Katharina Herzog, 1 Tomas Andersson, 1,2 Valdemar Grill, 3 Niklas Hammar, 1 Håkan Malmstr€ om, 1,4 Mats Talb€ ack 1 , G€ oran Walldius, 1 and Sofia Carlsson 1 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 https://doi.org/10.2337/dc21-1238 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 eleva- tions in glycemic, 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 prescrip- tion registers, we identified incident type 1 diabetes. Using Cox regression mod- els, 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 of patient at diagnosis: 53.3 years). The biomarkers glucose, fructosamine, triglycer- ides, the ratio of apolipoprotein (apo)B to apoA-I, uric acid, alkaline phosphatase, and BMI were positively associated with type 1 diabetes risk. Higher apoA-I was associated with lower type 1 diabetes incidence. Already 15 years before diagno- sis, type 1 diabetes cases had higher mean glucose, fructosamine, triglycerides, and uric acid levels compared with control subjects. CONCLUSIONS Alterations in biomarker levels related to glycemia, lipid metabolism, and inflam- mation are associated with clinically diagnosed type 1 diabetes risk, and these may be elevated many years preceding diagnosis. Type 1 diabetes accounts for 99% of all diabetes in children and adolescents but can develop at any age. Notably, a recent study based on data from UK biobank 1 Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden 2 Centre for Occupational and Environmental Medicine, Stockholm County Council, Stockholm, Sweden 3 Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway 4 R&D, Swedish Orphan Biovitrum AB, Stockholm, Sweden Corresponding author: Katharina Herzog, katharina.herzog@ki.se Received 14 June 2021 and accepted 9 November 2021 This article contains supplementary material online at https://doi.org/10.2337/figshare.16967647. © 2022 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www. diabetesjournals.org/content/license. EPIDEMIOLOGY/HEALTH SERVICES RESEARCH Diabetes Care 1 Downloaded from http://diabetesjournals.org/care/article-pdf/doi/10.2337/dc21-1238/634221/dc211238.pdf by guest on 24 December 2021