Our Research:
Precision Prediction & Precision Medicine
Precision Prediction & Precision Medicine
Risk assessment, which includes identifying the stage to which the disease has progressed in the individual person with diabetes, is just as important in children and adolescents as it is in adults. If we can identify individuals who are at an increased risk of developing a specific complication, or who already show early signs of complications, action can be taken to address this, including the use of additional and/or more intensive treatment.
EDDDY-S study
The ‘Early Detection of Diabetes Damage in Youth and Search for early prevention‘ (EDDDY-S) study was a research project designed to find ways to help clinicians better assess risks in children and adolescents with type 1 diabetes. It investigated new techniques for identifying early signs of micro- and macrovascular complications. Traditionally, surrogate endpoints and early signs of complications have included HbA1c, neurological physical examination, albumin excretion ratio (AER), atherogenic profile, objective neurological examination.
Newer endpoints and early signs include Advanced glycation endproducts (AGEs: measure by auto-fluorescence), intima-media thickness of the carotid artery (cIMT), markers reflecting endothelial dysfunction and measuring endothelial dysfunction itself, flow-mediated dilation (FMD) of the brachial artery, measures for arterial stiffness by pulse-wave analysis, measurement of Cystatine C and C-peptide, corneal nerve fibre density (CNFD) and corneal nerve fibre branch density (CNFBD), corneal sensation threshold measurements, new methods to measure vibration perception threshold, testing tactile function with smaller (1 mN) rather than thicker monofilaments and determining retinal vascular geometry.
Sub-studies of EDDDY-S addressed some of these newer endpoints/signs, with the aim of investigating their applicability in children and adolescents with type 1 diabetes, and if they can be usefully integrated along with older endpoints/signs into a more effective staging system for risk assessment.
Diabeter is ideally placed to conduct such research: the sub-study populations include people with diabetes attending our outpatient clinics, with the new tests and evaluations incorporated into the standard battery of assessments.
BIOMARKER study
Originally thought to result from a complete loss of beta-cells due to a specific immune attack on these cells, type 1 diabetes has been found to involve various beta-cell-specific processes, different genetic predispositions, and several disease stages. In order to tailor treatment, it is essential to find biomarkers to identify this heterogeneity, different phases of disease and the effects of interventions and cures. To this end the JDRF-funded BIOMARKER study was initiated in collaboration with the University Medical Center Groningen (UMCG).
Projects
Hybrid closed-loop Automated Insulin Delivery systems and physical activity
Glycemic variability and pregnancy
Biomarker study
Biomarkers of heterogeneity in type 1 diabetes
Diagnode 1, 2 and 3 studies
EDDDY-S: Neuronal damage in motor and sensory neurons
EDDDY-S: Carotid Intima Media Thickness (cIMT)
Trends in lipid-profiles: do aberrant lipid values track over time and do they predict diabetes damage?
EDDDY-S: Continuation
EDDDY-S: Advanced Glycation End-products (AGEs)
Diabil-2 study
Publications
‘Biomarkers of heterogeneity in type 1 diabetes’ study
HJ Aanstoot, R Varkevisser, D Mul, P Dekker, E Birnie, L Boesten, M Brugts, P van Dijk, N Duijvestijn, S Dutta, C Fransman, R Gonera, K Hoogenberg, A Kooy, E Latres, S Loves, G Nefs, T Sas, C Vollenbrock, M Vosjan-Noeverman, M de Vries-Velraeds, H Veeze, B Wolffenbuttel, M van der Klauw
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.
Metabolomics and hypoglycemia awareness
Rita Varkevisser, Alexander Cecil, Cornelia Prehn, Dick Mul, Henk-Jan Aanstoot, Andrew Paterson, Bruce Wolffenbuttel, Melanie van der Klauw
Metabolomic associations of impaired awareness of hypoglycaemia in type 1 diabetes. Sci Rep. 2024 Feb 23;14(1):4485.
C-peptide in long-standing T1D
Charlotte Vollenbrock, Dick Mul, Pim Dekker, Erwin Birnie, Martine de Vries, Lianne Boesten, Joost Groen, Nel Geelhoed-Duijvestijn, Henk-Jan Aanstoot, Bruce Wolffenbuttel
Fasting and meal-stimulated serum C-peptide in long-standing type 1 diabetes mellitus. Diabet Med . 2023 Feb;40(2):e15012.
Diabetes vaccine Diamyd® (GAD65-alum) improves glycemic control in recently diagnosed T1D
Christoph Nowak, Marcus Lind, Zdenek Sumnik, et al. (including Theo Sas of Diabeter)
Intralymphatic GAD-Alum (Diamyd®) Improves Glycemic Control in Type 1 Diabetes With HLA DR3-DQ2. J Clin Endocrinol Metab. 2022 Aug 18;107(9):2644-2651.
Glycemic variability and pregnancy
Riëlle Hoek-Hogchem, Sarah Bovenberg, Pim Dekker, Erwin Birnie, Henk Veeze, Hans J. Duvekot, Sander Galjaard, Henk-Jan Aanstoot
Effects of peri-conception and pregnancy glycemic variability on pregnancy and perinatal complications in type 1 diabetes: a pilot study. Exp Clin Endocrinol Diabetes. 2022 Nov;130(11):740-750.
Availability & reporting of technical specifications of C-peptide assays
Pim Dekker, Martine de Vries, Henk-Jan Aanstoot, Joost Groen
Which C-peptide assay do you use? Increasing need for describing C-peptide assay performance. Pediatr Endocrinol Diabetes Metab 2022; 28 (1): 101–103
Detection limits of C-peptide assays in diabetes research
Kitty de Leur, Charlotte Vollenbrock, Pim Dekker, Martine de Vries, Erwin Birnie, Dick Mul, Bruce H. R. Wolffenbuttel, Joost Groen, Henk-Jan Aanstoot, Lianne Boesten
How low is really low? Comparison of two C-peptide assays to establish residual C-peptide production in type 1 diabetes. Diabet Med. 2022 May;39(5):e14785.
C-peptide and impaired awareness of hypoglycemia
Martine J Wellens, Charlotte E Vollenbrock, Pim Dekker, Lianne S M Boesten, Petronella H Geelhoed-Duijvestijn, Martine M C de Vries-Velraeds, Giesje Nefs, Bruce H R Wolffenbuttel , Henk-Jan Aanstoot, Peter R van Dijk
Residual C-peptide secretion and hypoglycemia awareness in people with type 1 diabetes. BMJ Open Diabetes Res Care . 2021 Sep;9(1):e002288.
Diagnode-2: Results from trial with diabetes vaccine Diamyd® (GAD65-alum) published
Johnny Ludvigsson, Zdenek Sumnik, Terezie Pelikanova, et al. (including Theo Sas of Diabeter)
Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial. Diabetes Care . 2021 Jul;44(7):1604-1612.
Optimizing screening of lipids in children and adolescents with type 1 diabetes
Heyden JCV, Birnie E, Bovenberg SA, Dekker P, Veeze HJ, Mul D, Aanstoot HJ.
Losing Track of Lipids in Children and Adolescents with Type 1 Diabetes: Towards Individualized Patient Care. Exp Clin Endocrinol Diabetes. 2021 Jul;129(7):510-518.
Carotid intima media thickness (CIMT) increased in people with type 1 diabetes
Van der Heyden JC, Birnie E, Bovenberg SA, Cabezas MC, van der Meulen N, Mul D, Veeze HJ, Aanstoot HJ.
Do traditional cardiovascular risk factors solely explain intima-media thickening in youth with type 1 diabetes? J Diabetes Complications. 2016 Aug;30(6):1137-43.
Skin autofluorescence could be early surrogate marker for diabetic complications
van der Heyden JC, Birnie E, Mul D, Bovenberg S, Veeze HJ, Aanstoot HJ.
Increased skin autofluorescence of children and adolescents with type 1 diabetes despite a well-controlled HbA1c: results from an observational cohort study. BMC Endocr Disord. 2016 Sep 9;16(1):49.
Gada persistence and diabetes classification
Ten Kate Q, Aanstoot HJ, Birnie E, Veeze H, Mul D.
GADA persistence and diabetes classification. Lancet Diabetes Endocrinol. 2016;4:563–564.
Can subclinical nerve dysfunction be detected early?
Van der Heyden J, van der Meer P, Birnie E, de Coo IF, Castro Cabezas M, Ozcan B, Veeze H, Visser GH, Aanstoot HJ, Blok JH.
Decreased excitability of the distal motor nerve of young patients with type 1 diabetes mellitus. Pediatr Diabetes. 2013;14:519-25.