Up Front
(Source: Diabetologia)
Source: Diabetologia - September 15, 2023 Category: Endocrinology Source Type: research
Using race as a social construct when looking at differences in racial associations between non-alcoholic fatty liver disease and type 2 diabetes
(Source: Diabetologia)
Source: Diabetologia - September 7, 2023 Category: Endocrinology Source Type: research
The metabolic response of human trophoblasts derived from term placentas to metformin
Conclusions/interpretationIn primary trophoblasts derived from term placentas metformin treatment caused a reduction in oxidative phosphorylation through partial inactivation of complex I and potentially by other mechanisms. Metformin-treated trophoblasts accumulate lipids, particularly long- and very-long-chain polyunsaturated fatty acids. Our findings raise clinically important questions about the balance of risk of metformin use during pregnancy, particularly in situations where the benefits are not clear-cut and alternative therapies are available.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 5, 2023 Category: Endocrinology Source Type: research
Retinal inflammation in murine models of type 1 and type 2 diabetes with diabetic retinopathy
Conclusions/interpretationWe conclude that retinal inflammation is involved in and sustains pericyte loss as diabetic retinopathy progresses. Moreover, IFN γ plays a critical role in reducing pericyte survival in the retina by reducing activation of the PDGFRβ signalling pathway and increasing PKCδ levels and pericyte apoptosis.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 5, 2023 Category: Endocrinology Source Type: research
High proinsulin:C-peptide ratio identifies individuals with stage 2 type 1 diabetes at high risk for progression to clinical diagnosis and responses to teplizumab treatment
Conclusions/interpretationHigh pre-treatment PI:C identified individuals with stage 2 type 1 diabetes who were exhibiting rapid progression to stage 3 disease and who displayed benefit from teplizumab treatment. These data suggest that readouts of active disease, such as PI:C ratio, could serve to identify optimal candidates or timing for type 1 diabetes disease-modifying therapies.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 4, 2023 Category: Endocrinology Source Type: research
59 th EASD Annual Meeting of the European Association for the Study of Diabetes
(Source: Diabetologia)
Source: Diabetologia - September 4, 2023 Category: Endocrinology Source Type: research
Metformin for the prevention of diabetes among people with HIV and either impaired fasting glucose or impaired glucose tolerance (prediabetes) in Tanzania: a Phase II randomised placebo-controlled trial
Conclusions/interpretationBlood glucose decreased over time in both the metformin and placebo arms during the trial but did not differ significantly between the arms at 12 months of follow up. Metformin therapy was found to be safe for use in individuals with HIV and prediabetes. A larger trial with longer follow up is needed to establish if metformin can be safely used for the prevention of diabetes in people who have HIV.Trial registrationThe trial is registered on the International Standard Randomised Controlled Trial Number (ISRCTN) registry (www.isrctn.com/), registration number: ISCRTN76157257.FundingThis research wa...
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
Incretin hormones and type 2 diabetes
AbstractIncretin hormones (glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide-1 [GLP-1]) play a role in the pathophysiology of type 2 diabetes. Along with their derivatives they have shown therapeutic success in type 2 diabetes, with the potential for further improvements in glycaemic, cardiorenal and body weight-related outcomes. In type 2 diabetes, the incretin effect (greater insulin secretory response after oral glucose than with ‘isoglycaemic’ i.v. glucose, i.e. with an identical glycaemic stimulus) is markedly reduced or absent. This appears to be because of a reduced ability of GIP to s...
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
Strength training is more effective than aerobic exercise for improving glycaemic control and body composition in people with normal-weight type 2 diabetes: a randomised controlled trial
Conclusions/interpretationIn normal-weight type 2 diabetes, strength training was superior to aerobic training alone, while no significant difference was observed between strength training and combination training for HbA1c reduction. Increased lean mass relative to decreased fat mass was an independent predictor of reduction in HbA1c level.Trial registrationClinicalTrials.gov NCT02448498.FundingThis study was funded by the National Institutes of Health (NIH; R01DK081371).Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
The expanding incretin universe: from basic biology to clinical translation
AbstractIncretin hormones, principally glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1(GLP-1), potentiate meal-stimulated insulin secretion through direct (GIP + GLP-1) and indirect (GLP-1) actions on islet β-cells. GIP and GLP-1 also regulate glucagon secretion, through direct and indirect pathways. The incretin hormone receptors (GIPR and GLP-1R) are widely distributed beyond the pancreas, principally in the brain, cardiovascular and immune systems, gut and kidney, consistent with a broad array of e xtrapancreatic incretin actions. Notably, the glucoregulatory and anorectic activities of G...
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
Reversal of dual epigenetic repression of non-canonical Wnt-5a normalises diabetic corneal epithelial wound healing and stem cells
Conclusions/interpretationWe provide the first account of epigenetic changes in diabetic corneas including dual inhibition ofWNT5A by DNA methylation and miRNA action. Overall, Wnt-5a is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea.Data availabilityThe DNA methylation dataset is available from the public GEO repository under accession no. GSE229328 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229328).Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
Hyperglucagonaemia in diabetes: altered amino acid metabolism triggers mTORC1 activation, which drives glucagon production
Conclusions/interpretationAlpha cell exposure to hyperglycaemia enhances amino acid synthesis and transport, resulting in sustained activation of mTORC1, thereby increasing glucagon secretion. mTORC1 therefore plays a major role in mediating alpha cell dysfunction in diabetes.Data availabilityAll sequencing data are available from the Gene Expression Omnibus (GEO) repository (accession no. GSE154126;https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154126)Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
Socioeconomic aspects of incretin-based therapy
AbstractIncretin-based therapies, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have demonstrated cardiovascular benefits in people with type 2 diabetes. However, socioeconomic disparities in their uptake may constrain the collective advantages offered by these medications to the broader population. In this review we examine the socioeconomic disparities in the utilisation of incretin-based therapies and discuss strategies to address these inequalities. Based on real-world evidence, the uptake of GLP-1 RAs is reduced in people who live in socioeconomically disadvantaged areas, have low income and educ...
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
Glycaemic control, risk of hypoglycaemia and all-cause mortality in new users of second-generation basal insulin with type 2 diabetes and chronic kidney disease: a nationwide register-based cohort study
Conclusions/interpretationWe found no difference in HbA1c reduction, hospitalisation for hypoglycaemia or all-cause mortality between Gla-300 and Deg-100 in a real-world population of new users with type 2 diabetes and moderate to end-stage chronic kidney disease. Therefore, we conclude that these two treatment options are equally effective and safe in this vulnerable population.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
Genetic associations vary across the spectrum of fasting serum insulin: results from the European IDEFICS/I.Family children ’s cohort
Conclusions/interpretationThe above results support the notion of a shared genetic architecture for dementia and metabolic traits. Our approach identified genetic variants that were associated with the tails of the insulin spectrum only. Because traditional heritability estimates assume that genetic effects are constant throughout the phenotype distribution, the new findings may have implications for understanding the discrepancy in heritability estimates from GWA and family studies and for the study of U-shaped biomarker –disease associations.Graphical Abstract (Source: Diabetologia)
Source: Diabetologia - September 3, 2023 Category: Endocrinology Source Type: research
