Introduction and Objective: Investigating the intestinal gene expression in type 2 Diabetes (T2D) may reveal novel insights into its pathophysiology. We conducted a comprehensive investigation to compare gene expression profiles along the entire human intestinal tract of individuals with T2D and healthy counterparts, aiming to identify unique gene expression patterns associated with T2D.

Methods: Mucosal biopsies from 16 intestinal sites were collected via anterograde and retrograde double-balloon endoscopy in 12 individuals with T2D and 12 matched individuals. Bulk transcriptome profiles were compared between T2D individuals and healthy individuals.

Results: Healthy participants (8M/4F, mean age: 50 years, BMI: 27.1 kg/m2, HbA1c: 5.3%) were compared to individuals of T2D (9M/3F, mean age: 51 years, BMI: 26.8 kg/m2, HbA1c: 6.5%, diabetes duration: 5 years). All were of European descent. Altered mitochondrial function and immune system activity were observed in the ileocecal segment and large intestine, respectively, in individuals with T2D compared to healthy individuals.

Conclusion: The notable changes in mitochondrial function and immune system activity in the ileocecal segment and the large intestine of individuals with T2D underscore the complex pathophysiology of the disease and its influence on intestinal function and health. The publicly and freely available database generated from this study provides a comprehensive reference for future research on intestinal gene expression in T2D and is a valuable resource for the exploration of the mucosal transcriptome along the human intestinal tract.

Disclosure

H. Gilliam-Vigh: Research Support; Zealand Pharma A/S. A. Ellegaard: None. M.R. Madsen: Employee; Gubra. B.A.H. Jensen: None. K. Rigbolt: None. F.K. Knop: Advisory Panel; AstraZeneca. Consultant; AstraZeneca. Speaker's Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Consultant; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim. Advisory Panel; Eli Lilly and Company. Consultant; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Employee; Novo Nordisk A/S. Research Support; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S. Advisory Panel; Sanofi. Speaker's Bureau; Lundbeck. Advisory Panel; Zealand Pharma A/S. Consultant; Zealand Pharma A/S. Research Support; Zealand Pharma A/S. Speaker's Bureau; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S.

Funding

This work was supported by a research grant from the Danish Diabetes and Endocrine Academy, which is funded by the Novo Nordisk Foundation, grant number NNF22SA0079901

© 2024 by the American Diabetes Association
2024
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