ORCID Profile
0000-0002-1531-4294
Current Organisations
IT University of Copenhagen
,
Steno Diabetes Center Copenhagen
,
The Capital Region of Denmark
,
Københavns Universitet
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Publisher: Wiley
Date: 21-04-2012
Publisher: Wiley
Date: 17-02-2017
DOI: 10.1111/DOM.12840
Publisher: BMJ
Date: 29-01-2013
DOI: 10.1136/BMJ.F324
Publisher: Oxford University Press (OUP)
Date: 12-12-2012
DOI: 10.1093/IJE/DYS173
Abstract: The Chronic Kidney Disease Prognosis Consortium (CKD-PC) was established in 2009 to provide comprehensive evidence about the prognostic impact of two key kidney measures that are used to define and stage CKD, estimated glomerular filtration rate (eGFR) and albuminuria, on mortality and kidney outcomes. CKD-PC currently consists of 46 cohorts with data on these kidney measures and outcomes from >2 million participants spanning across 40 countries/regions all over the world. CKD-PC published four meta-analysis articles in 2010-11, providing key evidence for an international consensus on the definition and staging of CKD and an update for CKD clinical practice guidelines. The consortium continues to work on more detailed analysis (subgroups, different eGFR equations, other exposures and outcomes, and risk prediction). CKD-PC preferably collects in idual participant data but also applies a novel distributed analysis model, in which each cohort runs statistical analysis locally and shares only analysed outputs for meta-analyses. This distributed model allows inclusion of cohorts which cannot share in idual participant level data. According to agreement with cohorts, CKD-PC will not share data with third parties, but is open to including further eligible cohorts. Each cohort can opt in/out for each topic. CKD-PC has established a productive and effective collaboration, allowing flexible participation and complex meta-analyses for studying CKD.
Publisher: Springer Science and Business Media LLC
Date: 25-11-2027
Publisher: Springer Science and Business Media LLC
Date: 2010
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1038/KI.2010.550
Publisher: American College of Physicians
Date: 03-2021
DOI: 10.7326/M20-5938
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 19-09-2019
Abstract: Although studies show that diabetic kidney disease has a heritable component, searches for the genetic determinants of this complication of diabetes have had limited success. In this study, a new international genomics consortium, the JDRF funded Diabetic Nephropathy Collaborative Research Initiative, assembled nearly 20,000 s les from participants with type 1 diabetes, with and without kidney disease. The authors found 16 new diabetic kidney disease–associated loci at genome-wide significance. The strongest signal centers on a protective missense coding variant at COL4A3 , a gene that encodes a component of the glomerular basement membrane that, when mutated, causes the progressive inherited nephropathy Alport syndrome. These GWAS-identified risk loci may provide insights into the pathogenesis of diabetic kidney disease and help identify potential biologic targets for prevention and treatment. Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown. To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function. Our GWAS meta-analysis included association results for up to 19,406 in iduals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain ( COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in COL4A3 are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition ( BMP7) or renal biology ( COLEC11 and DDR1 ). The 16 diabetic kidney disease–associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 25-08-2010
DOI: 10.1126/SCITRANSLMED.3001249
Abstract: Recommendations about structuring proteomic biomarker studies should increase the probability that such markers will be clinically useful.
Publisher: American Diabetes Association
Date: 27-04-2018
DOI: 10.2337/DB17-0914
Abstract: Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication s les, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 × 10−8) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased s le sizes will continue to provide more robust inference regarding risk variant discovery for DKD.
Publisher: Wiley
Date: 08-03-2021
DOI: 10.1111/DOM.14350
Abstract: To determine whether metformin's effects on carotid artery intima‐media thickness (cIMT) in type 1 diabetes differ according to smoking status. Regression model effect estimates for the effect of metformin versus placebo (double‐blind) on carotid IMT were calculated as a subgroup analysis of the REMOVAL trial. In 428 randomized participants (227 never‐smokers, 201 ever‐smokers), averaged mean carotid IMT progression (per year) was reduced by metformin versus placebo in never‐smokers (−0.012 mm, 95% CI −0.021 to −0.002 p = .0137) but not in ever‐smokers (0.003 mm, 95% CI −0.008 to 0.014 p = .5767) and similarly in non‐current smokers (−0.008 mm, 95% CI −0.015 to −0.00001 p = .0497) but not in current smokers (0.013 mm, 95% CI −0.007 to 0.032 p = .1887). Three‐way interaction terms (treatment*time*smoking status) were significant for never versus ever smoking ( p = .0373, prespecified) and non‐current versus current smoking ( p = .0496, exploratory). Averaged maximal carotid IMT progression (per year) was reduced by metformin versus placebo in never‐smokers (−0.020 mm, 95% CI −0.034 to −0.006 p = .0067) but not in ever‐smokers (−0.006 mm, 95% CI −0.020 to 0.008 p = .4067), although this analysis was not supported by a significant three‐way interaction term. This subgroup analysis of the REMOVAL trial provides additional support for a potentially wider role of adjunct metformin therapy in cardiovascular risk management in type 1 diabetes, particularly for in iduals who have never smoked cigarettes.
Publisher: Oxford University Press (OUP)
Date: 30-01-2021
DOI: 10.1093/HMG/DDAB023
Abstract: Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) in iduals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10−10) in the combined meta-analyses of all s les. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10−122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.KINT.2022.06.013
Abstract: The Kidney Disease: Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (CKD) represents a focused update of the KDIGO 2020 guideline on the topic. The guideline targets a broad audience of clinicians treating people with diabetes and CKD. Topic areas for which recommendations are updated based on new evidence include Chapter 1: Comprehensive care in patients with diabetes and CKD and Chapter 4: Glucose-lowering therapies in patients with type 2 diabetes (T2D) and CKD. The content of previous chapters on Glycemic monitoring and targets in patients with diabetes and CKD (Chapter 2), Lifestyle interventions in patients with diabetes and CKD (Chapter 3), and Approaches to management of patients with diabetes and CKD (Chapter 5) has been deemed current and was not changed. This guideline update was developed according to an explicit process of evidence review and appraisal. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence, and the strength of recommendations followed the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. Limitations of the evidence are discussed, and areas for which additional research is needed are presented.
Publisher: American Diabetes Association
Date: 15-08-2022
DOI: 10.2337/DC22-0294
Publisher: Springer Science and Business Media LLC
Date: 03-11-2017
Publisher: Elsevier BV
Date: 11-2012
Publisher: Elsevier BV
Date: 11-2012
Publisher: American Diabetes Association
Date: 15-07-2015
DOI: 10.2337/DC15-0851
Abstract: Mannan-binding lectin (MBL) is a complement-activating carbohydrate-recognizing molecule associated with diabetic nephropathy. MBL is associated with all-cause mortality in type 2 diabetes, but whether MBL is associated with mortality in type 1 diabetes remains unknown. We therefore aimed to investigate this. We studied an existing 12-year prospective cohort with type 1 diabetes with 198 patients with diabetic nephropathy (121 men, age 41 years [95% CI 40–42], estimated glomerular filtration rate [eGFR] 67 mL/min/1.73 m2 [95% CI 63–70]) and 174 normoalbuminuric patients (103 men, age 43 years [95% CI 41–44], eGFR 93 mL/min/1.73 m2 [95% CI 91–95]). Mortality rates were compared according to the concentration-determining MBL2 genotype or the MBL concentration. Patients were classified as having high or low MBL expression genotypes. The effect of MBL concentration was estimated by comparing patients with MBL concentrations above or below the median. Ninety-eight patients died during follow-up. The unadjusted hazard ratio (HR) for all-cause mortality was 1.61 (95% CI 1.07–2.43) for patients with high MBL expression genotypes versus patients with low MBL expression genotypes (P = 0.023). All-cause mortality was higher in patients with MBL concentrations above the median than in patients with MBL concentrations below the median (unadjusted HR 1.90 [95% CI 1.26–2.87], P = 0.002). High MBL expression genotypes and high MBL concentrations are both associated with increased mortality rates in type 1 diabetes compared with low MBL expression genotypes and low MBL concentrations.
Publisher: Springer Science and Business Media LLC
Date: 21-08-2018
Publisher: Springer Science and Business Media LLC
Date: 28-07-2014
DOI: 10.1007/S00125-014-3332-7
Abstract: Increasing evidence links complement activation through the lectin pathway to diabetic nephropathy. Adverse complement recognition of proteins modified by glycation has been suggested to trigger complement auto-attack in diabetes. H-ficolin (also known as ficolin-3) is a pattern recognition molecule that activates the complement cascade on binding to glycated surfaces, but the role of H-ficolin in diabetic nephropathy is unknown. We aimed to investigate the association between circulating H-ficolin levels and the incidence of microalbuminuria in type 1 diabetes. We measured baseline H-ficolin levels and tracked the development of persistent micro- and macroalbuminuria in a prospective 18 year observational follow-up study of an inception cohort of 270 patients with newly diagnosed type 1 diabetes. Patients were followed for a median of 18 years (range 1-22 years). During follow-up, 75 patients developed microalbuminuria, defined as a persistent urinary albumin excretion rate (UAER) above 30 mg/24 h. When H-ficolin levels were ided into quartile groups an unadjusted Cox proportional hazards regression model showed a significant association with risk of incident microalbuminuria during follow-up (HR, fourth vs first quartile, 2.45 95% CI 1.24, 4.85) (p = 0.01). This remained significant after adjusting for HbA1c, systolic blood pressure, smoking and baseline UAER (HR 2.09 95% CI 1.03, 4.25) (p = 0.04). Our data suggest that high levels of the complement activating molecule H-ficolin are associated with an increased risk of future progression to microalbuminuria in patients with newly diagnosed type 1 diabetes.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2010
Publisher: Springer Science and Business Media LLC
Date: 09-2021
Publisher: Springer Science and Business Media LLC
Date: 30-07-2015
DOI: 10.1038/NRDP.2015.18
Publisher: Oxford University Press (OUP)
Date: 03-02-2010
DOI: 10.1093/NDT/GFQ025
Publisher: American College of Physicians
Date: 03-2023
DOI: 10.7326/M22-2904
Publisher: Elsevier BV
Date: 08-2017
Publisher: American Medical Association (AMA)
Date: 12-12-2012
Publisher: Elsevier BV
Date: 2012
Publisher: Wiley
Date: 11-04-2017
DOI: 10.1002/DMRR.2895
Abstract: Evidence links the lectin pathway of complement activation to diabetic kidney disease. Upon carbohydrate-recognition by pattern-recognition molecules, eg, mannan-binding lectin (MBL), the MBL-associated serine protease (MASP-2) is activated and initiates the complement cascade. The MASP2 gene encodes MASP-2 and the alternative splice product MBL-associated protein 19 (MAp19). Both MAp19 and MASP-2 circulate in complex with MBL. We tested the hypothesis that MAp19 and MASP-2 concentrations predict the risk of incident microalbuminuria. Baseline MAp19 and MASP-2 were measured in 270 persons with newly diagnosed type 1 diabetes tracked for incidence of persistent microalbuminuria in a prospective observational 18-year-follow-up study. Seventy-five participants (28%) developed microalbuminuria during follow-up. MBL-associated protein 19 concentrations were higher in participants that later progressed to microalbuminuria as compared with those with persistent normoalbuminuria (268 ng/mL [95% CI, 243-293] vs 236 ng/mL [95% CI, 223-250], P = .02). Participants with MAp19 concentration within the highest quartile of the cohort had an increased risk of microalbuminuria as compared with participants with MAp19 concentration within the combined lower 3 quartiles in unadjusted Cox analysis, hazard ratio 1.86 ([95% CI, 1.17-2.96], P = .009). This remained significant in adjusted models, eg, adjusting for age, sex, HbA In conclusion, the results show an association between baseline MAp19 concentration and the incidence of microalbuminuria in an 18-year-follow-up study on persons with newly diagnosed type 1 diabetes.
Publisher: Springer Science and Business Media LLC
Date: 18-05-2022
DOI: 10.1186/S13063-022-06259-Z
Abstract: The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from in iduals with newly diagnosed type 1 diabetes combined with centralised collection of clinical s les to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of phase 2 clinical trials. In this context, we have developed a Master Protocol, based on the “backbone” of the INNODIA natural history study, which we believe could improve the delivery of phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in in iduals with newly diagnosed type 1 diabetes. Although many IMPs have demonstrated potential efficacy in phase 2 studies, few subsequent phase 3 studies have confirmed these benefits. Currently, phase 2 drug development for this indication is limited by poor evaluation of drug dosage and lack of mechanistic data to understand variable responses to the IMPs. Identification of biomarkers which might permit more robust stratification of participants at baseline has been slow. The Master Protocol provides (1) standardised assessment of efficacy and safety, (2) comparable collection of mechanistic data, (3) the opportunity to include adaptive designs and the use of shared control groups in the evaluation of combination therapies, and (4) benefits of greater understanding of endpoint variation to ensure more robust s le size calculations and future baseline stratification using existing and novel biomarkers.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.KINT.2022.05.021
Abstract: Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 in iduals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 in iduals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics.
Publisher: Oxford University Press (OUP)
Date: 29-05-2023
DOI: 10.1093/EURHEARTJ/EHAD260
Abstract: To develop and validate a recalibrated prediction model (SCORE2-Diabetes) to estimate the 10-year risk of cardiovascular disease (CVD) in in iduals with type 2 diabetes in Europe. SCORE2-Diabetes was developed by extending SCORE2 algorithms using in idual-participant data from four large-scale datasets comprising 229 460 participants (43 706 CVD events) with type 2 diabetes and without previous CVD. Sex-specific competing risk-adjusted models were used including conventional risk factors (i.e. age, smoking, systolic blood pressure, total, and HDL-cholesterol), as well as diabetes-related variables (i.e. age at diabetes diagnosis, glycated haemoglobin [HbA1c] and creatinine-based estimated glomerular filtration rate [eGFR]). Models were recalibrated to CVD incidence in four European risk regions. External validation included 217 036 further in iduals (38 602 CVD events), and showed good discrimination, and improvement over SCORE2 (C-index change from 0.009 to 0.031). Regional calibration was satisfactory. SCORE2-Diabetes risk predictions varied several-fold, depending on in iduals’ levels of diabetes-related factors. For ex le, in the moderate-risk region, the estimated 10-year CVD risk was 11% for a 60-year-old man, non-smoker, with type 2 diabetes, average conventional risk factors, HbA1c of 50 mmol/mol, eGFR of 90 mL/min/1.73 m2, and age at diabetes diagnosis of 60 years. By contrast, the estimated risk was 17% in a similar man, with HbA1c of 70 mmol/mol, eGFR of 60 mL/min/1.73 m2, and age at diabetes diagnosis of 50 years. For a woman with the same characteristics, the risk was 8% and 13%, respectively. SCORE2-Diabetes, a new algorithm developed, calibrated, and validated to predict 10-year risk of CVD in in iduals with type 2 diabetes, enhances identification of in iduals at higher risk of developing CVD across Europe.
Publisher: Massachusetts Medical Society
Date: 03-12-2020
Publisher: American Diabetes Association
Date: 14-08-2017
DOI: 10.2337/DCI17-0026
Publisher: American Medical Association (AMA)
Date: 09-05-2012
Publisher: American Medical Association (AMA)
Date: 20-09-2019
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1038/KI.2013.553
Publisher: Oxford University Press (OUP)
Date: 08-03-2011
DOI: 10.1093/NDT/GFR102
Abstract: In vitro and animal experiments have shown inhibiting effects of angiotensin receptor blockers (ARBs) on the formation of advanced glycation end products (AGEs), which are known to be involved in the development of cardiovascular complications in diabetes. However, sufficient human data to confirm such beneficial effects of ARBs on AGEs are lacking. Therefore, we investigated the effects of irbesartan treatment on plasma levels of the AGEs N(ε)(1-carboxymethyl)lysine (CML) and N(ε)(1-carboxyethyl)lysine (CEL) in hypertensive patients with type 2 diabetes and microalbuminuria. We analysed data from a multicentre, double-blind, parallel, randomized controlled trial in patients with type 2 diabetes and microalbuminuria, the primary goal of which was to examine the renoprotective effects of irbesartan treatment (150 or 300 mg daily). Secondary end points included plasma CML and CEL in the treatment arm receiving 300 mg irbesartan (n = 139) and in the placebo group (n = 125). Effects of treatment at 1- and 2-year follow-up were analysed by means of generalized estimating equations according to an intention-to-treat principle. Levels of CML and CEL did not differ between groups at baseline. No significant changes were observed in CML and CEL over time in either group and there was no effect of treatment on CML and CEL at any time-point. Mean differences for the irbesartan versus placebo group over time were -0.96 μmol/mol lysine (95% confidence interval: -3.43 to 1.51) for CML and -0.10 μmol/mol lysine (-0.76 to 0.56) for CEL. Long-term irbesartan treatment does not influence plasma levels of the AGE CML and CEL in patients with type 2 diabetes and microalbuminuria.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Wiley
Date: 29-04-2010
Abstract: Purpose and experimental design : Diabetic nephropathy (DN) is the most common cause of end‐stage renal disease and improved biomarkers would help identify high‐risk in iduals. The aim of this study was to discover candidate biomarkers for DN in the plasma peptidome in an in‐house cross‐sectional cohort ( n =122) of type 1 diabetic patients diagnosed with normo‐, micro‐, and macroalbuminuria. Results : Automated, high‐throughput, and reproducible (interassay median CV: 13–14%) plasma peptide profiling protocols involving RPC18 and weak cation exchange magnetic beads on a liquid handling workstation with a MALDI‐TOF‐MS readout were successfully established. Using these protocols and a combined univariate (Kruskal–Wallis) and multivariate (independent component analysis) statistical analysis approach, ten single peptides and three multi‐peptide candidate biomarkers were found. Employment of RPC18 and weak cation exchange magnetic beads proved to be complementary. Conclusions and clinical relevance : The proteins found in this study, including C3f and apolipoprotein C‐I, represent new candidate biomarkers for DN from the plasma peptidome. The automated procedures and implementation of independent components analysis provide a fast and informative system for analyzing in idual patient s les in protein biomarker discovery.
Publisher: American Diabetes Association
Date: 21-01-2022
DOI: 10.2337/DC21-1944
Publisher: Elsevier BV
Date: 05-2020
Publisher: Springer Science and Business Media LLC
Date: 05-08-2019
Publisher: Public Library of Science (PLoS)
Date: 20-09-2012
Publisher: Springer Science and Business Media LLC
Date: 14-07-2020
DOI: 10.1038/S41598-020-68130-Y
Abstract: Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). In iduals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual ß-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D in iduals showed elevated levels of picolinic acid as compared to the healthy in iduals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in in iduals with long-term T1D.
Publisher: Springer Science and Business Media LLC
Date: 07-05-2020
Publisher: American Society for Clinical Investigation
Date: 15-02-2023
DOI: 10.1172/JCI160959
Publisher: MDPI AG
Date: 14-09-2023
DOI: 10.3390/PH16091298
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-10-2023
Publisher: IEEE
Date: 12-2010
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14177
Publisher: Elsevier BV
Date: 08-2017
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.KINT.2016.09.010
Abstract: The prevalence of diabetes around the world has reached epidemic proportions and is projected to increase to 642 million people by 2040. Diabetes is already the leading cause of end-stage kidney disease (ESKD) in most developed countries, and the growth in the number of people with ESKD around the world parallels the increase in diabetes. The presence of kidney disease is associated with a markedly elevated risk of cardiovascular disease and death in people with diabetes. Several new therapies and novel investigational agents targeting chronic kidney disease patients with diabetes are now under development. This conference was convened to assess our current state of knowledge regarding optimal glycemic control, current antidiabetic agents and their safety, and new therapies being developed to improve kidney function and cardiovascular outcomes for this vulnerable population.
Publisher: Springer Science and Business Media LLC
Date: 11-02-2015
DOI: 10.1038/NATURE14132
No related grants have been discovered for peter rossing.