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

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.