K.F. Pietersma, S. Wopereis, R.J.M. Kamstra, T.J. van den Broek, W.J. van den Brink;
Microbiology and Systems Biology, Netherlands Organization for Applied Scientific Research (TNO), the Netherlands.
Background: Growing evidence supports the existence of tissue-specific insulin-resistant subtypes in individuals with type 2 (pre)diabetes (T2D). These subtypes respond differently to lifestyle interventions, highlighting the need for personalized treatment. Currently, diabetes subtyping relies on an extended oral glucose tolerance test (OGTT), which requires multiple blood draws and ingestion of a high-glucose beverage, making it burdensome and often causing adverse effects such as nausea. We therefore evaluated minimally invasive alternatives for diabetes subtyping.
Methods: In this observational study, 56 adults with overweight and/or (pre)T2D were included. Participants wore a continuous glucose monitor (CGM) for 20 days and attended two clinic visits after an overnight fast: a traditional OGTT (75 g glucose) and a modified OGTT using a standardized gingerbread snack (2 × 65 g Snelle Jelle). Glucose and insulin were measured using venous and capillary blood sampling. Agreement between subtype classifications was assessed using quadratically weighted Cohen’s kappa. Comparisons included the traditional and modified OGTT and measurement methods (venous, capillary, and CGM-derived glucose). Participants also completed a post-study questionnaire on test preferences.
Results: Moderate to substantial agreement was observed between subtype classifications from the traditional and modified OGTT with venous sampling (weighted κ=0.78). Within the traditional OGTT, agreement was also moderate to substantial between classifications based on venous measurements and venous insulin combined with CGM-derived glucose measurements (weighted κ = 0.79). Agreement between venous and capillary measurements was substantial (weighted κ = 0.82). Most participants preferred the modified OGTT (61%), and 55% preferred venous over capillary sampling.
Conclusion: A modified OGTT with venous sampling appears to be a feasible alternative to the traditional OGTT and may reduce participant burden. Capillary sampling, alone or combined with CGM, is also promising. However, subtype-specific cut-offs may require adaptation for CGM-based approaches. Ongoing analyses are evaluating whether multi-day CGM alone can classify diabetes subtypes.