesity and glycaemia. This article outlines the complex mechanistic and clinical interplay between diabetes and COVID-19, the clinical and research questions which arise from this relationship, and the types of studies needed to answer those questions. The authors are clinicians and academics working in diabetes and obesity medicine, but the article is pitched to an audience of generalists with clinical experience of or interest in the management of COVID-19.