Knockdown of ketohexokinase versus inhibition of its kinase activity exert divergent effects on fructose metabolism.

Excessive fructose intake is a risk factor for the development of obesity and its complications. Targeting ketohexokinase (KHK), the first enzyme of fructose metabolism, has been investigated for the management of metabolic dysfunction-associated steatotic liver disease (MASLD). We compared the effects of systemic, small molecule inhibitor of KHK enzymatic activity with hepatocyte-specific, N-acetylgalactosamine siRNA-mediated knockdown of KHK in mice on an HFD.

Identification of kidney cell types in scRNA-seq and snRNA-seq data using machine learning algorithms.

Introduction: Single-cell RNA sequencing (scRNA-seq) and single-nucleus RNA sequencing (snRNA-seq) provide valuable insights into the cellular states of kidney cells. However, the annotation of cell types often requires extensive domain expertise and time-consuming manual curation, limiting scalability and generalizability. To facilitate this process, we tested the performance of five supervised classification methods for automatic cell type annotation.

Pharmacometrics-Enhanced Bayesian Borrowing for Pediatric Extrapolation - A Case Study of the DINAMO Trial.

Bayesian borrowing analyses have an important role in the design and analysis of pediatric trials. This paper describes use of a prespecified Pharmacometrics Enhanced Bayesian Borrowing (PEBB) analysis that was conducted to overcome an expectation for reduced statistical power in the pediatric DINAMO trial due to a greater than expected variability in the primary endpoint. The DINAMO trial assessed the efficacy and safety of an empagliflozin dosing regimen versus placebo and linagliptin versus placebo on glycemic control (change in HbA1c over 26 weeks) in young people with type 2 diabetes (T2D).

Enhancement of Subcutaneous Islet Transplant Performance by Collagen 1 Gel.

Human islets can be transplanted into the portal vein for T1 diabetes, and a similar procedure is being used in a clinical trial for stem cell-derived beta-like cells. Efforts have been underway to find an alternative transplant site that will foster better islet cell survival and function. Although conceptually attractive, the subcutaneous (SC) site has yielded disappointing results, in spite of some improvements resulting from more attention paid to vascularization and differentiation factors, including collagen.

Altered oxidant and antioxidant levels are associated with vascular stiffness and diabetic kidney disease in type 1 diabetes after exposure to acute and chronic hyperglycemia.

Background: Hyperglycemia-induced oxidative stress is a well-established pathological mediator of vascular complications in diabetes. We assessed plasma oxidant and antioxidant levels in response to acute and chronic hyperglycemia in relation to vascular stiffness and varying degrees of kidney disease in type 1 diabetes individuals.

Methods: The acute hyperglycemia study included 22 type 1 diabetic individuals with normal albumin excretion rate (AER) and 13 non-diabetic controls.

Role of Divalent Cations in Infections in Host-Pathogen Interaction.

With increasing numbers of patients worldwide diagnosed with diabetes mellitus, renal disease, and iatrogenic immune deficiencies, an increased understanding of the role of electrolyte interactions in mitigating pathogen virulence is necessary. The levels of divalent cations affect host susceptibility and pathogen survival in persons with relative immune insufficiency. For instance, when host cellular levels of calcium are high compared to magnesium, this relationship contributes to insulin resistance and triples the risk of clinical tuberculosis.

Characterizing Vascular Wall and Lumen Caliber in Eyes with Diabetic Retinopathy Based on Adaptive Optics Scanning Laser Ophthalmoscopy.

Unlabelled: (200/200) Purpose: Our aim was to evaluate structural alterations of retinal arterioles due to type 1 diabetes (T1D) and/or diabetic retinopathy (DR) under AOSLO imaging.

Methods: Each study eye underwent mydriasis and AOSLO imaging in a single-visit study. The instrument's arrangement of four offset aperture images provided two orthogonal split-detector images and enabled isotropic analysis of the arteriolar boundaries.

Placenta-derived SOD3 deletion impairs maternal behavior via alterations in FGF/FGFR-prolactin signaling axis.

Offspring growth requires establishing maternal behavior associated with the maternal endocrine profile. Placentae support the adaptations of the mother, producing bioactive molecules that affect maternal organs. We recently reported that placentae produce superoxide dismutase 3 (SOD3) that exerts sustained effects on the offspring liver via epigenetic modifications.

Exercise activates AMPK in mouse and human pancreatic islets to decrease senescence.

Beta (β)-cell senescence contributes to type 2 diabetes mellitus (T2DM). While exercise is vital for T2DM management and significantly affects cellular ageing markers, its effect on β-cell senescence remains unexplored. Here, we show that short-term endurance exercise training (treadmill running, 1 h per day for 10 days) in two male and female mouse models of insulin resistance decreases β-cell senescence.

The Dietetics Profession Privilege Scale: Development, Psychometric Testing, and Application Among a Diverse Cohort of Dietetics Professionals.

Background: Privilege (defined as the unearned advantage or disadvantage experienced by social groups resulting from structural power differences) impacts efforts to create a diverse and inclusive dietetics profession. Yet, no current measures exist to assess and observe privilege, and the relative privilege among dietetics professionals (DPs) is unknown.

Objective: The purpose of this study was to develop and validate a scale to measure DP privilege and to use that scale to assess privilege among a sample of DPs in the United States.

Psychosocial outcomes with the Omnipod® 5 Automated Insulin Delivery System in caregivers of very young children with type 1 diabetes.

Aim: Automated insulin delivery (AID) systems have demonstrated improved glycaemic outcomes in people with type 1 diabetes (T1D), yet limited data exist on these systems in very young children and their impact on caregivers. We evaluated psychosocial outcomes following use of the tubeless Omnipod® 5 AID System in caregivers of very young children.

Materials And Methods: This 3-month single-arm, multicentre, pivotal clinical trial enrolled 80 children aged 2.

Strategies for minimizing muscle loss during use of incretin-mimetic drugs for treatment of obesity.

The rapid and widespread clinical adoption of highly effective incretin-mimetic drugs (IMDs), particularly semaglutide and tirzepatide, for the treatment of obesity has outpaced the updating of clinical practice guidelines. Consequently, many patients may be at risk for adverse effects and uncertain long-term outcomes related to the use of these drugs. Of emerging concern is the loss of skeletal muscle mass and function that can accompany rapid substantial weight reduction; such losses can lead to reduced functional and metabolic health, weight cycling, compromised quality of life, and other adverse outcomes.

DIABETIC RETINOPATHY LESION TYPES AND DISTRIBUTION ON ULTRAWIDE FIELD IMAGING AND THE RISK OF DISEASE WORSENING OVER TIME.

Purpose: To evaluate the effect of diabetic retinopathy (DR) lesion type (hemorrhages and/or microaneurysms, intraretinal microvascular abnormalities, new vessels elsewhere, and venous beading), severity, and distribution on disease worsening based on the Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale.

Methods: Post hoc analysis of a multicenter observational study of 544 eyes with nonproliferative DR and an Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale score of Level 35 to 53. Disease worsening was defined as Early Treatment Diabetic Retinopathy Study Diabetic Retinopathy Severity Scale worsening by ≥2 steps from baseline or receipt of DR treatment over 4 years.

Postprandial metabolomics analysis reveals disordered serotonin metabolism in post-bariatric hypoglycemia.

BACKGROUNDBariatric surgery is a potent therapeutic approach for obesity and type 2 diabetes but can be complicated by post-bariatric hypoglycemia (PBH). PBH typically occurs 1-3 hours after meals, in association with exaggerated postprandial levels of incretins and insulin.METHODSTo identify mediators of disordered metabolism in PBH, we analyzed the plasma metabolome in the fasting state and 30 and 120 minutes after mixed meal in 3 groups: PBH (n = 13), asymptomatic post-Roux-en-Y gastric bypass (post-RYGB) (n = 10), and nonsurgical controls (n = 8).

Walking away from depression: the mediating role of walking activity in depression impacting blood glucose levels of people with diabetes or prediabetes.

Introduction: Depression can exacerbate diabetes by impairing self-care behaviors and increasing the risk of complication; however, the underlying mechanism is still unclear. Given the suggested associations between walking activity, depression status, and blood glucose levels this study explores the intricate relationship between depression and blood glucose (BG) control, with a focus on walking activity as a behavioral mediator. The purpose of this study is to examine walking activity's mediating role in depression's impact on BG levels, investigating and validating the non-linear association between BG levels and walking activity.

mA mRNA methylation in brown fat regulates systemic insulin sensitivity via an inter-organ prostaglandin signaling axis independent of UCP1.

Brown adipose tissue (BAT) regulates systemic metabolism by releasing signaling lipids. N-methyladenosine (mA) is the most prevalent and abundant post-transcriptional mRNA modification and has been reported to regulate BAT adipogenesis and energy expenditure. Here, we demonstrate that the absence of mA methyltransferase-like 14 (METTL14) modifies the BAT secretome to improve systemic insulin sensitivity independent of UCP1.