Relation of plasma ceramides to visceral adiposity, insulin resistance and the development of type 2 diabetes mellitus

the Dallas Heart Study

Ian J Neeland, Shruti Singh, Darren K McGuire, Gloria L Vega, Thomas Roddy, Dermot F. Reilly, Jose Castro-Perez, Julia Kozlitina, Philipp E Scherer

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Aims/hypothesis: Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort. Methods: A total of 1557 participants in the Dallas Heart Study without type 2 diabetes underwent measurements of metabolic biomarkers, fat depots by MRI and plasma ceramides by liquid chromatography-mass spectrometry. Diabetes outcomes were assessed after 7 years. Associations of body fat and insulin resistance with ceramides at baseline and of ceramides with incident diabetes outcomes were analysed. Results: The cohort had a mean age of 43 years, with 58% women, 45% black participants and a mean BMI of 28 kg/m2. Total cholesterol levels were associated with all ceramides, but higher triacylglycerols and lower HDL-cholesterol and adiponectin were associated only with saturated fatty acid chain ceramides (p < 0.0003). After adjusting for clinical characteristics and total body fat, visceral adipose tissue was positively associated with saturated fatty acid ceramides (per SD, β = 0.16 to 0.18) and inversely associated with polyunsaturated fatty acid ceramides (β = −0.14 to −0.16, p < 0.001 for all). Lower-body subcutaneous fat showed an opposite pattern to that for visceral fat. HOMA-IR was positively associated with saturated (β = 0.08 to 0.09, p < 0.001) and inversely with polyunsaturated ceramides (β = −0.06 to −0.07, p < 0.05). Ceramides were not associated with incident type 2 diabetes after adjustment for clinical factors. Conclusions/interpretation: Plasma ceramides demonstrate a biologically complex relationship with metabolic and imaging indicators of dysfunctional adiposity. The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation.

Original languageEnglish (US)
JournalDiabetologia
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Ceramides
Adiposity
Type 2 Diabetes Mellitus
Insulin Resistance
Intra-Abdominal Fat
Adipose Tissue
Fatty Acids
Body Fat Distribution
Sphingolipids
Subcutaneous Fat
Adiponectin
Metabolic Networks and Pathways
Unsaturated Fatty Acids
Liquid Chromatography
HDL Cholesterol
Mass Spectrometry
Triglycerides
Biomarkers
Fats

Keywords

  • Ceramides
  • Liver fat
  • Obesity
  • Prediabetes
  • Type 2 diabetes mellitus
  • Visceral adiposity

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{a12c0342665d4aee9e732bc80302ea83,
title = "Relation of plasma ceramides to visceral adiposity, insulin resistance and the development of type 2 diabetes mellitus: the Dallas Heart Study",
abstract = "Aims/hypothesis: Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort. Methods: A total of 1557 participants in the Dallas Heart Study without type 2 diabetes underwent measurements of metabolic biomarkers, fat depots by MRI and plasma ceramides by liquid chromatography-mass spectrometry. Diabetes outcomes were assessed after 7 years. Associations of body fat and insulin resistance with ceramides at baseline and of ceramides with incident diabetes outcomes were analysed. Results: The cohort had a mean age of 43 years, with 58{\%} women, 45{\%} black participants and a mean BMI of 28 kg/m2. Total cholesterol levels were associated with all ceramides, but higher triacylglycerols and lower HDL-cholesterol and adiponectin were associated only with saturated fatty acid chain ceramides (p < 0.0003). After adjusting for clinical characteristics and total body fat, visceral adipose tissue was positively associated with saturated fatty acid ceramides (per SD, β = 0.16 to 0.18) and inversely associated with polyunsaturated fatty acid ceramides (β = −0.14 to −0.16, p < 0.001 for all). Lower-body subcutaneous fat showed an opposite pattern to that for visceral fat. HOMA-IR was positively associated with saturated (β = 0.08 to 0.09, p < 0.001) and inversely with polyunsaturated ceramides (β = −0.06 to −0.07, p < 0.05). Ceramides were not associated with incident type 2 diabetes after adjustment for clinical factors. Conclusions/interpretation: Plasma ceramides demonstrate a biologically complex relationship with metabolic and imaging indicators of dysfunctional adiposity. The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation.",
keywords = "Ceramides, Liver fat, Obesity, Prediabetes, Type 2 diabetes mellitus, Visceral adiposity",
author = "Neeland, {Ian J} and Shruti Singh and McGuire, {Darren K} and Vega, {Gloria L} and Thomas Roddy and Reilly, {Dermot F.} and Jose Castro-Perez and Julia Kozlitina and Scherer, {Philipp E}",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s00125-018-4720-1",
language = "English (US)",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",

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TY - JOUR

T1 - Relation of plasma ceramides to visceral adiposity, insulin resistance and the development of type 2 diabetes mellitus

T2 - the Dallas Heart Study

AU - Neeland, Ian J

AU - Singh, Shruti

AU - McGuire, Darren K

AU - Vega, Gloria L

AU - Roddy, Thomas

AU - Reilly, Dermot F.

AU - Castro-Perez, Jose

AU - Kozlitina, Julia

AU - Scherer, Philipp E

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Aims/hypothesis: Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort. Methods: A total of 1557 participants in the Dallas Heart Study without type 2 diabetes underwent measurements of metabolic biomarkers, fat depots by MRI and plasma ceramides by liquid chromatography-mass spectrometry. Diabetes outcomes were assessed after 7 years. Associations of body fat and insulin resistance with ceramides at baseline and of ceramides with incident diabetes outcomes were analysed. Results: The cohort had a mean age of 43 years, with 58% women, 45% black participants and a mean BMI of 28 kg/m2. Total cholesterol levels were associated with all ceramides, but higher triacylglycerols and lower HDL-cholesterol and adiponectin were associated only with saturated fatty acid chain ceramides (p < 0.0003). After adjusting for clinical characteristics and total body fat, visceral adipose tissue was positively associated with saturated fatty acid ceramides (per SD, β = 0.16 to 0.18) and inversely associated with polyunsaturated fatty acid ceramides (β = −0.14 to −0.16, p < 0.001 for all). Lower-body subcutaneous fat showed an opposite pattern to that for visceral fat. HOMA-IR was positively associated with saturated (β = 0.08 to 0.09, p < 0.001) and inversely with polyunsaturated ceramides (β = −0.06 to −0.07, p < 0.05). Ceramides were not associated with incident type 2 diabetes after adjustment for clinical factors. Conclusions/interpretation: Plasma ceramides demonstrate a biologically complex relationship with metabolic and imaging indicators of dysfunctional adiposity. The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation.

AB - Aims/hypothesis: Ceramides are sphingolipids that contribute to insulin resistance in preclinical studies. We hypothesised that plasma ceramides would be associated with body fat distribution, insulin resistance and incident type 2 diabetes in a multi-ethnic cohort. Methods: A total of 1557 participants in the Dallas Heart Study without type 2 diabetes underwent measurements of metabolic biomarkers, fat depots by MRI and plasma ceramides by liquid chromatography-mass spectrometry. Diabetes outcomes were assessed after 7 years. Associations of body fat and insulin resistance with ceramides at baseline and of ceramides with incident diabetes outcomes were analysed. Results: The cohort had a mean age of 43 years, with 58% women, 45% black participants and a mean BMI of 28 kg/m2. Total cholesterol levels were associated with all ceramides, but higher triacylglycerols and lower HDL-cholesterol and adiponectin were associated only with saturated fatty acid chain ceramides (p < 0.0003). After adjusting for clinical characteristics and total body fat, visceral adipose tissue was positively associated with saturated fatty acid ceramides (per SD, β = 0.16 to 0.18) and inversely associated with polyunsaturated fatty acid ceramides (β = −0.14 to −0.16, p < 0.001 for all). Lower-body subcutaneous fat showed an opposite pattern to that for visceral fat. HOMA-IR was positively associated with saturated (β = 0.08 to 0.09, p < 0.001) and inversely with polyunsaturated ceramides (β = −0.06 to −0.07, p < 0.05). Ceramides were not associated with incident type 2 diabetes after adjustment for clinical factors. Conclusions/interpretation: Plasma ceramides demonstrate a biologically complex relationship with metabolic and imaging indicators of dysfunctional adiposity. The role of ceramides in a shared pathway of metabolic dysfunction linking visceral adiposity and insulin resistance requires further investigation.

KW - Ceramides

KW - Liver fat

KW - Obesity

KW - Prediabetes

KW - Type 2 diabetes mellitus

KW - Visceral adiposity

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