Clinical correlates of plasma insulin levels over the life course and association with incident type 2 diabetes: The Framingham Heart Study

Wolfgang Lieb, Camila Mac Iel De Oliveira, Stephanie Pan, Justin Basile Echouffo-Tcheugui, Katharina Susanne Weber, Ramachandran S. Vasan, Vanessa Xanthakis

Research output: Contribution to journalArticlepeer-review


Introduction Insulin is a glucose-lowering hormone that affects carbohydrate, lipid, and protein metabolism. Limited data exist on the correlates of insulin levels over the life course in healthy community-dwelling individuals. Research design and methods Using multilevel modeling of multiple serial observations over 21 years, we assessed the longitudinal correlates of fasting insulin and the cross-sectional correlates of fasting and 2-hour (2h, post 75 g glucose challenge) plasma insulin concentrations in 2140 relatively healthy Framingham Heart Study participants without diabetes (61% women; mean age, 42 years). We used multivariable-adjusted Cox regression to relate glycemic markers (fasting and 2h-insulin, fasting glucose, 2h-glucose, and hemoglobin A 1C) to the risk of type 2 diabetes during follow-up. Results Over the life course, fasting insulin concentrations were inversely associated with age, male sex, and physical activity, whereas waist circumference, the total/high-density lipoprotein (HDL) cholesterol ratio, and blood triglycerides were positively associated with insulin levels (p<0.005 for all). Male sex (inversely related) and the total/HDL cholesterol ratio (positively related) emerged as the most important cross-sectional correlates of 2h-insulin (p<0.005 for all). All markers were associated with higher risk of type 2 diabetes (352 cases, median follow-up 18 years, p<0.001 for all). Conclusions We observed common and distinct correlates of fasting and 2h-insulin levels. Our findings highlight a potential role of insulin in lipid and lipoprotein metabolism. Furthermore, fasting and 2h-insulin are critical markers of future diabetes risk. Further studies are needed to confirm our findings.

Original languageEnglish (US)
Article numbere002581
JournalBMJ Open Diabetes Research and Care
Issue number1
StatePublished - Feb 21 2022
Externally publishedYes


  • diabetes mellitus
  • fasting
  • insulin
  • longitudinal studies
  • type 2

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism


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