Call to action for Clinicians in the South-East Asian Regions on Primary Prevention of Diabetes in people with Prediabetes- A Consensus statement.

Primary prevention of diabetes still remains as an unmet challenge in a real world setting. While, translational programmes have been successful in the developed nations, the prevailing social and economic inequities in the low and middle income countries, fail to integrate diabetes prevention into their public health systems. The resulting exponential increase in the prevalence of diabetes and the cost of treatment has put primary prevention in the back seat.

Comparison of GFR estimation in patients with diabetes mellitus using the EKFC and CKD-EPI equations.

Background: The estimation of glomerular filtration rate (eGFR) is essential in the early detection of diabetic nephropathy. We herein compare the performance of common eGFR formulas against a gold standard measurement of GFR in patients with diabetes mellitus.

Methods: GFR was measured in 93 patients with diabetes mellitus using iohexol clearance as the reference standard.

Judged by your neighbors: Brain structural normativity profiles for large and heterogeneous samples.

The detection of norm deviations is fundamental to clinical decision making and impacts our ability to diagnose and treat diseases effectively. Current normative modeling approaches rely on generic comparisons and quantify deviations in relation to the population average. However, generic models interpolate subtle nuances and risk the loss of critical information, thereby compromising effective personalization of health care strategies.

Developmental beta-cell death orchestrates the islet's inflammatory milieu by regulating immune system crosstalk.

While pancreatic beta-cell proliferation has been extensively studied, the role of cell death during islet development remains incompletely understood. Using a genetic model of caspase inhibition in beta cells coupled with mathematical modeling, we here discover an onset of beta-cell death in juvenile zebrafish, which regulates beta-cell mass. Histologically, this beta-cell death is underestimated due to phagocytosis by resident macrophages.

Symmetric dimethylguanidino valeric acid, a novel single biomarker of hepatic steatosis.

There is an unmet need for a biomarker of liver fat. We identified dimethylguanidino valeric acid (DMGV) as a circulating biomarker of liver fat. Here, we assess its two isoforms-symmetric (SDGV) and asymmetric (ADGV)-as biomarkers of steatosis.

Increase in PUFA and protein, and decrease in carbohydrate intake improves liver fat in 12 months and the role of weight loss as a mediator: A randomized controlled trial.

Background & Aims: Recently, a beneficial effect of high intake of unsaturated fatty acids (UFA) and protein on intrahepatic lipids (IHL) was demonstrated over 12 months within a randomized controlled trial (the NutriAct trial). We now aimed to explore the specific macronutrient components driving this IHL improvement within this trial in middle-aged and elderly subjects (50-80 y) at risk for age-related diseases.

Methods: The NutriAct trial (n = 502) analyzed the effect of a high-protein and high-UFA diet on age related diseases including fatty liver disease.

Incretin-responsive human pancreatic adipose tissue organoids: A functional model for fatty pancreas research.

Objective: Infiltration of adipocytes into the pancreatic parenchyma has been linked to impaired insulin secretion in individuals with increased genetic risk of T2D and prediabetic conditions. However, the study of this ectopic fat depot has been limited by the lack of suitable in vitro models.

Methods: Here, we developed a novel 3D model of functionally mature human pancreatic adipose tissue organoids by aggregating human pancreatic adipose tissue-derived stromal vascular fraction (SVF) cells into organoids and differentiating them over 19 days.

Blood flow-induced angiocrine signals promote organ growth and regeneration.

Recently, we identified myeloid-derived growth factor (MYDGF) as a blood flow-induced angiocrine signal that promotes human and mouse hepatocyte proliferation and survival. Here, we review literature reporting changes in blood flow after partial organ resection in the liver, lung, and kidney, and we describe the angiocrine signals released by endothelial cells (ECs) upon blood flow alterations in these organs. While hepatocyte growth factor (HGF) and MYDGF are important angiocrine signals for liver regeneration, by now, angiocrine signals have also been reported to stimulate hyperplasia and/or hypertrophy during the regeneration of lungs and kidneys.

GDF15 is required for maintaining subcutaneous adipose tissue lipid metabolic signature.

Recent research has identified growth differentiation factor 15 (GDF15) as a crucial factor in various physiological and pathological processes, particularly in energy balance regulation. While the role of GDF15 in modulating energy metabolism through hindbrain GDNF family receptor alpha-like (GFRAL) signaling has been extensively studied, emerging evidence suggests direct peripheral metabolic actions of GDF15. Using knockout mouse models, we investigated GDF15 and GFRAL's roles in adipose tissue metabolism.

Depression symptoms, wellbeing, health-related quality of life, and diabetes-related distress in novel subtypes of recent-onset diabetes in Germany: a 5-year observational follow-up study.

Background: The subjective experiences of individuals living with diabetes is commonly assessed with patient-reported outcomes (PROs; eg, depression symptoms, wellbeing, health-related quality of life [HRQOL], and diabetes-related distress). Cluster analyses have identified novel diabetes subtypes differing in phenotypic and metabolic characteristics. We aimed to investigate associations between these subtypes and PROs and whether subtype predicted PROs 5 years later.

Evidence from clinical studies of leptin: current and future clinical applications in humans.

Leptin has been established as the prototype adipose tissue secreted hormone and as a major regulator of several human physiology functions. Here, we are primarily reviewing the findings from studies in humans involving leptin administration. We are describing the metabolic, endocrine and immunologic effects of leptin replacement in conditions of leptin deficiency, such as short-term fasting in healthy individuals, relative energy deficiency in sports (REDS), congenital leptin deficiency (CLD), generalized (GL) and partial lipodystrophy (PL), HIV-associated lipodystrophy (HIV-L) and of leptin treatment in conditions of leptin excess (common obesity, type 2 diabetes, steatotic liver disease).

Role of patatin-like phospholipase domain-containing 3 gene for decreasing kidney function in recently diagnosed diabetes mellitus.

Aims: We examined the association of the G allele in the single-nucleotide polymorphism (SNP) rs738409 in the third exon of patatin-like phospholipase domain-containing 3 gene (PNPLA3) gene, with chronic kidney disease in diabetes endotypes.

Methods: Participants with recent-onset diabetes (n = 707) from the prospective German Diabetes Study (GDS) underwent cluster assignment, detailed phenotyping, genotyping and magnetic resonance spectroscopy to quantify hepatocellular lipid content (HCL).

Results: Severe insulin-resistant diabetes (SIRD) had the lowest glomerular filtration rates (eGFR) and highest HCL compared to severe insulin-deficient, moderate obesity-related, moderate age-related and severe autoimmune diabetes endotypes (all p < 0.

Accurate locomotor activity profiles of group-housed mice derived from home cage monitoring data.

Introduction: Holistic phenotyping of rodent models is increasing, with a growing awareness of the 3Rs and the fact that specialized experimental setups can also impose artificial restrictions. Activity is an important parameter for almost all basic and applied research areas involving laboratory animals. Locomotor activity, the main form of energy expenditure, influences metabolic rate, muscle mass, and body weight and is frequently investigated in metabolic disease research.

The Effect of Individual Attitude toward Healthy Nutrition on Adherence to a High-UFA and High-Protein Diet: Results of a Randomized Controlled Trial.

Unlabelled: Despite beneficial cardiovascular effects, substantial long-term modulation of food pattern could only be achieved in a limited number of participants. The impact of attitude towards healthy nutrition (ATHN) on successful modulation of dietary behavior is unclear, especially in the elderly. We aimed to analyze whether the personal ATHN influences 12-month adherence to two different dietary intervention regimes within a 36-month randomized controlled trial.

Diabetes as a risk factor for MASH progression.

Non-alcoholic (now: metabolic) steatohepatitis (MASH) is the progressive inflammatory form of metabolic dysfunction-associated steatotic liver disease (MASLD), which often coexists and mutually interacts with type 2 diabetes (T2D), resulting in worse hepatic and cardiovascular outcomes. Understanding the intricate mechanisms of diabetes-related MASH progression is crucial for effective therapeutic strategies. This review delineates the multifaceted pathways involved in this interplay and explores potential therapeutic implications.

Dysglycemia and liver lipid content determine the relationship of insulin resistance with hepatic OXPHOS capacity in obesity.

Background & Aims: Hepatic mitochondrial respiration is higher in steatosis, but lower in overt type 2 diabetes. We hypothesized that hepatic oxidative phosphorylation (OXPHOS) capacity increases with a greater degree of insulin resistance in obesity, independent of other metabolic diseases.

Methods: We analyzed 65 humans without diabetes (BMI 50 ± 7 kg/m, hemoglobin A1c 5.

Picalm, a novel regulator of GLUT4-trafficking in adipose tissue.

Objective: Picalm (phosphatidylinositol-binding clathrin assembly protein), a ubiquitously expressed clathrin-adapter protein, is a well-known susceptibility gene for Alzheimer's disease, but its role in white adipose tissue (WAT) function has not yet been studied. Transcriptome analysis revealed differential expression of Picalm in WAT of diabetes-prone and diabetes-resistant mice, hence we aimed to investigate the potential link between Picalm expression and glucose homeostasis, obesity-related metabolic phenotypes, and its specific role in insulin-regulated GLUT4 trafficking in adipocytes.

Methods: Picalm expression and epigenetic regulation by microRNAs (miRNAs) and DNA methylation were analyzed in WAT of diabetes-resistant (DR) and diabetes-prone (DP) female New Zealand Obese (NZO) mice and in male NZO after time-restricted feeding (TRF) and alternate-day fasting (ADF).

Regional gray matter changes in steatotic liver disease provide a neurobiological link to depression: A cross-sectional UK Biobank cohort study.

Background: Steatotic liver disease (SLD) is characterized by excessive accumulation of lipids in the liver. It is associated with elevated risk of hepatic and cardiometabolic diseases, as well as mental disorders such as depression. Previous studies revealed global gray matter reduction in SLD.

Impact of peripheral thyroid hormone balance on liver fat: insights from the NutriAct trial.

Objective: Hypothyroidism has been proposed as a potential contributor to steatotic liver disease (SLD), but existing data shows conflicting results in euthyroid subjects. Therefore, we investigated the association between thyroid function and intrahepatic lipids (IHLs) during a 36-month randomized controlled trial evaluating a diet known to reduce liver fat.

Design: 502 eligible subjects (aged 50-80 years, ≥1 risk factor for unhealthy aging) were randomly assigned to either follow a diet rich in unsaturated fatty acids, plant protein, and fiber (intervention group, IG), or dietary recommendations of the German Nutrition Society (control group, CG).

Different effects of bariatric surgery on epigenetic plasticity in skeletal muscle of individuals with and without type 2 diabetes.

Aim: Bariatric surgery is highly effective for the treatment of obesity in individuals without (OB) and in those with type 2 diabetes (T2D). However, whether bariatric surgery triggers similar or distinct molecular changes in OB and T2D remains unknown. Given that individuals with type 2 diabetes often exhibit more severe metabolic deterioration, we hypothesized that bariatric surgery induces distinct molecular adaptations in skeletal muscle, the major site of glucose uptake, of OB and T2D after surgery-induced weight loss.

Inhibition of proline-rich tyrosine kinase 2 restores cardioprotection by remote ischaemic preconditioning in type 2 diabetes.

Background And Purpose: Remote ischaemic preconditioning (rIPC) for cardioprotection is severely impaired in diabetes, and therapeutic options to restore it are lacking. The vascular endothelium plays a key role in rIPC. Given that the activity of endothelial nitric oxide synthase (eNOS) is inhibited by proline-rich tyrosine kinase 2 (Pyk2), we hypothesized that pharmacological Pyk2 inhibition could restore eNOS activity and thus restore remote cardioprotection in diabetes.

Optogenetic β cell interrogation in vivo reveals a functional hierarchy directing the Ca response to glucose supported by vitamin B6.

Coordination of cellular activity through Ca enables β cells to secrete precise quantities of insulin. To explore how the Ca response is orchestrated in space and time, we implement optogenetic systems to probe the role of individual β cells in the glucose response. By targeted β cell activation/inactivation in zebrafish, we reveal a hierarchy of cells, each with a different level of influence over islet-wide Ca dynamics.