Proteomic Analysis Uncovers Multiprotein Signatures Associated with Early Diabetic Kidney Disease in Youth with Type 2 Diabetes Mellitus.

Key Points: Proteomics analyses identified seven proteins predictive of time to development of albuminuria among youth with type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth cohort, 118 proteins predictive of time to development of hyperfiltration, and three proteins predictive of time to rapid eGFR decline. Seven proteins were predictive of all three outcomes (SEM4A, PSB3, dihydroxyphenylalanine decarboxylase, C1RL1, T132A, pyruvate carboxylase, and C1-esterase inhibitor) and have been implicated in immune regulatory mechanisms, metabolic dysregulation, proteostasis, and cellular signaling pathways. Elastic net Cox proportional hazards model identified distinct multiprotein signatures (38–68 proteins) of time to albuminuria, hyperfiltration, and rapid eGFR decline with concordance for models with clinical covariates and selected proteins between 0.

Kidney Energetics and Cyst Burden in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study.

Rationale & Objective: In this pilot study, we hypothesized that autosomal dominant polycystic kidney disease (ADPKD) is characterized by impaired kidney oxidative metabolism that associates with kidney size and cyst burden.

Study Design: Cross-sectional study.

Setting & Participants: Twenty adults with ADPKD (age, 31±6 years; 65% women; body mass index [BMI], 26.

Sleep duration and association with cardiometabolic health in adolescents and adults with type 1 diabetes: Results from the BCQR-T1D study.

Aim: Type 1 diabetes (T1D) increases the risk of morbidity and mortality from cardiovascular disease, and insufficient sleep is prevalent. Emerging evidence suggests a link between sleep and cardiometabolic health, but this has not been examined across the lifespan in individuals with T1D. We aimed to examine associations between sleep and cardiometabolic health in adolescents and adults with T1D in a secondary analysis of data from a 4-week double-blind, random-order, placebo-controlled crossover trial of bromocriptine quick release (BCQR) therapy with a 4-week washout in between conditions.

Hypoglycemia in children and young adults with cystic fibrosis during oral glucose tolerance testing vs. continuous glucose monitoring.

Background: Hypoglycemia is common in people with cystic fibrosis (pwCF) during oral glucose tolerance tests (OGTTs) and in the free-living setting, yet its pathophysiology remains unclear.

Objective: To evaluate hypoglycemia in children and young adults with CF by OGTT and continuous glucose monitoring (CGM).

Methods: A 3-h OGTT was performed in children and young adults with CF and healthy controls (HC).

The impact of elexacaftor/tezacaftor/ivacaftor on body composition in a small cohort of youth with cystic fibrosis.

Background: The effects of elexacaftor-tezacaftor-ivacaftor (ETI) on body composition in people with CF (pwCF) are unknown.

Methods: Dual-energy X-ray absorptiometry fat-free mass and fat mass adjusted for height (FMI) as well as oral glucose tolerance test derived measures of insulin secretion and sensitivity were compared before and after ETI initiation in eight pwCF.

Results: Patients median age: 22 years interquartile range (IQR: 16-28), 87.

Glycemia and β-cell function before and after elexacaftor/tezacaftor/ivacaftor in youth and adults with cystic fibrosis.

Background: Diabetes is prevalent among people with CF (PwCF) and associated with worse clinical outcomes. CFTR modulators are highly effective in improving the disease course of CF. However, the effects of elexacaftor/tezacaftor/ivacaftor (ETI) on glucose metabolism in PwCF are unclear.

Bromocriptine quick-release as adjunct therapy in youth and adults with type 1 diabetes: A randomized, placebo-controlled crossover study.

Aim: To evaluate the potential for glycaemic, renal and vascular benefits of bromocriptine quick release (BCQR) in adolescents and adults with type 1 diabetes.

Materials And Methods: Forty adolescents and 40 adults with type 1 diabetes aged 12-60 years old were enrolled in a double-blind, placebo-controlled, random order crossover study of 4 weeks of treatment in the morning with BCQR (titrated weekly from 0.8 mg to 1.

Plasma levels of carboxylic acids are markers of early kidney dysfunction in young people with type 1 diabetes.

Background: We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics.

Methods: Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls.

Epigenome-Wide Association Study of Infant Feeding and DNA Methylation in Infancy and Childhood in a Population at Increased Risk for Type 1 Diabetes.

We assessed associations between infant diet (e.g., breastfeeding and introduction to solid foods) and DNA methylation in infancy and childhood.

Inverse probability weighting is an effective method to address selection bias during the analysis of high dimensional data.

Omics studies frequently use samples collected during cohort studies. Conditioning on sample availability can cause selection bias if sample availability is nonrandom. Inverse probability weighting (IPW) is purported to reduce this bias.

Real-World Use of a New Hybrid Closed Loop Improves Glycemic Control in Youth with Type 1 Diabetes.

To describe real-world outcomes for youth using the Tandem t:slim X2 insulin pump with Control-IQ technology ("Control-IQ") for 6 months at a large pediatric clinic. Youth with type 1 diabetes, who started Control-IQ for routine care, were prospectively followed. Data on system use and glycemic control were collected before Control-IQ start, and at 1, 3, and 6 months after start.

Real-world performance of hybrid closed loop in youth, young adults, adults and older adults with type 1 diabetes: Identifying a clinical target for hybrid closed-loop use.

Aim: To describe real-world hybrid closed loop (HCL) use and glycaemic outcomes across the lifespan and identify a clinical threshold for HCL use associated with meeting the internationally recommended target of 70% sensor glucose time in range (TIR; 70-180 mg/dL).

Materials And Methods: Mixed models examined MiniMed 670G HCL use and glycaemic outcomes in 276 people with type 1 diabetes from four age groups: youth (aged <18 years), young adults (18-25 years), adults (26-49 years) and older adults (≥50 years) for 1 year. ROC analysis identified the minimum percentage HCL use associated with meeting the TIR goal of 70%.

Acute Hyperinsulinemia Alters Bone Turnover in Women and Men With Type 1 Diabetes.

Type 1 diabetes (T1D) increases fracture risk across the lifespan. The low bone turnover associated with T1D is thought to be related to glycemic control, but it is unclear whether peripheral hyperinsulinemia due to dependence on exogenous insulin has an independent effect on suppressing bone turnover. The purpose of this study was to test the bone turnover marker (BTM) response to acute hyperinsulinemia.

Hemoglobin A Accurately Predicts Continuous Glucose Monitoring-Derived Average Glucose in Youth and Young Adults With Cystic Fibrosis.

Objective: In cystic fibrosis (CF), hemoglobin A (HbA) is thought to underestimate glycemia. However, few studies have directly assessed the relationship between HbA and average glucose in CF. We determined the relationships among glycemic markers-HbA, fructosamine (FA), glycated albumin (%GA), and 1,5-anhydroglucitol (1,5-AG)-and continuous glucose monitoring (CGM) in CF, hypothesizing that alternate markers would better predict average sensor glucose (ASG) than HbA.

Continuous glucose monitoring abnormalities in cystic fibrosis youth correlate with pulmonary function decline.

Background: To characterize glucose patterns with continuous glucose monitoring (CGM) in cystic fibrosis (CF) and assess relationships between CGM and clinical outcomes.

Methods: 110 CF youth and healthy controls (HC), 10-18 years, wore CGM up to 7 days. Correlations between CGM and lung function and BMI z-score change over the prior year were determined.