Publications by authors named "Allan Vaag"
Aims/hypothesis: An intronic variant (rs10830963) in MTNR1B (encoding the melatonin receptor type 2 [MT2]) has been shown to strongly associate with impaired glucose regulation and elevated type 2 diabetes prevalence. However, MTNR1B missense variants have shown conflicting results on type 2 diabetes. Thus, we aimed to gain further insights into the impact of MTNR1B coding variants on type 2 diabetes prevalence and related phenotypes.
View Article and Find Full Text PDFLow birthweight is a risk factor for type 2 diabetes. We hypothesised that differential associations between birthweight and clinical characteristics in persons with and without type 2 diabetes may provide novel insights into the role of birthweight in type 2 diabetes and its progression. We analysed UK Biobank data from 9,442 persons with and 254,446 without type 2 diabetes.
View Article and Find Full Text PDFIntroduction: The physical activity health paradox refers to the contrasting associations of leisure-time physical activity and occupational physical activity with cardiovascular disease, but whether this applies to Type 2 diabetes risk is unknown. This study aimed to investigate the physical activity health paradox and age-specific Type 2 diabetes.
Methods: Working adults (N=5,866) in Denmark aged 30-60 years enrolled in the Inter99 cohort at baseline in 1999 were followed in a Diabetes Register.
Aims/hypothesis: Low birthweight (LBW) is associated with younger age, less obesity and more hypertension among people recently diagnosed with type 2 diabetes, as well as increased cardiovascular morbidity and mortality risk. It is not known whether LBW is associated with an increased risk of incident chronic kidney disease (CKD) among people with a type 2 diabetes diagnosis.
Methods: Original midwife records were retrieved for 5982 participants with recently diagnosed type 2 diabetes enrolled in the Danish Center for Strategic Research in Type 2 Diabetes (DD2) cohort between 2010 and 2024.
Aims: TCF7L2 rs7903146 is the most impactful single genetic risk variant for type 2 diabetes. However, its role on disease progression, complications and mortality among people with type 2 diabetes at diagnosis remains unclear.
Materials And Methods: We assessed the per allele impact of the rs7903146 T-allele on clinical characteristics and complication risk in 9231 individuals with type 2 diabetes at diagnosis and over a 10-year follow-up period.
Aims: We investigated the association of the inflammatory biomarker YKL-40 with cardiovascular events (CVEs) and mortality in individuals with type 2 diabetes.
Methods: We followed 11,346 individuals recently diagnosed with type 2 diabetes for up to 14 years. Baseline YKL-40 levels (measured in 9,010 individuals) were grouped into percentiles (0-33 %, 34-66 %, 67-90 %, and 91-100 %) and analyzed continuously (per 1 SD log increment), with comparisons to CRP (measured in 9,644 individuals).
Aims/hypothesis: A better understanding of the mechanisms underlying an elevated infection risk in individuals with type 2 diabetes is needed to guide risk stratification and prevention. We investigated the risk of infection in subgroups of individuals with type 2 diabetes according to indices of insulin sensitivity and beta cell function.
Methods: We classified 7265 individuals with recently diagnosed type 2 diabetes (median duration 1.
Objective: We investigated whether prepregnancy BMI (prePregBMI) in women with obesity was associated with differential DNA methylation (DNAm) in cord blood (CB) and whether DNAm may mediate the association of prePregBMI and early childhood BMI z score (BMIz).
Methods: From the Treatment of Obese Pregnant Women (TOP) study, 232 mother-child pairs were included. We conducted an epigenome-wide association study on prePregBMI and CB DNAm (450k array), followed by causal mediation analyses to test whether DNAm may mediate effects of prePregBMI on BMIz at age 36 months (BMIz36).
Background: A large proportion of skeletal muscle insulin resistance in type 2 diabetes (T2D) is caused by environmental factors.
Methods: By applying multiomics mRNA, microRNA (miRNA), and DNA methylation platforms in biopsies from 20 monozygotic twin pairs discordant for T2D, we aimed to delineate the epigenetic and transcriptional machinery underlying non-genetic muscle insulin resistance in T2D.
Results: Using gene set enrichment analysis (GSEA), we found decreased mRNA expression of genes involved in extracellular matrix organization, branched-chain amino acid catabolism, metabolism of vitamins and cofactors, lipid metabolism, muscle contraction, signaling by receptor tyrosine kinases pathways, and translocation of glucose transporter 4 (GLUT4) to the plasma membrane in muscle from twins with T2D.
Purpose: This paper provides an overview of the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort and biobank, including baseline characteristics of participants enrolled up to 2023, and post-enrollment rates of cardiovascular disease outcomes and mortality.
Methods: Since 2010, the DD2 project has enrolled individuals with type 2 diabetes mellitus (T2DM) recently diagnosed by general practitioners and by hospital-based clinicians across Denmark. Data from questionnaires, clinical examinations, and biological samples are collected at enrollment.
Article Synopsis
- The Hypo-METRICS study explored how continuous glucose monitoring (CGM) detects hypoglycemia and its relevance for people with type 1 and insulin-treated type 2 diabetes.
- Researchers tracked 276 type 1 and 321 type 2 diabetes participants using CGM for 10 weeks, correlating sensor-detected hypoglycemia (SDH) with person-reported hypoglycemia (PRH).
- Results indicated that a significant portion of CGM-detected hypoglycemia is asymptomatic, with 65% of low readings (under 70 mg/dL) not accompanied by symptoms and many reported symptoms occurring at higher glucose levels (over 70 mg/dL).
Article Synopsis
- The study aimed to explore how experiencing hypoglycemia affects daily life in adults with type 1 and insulin-treated type 2 diabetes using the Hypo-METRICS app over 70 days.
- Participants reported their hypoglycemia experiences through daily check-ins while wearing a glucose sensor that provided data without their knowledge.
- Results indicated that self-reported hypoglycemia negatively impacted energy, mood, cognitive function, and sleep quality, while sensor-detected hypoglycemia alone did not show these associations.
Background: Birth weight (BW) is associated with risk of cardiometabolic disease (CMD) in adulthood, which may depend on the state of obesity, in particular if developed at a young age. We hypothesised that BW and a polygenic score (PGS) for BW were associated with cardiometabolic risk and related plasma protein levels in children and adolescents. We aimed to determine the modifying effect of childhood obesity on these associations.
View Article and Find Full Text PDFIncretin-based therapies are highly successful in combatting obesity and type 2 diabetes. Yet both activation and inhibition of the glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) in combination with glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) activation have resulted in similar clinical outcomes, as demonstrated by the GIPR-GLP-1R co-agonist tirzepatide and AMG-133 (ref. ) combining GIPR antagonism with GLP-1R agonism.
View Article and Find Full Text PDFAims/hypothesis: Low birthweight is a risk factor for type 2 diabetes and CVD. This prospective cohort study investigated whether lower birthweight increases CVD risk after diagnosis of type 2 diabetes.
Methods: Original midwife records were evaluated for 8417 participants recently diagnosed with type 2 diabetes in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort.
Article Synopsis
- The Hypo-METRICS app was developed to gather real-time data on the physical, psychological, and social effects of hypoglycaemia in adults with type 1 and insulin-treated type 2 diabetes, overcoming limitations of traditional retrospective reporting methods.
- Participants in the study wore continuous glucose monitors and provided daily assessments of their hypoglycaemia experiences and daily functioning over a 10-week period, achieving a high overall app completion rate of 91%.
- Factors such as older age, routine continuous glucose monitoring use, and greater time spent below critical glucose levels were positively linked to higher app engagement, suggesting the app is a valuable tool for diabetes research.
Background: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy.
View Article and Find Full Text PDFArticle Synopsis
- - The study explored how awareness of hypoglycemia affects the real-time symptoms reported by adults with insulin-treated type 1 (T1D) and type 2 diabetes (T2D) using a smartphone app called Hypo-METRICS.
- - Among the 531 participants, those with impaired awareness of hypoglycemia (IAH) were less likely to report certain symptoms compared to those with normal awareness, especially at lower glucose levels.
- - The findings suggest that the Hypo-METRICS app effectively captures differences in hypoglycemia symptoms based on awareness levels, making it a potentially valuable tool for both research and clinical practices.
Aims: To determine the magnitude of the association between abdominal adiposity and low-grade inflammation in persons with recently diagnosed type 2 diabetes (T2D) and to determine to what extent this association is mediated by low physical activity level, hyperinsulinaemia, hyperglycaemia, dyslipidaemia, hypertension, and comorbidities.
Materials And Methods: We measured waist circumference, clinical characteristics, and inflammatory markers i.e.
Article Synopsis
- The study investigates whether the traditional measurement of nocturnal hypoglycemia (00:00-06:00) accurately captures hypoglycemic episodes in adults with type 1 (T1D) or insulin-treated type 2 diabetes (T2D) by comparing it to actual sleep patterns.
- Participants used continuous glucose monitors and activity trackers to record episodes of hypoglycemia over 10 weeks, revealing that rates of hypoglycemia during actual sleep were higher than those measured during the standard clock-based hours.
- The findings suggest that using a fixed overnight time frame may underestimate the incidence of hypoglycemia while asleep, and future research should incorporate sleep tracking technology for more accurate assessments.
Introduction: The population-based Inter99 cohort has contributed extensively to our understanding of effects of a systematic screening and lifestyle intervention, as well as the multifactorial aetiology of type 2 diabetes (T2D) and cardiovascular disease. To understand causes, trajectories and patterns of early and overt cardiometabolic disease manifestations, we will perform a combined clinical deep phenotyping and registry follow-up study of the now 50-80 years old Inter99 participants.
Methods And Analysis: The Inter99 cohort comprises individuals aged 30-60 years, who lived in a representative geographical area of greater Copenhagen, Denmark, in 1999.
Diabetes is associated with excess morbidity and mortality due to both micro- and macrovascular complications, as well as a range of non-classical comorbidities. Diabetes-associated microvascular complications are those considered most closely related to hyperglycaemia in a causal manner. However, some individuals with hyperglycaemia (even those with severe hyperglycaemia) do not develop microvascular diseases, which, together with evidence of co-occurrence of microvascular diseases in families, suggests a role for genetics.
View Article and Find Full Text PDFObjective: Metabolic syndrome components may cumulatively increase the risk of diabetic polyneuropathy (DPN) in type 2 diabetes mellitus (T2DM) patients, driven by insulin resistance and hyperinsulinemia. We investigated the prevalence of DPN in three T2DM subgroups based on indices of β-cell function and insulin sensitivity.
Research Design And Methods: We estimated β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) in 4,388 Danish patients with newly diagnosed T2DM.
Background: Maternal malaria may restrict foetal growth. Impaired utero-placental blood flow due to malaria infection may cause hypoxia-induced altered skeletal muscle fibre type distribution in the offspring, which may contribute to insulin resistance and impaired glucose metabolism. This study assessed muscle fibre distribution 20 years after placental and/or peripheral malaria exposure compared to no exposure, i.
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