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

• Published in: BMJ open Vol. 14; no. 6; p. e082453
• Main Authors: Aanstoot, Henk-Jan, Varkevisser, Rita D M, Mul, Dick, Dekker, Pim, Birnie, Erwin, Boesten, Lianne S M, Brugts, Michael P, van Dijk, Peter R, Duijvestijn, Petronella H L M, Dutta, Sanjoy, Fransman, Christine, Gonera, Rob K, Hoogenberg, Klaas, Kooy, Adriaan, Latres, Esther, Loves, Sandra, Nefs, Giesje, Sas, Theo, Vollenbrock, Charlotte E, Vosjan-Noeverman, Marleen J, de Vries-Velraeds, Martine M C, Veeze, Henk J, Wolffenbuttel, Bruce H R, van der Klauw, Melanie M, Varkevisser, Rita DM, Boesten, Lianne SM, Dijk, Peter R van, Duijvestijn, Petronella HLM, Vries-Velraeds, Martine MC de, Wolffenbuttel, Bruce HR, Klauw, Melanie M van der
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 19.06.2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Series: Cohort profile
• Subjects: Adolescent; Adult; Aged; Biomarkers; Biomarkers - blood; Blood Glucose - analysis; Blood Glucose - metabolism; Breastfeeding & lactation; C-Peptide - blood; Cohort analysis; Cross-Sectional Studies; Diabetes; DIABETES & ENDOCRINOLOGY; Diabetes and Endocrinology; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - metabolism; Disease Progression; EPIDEMIOLOGY; Fatty acids; Female; General diabetes; Glucose; Glycated Hemoglobin - analysis; Glycated Hemoglobin - metabolism; Hospitals; Humans; Immunology; Insulin resistance; Male; Metabolism; Middle Aged; Netherlands; Peptides; Phenotype; Prospective Studies; Young Adult; Netherlands; General diabetes; EPIDEMIOLOGY; DIABETES & ENDOCRINOLOGY
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2023-082453

PurposeThe ‘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).ParticipantsData 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 dateStimulated 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 plansResearch 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.