Comparing long-term outcomes of children treated with new-onset type 2 diabetes in an outpatient versus inpatient setting: A retrospective chart review.

BACKGROUND: Early identification and management of pediatric type 2 diabetes mellitus (T2DM) is crucial for improving long-term outcomes. This study aimed to assess if the severity of T2DM at presentation, inferred by the location of treatment initiation (inpatient or outpatient), influences long-term clinical outcomes. METHODS: A retrospective chart review was conducted on 116 pediatric T2DM patients. Data on treatment initiation location, initial and subsequent glycated hemoglobin (HbA1c) levels, prescribed insulin, and body mass index were collected from electronic medical records. RESULTS: Of the 116 patients, 69 were initially treated in an inpatient setting, and 47 received outpatient treatment. At treatment initiation, the inpatient group had significantly higher HbA1c levels compared to the outpatient group (p < .001), but 3 years after treatment initiation, no significant difference in HbA1c was observed between the two groups (p = .057). Prescribed insulin dosages were higher in the inpatient group at treatment initiation (p < .001) and remained higher after 3 years (p < 0.003) compared to the outpatient group. CONCLUSIONS: Pediatric patients initially treated in an inpatient setting had poorer glycemic control and higher prescribed insulin dosing at baseline. After 3 years, there was no significant difference in HbA1c levels, but patients treated as inpatients continued to have higher prescribed insulin. These findings suggest that the severity of diabetes at initial presentation may affect long-term clinical outcomes in children with T2DM.

Maternal and Cord Blood Serum Metabolite Associations with Childhood Adiposity and Body Composition Outcomes.

Maternal metabolites influence the size of newborns independently of maternal body mass index (BMI) and glycemia, highlighting the importance of maternal metabolism on offspring outcomes. This study examined associations of maternal metabolites during pregnancy with childhood adiposity, and cord blood metabolites with childhood adiposity using phenotype and metabolomic data from the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and the HAPO Follow-Up Study. The maternal metabolites analyses included 2324 mother-offspring pairs, while the cord blood metabolites analyses included 937 offspring. Multiple logistic and linear regression were used to examine associations between primary predictors, maternal or cord blood metabolites, and childhood adiposity outcomes. Multiple maternal fasting and 1 hr metabolites were significantly associated with childhood adiposity outcomes in Model 1 but were no longer significant after adjusting for maternal BMI and/or maternal glycemia. In the fully adjusted model, fasting lactose levels were negatively associated with child BMI z-scores and waist circumference, while fasting urea levels were positively associated with waist circumference. One-hour methionine was positively associated with fat-free mass. There were no significant associations between cord blood metabolites and childhood adiposity outcomes. Few metabolites were associated with childhood adiposity outcomes after adjusting for maternal BMI and glucose, suggesting that maternal BMI accounts for the association between maternal metabolites and childhood adiposity.

Barriers to and solutions for representative inclusion across the lifespan and in life course research: The need for structural competency highlighted by the COVID-19 pandemic.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the "Lifespan and Life Course Research: integrating strategies" "Un-Meeting" to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.

Impact of SARS-CoV2 on youth onset type 2 diabetes new diagnoses and severity.

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 HbA1c 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.

The Coronavirus Disease 2019 Pandemic is Associated with a Substantial Rise in Frequency and Severity of Presentation of Youth-Onset Type 2 Diabetes.

OBJECTIVES: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years. STUDY DESIGN: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups. RESULTS: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic. CONCLUSIONS: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.

Long-term follow-up of children with in utero exposure to sulfonylurea medications.

BACKGROUND: Offspring born to mothers with gestational diabetes mellitus (GDM) are more likely to have negative neurodevelopmental health outcomes, early obesity, type 2 diabetes, and metabolic syndrome in childhood, adolescence, and adulthood. Standard of care management for GDM and type 2 diabetes mellitus during pregnancy is insulin, but oral sulfonylurea use is increasing, and these medications cross the placenta. Literature on treatment with sulfonylureas for maternal GDM has focused on maternal glycemic control and neonatal outcomes. Studies that have evaluated the long-term outcomes of children exposed to sulfonylureas in utero are limited. OBJECTIVE: This study evaluated anthropometric and neurodevelopmental outcomes of 55 children (ages 5-10) born to mothers with diabetes during pregnancy treated with sulfonylurea or insulin. METHODS AND RESULTS: A group of 25 sulfonylurea-exposed and 30 insulin-exposed participants were age- and sex-matched between groups. No significant differences were identified in z-scores for body mass index (BMI), waist circumference, skinfold measurements, and body fat or rates of overweight/obese BMI between groups. On performance-based cognitive assessment, the sulfonylurea-exposed group had significantly lower scores on inhibition (p = 0.043). CONCLUSION: In summary, children with in utero sulfonylurea exposure had similar physical measurements compared to children with insulin exposure and lower performance on a measure of executive function (inhibition), which is associated with adverse health outcomes.

Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study: newborn anthropometrics and childhood glucose metabolism.

AIMS/HYPOTHESIS: We aimed to examine associations of newborn anthropometric measures with childhood glucose metabolism with the hypothesis that greater newborn birthweight, adiposity and cord C-peptide are associated with higher childhood glucose levels and lower insulin sensitivity. METHODS: Data from the international, multi-ethnic, population-based Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and the HAPO Follow-Up Study were used. The analytic cohort included 4155 children (mean age [SD], 11.4 [1.2] years; 51.0% male). Multiple linear regression was used to examine associations of primary predictors, birthweight, newborn sum of skinfolds (SSF) and cord C-peptide, from HAPO with continuous child glucose outcomes from the HAPO Follow-Up Study. RESULTS: In an initial model that included family history of diabetes and maternal BMI during pregnancy, birthweight and SSF demonstrated a significant, inverse association with 30 min and 1 h plasma glucose levels. In the primary model, which included further adjustment for maternal sum of glucose z scores from an oral glucose tolerance test during pregnancy, the associations were strengthened, and birthweight and SSF were inversely associated with fasting, 30 min, 1 h and 2 h plasma glucose levels. Birthweight and SSF were also associated with higher insulin sensitivity (Matsuda index) (ß = 1.388; 95% CI 0.870, 1.906; p < 0.001; ß = 0.792; 95% CI 0.340, 1.244; p < 0.001, for birthweight and SSF higher by 1 SD, respectively) in the primary model, while SSF, but not birthweight, was positively associated with the disposition index, a measure of beta cell compensation for insulin resistance (ß = 0.034; 95% CI 0.012, 0.056; p = 0.002). Cord C-peptide levels were inversely associated with Matsuda index (ß = -0.746; 95% CI -1.188, -0.304; p < 0.001 for cord C-peptide higher by 1 SD) in the primary model. CONCLUSIONS/INTERPRETATION: This study demonstrates that higher birthweight and SSF are associated with greater childhood insulin sensitivity and lower glucose levels following a glucose load, associations that were further strengthened after adjustment for maternal glucose levels during pregnancy. Graphical abstract.

Hyperglycemia During Pregnancy and Long-Term Offspring Outcomes.

PURPOSE OF REVIEW: This review will focus on the long-term outcomes in offspring exposed to in utero hyperglycemia and gestational diabetes (GDM), including obesity, adiposity, glucose metabolism, hypertension, hyperlipidemia, nonalcoholic fatty liver disease, and puberty. RECENT FINDINGS: There is evidence, mostly from observational studies, that offspring of GDM mothers have increased risk of obesity, increased adiposity, disorders of glucose metabolism (insulin resistance and type 2 diabetes), and hypertension. In contrast, evidence from the two intervention studies of treatment of mild GDM and childhood measures of BMI, adiposity, and glucose tolerance do not demonstrate that GDM treatment significantly reduces adverse childhood metabolic outcomes. Thus, more evidence is needed to understand the impact of maternal GDM on offspring's adiposity, glucose metabolism, lipid metabolism, risk of fatty liver disease, and pubertal onset. Offspring of GDM mothers may have increased risk for metabolic and cardiovascular complications. Targeting this group for intervention studies to prevent obesity and disorders of glucose metabolism is one potential strategy to prevent adverse metabolic health outcomes.

Ethanol exposure suppresses bone marrow-derived dendritic cell inflammatory responses independent of TLR4 expression.

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.