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

BMJ Open. 2024 Jun 19;14(6):e082453. doi: 10.1136/bmjopen-2023-082453.

Abstract

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.

Keywords: DIABETES & ENDOCRINOLOGY; EPIDEMIOLOGY; General diabetes.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers* / blood
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1* / blood
  • Diabetes Mellitus, Type 1* / metabolism
  • Disease Progression
  • Female
  • Glycated Hemoglobin* / analysis
  • Glycated Hemoglobin* / metabolism
  • Humans
  • Male
  • Middle Aged
  • Netherlands
  • Phenotype
  • Prospective Studies
  • Young Adult

Substances

  • Glycated Hemoglobin
  • Biomarkers
  • Blood Glucose
  • C-Peptide

Associated data

  • ClinicalTrials.gov/NCT04977635