Diabetes-related lower extremity complications in a multi-ethnic Asian population: a 10  year observational study in Singapore
In this study, we sought to understand the epidemiology of diabetes-related lower extremity complications (DRLECs: symptomatic peripheral arterial disease, ulceration, infection, gangrene) and amputations in a multi-ethnic Asian population.MethodsThis was a retrospective observational study using data obtained from one of three integrated public healthcare clusters in Singapore. The population consisted of individuals with incident type 2 diabetes who were of Chinese, Malay, Indian or Other ethnicity. We examined incidence, time to event and risk factors of DRLECs and amputation.ResultsBetween 2007 and 2017, of the 156,593...
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

IGFBP-1 expression is reduced in human type 2 diabetic glomeruli and modulates β1-integrin/FAK signalling in human podocytes
Conclusions/interpretationThis work identifies a novel role for IGFBP-1 in the regulation of podocyte function and that the glomerular expression ofIGFBP-1 is reduced in the early stages of type 2 DKD, via reduced FoxO1 activity. Thus, we hypothesise that strategies to maintain glomerular IGFBP-1 levels may be beneficial in maintaining podocyte function early in DKD.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Vitamin D concentrations from neonatal dried blood spots and the risk of early-onset type 2 diabetes in the Danish D-tect case-cohort study
Conclusions/interpretationThe results of this study do not support the hypothesis that higher neonatal vitamin D concentrations are associated with a lower risk of early-onset type 2 diabetes in adulthood.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Fasting and fasting-mimicking treatment activate SIRT1/LXR α and alleviate diabetes-induced systemic and microvascular dysfunction
Conclusions/interpretationTaken together, activation of SIRT1 signalling by IF or through pharmacological activation represents an effective therapeutic strategy that provides a mechanistic link between the advantageous effects associated with fasting regimens and prevention of microvascular and bone marrow dysfunction in diabetes.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Prognostic models for predicting the risk of foot ulcer or amputation in people with type 2 diabetes: a systematic review and external validation study
Conclusions/interpretationThirty-four prognostic models for the risk of foot ulcer or amputation were identified. Although the performance of the models varied considerably, three models performed well to predict foot ulcer or amputation and may be applicable to clinical practice.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Postpartum circulating microRNA enhances prediction of future type 2 diabetes in women with previous gestational diabetes
AbstractAims/hypothesisType 2 diabetes mellitus is a major cause of morbidity and death worldwide. Women with gestational diabetes mellitus (GDM) have greater than a sevenfold higher risk of developing type 2 diabetes in later life. Accurate methods for postpartum type 2 diabetes risk stratification are lacking. Circulating microRNAs (miRNAs) are well recognised as biomarkers/mediators of metabolic disease. We aimed to determine whether postpartum circulating miRNAs can predict the development of type 2 diabetes in women with previous GDM.MethodsIn an observational study, plasma samples were collected at 12  weeks pos...
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Sodium –glucose cotransporter 2 inhibitors and risk of nephrolithiasis
Conclusions/interpretationInitiation of treatment with SGLT2Is was associated with a clinically significant reduced risk of incident and recurrent nephrolithiasis.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Impact of high glucose levels and glucose lowering on risk of ischaemic stroke: a Mendelian randomisation study and meta-analysis
Conclusions/interpretationGenetically high plasma glucose has a causal impact on increased risk of ischaemic stroke. Treatment with glucose-lowering glucagon-like peptide-1 receptor agonists and thiazolidinediones reduces this risk. These results may guide clinicians in the treatment of individuals at high risk of ischaemic stroke.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Can placental growth factors explain birthweight variation in offspring of women with type 1 diabetes?
Conclusions/interpretationIn women with type 1 diabetes, infant birthweight is influenced by both glycaemic status and placental function. In women with suboptimal glycaemia, infant birthweight was heavier when placentas were healthy. Suboptimal placental function should be considered in the setting of suboptimal glycaemia and apparently ‘normal’ birthweight.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Development and validation of optimal phenomapping methods to estimate long-term atherosclerotic cardiovascular disease risk in patients with type 2 diabetes
AbstractAims/hypothesisType 2 diabetes is a heterogeneous disease process with variable trajectories of CVD risk. We aimed to evaluate four phenomapping strategies and their ability to stratify CVD risk in individuals with type 2 diabetes and to identify subgroups who may benefit from specific therapies.MethodsParticipants with type 2 diabetes and free of baseline CVD in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial were included in this study (N = 6466). Clustering using Gaussian mixture models, latent class analysis, finite mixture models (FMMs) and principal component analysis was co...
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Exercise training improves mitochondrial respiration and is associated with an altered intramuscular phospholipid signature in women with obesity
This study reports a secondary analysis of a randomised controlled trial including additional measures of mitochondrial respiration, skeletal muscle lipidomics, metabolomics and protein content. Women with obesity were randomised into 12  weeks of combined aerobic and resistance exercise training (n = 20) or control (n = 15) groups. Pre- and post-intervention testing included peak oxygen consumption, whole-body insulin sensitivity (intravenous glucose tolerance test), skeletal muscle mitochondrial respiration (high-resolution respirometry), lipidomics and metabolomics (mass spectrometry) an...
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Oestrogen receptor α in T cells controls the T cell immune profile and glucose metabolism in mouse models of gestational diabetes mellitus
AbstractAims/hypothesisThe imbalance between maternal insulin resistance and a relative lack of insulin secretion underlies the pathogenesis of gestational diabetes mellitus (GDM). Alterations in T cell subtypes and increased levels of circulating proinflammatory cytokines have been proposed as potential mechanisms underlying the pathophysiology of insulin resistance in GDM. Since oestrogen modulates T cell immunity, we hypothesised that oestrogen plays a homeostatic role in visceral adipose tissue by coordinating T cell immunity through oestrogen receptor α (ERα) in T cells to prevent GDM.MethodsFemale CD4-cre...
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Liver-targeting drugs and their effect on blood glucose and hepatic lipids
AbstractThe global epidemic of non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) and the high prevalence among individuals with type 2 diabetes has attracted the attention of clinicians specialising in liver disorders. Many drugs are in the pipeline for the treatment of NAFLD/NASH, and several glucose-lowering drugs are now being tested specifically for the treatment of liver disease. Among these are nuclear hormone receptor agonists (e.g. peroxisome proliferator-activated receptor agonists, farnesoid X receptor agonists and liver X receptor agonists), fibroblast growth factor-19 and -21, single, dual or...
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Multi-omics analysis identifies CpGs near G6PC2 mediating the effects of genetic variants on fasting glucose
This study aimed to identify the mediation effects of DNA methylation between SNPs identified as significant from GWAS and fasting glucose using Mendelian randomisation (MR) analyses.MethodsWe first performed GWAS analyses for three cohorts (Taiwan Biobank with 18,122 individuals, the Healthy Aging Longitudinal Study in Taiwan with 1989 individuals and the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance with 416 individuals) with individuals of Han Chinese ancestry in Taiwan, followed by a meta-analysis for combining the three GWAS analysis results to identify significant and independent SNPs for fast...
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Effect of flash glucose monitoring in adults with type 1 diabetes: a nationwide, longitudinal observational study of 14,372 flash users compared with 7691 glucose sensor naive controls
AbstractAims/hypothesisThe aim of this work was to evaluate changes in glycaemic control (HbA1c) and rates of severe hypoglycaemia over a 2  year period after initiation of flash glucose monitoring (FM) in type 1 diabetes.MethodsUsing data from the Swedish National Diabetes Registry, 14,372 adults with type 1 diabetes with a new registration of FM during 2016 –2017 and with continued FM for two consecutive years thereafter, and 7691 control individuals using conventional self-monitoring of blood glucose (SMBG) during the same observation period, were included in a cohort study. Propensity sores and inverse proba...
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Risk phenotypes of diabetes and association with COVID-19 severity and death: a living systematic review and meta-analysis
Conclusions/interpretationIndividuals with a more severe course of diabetes have a poorer prognosis of COVID-19 compared with individuals with a milder course of disease. To further strengthen the evidence, more studies on this topic that account for potential confounders are warranted.RegistrationPROSPERO registration ID CRD42020193692.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Derivation and validation of a machine learning risk score using biomarker and electronic patient data to predict progression of diabetic kidney disease
AbstractAimPredicting progression in diabetic kidney disease (DKD) is critical to improving outcomes. We sought to develop/validate a machine-learned, prognostic risk score (KidneyIntelX ™) combining electronic health records (EHR) and biomarkers.MethodsThis is an observational cohort study of patients with prevalent DKD/banked plasma from two EHR-linked biobanks. A random forest model was trained, and performance (AUC, positive and negative predictive values [PPV/NPV], and net reclassification index [NRI]) was compared with that of a clinical model and Kidney Disease: Improving Global Outcomes (KDIGO) categories for...
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Identification and characterisation of tertiary lymphoid organs in human type 1 diabetes
Conclusions/interpretationWe demonstrate a novel feature of pancreas pathology in type 1 diabetes. TLOs represent a potential site of autoreactive effector T cell generation in islet autoimmunity and our data from mouse and human tissues suggest that they disappear once the destructive process has run its course. Thus, TLOs may be important for type 1 diabetes progression.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Case report: coeliac disease as a cause of secondary failure of glibenclamide therapy in a patient with permanent neonatal diabetes due to KCNJ11/R201C mutation
(Source: Diabetologia)
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Up front
(Source: Diabetologia)
Source: Diabetologia - June 8, 2021 Category: Endocrinology Source Type: research

Data-driven assessment, contextualisation and implementation of 134 variables in the risk for type 2 diabetes: an analysis of Lifelines, a prospective cohort study in the Netherlands
ConclusionsMany variables show weak or inconsistent associations with the development of type 2 diabetes, and only a handful can reliably explain disease risk. Newly discovered risk variables will yield little over established factors, and existing prediction models can be simplified. A systematic, data-driven approach to identify risk variables for the prediction of type 2 diabetes is necessary for the practice of precision medicine.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Peak glucose during an oral glucose tolerance test is associated with future diabetes risk in adults with cystic fibrosis
AbstractAims/hypothesisCystic fibrosis-related diabetes (CFRD) affects up to 50% of adults with cystic fibrosis (CF) and its presence is associated with adverse effects on nutritional status and pulmonary function. Early diagnosis could minimise CFRD morbidity, yet current methods of an OGTT at 0 and 2  h yield unreliable results. Our aim was to determine which indices from a 2 h OGTT with sampling every 30 min might improve prediction of CFRD.MethodsCross-sectional analysis at baseline (n = 293) and observational prospective analysis (n = 185; mean follow-up of 7.5 ±...
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

The hepatokine fetuin-A disrupts functional maturation of pancreatic beta cells
Conclusions/interpretationOur results suggest that the perinatal decline of fetuin-A relieves TGFBR signalling in islets, a process that facilitates functional maturation of neonatal beta cells. Functional maturity remains revocable in later life, and the occurrence of a metabolically unhealthy milieu, such as liver steatosis and elevated plasma fetuin-A, can impair both function and adaptive proliferation of beta cells.Data availabilityThe RNAseq datasets and computer code produced in this study are available in the Gene Expression Omnibus (GEO): GSE144950;https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE144950Graphi...
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Somatosensory network functional connectivity differentiates clinical pain phenotypes in diabetic neuropathy
Conclusions/interpretationThis study demonstrates differences in functional connectivity in nociceptive processing brain regions between IR and NIR phenotypes in painful DPN. We also establish proof of concept for the utility of multimodal MRI as a biomarker for painful DPN by using a machine-learning approach to classify individuals into sensory phenotypes.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Analysis of overlapping genetic association in type 1 and type 2 diabetes
AbstractAims/hypothesisGiven the potential shared aetiology between type 1 and type 2 diabetes, we aimed to identify any genetic regions associated with both diseases. For associations where there is a shared signal and the allele that increases risk to one disease also increases risk to the other, inference about shared aetiology could be made, with the potential to develop therapeutic strategies to treat or prevent both diseases simultaneously. Alternatively, if a genetic signal co-localises with divergent effect directions, it could provide valuable biological insight into how the association affects the two diseases di...
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Marked improvements in glycaemic outcomes following insulin pump therapy initiation in people with type 1 diabetes: a nationwide observational study in Scotland
Conclusions/interpretationCSII therapy was associated with marked falls in HbA1c especially in those with high baseline HbA1c. CSII was independently associated with reduced DKA and SHH rates. CSII appears to be an effective option for intensive insulin therapy in people with diabetes for improving suboptimal glycaemic control.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Cold-induced dishabituation in rodents exposed to recurrent hypoglycaemia
AbstractAims/hypothesisRecurrent hypoglycaemia in people with diabetes leads to progressive suppression of counterregulatory hormonal responses to subsequent hypoglycaemia. Recently it has been proposed that the mechanism underpinning this is a form of adaptive memory referred to as habituation. To test this hypothesis, we use two different durations of cold exposure to examine whether rodents exposed to recurrent hypoglycaemia exhibit two characteristic features of habituation, namely stimulus generalisation and dishabituation.MethodsIn the first study (stimulus generalisation study), hyperinsulinaemic –hypoglycaemi...
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Screening, prevalence, treatment and control of kidney disease in patients with type 1 and type 2 diabetes in low-to-middle-income countries (2005 –2017): the International Diabetes Management Practices Study (IDMPS)
Conclusions/interpretationIn LMICs, real-world data suggest improvement in screening and treatment for kidney disease in patients with type 1 and type 2 diabetes attending non-nephrology clinics. This was accompanied by decreasing proportions of patients with microalbuminuria and proteinuria, with fewer patients who reported receiving dialysis over a 12-year period.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Associations of progression to diabetes and regression to normal glucose tolerance with development of cardiovascular and microvascular disease among people with impaired glucose tolerance: a secondary analysis of the 30  year Da Qing Diabetes Prevention Outcome Study
AbstractAims/hypothesisWe aimed to determine associations of regression to normal glucose tolerance (NGT), maintaining impaired glucose tolerance (IGT) or progression to diabetes with subsequent risks of CVD and microvascular disease among Chinese adults with IGT.MethodsWe conducted an observational study among 540 participants in the Da Qing Diabetes Prevention Study, a 6  year lifestyle intervention trial in people with IGT, defined by 1985 WHO criteria as fasting plasma glucose
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Impact of maternal HbA 1c on offspring glucose at 4 –7 years of age: role of childhood adiposity and other potential confounders. Reply to Periyathambi N, Sukumar N, Weldeselassie Y, Saravanan P [letter]
(Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Up front
(Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Impact of maternal HbA 1c on offspring glucose at 4 –7 years of age: role of childhood adiposity and other potential confounders
(Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Correction to: Maternal blood glucose level and offspring glucose –insulin homeostasis: what is the role of offspring adiposity?
A Correction to this paper has been published:https://doi.org/10.1007/s00125-021-05432-4 (Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Correction to: New closed-loop insulin systems
A Correction to this paper has been published:https://doi.org/10.1007/s00125-021-05443-1 (Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Correction to: The discovery of insulin in Toronto: beginning a 100  year journey of research and clinical achievement
A Correction to this paper has been published:https://doi.org/10.1007/s00125-021-05445-z (Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Correction to: Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study: newborn anthropometrics and childhood glucose metabolism
A Correction to this paper has been published:https://doi.org/10.1007/s00125-021-05421-7 (Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Correction to: High extracellular ATP levels released through pannexin-1 channels mediate inflammation and insulin resistance in skeletal muscle fibres of diet-induced obese mice
A Correction to this paper has been published:https://doi.org/10.1007/s00125-021-05451-1 (Source: Diabetologia)
Source: Diabetologia - May 5, 2021 Category: Endocrinology Source Type: research

Acute hyperglycaemia does not have a consistent adverse effect on exercise performance in recreationally active young people with type 1 diabetes: a randomised crossover in-clinic study
Conclusions/interpretationAcute marked hyperglycaemia in the higher but not low insulin state impaired\( \dot{V}{\mathrm{O}}_{2\mathrm{peak}} \) but to a small extent. Acute hyperglycaemia had an insulin-dependent effect on sprint cycling absolute power output and reaction time but with differing directionality (positive for sprint cycling and negative for reaction time) and no effect on the other indicators of exercise performance examined. We find that acute hyperglycaemia is not consistently adverse and does not impair overall exercise performance to an extent clinically relevant for recreationally active individuals wi...
Source: Diabetologia - May 4, 2021 Category: Endocrinology Source Type: research

Reduced beta cell number rather than size is a major contributor to beta cell loss in type 2 diabetes
AbstractAims/hypothesisType 2 diabetes is characterised by reduced beta cell mass (BCM). However, it remains uncertain whether the reduction in BCM in type 2 diabetes is due to a decrease in size or number of beta cells. Our aim was to examine the impact of beta cell size and number on islet morphology in humans with and without type 2 diabetes.MethodsPancreas samples were obtained from 64 Japanese adults with (n = 26) and without (n = 38) type 2 diabetes who underwent pancreatectomy. Using pancreatic tissues stained for insulin, we estimated beta cell size based on beta cell diameter. Beta cell...
Source: Diabetologia - May 3, 2021 Category: Endocrinology Source Type: research

Celebrating 100  years of insulin
(Source: Diabetologia)
Source: Diabetologia - March 31, 2021 Category: Endocrinology Source Type: research

The promise of stem cell-derived islet replacement therapy
AbstractPresent-day treatments for people that are insulin dependent require multiple insulin injections, sometimes with an insulin pump, coupled with regular blood glucose monitoring. The availability of modified insulins, each with peaks of activity at varying times, has improved diabetes management. On the other hand, there have been impressive results leading to insulin independence by transplantation of cadaveric islets coupled with immune suppression. This review focuses on the possibility of treating diabetes with cellular transplants, specifically with the use of pluripotent stem cells, to produce a virtually unlim...
Source: Diabetologia - March 31, 2021 Category: Endocrinology Source Type: research

The discovery of insulin in Toronto: beginning a 100  year journey of research and clinical achievement
AbstractThere has been a great deal of controversy regarding priority of discovery of insulin. Indeed, many scientists made important and, in some cases, seminal contributions to identifying the endocrine role of the pancreas and the potential for pancreatic extracts to have a glucose-lowering effect. The purpose of this article is to describe the early experiences with respect to research leading to the discovery of insulin in Toronto (ON, Canada). The experiments conducted at the University of Toronto resulted in the first demonstration that a pancreatic extract could be prepared that would consistently lower glucose, re...
Source: Diabetologia - March 31, 2021 Category: Endocrinology Source Type: research

Size for gestational age affects the risk for type 1 diabetes in children and adolescents: a Swedish national case –control study
AbstractAim/hypothesisEnvironmental factors are believed to contribute to the risk of developing type 1 diabetes. The aim of this study was to investigate how size for gestational age affects the risk of developing childhood type 1 diabetes.MethodsUsing the Swedish paediatric diabetes quality register and the Swedish medical birth register, children with type 1 diabetes diagnosed between 2000 and 2012 (n = 9376) were matched with four control children (n = 37,504). Small for gestational age (SGA) and large for gestational age (LGA) were defined according to Swedish national standards. Data were ...
Source: Diabetologia - March 31, 2021 Category: Endocrinology Source Type: research

Current and future therapies for type 1 diabetes
AbstractIn type 1 diabetes, insulin remains the mature therapeutic cornerstone; yet, the increasing number of individuals developing type 1 diabetes (predominantly children and adolescents) still face severe complications. Fortunately, our understanding of type 1 diabetes is continuously being refined, allowing for refocused development of novel prevention and management strategies. Hitherto, attempts based on immune suppression and modulation have been only partly successful in preventing the key pathophysiological feature in type 1 diabetes: the immune-mediated derangement or destruction of beta cells in the pancreatic i...
Source: Diabetologia - March 31, 2021 Category: Endocrinology Source Type: research

Oral insulin immunotherapy in children at risk for type 1 diabetes in a randomised controlled trial
Conclusions/interpretationThe study demonstrated that oral insulin immunotherapy in young genetically at-risk children was safe, but was not associated with an immune response as predefined in the trial primary outcome. Exploratory analyses suggested that antibody responses to oral insulin may occur in children with a susceptibleINS genotype, and that inflammatory episodes may promote the activation of insulin-responsive T cells.Trial registrationClinicaltrials.gov NCT02547519FundingThe main funding source was the German Center for Diabetes Research (DZD e.V.)Graphical abstract (Source: Diabetologia)
Source: Diabetologia - March 31, 2021 Category: Endocrinology Source Type: research

Hypothalamic glucose-sensing mechanisms
AbstractChronic metabolic diseases, including diabetes and obesity, have become a major global health threat of the twenty-first century. Maintaining glucose homeostasis is essential for survival in mammals. Complex and highly coordinated interactions between glucose-sensing mechanisms and multiple effector systems are essential for controlling glucose levels in the blood. The central nervous system (CNS) plays a crucial role in regulating glucose homeostasis. Growing evidence indicates that disruption of glucose sensing in selective CNS areas, such as the hypothalamus, is closely interlinked with the pathogenesis of obesi...
Source: Diabetologia - March 31, 2021 Category: Endocrinology Source Type: research

Biphasic dynamics of beta cell mass in a mouse model of congenital hyperinsulinism: implications for type 2 diabetes
AbstractAims/hypothesisAcute hyperglycaemia stimulates pancreatic beta cell proliferation in the mouse whereas chronic hyperglycaemia appears to be toxic. We hypothesise that this toxic effect is mediated by increased beta cell workload, unrelated to hyperglycaemia per se.MethodsTo test this hypothesis, we developed a novel mouse model of cell-autonomous increased beta cell glycolytic flux caused by a conditional heterozygous beta cell-specific mutation that activates glucokinase (GCK), mimicking key aspects of the rare human genetic disease GCK-congenital hyperinsulinism.ResultsIn the mutant mice, we observed random and f...
Source: Diabetologia - March 31, 2021 Category: Endocrinology Source Type: research

Consequences of recurrent hypoglycaemia on brain function in diabetes
AbstractThe discovery of insulin and its subsequent mass manufacture transformed the lives of people with type 1 and 2 diabetes. Insulin, however, was a drug with a ‘dark side’. It brought with it the risk of iatrogenic hypoglycaemia. In this short review, the cellular consequences of recurrent hypoglycaemia, with a particular focus on the brain, are discussed. Using the ventromedial hypothalamus as an exemplar, this review highlights how recurrent hypoglyc aemia has an impact on the specialised cells in the brain that are critical to the regulation of glucose homeostasis and the counterregulatory response to h...
Source: Diabetologia - March 31, 2021 Category: Endocrinology Source Type: research

Retinal venular tortuosity and fractal dimension predict incident retinopathy in adults with type 2 diabetes: the Edinburgh Type 2 Diabetes Study
Conclusions/interpretationIncreased retinal venular tortuosity and decreased fractal dimension are associated with incident diabetic retinopathy, independent of classical risk factors. There is some evidence that venular tortuosity may be a useful biomarker to improve the predictive ability of models based on established retinopathy risk factors, and its inclusion in further risk prediction modelling is warranted.Graphical abstract (Source: Diabetologia)
Source: Diabetologia - March 31, 2021 Category: Endocrinology Source Type: research

Heterogeneity in insulin-stimulated glucose uptake among different muscle groups in healthy lean people and people with obesity
AbstractAims/hypothesisIt has been proposed that muscle fibre type composition and perfusion are key determinants of insulin-stimulated muscle glucose uptake, and alterations in muscle fibre type composition and perfusion contribute to muscle, and consequently whole-body, insulin resistance in people with obesity. The goal of the study was to evaluate the relationships among muscle fibre type composition, perfusion and insulin-stimulated glucose uptake rates in healthy, lean people and people with obesity.MethodsWe measured insulin-stimulated whole-body glucose disposal and glucose uptake and perfusion rates in five major ...
Source: Diabetologia - March 31, 2021 Category: Endocrinology Source Type: research