Reduced expression of OXPHOS and DNA damage genes is linked to protection from microvascular complications in long-term type 1 diabetes: the PROLONG study.

Autor:	Özgümüş T; Department of Clinical Science, Center for Diabetes Research, University of Bergen, 5032, Bergen, Norway., Sulaieva O; Medical Laboratory CSD, Vasylkivska Str. 45, Kyiv, Ukraine., Jessen LE; Section for Bioinformatics, Department of Health Technology, Technical University of Denmark, Lyngby, Denmark., Jain R; Department of Clinical Sciences/Genomics, Diabetes and Endocrinology, Lund University Diabetes Centre, 205 02, Malmö, Sweden., Falhammar H; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden., Nyström T; Unit for Diabetes Research, Division of Internal Medicine, Department of Clinical Science and Education, Karolinska Institute, South Hospital, Stockholm, Sweden., Catrina SB; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.; Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, Stockholm, Sweden.; Center for Diabetes, Academic Specialist Centrum, Stockholm, Sweden., Jörneskog G; Division of Internal Medicine, Department of Clinical Sciences, Karolinska Institute, Danderyd University Hospital, Stockholm, Sweden., Groop L; Department of Clinical Sciences/Genomics, Diabetes and Endocrinology, Lund University Diabetes Centre, 205 02, Malmö, Sweden.; Institute for Molecular Medicine Finland FIMM, University of Helsinki, Helsinki, Finland., Eliasson M; Sunderby Research Unit, Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden., Eliasson B; Department of Medicine, University of Gothenburg, Gothenburg, Sweden., Brismar K; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden., Stokowy T; Department of Clinical Science, University of Bergen, 5021, Bergen, Norway., Nilsson PM; Department of Clinical Sciences/Genomics, Diabetes and Endocrinology, Lund University Diabetes Centre, 205 02, Malmö, Sweden., Lyssenko V; Department of Clinical Science, Center for Diabetes Research, University of Bergen, 5032, Bergen, Norway. Valeriya.Lyssenko@uib.no.; Department of Clinical Sciences/Genomics, Diabetes and Endocrinology, Lund University Diabetes Centre, 205 02, Malmö, Sweden. Valeriya.Lyssenko@uib.no.
Jazyk:	angličtina
Zdroj:	Scientific reports [Sci Rep] 2021 Oct 20; Vol. 11 (1), pp. 20735. Date of Electronic Publication: 2021 Oct 20.
DOI:	10.1038/s41598-021-00183-z
Abstrakt:	Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes. (© 2021. The Author(s).)
Databáze:	MEDLINE
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