The epidemiology of prediabetes and its metabolomic features remain poorly characterized in the oldest old. Therefore, we characterized the serum lipidome in 635 nonagenarians and centenarians without type 2 diabetes (T2D) from the Long Life Family Study, a multicenter study of 583 families with a clustering of exceptional longevity. Despite a low T2D prevalence and incidence in the LLFS cohort, 361 (56.9%) of participants aged 90+ years had prediabetes at study entry based on either glycated hemoglobin or fasting serum glucose levels. We used LC/MS to initially assess 193 lipid metabolites in fasting serum in those with and without prediabetes. We tested the association of log transformed lipid metabolites with prediabetes using logistic regression with the Benjamini-Hochberg false-discovery rate method (FDR<0.05) , while adjusting for age, sex, fasting time, field center, and familial relatedness. 17 out of 193 annotated lipid metabolites were associated with prevalent prediabetes, with the strongest association found for phosphatidylethanolamine (PE 40:7) , which remained significant after additional adjustment for BMI (odds ratio (OR) =2.83; 95% confidence interval (CI) : 1.7-4.7) . Phosphatidylethanolamine might have proinflammatory properties and act as a positive modulator of membrane disruption induced by islet amyloid polypeptide, an amyloidogenic protein involved in T2D. Our data suggest that among the oldest old with exceptional longevity prediabetes burden is high, and that the phosphatidylethanolamine pathway might have an important role in the development of prediabetes. Future untargeted metabolomic analyses will investigate potential biomarkers that predict the transition from prediabetes to diabetes among the oldest old in this unique family study of healthy aging and exceptional longevity.


I. Miljkovic: None. R. Cvejkus: None. P. An: None. B. Thyagarajan: n/a. J. Mengel-from: None. M. Feitosa: None. A. N. Benbourenane: None. J. M. Zmuda: None.


National Institute of Health (U01AG023746)

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