Obesity-induced reduced expression of the lncRNA ROIT impairs insulin transcription by downregulation of Nkx6.1 methylation
Conclusions/interpretationThese findings functionally suggest a novel link between obesity and beta cell dysfunction via ROIT. Elucidating a precise mechanism for the effect of obesity on lncRNA expression will broaden our understanding of the pathophysiological development of diabetes and facilitate the design of better tools for diabetes prevention and treatment.Data availabilityThe raw RNA sequencing data are available from the NCBI Gene Expression Omnibus (GEO series accession number GSE139991). (Source: Diabetologia)
Source: Diabetologia - February 1, 2020 Category: Endocrinology Source Type: research

Exposure to maternal obesity programs sex differences in pancreatic islets of the offspring in mice
AbstractAims/hypothesisObesity during pregnancy increases offspring type 2 diabetes risk. Given that nearly half of women of child-bearing age in many populations are currently overweight/obese, it is key that we improve our understanding of the impact of the in utero/early life environment on offspring islet function. Whilst a number of experimental studies have examined the effect of maternal obesity on offspring islet architecture and/or function, it has not previously been delineated whether these changes are independent of other confounding risk factors such as obesity, postnatal high-fat-feeding and ageing. Thus, we ...
Source: Diabetologia - January 7, 2020 Category: Endocrinology Source Type: research

Clinical and genetic correlates of islet-autoimmune signatures in juvenile-onset type 1 diabetes
Conclusions/interpretationCollectively, these data provide new insights into type 1 diabetes disease heterogeneity and highlight the importance of stratifying patients on the basis of their genetic and autoimmune signatures for immunotherapy and personalised disease management. (Source: Diabetologia)
Source: Diabetologia - January 7, 2020 Category: Endocrinology Source Type: research

Stearoyl CoA desaturase is a gatekeeper that protects human beta cells against lipotoxicity and maintains their identity
Conclusions/interpretationThe present study delineates an important role for SCD in the protection against lipotoxicity and in the maintenance of human beta cell identity.Data availabilityMicroarray data and all experimental details that support the findings of this study have been deposited in in the GEO database with the GSE130208 accession code. (Source: Diabetologia)
Source: Diabetologia - January 7, 2020 Category: Endocrinology Source Type: research

Diabetes digital app technology: benefits, challenges, and recommendations. A consensus report by the European Association for the Study of Diabetes (EASD) and the American Diabetes Association (ADA) Diabetes Technology Working Group
AbstractDigital health technology, especially digital and health applications ( ‘apps’), have been developing rapidly to help people manage their diabetes. Numerous health-related apps provided on smartphones and other wireless devices are available to support people with diabetes who need to adopt either lifestyle interventions or medication adjustments in response to gluc ose-monitoring data. However, regulations and guidelines have not caught up with the burgeoning field to standardise how mobile health apps are reviewed and monitored for patient safety and clinical validity. The available evidence on the sa...
Source: Diabetologia - January 7, 2020 Category: Endocrinology Source Type: research

Mesenchymal stromal cell-derived exosomes ameliorate peripheral neuropathy in a mouse model of diabetes
Conclusions/interpretationMSC-derived exosomes alleviate neurovascular dysfunction and improve functional recovery in mice with DPN by suppression of proinflammatory genes. (Source: Diabetologia)
Source: Diabetologia - January 7, 2020 Category: Endocrinology Source Type: research

Heterozygous deletion of Seipin in islet beta cells of male mice has an impact on insulin synthesis and secretion through reduced PPAR γ expression
Conclusions/interpretationHeterozygous deletion ofSeipin in islet beta cells impacts on insulin synthesis and secretion through reduced PPAR γ expression. This leads to glucose intolerance and is relieved by oestradiol, which rescues PPARγ expression. (Source: Diabetologia)
Source: Diabetologia - January 7, 2020 Category: Endocrinology Source Type: research

Hyaluronan deposition in islets may precede and direct the location of islet immune-cell infiltrates
Conclusions/interpretationThis study indicates that HA deposition in islets occurs early in type 1 diabetes and prior to insulitis, and points to a potential role of HA in triggering islet immune-cell infiltration and the promotion of insulitis. (Source: Diabetologia)
Source: Diabetologia - January 6, 2020 Category: Endocrinology Source Type: research

Persistent poor glycaemic control in individuals with type 2 diabetes in developing countries: 12  years of real-world evidence of the International Diabetes Management Practices Study (IDMPS)
AbstractAims/hypothesisWe evaluated the secular trend of glycaemic control in individuals with type 2 diabetes in developing countries, where data are limited.MethodsThe International Diabetes Management Practices Study provides real-world evidence of patient profiles and diabetes care practices in developing countries in seven cross-sectional waves (2005 –2017). At each wave, each physician collected data from ten consecutive participants with type 2 diabetes during a 2 week period. The primary objective of this analysis was to evaluate trends of glycaemic control over time.ResultsA total of 66,088 individuals ...
Source: Diabetologia - January 4, 2020 Category: Endocrinology Source Type: research

Luseogliflozin increases beta cell proliferation through humoral factors that activate an insulin receptor- and IGF-1 receptor-independent pathway
Conclusions/interpretationThese results suggest that luseogliflozin can increase beta cell proliferation through the activation of the FoxM1/PLK1/CENP-A pathway via humoral factors that act in an insulin/IGF-1 receptor-independent manner. (Source: Diabetologia)
Source: Diabetologia - January 3, 2020 Category: Endocrinology Source Type: research

The changing face of paediatric diabetes
AbstractThe purpose of this review is to provide an update on the changing face of paediatric type 1 diabetes and type 2 diabetes. Paediatric diabetes is on the rise, with extensive research dedicated to understanding its pathophysiology, comorbidities and complications. As obesity continues to increase among all youth, differentiating between type 1 diabetes and type 2 diabetes has become increasingly difficult but remains important for optimising treatment, anticipating complications and predicting disease risk. Novel treatments are emerging, with the ultimate goal being to achieve glycaemic control, limit weight gain, i...
Source: Diabetologia - January 2, 2020 Category: Endocrinology Source Type: research

Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised controlled clinical trial
Conclusions/interpretationIn individuals with uncontrolled type 2 diabetes on stable-dose metformin therapy, the changes in body composition with semaglutide and canagliflozin were not significantly different. Although numerical improvements in body composition were observed following treatment in both treatment arms, the specific impact of both treatments on body composition in the absence of a placebo arm is speculative at this stage.Trial registrationClinicalTrials.gov NCT03136484.FundingThis trial was supported by Novo Nordisk A/S, Denmark. (Source: Diabetologia)
Source: Diabetologia - January 2, 2020 Category: Endocrinology Source Type: research

A nanobody-based nuclear imaging tracer targeting dipeptidyl peptidase 6 to determine the mass of human beta cell grafts in mice
Conclusions/interpretationThese findings suggest that the anti-DPP6 4hD29 nanobody may become a useful tool for the quantification of human islet grafts in mice and, pending future development, islet mass in individuals with diabetes. (Source: Diabetologia)
Source: Diabetologia - December 23, 2019 Category: Endocrinology Source Type: research

A single bout of resistance exercise improves postprandial lipid metabolism in overweight/obese men with prediabetes
AbstractAims/hypothesisPrediabetes is associated with postprandial hypertriacylglycerolaemia. Resistance exercise acutely lowers postprandial plasma triacylglycerol (TG); however, the changes in lipid metabolism that mediate this reduction are poorly understood. The aim of this study was to identify the constitutive metabolic mechanisms underlying the changes in postprandial lipid metabolism after resistance exercise in obese men with prediabetes.MethodsWe evaluated the effect of a single bout of whole-body resistance exercise (seven exercises, three sets, 10 –12 repetitions at 80% of one-repetition maximum) on postp...
Source: Diabetologia - December 23, 2019 Category: Endocrinology Source Type: research

Incidence and relative risk of renal replacement therapy in people with and without diabetes between 2002 and 2016 in a German region
Conclusions/interpretationPeople with diabetes have a higher risk of needing renal replacement therapy than those without diabetes, a fact that remained constant over a time period of 15  years. (Source: Diabetologia)
Source: Diabetologia - December 21, 2019 Category: Endocrinology Source Type: research

Age of obesity onset, cumulative obesity exposure over early adulthood and risk of type 2 diabetes
AbstractAims/hypothesisObesity is a risk factor for type 2 diabetes, yet little is known about how timing and cumulative exposure of obesity are related to disease risk. The aim of this study was to examine the associations between BMI trajectories, age of onset of obesity and obese-years (a product of degree and duration of obesity) over early adulthood and subsequent risk of type 2 diabetes.MethodsWomen aged 18 –23 years at baseline (n = 11,192) enrolled in the Australian Longitudinal Study on Women’s Health (ALSWH) in 1996 were followed up about every 3 years via surveys for up to 19&...
Source: Diabetologia - December 20, 2019 Category: Endocrinology Source Type: research

Up front
(Source: Diabetologia)
Source: Diabetologia - December 19, 2019 Category: Endocrinology Source Type: research

2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
AbstractThe American Diabetes Association and the European Association for the Study of Diabetes have briefly updated their 2018 recommendations on management of hyperglycaemia, based on important research findings from large cardiovascular outcomes trials published in 2019. Important changes include: (1) the decision to treat high-risk individuals with a glucagon-like-peptide 1 (GLP-1) receptor agonist or sodium –glucose cotransporter 2 (SGLT2) inhibitor to reduce major adverse cardiovascular events (MACE), hospitalisation for heart failure (hHF), cardiovascular death or chronic kidney disease (CKD) progression shou...
Source: Diabetologia - December 19, 2019 Category: Endocrinology Source Type: research

Geospatial mapping and data linkage uncovers variability in outcomes of foot disease according to multiple deprivation: a population cohort study of people with diabetes
AbstractAims/hypothesisOur aim was to investigate the geospatial distribution of diabetic foot ulceration (DFU), lower extremity amputation (LEA) and mortality rates in people with diabetes in small geographical areas with varying levels of multiple deprivation.MethodsWe undertook a population cohort study to extract the health records of 112,231 people with diabetes from the Scottish Care Information – Diabetes Collaboration (SCI-Diabetes) database. We linked this to health records to identify death, LEA and DFU events. These events were geospatially mapped using multiple deprivation maps for the geographical area o...
Source: Diabetologia - December 17, 2019 Category: Endocrinology Source Type: research

A comparison of obesity indices in relation to mortality in type 2 diabetes: the Fremantle Diabetes Study
AbstractAims/hypothesisThis prospective association study aimed to compare the relationship between each of four obesity indices and mortality risk in people with type 2 diabetes.MethodsThe associations of BMI, waist circumference, WHR and A Body Shape Index (ABSI) with all-cause mortality were analysed in 1282 participants of the Fremantle Diabetes Study, followed for up to 20  years after baseline assessment. Models were adjusted for age and other confounders; assessments as continuous measures and by quintile were carried out for men and women separately. Sensitivity analyses were conducted to minimise reverse caus...
Source: Diabetologia - December 14, 2019 Category: Endocrinology Source Type: research

Pregnant women with gestational diabetes and with well controlled glucose levels have decreased concentrations of individual fatty acids in maternal and cord serum
Conclusions/interpretationThe expression of fatty acids in molar concentrations reveals that GDM decreases the concentration of most fatty acids in both maternal and cord serum. There is a high fetal dependence on maternal AA and DHA, but our findings do not support the existence of a fetal biomagnification of those two LCPUFA. (Source: Diabetologia)
Source: Diabetologia - December 12, 2019 Category: Endocrinology Source Type: research

Type 2 diabetes does not account for ethnic differences in exercise capacity or skeletal muscle function in older adults
AbstractAims/hypothesisThe aim of this study was to compare exercise capacity, strength and skeletal muscle perfusion during exercise, and oxidative capacity between South Asians, African Caribbeans and Europeans, and determine what effect ethnic differences in the prevalence of type 2 diabetes has on these functional outcomes.MethodsIn total, 708 participants (aged [mean ±SD] 73 ± 7 years, 56% male) were recruited from the Southall and Brent Revisited (SABRE) study, a UK population-based cohort comprised of Europeans (n = 311) and South Asian (n = 232) and Afric...
Source: Diabetologia - December 9, 2019 Category: Endocrinology Source Type: research

Longitudinal changes in glucose metabolism in women with gestational diabetes, from late pregnancy to the postpartum period
This study aimed to determine, in women with gestational diabetes (GDM), the changes in insulin sensitivity (Matsuda Insulin Sensitivity Index; ISOGTT), insulin response and disposition index (DI) from late pregnancy (34 –37 weeks gestation, T1), to early postpartum (1–5 days, T2) and late postpartum (6–12 weeks, T3). A secondary aim was to correlate the longitudinal changes in maternal lipids, adipokines, cytokines and weight in relation to the changes in ISOGTT, insulin response and DI.MethodsISOGTT, insulin response and DI were calculated at the three time points (T1, T2 and T3) using th...
Source: Diabetologia - December 9, 2019 Category: Endocrinology Source Type: research

Allostasis and the origins of adult-onset diabetes
AbstractPhysiological plasticity enables homeostasis to be maintained in biological systems, but when such allostasis fails, then disease can develop. In a new population-based study by Rolandsson et al (https://doi.org/10.1007/s00125-019-05016-3), autoimmunity, defined by an immunogenotype, predicted adult-onset non-insulin requiring diabetes. Type 1 diabetes is no longer viewed as a disease confined to children, with a significant proportion, maybe the majority, presenting in adulthood. Such cases masquerade as type 2 diabetes and their identification has clinical utility. Nevertheless, in this study, autoimmunity had a ...
Source: Diabetologia - December 7, 2019 Category: Endocrinology Source Type: research

Predicting renal disease progression in a large contemporary cohort with type 1 diabetes mellitus
AbstractAims/hypothesisThe aim of this study was to provide data from a contemporary population-representative cohort on rates and predictors of renal decline in type 1 diabetes.MethodsWe used data from a cohort of 5777 people with type 1 diabetes aged 16 and older, diagnosed before the age of 50, and representative of the adult population with type 1 diabetes in Scotland (Scottish Diabetes Research Network Type 1 Bioresource; SDRNT1BIO). We measured serum creatinine and urinary albumin/creatinine ratio (ACR) at recruitment and linked the data to the national electronic healthcare records.ResultsMedian age was 44.1  y...
Source: Diabetologia - December 5, 2019 Category: Endocrinology Source Type: research

Metabolomic profiles associated with subtypes of prediabetes among Mexican Americans in Starr County, Texas, USA
Conclusions/interpretationPeople with each subtype of prediabetes have a distinctive metabolomic signature, beyond the well-known differences in branched-chain amino acids.Data availabilityMetabolomics data are available through the NCBI database of Genotypes and Phenotypes (dbGaP, accession number phs001166;www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs001166.v1.p1). (Source: Diabetologia)
Source: Diabetologia - December 4, 2019 Category: Endocrinology Source Type: research

miR-409-3p is reduced in plasma and islet immune infiltrates of NOD diabetic mice and is differentially expressed in people with type 1 diabetes
Conclusions/interpretationWe propose that miR-409-3p may represent a new circulating biomarker of islet inflammation and type 1 diabetes severity. (Source: Diabetologia)
Source: Diabetologia - December 3, 2019 Category: Endocrinology Source Type: research

Incidence and prevalence of type 2 diabetes by occupation: results from all Swedish employees
Conclusions/interpretationProfessional drivers, manufacturing workers and cleaners have a threefold increased risk of type 2 diabetes compared with university teachers and physiotherapists. These differences most likely reflect dramatic differences in the prevalence of lifestyle risk factors. If workplace interventions could reduce weight and increase physical activity among employees in these occupations, major health gains may be made. (Source: Diabetologia)
Source: Diabetologia - December 3, 2019 Category: Endocrinology Source Type: research

Functional cytochrome P450 1A enzymes are induced in mouse and human islets following pollutant exposure
Conclusions/interpretationTransient exposure to TCDD results in long-term upregulation of CYP1A1 enzyme activity in islets. This provides evidence for direct exposure of islets to lipophilic pollutants in vivo and may have implications for islet physiology. (Source: Diabetologia)
Source: Diabetologia - December 3, 2019 Category: Endocrinology Source Type: research

Preventing foot ulceration in diabetes: systematic review and meta-analyses of RCT data
Conclusions/interpretationFour interventions were identified as being effective in preventing foot ulcers in people with diabetes, but uncertainty remains about what works and who is most likely to benefit. (Source: Diabetologia)
Source: Diabetologia - December 3, 2019 Category: Endocrinology Source Type: research

Cognitive dysfunction in diabetes: how to implement emerging guidelines
AbstractCognitive dysfunction, including mild cognitive impairment and dementia, is increasingly recognised as an important comorbidity and complication of diabetes that affects an individual ’s well-being and diabetes management, and is associated with diabetes treatment-related complications. Recent guidelines therefore recommend screening for cognitive impairment in older individuals with diabetes. In addition, these guidelines suggest that glucose-lowering treatment should be tailo red in those diagnosed with cognitive impairment, to reduce the risk of hypoglycaemia and improve treatment adherence. This review gi...
Source: Diabetologia - December 3, 2019 Category: Endocrinology Source Type: research

Trends in cancer mortality among people with vs without diabetes in the USA, 1988 –2015
AbstractAims/hypothesisCancer-related death is higher among people with vs without diabetes. However, it is not known if this excess risk has changed over time or what types of cancer may be driving these changes.MethodsTo estimate rates of site-specific cancer mortality in adults with vs without self-reported diagnosed diabetes, we used data from adults aged ≥18 years at the time of the interview who participated in the 1985—2012 National Health Interview Survey. Participants’ data were linked to the National Death Index by the National Center for Health Statistics to determine vital status and cause o...
Source: Diabetologia - December 3, 2019 Category: Endocrinology Source Type: research

Breast, cervical and colorectal cancer screening in adults with diabetes: a systematic review and meta-analysis
Conclusions/interpretationOur findings suggest that women with diabetes have suboptimal breast, cervical and colorectal cancer screening rates, compared with women without diabetes, although the absolute differences might be modest. Given the increased risk of cancer in this population, higher quality prospective evidence is necessary to evaluate the contribution of diabetes to cancer screening disparities in relation to other patient-, provider- and system-level factors.RegistrationPROSPERO registration ID CRD42017073107. (Source: Diabetologia)
Source: Diabetologia - December 3, 2019 Category: Endocrinology Source Type: research

Lipid-associated metabolic signalling networks in pancreatic beta cell function
AbstractSignificant advances have been made in deciphering the mechanisms underlying fuel-stimulated insulin secretion by pancreatic beta cells. The contribution of the triggering/ATP-sensitive potassium (KATP)-dependent Ca2+ signalling and KATP-independent amplification pathways, that include anaplerosis and lipid signalling of glucose-stimulated insulin secretion (GSIS), are well established. A proposed model included a key role for a metabolic partitioning ‘switch’, the acetyl-CoA carboxylase (ACC)/malonyl-CoA/carnitine palmitoyltransferase-1 (CPT-1) axis, in beta cell glucose and fatty acid signalling for i...
Source: Diabetologia - December 3, 2019 Category: Endocrinology Source Type: research

Upfront
(Source: Diabetologia)
Source: Diabetologia - December 3, 2019 Category: Endocrinology Source Type: research

GLP-1 secretion is regulated by IL-6 signalling: a randomised, placebo-controlled study
This study aimed to identify whether exercise-induced IL-6 has a similar effect in humans.MethodsIn a multicentre, double-blind clinical trial, we randomly assigned patients with type 2 diabetes or obesity to intravenous tocilizumab (an IL-6 receptor antagonist) 8  mg/kg every 4 weeks, oral sitagliptin (a dipeptidyl peptidase-4 inhibitor) 100 mg daily or double placebos (a placebo saline infusion every 4 weeks and a placebo pill once daily) during a 12 week training intervention. The primary endpoints were the difference in change of active GLP-1 respons e to an acute exercise bout and change in th...
Source: Diabetologia - December 3, 2019 Category: Endocrinology Source Type: research

Association of moderate and vigorous physical activity with incidence of type 2 diabetes and subsequent mortality: 27  year follow-up of the Whitehall II study
Conclusions/interpretationModerate-to-vigorous physical activity plays an important role in diabetes, influencing both its incidence and prognosis. A protective effect on incidence was seen for durations of activity below recommendations and a marginal additional benefit was observed at higher durations. Among individuals with type 2 diabetes, any duration of moderate-to-vigorous physical activity was associated with reduced all-cause mortality while recommended durations of physical activity were required for protection against cardiovascular disease-related mortality.Data availabilityWhitehall II data, protocols and othe...
Source: Diabetologia - December 2, 2019 Category: Endocrinology Source Type: research

Associations of short stature and components of height with incidence of type 2 diabetes: mediating effects of cardiometabolic risk factors
Conclusions/interpretationWe observed inverse associations between height and risk of type 2 diabetes, which was largely related to leg length among men. The inverse associations may be partly driven by lower liver fat content and a more favourable cardiometabolic profile. (Source: Diabetologia)
Source: Diabetologia - November 18, 2019 Category: Endocrinology Source Type: research

Fenofibrate increases very-long-chain sphingolipids and improves blood glucose homeostasis in NOD mice
Conclusions/interpretationThese data indicate that fenofibrate alters the pancreatic lipidome to a more anti-inflammatory and anti-apoptotic state. The beneficial effects on islet sympathetic nerve fibres and blood glucose homeostasis indicate that fenofibrate could be used as a therapeutic approach to improve blood glucose homeostasis and prevent diabetes-associated pathologies. (Source: Diabetologia)
Source: Diabetologia - November 18, 2019 Category: Endocrinology Source Type: research

Circulating metabolites in progression to islet autoimmunity and type 1 diabetes
Conclusions/interpretationOur findings suggest that children who progress to type 1 diabetes have a unique metabolic profile, which is, however, altered with the appearance of islet autoantibodies. Our findings may assist with early prediction of the disease. (Source: Diabetologia)
Source: Diabetologia - November 18, 2019 Category: Endocrinology Source Type: research

Echocardiography improves prediction of major adverse cardiovascular events in a population with type 1 diabetes and without known heart disease: the Thousand & amp; 1 Study
AbstractAims/hypothesisCardiovascular disease is the most common comorbidity in type 1 diabetes. However, current guidelines do not include routine assessment of myocardial function. We investigated whether echocardiography provides incremental prognostic information in individuals with type 1 diabetes without known heart disease.MethodsA prospective cohort of individuals with type 1 diabetes without known heart disease was recruited from the outpatient clinic. Follow-up was performed through Danish national registers. The association of echocardiography with major adverse cardiovascular events (MACE) and the incremental p...
Source: Diabetologia - November 18, 2019 Category: Endocrinology Source Type: research

Dietary inflammatory index and type 2 diabetes risk in a prospective cohort of 70,991 women followed for 20  years: the mediating role of BMI
AbstractAims/hypothesisDiet is one of the main lifestyle-related factors that can modulate the inflammatory process. Surprisingly the dietary inflammatory index (DII) has been little investigated in relation to type 2 diabetes, and the role of BMI in this relationship is not well established. We studied this association and the role of BMI in the inflammatory process in a large population-based observational study.MethodsA total of 70,991 women from the E3N (Etude Epid émiologique auprès de femmes de la Mutuelle Générale de l’Education Nationale) cohort study were followed for 20 year...
Source: Diabetologia - November 18, 2019 Category: Endocrinology Source Type: research

Short-term strength and balance training does not improve quality of life but improves functional status in individuals with diabetic peripheral neuropathy: a randomised controlled trial
Conclusions/interpretationShort-term structured strength and balance training did not influence HRQoL but produced sustained improvements in functional status and balance confidence at 6  months. More intensive interventions may be needed to influence HRQoL in these individuals. However, this intervention may be a useful treatment option for individuals with DPN to reduce the risk of falls and injuries.Trial registrationClinicalTrials.gov NCT02115932FundingThis work was supported by the National Medical Research Council, Singapore. (Source: Diabetologia)
Source: Diabetologia - November 18, 2019 Category: Endocrinology Source Type: research

Adipocyte-specific disruption of ATPase copper transporting α in mice accelerates lipoatrophy
Conclusions/interpretationOur results show a previously unappreciated role of adipocyteAtp7a in the regulation of ageing-related metabolic disease and identify new metallophysiologies in whole-body fat metabolism.Data availabilityThe datasets generated during the current study are available in the Genome Sequence Archive in BIG Data Center, Beijing Institute of Genomics (BIG), Chinese Academy of Sciences, under accession number CRA001769 (http://bigd.big.ac.cn/gsa). (Source: Diabetologia)
Source: Diabetologia - November 18, 2019 Category: Endocrinology Source Type: research

Induced pluripotent stem cell macrophages present antigen to proinsulin-specific T cell receptors from donor-matched islet-infiltrating T cells in type 1 diabetes
Conclusions/interpretationThis study provides a proof of principle for the use of iPSC-derived immune cells for modelling key cellular interactions in human type 1 diabetes. (Source: Diabetologia)
Source: Diabetologia - November 18, 2019 Category: Endocrinology Source Type: research

Deficiency in AIM2 induces inflammation and adipogenesis in white adipose tissue leading to obesity and insulin resistance
Conclusions/interpretationThese results demonstrate a fundamental role for AIM2 in energy metabolism, inflammation and insulin resistance. Our studies establish a novel link between the innate immunity proteins, AIM2 and p202, and metabolism. (Source: Diabetologia)
Source: Diabetologia - November 18, 2019 Category: Endocrinology Source Type: research

Potential impact of diabetes prevention on mortality and future burden of dementia and disability: a modelling study
Conclusions/interpretationReducing the burden of diabetes could result in substantial reductions in the incidence of dementia and disability over the medium to long term. (Source: Diabetologia)
Source: Diabetologia - November 15, 2019 Category: Endocrinology Source Type: research

Structure-functional changes in eNAMPT at high concentrations mediate mouse and human beta cell dysfunction in type 2 diabetes
Conclusions/interpretationWe have characterised a novel mechanism of beta cell dysfunction in type 2 diabetes. At low physiological levels, eNAMPT exists in dimer form and maintains beta cell function and identity through NAD-dependent mechanisms. However, as eNAMPT levels rise, as in type 2 diabetes, structure-functional changes occur resulting in marked elevation of monomeric eNAMPT, which induces a diabetic phenotype in pancreatic islets. Strategies to selectively target monomeric eNAMPT could represent promising therapeutic strategies for the treatment of type 2 diabetes. (Source: Diabetologia)
Source: Diabetologia - November 15, 2019 Category: Endocrinology Source Type: research

Plasma ascorbic acid and the risk of islet autoimmunity and type 1 diabetes: the TEDDY study
Conclusions/interpretationHigher plasma ascorbic acid levels may protect against islet autoimmunity in children genetically at risk for type 1 diabetes. Further studies are warranted to confirm these findings.Data availabilityThe datasets generated and analysed during the current study will be made available in the NIDDK Central Repository athttps://www.niddkrepository.org/studies/teddy. (Source: Diabetologia)
Source: Diabetologia - November 14, 2019 Category: Endocrinology Source Type: research

Activation of the HIF1 α/PFKFB3 stress response pathway in beta cells in type 1 diabetes
AbstractAims/hypothesisThe conserved hypoxia inducible factor 1 α (HIF1α) injury-response pro-survival pathway has recently been implicated in early beta cell dysfunction but slow beta cell loss in type 2 diabetes. We hypothesised that the unexplained prolonged prediabetes phase in type 1 diabetes may also be, in part, due to activation of the HIF1α signallin g pathway.MethodsRNA sequencing (RNA-Seq) data from human islets with type 1 diabetes or after cytokine exposure in vitro was evaluated for activation of HIF1 α targets. This was corroborated by immunostaining human pancreases from individuals ...
Source: Diabetologia - November 13, 2019 Category: Endocrinology Source Type: research