Understanding genetic regulation of metabolism is critical for gaining insights into the causes of metabolic diseases. Traditional metabolome-based genome-wide association studies (mGWAS) focus on static associations between single nucleotide polymorphisms (SNPs) and metabolite levels, overlooking the changing relationships caused by genotypes within the metabolic network. Notably, some metabolites exhibit changes in correlation patterns with other metabolites under certain physiological conditions while maintaining their overall abundance level. In this manuscript, we develop Metabolic Differential-coordination GWAS (mdGWAS), an innovative framework that detects SNPs associated with the changing correlation patterns between metabolites and metabolic pathways. This approach transcends and complements conventional mean-based analyses by identifying latent regulatory factors that govern the system-level metabolic coordination. Through comprehensive simulation studies, mdGWAS demonstrated robust performance in detecting SNP-metabolite-metabolite associations. Applying mdGWAS to genotyping and mass spectrometry (MS)-based metabolomics data of the METabolic Syndrome In Men (METSIM) Study revealed novel SNPs and genes potentially involved in the regulation of the coordination between metabolic pathways.

Previous evidence suggests that infectious diseases may contribute to the development of neurodegenerative diseases (NDDs) while individuals with hyperglycemia may be at increased risk for both infection and NDDs due to dysregulated inflammation levels. This study aimed to examine the association between hospital-treated infectious diseases and the risk of NDDs among patients with prediabetes and diabetes and whether the associations differed by the number of infections and potential effect modifiers.

Using data from the UK Biobank, we conducted a prospective study involving 69,731 individuals, consisting of 48,149 participants with prediabetes and 21,582 participants with diabetes. Hospital-treated infectious diseases and NDDs were identified through record linkage to Health Episode Statistics and the Scottish Morbidity Records. Cox regression models were applied to assess the association between hospital-treated infectious diseases and the risk of developing NDDs, and to evaluate the trend of this association in relation to the number of infections. The modification effects by age, sex, smoking status, alcohol consumption, sleep duration, body mass index (BMI), glycated hemoglobin (HbA1c) levels, comorbidities, and diabetes medication use were investigated.

Over a median follow-up of 10.75 years, 1,867 participants (2.57 per 1,000 person-years) were diagnosed with NDDs. We found hospital-treated infectious diseases were significantly associated with an increased risk of NDDs among both individuals with prediabetes or diabetes (adjusted HR [aHR] 3.11, 95 % CI 2.83-3.42). Specifically, hospital-treated infectious diseases were associated with a higher risk of developing Alzheimer's disease, vascular dementia, all-cause dementia, Parkinson's disease, and multiple sclerosis. Moreover, a greater number of infection diagnoses was associated with a higher risk of NDDs. Consistent associations between infection and an increased risk of NDDs were observed, regardless of factors representing age, sex, lifestyle, and diabetes severity.

Hospital-treated infectious diseases were significantly associated with the risk of NDDs in individuals with diabetes and prediabetes, with similar associations observed for bacterial and viral infections. These findings emphasize the importance of implementing infection prevention strategies and monitoring of infectious comorbidities in the management of NDDs among patients with prediabetes and diabetes.

A growing body of evidence emphasizes the role of glycemic variability (GV) in the development of conventional diabetes-related complications. Furthermore, advancements in diabetes management and increased life expectancy have led to the emergence of new complications, such as cancer, liver disease, fractures, infections, and cognitive dysfunction. GV is considered to exacerbate oxidative stress and inflammation, acting as a major mechanism underlying these complications. However, few reviews have synthesized the association between GV and these emerging complications or examined their underlying mechanisms. Hence, this narrative review provides a comprehensive discussion of the burden, risks, and mechanisms of GV in these complications, offering further evidence supporting GV as a potential therapeutic target for diabetes management.

To overview the recent literature regarding the relationship between COVID-19 vaccines and glycemic control.

Data were extracted from text and tables of all available articles published up to September 2023 in PubMed Database describing glucose homeostasis data in subjects exposed to COVID-19 vaccines, focusing on patients with diabetes mellitus (DM).

It is debated if the immune system impairment observed in diabetic patients makes them susceptible to lower efficacy of vaccines, but evidence suggests a possible improvement in immune response in those with good glycemic control. Despite their proven protective role lowering infection rates and disease severity, COVID-19 vaccines can result in diabetic ketoacidosis, new-onset diabetes, or episodes of hyper- or hypoglycemia.

Evidence with COVID-19 vaccines highlights the strong relationship existing between DM and immune system function. Clinicians should strive to achieve optimal glucose control before vaccination and promptly manage possible glucose homeostasis derangement following vaccine exposure.

The prevalence of diabetes was estimated at 5.3% of the French population in 2020. People with type 2 diabetes have an increased risk of infection. Currently, there is no consensus on the impact of glycemic control on infectious risk. The objective was to evaluate whether glycemic control and diabetes severity were associated with infectious risk in type 2 diabetes.

We designed a multicenter retrospective cohort study using data from a French primary care database. Data were collected from January 2012 to January 2022. Glycemic control was estimated by the threshold of glycated hemoglobin and diabetes severity by the number, and the type, of antidiabetic treatments. Infectious risk was evaluated by the mean of antibiotic prescriptions per year.

Among 59,020 patients, 1959 patients were included in the final analysis. The threshold of glycated hemoglobin was not associated with the mean of antibiotic prescriptions per year (ANOVA p = 0.228). Secondary analyses did not show an association between the number, or the type, of antidiabetic treatments and the mean of antibiotic prescriptions per year (p = 0.53 and p = 0.018, respectively). No association was observed between glycemic control, diabetes severity and infectious risk in patients with type 2 diabetes. This is the first European study using data from primary care to examine bacterial infectious risk in patients with type 2 diabetes, demonstrating the possibilities offered by the use of databases in primary care research.

Long-term glycemic control was not associated with bacterial infectious risk in patients with type 2 diabetes.

COVID-19 commonly presents as pneumonia, with those most severely affected progressing to respiratory failure. Patient responses to SARS-CoV-2 infection are varied, with comorbidities acting as major contributors to varied outcomes. Focusing on one such major comorbidity, we assessed whether pharmacological induction of type 1 diabetes mellitus (T1DM) would increase the severity of lung injury in a murine model of COVID-19 pneumonia utilizing wild-type mice infected with mouse-adapted SARS-CoV-2. Hyperglycemic mice exhibited increased weight loss and reduced blood oxygen saturation in comparison with their euglycemic counterparts, suggesting that these animals indeed experienced more severe lung injury. Transcriptomic analysis revealed a significant impairment of the adaptive immune response in the lungs of diabetic mice compared with those of control. To expand the limited options available for tissue analysis due to biosafety restrictions, we also employed a new technique to digest highly fixed tissue into a single-cell suspension, originally designed for scRNA-Seq, which we then adapted for flow cytometric analysis. Flow immunophenotyping and scRNA-Seq confirmed impaired recruitment of T-cells into the lungs of T1DM animals. In addition, scRNA-Seq revealed a distinct, highly inflammatory macrophage profile in the diabetic cohort that correlates with the more severe infection these mice experienced clinically, allowing insight into a possible mechanism for this phenomenon. Recognizing the near certainty that respiratory viruses will continue to present significant public health concerns for the foreseeable future, our study provides key insights into how T1DM results in a much more severe infection and identifies possible targets to ameliorate comorbidity-associated severe disease.NEW & NOTEWORTHY We define the exacerbating effects of type 1 diabetes mellitus (T1DM) on COVID-19 pneumonia severity in mice. Hyperglycemic mice experienced increased weight loss and reduced oxygen saturation. Transcriptomic analysis revealed impaired immune responses in diabetic mice, while flow cytometry and single-cell RNA sequencing confirmed reduced T-cell recruitment and an inflammatory macrophage profile. In addition, we introduced a novel technique for tissue analysis, enabling flow cytometric analysis on highly fixed tissue samples.

People with HIV (PWH) and people with diabetes mellitus have increased risk of severe COVID-19, but little is known about humoral response to COVID-19 vaccines in PWH with DM. We investigated SARS-CoV-2 antireceptor-binding domain (anti-RBD) immunoglobulin G (IgG) geometrical concentrations and neutralizing antibody capacity (nAB) in PWH with and without diabetes mellitus. Anti-RBD IgG and nAB in COVID-19-vaccinated PWH were not associated with diabetes mellitus-status or HbA1c 24 months after the initial COVID-19 vaccination.

To compare the risk of hospitalization for infection among patients who achieve intensive versus relaxed glycemic control.

This retrospective cohort study included adults age ≥65 years with type 2 diabetes from an integrated health care delivery system. Negative binomial models were used to estimate incidence rates and relative risk (RR) of hospitalization for infections (respiratory; genitourinary; skin, soft tissue, and bone; and sepsis), comparing two levels of relaxed (hemoglobin A1c [HbA1c] 7% to <8% and 8% to <9%) with intensive (HbA1c 6% to <7%) glycemic control from 1 January 2019 to 1 March 2020.

Among 103,242 older patients (48.5% with HbA1c 6% to <7%, 35.3% with HbA1c 7% to <8%, and 16.1% with HbA1c 8% to <9%), the rate of hospitalization for infections was 51.3 per 1,000 person-years. Compared with HbA1c 6% to <7%, unadjusted risk of hospitalization for infections was significantly elevated among patients with HbA1c 8% to <9% (RR 1.25; 95% CI 1.13, 1.39) but not among patients with HbA1c 7% to <8% (RR 0.99; 95% CI 0.91, 1.08), and the difference became nonsignificant after adjustment. Across categories of infections, the adjusted RR of hospitalization was significantly higher among patients with HbA1c 8% to <9% only for skin, soft tissue, and bone infection (RR 1.33; 95% CI 1.05, 1.69).

Older patients with type 2 diabetes who achieve relaxed glycemic control levels endorsed by clinical guidelines are not at significantly increased risk of hospitalization for most infections, but HbA1c 8% to <9% is associated with an increased risk of hospitalization for skin, soft tissue, and bone infections.

Diabetes mellitus (DM) is associated with lower antiretroviral (ART) drug exposure among persons with HIV (PWH) compared to PWH without DM. The association between DM and virologic control in PWH, however, remains unknown.

We included participants in the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) who had initiated ART between 1999 and 2020 and had a suppressed HIV viral load (≤200 copies/ml) within 1 year of ART initiation. We compared the frequency of incident HIV viremia (HIV-1 RNA >200 copies/ml) between adult PWH with and without DM. Poisson regression was used to examine the rate of incident viremia based on the diagnosis of DM among PWH. DM was defined as two consecutive fasting glucose measurements ≥126 mg/dl, use of antidiabetic medications, preexisting DM diagnosis, or a confirmed HbA1c >6.5%.

1061 women (112 with DM, 949 without DM) and 633 men (41 with DM, and 592 without DM) were included in the analysis. The relative rate (RR) of incident HIV viremia for women with HIV and DM was lower when compared to women without DM (0.85 [95% CI: 0.72-0.99]; P  = 0.04). The RR of incident viremia for women with uncontrolled DM (HbA1c > 7.5%) was higher when compared to women with controlled DM (HbA1c < 7.5%) (1.46 [95% CI: 1.03-2.07]; P  = 0.03). In contrast, the RR of incident viremia for men with HIV and DM was not statistically different compared to men without DM (1.2 [95% CI: 0.96-1.50]; P  = 0.12). The results were stratified by adherence levels (100%, 95-99%, and <95% based on self-report).

Women with DM who are highly adherent to ART (100% self-reported adherence) have a lower risk of viremia compared to women with HIV without DM. However, women with poorly controlled DM were at higher risk of HIV viremia than women with controlled DM. Further research is necessary to understand the impact of sex, DM, and ART adherence on HIV viremia.

The triglyceride-glucose index, a reliable surrogate biomarker of insulin resistance, has been reported to be associated with cardiovascular events and atherosclerosis. However, few studies have investigated the association of the triglyceride-glucose index with postoperative infections. This study aimed to study the clinical risk values of the preoperative triglyceride-glucose index in postoperative infection complications in elderly patients undergoing gastrointestinal-related abdominal and pelvic surgery.

This retrospective cohort study included 3,225 older patients who underwent gastrointestinal-related abdominal and pelvic surgery between 2014 and 2019. The patients were divided into groups of triglyceride-glucose index ≤8.268 and triglyceride-glucose index >8.268 according to the optimal triglyceride-glucose index cut-off value. The outcome of interest was postoperative infections within 30 days after surgery. Primary and subgroup analyses were performed to confirm that preoperative triglyceride-glucose index qualifies as a reliable, independent risk indicator. Propensity score matching analysis was further applied to address covariates' potential residual confounding effect and test the robustness of the results.

In this study, the median age was 71 years (interquartile range, 67, 75 years), the proportion of male patients was 66.3%, and 1,058 (32.8%) were infected within 30 days after surgery. A triglyceride-glucose index >8.268 was associated with an increased risk of postoperative infections in multivariate regression analysis (odds ratio, 1.37; 95% confidence interval, 1.15-1.64; P < .001). The correlation between the triglyceride-glucose index and postoperative infections remained significantly robust (odds ratio, 1.52; 95% confidence interval, 1.21-1.92; P < .001) in the propensity score matching analysis.

The triglyceride-glucose index elevation determined by the optimal cutoff value of 8.268 was an independent risk factor for developing postoperative infections.

To investigate the correlation between the level of glycosylated hemoglobin (HbA1c) and postherpetic neuralgia (PHN).

This cohort study included 100 patients with herpes zoster (HZ) undergoing treatment with pulsed radiofrequency (PRF). Patients with comorbid type 2 diabetes mellitus (T2DM) were divided into three groups based on their glycemic control levels: good [HbA1c < 7% (53.01 mmol/mol), group D1], fair [7% (53.01 mmol/mol) ≤ HbA1c < 9% (74.86 mmol/mol), group D2], and poor [9% (74.86 mmol/mol) ≤ HbA1c, group D3]. The control group (group N) consisted of patients without T2DM. The main outcome measured was the occurrence of PHN in the four groups.

A total of 90 patients were included in the cohort. The occurrence of PHN was found to be higher in groups D2 and D3 when compared to group N (N vs D2, P = 0.007; N vs D3, P < 0.001). Furthermore, the occurrence of PHN was higher in groups D2 and D3 in comparison to group D1 (D1 vs D2, P = 0.022; D1 vs D3, P < 0.001), with the incidence of PHN in group D3 being greater than in group D2 (P < 0.001).

Preoperative HbA1c predicts the incidence of PHN after PRF in T2DM patients.

Diabetes mellitus (DM) is predisposing to the development of latent tuberculosis infection (LTBI). An understanding of the underlying factors of LTBI-DM is important for tuberculosis prevention and control. This study aims to evaluate the association between LTBI and DM among the noninstitutionalized civilian population in the United States, focusing on the impact of serum globulins. We performed a cross-sectional study design using public data from 2011 to 2012 National Health and Nutrition Examination Survey, focusing on participants diagnosed with LTBI who were aged 20 and above. Weighted Wilcoxon rank-sum and weighted chi-square tests were used to compare group differences. A multivariable logistic regression model was constructed to assess the association between serum globulin and DM, with subgroup analyses and evaluations of nonlinear relationships. Receiver operating characteristic curves were used to assess the predictive power of the models. A total of 694 participants (512 DM and 182 nonDM) were included in our study and the incidence of DM was 22%. Higher serum globulin levels were significantly associated with an increased risk of DM, with a 21% increase in risk for each unit increase in serum globulin (odds ratio = 1.21, 95% confidence interval [1.03, 1.43], P < .001). The relationship between serum globulin and DM was linear, and higher serum globulin levels were associated with a higher risk of DM, particularly in males (P = .043) and obese individuals (P = .019). The area under the curve for serum globulin predicting DM was 0.795, with an optimal cutoff value of 2.9. Elevated serum globulin levels are significantly associated with an increased risk of DM among individuals with LTBI, highlighting the potential role of serum globulin as a predictive biomarker for DM in this population. However, the specific mechanism between globulin and LTBI-DM needs to be further investigated.

Patients with diabetes mellitus (DM) are at a higher risk of infectious diseases, and exercise is an important treatment modality for DM. Despite their susceptibility to infection in diabetic patients, the association between the amount of physical activity and the incidence of infective endocarditis (IE) is unclear. We attempted to demonstrate risk reduction by physical activity in diabetic patients with IE. From the National Health Insurance database, patients with DM were verified, and the incidence of IE was investigated. The level of physical activity was categorized into < 500, 500-999, 1,000-1,499, and ≥ 1,500 metabolic equivalent task (METs) minutes/week. Cox proportional hazard models were used to analyze the relationship between incident IE and physical activity. A total of 2,603,012 patients were included in this study. The incidence rate of IE was 10.06, 9.45, 7.78, and 8.84 in < 500, 500-999, 1,000-1,499, and ≥ 1,500 METs-minutes/week groups, respectively (100,000 person/year). A significant risk reduction of incident IE was observed in the 1,000-1499 and ≥ 1,500 METs-min/week groups compared to the < 500 METs-min/week group (Hazard ratio = 0.82, 95% confidence interval [0.690-0.976], HR = 0.831, 95% CI [0.704-0.981]). An analysis of a large national cohort database demonstrated that physical exercise reduced the risk of IE in patients with DM.

During the COVID-19 pandemic, diabetic and obese patients experienced higher rates of hospital admissions, severe illness, and mortality. However, vaccinations failed to provide those vulnerable populations the same level of protection against COVID-19 severity as those without diabetic and obese phenotypes. Our study aimed to investigate how diabetes mellitus (DM) impacts the immune response following vaccination including the artificially designed trimeric SARS-CoV-2 spike (S)-protein. By using two diabetic mouse models, ob/ob mice (obese, hyperglycemic, and insulin-resistant) and STZ-treated mice (insulin-deficient and hyperglycemic), we observed a significant reduction in S-protein-specific IgG antibody titer post-vaccination in both diabetic models compared to wild-type (WT) mice. Both diabetic mouse models exhibited significant abnormalities in spleen tissue, including marked reductions in splenic weight and the size of the white pulp regions. Furthermore, the splenic T-cell and B-cell zones were notably diminished, suggesting an underlying immune dysfunction that could contribute to impaired antibody production. Notably, vaccination with the S-protein, when paired with an optimal adjuvant, did not exacerbate diabetic cardiomyopathy, blood glucose levels, or liver function, providing reassurance about the vaccine's safety. These findings offer valuable insights into potential mechanisms responsible for the decreased persistence of antibody production in diabetic patients.

Periodontitis is a chronic inflammatory disease and is the primary contributor to adult tooth loss. Diabetes exacerbates periodontitis, accelerates periodontal bone resorption. Thus, effectively managing periodontitis in individuals with diabetes is a long-standing challenge. This review introduces the etiology and pathogenesis of periodontitis, and analyzes the bidirectional relationship between diabetes and periodontitis. In this review, we comprehensively summarize the four pathological microenvironments influenced by diabetic periodontitis: high glucose microenvironment, bacterial infection microenvironment, inflammatory microenvironment, and bone loss microenvironment. The hydrogel design strategies and latest research development tailored to the four microenvironments of diabetic periodontitis are mainly focused on. Finally, the challenges and potential solutions in the treatment of diabetic periodontitis are discussed. We believe this review will be helpful for researchers seeking novel avenues in the treatment of diabetic periodontitis.

People with diabetes are at higher risk of serious complications from many vaccine-preventable diseases (VPDs). Some studies have highlighted the potential impact of glycosylated hemoglobin levels (HbA1c), but no systematic review has synthesized these findings. Of the 823 identified studies, 3 were included, for a total of 705,349 participants. Regarding the incidence of herpes zoster (HZ), one study found that higher HbA1c levels at the baseline (>10.3%) were associated with a significantly higher risk of HZ of 44%, compared to those with a good HbA1c control (6.7%). On the contrary, the second one reported that when compared to the reference group (HbA1c of 5.0-6.4%), participants with a HbA1c less than 5.0% were at higher risk of HZ of 63%, whilst participants with a HBA1c more than 9.5% had a similar risk. Finally, the third study observed that diabetes, defined using a value of HbA1c more than 7.5%, was associated with an increased risk of mortality in men with COVID-19. In conclusion, both high and low HBA1c levels appear to be associated with a higher risk of HZ. Regarding COVID-19, a value of HbA1c more than 7.5% was associated with a higher risk of death in COVID-19, but only in men.

Background and aim Type 2 diabetes mellitus (T2DM) is associated with several infections due to hyperglycemia and impaired immunity. This study aims to analyze the clinical and microbiological profile of critically ill T2DM patients with sepsis due to gram-negative bacteria (GNB). Materials and methods A prospective cross-sectional observational study was conducted at Dr. D. Y. Patil Medical College, Hospital & Research Centre, Pune, India, between December 2023 and May 2024, after ethics committee approval. A total of 100 patients (50 T2DM cases and 50 nondiabetic controls), diagnosed with sepsis due to GNB and admitted to the medical ICU, were included in the study. The clinical profile and laboratory investigations of these patients were studied. Cultures were obtained from peripheral/central venous samples, tracheal secretions, and urine samples. Cultures from other specimens, such as ascitic fluid, cerebrospinal fluid, and pus from skin and soft tissue infections, were also obtained. The statistical tests that were applied were two-tailed with a 95% CI, and a p-value of less than 0.05 was considered statistically significant. Results The mean age of critically ill T2DM cases was 60.52 ± 12.88 years. Of the 50 T2DM cases, 28 were males and 22 were females. The most common infection in critically ill T2DM patients was bloodstream infection (n = 21), followed by bronchopneumonia (n = 16) and urinary tract infections (n = 10). Escherichia coli (n = 15) and Klebsiella pneumoniae (n = 15) were the most common gram-negative pathogens isolated. The most common GNB isolated from the blood cultures of critically ill T2DM patients was Acinetobacter spp. (n = 6). The death rate was significantly higher in T2DM patients with GNB sepsis as compared to nondiabetic controls. Conclusion GNBs like E. coli, K. pneumoniae, and Acinetobacter spp. are commonly found in critically ill T2DM patients with sepsis. Bloodstream infection was the most common site of infection in critically ill T2DM cases. Acinetobacter spp. was the most common isolate found in the blood cultures of critically ill T2DM patients. It is important to identify the site of sepsis, isolate the organism, and treat it with appropriate antibiotics promptly in critically ill T2DM patients to improve the outcomes of these patients.

Diabetes mellitus (DM) is a worldwide pandemic affecting 500 million people. It is known to be associated with increased susceptibility to soft tissue infections (STI). Despite being a major public health burden, the literature relating the effects of DM and the presentation, severity and healing of STIs in general surgical patients remain limited.

We conducted a retrospective review of all patients admitted with STI in a tertiary teaching hospital over a 12-month period. Patient demographics and surgical outcomes were collected and analysed.

During the study period, 1059 patients were admitted for STIs (88% required surgery). DM was an independent risk factor for LOS. Diabetic patients presented with higher body-mass index (28 vs. 26), larger abscess size (24 vs. 14 cm2) and had a longer length of stay (4.4 days vs. 2.9 days). They also underwent a higher proportion of wide debridement and application of negative pressure wound therapy (42% vs. 35%). More diabetic patients underwent subsequent re-operation within the same sitting (8 vs. 4). Diabetic patients were two times more likely to present with carbuncles (p = 0.02).

The incidence of STIs among DM patients represent a significant disease burden, surgeons should consider intensive patient counselling and partnering with primary care providers in order to help reduce the incidence of future STI admissions based upon lifestyle modification and glucose control.

Diabetes and stress hyperglycemia have been related with poorer clinical outcomes in patients infected by SARS-CoV-2 and at risk for severe disease.

To evaluate clinical outcomes in three groups of patients (with diabetes, without diabetes and with stress hyperglycemia) with SARS-CoV-2 infection.

A retrospective cohort study was conducted in Cali (Colombia). We included patients 18 years old or older with a diagnosis of SARS-CoV-2 infection, managed in the emergency room, hospitalization, or intensive care unit between March 2020 and December 2021. Immunocompromised patients and pregnant women were excluded. Patients were classified into three groups: without diabetes, with diabetes, and with stress hyperglycemia. A comparison between the groups was performed.

A total of 945 patients were included (59.6% without diabetes, 27% with diabetes, and 13.4% with stress hyperglycemia). Fifty-five-point three percent required intensive care unit management, with a higher need in patients with stress hyperglycemia (89.8%) and diabetes (67.1%), with no difference between these groups (p = 0.249). We identified a higher probability of death in the group with stress hyperglycemia versus the one without diabetes (adjusted OR = 8.12; 95% CI: 5.12-12.88; p < 0.01). Frequency of acute respiratory distress syndrome, need for invasive mechanical ventilation, use of vasopressors and inotropes, need for de novo renal replacement therapy, and mortality was higher in patients with metabolic alterations (diabetes and stress hyperglycemia).

Diabetes and stress hyperglycemia were associated with worse clinical outcomes and mortality in patients with COVID-19. These patients should be identified early and considered them high risk at the COVID-19 diagnosis to mitigate adverse outcomes.

The aim of this study is to estimate the excess mortality burden of influenza virus infection in China from 2012 to 2021, with a concurrent analysis of its associated disease manifestations.

Laboratory surveillance data on influenza, relevant population demographics, and mortality records, including cause of death data in China, spanning the years 2012 to 2021, were incorporated into a comprehensive analysis. A negative binomial regression model was utilized to calculate the excess mortality rate associated with influenza, taking into consideration factors such as year, subtype, and cause of death.

There was no evidence to indicate a correlation between malignant neoplasms and any subtype of influenza, despite the examination of the effect of influenza on the mortality burden of eight diseases. A total of 327,520 samples testing positive for influenza virus were isolated between 2012 and 2021, with a significant decrease in the positivity rate observed during the periods of 2012-2013 and 2019-2020. China experienced an average annual influenza-associated excess deaths of 201721.78 and an average annual excess mortality rate of 14.53 per 100,000 people during the research period. Among the causes of mortality that were examined, respiratory and circulatory diseases (R&C) accounted for the most significant proportion (58.50%). Fatalities attributed to respiratory and circulatory diseases exhibited discernible temporal patterns, whereas deaths attributable to other causes were dispersed over the course of the year.

Theoretically, the contribution of these disease types to excess influenza-related fatalities can serve as a foundation for early warning and targeted influenza surveillance. Additionally, it is possible to assess the costs of prevention and control measures and the public health repercussions of epidemics with greater precision.

Background: We retrospectively evaluated the usefulness of an elevated glucose-to-lymphocyte ratio (GLR) as a sensitive prognostic biomarker of disease-specific survival in 338 patients who underwent surgical resection of pancreatic ductal adenocarcinoma (PDAC). Methods: The optimal GLR cutoff value was determined using the method of Contal and O'Quigley. Patient demographics, clinical information, and imaging data were analyzed to identify preoperative predictors of long-term survival outcomes. Results: Elevated GLR correlated significantly with aggressive tumor biologic behaviors, such as a high carbohydrate antigen (CA) 19-9 level (p = 0.003) and large tumor size (p = 0.011). Multivariate analysis identified (1) GLR > 92.72 [hazard ratio (HR) = 2.475, p < 0.001], (2) CA 19-9 level > 145.35 (HR = 1.577, p = 0.068), and (3) symptoms (p = 0.064) as independent predictors of long-term, cancer-specific survival. These three risk factors were used to group patients into groups 1 (0 factors), 2 (1-2 factors), and 3 (3 factors), which corresponded to significantly different 5-year overall survival rates (50.2%, 34.6%, and 11.7%, respectively; p < 0.001). Conclusions: An elevated preoperative GLR is associated with aggressive tumor characteristics and is an independent predictor of poor postoperative prognosis in patients with PDAC. Further prospective studies are required to verify these findings.

There is increasing evidence of a higher risk and poorer prognosis of cervical cancer among women with diabetes mellitus (DM) compared to the general population. These are mediated by higher susceptibility to persistent high-risk human papillomavirus (hr-HPV) infection due to dysfunctional clearance in an immunocompromised state. We aimed to determine the prevalence of hr-HPV infection and cervical lesions in a cohort of women with DM in Ghana. We further disaggregated the prevalence according to DM type and explored factors associated with hr-HPV infection.

This retrospective descriptive cross-sectional study assessed 198 women with DM who underwent cervical screening via concurrent hr-HPV DNA testing and visual inspection with acetic acid in an outpatient department of the National Diabetes Management and Research Centre in Korle-Bu Teaching Hospital, Accra from March to May 2022. Univariate and multivariable binary logistic regression were used to explore factors associated with hr-HPV positivity.

Among 198 women with DM (mean age, 60.2 ± 12.1 years), the overall hr-HPV prevalence rate was 21.7% (95% CI, 16.1-28.1), disaggregated as 1.5% (95% CI, 0.3-4.4) each for HPV16 and HPV18 and 20.7% (95% CI, 15.3-27.0) for other HPV genotype(s). Respective hr-HPV prevalence rates were 37.5% (95% CI, 15.2-64.6) for type 1 DM, 19.8% (95% CI, 13.9-26.7) for type 2 DM, and 25.0% (95% CI, 8.7-49.1) for unspecified/other DM types. Past use of the combined contraceptive pill independently increased the risk of hr-HPV infection by approximately three times (adjusted odds ratio [aOR] = 2.98; 95% CI, 1.03 - 8.64; p-value = 0.045), whereas each unit increase in FBG level increased the odds of hr-HPV infection by about 15% (aOR = 1.15; 95% CI, 1.02 - 1.30; p-value = 0.021).

Our study points to a high prevalence of hr-HPV among women with DM and highlights a need for glycemic control among them as this could contribute to lowering their odds of hr-HPV infection. The low overall rates of HPV vaccination and prior screening also indicate a need to build capacity and expand the scope of education and services offered to women with DM as regards cervical precancer screening.

We discuss a case of an immunocompetent patient who presented with fever and tachypnoea, found to have Candida parapsilosis bone marrow infection, cultured on bone marrow aspirate sample. Candida parapsilosis is an opportunistic yeast pathogen that typically affects immunocompromised individuals, or occurs in patients with apparent introduced source; neither of these factors were present for this case. Bone marrow aspirates and trephines are not regular investigations for fever; however they can be useful diagnostic aids as evidenced in this case.

An 83-year-old woman presenting with fevers and tachypnoea was being treated for a systemic bacterial infection, however was unresponsive to empirical antibiotic therapy. To exclude an occult malignancy, an 18-fluorodeoxyglucose positron emission tomography scan was conducted. Significant bone marrow uptake was noted, prompting a bone marrow aspirate and trephine to investigate for a hematological malignancy. While the trephine biopsy was benign, a culture of the aspirate grew Candida parapsilosis. Intravenous antifungal therapy was initiated; however, the patient did not improve despite targeted therapy likely due to delays in diagnosis, and was palliated.

Our case seeks to demonstrate a novel case whereby a bone marrow aspirate culture provided a conclusive diagnosis of invasive Candida parapsilosis bone marrow infection, and guided treatment in an immunocompetent patient. It is important for clinicians to consider invasive fungal infections in febrile patients regardless of immune status. Additionally, when performing a bone marrow aspirate and trephine on a febrile patient, we recommend including aspirate fungal cultures to investigate for an invasive fungal infection.

Influenza is associated with a substantial health burden, especially in high-risk subjects such as older adults, frail individuals and those with underlying chronic diseases. In this review, we summarized clinical findings regarding the impact of influenza in vulnerable populations, highlighted the benefits of influenza vaccination in preventing severe illness and complications and reviewed the main evidence on the efficacy, effectiveness and safety of the vaccines that are best suited to older adults among those available in Italy. The adverse outcomes associated with influenza infection in elderly and frail subjects and those with underlying chronic diseases are well documented in the literature, as are the benefits of vaccination (mostly in older adults and in patients with cardiovascular diseases, diabetes and chronic lung disease). High-dose and adjuvanted inactivated influenza vaccines were specifically developed to provide enhanced immune responses in older adults, who generally have low responses mainly due to immunosenescence, comorbidities and frailty. These vaccines have been evaluated in clinical studies and systematic reviews by international immunization advisory boards, including the European Centre for Disease Prevention and Control. The high-dose vaccine is the only licensed influenza vaccine to have demonstrated greater efficacy versus a standard-dose vaccine in preventing laboratory-confirmed influenza in a randomized controlled trial. Despite global recommendations, the vaccination coverage in high-risk populations is still suboptimal. All healthcare professionals (including specialists) have an important role in increasing vaccination rates.

Diabetes mellitus is characterized by elevated blood sugar level due to a deficiency in insulin production and/or action. Balanites aegyptiaca (BA) has been employed as a hypoglycemic medication. Nanoparticles (NPs) have many advantages like minimized drug dose, sustainable drug release, maximized bioavailability and delivery of drugs. The study aimed to synthesize novel chitosan (CS) NPs loaded with BA extract (BA Ex). The prepared NPs were examined in treatment of streptozotocin-induced diabetes in rats. The anti-diabetic efficiency was evaluated through measuring of levels of blood glucose, insulin, lipid profile, oxidative stress markers, pro-inflammatory cytokines. GC-MS, HPLC and ICP techniques showed the presence of numerous bioactive components that have an anti-diabetic effectiveness. BA Ex-CS NPs succeeded in treatment of diabetes; where, it increased insulin secretion, lowered both FBG and FTA levels and helped in neogenesis of pancreatic islets beta cells. The regenerative activity of BA Ex-CS NPs is attributed to its high antioxidant and anti-inflammatory properties. This antioxidant activity scavenged the generated free radicles that resulted from STZ administration. CS NPs raised the plant extract efficacy, prevented its degradation, and regulated the release of its components. The delivery of BA Ex bioactive components has been revolutionized by CS NPs.

Due to the paucity of literature on risk factors for tuberculosis (TB)-related death, we determine the sociodemographic and clinical risk factors associated with TB-related deaths among adult pulmonary TB (PTB) patients on treatment in Selangor, Malaysia.

Retrospective cohort study.

Routinely collected primary care data from all government TB clinics in Selangor.

Data of 24 570 eligible adult PTB patients from 2013 to 2019 were obtained from Selangor's State Health Department surveillance records. We included PTB patients aged at least 15 years old at the time of diagnosis with complete documentation of the dates of diagnosis, treatment initiation, end of treatment/follow-up and treatment outcomes. We excluded patients whose diagnoses were changed to non-TB, post-mortem TB diagnosis and multidrug-resistant TB (MDR-TB) patients.

TB-related death, determined from the recorded physicians' consensus during the TB mortality meeting.

TB-related death was significantly associated with far (adjusted HR (aHR) 9.98, 95% CI 4.28 to 23.28) and moderately advanced (aHR 3.23, 95% CI 1.43 to 7.31) radiological findings at diagnosis; concurrent TB meningitis (aHR 7.67, 95% CI 4.53 to 12.98) and miliary TB (aHR 6.32, 95% CI 4.10 to 9.74) involvement; HIV positive at diagnosis (aHR 2.81, 95% CI 2.21 to 3.57); Hulu Selangor (aHR 1.95, 95% CI 1.29 to 2.93), Klang (aHR 1.53, 95% CI 1.18 to 1.98) and Hulu Langat (aHR 1.31, 95% CI 1.03 to 1.68) residing districts; no formal education (aHR 1.70, 95% CI 1.23 to 2.35); unemployment (aHR 1.54, 95% CI 1.29 to 1.84), positive sputum smear acid-fast bacilli (AFB) at diagnosis (aHR 1.51, 95% CI 1.22 to 1.85); rural residency (aHR 1.39, 95% CI 1.13 to 1.72) and advancing age (aHR 1.03, 95% CI 1.02 to 1.03).

Far and moderately advanced radiological findings, concurrent TB meningitis and miliary TB involvement, HIV positive, Hulu Selangor, Klang and Hulu Langat residing districts, no formal education, unemployment, positive sputum smear AFB, rural residency and advancing age are risk factors of TB-related death. Our findings should assist in identifying high-risk patients requiring interventions against TB-related death.

Introduction Carbapenem-resistant Enterobacterales (CRE) infections have high mortality. We aimed to examine the diabetes mellitus (DM) association with CRE mortality. Methodology Our study is a retrospective cohort study including patients who were admitted to the medical wards in the main district hospital (New Jahra Hospital, Kuwait) between January 1, 2022, and January 1, 2023, and diagnosed with CRE infections during hospitalization. The patients were divided into diabetic and non-diabetic groups. Clinical and laboratory data were collected. The presence of carbapenemase genes was detected. The primary outcome was 30-day hospital mortality. We assessed the effect of glycemic control on the outcomes. Results We included 47 patients in the diabetic group and 39 patients in the non-diabetic group. Females represented 54.7% of patients, and the median age was 73 and 55 years in the two groups, respectively. Klebsiella pneumonia (86%) and Escherichia coli (12.8%) were the most frequently isolated CRE. Carbapenemase genes were detected in all patients: NDM-1 in 67.4%, OXA-48 in 18.6%, and both genes coexisted in 14%. The 30-day hospital mortality was significantly higher in the diabetic group compared to the non-diabetic group (48.9% vs. 28.2%, P = 0.041). Among the diabetic patients, there was no significant difference between survivors and non-survivors regarding median glucose or glycated hemoglobin (HbA1c) levels (P = 0.465 and 0.932, respectively). Moreover, levels of glucose (odds ratio (OR) 0.928, confidence interval (CI) 0.763-1.13, P = 0.457) and HbA1c (OR 0.89, CI 0.63-1.26, P = 0.507) were not risk factors for increased mortality among diabetic patients.  Conclusion We demonstrated the association between DM and increased CRE mortality regardless of the level of glycemic control. This study demonstrates the interaction between communicable and non-communicable diseases.

With the deepening of aging in China, the prevalence of diabetes in older people has increased noticeably, and standardized diabetes management is critical for improving clinical outcomes of diabetes in older people. In 2021, the National Center of Gerontology, Chinese Society of Geriatrics, and Diabetes Professional Committee of Chinese Aging Well Association organized experts to write the first guideline for diabetes diagnosis and treatment in older people in China, the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2021 Edition). The guideline emphasizes that older patients with diabetes are a highly heterogeneous group requiring comprehensive assessment and stratified and individualized management strategies. The guideline proposes simple treatments and de-intensified treatment strategies for older patients with diabetes. This edition of the guideline provides clinicians with practical and operable clinical guidance, thus greatly contributing to the comprehensive and full-cycle standardized management of older patients with diabetes in China and promoting the extensive development of clinical and basic research on diabetes in older people and related fields. In the past 3 years, evidence-based medicine for older patients with diabetes and related fields has further advanced, and new treatment concepts, drugs, and technologies have been developed. The guideline editorial committee promptly updated the first edition of the guideline and compiled the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition). More precise management paths for older patients with diabetes are proposed, for achieving continued standardization of the management of older Chinese patients with diabetes and improving their clinical outcomes.

People with type 1 diabetes (T1D) have raised infection rates compared to those without, but how these risks vary by age, sex and ethnicity, or by glycated haemoglobin (HbA1c), remain uncertain.

33,829 patients with T1D in Clinical Practice Research Datalink on 01/01/2015 were age-sex-ethnicity matched to two non-diabetes patients. Infections were collated from primary care and linked hospitalisation records during 2015-2019, and incidence rate ratios (IRRs) were estimated versus non-diabetes. For 26,096 people with T1D, with ≥3 HbA1c measurements in 2012-2014, mean and coefficient of variation were estimated, and compared across percentiles.

People with T1D had increased risk for infections presenting in primary care (IRR = 1.81, 95%CI 1.77-1.85) and hospitalisations (IRR = 3.37, 3.21-3.53) compared to non-diabetes, slightly attenuated after further adjustment. Younger ages and non-White ethnicities had greater relative risks, potentially explained by higher HbA1c mean and variability amongst people with T1D within these sub-groups. Both mean HbA1c and greater variability were strongly associated with infection risks, but the greatest associations were at the highest mean levels (hospitalisations IRR = 4.09, 3.64-4.59) for >97 versus ≤53 mmol/mol.

Infections are a significant health burden in T1D. Improved glycaemic control may reduce infection risks, while prompter infection treatments may reduce hospital admissions.

Diabetes mellitus is a chronic metabolic disease, the prevalence of which is constantly increasing worldwide. It is often burdened by disabling comorbidities that reduce the quality and expectancy of life of the affected individuals. The traditional complications of diabetes are generally described as macrovascular complications (e.g., coronary heart disease, peripheral arterial disease, and stroke), and microvascular complications (e.g., diabetic kidney disease, retinopathy, and neuropathy). Recently, due to advances in diabetes management and the increased life expectancy of diabetic patients, a strong correlation between diabetes and other pathological conditions (such as liver diseases, cancer, neurodegenerative diseases, cognitive impairments, and sleep disorders) has emerged. Therefore, these comorbidities have been proposed as emerging complications of diabetes. P66Shc is a redox protein that plays a role in oxidative stress, apoptosis, glucose metabolism, and cellular aging. It can be regulated by various stressful stimuli typical of the diabetic milieu and is involved in various types of organ and tissue damage under diabetic conditions. Although its role in the pathogenesis of diabetes remains controversial, there is strong evidence regarding the involvement of p66Shc in the traditional complications of diabetes. In this review, we will summarize the evidence supporting the role of p66Shc in the pathogenesis of diabetes and its complications, focusing for the first time on the emerging complications of diabetes.

Advanced glycation end products (AGEs) are a heterogeneous group of compounds that are non-enzymatically produced by reactions between carbonyl compounds and proteins. Many types of AGEs are produced according to the type or concentration of the reacting carbonyl compound. We have previously demonstrated that a glycolaldehyde-derived AGE suppresses stimulator of interferon gene (STING)/TANK-binding kinase 1 (TBK1)/interferon regulatory transcription factor 3 (IRF3), which is a component of the innate immune system. In this report, we investigated the effects of AGEs prepared by several carbonyl compounds on STING/TBK1/IRF3 signaling. AGEs used in the present study were numbered based on the carbonyl compound type: AGE1, derived from glucose; AGE2, derived from glyceraldehyde; AGE3, derived from glycolaldehyde; AGE4, derived from methylglyoxal; and AGE5, derived from glyoxal. AGEs derived from aldehyde (AGE2 and AGE3) and dicarbonyl compounds (AGE4 and AGE5) suppressed cyclic GMP-AMP (cGAMP)-induced activation of STING/TBK1/IRF3 signaling, with different suppression efficiencies observed. Lysine modification by carbonyl compounds was related to the efficiency of the suppressive effect on STING/TBK1/IRF3 signaling. Among the AGEs used, only AGE1 enhanced cGAMP-induced activation of STING/TBK1/IRF3 signaling. Enhancing the modulation of STING/TBK1/IRF3 signaling by AGE1 was mediated by toll-like receptor 4. These results indicated that modulation of STING/TBK1/IRF3 signaling by prepared AGEs is dependent on the type and concentration of the carbonyl compound present. Modulating STING/TBK1/IRF3 signaling by AGEs may involve modification of lysine residues in proteins.

Bone has the rare capability of scarless regeneration that enables the complete restoration of the injured bone area. In recent decades, promising new technologies have emerged from basic, translational and clinical research for fracture treatment; however, 5-10 % of all bone fractures still fail to heal successfully or heal in a delayed manner. Several comorbidities and risk factors have been identified which impair bone healing and might lead to delayed bone union or non-union. Therefore, a considerable amount of research has been conducted to elucidate molecular mechanisms of successful and delayed fracture healing to gain further insights into this complex process. One focus of recent research is to investigate the complex interactions of different cell types and the action of progenitor cells during the healing process. Of particular interest is also the identification of patient-specific comorbidities and how these affect fracture healing. In this review, we discuss the recent knowledge about progenitor cells for long bone repair and the influence of comorbidities such as diabetes, postmenopausal osteoporosis, and chronic stress on the healing process. The topic selection for this review was made based on the presented studies at the 2022 annual meeting of the European Calcified Tissue Society (ECTS) in Helsinki.

Obesity and type 2 diabetes mellitus (T2DM) are associated with an increased risk of severe outcomes from infectious diseases, including coronavirus disease 2019. These conditions are also associated with distinct responses to immunization, including an impaired response to widely used severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines.

We sought to establish a connection between reduced immunization efficacy via modeling the effects of metabolic diseases on vaccine immunogenicity that is essential for the development of more effective vaccines for this distinct vulnerable population.

A murine model of diet-induced obesity and insulin resistance was used to model the effects of comorbid T2DM and obesity on vaccine immunogenicity and protection.

Mice fed a high-fat diet (HFD) developed obesity, hyperinsulinemia, and glucose intolerance. Relative to mice fed a normal diet, HFD mice vaccinated with a SARS-CoV-2 mRNA vaccine exhibited significantly lower anti-spike IgG titers, predominantly in the IgG2c subclass, associated with a lower type 1 response, along with a 3.83-fold decrease in neutralizing titers. Furthermore, enhanced vaccine-induced spike-specific CD8+ T-cell activation and protection from lung infection against SARS-CoV-2 challenge were seen only in mice fed a normal diet but not in HFD mice.

The study demonstrated impaired immunity following SARS-CoV-2 mRNA immunization in a murine model of comorbid T2DM and obesity, supporting the need for further research into the basis for impaired anti-SARS-CoV-2 immunity in T2DM and investigation of novel approaches to enhance vaccine immunogenicity among those with metabolic diseases.

(1) Background: Given the growing global diabetes crisis, this study examined the causes of mortality in diabetic patients at a Mongolian tertiary care hospital. (2) Between 2017 and 2021, data from 100 individuals with diabetes (53% male, mean age 58.5 years, duration of diabetes, 9.6 years, HbA1c level, 9.7%, 11.1% type 1 diabetes) were reviewed. (3) Results: The predominant cause of mortality was sepsis, accounting for 65.0% of cases and emerging as a contributing factor in 75.0% of instances. Renal failure constituted the second leading cause of death, accounting for 19.0% of mortalities. Other contributing factors included chronic liver disease (6.0%) and ARDS (3.0%). Regarding sepsis, the individuals affected were relatively younger (57.5 ± 11.2 vs. 61.7 ± 11.2, p = 0.988), with a slightly higher prevalence among female patients (77.4%) and those with T1DM (81.8%), though these differences were not statistically significant (p > 0.05). Patients with sepsis exhibited lower BMI values (26.7 ± 4.1 vs. 28.5 ± 6.2, p = 0.014) and poorer glycemic control (9.8 ± 3.1 vs. 9.6 ± 5.1, p = 0.008); (4) Conclusions: This hospital-based data analysis in Mongolia highlights sepsis as the primary cause of mortality among diabetes patients in tertiary hospitals regardless of age, gender, or diabetes type while also indicating a potential association between a lower BMI, poor glycemic control, smoking, and the risk of sepsis.

Diabetes mellitus is a chronic disease that, untreated or poorly controlled, can lead to serious complications, reducing life expectancy and quality. Diabetic patients are more likely to develop infections, including many common infections, but also pathognomonic ones such as emphysematous pyelonephritis, malignant otitis externa, mucormycosis and Fournier's gangrene. Considering the fact that diabetic patients experience more frequently urinary tract infections (UTIs) with a worse prognosis than non-diabetic people, we conducted a review study based on data in the literature, following the particularities of UTIs in this group of patients, the risk factors, the mechanisms involved and the challenges in their management. The findings highlight that UTI in diabetic patients have some particularities, including a more frequent evolution to bacteremia, increased hospitalizations, and elevated rates of recurrence and mortality than non-diabetic patients. The possible risk factors identified seem to be female gender, pregnancy, older age, UTI in the previous six months, poor glycemic control and duration of diabetes. The mechanisms involved are related to glucosuria and bladder dysfunction, factors related to bacterial strains and host response. The bacterial strains involved in UTIs in diabetic patients and their antibiotic susceptibility profile are, with some exceptions, similar to those in non-diabetic people; however, the antimicrobial agents should be carefully chosen and the duration of the treatment should be as those required for a complicated UTI. The data related to the risk of developing UTIs in patients treated with SGLT-2 inhibitors, a new class of oral hypoglycaemic agents with cardiovascular and renal benefits, are controversial; overall, it was evidenced that UTIs occurred at the initiation of the treatment, recurrent infection was uncommon and the majority of UTIs responded to treatment with standard antibiotics. Moreover, interruption or discontinuation of SGLT-2 inhibitor as a result of UTI was rare and SGLT-2 inhibitors did not increase the risk of severe infections such as urosepsis and pyelonephritis.

Smoking patients with diabetes mellitus (DM) are at greater risk of developing pneumonia. How smoking behavior changes affect the risk of pneumonia hospitalization, however, remains unclear. Therefore, we investigated the association between smoking behavior change and the risk of pneumonia hospitalization in patients with DM. From January 1, 2009 and December 31, 2018, we investigated the association between smoking behavior change and the risk of pneumonia hospitalization in patients with DM. A total of 332,798 adult patients with DM from the Korean National Health Insurance System database who underwent health screening examination between 2009 and 2012, and were smokers at the first health examination were included. During a mean follow-up of 4.89 years, 14,598 (4.39%) incident pneumonia hospitalization cases were identified. Reducers had a slightly increased risk of pneumonia hospitalization (aHR 1.06, 95% CI 1.01-1.10) compared to sustainers. Quitters did not have a significant association with incidence of pneumonia hospitalization. However, increasers had 13% higher risk of pneumonia hospitalization (aHR 1.13, 95% CI 1.07-1.18), regardless of whether initial smoking was light, moderate, or heavy. Our study showed that an increase in smoking intensity was associated with an increased risk of pneumonia hospitalization in people with DM. However, a protective effect of smoking reduction or cessation on pneumonia risk was not demonstrated.

During the COVID-19 pandemic, diabetes mellitus (DM) and obesity were associated with high rates of morbidity and mortality. The aim of this study was to investigate the relationship between markers of inflammation, disease severity, insulin resistance, hyperglycemia, and outcomes in COVID-19 patients with and without diabetes and obesity.

Epidemiological, clinical, and laboratory data were collected from the University Hospital of Ioannina COVID-19 Registry and included hospitalized patients from March 2020 to December 2022. The study cohort was divided into three subgroups based on the presence of DM, obesity, or the absence of both.

In diabetic patients, elevated CRP, IL-6, TRG/HDL-C ratio, and TyG index, severe pneumonia, and hyperglycemia were associated with extended hospitalization. Increased IL-6, NLR, and decreased PFR were associated with a higher risk of death. In the obese subgroup, lower levels of PFR were associated with longer hospitalization and a higher risk of death, while severe lung disease and hyperglycemia were associated with extended hospitalization. In patients without DM or obesity severe pneumonia, NLR, CRP, IL-6, insulin resistance indices, and hyperglycemia during hospitalization were associated with longer hospitalization.

Inflammatory markers and disease severity indices were strongly associated with disease outcomes and hyperglycemia across all subgroups.