Diabetologia最新文献

{"title":"In Memoriam Werner Waldhäusl, 27 September 1937-22 May 2025.","authors":"Michael Roden","doi":"10.1007/s00125-025-06489-1","DOIUrl":"https://doi.org/10.1007/s00125-025-06489-1","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"694 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin's impact on hormonal regulation and ketogenesis in type 1 diabetes: a randomised controlled crossover trial.","authors":"Andreas Gübeli,Nicole Steiner,Andreas Limacher,Déborah Mathis,Andreas Melmer,Markus Laimer","doi":"10.1007/s00125-025-06481-9","DOIUrl":"https://doi.org/10.1007/s00125-025-06481-9","url":null,"abstract":"AIMS/HYPOTHESISThis study aimed to assess the impact of adding dapagliflozin to insulin therapy on key hormonal determinants of glucose regulation and ketogenesis. We hypothesise that dapagliflozin increases glucagon-like peptide 1 (GLP-1), glucagon and ketone body concentrations, based on the results of a pilot study.METHODSThe study was designed as a randomised, placebo-controlled, open-label, crossover intervention study with two periods (dapagliflozin and placebo intake), including patients of the Department of Diabetes, Endocrinology, Clinical Nutrition & Metabolism, Inselspital, Bern University Hospital, University of Bern. Individuals with type 1 diabetes (C-peptide concentrations <0.1 nmol/l) with a duration >5 years and a BMI of 20-29 kg/m2 were included. They received 10 mg of dapagliflozin or placebo daily for 7 days throughout two independent treatment periods, separated by a 14 day washout period. Allocation was done by a computed randomisation tool (REDCap), without blinding of the participants or the investigators. On day 7 of each treatment period, hyperinsulinaemic-euglycaemic clamps (HECs) and OGTT clamps (OGTTCs) were performed to assess changes in the secretion of GLP-1, glucagon, somatostatin and total ketone bodies. The objective was to evaluate the effects of adding the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin to insulin therapy on GLP-1 during OGTTC (primary endpoint), GLP-1 secretion during HEC, and glucagon, somatostatin and ketogenesis during OGTTC and HEC (secondary endpoints). The primary endpoint was concentrations of GLP-1 during OGTTC. Secondary endpoints included GLP-1 during HEC and glucagon, somatostatin and ketone body concentrations during OGTTC and HEC.RESULTSA total of 13 individuals with type 1 diabetes were included and randomised. All of them received dapagliflozin and placebo, finished the sequences per protocol and were analysed per protocol. GLP-1 concentrations did not differ significantly between treatments in the OGTTC (median [IQR] dapagliflozin 192.8 [129.8-257.2] pmol/l vs placebo 176.3 [138.4-227.4] pmol/l; p=0.7) or HEC (median [IQR] dapagliflozin 208.6 [133.6-294.0] pmol/l vs placebo 203.1 [150.2-291.8] pmol/l; p=0.7). Glucagon concentrations did not significantly differ between treatments in the OGTTC (median [IQR] dapagliflozin 1.54 [0.84-3.68] ng/l vs placebo 1.54 [0.82-4.64] ng/l; p=0.8) or HEC (median [IQR] dapagliflozin 1.59 [0.87-3.54] ng/l vs placebo 1.63 [0.91-3.96] ng/l; p=0.3). Somatostatin concentrations remained comparable between treatments during the HEC (median [IQR] dapagliflozin 41.1 [26.8-73.8] pmol/l vs placebo 47.0 [23.0-77.6] pmol/l; p=0.2) and OGTTC (median [IQR] dapagliflozin 51.1 [31.1-77.0] pmol/l vs placebo 45.3 [30.0-70.5] pmol/l; p=0.2). Plasma ketone bodies were higher with dapagliflozin during the HEC (median [IQR] dapagliflozin 0.15 [0.04-0.47] mmol/l vs placebo 0.03 [0.01-0.12] mmol/l; p<0.001) and OGTTC (median [IQR] dapagliflozin 0.10 [0","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"17 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144586671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers of inflammation and improvement in depressive symptoms in type 1 and type 2 diabetes: differential associations with depressive symptom clusters.","authors":"Christian Herder,Anna Zhu,Andreas Schmitt,Maria C Spagnuolo,Bernhard Kulzer,Michael Roden,Dominic Ehrmann,Norbert Hermanns","doi":"10.1007/s00125-025-06472-w","DOIUrl":"https://doi.org/10.1007/s00125-025-06472-w","url":null,"abstract":"AIMS/HYPOTHESISPeople with diabetes and depression show large heterogeneity in their response to depression treatment. This study aimed to identify biomarkers of subclinical inflammation that were associated with improvement of depressive symptoms in people with type 1 diabetes and type 2 diabetes.METHODSThe prospective analysis combined data from three studies (DIAMOS, ECCE HOMO and DDCT). A total of 332 people with type 1 diabetes and 189 people with type 2 diabetes completed both the baseline and 1 year follow-up examinations. Depressive symptoms were assessed using the Center for Epidemiological Studies depression scale (CES-D). Associations between baseline serum levels of 76 biomarkers of inflammation and 1 year changes in depressive symptoms were estimated using multiple linear regression.RESULTSIn people with type 2 diabetes, higher levels of 26 biomarkers were associated with greater reductions in depressive symptoms (β=0.128 to 0.255; p<0.05), whereas in people with type 1 diabetes, higher levels of 13 biomarkers were linked with lower reductions in depressive symptoms (β=-0.189 to -0.094; p<0.05). A significant effect modification was observed for 33 biomarkers (pinteraction<0.05). The positive associations in type 2 diabetes were strongest for improvements in cognitive-affective and anhedonia symptoms, while the inverse associations in type 1 diabetes were strongest for improvements in somatic symptoms.CONCLUSIONS/INTERPRETATIONHigher baseline levels of multiple biomarkers of inflammation were associated with greater depression reduction in type 2 diabetes but lower depression reduction in type 1 diabetes. There were also diabetes type-specific differences in the associations with symptom clusters of depression. This suggests that different inflammation-related pathways may be relevant for the response to depression treatment in people with type 1 diabetes or type 2 diabetes.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"3 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of SLC19A2 variants in the wide spectrum of non-autoimmune abnormalities of glucose homeostasis.","authors":"Antonella Marucci,Mehdi Derhourhi,Claudia Menzaghi,Grazia Fini,Marina Valenzano,Simona Zampetti,Alessandro Doria,Philippe Froguel,Amélie Bonnefond,Vincenzo Trischitta,Rosa Di Paola","doi":"10.1007/s00125-025-06485-5","DOIUrl":"https://doi.org/10.1007/s00125-025-06485-5","url":null,"abstract":"AIMS/HYPOTHESISBiallelic pathogenic variants in SLC19A2 (the solute carrier family 19 member 2, which encodes thiamine transporter 1, responsible for thiamine intake) cause a recessive syndromic diabetes of infancy or early childhood in the context of thiamine-responsive megaloblastic anaemia, characterised by sensorineural deafness. Indeed, it has been reported, although only once, that even a heterozygous missense loss-of-function variant of SLC19A2 causes dominantly inherited non-syndromic diabetes. Finally, it is unknown whether rare SLC19A2 pathogenic variants modulate the risk of type 2 diabetes at the population level. We investigated the role of SLC19A2 heterozygous variants in both autosomal dominant mild hyperglycaemia and type 2 diabetes.METHODSWe performed whole exome sequencing in two probands with mild hyperglycaemia and in 191,140 samples from the UK Biobank.RESULTSHere we report two different heterozygous missense likely pathogenic variants of SLC19A2 (NM_006996.2) associated with non-syndromic mild hyperglycaemia in two pedigrees (c.515G>T and c.1063A>C missense variants, respectively), clearly confirming the only report available so far suggesting this link. In both pedigrees, individuals who carried an additional variant in one of the established monogenic diabetes genes (i.e. PDX1, NM_000209.3 and KCNJ11, NM_000525.3) showed an anticipation of disease onset of 25-31 years. Finally, 12 rare null variants in SLC19A2 were associated with type 2 diabetes (p=0.00033; OR 3.7; 95% CI 1.3, 227) and increased HbA1c levels (p=0.019, effect [π]=2.2 ± 0.92) in the UK Biobank.CONCLUSIONS/INTERPRETATIONTaken together with previous evidence, these data indicate that SLC19A2 variability modulates glucose homeostasis, from recessive syndromic diabetes, to autosomal dominant mild hyperglycaemia, to type 2 diabetes.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"638 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rethinking the link between gestational diabetes and dementia risk.","authors":"Qiu-Han Xu,Ya-Jing Huang","doi":"10.1007/s00125-025-06480-w","DOIUrl":"https://doi.org/10.1007/s00125-025-06480-w","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"29 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stem-cell-derived beta cells mature metabolically upon murine engraftment.","authors":"Eliisa Vähäkangas,Jonna Saarimäki-Vire,Hossam Montaser,Väinö Lithovius,Solja Eurola,Hazem Ibrahim,Emilia Kuuluvainen,Diego Balboa,Pekka Katajisto,Tom Barsby,Timo Otonkoski","doi":"10.1007/s00125-025-06474-8","DOIUrl":"https://doi.org/10.1007/s00125-025-06474-8","url":null,"abstract":"AIMS/HYPOTHESISThe use of stem-cell-derived islets (SC-islets) as a source for cell-based therapy of type 1 diabetes shows great potential. However, SC-islets have a metabolically immature phenotype compared with primary human islets, the current 'gold standard' cell therapy. SC-islet metabolic immaturity is most evident in their aberrant reactivity to pyruvate, which could be associated with clinically significant dysregulation of insulin secretion. We thus aimed to study whether this immature metabolic phenotype persists upon engraftment in mice.METHODSThis study was conducted by differentiating the H1 human embryonic stem-cell line into pancreatic islets (SC-islets) using a well-established seven-stage differentiation protocol. SC-islets were implanted under the kidney capsule of immunocompromised NOD-scid-gamma mice for 1-4 months. Metabolic and morphological assays of SC-islets pre- and post-implantation were performed (in parallel to cadaveric donor islets) using LC-MS metabolomics, electron microscopy, immunohistochemistry analyses and dynamic insulin secretion assays.RESULTSSC-islets had the capability of dynamically controlling mouse blood glucose levels by 3 months post-implantation. Murine engraftment led to maturation of various metabolic aspects of SC-islets, leading them to resemble human donor islets more closely. Mitochondrial number increased from a mean of 0.38 mitochondria/µm2 in vitro to 0.67 mitochondria/µm2 following 4 months of engraftment (p=0.0004). Conversely, changes in mitochondrial morphology were cell-specific and correlated more with the insulin granule crystallisation status of a given beta cell than the timepoint of the SC-islet sample. Glucose-sensitive tricarboxylic acid cycle activity increased, with the enrichment of labelled carbons into citrate in high glucose increasing from 12% in vitro to 28.7% 4 months post-engraftment (p<0.0001). Additionally, glucose-sensitive insulin secretion increased at the same time as pyruvate-reactive insulin secretion decreased, with the pyruvate-to-glucose reactivity ratio decreasing from 2.1 in vitro to 0.5 at 4 months post-engraftment (p=0.013). Lowered pyruvate reactivity was accompanied by the downregulation of the pyruvate/lactate transporter monocarboxylate transporter 1 (MCT1).CONCLUSIONS/INTERPRETATIONAn in vivo environment is beneficial for the metabolic maturation of SC-islets, leading them to more closely resemble human donor islets. We show that the aberrant metabolite trafficking pathways seen in SC-islets are robustly diminished following engraftment. Our results suggest that metabolic dysregulation is not a major safety concern for clinical SC-islet implantation after prolonged periods of engraftment.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"27 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between maternal glucose levels in pregnancy and offspring's metabolism and adiposity: an 18-year birth cohort study.","authors":"Yuzhi Deng,Hanbin Wu,Noel Y H Ng,Claudia H T Tam,Atta Y T Tsang,Michael H M Chan,Kenneth Ka Hei Lo,Chi Chiu Wang,Wing Hung Tam,Ronald C W Ma","doi":"10.1007/s00125-025-06476-6","DOIUrl":"https://doi.org/10.1007/s00125-025-06476-6","url":null,"abstract":"AIMS/HYPOTHESISThe study aimed to explore the association between maternal glucose levels in pregnancy and offspring's metabolism and adiposity at approximately 18 years of age.METHODSPregnant women from the Hong Kong Field Centre enrolled in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study underwent a 75 g OGTT at 24-32 gestational weeks. Offspring's metabolic and adiposity traits were assessed at 18 years postpartum. Associations were evaluated using multiple linear regression and logistic regression.RESULTSAmong the 506 mother-child pairs followed up to 18 years, maternal fasting plasma glucose (FPG) in pregnancy was positively associated with offspring's FPG (β = 0.06 [95% CI 0.02, 0.09]), while maternal 1 h plasma glucose (PG) showed a positive association with offspring's FPG (β = 0.05), 30 min PG (β = 0.21) and 2 h PG (β = 0.14). All maternal glycaemic levels were associated with an increased risk of offspring being overweight/obese, particularly maternal 1 h PG (OR 1.50 [95% CI 1.17, 1.93]). Offspring of mothers with gestational diabetes mellitus showed a higher prevalence of abnormal glucose tolerance (11.86% vs 7.97%), impaired fasting glucose (1.89% vs 0.49%) and impaired glucose tolerance (10.34% vs 7.13%) than offspring of mothers with normal glucose tolerance, although these associations did not reach statistical significance in fully adjusted models, underscoring the benefit of considering maternal glucose as a continuous trait.CONCLUSIONS/INTERPRETATIONMaternal glucose levels in pregnancy showed a long-term association with offspring's metabolic health into young adulthood, with continuous associations across the full maternal glucose spectrum, suggesting a graded effect of maternal hyperglycaemia on offspring's metabolic risk.","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"20 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased inflammation as well as decreased endoplasmic reticulum stress and translation differentiate pancreatic islets from donors with pre-symptomatic stage 1 type 1 diabetes and non-diabetic donors.","authors":"Adam C Swensen, Paul D Piehowski, Jing Chen, X'avia Y Chan, Shane S Kelly, Vladislav A Petyuk, Ronald J Moore, Lith Nasif, Elizabeth A Butterworth, Mark A Atkinson, Rohit N Kulkarni, Martha Campbell-Thompson, Clayton E Mathews, Wei-Jun Qian","doi":"10.1007/s00125-025-06417-3","DOIUrl":"10.1007/s00125-025-06417-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;Progression to type 1 diabetes is associated with genetic factors, the presence of autoantibodies and a decline in beta cell insulin secretion in response to glucose. Very little is known regarding the molecular changes that occur in human insulin-secreting beta cells prior to the onset of type 1 diabetes. Herein, we applied an unbiased proteomics approach to identify changes in proteins and potential mechanisms of islet dysfunction in islet-autoantibody-positive organ donors with pre-symptomatic stage 1 type 1 diabetes (HbA&lt;sub&gt;1c&lt;/sub&gt; ≤42 mmol/mol [6.0%]). We aimed to identify pathways in islets that are indicative of beta cell dysfunction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Multiple islet sections were collected through laser microdissection of frozen pancreatic tissues from organ donors positive for single or multiple islet autoantibodies (AAb&lt;sup&gt;+&lt;/sup&gt;, n=5), and age (±2 years)- and sex-matched non-diabetic (ND) control donors ( n=5) obtained from the Network for Pancreatic Organ donors with Diabetes (nPOD). Islet sections were subjected to MS-based proteomics and analysed with label-free quantification followed by pathway and functional annotations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Analyses resulted in ~4500 proteins identified with low false discovery rate (&lt;1%), with 2165 proteins reliably quantified in every islet sample. We observed large inter-donor variations that presented a challenge for statistical analysis of proteome changes between donor groups. We therefore focused on only the donors with stage 1 type 1 diabetes who were positive for multiple autoantibodies (mAAb&lt;sup&gt;+&lt;/sup&gt;, n=3) and genetic risk compared with their matched ND controls (n=3) for the final statistical analysis. Approximately 10% of the proteins (n=202) were significantly different (unadjusted p&lt;0.025, q&lt;0.15) for mAAb&lt;sup&gt;+&lt;/sup&gt; vs ND donor islets. The significant alterations clustered around major functions for upregulation in the immune response and glycolysis, and downregulation in endoplasmic reticulum (ER) stress response as well as protein translation and synthesis. The observed proteome changes were further supported by several independent published datasets, including a proteomics dataset from in vitro proinflammatory cytokine-treated human islets and single-cell RNA-seq datasets from AAb&lt;sup&gt;+&lt;/sup&gt; individuals.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions/interpretation: &lt;/strong&gt;In situ human islet proteome alterations in stage 1 type 1 diabetes centred around several major functional categories, including an expected increase in immune response genes (elevated antigen presentation/HLA), with decreases in protein synthesis and ER stress response, as well as compensatory metabolic response. The dataset serves as a proteomics resource for future studies on beta cell changes during type 1 diabetes progression and pathogenesis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Data availability: &lt;/strong&gt;The LC-MS raw datasets that support the findings of this study have ","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1463-1475"},"PeriodicalIF":8.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential associations of somatic and cognitive-affective symptoms of depression with inflammation and insulin resistance: cross-sectional and longitudinal results from the Emotional Distress Sub-Study of the GRADE study.","authors":"Dominic Ehrmann, Heidi Krause-Steinrauf, Diane Uschner, Hui Wen, Claire J Hoogendoorn, Gladys Crespo-Ramos, Caroline Presley, Valerie L Arends, Robert M Cohen, W Timothy Garvey, Thomas Martens, Holly J Willis, Andrea Cherrington, Jeffrey S Gonzalez","doi":"10.1007/s00125-025-06369-8","DOIUrl":"10.1007/s00125-025-06369-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Aims/hypothesis: &lt;/strong&gt;Insulin resistance and inflammation are components of a biological framework that is hypothesised to be shared by type 2 diabetes and depression. However, depressive symptoms include a large heterogeneity of somatic and cognitive-affective symptoms, and this may obscure the associations within this biological framework. Cross-sectional and longitudinal data were used to disentangle the contributions of insulin resistance and inflammation to somatic and cognitive-affective symptoms of depression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This secondary analysis used data from the Emotional Distress Sub-Study of the GRADE trial. Insulin resistance and inflammation were assessed using the HOMA-IR estimation and high-sensitivity C-reactive protein (hsCRP) levels, respectively, at baseline and at the study visits at year 1 and year 3 (HOMA-IR) and every 6 months (hsCRP) for up to 3 years of follow-up. Depressive symptoms were assessed at baseline using the Patient Health Questionnaire (PHQ-8), and a total score as well as symptom cluster scores for cognitive-affective and somatic symptoms were calculated. For the cross-sectional analyses, linear regression analyses were performed, with inflammation and insulin resistance at baseline as dependent variables. For the longitudinal analyses, linear mixed-effect regression analyses were performed, with inflammation and insulin resistance at the various time points as dependent variables. In all analyses, depressive symptoms (total score and symptom cluster scores) were the independent variables, controlled for important demographic, anthropometric and metabolic confounders. For the analysis of insulin resistance (HOMA-IR), data from 1321 participants were analysed. For the analysis of inflammation (hsCRP), data from 1739 participants were analysed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In cross-sectional analysis and after adjustment for potential confounders, a one-unit increase in PHQ-8 total score was significantly associated with a 0.8% increase in HOMA-IR (p=0.007), but not with hsCRP (0.6% increase, p=0.283). The somatic symptom score was associated with a 5.8% increase in HOMA-IR (p=0.004). Single-item analyses of depressive symptoms showed that fatigue (3.6% increase, p=0.002) and increased/decreased appetite (3.5% increase, p=0.009) were significantly associated with HOMA-IR cross-sectionally. The cognitive-affective symptom score was not significantly associated with HOMA-IR at baseline. In longitudinal analyses, a one-unit increase in PHQ-8 total score was significantly associated with a 0.8% increase in hsCRP over time (p=0.014), but not with HOMA-IR over time (0.1% decrease, p=0.564). Again, only the somatic symptom cluster was significantly associated with hsCRP over time (5.2% increase, p=0.017), while the cognitive-affective symptom score was not.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion/interpretation: &lt;/strong&gt;The results highlight the associations of depressive symptoms with markers ","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":" ","pages":"1403-1415"},"PeriodicalIF":8.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12176517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Raising the bar for publication of Mendelian randomisation studies in Diabetologia.","authors":"Laura J Corbin,Jordi Merino,Tove Fall,Christian Herder","doi":"10.1007/s00125-025-06484-6","DOIUrl":"https://doi.org/10.1007/s00125-025-06484-6","url":null,"abstract":"","PeriodicalId":11164,"journal":{"name":"Diabetologia","volume":"89 1","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144521216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}