Author:
Jain Ruchi,Özgümüş Türküler,Jensen Troels Mygind,du Plessis Elsa,Keindl Magdalena,Møller Cathrine Laustrup,Falhammar Henrik,Nyström Thomas,Catrina Sergiu-Bogdan,Jörneskog Gun,Jessen Leon Eyrich,Forsblom Carol,Haukka Jani K.,Groop Per-Henrik,Rossing Peter,Groop Leif,Eliasson Mats,Eliasson Björn,Brismar Kerstin,Al-Majdoub Mahmoud,Nilsson Peter M.,Taskinen Marja-Riitta,Ferrannini Ele,Spégel Peter,Berg Tore Julsrud,Lyssenko Valeriya
Abstract
AbstractIdentification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual ß-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.
Publisher
Springer Science and Business Media LLC
Reference64 articles.
1. Jacobson, A. M. et al. The long-term effects of type 1 diabetes treatment and complications on health-related quality of life: a 23-year follow-up of the Diabetes Control and Complications/Epidemiology of Diabetes Interventions and Complications cohort. Diabetes Care 36, 3131–3138 (2013).
2. Ortiz, F. et al. Long-term mortality after kidney transplantation in a nationwide cohort of patients with type 1 diabetes in Finland. Diabetes Care 42, 55–61 (2019).
3. List of countries by incidence of Type 1 diabetes ages 0–14. Diabetes UK https://www.diabetes.org.uk/about_us/news_landing_page/uk-has-worlds-5th-highest-rate-of-type-1-diabetes-in-children/list-of-countries-by-incidence-of-type-1-diabetes-ages-0-to-14.
4. Pathak, V., Pathak, N. M., O’Neill, C. L., Guduric-Fuchs, J. & Medina, R. J. Therapies for type 1 diabetes: current scenario and future perspectives. Clin. Med. Insights Endocrinol. Diabetes 12, 1179551419844521 (2019).
5. Heilig, C. W. et al. Overexpression of glucose transporters in rat mesangial cells cultured in a normal glucose milieu mimics the diabetic phenotype. J. Clin. Invest. 96, 1802–1814 (1995).
Cited by
9 articles.
订阅此论文施引文献
订阅此论文施引文献，注册后可以免费订阅5篇论文的施引文献，订阅后可以查看论文全部施引文献