Insulin clearance at randomisation and in response to treatment in youth with type 2 diabetes: a secondary analysis of the TODAY randomised clinical trial.

Aims/hypothesis: Insulin resistance and compensatory hyperinsulinaemia are core features leading to beta cell failure in youth-onset type 2 diabetes. Insulin clearance (IC) is also a key regulator of insulin concentrations, but few data exist on IC in youth-onset type 2 diabetes. In a secondary analysis of our Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) randomised clinical trial, we investigated potential sex-, race-, ethnicity- and treatment-related differences in IC in youth-onset type 2 diabetes and aimed to identify metabolic phenotypes associated with IC at baseline and in response to metformin, metformin plus a lifestyle intervention, and metformin plus rosiglitazone.

Expansion of Medicaid Coverage of Continuous Glucose Monitor Reduces Health Disparity in Children and Young Adults With Type 1 Diabetes.

Background: Continuous glucose monitor (CGM) usage improves glycemia in people with type 1 diabetes (PWD) and is accepted as the standard of care. The CGM utilization is lower in patients with public insurance and minorized ethnicities. In 2022, California Medicaid reduced its barriers to obtaining CGM coverage for PWD.

Qualitative Study Guiding the Design of a Person-Centered Shared Medical Appointment Model to Optimize Diabetes Care Delivery.

Purpose: The purpose of the study was to explore the shared medical appointment model (SMA) with youth with type 2 diabetes (T2DM) and their caregivers to identify health education needs, access barriers, and recommendations for intervention design.

Methods: Patient and caregiver focus group interviews were conducted in English and Spanish to address these objectives: (1) identify barriers to participation in group sessions, (2) identify barriers to diabetes self-management, and (3) prioritize preference for SMA themes. Qualitative analysis identified strategies for patient recruitment and engagement and recommendations for curriculum design of a future SMA model for youth with T2DM.

Decline in case rates of youth onset type 2 diabetes in year three of the COVID-19 pandemic.

Objectives: To determine changes in case rates of youth onset type 2 diabetes in the three years following the COVID-19 pandemic.

Methods: A single-center, retrospective medical record review was conducted for patients newly diagnosed with T2D between 3/1/18 and 2/28/23 at a pediatric tertiary care center. The number of patients referred to CHLA with a T2D diagnosis date between 3/1/2020 and 2/28/2023 was compared to historical rates between 3/1/2018 and 2/29/2020.

Risk Factors for Hyperosmolar Hyperglycemic State in Pediatric Type 2 Diabetes.

Background: There is a paucity of data on the risk factors for the hyperosmolar hyperglycemic state (HHS) compared with diabetic ketoacidosis (DKA) in pediatric type 2 diabetes (T2D).

Methods: We used the national Kids' Inpatient Database to identify pediatric admissions for DKA and HHS among those with T2D in the years 2006, 2009, 2012, and 2019. Admissions were identified using ICD codes.

Association Between COVID-19 and Severity of Illness for Children With Hyperglycemic Crisis.

Objectives: Admissions to the ICU for children with hyperglycemic crisis (HGC, defined as diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, or hyperosmolar ketoacidosis) increased during the COVID-19 pandemic. We sought to identify if severity of illness for HGC also increased from prepandemic to pandemic years 1 and 2.

Methods: Retrospective study of children aged ≤18 years hospitalized in the Pediatric Health Information System for HGC.

Glucagon-like Peptide-1 Receptor Agonists for the Treatment of Type 2 Diabetes in Youth.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained traction for the management of type 2 diabetes and obesity. Unlike several classes of antidiabetic medications that contribute to weight gain, GLP-1RAs not only reduce haemoglobin A1c, but also promote weight loss. While there is a large body of evidence supporting its safety and efficacy in adults, paediatric clinical trial data have only emerged in recent years.

An Observational Crossover Study of People Using Real-Time Continuous Glucose Monitors Versus Self-Monitoring of Blood Glucose: Real-World Evidence Using EMR Data From More Than 12,000 People With Type 1 Diabetes.

Background: We used real-world electronic health record (EHR) data to examine HbA1c levels among children and adults with type 1 diabetes (T1D) who are classified as continuous glucose monitor (CGM) users after T1D diagnosis and switch to self-monitoring of blood glucose (SMBG) during follow-up, versus people who opt for SMBG after T1D diagnosis and switch to CGM during follow-up visits.

Methods: We conducted an observational, case-crossover study using electronic medical record (EMR) data from the T1D Exchange Quality Improvement Collaborative. The primary outcome in this study was HbA1c.

Making Diabetes Electronic Medical Record Data Actionable: Promoting Benchmarking and Population Health Improvement Using the T1D Exchange Quality Improvement Portal.

This article describes how the T1D Exchange Quality Improvement Collaborative leverages an innovative web platform, the QI Portal, to gather and store electronic medical record (EMR) data to promote benchmarking and population health improvement in a type 1 diabetes learning health system. The authors explain the value of the QI Portal, the process for mapping center-level data from EMRs using standardized data specifications, and the QI Portal's unique features for advancing population health.

Youth-onset type 2 diabetes mellitus: an urgent challenge.

The incidence and prevalence of youth-onset type 2 diabetes mellitus (T2DM) and its complications are increasing worldwide. Youth-onset T2DM has been reported in all racial and ethnic groups, but Indigenous peoples and people of colour are disproportionately affected. People with youth-onset T2DM often have a more aggressive clinical course than those with adult-onset T2DM or those with type 1 diabetes mellitus.

Once-Weekly Dulaglutide for the Treatment of Youths with Type 2 Diabetes.

Background: The incidence of type 2 diabetes mellitus is increasing among youths. Once-weekly treatment with dulaglutide, a glucagon-like peptide-1 receptor agonist, may have efficacy with regard to glycemic control in youths with type 2 diabetes.

Methods: In a double-blind, placebo-controlled, 26-week trial, we randomly assigned participants (10 to <18 years of age; body-mass index [BMI], >85th percentile) being treated with lifestyle modifications alone or with metformin, with or without basal insulin, in a 1:1:1 ratio to receive once-weekly subcutaneous injections of placebo, dulaglutide at a dose of 0.

Diabetes Distress in Young Adults With Youth-Onset Type 2 Diabetes: TODAY2 Study Results.

Objective: To assess the prevalence of high diabetes distress and associated factors in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY2) study cohort of young adults with youth-onset type 2 diabetes.

Research Design And Methods: Participants completed the Diabetes Distress Scale (DDS) at end-of-study visits. Factors examined for association with high distress were demographic (sex, race/ethnicity, age, education, income), medical (HbA1c, BMI, complications), psychological (depressive and anxiety symptoms), and social (number in household, offspring, health care coverage, established with diabetes care provider).

SARS-CoV2 infects pancreatic beta cells in vivo and induces cellular and subcellular disruptions that reflect beta cell dysfunction.

Increasing evidence of new-onset diabetes during the COVID19 pandemic indicates that the SARS-CoV2 virus may drive beta-cell dysfunction leading to diabetes, but it is unclear if it is a primary or secondary effect. Here, we present evidence of SARS-CoV-2 infection of pancreatic beta cells using a robust and reproducible non-human primates model of mild to moderate COVID19 pathogenesis. Pancreas from SARS-CoV-2 infected subjects were positive for the SARS-CoV2 spike protein by immunohistochemistry and structures indicative of viral replication were evident by electron microscopy.

Spike in Diabetic Ketoacidosis Rates in Pediatric Type 2 Diabetes During the COVID-19 Pandemic.

Objective: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) on the incidence of new-onset type 2 diabetes and diabetic ketoacidosis (DKA) is unclear. It is unknown whether the coincidence of DKA noted in adult patients with type 2 diabetes is an issue for youth during the coronavirus disease 2019 pandemic.

Research Design And Methods: A retrospective single-center medical record review was conducted in a large, urban children's hospital of pediatric subjects presenting with new-onset type 2 diabetes between March and August of 2018 to 2020.

Glycemic control in youth-onset type 2 diabetes correlates with weight loss.

Objective: To identify risk factors for glycemic failure in youth with type 2 diabetes (T2D).

Methods: A retrospective review of HbA1c, anthropomorphic measures, medication records, and laboratory studies was performed using registry data from a dedicated pediatric T2D clinic. Latent profile analysis (LPA) was performed to model longitudinal trajectory of HbA1c over 5 years.

Nur77 deletion impairs muscle growth during developmental myogenesis and muscle regeneration in mice.

Muscle atrophy is a prevalent condition in illness and aging. Identifying novel pathways that control muscle mass may lead to therapeutic advancement. We previously identified Nur77 as a transcriptional regulator of glycolysis in skeletal muscle.

Rewriting yeast central carbon metabolism for industrial isoprenoid production.

A bio-based economy has the potential to provide sustainable substitutes for petroleum-based products and new chemical building blocks for advanced materials. We previously engineered Saccharomyces cerevisiae for industrial production of the isoprenoid artemisinic acid for use in antimalarial treatments. Adapting these strains for biosynthesis of other isoprenoids such as β-farnesene (CH), a plant sesquiterpene with versatile industrial applications, is straightforward.

The orphan nuclear receptor Nur77 is a determinant of myofiber size and muscle mass in mice.

We previously showed that the orphan nuclear receptor Nur77 (Nr4a1) plays an important role in the regulation of glucose homeostasis and oxidative metabolism in skeletal muscle. Here, we show using both gain- and loss-of-function models that Nur77 is also a regulator of muscle growth in mice. Transgenic expression of Nur77 in skeletal muscle in mice led to increases in myofiber size.

Nkx6.1 regulates islet β-cell proliferation via Nr4a1 and Nr4a3 nuclear receptors.

Loss of functional β-cell mass is a hallmark of type 1 and type 2 diabetes, and methods for restoring these cells are needed. We have previously reported that overexpression of the homeodomain transcription factor NK6 homeobox 1 (Nkx6.1) in rat pancreatic islets induces β-cell proliferation and enhances glucose-stimulated insulin secretion, but the pathway by which Nkx6.

The macrophage LBP gene is an LXR target that promotes macrophage survival and atherosclerosis.

The liver X receptors (LXRs) are members of the nuclear receptor superfamily that regulate sterol metabolism and inflammation. We sought to identify previously unknown genes regulated by LXRs in macrophages and to determine their contribution to atherogenesis. Here we characterize a novel LXR target gene, the lipopolysaccharide binding protein (LBP) gene.