Emma Ahlqvist
Lunds Universitet
H-index: 40
Europe-Sweden
About Emma Ahlqvist
Emma Ahlqvist, With an exceptional h-index of 40 and a recent h-index of 35 (since 2020), a distinguished researcher at Lunds Universitet,
His recent articles reflect a diverse array of research interests and contributions to the field:
Does a prior diagnosis of infectious disease confer an increased risk of latent autoimmune diabetes in adults?
RNA sequencing unravels novel L cell constituents and mechanisms of GLP-1 secretion in human gastric bypass-operated intestine
All-cause mortality and cardiovascular and microvascular diseases in latent autoimmune diabetes in adults
Endogenous incretin levels and risk of first incident cancer: a prospective cohort study
Identifying blood biomarkers for type 2 diabetes subtyping: a report from the ORIGIN trial
GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification
Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults
Antioxidant Nutrients and Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes: A Swedish Case-Control Study and Mendelian Randomization Analysis
Emma Ahlqvist Information
University | Lunds Universitet |
---|---|
Position | Diabetes & Endocrinology |
Citations(all) | 8336 |
Citations(since 2020) | 6224 |
Cited By | 4294 |
hIndex(all) | 40 |
hIndex(since 2020) | 35 |
i10Index(all) | 80 |
i10Index(since 2020) | 75 |
University Profile Page | Lunds Universitet |
Top articles of Emma Ahlqvist
Does a prior diagnosis of infectious disease confer an increased risk of latent autoimmune diabetes in adults?
Authors
Jessica Edstorp,Marios Rossides,Emma Ahlqvist,Bahareh Rasouli,Tiinamaija Tuomi,Sofia Carlsson
Journal
Diabetes/Metabolism Research and Reviews
Published Date
2024/3
Aims Infections are proposed risk factors for type 1 diabetes in children. We examined whether a diagnosis of infectious disease also confers an increased risk of latent autoimmune diabetes in adults (LADA). Materials and methods We used data from a population‐based Swedish case‐control study with incident cases of LADA (n = 597) and matched controls (n = 2386). The history of infectious disease was ascertained through national and regional patient registers. We estimated adjusted odds ratios (OR) with 95% confidence intervals for ≥1 respiratory (any/upper/lower), gastrointestinal, herpetic, other or any infectious disease episode, or separately, for 1 and ≥2 infectious disease episodes, within 0–1, 1–3, 3–5 and 5–10 years before LADA diagnosis/matching. Stratified analyses were performed on the basis of HLA risk genotypes and Glutamic acid decarboxylase antibodies (GADA) levels. Results …
RNA sequencing unravels novel L cell constituents and mechanisms of GLP-1 secretion in human gastric bypass-operated intestine
Authors
Michael G Miskelly,Andreas Lindqvist,Elena Piccinin,Alexander Hamilton,Elaine Cowan,Bent-Johnny Nergård,Rita Del Giudice,Mtakai Ngara,Luis R Cataldo,Dmytro Kryvokhyzha,Petr Volkov,Luke Engelking,Isabella Artner,Jens O Lagerstedt,Lena Eliasson,Emma Ahlqvist,Antonio Moschetta,Jan Hedenbro,Nils Wierup
Journal
Diabetologia
Published Date
2024/2
Aims/hypothesisRoux-en-Y gastric bypass surgery (RYGB) frequently results in remission of type 2 diabetes as well as exaggerated secretion of glucagon-like peptide-1 (GLP-1). Here, we assessed RYGB-induced transcriptomic alterations in the small intestine and investigated how they were related to the regulation of GLP-1 production and secretion in vitro and in vivo.MethodsHuman jejunal samples taken perisurgically and 1 year post RYGB (n=13) were analysed by RNA-seq. Guided by bioinformatics analysis we targeted four genes involved in cholesterol biosynthesis, which we confirmed to be expressed in human L cells, for potential involvement in GLP-1 regulation using siRNAs in GLUTag and STC-1 cells. Gene expression analyses, GLP-1 secretion measurements, intracellular calcium imaging and RNA-seq were performed in vitro. OGTTs were performed in C57BL/6j and iScd1−/− mice and …
All-cause mortality and cardiovascular and microvascular diseases in latent autoimmune diabetes in adults
Authors
Yuxia Wei,Katharina Herzog,Emma Ahlqvist,Tomas Andersson,Thomas Nyström,Yiqiang Zhan,Tiinamaija Tuomi,Sofia Carlsson
Journal
Diabetes Care
Published Date
2023/10/1
OBJECTIVE Latent autoimmune diabetes in adults (LADA) is a heterogenous, slowly progressing autoimmune diabetes. We aim to contribute new knowledge on the long-term prognosis of LADA with varying degrees of autoimmunity by comparing it to type 2 diabetes and adult-onset type 1 diabetes. RESEARCH DESIGN AND METHODS This Swedish population-based study included newly diagnosed LADA (n = 550, stratified into LADAlow and LADAhigh by median autoimmunity level), type 2 diabetes (n = 2,001), adult-onset type 1 diabetes (n = 1,573), and control subjects without diabetes (n = 2,355) in 2007–2019. Register linkages provided information on all-cause mortality, cardiovascular diseases (CVDs), diabetic retinopathy, nephropathy, and clinical characteristics during follow-up. RESULTS Mortality was higher in LADA (hazard ratio [HR] 1.44; 95 …
Endogenous incretin levels and risk of first incident cancer: a prospective cohort study
Authors
Amra Jujić,Christopher Godina,Mattias Belting,Olle Melander,Jens Juul Holst,Emma Ahlqvist,Maria F Gomez,Peter M Nilsson,Helena Jernström,Martin Magnusson
Journal
Scientific Reports
Published Date
2023/1/7
Concerns have been raised regarding a potentially increased risk of cancer associated with treatment with glucagon-like peptide-1 (GLP-1) receptor agonists. Here, we explored whether fasting and oral glucose tolerance test post-challenge glucose-dependent insulinotropic peptide (GIP) and GLP-1 levels were associated with incident first cancer. Within the cardiovascular re-examination arm of the population-based Malmö Diet Cancer study (n = 3734), 685 participants with a previous cancer diagnosis were excluded, resulting in 3049 participants (mean age 72.2 ± 5.6 years, 59.5% women), of whom 485 were diagnosed with incident first cancer (median follow-up time 9.9 years). Multivariable Cox-regression and competing risk regression (death as competing risk) were used to explore associations between incretin levels and incident first cancer. Higher levels of fasting GLP-1 (462 incident first cancer cases …
Identifying blood biomarkers for type 2 diabetes subtyping: a report from the ORIGIN trial
Authors
Marie Pigeyre,Hertzel Gerstein,Emma Ahlqvist,Sibylle Hess,Guillaume Paré
Journal
Diabetologia
Published Date
2023/6
Aims/hypothesisIndividuals with diabetes can be clustered into five subtypes using up to six routinely measured clinical variables. We hypothesised that circulating protein levels might be used to distinguish between these subtypes. We recently used five of these six variables to categorise 7017 participants from the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial into these subtypes: severe autoimmune diabetes (SAID, n=241), severe insulin-deficient diabetes (SIDD, n=1594), severe insulin-resistant diabetes (SIRD, n=914), mild obesity-related diabetes (MOD, n=1595) and mild age-related diabetes (MARD, n=2673).MethodsForward-selection logistic regression models were used to identify a subset of 233 cardiometabolic protein biomarkers that were independent determinants of one subtype vs the others. We then assessed the performance of adding identified biomarkers (one after one …
GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification
Authors
Vasiliki Lagou,Longda Jiang,Anna Ulrich,Liudmila Zudina,Karla Sofia Gutiérrez González,Zhanna Balkhiyarova,Alessia Faggian,Jared G Maina,Shiqian Chen,Petar V Todorov,Sodbo Sharapov,Alessia David,Letizia Marullo,Reedik Mägi,Roxana-Maria Rujan,Emma Ahlqvist,Gudmar Thorleifsson,Ηe Gao,Εvangelos Εvangelou,Beben Benyamin,Robert A Scott,Aaron Isaacs,Jing Hua Zhao,Sara M Willems,Toby Johnson,Christian Gieger,Harald Grallert,Christa Meisinger,Martina Müller-Nurasyid,Rona J Strawbridge,Anuj Goel,Denis Rybin,Eva Albrecht,Anne U Jackson,Heather M Stringham,Ivan R Corrêa Jr,Eric Farber-Eger,Valgerdur Steinthorsdottir,André G Uitterlinden,Patricia B Munroe,Morris J Brown,Julian Schmidberger,Oddgeir Holmen,Barbara Thorand,Kristian Hveem,Tom Wilsgaard,Karen L Mohlke,Zhe Wang,GWA-PA Consortium den Hoed Marcel 57,Aleksey Shmeliov,Marcel den Hoed,Ruth JF Loos,Wolfgang Kratzer,Mark Haenle,Wolfgang Koenig,Bernhard O Boehm,Tricia M Tan,Alejandra Tomas,Victoria Salem,Inês Barroso,Jaakko Tuomilehto,Michael Boehnke,Jose C Florez,Anders Hamsten,Hugh Watkins,Inger Njølstad,H-Erich Wichmann,Mark J Caulfield,Kay-Tee Khaw,Cornelia M van Duijn,Albert Hofman,Nicholas J Wareham,Claudia Langenberg,John B Whitfield,Nicholas G Martin,Grant Montgomery,Chiara Scapoli,Ioanna Tzoulaki,Paul Elliott,Unnur Thorsteinsdottir,Kari Stefansson,Evan L Brittain,Mark I McCarthy,Philippe Froguel,Patrick M Sexton,Denise Wootten,Leif Groop,Josée Dupuis,James B Meigs,Giuseppe Deganutti,Ayse Demirkan,Tune H Pers,Christopher A Reynolds,Yurii S Aulchenko,Marika A Kaakinen,Ben Jones,Inga Prokopenko,Meta-Analysis of Glucose and Insulin-Related Traits Consortium (MAGIC) van Duijn Cornelia M. 7 72 73
Journal
Nature genetics
Published Date
2023/9
Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on ‘around the clock’ glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular …
Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults
Authors
Jessica Edstorp,Yuxia Wei,Emma Ahlqvist,Lars Alfredsson,Valdemar Grill,Leif Groop,Bahareh Rasouli,Elin P Sørgjerd,Per M Thorsby,Tiinamaija Tuomi,Bjørn O Åsvold,Sofia Carlsson
Journal
Diabetologia
Published Date
2023/1
Aims/hypothesesSmoking and use of smokeless tobacco (snus) are associated with an increased risk of type 2 diabetes. We investigated whether smoking and snus use increase the risk of latent autoimmune diabetes in adults (LADA) and elucidated potential interaction with HLA high-risk genotypes.MethodsAnalyses were based on Swedish case–control data (collected 2010–2019) with incident cases of LADA (n=593) and type 2 diabetes (n=2038), and 3036 controls, and Norwegian prospective data (collected 1984–2019) with incident cases of LADA (n=245) and type 2 diabetes (n=3726) during 1,696,503 person-years of follow-up. Pooled RRs with 95% CIs were estimated for smoking, and ORs for snus use (case–control data only). The interaction was assessed by attributable proportion (AP) due to interaction. A two-sample Mendelian randomisation (MR) study on smoking and LADA/type 2 diabetes was …
Antioxidant Nutrients and Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes: A Swedish Case-Control Study and Mendelian Randomization Analysis
Authors
Anna-Maria Lampousi,Josefin E Löfvenborg,Emma Ahlqvist,Tiinamaija Tuomi,Alicja Wolk,Sofia Carlsson
Journal
Nutrients
Published Date
2023/5/30
Antioxidant vitamins C and E are inversely associated with type 1 diabetes (T1D). We investigated if antioxidants are also associated with latent autoimmune diabetes in adults (LADA), with low (LADAlow) and high (LADAhigh) autoantibody levels, type 2 diabetes (T2D), and estimates of beta cell function (HOMA-B) and insulin resistance (HOMA-IR). We used Swedish case-control data with incident cases of LADA (n = 584) and T2D (n = 1989) and matched population-based controls (n = 2276). Odds ratios (OR) and 95% confidence intervals (CI) were calculated per one standard deviation higher beta-carotene, vitamin C, vitamin E, selenium, and zinc intakes. Two-sample Mendelian randomization (MR) analyses assessed causality between genetically predicted circulating antioxidants and LADA, T1D, and T2D, using summary statistics from genome-wide association studies. Among the antioxidants, vitamins C and E were inversely associated with LADAhigh (OR 0.84, CI 0.73, 0.98 and OR 0.80, CI 0.69, 0.94 respectively), but not with LADAlow or T2D. Vitamin E was also associated with higher HOMA-B and lower HOMA-IR. MR analyses estimated an OR of 0.50 (CI 0.20, 1.25) for the effect of vitamin E on T1D, but did not support causal relationships between antioxidants and either LADA or T2D. In conclusion, vitamin E may have a protective effect on autoimmune diabetes, possibly through preserved beta cell function and less insulin resistance.
DNA methylation partially mediates antidiabetic effects of metformin on HbA1c levels in individuals with type 2 diabetes
Authors
Sonia García-Calzón,Silja Schrader,Alexander Perfilyev,Mats Martinell,Emma Ahlqvist,Charlotte Ling
Journal
Diabetes Research and Clinical Practice
Published Date
2023/8/1
AimsDespite metformin being used as first-line pharmacological therapy for type 2 diabetes, its underlying mechanisms remain unclear. We aimed to determine whether metformin altered DNA methylation in newly-diagnosed individuals with type 2 diabetes.Methods and ResultsWe found that metformin therapy is associated with altered methylation of 26 sites in blood from Scandinavian discovery and replication cohorts (FDR < 0.05), using MethylationEPIC arrays. The majority (88%) of these 26 sites were hypermethylated in patients taking metformin for ∼ 3 months compared to controls, who had diabetes but had not taken any diabetes medication. Two of these blood-based methylation markers mirrored the epigenetic pattern in muscle and adipose tissue (FDR < 0.05). Four type 2 diabetes-associated SNPs were annotated to genes with differential methylation between metformin cases and controls, e.g., GRB10 …
Incidence and Risk Factors for Heart Failure in 20 000 Newly Diagnosed Diabetes Patients
Authors
Carl Lejonberg,Tomasz Czuba,Louise Bennet,Olle Melander,Maria F Gomez,Emma Ahlqvist,Gustav Smith
Journal
Circulation
Published Date
2023/11/7
Introduction: Heart Failure (HF) is a diabetes complication causing high mortality and morbidity but has received relatively limited attention compared to other complications such as acute myocardial infarction (AMI). Substantial residual HF risk remains after achieving current treatment targets, suggesting important additional pathophysiological mechanisms beyond conventional risk factors. Aim: to study the incidence and risk factors for HF in newly diagnosed diabetes patients. Methods: We used a contemporary, regional inception cohort (n=19,938) from Scania County in Sweden, to study the incidence and risk factors for HF from initial diabetes diagnosis. Biochemical and questionnaire data were collected within 1 year from initial diagnosis in newly diagnosed diabetes patients (>90% participation rate). We combined baseline data with information on incident HF and AMI diagnoses from a nationwide patient …
Identification of biomarkers for glycaemic deterioration in type 2 diabetes
Authors
Roderick C Slieker,Louise A Donnelly,Elina Akalestou,Livia Lopez-Noriega,Rana Melhem,Ayşim Güneş,Frederic Abou Azar,Alexander Efanov,Eleni Georgiadou,Hermine Muniangi-Muhitu,Mahsa Sheikh,Giuseppe N Giordano,Mikael Åkerlund,Emma Ahlqvist,Ashfaq Ali,Karina Banasik,Søren Brunak,Marko Barovic,Gerard A Bouland,Frédéric Burdet,Mickaël Canouil,Iulian Dragan,Petra JM Elders,Celine Fernandez,Andreas Festa,Hugo Fitipaldi,Phillippe Froguel,Valborg Gudmundsdottir,Vilmundur Gudnason,Mathias J Gerl,Amber A van der Heijden,Lori L Jennings,Michael K Hansen,Min Kim,Isabelle Leclerc,Christian Klose,Dmitry Kuznetsov,Dina Mansour Aly,Florence Mehl,Diana Marek,Olle Melander,Anne Niknejad,Filip Ottosson,Imre Pavo,Kevin Duffin,Samreen K Syed,Janice L Shaw,Over Cabrera,Timothy J Pullen,Kai Simons,Michele Solimena,Tommi Suvitaival,Asger Wretlind,Peter Rossing,Valeriya Lyssenko,Cristina Legido Quigley,Leif Groop,Bernard Thorens,Paul W Franks,Gareth E Lim,Jennifer Estall,Mark Ibberson,Joline WJ Beulens,Leen M ’t Hart,Ewan R Pearson,Guy A Rutter
Journal
Nature communications
Published Date
2023/5/3
We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards …
Polygenic scores of diabetes-related traits in subgroups of type 2 diabetes in India: a cohort study
Authors
Chittaranjan S Yajnik,Rucha Wagh,Pooja Kunte,Olof Asplund,Emma Ahlqvist,Dattatrey Bhat,Sharvari R Shukla,Rashmi B Prasad
Journal
The Lancet Regional Health-Southeast Asia
Published Date
2023/7/1
BackgroundA machine-learning approach identified five subgroups of diabetes in Europeans which included severe autoimmune diabetes (SAID), severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), mild obesity-related diabetes (MOD) and mild age-related diabetes (MARD) with partially distinct genetic aetiologies. We previously validated four of the non-autoimmune subgroups in people with young-onset type 2 diabetes (T2D) from the Indian WellGen study. Here, we aimed to apply European-derived centroids and genetic risk scores (GRSs) to the unselected (for age) WellGen to test their applicability and investigate the genetic aetiology of the Indian T2D subgroups.MethodsWe applied European derived centroids and GRSs to T2D participants of Indian ancestry (WellGen, n = 2217, 821 genotyped) and compared them with normal glucose tolerant controls (Pune Maternal Nutrition …
Genetic dissection of serum vaspin highlights its causal role in lipid metabolism
Authors
Jana Breitfeld,Katrin Horn,Diana Le Duc,Akhil Velluva,Carola Marzi,Harald Grallert,Nele Friedrich,Maik Pietzner,Uwe Völker,Henry Völzke,Emma Ahlqvist,Dina Mansour Aly,Tiinamaija Tuomi,Ronny Baber,Jürgen Kratzsch,Joachim Thiery,Berend Isermann,Markus Loeffler,Nora Klöting,Matthias Blüher,Michael Stumvoll,John T Heiker,Anke Tönjes,Markus Scholz,Peter Kovacs
Journal
Obesity
Published Date
2023/11
Objective Vaspin (visceral adipose tissue derived serine protease inhibitor, SERPINA12) is associated with obesity‐related metabolic traits, but its causative role is still elusive. The role of genetics in serum vaspin variability to establish its causal relationship with metabolically relevant traits was investigated. Methods A meta‐analysis of genome‐wide association studies for serum vaspin from six independent cohorts (N = 7446) was conducted. Potential functional variants of vaspin were included in Mendelian randomization (MR) analyses to assess possible causal pathways between vaspin and homeostasis model assessment and lipid traits. To further validate the MR analyses, data from Genotype‐Tissue Expression (GTEx) were analyzed, db/db mice were treated with vaspin, and serum lipids were measured. Results A total of 468 genetic variants represented by five independent variants (rs7141073 …
Incidence of lada and type 2 diabetes in relation to tobacco use and genetic susceptibility to type 2 diabetes and related traits: Findings from a swedish case-control study …
Authors
Jessica Edstorp,Emma Ahlqvist,Lars Alfredsson,Dina Mansour Aly,Valdemar Grill,Bahareh Rasouli,Elin P Sørgjerd,Tiinamaija Tuomi,Bjørn O Åsvold,Sofia Carlsson
Journal
Diabetes Care
Published Date
2023/5/1
OBJECTIVE Smoking and Swedish smokeless tobacco (snus) are associated with latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2D). Our aim was to investigate whether genetic susceptibility to T2D, insulin resistance (IR), and insulin secretion (IS) aggravate these associations. RESEARCH DESIGN AND METHODS We used data from two population-based Scandinavian studies with case subjects with LADA (n = 839) and T2D (n = 5,771), matched control subjects (n = 3,068), and 1,696,503 person-years at risk. Pooled, multivariate relative risks (RR) with 95% CI were estimated for smoking/genetic risk scores (T2D-GRS, IS-GRS, and IR-GRS), and ORs for snus or tobacco/GRS (case-control data). We estimated additive (proportion attributable to interaction [AP]) and multiplicative interaction between tobacco use and GRS. RESULTS The …
Genetically proxied impaired GIPR signaling and risk of 6 cancers
Authors
Miranda Rogers,Dipender Gill,Emma Ahlqvist,Tim Robinson,Daniela Mariosa,Mattias Johansson,Ricardo Cortez Cardoso Penha,Laure Dossus,Marc J Gunter,Victor Moreno,George Davey Smith,Richard M Martin,James Yarmolinsky
Journal
Iscience
Published Date
2023/6/16
Preclinical and genetic studies suggest that impaired glucose-dependent insulinotropic polypeptide receptor (GIPR) signaling worsens glycemic control. The relationship between GIPR signaling and the risk of cancers influenced by impaired glucose homeostasis is unclear. We examined the association of a variant in GIPR, rs1800437 (E354Q), shown to impair long-term GIPR signaling and lower circulating glucose-dependent insulinotropic peptide concentrations, with risk of 6 cancers influenced by impaired glucose homeostasis (breast, colorectal, endometrial, lung, pancreatic, and renal) in up to 235,698 cases and 333,932 controls. Each copy of E354Q was associated with a higher risk of overall and luminal A-like breast cancer and this association was consistent in replication and colocalization analyses. E354Q was also associated with higher postprandial glucose concentrations but diminished insulin …
Digital lifestyle treatment improves long-term metabolic control in type 2 diabetes with different effects in pathophysiological and genetic subgroups
Authors
Vishal A Salunkhe,Neha Sinha,Emma Ahlqvist,Rashmi B Prasad,Svetlana Johansson,Birgitta Abrahamsson,Anders H Rosengren
Journal
npj Digital Medicine
Published Date
2023/10/26
To address the unmet need for scalable solutions for lifestyle treatment, we developed a new digital method to promote behavioral change. Here we report that patients with type-2 diabetes in Sweden (n = 331) exposed to the intervention have significantly improved HbA1c during a median follow-up of 1038 days (4 mmol/mol compared with matched controls; P = 0.009). This is paralleled by reduced body weight, ameliorated insulin secretion, increased physical activity, and cognitive eating restraints. Participants with high BMI and insulin resistance have an even larger response, as have non-risk allele carriers for the FTO gene. The findings open a new avenue for scalable lifestyle management with sustained efficacy and highlight a previously unrecognized opportunity for digital precision treatment based on genetics and individual pathophysiology. ClinicalTrials.gov NCT04624321.
Four missense genetic variants in CUBN are associated with higher levels of eGFR in non-diabetes but not in diabetes mellitus or its subtypes: A genetic …
Authors
Nicoline Uglebjerg,Fariba Ahmadizar,Dina M Aly,Marisa Cañadas-Garre,Claire Hill,Annemieke Naber,Laura Smyth,David-Alexandre Trégouët,Layal Chaker,Mohsen Ghanbari,Samy Hadjadj,Mandy Van Hoek,Maryam Kavousi,Amy Jayne McKnight,Eric J Sijbrands,Peter Rossing,Tarunveer S Ahluwalia
Journal
Frontiers in Endocrinology
Published Date
2023/2/28
AimRare genetic variants in the CUBN gene encoding the main albumin-transporter in the proximal tubule of the kidneys have previously been associated with microalbuminuria and higher urine albumin levels, also in diabetes. Sequencing studies in isolated proteinuria suggest that these variants might not affect kidney function, despite proteinuria. However, the relation of these CUBN missense variants to the estimated glomerular filtration rate (eGFR) is largely unexplored. We hereby broadly examine the associations between four CUBN missense variants and eGFRcreatinine in Europeans with Type 1 (T1D) and Type 2 Diabetes (T2D). Furthermore, we sought to deepen our understanding of these variants in a range of single- and aggregate- variant analyses of other kidney-related traits in individuals with and without diabetes mellitus.MethodsWe carried out a genetic association-based linear regression analysis between four CUBN missense variants (rs141640975, rs144360241, rs45551835, rs1801239) and eGFRcreatinine (ml/min/1.73 m2, CKD-EPIcreatinine(2012), natural log-transformed) in populations with T1D (n ~ 3,588) or T2D (n ~ 31,155) from multiple European studies and in individuals without diabetes from UK Biobank (UKBB, n ~ 370,061) with replication in deCODE (n = 127,090). Summary results of the diabetes-group were meta-analyzed using the fixed-effect inverse-variance method.ResultsAlbeit we did not observe associations between eGFRcreatinine and CUBN in the diabetes-group, we found significant positive associations between the minor alleles of all four variants and eGFRcreatinine in the UKBB individuals …
Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake
Authors
Alice Williamson,Dougall M Norris,Xianyong Yin,K Alaine Broadaway,Anne H Moxley,Swarooparani Vadlamudi,Emma P Wilson,Anne U Jackson,Vasudha Ahuja,Mette K Andersen,Zorayr Arzumanyan,Lori L Bonnycastle,Stefan R Bornstein,Maxi P Bretschneider,Thomas A Buchanan,Yi-Cheng Chang,Lee-Ming Chuang,Ren-Hua Chung,Tine D Clausen,Peter Damm,Graciela E Delgado,Vanessa D de Mello,Josée Dupuis,Om P Dwivedi,Michael R Erdos,Lilian Fernandes Silva,Timothy M Frayling,Christian Gieger,Mark O Goodarzi,Xiuqing Guo,Stefan Gustafsson,Liisa Hakaste,Ulf Hammar,Gad Hatem,Sandra Herrmann,Kurt Højlund,Katrin Horn,Willa A Hsueh,Yi-Jen Hung,Chii-Min Hwu,Anna Jonsson,Line L Kårhus,Marcus E Kleber,Peter Kovacs,Timo A Lakka,Marie Lauzon,I-Te Lee,Cecilia M Lindgren,Jaana Lindström,Allan Linneberg,Ching-Ti Liu,Jian’an Luan,Dina Mansour Aly,Elisabeth Mathiesen,Angela P Moissl,Andrew P Morris,Narisu Narisu,Nikolaos Perakakis,Annette Peters,Rashmi B Prasad,Roman N Rodionov,Kathryn Roll,Carsten F Rundsten,Chloé Sarnowski,Kai Savonen,Markus Scholz,Sapna Sharma,Sara E Stinson,Sufyan Suleman,Jingyi Tan,Kent D Taylor,Matti Uusitupa,Dorte Vistisen,Daniel R Witte,Romy Walther,Peitao Wu,Anny H Xiang,Björn Zethelius,Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) de Mello Vanessa D. 25,Emma Ahlqvist,Richard N Bergman,Yii-Der Ida Chen,Francis S Collins,Tove Fall,Jose C Florez,Andreas Fritsche,Harald Grallert,Leif Groop,Torben Hansen,Heikki A Koistinen,Pirjo Komulainen,Markku Laakso,Lars Lind,Markus Loeffler,Winfried März,James B Meigs,Leslie J Raffel,Rainer Rauramaa,Jerome I Rotter,Peter EH Schwarz,Michael Stumvoll,Johan Sundström,Anke Tönjes,Tiinamaija Tuomi,Jaakko Tuomilehto,Robert Wagner,Inês Barroso,Mark Walker,Niels Grarup,Michael Boehnke,Nicholas J Wareham,Karen L Mohlke,Eleanor Wheeler,Stephen O’Rahilly,Daniel J Fazakerley,Claudia Langenberg
Journal
Nature genetics
Published Date
2023/6
Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10−8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms …
Type 2 diabetes classification: a data-driven cluster study of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort
Authors
Diana Hedevang Christensen,Sia K Nicolaisen,Emma Ahlqvist,Jacob V Stidsen,Jens Steen Nielsen,Kurt Hojlund,Michael H Olsen,Sonia García-Calzón,Charlotte Ling,Jørgen Rungby,Ivan Brandslund,Peter Vestergaard,Niels Jessen,Torben Hansen,Charlotte Brøns,Henning Beck-Nielsen,Henrik T Sørensen,Reimar W Thomsen,Allan Vaag
Journal
BMJ Open Diabetes Research and Care
Published Date
2022/4/1
IntroductionA 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 methodsIn 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 …
Genome wide association meta study of diabetic foot ulcers
Authors
Sule Altintas,G Bouland,A Veluchamy,M Thangam,E Lindholm,W Meng,JA Andersen,CS Hansen,LT Dalgaard,C Palmer,E Ahlqvist,LMT Hart,A Rasmussen,P Rossing,TS Ahluwalia
Journal
Diabetologia
Published Date
2022/9/20
Background and aims: Diabetic foot ulcers (DFUs) are a severe complication of diabetes mellitus. Globally, a lower limb is amputated due to diabetes every 30 seconds; foot ulceration precedes 85% of diabetes-related amputations. While several risk factors are known-including sensorimotor peripheral neuropathy (DSPN), peripheral artery disease, foot deformities, and poor glycemic control-the genetics of DFUs are poorly understood. In this study, we conducted the first genome-wide association meta-study of diabetic foot ulcers with the aim of identifying genetic loci associated with DFU risk in diabetic (type 1 and type 2) individuals with DSPN.Materials and methods: A meta-analysis of DFUs was conducted, comprising four independent genome-wide association studies from diabetes cohorts of European ancestry (AfterEU, Denmark; SDR, Sweden; GoShare, Scotland; DCS, Netherlands). This case-control study comprised a total of 980 cases (with DFU and DSPN) and 6196 controls (no history of DFU, but with DSPN). DSPN was defined as bilateral vibration sensation threshold≥ 25V or absent sensation to monofilament. Logistic regression models were applied adjusting for sex, duration of diabetes and principal components. Summary statistics from the four European cohorts were meta-analysed using fixed effects inverse-variance based metaanalysis.Results: In the GWAS meta-analysis, we identified three common single nucleotide polymorphisms (SNPs) that were suggestive (p-valueConclusion: Three suggestive loci associated with DFU risk were identified in the current ongoing study. Two loci were located in COL4A2 and ALK, which …
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All-cause mortality and cardiovascular and microvascular diseases in latent autoimmune diabetes in adults
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Identifying blood biomarkers for type 2 diabetes subtyping: a report from the ORIGIN trial
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Smoking, use of smokeless tobacco, HLA genotypes and incidence of latent autoimmune diabetes in adults
Antioxidant Nutrients and Risk of Latent Autoimmune Diabetes in Adults and Type 2 Diabetes: A Swedish Case-Control Study and Mendelian Randomization Analysis
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are the top articles of Emma Ahlqvist at Lunds Universitet.
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Emma Ahlqvist has 8,336 citations in total.