Longitudinal plasma protein profiling of newly diagnosed type 2 diabetes
Anders Gummesson,
Elias Björnson,
Linn Fagerberg,
Wen Zhong,
Abdellah Tebani,
Fredrik Edfors,
Caroline Schmidt,
Annika Lundqvist,
Martin Adiels,
Fredrik Bäckhed,
Jochen M Schwenk,
Per-Anders Jansson,
Mathias Uhlén,
Göran Bergström
Affiliations
Anders Gummesson
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Clinical Genetics and Genomics, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden; Corresponding author at: Department of Clinical Genetics and Genomics, Sahlgrenska University Hospital, SE-41345 Gothenburg, Sweden.
Elias Björnson
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
Linn Fagerberg
Science for Life Laboratory, Department of Protein Science, KTH-Royal Institute of Technology, Stockholm, Sweden
Wen Zhong
Science for Life Laboratory, Department of Protein Science, KTH-Royal Institute of Technology, Stockholm, Sweden
Abdellah Tebani
Science for Life Laboratory, Department of Protein Science, KTH-Royal Institute of Technology, Stockholm, Sweden
Fredrik Edfors
Science for Life Laboratory, Department of Protein Science, KTH-Royal Institute of Technology, Stockholm, Sweden
Caroline Schmidt
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
Annika Lundqvist
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
Martin Adiels
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
Fredrik Bäckhed
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Physiology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
Jochen M Schwenk
Science for Life Laboratory, Department of Protein Science, KTH-Royal Institute of Technology, Stockholm, Sweden
Per-Anders Jansson
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
Mathias Uhlén
Science for Life Laboratory, Department of Protein Science, KTH-Royal Institute of Technology, Stockholm, Sweden; Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
Göran Bergström
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Clinical Physiology, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden
Background: Comprehensive proteomics profiling may offer new insights into the dysregulated metabolic milieu of type 2 diabetes, and in the future, serve as a useful tool for personalized medicine. This calls for a better understanding of circulating protein patterns at the early stage of type 2 diabetes as well as the dynamics of protein patterns during changes in metabolic status. Methods: To elucidate the systemic alterations in early-stage diabetes and to investigate the effects on the proteome during metabolic improvement, we measured 974 circulating proteins in 52 newly diagnosed, treatment-naïve type 2 diabetes subjects at baseline and after 1 and 3 months of guideline-based diabetes treatment, while comparing their protein profiles to that of 94 subjects without diabetes. Findings: Early stage type 2 diabetes was associated with distinct protein patterns, reflecting key metabolic syndrome features including insulin resistance, adiposity, hyperglycemia and liver steatosis. The protein profiles at baseline were attenuated during guideline-based diabetes treatment and several plasma proteins associated with metformin medication independently of metabolic variables, such as circulating EPCAM. Interpretation: The results advance our knowledge about the biochemical manifestations of type 2 diabetes and suggest that comprehensive protein profiling may serve as a useful tool for metabolic phenotyping and for elucidating the biological effects of diabetes treatments. Funding: This work was supported by the Swedish Heart and Lung Foundation, the Swedish Research Council, the Erling Persson Foundation, the Knut and Alice Wallenberg Foundation, and the Swedish state under the agreement between the Swedish government and the county councils (ALF-agreement).
