Diabetes and other vascular risk factors in association with the risk of lower extremity amputation in chronic limb-threatening ischemia: a prospective cohort study

Background Patients with diabetes are at increased risk of developing chronic limb-threatening ischemia (CLTI) due to peripheral arterial disease, and this often results in lower extremity amputation (LEA). Little is known of the interaction between diabetes and other vascular risk factors in affecting the risk of CLTI. Methods We investigated the association of diabetes, and its interaction with hypertension, body mass index (BMI) and smoking, with the risk of LEA due to CLTI in the population-based Singapore Chinese Health Study. Participants were interviewed at recruitment (1993–1998) and 656 incident LEA cases were identified via linkage with nationwide hospital database through 2017. Multivariate-adjusted Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% CIs for the associations. Results The HR (95% CI) for LEA risk was 13.41 (11.38–15.79) in participants with diabetes compared to their counterparts without diabetes, and the risk increased in a stepwise manner with duration of diabetes (P for trend < 0.0001). Hypertension and increased BMI independently increased LEA risk in those without diabetes but did not increase the risk in those with diabetes (P for interaction with diabetes ≤ 0.0006). Conversely, current smoking conferred a risk increment of about 40% regardless of diabetes status. Conclusions Although diabetes conferred more than tenfold increase in risk of LEA, hypertension and increased BMI did not further increase LEA risk among those with diabetes, suggesting a common mechanistic pathway for these risk factors. In contrast, smoking may act via an alternative pathway and thus confer additional risk regardless of diabetes status.

Inflammation and mortality in COVID-19 hospitalized patients with and without type 2 diabetes

Background The aim of this study was to determine the relationship of inflammation with mortality in COVID-19 hospitalized patients and to assess if the relationship differed by strata of type 2 diabetes status. We hypothesized that the association of inflammation with mortality was different by type 2 diabetes status. Methods A case-control (died-survived) study of 538 COVID-19 hospitalized patients, stratified by diabetes status, was conducted at Columbia University Irving Medical Center. We quantified the levels of eight cytokines and chemokines in serum, including interferon(IFN)-α2, IFN-γ, Interleukin(IL)-1α, IL-1β, IL-6, IL-8/CXCL8, IFNγ-induced protein 10 (IP10)/CXCL10 and tumor necrosis factor α (TNF-α) using immunoassays. Logistic regression models were used to model the relationships of log-transformed inflammatory markers (or their principal components) and mortality. Results In multiple logistic regression models, higher serum levels of IL-6 (adjusted odds ratio (aOR):1.74, 95% confidence intervals (CI): (1.48, 2.06)), IL-8 (aOR: 1.75 (1.41, 2.19)) and IP10 (aOR: 1.36 (1.24, 1.51)), were significantly associated with mortality. This association was also seen in second principal component (PC) with loadings reflecting similarities among these three markers (aOR: 1.88 (1.54-2.31)). Significant positive association of these same inflammatory markers with mortality was also observed within each strata of diabetes. Conclusions We show that mortality in COVID19 patients is associated with elevated serum levels of innate inflammatory cytokine IL-6 and inflammatory chemokines IL-8 and IP10. This relationship is consistent across strata of diabetes, suggesting interventions targeting these innate immune pathways could potentially also benefit patients with diabetes.

Glycemic Variability Is Associated With All-Cause Mortality In COVID-19 Patients With ARDSFindings From The COVAS Cohort

There is high mortality among intensive care unit (ICU) patients with acute respiratory distress syndrome (ARDS) caused by coronavirus disease 19 (COVID-19). Important factors for COVID-19 mortality are diabetes status and elevated fasting plasma glucose (FPG). However, the effect of glycemic variability on survival has not been explored in patients with COVID-19 and ARDS. This single-centre cohort-study compared several metrics of daily glycemic variability (DGV) for goodness-of-fit in patients requiring mechanical ventilation due to COVID-19 ARDS in the ICU at University Hospital Aachen, Germany. 106 patients had moderate to severe ARDS (P/F ratio median [IQR]: 112 [87-148] mmHg). Continuous HRs showed a proportional increase in mortality risk with DGV. Multivariable unadjusted and adjusted Cox-models showed a statistically significant difference in mortality for DGV (HR: 1.02, (P)<0.001, LR(P)<0.001; HR: 1.016, (P)=0.001, LR(P)<0.001, respectively). Kaplan-Meier estimators yielded a shorter median survival (25 vs. 87 days) and higher likelihood of death (75% vs. 31%) in patients with DGV ≥ 25.5mg/dl (P<0.0001). High glycemic variability during ICU admission is associated with significant increase in all-cause mortality for patients admitted with COVID-19 ARDS to the ICU. This effect persisted even after adjustment for clinically predetermined confounders, including diabetes, procalcitonin and FPG levels at baseline.

Diabetes status and postoperative complications for patients receiving open rotator cuff repair

Background Diabetic patients are known to have poor wound healing and worse outcomes following surgeries. The purpose of this study is to evaluate diabetes status and complications for patients receiving open rotator cuff repair. Methods Patients undergoing open rotator cuff repair from 2006 to 2018 were identified in a national database. Patients were stratified into 3 cohorts: no diabetes mellitus, non-insulin dependent diabetes mellitus (NIDDM), and insulin dependent diabetes mellitus (IDDM). Differences in demographics, comorbidities, and complications were assessed with the use of bivariate and multivariate analyses. Results Of 7678 total patients undergoing open rotator cuff repair, 6256 patients (81.5%) had no diabetes, 975 (12.7%) had NIDDM, and 447 (5.8%) had IDDM. Bivariate analyses revealed that IDDM patients had increased risk of mortality, extended length of stay, and readmission compared to non-diabetic patients ( p < 0.05 for all). IDDM patients had higher risks of major complications and readmission relative to NIDDM patients ( p < 0.05 for both). On multivariate analysis, there were no differences in any postoperative complications between the non-diabetic, NIDDM, and IDDM groups. Discussion Diabetes does not affect postoperative complications following open rotator cuff repairs. Physicians should be aware of this finding and counsel their patients appropriately. Level of Evidence: III

Evaluation of retinal nerve fibre layer thickness as a possible measure of diabetic retinal neurodegeneration in the EPIC-Norfolk Eye Study

Background/aimsMarkers to clinically evaluate structural changes from diabetic retinal neurodegeneration (DRN) have not yet been established. To study the potential role of peripapillary retinal nerve fibre layer (pRNFL) thickness as a marker for DRN, we evaluated the relationship between diabetes, as well as glycaemic control irrespective of diabetes status and pRNFL thickness.MethodsLeveraging data from a population-based cohort, we used general linear mixed models (GLMMs) with a random intercept for patient and eye to assess the association between pRNFL thickness (measured using GDx) and demographic, systemic and ocular parameters after adjusting for typical scan score. GLMMs were also used to determine: (1) the relationship between: (A) glycated haemoglobin (HbA1c) irrespective of diabetes diagnosis and pRNFL thickness, (B) diabetes and pRNFL thickness and (2) which quadrants of pRNFL may be affected in participants with diabetes and in relation to HbA1c.Results7076 participants were included. After controlling for covariates, inferior pRNFL thickness was 0.94 µm lower (95% CI −1.28 µm to −0.60 µm), superior pRNFL thickness was 0.83 µm lower (95% CI −1.17 µm to −0.49 µm) and temporal pRNFL thickness was 1.33 µm higher (95% CI 0.99 µm to 1.67 µm) per unit increase in HbA1c. Nasal pRNFL thickness was not significantly associated with HbA1c (p=0.23). Similar trends were noted when diabetes was used as the predictor.ConclusionSuperior and inferior pRNFL was significantly thinner among those with higher HbA1c levels and/or diabetes, representing areas of the pRNFL that may be most affected by diabetes.

Sporadic, late-onset, and multistage diseases

Somatic mutations can cause cancer and have recently been linked with a range of non-malignant diseases. Multistage models can characterise how mutations lead to cancer, and may also be applicable to these other diseases. Here we found the incidence of over 60% of common diseases in UK Biobank were consistent with a multistage model with an ordered sequence of stages, as approximated by a Weibull distribution, with the log of incidence linearly related to the log of age and the slope often interpreted as the number of stages. A model where the stages can occur in any order was also explored, as was stratification by smoking and diabetes status. Most importantly, we find that many diseases are low risk when young but then become inevitable in old age, but many other diseases do not, being more sporadic with a modest and modifiable risk that slowly increases with age.

Disparities in Cervical Cancer Screening with HPV Test among Females with Diabetes in the Deep South

Background: Due to diabetes being linked with poorer cervical cancer prognosis, this study aimed to evaluate HPV testing behaviors among females with and without diabetes across the U.S. by geographic area in 2016, 2018, and 2020. Methods: This cross-sectional study used the Behavioral Risk Factor Surveillance System (BRFSS) from 2016, 2018, and 2020. The study population included females aged 25–69 years old, stratified by self-reported diabetes status. The primary outcome measure was cervical cancer screening behavior, which was evaluated by self-reported HPV test uptake/receipt (yes/no). Results: A total of 361,546 females from across the U.S. were sampled. Within the study population combined from all study years, the overall likelihood of receiving an HPV test was significantly lower among females with diabetes [37.95% (95% CI: 36.87–39.04)] compared to those without diabetes [46.21% (95% CI: 45.84–46.58)] (p < 0.001). Screening rates with HPV tests were lowest among females with diabetes in the South in 2016 (29.32% (95% CI: 26.82–31.83)), 2018 (39.63% (95% CI: 36.30–42.96)), and 2020 (41.02% (95% CI: 37.60–44.45)). Conclusions: Females with diabetes are screening with HPV tests less frequently than females without diabetes, and females living in the South, particularly states in the Deep South, report the lowest rates of HPV testing.