Abstract Background Diet and metabolic dysfunction are both associated with IBD development and progression1. Current dietary guidelines focus on ingredients, while cooking methods are overlooked. During thermal treatment of foods, advanced glycation end products (AGEs) can be formed, which are hypothesised to be involved in inflammation and metabolic diseases. Therefore, our research group conducted the STEAMM study2, a randomized cross-over trial where healthy participants followed a high- and low-AGEs diet, which contained identical ingredients but differed in cooking methods, and showed that cooking methods impact serum lipids and cholesterol, and faecal short-chain fatty acids. Now, building on the STEAMM study, we further explore the impact of a high- and low-AGEs diet on metabolic outcomes related to insulin sensitivity. Methods In a cross-over design, twenty healthy volunteers were randomly allocated to a high-to-low AGEs diet (HL) group or a low-to-high AGEs diet (LH) group, based on different cooking instructions. Fasting serum and faecal samples were taken at three timepoints: at baseline, after the first 2-week intervention period (T1), and after the second 2-week intervention period (T2). Serum levels of insulin, glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP) were determined by enzyme-linked immunosorbent assays (ELISAs). Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was calculated from fasting insulin and glucose concentrations3. Results Over the course of the study, weight (mean -1.8 kg, p = 0.0005), and fasting levels of serum insulin (p = 0.002; Fig 1A) and GLP-1 (p = 0.0004; Fig 1B) decreased across all participants. In line, HOMA-IR was significantly lower after T2 compared to baseline (p = 0.006; Fig 1D). When separating the different groups, we observed a reduction of insulin (p = 0.032; Fig 1A), GLP-1 (p = 0.0009; Fig 1B) and HOMA-IR (p = 0.032; Fig 1D) in the HL group, while this was not significant in the LH group. Serum levels of GIP remained constant throughout the study (Fig 1C). Correlation analysis showed significant correlations between insulin levels and C-reactive protein (p = 0.027), as well as carboxymethyl-lysine (p = 0.047), a common dietary AGE. Faecal calprotectin was positively correlated with serum GIP (p = 0.001) and pyrraline levels (p = 0.013), another dietary AGE. Conclusion Fasting insulin levels and HOMA-IR decreased after the low-AGEs diet in the HL group, reflecting an overall improvement of metabolic function. Interestingly, serum levels of pyrraline were associated with faecal calprotectin. Overall, this data supports the inclusion of cooking methods in dietary guidelines for patients with IBD, but further research is needed to confirm this and provide mechanistic insights. References: 1. Adolph TE, Meyer M, Schwärzler J, Mayr L, Grabherr F, Tilg H. The metabolic nature of inflammatory bowel diseases. Nature Reviews Gastroenterology 19(12):753-767. 2. Wellens J, Vissers E, Dumoulin A, et al. Cooking methods affect advanced glycation end products and lipid profiles: A randomized cross-over study in healthy subjects. Cell Reports Medicine. 2025;6(5):102091. 3. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412-419. Conflict of interest: Ms. Vissers, Eva: No conflict of interest Wellens, Judith: No conflict of interest Vanderstappen, Julie: No conflict of interest Hoekx, Sien: Consultancy fees from Ferring and Takeda Verstockt, Bram: Research support from AbbVie, Biora Therapeutics, Celltrion, Landos, Pfizer, Sanofi, Sossei Heptares/Nxera and Takeda. Speaker’s fees from Abbvie, Agomab, Alfasigma, Biogen, Bristol Myers Squibb, Celltrion, Eli Lily, Falk, Ferring, Galapagos, Materia Prima, Johnson and Johnson, Pfizer, Sandoz, Takeda, Tillots Pharma, Truvion and Viatris. Consultancy fees from Abbvie, Alfasigma, Alimentiv, Anaptys Bio, Applied Strategic, Astrazeneca, Atheneum, BenevolentAI, Biora Therapeutics, Boxer Capital, Bristol Myers Squibb, Domain Therapeutics, Eli Lily, Galapagos, Guidepont, Landos, Merck, Mirador Therapeutics, Mylan, Nxera, Inotrem, Ipsos, Johnson and Johnson, Pfizer, Sandoz, Sanofi, Santa Ana Bio, Sapphire Therapeutics, Sosei Heptares, Takeda, Tillots Pharma and Viatris. Stock options Vagustim and Thethis Pharma. Ferrante, Marc: Research grants from AbbVie, EG Pharma, Celltrion, Janssen, Pfizer, Takeda and Viatris Consultancy fees from AbbVie, AgomAb Therapeutics, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Janssen-Cilag, MRM Health, Merck Sharp and Dohme, Pfizer, Takeda and ThermoFisher Speakers’ fees from AbbVie, Biogen, Boehringer Ingelheim, Dr Falk Pharma, Ferring, Janssen-Cilag, Merck Sharp and Dohme, Pfizer, Takeda, Truvion Healthcare and Viatris Vermeire, Séverine: Grant: AbbVie, Pfizer, Takeda, J&J, Galapagos Personal Fees: AbbVie - AbolerIS Pharma - AgomAb - Alimentiv - Arena Pharmaceuticals - AstraZeneca - Avaxia- BMS - Boehringer Ingelheim - Celgene - CVasThera - Dr Falk Pharma - Ferring - Galapagos - Genentech-Roche - Gilead - GSK - Hospira - Imidomics - Janssen - J&J - Lilly - Materia Prima - MiroBio - Morphic - MrMHealth - Mundipharma - MSD - Pfizer - Prodigest - Progenity - Promakhos Therapeutics - Prometheus - Robarts Clinical Trials - Second Genome - Shire - Surrozen - Takeda - Theravance - Tillots Pharma AG - Zealand Pharma - Other: AbbVie, MSD, Takeda, Ferring, Genentech/Roche, Shire, Pfizer Inc, Galapagos, Mundipharma, Guedelha Sabino, João: Speaker’s fees: Lilly, Pfizer, Abbvie, Ferring, Falk, Takeda, Janssen, Fresenius, and Galapagos. Consultancy fees: Takeda, Pfizer, Janssen, Ferring, Fresenius, Abbvie, Galapagos, Celltrion, Pharmacosmos, and Pharmanovia. Research support: Galapagos, Viatris, and Eurogenerics. JS is supported by a Senior Clinical researcher grant from the Research foundation – Flanders.
Vissers et al. (Thu,) studied this question.