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

Abstract

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
Volume10
Issue number1
DOIs
StatePublished - Feb 21 2022
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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