Precision Prediction & Precision Medicine
Type 1 diabetes (T1D) is a heterogeneous disease that differs between individuals in its causes, progression and response to treatment. Precision prediction and precision medicine aim to improve our ability to identify who is at risk of developing T1D or its complications, to determine disease stage, and to tailor therapy to the individual.
Research in this area increasingly combines established clinical markers with novel biomarkers and advanced measurement techniques to detect early changes in vascular, neurological and metabolic health, as well as differences in beta-cell function.
By integrating these approaches into clinical care and research, and through close collaboration with academic partners, we work towards translating scientific advances into practical tools for personalised diabetes care. Below, related projects and publications highlight how this research contributes to earlier prediction and more individualised treatment in type 1 diabetes.
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
Microbiome Capsules to Stabilize Beta-Cell Function in T1D
Pleun de Groen, Coco M. Fuhri Snethlage, Koen Wortelboer, Sevilay Tokgöz, Mark Davids, Xanthe Verdoes, Florine H.M. Westerbeke, Rick I. Meijer, Martin Gotthardt, Willem M. de Vos, Hilde Herrema, Max Nieuwdorp, Nordin M.J. Hanssen
Autologous fecal microbiota capsules are safe and potentially preserve beta-cell function in individuals with type 1 diabetes Gut Microbes. 2025 Dec 31;17(1):2563155.
Immune–Microbiome interactions & new T1D therapie
Pleun de Groen, Lente C.H.M. Blok, Coco M. Fuhri Snethlage, Nordin M.J. Hanssen, Elena Rampanelli, Max Nieuwdorp
Unraveling Type 1 Diabetes: Integrating Microbiome, Metabolomics, and Immunomodulation for Next-Generation Therapies. Int J Mol Sci . 2025 Nov 6;26(21):10788.
Persisting proinsulin production in T1D
Douwe Frank de Wit, Coco Marjolein Fuhri Snethlage, Rana Minab, Elena Rampanelli, Pleun de Groen, Manon Balvers, Timothy J. McDonald, Richard A. Oram, Bart O. Roep, Daniel H. van Raalte, Cameron B. Verchere, Max Nieuwdorp, Nordin M. J. Hanssen
Persisting plasma proinsulin levels in a cohort of 482 individuals with long-standing type 1 diabetes mellitus. Diabetes Obes Metab . 2025 Oct;27(10):5566-5575.
Differential signalling in Impaired Hypoglycemia Awareness
Rita D. M. Varkevisser, Agnese Petrera, Stefanie M. Hauck, Dick Mul, Henk-Jan Aanstoot, Andrew Paterson, Bruce H. R. Wolffenbuttel, Melanie M. van der Klauw & the Dutch Type 1 Diabetes Biomarker Group
Targeted proteomics analysis in type 1 diabetes identifies lower agouti-related protein levels in individuals with impaired hypoglycaemia awareness. Sci Rep. 2025 Oct 17;15(1):36448.
The gut, oxidative stress & T1D
luwatomisono I. Akinrimisi, Kim Maasen, Jean L.J.M. Scheijen, Ina Nemet, Max Nieuwdorp, Casper G. Schalkwijk, Nordin M.J. Hanssen
Does Gut Microbial Methylglyoxal Metabolism Impact Human Physiology? Antioxidants (Basel). 2025 Jun 21;14(7):763.
Calcium-phosphate metabolism and cardiovascular risk in T1D
Stephanie Vermeulen, Mirjam E.A. Scheffer-Rath, Martine T.P. Besouw, Amarens van der Vaart, Martin H. de Borst, Annemieke M. Boot
Fibroblast growth factor 23 and calcium-phosphate metabolism in relation to cardiovascular risk factors in patients with type 1 diabetes. J Diabetes. 2024 Jun;16(6):e13500.
‘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.