| 1. |
- Allesøe, Rosa Lundbye, et al.
(författare)
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Discovery of drug–omics associations in type 2 diabetes with generative deep-learning models
- 2023
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Ingår i: Nature Biotechnology. - : Springer Nature. - 1087-0156 .- 1546-1696. ; 41:3, s. 399-408
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Tidskriftsartikel (refereegranskat)abstract
- The application of multiple omics technologies in biomedical cohorts has the potential to reveal patient-level disease characteristics and individualized response to treatment. However, the scale and heterogeneous nature of multi-modal data makes integration and inference a non-trivial task. We developed a deep-learning-based framework, multi-omics variational autoencoders (MOVE), to integrate such data and applied it to a cohort of 789 people with newly diagnosed type 2 diabetes with deep multi-omics phenotyping from the DIRECT consortium. Using in silico perturbations, we identified drug–omics associations across the multi-modal datasets for the 20 most prevalent drugs given to people with type 2 diabetes with substantially higher sensitivity than univariate statistical tests. From these, we among others, identified novel associations between metformin and the gut microbiota as well as opposite molecular responses for the two statins, simvastatin and atorvastatin. We used the associations to quantify drug–drug similarities, assess the degree of polypharmacy and conclude that drug effects are distributed across the multi-omics modalities.
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| 2. |
- Munch Roager, Henrik, et al.
(författare)
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Whole grain-rich diet reduces body weight and systemic low-grade inflammation without inducing major changes of the gut microbiome: A randomised cross-over trial
- 2019
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 68:1, s. 83-93
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Tidskriftsartikel (refereegranskat)abstract
- Objective T o investigate whether a whole grain diet alters the gut microbiome and insulin sensitivity, as well as biomarkers of metabolic health and gut functionality. Design 60 Danish adults at risk of developing metabolic syndrome were included in a randomised cross-over trial with two 8-week dietary intervention periods comprising whole grain diet and refined grain diet, separated by a washout period of =6 weeks. The response to the interventions on the gut microbiome composition and insulin sensitivity as well on measures of glucose and lipid metabolism, gut functionality, inflammatory markers, anthropometry and urine metabolomics were assessed. Results 50 participants completed both periods with a whole grain intake of 179±50 g/day and 13±10 g/day in the whole grain and refined grain period, respectively. Compliance was confirmed by a difference in plasma alkylresorcinols (p<0.0001). Compared with refined grain, whole grain did not significantly alter glucose homeostasis and did not induce major changes in the faecal microbiome. Also, breath hydrogen levels, plasma short-chain fatty acids, intestinal integrity and intestinal transit time were not affected. The whole grain diet did, however, compared with the refined grain diet, decrease body weight (p<0.0001), serum inflammatory markers, interleukin (IL)-6 (p=0.009) and C-reactive protein (p=0.003). The reduction in body weight was consistent with a reduction in energy intake, and IL-6 reduction was associated with the amount of whole grain consumed, in particular with intake of rye. Conclusion C ompared with refined grain diet, whole grain diet did not alter insulin sensitivity and gut microbiome but reduced body weight and systemic lowgrade inflammation.
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| 3. |
- Bizzotto, Roberto, et al.
(författare)
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Processes Underlying Glycemic Deterioration in Type 2 Diabetes : An IMI DIRECT Study
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44:2, s. 511-518
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression. RESULTS: Faster HbA1c progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role. CONCLUSIONS: Deteriorating insulin sensitivity and β-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, β-cell function, and insulin clearance may be relevant to prevent progression.
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| 4. |
- Gudmundsdottir, Valborg, et al.
(författare)
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Whole blood co-expression modules associate with metabolic traits and type 2 diabetes : an IMI-DIRECT study
- 2020
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Ingår i: Genome Medicine. - : BioMed Central. - 1756-994X .- 1756-994X. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D.Methods: Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts.Results: We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling.Conclusions: Our results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.
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| 5. |
- Hansen, Lea B.S., et al.
(författare)
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A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults
- 2018
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723 .- 2041-1723. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- © 2018, The Author(s). Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.
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| 6. |
- Andersson, Ronny, et al.
(författare)
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Digitalt byggeri og svensk og dansk byggeklkassifikation i et Öresundsperspektiv
- 2008
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Rapporten som er opdelt i fire delrapporter er udarbejdet i projektet ”ICT i byggesektoren – Netværk til udvikling”, som er delfinansieret af regionsudviklingsprojektet Interreg IIIA. ”ICT i byggesektoren – netværk til udvikling”. Projektet styrer mod, via et netværk om IKT omkring Øresund, at muliggøre bedre, billigere og mere miljørigtigt byggeri og boliger, ved at identificere og fjerne hindringer, såvel som at skabe en udvikling. Projektet har tre effektmålsætninger: • En plan for, hvordan et fremtidigt samarbejde mellem Øresundsregionens universitet, institut og offentlige og private virksomheder etc. kan fremmes. • Gennemførelse af et casestudie i interoperabilitet mellem byggesektoren i DK og SE i et konkret byggeprojekt/vidensområde. • Gennemgang af et program til uddannelse inden for industrielt byggeri. Byggesektoren står over for den store udfordring at skulle implementere ny informations- og kommunikationsteknologi (IKT) i byggeprocessen – digitalisering. Det er ikke kun nye IT-systemer, der skal indføres. Det handler lige så meget om nye arbejdsmetoder og rollefordelinger og om at skabe bedre integration mellem parterne, samt nye måder at organisere sig på, nye samarbejdsformer og dermed nye forretningsgrundlag for virksomhederne. At digitaliseringen er en dynamisk proces betyder, at disse værktøjer er genstand for forandringer løbende, i og med at byggeriets parter opbygger større kompetencer indenfor IKT og får adgang til software, der forbedrer interoperabiliteten. I et sådant udviklingsforløb vil et samarbejde og parallelle studier på hver side af Øresund kunne bidrage til at kvalificere udviklingsresultaterne både i Danmark og i Sverige. Alle fyre delrapporter fokuserer på spørgsmålet om hvordan man kan sikre interoperabilitet mellem dansk og svensk byggeri. Den danske og den svenske byggesektor står over for de samme udfordringer i forbindelse med at udvikle og opdatere retningslinier og standarder, der sikrer interoperabilitet mellem parterne, når der anvendes nye, 3D objektorienterede arbejdsmetoder, byggeklassifikation, og når der generelt udveksles information og kommunikation mellem parterne i byggeprocessen. Studiet har som formål at undersøge mulighederne for at skabe en fælles informationsplatform for derigennem at sikre kvaliteten i dansk/svenske byggeprojekter – interregionale projekter. Studiet har udmøntet sig i fire delrapporter: Del rapport 1 – DBK, BSAB og anvendelsen af 3D-arbejdsmetode i ”The Icelandic Concert and Conference Centre” - et dansk/svensk perspektiv – analyserer/sammenligner det danske initiativ "Det Digitale Byggeri", Dansk Bygge Klassifikation (DBK), 3D arbejdsmetode og det svenske klassifikationssystem BSAB. Endvidere er der et eksempel på, hvordan ingeniørfirmaet Rambøll arbejder med 3D arbejdsmetode i praksis i projektet The Icelandic Concert and Conference Centre. Analysen viser nogle forskelle mellem de to klassifikationer. Det danske arbejde med Det Digitale Byggeri sigter mod at skabe forudsætninger for en overgang fra 2D tegningsbaseret informationshåndtering til 3D objektorienteret informationshåndtering i danske byggeprojekter. Her spiller byggeklassifikationen en vigtig rolle ved identifikation og navngivning af byggeobjekter. Studiet har vist forskellige opfattelser mellem det svenske byggeklassifikationssystem BSAB og det danske DBK med hensyn til klassifikation og objektorienteret modellering. Begge standarder siges at følge den internationale standard for byggeklassifikation ISO 12006-2. En vigtig forskel gælder synet på begrebet bygningsdel. BSAB følger ISO rammestandarden, som foreskriver, at bygningsdele identificeres ud fra et funktionelt aspekt. DBK anvender det, man benævner ”produktaspektet” - som man mener svarer til, hvordan ”de fleste ser på bygningsdele i dag” - til at identificere bygningsdele. Inddelingsgrundlaget er umiddelbart ikke i overensstemmelse med ISO-standarden. Motivet er, at man vil støtte successiv bestemmelse af egenskaber. En dybere undersøgelse er nødvendig for at afgøre, hvordan DBK og BSAB relaterer til ISO-standarden. I den beskrevne case, The Icelandic Concert and Conference Centre, anvendes en tilpasset DBK løsning og der anvendes blandt andet dele af 3D arbejdsmetode. Rambølls erfaringer med digitalisering er gode, det har givet overblik over mere komplekse geometriske og tekniske problemstillinger. Rambøll anvender forskellige digitaliseringselementer: 3D projektering (3D koncept/model), implementering af DBK, projektweb, BIM (fællesmodel), CFD beregninger, 3D-modeller (CAD) med mulighed for 3D plotning. Der er dog nogle begrænsninger i udveksling af data mellem forskellige systemer, pga. de digitale formaters forskellige indhold af information, her fremføres DWG formatet frem for IFC, når det er muligt. Der mangler stadig eksempler på en fuldskala afprøvning af DBK og DDB. Mange gode kræfter arbejder på at få en sådan afprøvning i stand, hvor relationen til ISO og BSAB også kunne blive inddraget. Del rapport 2 – Implementeringen af Det Digitale Byggeri’s standarder og arbejdsmetoder i Danmark - et udgangspunkt for et dansk/svensk samarbejde – beskriver de væsentlige standarder og retningslinier inden for det danske indsatsområde Det Digitale Byggeri, DDB, fra 2003 til 2006. Specielt er det formålet at beskrive baggrunden for dem, implementeringen af dem i den danske kontekst indenfor den relativt korte indkøringsperiode og udviklingsmuligheder og visionerne for digitaliseringen i Danmark. Der er fokus på 3D arbejdsmetoden og dens implementering i den danske praksis og specielt de udviklingstendenser, der er registreret. Baggrunden beskrives for metoden samt gennem eksempler på forskellige IKT- niveauer i forskellige projekter gives der et overblik over metodens anvendelsesmuligheder og dens rummelighed i forhold til konkret projekthåndtering. Her er Danmark langt fremme og vil kunne inspirere de svenske tiltag på området, Bygghandlinger 90, Digitala leveranser för bygg och forvaltning’, som for øjeblikket er under revision. Det samme gælder den danske ’3D CAD Manual 2006’, som ligeledes nu er under revision mod en version 2007 eller 2008. Et andet fokusområde er den danske klassifikation DBK. Den er på nuværende tidspunkt ikke implementeret i den danske praksis af mange forskellige grunde, og det er derfor ikke muligt at beskrive konkrete erfaringer og potentialer. Det svenske BSAB-system har haft en længere indkøringsperiode, over 10 år, og vil derfor kunne bidrage til revisionen og færdiggørelsen af DBK til et implementerbart niveau og specielt til en afklaring af, hvad klassifikation kan anvendes til i byggesektoren. En overordnet undersøgelse af de danske og svenske standarder inden for en objektorienteret arbejdsmetode viser, at de bygger på de samme grundlæggende internationale standarder og at man grundlæggende arbejder med de samme modelkoncepter og udvekslingsstrategier. Det danske system har haft meget fokus på bygningsmodelleringen og har udviklet et system af modeltyper (systemmodel-fagmodel-fællesmodel) og informationsniveauer, som håndterer specifikationen af bygningsobjekter og udvekslingen af projektinformationer. Der har været knapt så megen fokus på specifikation og udveksling af dokumenter. Dette løses gennem de revisioner af standarderne, der pågår for tiden. På klassifikationssiden har Danmark været handicappet af, at der først er blevet udviklet et dansk klassifikationssystem, DBK, til ikrafttrædelse af bygherrekravene den 1. januar 2007. Der tilbagestår en seriøs test af systemet og en implementering i software og i metoder til bygningsmodellering og udveksling. I tests og udviklingsprojekter vil en sammenligning med og inspiration fra det svenske BSAB være ønskelig. Rapporten anbefaler at etablere et interregionalt samarbejde på tværs af Øresund inden for de to hovedområder: 3D objektorienteret arbejdsmetode og interoperabilitet og Byggeklassifikation som struktureringsværktøj i byggeprocessen. På den ene side vil det kvalificere udviklingen af standarderne i begge lande, som løbende vil være under revision, og dels vil dette medføre, at de to landes standarder og rekommandationer vil nærme sig hinanden, så man også interregionalt vil kunne opnå en større interoperabilitet i byggeprojekter. Til denne del er der også et bilag: DBK Dansk Bygge Klassifikation 2006. Del rapport 3 - En teoretisk undersøgelse af dagens svenske nationale ”guidelines” – er en svensk gennemgang af ” Bygghandlingar 90” Byggbranschens rekommendationer för redovisning av byggprojekt, del 8, Digitala leveranser för bygg och förvaltning”, der på tilsvarende vis skal blive det lettilgængelige standardværk, som vi på de projekterende kontorer anvender som vejledning og guide Undersøgelsen begrænser sig til det seneste, vi kan se i nationale svenske guidelines, Forslagsudgaven af Bygghandlingar 90 del 8, BH90. Denne undersøgelse består af en kort beskrivelse af baggrund og hovedtræk i Bygghandlingar 90 samt kommentarer og kritiske synspunkter om indhold og anbefalinger i BH90. Bygghandlingar 90 i den udgave, den tidligere har været anvendt, har været en relativ lettilgængelig ledestjerne under projekteringen, dette gælder såvel benævnelser som leverancer mm. Håbet er, at den reviderede og opdaterede BH90 på tilsvarende vis skal blive det lettilgængelige standardværk, som de projekterende kontorer anvender som vejledning og guide. Som base for arbejdet indgår den foreliggende Bygghandlinger 90 del 8. I forhold til denne publikation er forslagsudgavens disposition dog væsentligt forandret og indholdet udvidet. Anbefalingerne skal omfatte håndtering af alle slags digitale dokumenter, både tekniske og administrative. Afgrænsningen skal ske i forhold til dokument/informationsmængder, som indgår i processe
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| 7. |
- Atabaki-Pasdar, Naeimeh, et al.
(författare)
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Inferring causal pathways between metabolic processes and liver fat accumulation: an IMI DIRECT study
- 2021
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) often co-occur. Defining causal pathways underlying this relationship may help optimize the prevention and treatment of both diseases. Thus, we assessed the strength and magnitude of the putative causal pathways linking dysglycemia and fatty liver, using a combination of causal inference methods.Measures of glycemia, insulin dynamics, magnetic resonance imaging (MRI)-derived abdominal and liver fat content, serological biomarkers, lifestyle, and anthropometry were obtained in participants from the IMI DIRECT cohorts (n=795 with new onset T2D and 2234 individuals free from diabetes). UK Biobank (n=3641) was used for modelling and replication purposes. Bayesian networks were employed to infer causal pathways, with causal validation using two-sample Mendelian randomization.Bayesian networks fitted to IMI DIRECT data identified higher basal insulin secretion rate (BasalISR) and MRI-derived excess visceral fat (VAT) accumulation as the features of dysmetabolism most likely to cause liver fat accumulation; the unconditional probability of fatty liver (>5%) increased significantly when conditioning on high levels of BasalISR and VAT (by 23%, 32% respectively; 40% for both). Analyses in UK Biobank yielded comparable results. MR confirmed most causal pathways predicted by the Bayesian networks.Here, BasalISR had the highest causal effect on fatty liver predisposition, providing mechanistic evidence underpinning the established association of NAFLD and T2D. BasalISR may represent a pragmatic biomarker for NAFLD prediction in clinical practice.Competing Interest StatementHR is an employee and shareholder of Sanofi. MIM: The views expressed in this article are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. MIM has served on advisory panels for Pfizer, NovoNordisk and Zoe Global, has received honoraria from Merck, Pfizer, Novo Nordisk and Eli Lilly, and research funding from Abbvie, Astra Zeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, NovoNordisk, Pfizer, Roche, Sanofi Aventis, Servier, and Takeda. As of June 2019, MIM is an employee of Genentech, and a holder of Roche stock. AM is a consultant for Lilly and has received research grants from several diabetes drug companies. PWF has received research grants from numerous diabetes drug companies and fess as consultant from Novo Nordisk, Lilly, and Zoe Global Ltd. He is currently the Scientific Director in Patient Care at the Novo Nordisk Foundation. Other authors declare non competing interests.Funding StatementThe work leading to this publication has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement 115317 (DIRECT) resources of which are composed of financial contribution from the European Union Seventh Framework Programme (FP7/2007-2013) and EFPIA companies in kind contribution. NAP is supported in part by Henning och Johan Throne-Holsts Foundation, Hans Werthen Foundation, an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. HPM is supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. AGJ is supported by an NIHR Clinician Scientist award (17/0005624). RK is funded by the Novo Nordisk Foundation (NNF18OC0031650) as part of a postdoctoral fellowship, an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. AK, PM, HF, JF and GNG are supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. TJM is funded by an NIHR clinical senior lecturer fellowship. S.Bru acknowledges support from the Novo Nordisk Foundation (grants NNF17OC0027594 and NNF14CC0001). ATH is a Wellcome Trust Senior Investigator and is also supported by the NIHR Exeter Clinical Research Facility. JMS acknowledges support from Science for Life Laboratory (Plasma Profiling Facility), Knut and Alice Wallenberg Foundation (Human Protein Atlas) and Erling-Persson Foundation (KTH Centre for Precision Medicine). MIM is supported by the following grants; Wellcome (090532, 098381, 106130, 203141, 212259); NIH (U01-DK105535). PWF is supported by an IRC award from the Swedish Foundation for Strategic Research and a European Research Council award ERC-2015-CoG - 681742_NASCENT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Approval for the study protocol was obtained from each of the regional research ethics review boards separately (Lund, Sweden: 20130312105459927, Copenhagen, Denmark: H-1-2012-166 and H-1-2012-100, Amsterdam, Netherlands: NL40099.029.12, Newcastle, Dundee and Exeter, UK: 12/NE/0132), and all participants provided written informed consent at enrolment. The research conformed to the ethical principles for medical research involving human participants outlined in the Declaration of Helsinki.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAuthors agree to make data and materials supporting the results or analyses presented in their paper available upon reasonable request
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| 8. |
- Christensen, Diana Hedevang, et al.
(författare)
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Type 2 diabetes classification : a data-driven cluster study of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort
- 2022
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Ingår i: BMJ Open Diabetes Research and Care. - : BMJ. - 2052-4897. ; 10:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction A Swedish data-driven cluster study identified four distinct type 2 diabetes (T2D) clusters, based on age at diagnosis, body mass index (BMI), hemoglobin A1c (HbA1c) level, and homeostatic model assessment 2 (HOMA2) estimates of insulin resistance and beta-cell function. A Danish study proposed three T2D phenotypes (insulinopenic, hyperinsulinemic, and classical) based on HOMA2 measures only. We examined these two new T2D classifications using the Danish Centre for Strategic Research in Type 2 Diabetes cohort. Research design and methods In 3529 individuals, we first performed a k-means cluster analysis with a forced k-value of four to replicate the Swedish clusters: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild age-related (MARD), and mild obesity-related (MOD) diabetes. Next, we did an analysis open to alternative k-values (ie, data determined the optimal number of clusters). Finally, we compared the data-driven clusters with the three Danish phenotypes. Results Compared with the Swedish findings, the replicated Danish SIDD cluster included patients with lower mean HbA1c (86 mmol/mol vs 101 mmol/mol), and the Danish MOD cluster patients were less obese (mean BMI 32 kg/m 2 vs 36 kg/m 2). Our data-driven alternative k-value analysis suggested the optimal number of T2D clusters in our data to be three, rather than four. When comparing the four replicated Swedish clusters with the three proposed Danish phenotypes, 81%, 79%, and 69% of the SIDD, MOD, and MARD patients, respectively, fitted the classical T2D phenotype, whereas 70% of SIRD patients fitted the hyperinsulinemic phenotype. Among the three alternative data-driven clusters, 60% of patients in the most insulin-resistant cluster constituted 76% of patients with a hyperinsulinemic phenotype. Conclusion Different HOMA2-based approaches did not classify patients with T2D in a consistent manner. The T2D classes characterized by high insulin resistance/hyperinsulinemia appeared most distinct.
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| 9. |
- Frederiksen, Lise, et al.
(författare)
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A multivariate approach to plant community distribution in the coastal dune zonation of NW Denmark
- 2006
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Ingår i: Phytocoenologia. - 0340-269X. ; 36:3, s. 321-342
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Tidskriftsartikel (refereegranskat)abstract
- A near-natural coastal dune system in NW Jutland, Denmark was investigated. The area contains a gradient in natural soil mobility with the highest values in dynamic white dunes dominated by Ammophila arenaria, and low mobility in fixed decalcified dune heath with Empetrum nigrum and Calluna vulgaris. A total of 267 plots was investigated and presence of mosses and rooted vascular plants recorded. Cluster analysis identified five communities: white dune, grey dune, outer dune heath, inner dune heath and humid dune heath. These communities were ordered along two main axes in a Detrended Correspondence Analysis (DCA). The relationship between DCA axes and several environmental variables, including soil characteristics and Ellenberg indicator values, were investigated by correlation. Two major complex gradients underlying compositional variation were identified; one short coenocline with an underlying steep gradient in habitat maturity, soil stability and nutrient-limited productivity, and one longer gradient in water-limited productivity and peat accumulation only applying to the older successional stages. Distance from the coast was an important correlate of several of the measured variables. Microclimatic indices, i.e. heat index and wind index, had limited value as descriptors of community patterns as they were not correlated with the DCA axes or with other environmental variables. However, within communities the microclimatic indices correlated with several explanatory variables.
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| 10. |
- Hansen, Aleksander L., et al.
(författare)
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Birthweight is associated with clinical characteristics in people with recently diagnosed type 2 diabetes
- 2023
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Ingår i: Diabetologia. - 0012-186X. ; 66:9, s. 1680-1692
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Low birthweight is a risk factor for type 2 diabetes but it is unknown whether low birthweight is associated with distinct clinical characteristics at disease onset. We examined whether a lower or higher birthweight in type 2 diabetes is associated with clinically relevant characteristics at disease onset. Methods: Midwife records were traced for 6866 individuals with type 2 diabetes in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort. Using a cross-sectional design, we assessed age at diagnosis, anthropomorphic measures, comorbidities, medications, metabolic variables and family history of type 2 diabetes in individuals with the lowest 25% of birthweight (<3000 g) and highest 25% of birthweight (>3700 g), compared with a birthweight of 3000–3700 g as reference, using log-binomial and Poisson regression. Continuous relationships across the entire birthweight spectrum were assessed with linear and restricted cubic spline regression. Weighted polygenic scores (PS) for type 2 diabetes and birthweight were calculated to assess the impact of genetic predispositions. Results: Each 1000 g decrease in birthweight was associated with a 3.3 year (95% CI 2.9, 3.8) younger age of diabetes onset, 1.5 kg/m2 (95% CI 1.2, 1.7) lower BMI and 3.9 cm (95% CI 3.3, 4.5) smaller waist circumference. Compared with the reference birthweight, a birthweight of <3000 g was associated with more overall comorbidity (prevalence ratio [PR] for Charlson Comorbidity Index Score ≥3 was 1.36 [95% CI 1.07, 1.73]), having a systolic BP ≥155 mmHg (PR 1.26 [95% CI 0.99, 1.59]), lower prevalence of diabetes-associated neurological disease, less likelihood of family history of type 2 diabetes, use of three or more glucose-lowering drugs (PR 1.33 [95% CI 1.06, 1.65]) and use of three or more antihypertensive drugs (PR 1.09 [95% CI 0.99, 1.20]). Clinically defined low birthweight (<2500 g) yielded stronger associations. Most associations between birthweight and clinical characteristics appeared linear, and a higher birthweight was associated with characteristics mirroring lower birthweight in opposite directions. Results were robust to adjustments for PS representing weighted genetic predisposition for type 2 diabetes and birthweight. Conclusion/interpretation: Despite younger age at diagnosis, and fewer individuals with obesity and family history of type 2 diabetes, a birthweight <3000 g was associated with more comorbidities, including a higher systolic BP, as well as with greater use of glucose-lowering and antihypertensive medications, in individuals with recently diagnosed type 2 diabetes.
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