Implications of noncoding regulatory functions in the development of insulinomas.

Insulinomas are rare neuroendocrine tumors arising from pancreatic β cells, characterized by aberrant proliferation and altered insulin secretion, leading to glucose homeostasis failure. With the aim of uncovering the role of noncoding regulatory regions and their aberrations in the development of these tumors, we coupled epigenetic and transcriptome profiling with whole-genome sequencing. As a result, we unraveled somatic mutations associated with changes in regulatory functions.

SUCNR1 regulates insulin secretion and glucose elevates the succinate response in people with prediabetes.

Pancreatic β-cell dysfunction is a key feature of type 2 diabetes, and novel regulators of insulin secretion are desirable. Here we report that the succinate receptor (SUCNR1) is expressed in β-cells and is up-regulated in hyperglycemic states in mice and humans. We found that succinate acts as a hormone-like metabolite and stimulates insulin secretion via a SUCNR1-Gq-PKC-dependent mechanism in human β-cells.

Interferons are key cytokines acting on pancreatic islets in type 1 diabetes.

Aims/hypothesis: The proinflammatory cytokines IFN-α, IFN-γ, IL-1β and TNF-α may contribute to innate and adaptive immune responses during insulitis in type 1 diabetes and therefore represent attractive therapeutic targets to protect beta cells. However, the specific role of each of these cytokines individually on pancreatic beta cells remains unknown.

Methods: We used deep RNA-seq analysis, followed by extensive confirmation experiments based on reverse transcription-quantitative PCR (RT-qPCR), western blot, histology and use of siRNAs, to characterise the response of human pancreatic beta cells to each cytokine individually and compared the signatures obtained with those present in islets of individuals affected by type 1 diabetes.

Cross-sectional association between severe periodontitis and diabetes mellitus: A nation-wide cohort study.

Aim: To evaluate the cross-sectional association between severe periodontitis and diabetes mellitus (DM), in a representative sample of Spanish population.

Materials And Methods: The di@bet.es epidemiological study is a population-based cohort study aimed to determine the prevalence and incidence of DM in the adult population of Spain.

Greater time spent with HbA1c less than 7.0% with oral semaglutide versus oral comparators: An exploratory analysis of the PIONEER studies.

Aim: To assess how long participants with type 2 diabetes spent with HbA1c less than 7.0% and how likely they were to maintain this target with oral semaglutide 7 mg versus sitagliptin 100 mg or oral semaglutide 14 mg versus empagliflozin 25 mg, sitagliptin 100 mg or subcutaneous liraglutide 1.8 mg.

NT-proBNP point-of-care measurement as a screening tool for heart failure and CVD risk in type 2 diabetes with hypertension.

Aims: We used N-terminal pro-B-type natriuretic peptide (NT-proBNP) point-of-care testing (POCT) for heart failure risk stratification of individuals with type 2 diabetes for >10 years and hypertension.

Methods: Overall 259 participants aged 50 years or older with type 2 diabetes (duration of >10 years), hypertension, and no overt cardiovascular disease (CVD) were recruited at two study centers. Patients' data were acquired and NT-proBNP levels were measured using the CARDIAC proBNP+ test (Roche) and the cobas h232 instrument (Roche).

The pancreatic β-cell in ageing: Implications in age-related diabetes.

The prevalence of type 2 diabetes (T2D) and impaired glucose tolerance (IGT) increases with ageing. T2D generally results from progressive impairment of the pancreatic islets to adapt β-cell mass and function in the setting of insulin resistance and increased insulin demand. Several studies have shown an age-related decline in peripheral insulin sensitivity.

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme.

Aims: To evaluate the efficacy and safety of oral semaglutide versus comparators by patient characteristic subgroups in patients with type 2 diabetes.

Materials And Methods: Change from baseline in glycated haemoglobin (HbA1c) and body weight, and achievement of HbA1c <7.0% with oral semaglutide 7 mg, oral semaglutide 14 mg, flexibly dosed oral semaglutide (flex) and comparators were assessed across baseline subgroups (age, race, ethnicity, diabetes duration, body mass index and HbA1c) from the PIONEER programme.

Association between long term exposure to particulate matter and incident hypertension in Spain.

Exposure to air particulate matter has been linked with hypertension and blood pressure levels. The metabolic risks of air pollution could vary according to the specific characteristics of each area, and has not been sufficiently evaluated in Spain. We analyzed 1103 individuals, participants in a Spanish nationwide population based cohort study (di@bet.

Digital intervention increases influenza vaccination rates for people with diabetes in a decentralized randomized trial.

People with diabetes (PWD) have an increased risk of developing influenza-related complications, including pneumonia, abnormal glycemic events, and hospitalization. Annual influenza vaccination is recommended for PWD, but vaccination rates are suboptimal. The study aimed to increase influenza vaccination rate in people with self-reported diabetes.

Fatty liver index as a predictor for type 2 diabetes in subjects with normoglycemia in a nationwide cohort study.

Our aim was to evaluate whether fatty liver index (FLI) is associated with the risk of type 2 diabetes (T2DM) development within the Spanish adult population and according to their prediabetes status; additionally, to examine its incremental predictive value regarding traditional risk factors. A total of 2260 subjects (Prediabetes: 641 subjects, normoglycemia: 1619 subjects) from the Di@bet.es cohort study were studied.

Incidence and regression of metabolic syndrome in a representative sample of the Spanish population: results of the cohort di@bet.es study.

Introduction: Metabolic syndrome (MetS) is an important predictor of cardiovascular mortality. Identification of occurrence and regression trends of MetS could permit elaboration of preventive strategies with new targets. The objective of this study was to analyze the occurrence and regression rates of MetS and its associated factors in the representative cohort of Spain of the di@bet.

Determining Beta Cell Mass, Apoptosis, Proliferation, and Individual Beta Cell Size in Pancreatic Sections.

Pancreatic beta cells have a significant remodeling capacity which plays an essential role in the maintenance of glucose homeostasis. Beta cell apoptosis, replication, size, dedifferentiation, and (neo)generation contribute to the beta cell mass regulation. However, the extent of their respective contribution varies significantly depending on the specific condition, and it is the balance among them that determines the eventual change in beta cell mass.

Use of Streptozotocin in Rodent Models of Islet Transplantation.

Streptozotocin (STZ) selectively destroys beta cells and is widely used to induce experimental diabetes in rodents. Rodent beta cells are very sensitive to the toxic effects of STZ, while human beta cells are highly resistant to STZ. Taking advantage of this characteristic, here, we describe two protocols for the induction of STZ-diabetes.

Incidence of diabetes mellitus in Spain as results of the nation-wide cohort di@bet.es study.

Our aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population based cohort from Spain (di@bet.es study). The target was the Spanish population.

Validation of self-reported measures of periodontitis in a Spanish Population.

Background And Objective: Use of self-reported questionnaires in Dentistry may be useful to estimate the prevalence of periodontitis in epidemiological studies. This study aims to assess the accuracy of self-reporting for predicting the prevalence of periodontitis in a Spanish population participating in a diabetes incidence study.

Materials And Methods: Data were collected from 231 patients participating in the Di@bet.

Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial.

Objective: Efficacy and safety of the glucagon-like peptide 1 (GLP-1) analog oral semaglutide and the sodium-glucose cotransporter 2 inhibitor empagliflozin were compared in patients with type 2 diabetes uncontrolled on metformin.

Research Design And Methods: Patients were randomized to once-daily open-label treatment with oral semaglutide 14 mg ( = 412) or empagliflozin 25 mg ( = 410) in a 52-week trial. Key end points were change from baseline to week 26 in HbA (primary) and body weight (confirmatory secondary).

Pancreatic ductal cells may have a negative effect on human islet transplantation.

Aim: To evaluate the effect of pancreatic ductal cells on experimental human islet transplantation.

Materials And Methods: Isolated islets were additionally purified by handpicking. Ductal cells were purified by magnetic cell sorting and then clustered into ductal pancreatospheres (DPS).

Fasting plasma glucose is an independent predictor of survival in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy.

Background: Diabetes is related with increased cancer mortality across multiple cancer types. Its role in lung cancer mortality is still unclear. We aim to determine the prognostic value of fasting plasma glucose (FPG) and diabetes mellitus in patients with locally advanced non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy.

A Model for Human Islet Transplantation to Immunodeficient Streptozotocin-Induced Diabetic Mice.

Streptozotocin (STZ) is a cytotoxic glucose analogue that causes beta cell death and is widely used to induce experimental diabetes in rodents. The sensitivity of beta cells to STZ is species-specific and human beta cells are resistant to STZ. In experimental islet transplantation to rodents, STZ-diabetes must be induced before transplantation to avoid destruction of grafted islets by STZ.

Cortistatin regulates glucose-induced electrical activity and insulin secretion in mouse pancreatic beta-cells.

Although there is growing evidence that cortistatin regulates several functions in different tissues, its role in the endocrine pancreas is not totally known. Here, we aim to study the effect of cortistatin on pancreatic beta-cells and glucose-stimulated insulin secretion (GSIS). Exposure of isolated mouse islets to cortistatin inhibited GSIS.

Limited Joint Mobility Progression in Type 1 Diabetes: A 15-Year Follow-Up Study.

Objective: To assess the evolution of joint mobility over a period of 15 years in type 1 diabetic patients and healthy controls and to determine whether microalbuminuria is associated with a different evolution of joint mobility.

Methods: Joint mobility of hand and wrist was determined in 63 patients with type 1 diabetes and 63 healthy subjects. Fifteen years later, 37 (58.

Publisher Correction: Purification of replicating pancreatic β-cells for gene expression studies.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.