Plasma Dihydroceramides Are Diabetes Susceptibility Biomarker Candidates in Mice and Humans

Cell Rep. 2017 Feb 28;18(9):2269-2279. doi: 10.1016/j.celrep.2017.02.019.

Abstract

Plasma metabolite concentrations reflect the activity of tissue metabolic pathways and their quantitative determination may be informative about pathogenic conditions. We searched for plasma lipid species whose concentrations correlate with various parameters of glucose homeostasis and susceptibility to type 2 diabetes (T2D). Shotgun lipidomic analysis of the plasma of mice from different genetic backgrounds, which develop a pre-diabetic state at different rates when metabolically stressed, led to the identification of a group of sphingolipids correlated with glucose tolerance and insulin secretion. Quantitative analysis of these and closely related lipids in the plasma of individuals from two population-based prospective cohorts revealed that specific long-chain fatty-acid-containing dihydroceramides were significantly elevated in the plasma of individuals who will progress to diabetes up to 9 years before disease onset. These lipids may serve as early biomarkers of, and help identify, metabolic deregulation in the pathogenesis of T2D.

Keywords: T2D; biomarkers; ceramides; diabetes; dihydroceramides; glucose intolerance; high-fat diet; human; insulin sensitivity; lipidomics; metabolic challenge; mouse; prognostic; prospective cohort.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biomarkers / blood*
  • Blood Glucose / metabolism
  • Ceramides / blood*
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / metabolism
  • Disease Susceptibility / blood*
  • Female
  • Glucose Intolerance / blood
  • Glucose Intolerance / metabolism
  • Glucose Tolerance Test / methods
  • Humans
  • Insulin / blood
  • Insulin Resistance / physiology
  • Lipids / blood
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Middle Aged
  • Prospective Studies
  • Sphingolipids / blood

Substances

  • Biomarkers
  • Blood Glucose
  • Ceramides
  • Insulin
  • Lipids
  • Sphingolipids
  • dihydroceramide