Acute alcohol (ethanol) exposure is linked with increased susceptibility to infection and increased mortality in trauma and burn patients. Dendritic cells (DCs) are central mediators in innate and adaptive immune responses, and they play a role in the presentation of pathogens to adaptive immune cells. We investigated the effects of acute ethanol exposure on bone marrow-derived DC (BM-DC) responses. Total bone marrow cells, obtained from 8 to 10 week old C57BL/6 male mice, were cultured in the presence of granulocyte/monocyte-colony stimulating factor and interleukin (IL)-4 for 7 days. BM-DCs were harvested and treated with increasing doses of ethanol (50, 100, and 250 mM) at the time of, or 3 h before, lipopolysaccharide (LPS). After LPS, supernatants were collected for cytokine measurement, and cells were harvested for flow cytometry. Concurrent acute ethanol exposure and LPS treatment resulted in a dose-dependent suppression of IL-6, IL-12p40, IL-23, and IL-10. In addition, ethanol exposure before LPS dysregulated the IL-12p40/IL-23 balance and more profoundly suppressed IL-6 and IL-10 secretion by BM-DCs, as compared with cells concurrently treated with ethanol and LPS. Ethanol treatment did not affect either toll-like receptor (TLR)4 or TLR2 expression. In summary, our study demonstrates that acute ethanol exposure suppresses BM-DC LPS-induced responses, irrespective of affecting TLR4 or TLR2 expression.

Introduction: Initial reports show an increase in youth onset type 2 diabetes during the COVID‐19 pandemic. We aim to expand on existing evidence by analyzing trends over a longer period.Objectives: Our study aims to describe change in the amount, severity, and demographics of youth onset type 2 diabetes diagnoses during the COVID‐19 pandemic compared to the five years before.Methods: We performed a retrospective cross‐sectional review of youth (age ≤ 21) diagnosed with type 2 diabetes during the COVID‐19 pandemic (1 May 2020–30 April 2021) and the five years before (1 May 2015–30 April 2020) at a tertiary care center. Children were identified by International Classification of Diseases codes. Charts were reviewed to confirm diagnosis. Chi‐square, t tests, and Fisher's exact tests were used for analyses.Results: In the prepandemic era annual diagnoses of type 2 diabetes ranged from 41–69 (mean = 54.2), whereas during the pandemic period 159 children were diagnosed, an increase of 293%. The increase resulted in a higher incidence rate ratio during the pandemic than before, 2.77 versus 1.07 (p = .006). New diagnoses increased most, by 490%, in Non‐Hispanic Black patients. The average HbA_1c at presentation was higher during the pandemic (9.5% ± 2.6) (79.9 mmol/mol ± 28.2) than before (8.7%±2.1) (72.1 mmol/mol ± 23.1) (p = .003). Of those diagnosed during the pandemic, 59% were tested for COVID‐19 and three tested positive.Conclusions: New diagnoses of type 2 diabetes increased during the pandemic, most notably in Non‐Hispanic Black youth. There was not a significant correlation found with clinical or biochemical COVID‐19 infection in those tested.

Objective: This study aimed to identify whether cord blood DNA methylation at specific loci is associated with neonatal adiposity, a key risk factor for childhood obesity.Methods: An epigenome‐wide association study was conducted using the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study as a discovery sample. Linear regression models adjusted for maternal and offspring covariates and cell counts were used to analyze associations between neonatal adiposity as measured by sum of three skinfold thicknesses and cord blood DNA methylation. Assays were performed with Illumina EPIC arrays (791,359 CpG sites after quality control). Replication was performed in an independent cohort, Genetics of Glucose regulation in Gestation and Growth (Gen3G).Results: In 2740 HAPO samples, significant associations were identified at 89 CpG sites after accounting for multiple testing (Bonferroni‐adjusted p < 0.05). Replication analyses conducted in 139 Gen3G participants confirmed associations for seven CpG sites. These included IGF1R, which encodes a transmembrane receptor involved in cell growth and survival that binds insulin‐like growth factor I and insulin, and KLF7, which encodes a regulator of cell proliferation and inhibitor of adipogenesis; both are key regulators of growth during fetal life.Conclusions: These findings support epigenetic mechanisms in the developmental origins of neonatal adiposity and as potential biomarkers of metabolic disease risk.

Background: Cystic fibrosis‐related diabetes (CFRD) can be associated with decline in pulmonary function and nutritional status. Earlier diagnosis of CFRD than offered by annual recommended oral glucose tolerance test (OGTT) and earlier initiation of insulin may help prevent clinical decline. This retrospective study investigates the utility of continuous glucose monitoring (CGM) for detection of hyperglycemia in patients with cystic fibrosis (CF). Methods: In this single‐center, retrospective study, we analyzed data from 18 patients with CF over age 10 who had an abnormal OGTT and subsequently had at least 24 h of CGM data. EasyGV software was used to calculate multiple measures of CGM variability. Differences in OGTT and CGM measures were explored across four glucose‐tolerance groups: indeterminate, fasting hyperglycemia, impaired glucose tolerance (with or without fasting hyperglycemia), and CFRD. Results: Multiple CGM measures correlated with components of the OGTT. Across glucose‐tolerance groups, significant differences were observed for the OGTT 2‐h glucose ( p = 0.002), mean of daily differences from CGM ( p = 0.03), and standard deviation from CGM ( p = 0.02). Approaching significance was the lability index ( p = 0.05) from the CGM data. Glucose management indicator (GMI), continuous overlapping net glycemic action (CONGA), glycemic risk assessment in diabetes equation (GRADE), and average daily risk range (ADRR) showed negative correlations with change in forced expiratory volume over 1 s (FEV1) over the year before OGTT. Conclusion: Markers of glycemic variability may be important variables distinguishing between degrees of abnormal glucose tolerance, including CFRD. This area warrants further research with a larger sample size.