Cohort profile: the ‘Biomarkers of heterogeneity in type 1 diabetes’ study—a national prospective cohort study of clinical and metabolic phenotyping of individuals with long-standing type 1 diabetes in the Netherlands

Autor: Erwin Birnie, Giesje Nefs, Bruce H R Wolffenbuttel, Melanie M van der Klauw, Peter R van Dijk, Klaas Hoogenberg, Henk J Veeze, Henk-Jan Aanstoot, Bruce HR Wolffenbuttel, Charlotte E Vollenbrock, Pim Dekker, Lianne S M Boesten, Martine M C de Vries-Velraeds, Adriaan Kooy, Dick Mul, Sanjoy Dutta, Rita D M Varkevisser, Michael P Brugts, Petronella H L M Duijvestijn, Christine Fransman, Rob K Gonera, Esther Latres, Sandra Loves, Theo Sas, Marleen J Vosjan-Noeverman, Rita DM Varkevisser, Lianne SM Boesten, Petronella HLM Duijvestijn, Martine MC de Vries-Velraeds
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: BMJ Open, Vol 14, Iss 6 (2024)
Druh dokumentu: article
ISSN: 2044-6055
DOI: 10.1136/bmjopen-2023-082453
Popis: Purpose The ‘Biomarkers of heterogeneity in type 1 diabetes’ study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D).Participants Data and samples were collected in two subsets. A prospective cohort of 611 participants aged ≥16 years with ≥5 years T1D duration from four Dutch Diabetes clinics between 2016 and 2021 (median age 32 years; median diabetes duration 12 years; 59% female; mean glycated haemoglobin (HbA1c) 61 mmol/mol (7.7%); 61% on insulin pump; 23% on continuous glucose monitoring (CGM)). Physical assessments were performed, blood and urine samples were collected, and participants completed questionnaires. A subgroup of participants underwent mixed-meal tolerance tests (MMTTs) at baseline (n=169) and at 1-year follow-up (n=104). Genetic data and linkage to medical and administrative records were also available. A second cross-sectional cohort included participants with ≥35 years of T1D duration (currently n=160; median age 64 years; median diabetes duration 45 years; 45% female; mean HbA1c 58 mmol/mol (7.4%); 51% on insulin pump; 83% on CGM), recruited from five centres and measurements, samples and 5-year retrospective data were collected.Findings to date Stimulated residual C-peptide was detectable in an additional 10% of individuals compared with fasting residual C-peptide secretion. MMTT measurements at 90 min and 120 min showed good concordance with the MMTT total area under the curve. An overall decrease of C-peptide at 1-year follow-up was observed. Fasting residual C-peptide secretion is associated with a decreased risk of impaired awareness of hypoglycaemia.Future plans Research groups are invited to consider the use of these data and the sample collection. Future work will include additional hormones, beta-cell-directed autoimmunity, specific immune markers, microRNAs, metabolomics and gene expression data, combined with glucometrics, anthropometric and clinical data, and additional markers of residual beta-cell function.Trial registration number NCT04977635.
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