Type 1 (T1D) and type 2 diabetes (T2D) are associated with an elevated incidence of infectious diseases and a higher risk of infections-related hospitalization and death.

In this study, we delineated the "vaccinome" landscape obtained with a large immunization schedule offered by the Regional Government of Lombardy in a cohort of 618 396 patients with diabetes (T1D and T2D).

Between September 2021 and September 2022, immunization coverage for influenza, meningococcus, pneumococcus, and herpes zoster was obtained from the public computerized registry of the health care system of Lombardy Region (Italy) in 618 396 patients with diabetes and in 9 534 087 subjects without diabetes. Type of diabetes, age, mortality, and hospitalizations were retrospectively analyzed in vaccinated and unvaccinated patients.

Among patients with diabetes (T1D and T2D), 44.6% received the influenza vaccine, 10.9% the pneumococcal vaccine, 2.5% the antimeningococcus vaccine, and 0.7% the antizoster vaccine. Patients with diabetes immunized for influenza, zoster, and meningococcus showed a 2-fold overall reduction in mortality risk and a decrease in hospitalizations. A 3-fold lower risk of mortality and a decrease in hospitalizations for both cardiac and pulmonary causes were also observed after influenza, zoster, and meningococcus immunization in older patients with diabetes.

Immunization coverage is still far from the recommended targets in patients with diabetes. Despite this, influenza vaccination protected nearly 3800 per 100 000 patients with diabetes from risk of death. The overall impressive decrease in mortality and hospitalizations observed in vaccinated patients strengthens the need for scaling up the "vaccinome" landscape in patients with diabetes.

This study evaluates the pathogenesis of COVID-19 and the therapeutic efficacy of sitagliptin in diabetic and obese mice. Using a novel double-transgenic mouse model (db/db and K18-hACE2), the findings demonstrates that SARS-CoV-2 infection (Delta variant) causes severe multi-organ damage, glucose metabolism abnormalities, insulin resistance, and pancreatic islet cell damage in diabetic mice. Infected diabetic mice displayed higher mortality, inflammation (elevated TNF-α, IL-6, IL-1β), and fibrinolytic activity (PAI-1), alongside dysregulated diabetes-related hormones (GLP-1, leptin, ghrelin, resistin) compared to non-diabetic controls. Sitagliptin treatment reduced organ injury, hyperglycemia, inflammation, and fibrinolytic activity while improving insulin resistance and glucose metabolism. This was evidenced by decreased fasting blood glucose levels, improved insulin sensitivity, and elevated insulin and GLP-1 levels. These findings suggest sitagliptin is a promising therapeutic strategy to mitigate the severity of COVID-19 in experimental diabetes by modulating inflammation and improving metabolic syndrome. Further mechanistic investigations revealed that the level of hACE2 expression, along with the activation of NF-κB and IRS-1, play critical roles in the development of SARS-CoV-2-induced diabetes, the exacerbation of pre-existing diabetes, and the therapeutic efficacy of sitagliptin.

Several studies have reported a reduced risk of COVID-19-related mortality in patients taking antidiabetic medications. This is an umbrella review, meta-analysis, and Bayesian sensitivity assessment of SGLT2 inhibitors (SGLT2is) in COVID-19 patients with type 2 diabetes mellitus (T2DM).

A search was conducted on the MEDLINE (PubMed), EMBASE, Cochrane, and ClinicalTrials.gov databases on 5/12/2023. We performed an umbrella review of systematic reviews and meta-analyses on the effects of SGLT2is in T2DM patients with COVID-19 and critically appraised them using AMSTAR 2.0. Trials investigating SGLT2i use in COVID-19 patients post-hospitalisation and observational studies on prior SGLT2i use among COVID-19 patients were included in the meta-analysis, adhering to the PRISMA guidelines.

SGLT2is exhibited significantly lower odds of mortality (OR 0.67, 95% CI 0.53-0.84) and hospitalisation (OR 0.84, 0.75-0.94) in COVID-19 patients with T2DM. Bayesian sensitivity analyses corroborated most of the findings, with differences observed in hospitalisation and mortality outcomes. SGLT-2 inhibitors showed an OR of 1.20 (95% CI 0.64-2.27) for diabetic ketoacidosis. Publication bias was observed for hospitalisation, but not for mortality. The GRADE assessment indicated a low to very low quality of evidence because of the observational studies included.

The prophylactic use of SGLT2is reduces mortality and hospitalisation among COVID-19 patients, particularly in patients with diabetes. The utility of SGLT2is after hospitalisation is uncertain and warrants further investigation. A limited efficacy has been observed under critical conditions. Individualised assessment is crucial before integration into COVID-19 management.

The effect of antidiabetic agents on mortality outcomes is unclear for individuals with diabetes mellitus (DM) who are hospitalized for COVID-19.

To examine the relationship between antidiabetic agent use and clinical outcomes in individuals with DM hospitalized for COVID-19.

A systematic review of the literature (2020-2024) was performed across five databases. Included articles reported primary research (English) reporting clinical outcomes of adult patients (≥18 yrs.) with DM receiving antidiabetic agents who were hospitalized for COVID-19. Following PRISMA guidelines articles underwent independent dual review. Quality appraisal was completed for included studies. Independent reviewers used a structured data extraction form to retrieve relevant data. Aggregated data were synthesized by treatment regimen and reported descriptively. Random effects meta-analyses were performed to assess relative risk and prevalence of mortality.

After removing duplicates, title and abstract screening of 4,898 articles identified 118 articles for full-text review and 35 articles were retained for analysis. Included articles were primarily from China (15/35, 43%) and retrospective in nature (31/35, 89%). Fourteen studies (40%) assessed multiple antidiabetic agents, fifteen studies (42%) focused on metformin, three studies (9%) assessed the use of DPP-4 inhibitors, and three single studies (9%) investigated the use of insulin, TZD, and SGLT2 inhibitors. Despite differences among studies, the overall relative risk of mortality among metformin and DPP-4 inhibitor users was 0.432 (95% CI = 0.268-0.695, z = 3.45, p < 0.001) and the overall prevalence of mortality among all antidiabetic users was 16% (95% CI = 13%-19%, z = 10.70, p < 0.001).

Synthesis of findings suggest that patients who remained on oral agents (with/without supplemental insulin therapy) exhibited decreased mortality and lower inflammatory markers. Results indicate that individuals with DM should continue oral antidiabetic agents with additional basal insulin as needed to improve glycemic control and reduce mortality. Further work is needed to uncover mechanism(s) and clarify medical management approaches.

This review aims to present current data on the course of COVID-19 in patients with Cushing syndrome (CS) and discuss treatment for CS during to the pandemic.

Literature review using PubMed (pubmed.ncbi.nlm.nih.gov). The search included the following terms: "COVID19" in combination with "Cushing syndrome", "Hypercortisolism" and "Glucocorticoid".

Chronic hypercortisolism has been reported to increase infectious risk and worsens prognostic of patients with COVID-19 potentially due to its direct impact on the immune system: lymphopenia, impairment of monocytes and neutrophils activity, diminution of complement activation. Main metabolic complications of CS - i.e. diabetes, hypertension and obesity - have been recognized as COVID-19 complications risk factors. Patients with CS treated with steroidogenesis inhibitors might experience adrenal insufficiency during COVID-19. Special attention should be paid to patients with CS and COVID-19. The pandemic has impacted - and delayed - care of chronic illnesses including CS. Specific recommendations had been provided during the pandemic: favor telemedicine consultations, limit in-hospital explorations and postpone surgery when feasible.

There are enough evidence for an increased prevalence and severity of COVID-19 to recommend a specific attention and caution in patients with CS.

To investigate possible associations of glucose patterns with outcomes of Corona Virus Disease 19 (COVID-19) using continuous glucose monitoring (CGM) in 43 patients hospitalized for COVID-19 mild-to-moderate pneumonia, regardless of diabetes.

Prospective observational study conducted during two pandemic waves in 2020-2021. Glucose sensor metrics of 7-day recording were obtained from blinded CGM. Respiratory function was evaluated as arterial partial pressure of oxygen (PaO2) to fraction of inspired oxygen (FiO2) ratio (PaO2:FiO2).

PaO2:FiO2 ratio was positively correlated with time in tight range (TITR) 70-140 (r = 0.49, p < 0.001) and time in range (TIR) 70-180 (r = 0.32, p < 0.05), and negatively correlated with average glucose (r =- 0.31, p < 0.05), coefficient of glucose variation (CV) (r =- 0.47, p < 0.01) and time above range (TAR) > 140 (r =- 0.49, p < 0.001). No relations were observed with HbA1c. Multivariate regression analysis showed that normal respiratory function at time of CGM removal correlated positively with TITR 70-140 mg/dL (p < 0.01), negatively with CV and TAR > 140 mg/dL (both p < 0.05) and not with TIR 70-180 and average glucose.

Lower glucose variability and optimal glucose control, expressed as CV and TITR, are CGM metrics predictive of a better prognosis in COVID-19 patients with pneumonia.

The COVID-19 pandemic has left a profound mark on global health, leading to substantial morbidity and mortality worldwide. Beyond the immediate symptoms of infection, the emergence of "long COVID", the long-term effects of SARS-CoV-2, has become a significant public health concern. Long COVID is a multifaceted condition affecting various organs and systems, including the cardiovascular, digestive, nervous, and endocrine systems. Individuals diagnosed with polycystic ovary syndrome (PCOS) may face an increased risk of severe COVID-19 symptoms and infection. It is crucial to comprehend how long COVID affects PCOS patients to devise effective treatment and care strategies. Here, we review the detrimental effects of COVID-19 and its long-term effects on reproductive health, endocrine function, inflammation, metabolism, cardiovascular health, body composition, lifestyle, and mental health in patients with PCOS. We offer recommendations for the post-covid-19 management of PCOS, emphasizing the necessity of a comprehensive, multidisciplinary approach to patient care. Furthermore, we discuss prospective research directions, highlighting the significance of continued investigations and clinical trials to evaluate treatment approaches for long COVID and its ramifications in individuals with PCOS.

Dipeptidyl peptidase-4 (DPP-4) is a multifunctional serine ectopeptidase that cleaves and modifies a plethora of substrates, including regulatory peptides, cytokines and chemokines. DPP-4 is implicated in the regulation of immune response, viral entry, cellular adhesion, metastasis and chemotaxis. Regarding its numerous substrates and extensive expression inside the body, multitasking DPP-4 has been assumed to participate in different pathophysiological mechanisms. DPP-4 inhibitors or gliptins are increasingly used for the treatment of type 2 diabetes mellitus. Several reports from experimental and clinical studies have clarified that DPP-4 inhibitors exert many beneficial pleiotropic effects beyond glycaemic control, which are mediated by anti-inflammatory, anti-oxidant, anti-fibrotic and anti-apoptotic actions. The present review will highlight the most recent findings in the literature about these pleiotropic effects and the potential mechanisms underlying these benefits, with a specific focus on the potential effectiveness of DPP-4 inhibitors in coronavirus disease-19 and diabetic kidney disease.

Diabetes, a chronic disease worldwide, may be associated with a poorer prognosis in patients with coronavirus disease 2019 (COVID-19). While some antihyperglycemic medications may be beneficial, others may increase the risk of adverse clinical outcomes of COVID-19. We aimed to analyze the effect of antihyperglycemic medications on COVID-19.

We searched the Web of Science, Cochrane Library, EMBASE, PubMed, and Scopus databases from December 2019 to June 2022 to identify literature related to patients with COVID-19 and type 2 diabetes mellitus (T2DM) treated with antihyperglycemic medications.

56 studies were included in the analysis. Metformin (OR 0.66; 95% CI 0.58-0.74; p < 0.05), Glucagon-like peptide-1 receptor agonist (GLP-1ra) (OR 0.73; 95% CI 0.59-0.91; p < 0.05), and sodium-dependent glucose transporters 2 inhibitor (SGLT 2i) (OR 0.77; 95% CI 0.69-0.87; p < 0.05) were associated with lower mortality risk, while insulin was associated with increased mortality risk (OR 1.40; 95% CI 1.26-1.55; p < 0.05). Meanwhile, metformin (OR 0.65; 95% CI 0.50-0.85; p < 0.05) and GLP-1ra (OR 0.84; 95% CI 0.76-0.94; p < 0.05) were significantly associated with decreased severe manifestation risk. What's more, metformin (OR 0.77; 95% CI 0.62-0.96; p < 0.05), GLP-1ra (OR 0.86; 95% CI 0.81-0.92; p < 0.05), and SGLT 2i (OR 0.87; 95% CI 0.79-0.97; p < 0.05) were also associated with a decreased risk of hospitalization, but insulin were associated with an increased risk of hospitalization (OR 1.31; 95% CI 1.12-1.52; p < 0.05). Nevertheless, the results of the subgroup analyses showed that the effects of different glucose-lowering agents on COVID-19 may be related to in-hospital use or out-hospital use, elderly or non-elderly patients use, and different geography.

Metformin, GLP-1ra, and SGLT 2i have shown a positive effect on clinical outcomes in COVID-19, particularly in non-elderly individuals. However, insulin use may pose a higher risk, especially in elderly patients, so need with caution. Meanwhile, DPP-4i, TZD, α-GLUi, and sulfonylureas appeared to have a neutral effect. These results need to be validated in future clinical studies.

Background: Diabetes Mellitus (DM) has been associated with a higher Coronavirus disease-19 (COVID-19) mortality, both in hospitalized patients and in the general population. A possible beneficial effect of metformin on the prognosis of COVID-19 has been reported in some observational studies, whereas other studies disagree. Methods: To investigate the possible effect of metformin on COVID-19 in-hospital mortality, we performed a retrospective study that included all SARS-CoV-2-positive patients with DM who were admitted to two Italian hospitals. In order to adjust for possible confounders accounting for the observed reduction of mortality in metformin users, we adopted the COVID-19 Mortality Risk Score (COVID-19 MRS) as a covariate. Results: Out of the 524 included patients, 33.4% died. A binomial logistic regression showed that metformin use was associated with a significant reduction in case fatality (OR 0.67 [0.45-0.98], p = 0.039), with no significant effect on the need for ventilation (OR 0.75 [0.5-1.11], p = 0.146). After adjusting for COVID-19 MRS, metformin did not retain a significant association with in-hospital mortality [OR 0.795 (0.495-1.277), p = 0.342]. Conclusions: A beneficial effect of metformin on COVID-19 was not proven after adjusting for confounding factors. The use of validated tools to stratify the risk for COVID-19 severe disease and death, such as COVID-19 MRS, may be useful to better explore the potential association of medications and comorbidities with COVID-19 prognosis.

The SARS-CoV-2 virus first emerged in China in December 2019 and quickly spread worldwide. Despite the absence of a vaccination or authorized drug specifically developed to combat this infection, certain medications recommended for other diseases have shown potential effectiveness in treating COVID-19, although without definitive confirmation. This review aims to evaluate the existing literature on the efficacy of these medications against COVID-19. The review encompasses various potential treatments, including antiviral medications, anti-malaria and anti-rheumatic drugs, vaccines, corticosteroids, non-steroidal anti-inflammatory drugs (NSAIDs), antipyretic and analgesic medicines, antiparasitic drugs, and statins. The analysis also addresses the potential benefits and drawbacks of these medications, as well as their effects on hypertension and diabetes. Although these therapies hold promise against COVID-19, further research, including suitable product production or clinical testing, is needed to establish their therapeutic efficacy.

To identify the features of the course of COVID-19 in patients with type 2 diabetes mellitus (T2DM), depending on the intake of hypoglycemic therapy at the prehospital stage, in conjunction with the functional state of the kidneys.

A retrospective analysis of 291 case histories of patients with COVID-19 and T2DM hospitalized in the infection department of Semashko Regional Clinical Hospital from January to December 2021, including the main clinical and laboratory parameters. Results. Among hospitalized patients with COVID-19, patients with T2DM had a higher mortality rate. An analysis of the case histories of deceased patients with COVID-19 and T2DM showed that at admission, body mass index (BMI), C-reactive protein, and creatinine were higher than those of survivors and amounted to BMI - 33 [30; 39] and 33 [28; 36] kg/m3; p=0.039, C-reactive protein - 77 [47.5; 106.0] and 57 [27.0; 89.0] mg/l; p=0.015, in terms of creatinine level - 89 [70.0; 144.0] and 82 [66.0; 101.0] µmol/l; p=0.039, respectively. It was found that in the second week of hospitalization in the group of deceased patients with COVID-19 and T2DM, the creatinine level was statistically significantly higher than in surviving patients and amounted to 94.5 [71.5; 141.0] and 72.5 [57.0; 88.0] µmol/L; p<0.001, respectively. The probability of death in hospitalized patients with type 2 COVID-19 and T2DM depended on BMI and creatinine levels at the second week of hospitalization. Patients with prehospital correction of hyperglycemia dipeptidyl peptidase-4 inhibitors (iDPP-4)/ glucagon-like peptide-1 receptor agonists (agGLP-1)/ sodium-glucose co-transporter 2 inhibitors (iSGLT-2) had significantly lower creatinine levels at week 2 of hospitalization.

In patients with moderate to severe COVID-19 with concomitant T2DM, special attention should be paid to the combination of high BMI and creatinine in the second week of hospitalization, which is a prognostically unfavorable predictor of death in such patients.

The pathophysiology of the severe course of COVID-19 is multifactorial and not entirely elucidated. However, it is well known that the hyperinflammatory response and cytokine storm are paramount events leading to further complications. In this paper, we investigated the vascular response in the pathophysiology of severe COVID-19 and aimed to identify novel biomarkers predictive of ICU admission. The study group consisted of 210 patients diagnosed with COVID-19 (age range: 18-93; mean ± SD: 57.78 ± 14.16), while the control group consisted of 80 healthy individuals. We assessed the plasma concentrations of various vascular factors using the Luminex technique. Then, we isolated RNA from blood mononuclear cells and performed a bioinformatics analysis investigating various processes related to vascular response, inflammation and angiogenesis. Our results confirmed that severe COVID-19 is associated with vWF/ADAMTS 13 imbalance. High plasma concentrations of VEGFR and low DPP-IV may be potential predictors of ICU admission. SARS-CoV-2 infection impairs angiogenesis, hinders the generation of nitric oxide, and thus impedes vasodilation. The hypercoagulable state develops mainly in the early stages of the disease, which may contribute to the well-established complications of COVID-19.

Diabetes mellitus is a prevalent chronic disease in patients who die of COVID-19. The aim of this study was to investigate the clinical and metabolic characteristics of diabetic patients with COVID-19 during the pre-vaccination phase.

A retrospective cohort study was conducted from February 2020 to February 2021 to examine the clinical and metabolic profiles of unvaccinated diabetic patients affected by COVID-19. Data were collected from claim databases, hospital discharge records, and clinical records within a healthcare district located in northeastern Italy with a population of 936,000. Potential prognostic indicators including sex, age, Body Mass Index (BMI), duration and type of diabetes, metabolic control, and the use of antidiabetic, antihypertensive, lipid-lowering, and antiplatelet therapies were investigated. For hospitalized patients, additional variables were recorded, such as length of hospital stay, blood pressure at admission, comorbidities, D-dimer levels, blood glucose (BG), in-hospital insulin and corticosteroid therapies, requirement for mechanical ventilation (i.e., orotracheal or tracheostomy), admission to the Intensive Care Unit (ICU), and mortality. Diabetic patients hospitalized for COVID-19 with a poorer prognosis were characterized by advanced age, longer diabetes duration, hypertension, higher usage of sulfonylureas, and lower usage of dietotherapy alone, metformin, Glucagon-Like Peptide-1 Receptor agonists (GLP1-Ra), and Renin-Angiotensin-Aldosterone System inhibitors (RAAS-i).

Considering the potential for COVID-19 to become endemic, special care should be taken in managing older diabetic patients' treatments.

2019 Coronavirus Disease (COVID-19) is a global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). A "cytokine storm", i.e., elevated levels of pro-inflammatory cytokines in the bloodstream, has been observed in severe cases of COVID-19. Normally, activation of the nucleotide-binding oligomeric domain-like receptor containing pyrin domain 3 (NLRP3) inflammatory vesicles induces cytokine production as an inflammatory response to viral infection. Recent studies have found an increased severity of necrobiosis infection in diabetic patients, and data from several countries have shown higher morbidity and mortality of necrobiosis in people with chronic metabolic diseases such as diabetes. In addition, COVID-19 may also predispose infected individuals to hyperglycemia. Therefore, in this review, we explore the potential relationship between NLRP3 inflammatory vesicles in diabetes and COVID-19. In contrast, we review the cellular/molecular mechanisms by which SARS-CoV-2 infection activates NLRP3 inflammatory vesicles. Finally, we propose several promising targeted NLRP3 inflammatory vesicle inhibitors with the aim of providing a basis for NLRP3-targeted drugs in diabetes combined with noncoronary pneumonia in the clinical management of patients.

The effects of diabetes medications on COVID-19 hospitalization outcomes have not been consistent. We sought to determine the effect of metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), and insulin on admission to the intensive care unit (ICU), need for assisted ventilation, development of renal insufficiency, and mortality in patients admitted with COVID-19 infection after controlling for clinical variables and other relevant diabetes-related medications in patients with type 2 diabetes mellitus (DM).

This was a retrospective study of patients hospitalized with COVID-19 from a single hospital system. Univariate and multivariate analyses were performed that included demographic data, glycated hemoglobin, kidney function, smoking status, insurance, Charlson comorbidity index, number of diabetes medications, and use of angiotensin-converting enzyme inhibitors and statin prior to admission and glucocorticoids during admission.

A total of 529 patients with type 2 DM were included in our final analysis. Neither metformin nor DPP4i prescription was associated with ICU admission, need for assisted ventilation, or mortality. Insulin prescription was associated with increased ICU admission but not with need for assisted ventilation or mortality. There was no association of any of these medications with development of renal insufficiency.

In this population, limited to type 2 DM and controlled for multiple variables that have not been consistently studied (such as a measure of general health, glycated hemoglobin, and insurance status), insulin prescription was associated with increased ICU admission. Metformin and DPP4i prescriptions did not have an association with the outcomes.

Few studies have identified the metabolic consequences of the post-acute phase of nonsevere COVID-19. This prospective study examined metabolic outcomes and associated factors in nonsevere, RT-PCR-confirmed COVID-19. The participants' metabolic parameters, the prevalence of long-term multiple metabolic abnormalities (≥ 2 components), and factors influencing the prevalence were assessed at 1, 3, and 6 months post-onset. Six hundred individuals (mean age 45.5 ± 14.5 years, 61.7% female, 38% high-risk individuals) with nonsevere COVID-19 attended at least one follow-up visit. The prevalence of worsening metabolic abnormalities was 26.0% for BMI, 43.2% for glucose, 40.5% for LDL-c, 19.1% for liver, and 14.8% for C-reactive protein. Except for lipids, metabolic-component abnormalities were more prevalent in high-risk hosts than in healthy individuals. The prevalence of multiple metabolic abnormalities at the 6-month follow-up was 41.3% and significantly higher in high-risk than healthy hosts (49.2% vs 36.5%; P = 0.007). Factors independently associated with a lower risk of these abnormalities were being female, having dyslipidemia, and receiving at least 3 doses of the COVID-19 vaccine. These findings suggest that multiple metabolic abnormalities are the long-term consequences of COVID-19. For both high-risk and healthy individuals with nonsevere COVID-19, healthcare providers should monitor metabolic profiles, encourage healthy behaviors, and ensure complete vaccination.

Novel antidiabetic drugs have the ability to produce anti-inflammatory effects regardless of their glucose-lowering action. For this reason, these molecules (including GLP-1 RAs and DPP-4is) were hypothesized to be effective against COVID-19, which is characterized by cytokines hyperactivity and multiorgan inflammation. The aim of our work is to explore the potential protective role of GLP-1 RAs and DPP-4is in COVID-19 (with the disease intended to be a model of an acute stressor) and non-COVID-19 patients over a two-year observation period. Retrospective and one-versus-one analyses were conducted to assess the impact of antidiabetic drugs on the need for hospitalization (in both COVID-19- and non-COVID-19-related cases), in-hospital mortality, and two-year mortality. Logistic regression analyses were conducted to identify the variables associated with these outcomes. Additionally, log-rank tests were used to plot survival curves for each group of subjects, based on their antidiabetic treatment. The performed analyses revealed that despite similar hospitalization rates, subjects undergoing home therapy with GLP-1 RAs exhibited significantly lower mortality rates, even over a two-year period. These individuals demonstrated improved survival estimates both within hospital and non-hospital settings, even during a longer observation period.

To provide a systematic overview of the current body of evidence on high-risk phenotypes of diabetes associated with COVID-19 severity and death.

This is the first update of our recently published living systematic review and meta-analysis. Observational studies investigating phenotypes in individuals with diabetes and confirmed SARS-CoV-2 infection with regard to COVID-19-related death and severity were included. The literature search was conducted from inception up to 14 February 2022 in PubMed, Epistemonikos, Web of Science and the COVID-19 Research Database and updated using PubMed alert to 1 December 2022. A random-effects meta-analysis was used to calculate summary relative risks (SRRs) with 95% CIs. The risk of bias was evaluated using the Quality in Prognosis Studies (QUIPS) tool and the certainty of evidence using the GRADE approach.

A total of 169 articles (147 new studies) based on approximately 900,000 individuals were included. We conducted 177 meta-analyses (83 on COVID-19-related death and 94 on COVID-19 severity). Certainty of evidence was strengthened for associations between male sex, older age, blood glucose level at admission, chronic insulin use, chronic metformin use (inversely) and pre-existing comorbidities (CVD, chronic kidney disease, chronic obstructive pulmonary disease) and COVID-19-related death. New evidence with moderate to high certainty emerged for the association between obesity (SRR [95% CI] 1.18 [1.04, 1.34], n=21 studies), HbA1c (53-75 mmol/mol [7-9%]: 1.18 [1.06, 1.32], n=8), chronic glucagon-like peptide-1 receptor agonist use (0.83 [0.71, 0.97], n=9), pre-existing heart failure (1.33 [1.21, 1.47], n=14), pre-existing liver disease (1.40 [1.17, 1.67], n=6), the Charlson index (per 1 unit increase: 1.33 [1.13, 1.57], n=2), high levels of C-reactive protein (per 5 mg/l increase: 1.07 [1.02, 1.12], n=10), aspartate aminotransferase level (per 5 U/l increase: 1.28 [1.06, 1.54], n=5), eGFR (per 10 ml/min per 1.73 m2 increase: 0.80 [0.71, 0.90], n=6), lactate dehydrogenase level (per 10 U/l increase: 1.03 [1.01, 1.04], n=7) and lymphocyte count (per 1×109/l increase: 0.59 [0.40, 0.86], n=6) and COVID-19-related death. Similar associations were observed between risk phenotypes of diabetes and severity of COVID-19, with some new evidence on existing COVID-19  vaccination status (0.32 [0.26, 0.38], n=3), pre-existing hypertension (1.23 [1.14, 1.33], n=49), neuropathy and cancer, and high IL-6 levels. A limitation of this study is that the included studies are observational in nature and residual or unmeasured confounding cannot be ruled out.

Individuals with a more severe course of diabetes and pre-existing comorbidities had a poorer prognosis of COVID-19 than individuals with a milder course of the disease.

PROSPERO registration no. CRD42020193692.

This is a living systematic review and meta-analysis. The previous version can be found at https://link.springer.com/article/10.1007/s00125-021-05458-8 FUNDING: The German Diabetes Center (DDZ) is funded by the German Federal Ministry of Health and the Ministry of Culture and Science of the State North Rhine-Westphalia. This study was supported in part by a grant from the German Federal Ministry of Education and Research to the German Center for Diabetes Research (DZD).

COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to enormous morbidity and mortality worldwide. After gaining entry into the human host, the virus initially infects the upper and lower respiratory tract, subsequently invading multiple organs, including the pancreas. While on one hand, diabetes mellitus (DM) is a significant risk factor for severe COVID-19 infection and associated death, recent reports have shown the onset of DM in COVID-19-recovered patients. SARS-CoV-2 infiltrates the pancreatic islets and activates stress response and inflammatory signaling pathways, impairs glucose metabolism, and consequently leads to their death. Indeed, the pancreatic autopsy samples of COVID-19 patients reveal the presence of SARS-CoV-2 particles in β-cells. The current review describes how the virus enters the host cells and activates an immunological response. Further, it takes a closer look into the interrelationship between COVID-19 and DM with the aim to provide mechanistic insights into the process by which SARS-CoV-2 infects the pancreas and mediates dysfunction and death of endocrine islets. The effects of known anti-diabetic interventions for COVID-19 management are also discussed. The application of mesenchymal stem cells (MSCs) as a future therapy for pancreatic β-cells damage to reverse COVID-19-induced DM is also emphasized.

Cystic fibrosis-related diabetes (CFRD) is a complication associated with a negative prognosis in patients with cystic fibrosis (CF). Although the oral glucose tolerance test (OGTT) is the widely recommended screening test for CFRD diagnosis, continuous glucose monitoring (CGM) is increasingly considered a useful and easy-to-perform test for diagnosis and follow-up in clinical practice. Regarding CFRD treatment, although insulin is the classic approved pharmacological option, incretins could also be a helpful alternative in early stages. CGM could be also a useful tool to measure the early response to this therapy.

We studied 25 CF patients with abnormal OGTT results and compared glucose and insulin levels during the OGTTs with CGM results as a tool for early CFRD diagnosis. In addition, we evaluated glycaemic control with CGM before and after treatment with sitagliptin.

A correlation was found between lower plasma insulin levels during the OGTTs and higher average sensor glucose (p = 0.009) and hyperglycaemic excursions (p = 0.017). The CGM data on sitagliptin treatment (n = 25) showed an average glycaemic improvement from 124.2 to 117.2 mg/dL (p = 0.002) with a 5.6-point standard deviation of glucose decrease (p < 0.001). Hyperglycaemic excursions ≥200 mg/dL diminished 57.1% (p = 0.021). Both time in range and time above 180 mg/dL improved during treatment (p = 0.036 and p = 0.006, respectively).

CGM is a useful tool that offers valuable information for both the diagnosis and the management of CFRD. Lower plasma insulin levels during OGTTs are associated with a poor ambulatory glucose profile in CGM. Sitagliptin could play an important role in the treatment of the early stages of CFRD.

The link between type 2 diabetes (T2D) and the severe outcomes of COVID-19 has raised concerns about the optimal management of patients with T2D. This study aimed to investigate the clinical characteristics and outcomes of T2D patients hospitalized with COVID-19 and explore the potential associations between chronic T2D treatments and adverse outcomes. This was a multicenter prospective cohort study of T2D patients hospitalized with COVID-19 in Greece during the third wave of the pandemic (February-June 2021). Among the 354 T2D patients included in this study, 63 (18.6%) died during hospitalization, and 16.4% required ICU admission. The use of DPP4 inhibitors for the chronic management of T2D was associated with an increased risk of in-hospital death (adjusted odds ratio (adj. OR) 2.639, 95% confidence interval (CI) 1.148-6.068, p = 0.022), ICU admission (adj. OR = 2.524, 95% CI: 1.217-5.232, p = 0.013), and progression to ARDS (adj. OR = 2.507, 95% CI: 1.278-4.916, p = 0.007). Furthermore, the use of DPP4 inhibitors was significantly associated with an increased risk of thromboembolic events (adjusted OR of 2.249, 95% CI: 1.073-4.713, p = 0.032) during hospitalization. These findings highlight the importance of considering the potential impact of chronic T2D treatment regiments on COVID-19 and the need for further studies to elucidate the underlying mechanisms.

According to recent researches, people with diabetes mellitus (type 1 and 2) have a higher incidence of coronavirus disease 2019 (COVID-19), which is caused by a SARS-CoV-2 infection. In this regard, COVID-19 may make diabetic patients more sensitive to hyperglycemia by modifying the immunological and inflammatory responses and increasing reactive oxygen species (ROS) predisposing the patients to severe COVID-19 and potentially lethal results. Actually, in addition to COVID-19, diabetic patients have been demonstrated to have abnormally high levels of inflammatory cytokines, increased virus entrance, and decreased immune response. On the other hand, during the severe stage of COVID-19, the SARS-CoV-2-infected patients have lymphopenia and inflammatory cytokine storms that cause damage to several body organs such as β cells of the pancreas which may make them as future diabetic candidates. In this line, the nuclear factor kappa B (NF-κB) pathway, which is activated by a number of mediators, plays a substantial part in cytokine storms through various pathways. In this pathway, some polymorphisms also make the individuals more competent to diabetes via infection with SARS-CoV-2. On the other hand, during hospitalization of SARS-CoV-2-infected patients, the use of some drugs may unintentionally lead to diabetes in the future via increasing inflammation and stress oxidative. Thus, in this review, we will first explain why diabetic patients are more susceptible to COVID-19. Second, we will warn about a future global diabetes tsunami via the SARS-CoV-2 as one of its long-term complications.

We evaluated the number of CD26 expressing cells in peripheral blood of patients with COVID-19 within 72 h of admission and on day 4 and day 7 after enrollment. The majority of CD26 expressing cells were presented by CD3+ CD4+ lymphocytes. A low number of CD26 expressing cells were found to be associated with critical-severity COVID-19 disease. Conversely, increasing numbers of CD26 expressing T cells over the first week of standard treatment was associated with good outcomes. Clinically, the number of circulating CD26 cells might be a marker of recovery or the therapeutic efficacy of anti-COVID-19 treatment. New therapies aimed at preserving and increasing the level of CD26 expressing T cells may prove useful in the treatment of COVID-19 disease.

Recent evidence relating to the impact of COVID-19 on people with diabetes is limited but continues to emerge. COVID-19 pneumonia is a newly identified illness spreading rapidly throughout the world and causes many disabilities and fatal deaths. Over the ensuing 2 years, the indirect effects of the pandemic on healthcare delivery have become prominent, along with the lingering effects of the virus on those directly infected. Diabetes is a commonly identified risk factor that contributes not only to the severity and mortality of COVID-19 patients, but also to the associated complications, including acute respiratory distress syndrome (ARDS) and multi-organ failure. Diabetic patients are highly affected due to increased viral entry into the cells and decreased immunity. Several hypotheses to explain the increased incidence and severity of COVID-19 infection in people with diabetes have been proposed and explained in detail recently. On the other hand, 20-50% of COVID-19 patients reported new-onset hyperglycemia without diabetes and new-onset diabetes, suggesting the two-way interactions between COVID-19 and diabetes. A systematic review is required to confirm diabetes as a complication in those patients diagnosed with COVID-19. Diabetes and diabetes-related complications in COVID-19 patients are primarily due to the acute illness caused during the SARS-CoV-2 infection followed by the release of glucocorticoids, catecholamines, and pro-inflammatory cytokines, which have been shown to drive hyperglycemia positively. This review provides brief insights into the potential mechanisms linking COVID-19 and diabetes, and presents clinical management recommendations for better handling of the disease.

Thyroid dysfunctions associated with SARS-CoV-2 acute infection have been extensively described since the beginning of COVID-19 pandemics. Conversely, few data are available on the occurrence of thyroid autoimmunity after COVID-19 resolution. We assessed the prevalence of autoimmune thyroid disease (ATD) and thyroid dysfunctions in COVID-19 survivors three months after hospital admission.

Single-center, prospective, observational, cohort study performed at ASST Papa Giovanni XXIII Hospital, Bergamo, Italy. 599 COVID-19 survivors were prospectively evaluated for thyroid function and autoimmunity thyroperoxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb). When a positive antibody concentration was detected, thyroid ultrasound was performed. Multiple logistic regression model was used to estimate the association between autoimmunity and demographic characteristics, respiratory support, and comorbidities. Autoimmunity results were compared to a cohort of 498 controls referred to our Institution for non-thyroid diseases before the pandemic onset. A sensitivity analysis comparing 330 COVID-19 patients with 330 age and sex-matched controls was performed.

Univariate and multivariate analysis found that female sex was positively associated (OR 2.01, SE 0.48, p = 0.003), and type 2 diabetes (T2DM) was negatively associated (OR 0.36, SE 0.16, p = 0.025) with thyroid autoimmunity; hospitalization, ICU admission, respiratory support, or COVID-19 treatment were not associated with thyroid autoimmunity (p > 0.05). TPOAb prevalence was greater in COVID-19 survivors than in controls: 15.7% vs 7.7%, p = 0.002. Ultrasonographic features of thyroiditis were present in 94.9% of the evaluated patients with positive antibodies. TSH was within the normal range in 95% of patients.

Autoimmune thyroid disease prevalence in COVID-19 survivors was doubled as compared to age and sex-matched controls, suggesting a role of SARS-CoV-2 in eliciting thyroid autoimmunity.

The outbreak of COVID-19 has become a global crisis, and brought severe disruptions to societies and economies. Until now, effective therapeutics against COVID-19 are in high demand. Along with our improved understanding of the structure, function, and pathogenic process of SARS-CoV-2, many small molecules with potential anti-COVID-19 effects have been developed. So far, several antiviral strategies were explored. Besides directly inhibition of viral proteins such as RdRp and Mpro, interference of host enzymes including ACE2 and proteases, and blocking relevant immunoregulatory pathways represented by JAK/STAT, BTK, NF-κB, and NLRP3 pathways, are regarded feasible in drug development. The development of small molecules to treat COVID-19 has been achieved by several strategies, including computer-aided lead compound design and screening, natural product discovery, drug repurposing, and combination therapy. Several small molecules representative by remdesivir and paxlovid have been proved or authorized emergency use in many countries. And many candidates have entered clinical-trial stage. Nevertheless, due to the epidemiological features and variability issues of SARS-CoV-2, it is necessary to continue exploring novel strategies against COVID-19. This review discusses the current findings in the development of small molecules for COVID-19 treatment. Moreover, their detailed mechanism of action, chemical structures, and preclinical and clinical efficacies are discussed.

Since the outbreak of coronavirus disease (COVID-19) in Wuhan, China, triggered by severe acute respiratory coronavirus 2 (SARS-CoV-2) in late November 2019, spreading to more than 200 countries of the world, the ensuing pandemic to an enormous loss of lives, mainly the older population with comorbidities, like diabetes, cardiovascular disease, chronic obstructive pulmonary disease, obesity, and hypertension. Amongst these immune-debilitating diseases, SARS-CoV-2 infection is the most common in patients with diabetes due to the absence of a normal active immune system to fight the COVID-19. Recovery of patients having a history of diabetes from COVID-19 encounters several complications, and their management becomes cumbersome. For control of coronavirus, antiviral medications, glucose-lowering agents, and steroids have been carefully evaluated. In the present review, we discuss the crosstalk between SARS-CoV-2 infection and patients with a history of diabetes. We mainly emphasize the molecular factors that are involved in diabetic individuals recently infected by SARS-CoV-2 and developed COVID-19 disease. Lastly, we examine the medications available for the long-term management of diabetic patients with SARS-CoV-2 infection.

Coronavirus disease 2019 (Covid-19) is caused by severe acute respiratory syndrome type 2 (SARS-CoV-2). Covid-19 is characterized by hyperinflammation, oxidative stress, and multi-organ injury (MOI) such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Covid-19 is mainly presented with respiratory manifestations; however, extra-pulmonary manifestations may also occur. Extra-pulmonary manifestations of Covid-19 are numerous including: neurological, cardiovascular, renal, endocrine, and hematological complications. Notably, a cluster of differentiation 26 (CD26) or dipeptidyl peptidase-4 (DPP-4) emerged as a new receptor for entry of SARS-CoV-2. Therefore, DPP-4 inhibitors like sitagliptin could be effective in treating Covid-19. Hence, we aimed in the present critical review to assess the potential role of sitagliptin in Covid-19. DPP-4 inhibitors are effective against the increased severity of SARS-CoV-2 infections. Moreover, DPP-4 inhibitors inhibit the interaction between DPP-4 and scaffolding proteins which are essential for endosome formation and replication of SARS-CoV-2. Therefore, sitagliptin through attenuation of the inflammatory signaling pathway and augmentation of stromal-derived factor-1 (SDF-1) may decrease the pathogenesis of SARS-CoV-2 infection and could be a possible therapeutic modality in treating Covid-19 patients. In conclusion, the DPP-4 receptor is regarded as a potential receptor for the binding and entry of SARS-CoV-2. Inhibition of these receptors by the DPP-4 inhibitor, sitagliptin, can reduce the pathogenesis of the infection caused by SARS-CoV-2 and their associated activation of the inflammatory signaling pathways.

Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality and complications in patients with diabetes mellitus. Achieving good glycemic control is very important in diabetic patients to reduce complications and mortality due to COVID-19. Recent studies have shown the mortality benefit and anti-inflammatory effects of Dipeptidyl-peptidase-4 inhibitors (DPP-4i) in diabetic patients with COVID-19. DPP-4i may have a beneficial role in halting the severity of infection primarily by three routes, namely viral entry inhibition, anti-inflammatory and anti-fibrotic effects and glycemic control. This has raised the pro-mising hypothesis that DPP-4i might be an optimal strategy for treating COVID-19 in patients with diabetes. This review aims to summarise the possible therapeutic non-glycemic effects of DPP-4i in diabetic patients diagnosed with COVID-19 in the light of available evidence.

The role of glycemic control, both prior and during hospitalization, on mortality from COVID-19 in diabetic patients is debated. Furthermore, it is not clear whether hyperglycemia has a direct effect or requires inflammatory mechanisms.

To identify predictors of clinical outcomes (in-hospital mortality, length of hospitalization, respiratory failure, need for intensive care), considering hyperglycemia, inflammation markers and clinical history.

Retrospective observational study of 291 diabetic patients hospitalized with COVID-19 in the Spedali Civili di Brescia from February 1th 2020 to March 31th 2021, with also outpatient electronic records. Glucose, inflammatory parameters, creatinine were collected within 24 h after admission to the hospital. A causal mediation analysis allowed the estimation of the direct and indirect effects of hyperglycemia on mortality.

Glucose at admission ≥ 165 mg/dL and reduced renal function were associated with an increased risk of in-hospital mortality and length of hospitalization (all p < 0.001), while an increase in inflammatory parameters was significantly associated with an increased risk of all outcomes. High basophil count was associated with reduced mortality (p < 0.001). Hyperglycemia had a direct effect on mortality (p < 0.001); the indirect, through inflammatory markers, was significant only for absolute neutrophil count, C-Reactive protein and procalcitonin (p = 0.007, p = 0.029, p = 0.042). Patients with microvascular complications and with chronic kidney disease showed higher mortality (p = 0.03, p = 0.01).

Hyperglycemia at admission, renal function and inflammatory parameters were found to be predictors of in-hospital mortality, while an increased basophil count was protective. Hyperglycemia had a direct effect on mortality, the indirect effect was only through few markers and markedly lower than the direct one.

Multiple studies show increased severity of SARS-CoV2-infection in patients with comorbidities such as hypertension and diabetes. In this study, we have prepared two herbal-based formulations, a pleiotropic herbal drink (Jin Si Herbal Tea, JHT) and a nasal drop (Jin Si nasal drop, JND), to provide preventive care against SARS-CoV2 infection. The effect of JHT and JND was determined in SARS-CoV2-S-pseudotyped lentivirus-infected bronchial and colorectal cell lines and in SKH-1 mouse models. For preliminary studies, ACE2 receptor abundant bronchial (Calu-3) and colorectal cells (Caco-2) were used to determine the effect of JHT and JND on the host entry of various variants of SARS-CoV2-S-pseudotyped lentivirus. A series of experiments were performed to understand the infection rate in SKH-1 mice (6 weeks old, n = 9), find the effective dosage of JHT and JND, and determine the combination effect of JHT and JND on the entry and adhesion of various variant SARS-CoV2-S-pseudotyped lentiviruses, which included highly transmissible delta and gamma mutants. Furthermore, the effect of combined JHT and JND was determined on diabetes-induced SKH-1 mice against the comorbidity-associated intense viral entry and accumulation. In addition, the effect of combined JHT and JND administration on viral transmission from infected SKH-1 mice to uninfected cage mate mice was determined. The results showed that both JHT and JND were effective in alleviating the viral entry and accumulation in the thorax and the abdominal area. While JHT showed a dose-dependent decrease in the viral load, JND showed early inhibition of viral entry from day 1 of the infection. Combined administration of 48.66 mg of JHT and 20 µL of JND showed rapid reduction in the viral entry and reduced the viral load (97-99%) in the infected mice within 3 days of treatment. Moreover, 16.22 mg of JHT and 20 µL JND reduced the viral infection in STZ-induced diabetic SKH-1 mice. Interestingly, combined JHT and JND also inhibited viral transmission among cage mates. The results, therefore, showed that combined administration of JHT and JND is a novel and an efficient strategy to potentially prevent SARS-CoV2 infection.