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Alterations in Biomarkers Related to Glycemia, Lipid Metabolism, and Inflammation up to 20 Years Before Diagnosis of Type 1 Diabetes in Adults: Findings From the AMORIS Cohort

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posted on 07.12.2021, 19:12 by Katharina Herzog, Tomas Andersson, Valdemar Grill, Niklas Hammar, Håkan Malmström, Mats Talbäck, Göran Walldius, Sofia Carlsson
Objective: Type 1 diabetes is described to have an acute onset, but autoantibodies can appear several years preceding diagnosis. This suggests a long preclinical phase, which may also include metabolic parameters. Here we assessed whether elevations in glycaemic, lipid, and other metabolic biomarkers were associated with future type 1 diabetes risk in adults.

Research Design and Methods: We studied 591,239 individuals from the Swedish AMORIS cohort followed from 1985-1996 to 2012. Through linkage to national patient, diabetes, and prescription registers, we identified incident type 1 diabetes. Using Cox regression models, we estimated hazard ratios for biomarkers at baseline and incident type 1 diabetes. We additionally assessed trajectories of biomarkers during the 25 years before type 1 diabetes diagnosis in a nested case-control design.

Results: We identified 1,122 type 1 diabetes cases during follow-up (average age at diagnosis: 53.3 years). The biomarkers glucose, fructosamine, triglycerides, the apolipoprotein B/A-I ratio, uric acid, alkaline phosphatase, and BMI were positively associated with type 1 diabetes risk. A higher apolipoprotein A-I was associated with a lower type 1 diabetes incidence. Already 15 years before diagnosis, type 1 diabetes cases had higher mean glucose, fructosamine, triglycerides, and uric acid levels compared to controls.

Conclusion: Alterations in biomarker levels related to glycaemia, lipid metabolism, and inflammation are associated with clinically diagnosed type 1 diabetes risk, and these may be elevated many years preceding diagnosis.

Funding

This study was supported by the Gunnar and Ingmar Jungner Foundation for Laboratory Medicine, Stockholm, Sweden [Dnr.1118/12-1]. SC is supported by grants from the Swedish Research Council [2018-03035] and FORTE (Swedish Research Council for Health, Working Life and Welfare) [2018-00337]. KH is supported by a Novo Nordisk postdoctoral fellowship run in partnership with Karolinska Institutet. The funding sources were not involved in the study design, the collection, analysis, and interpretation of data; nor in the writing of the report or in the decision to submit the article for publication.

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