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Diabetologia. 2018 Dec;61(12):2570-2579. doi: 10.1007/s00125-018-4720-1. Epub 2018 Aug 29.

Relation of plasma ceramides to visceral adiposity, insulin resistance and the development of type 2 diabetes mellitus: the Dallas Heart Study.

Author information

1
Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8830, USA. ian.neeland@utsouthwestern.edu.
2
Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8830, USA.
3
Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
4
Department of Clinical Nutrition, University of Texas Southwestern Medical Center, Dallas, TX, USA.
5
Dallas VA North Texas Health Care System, Dallas, TX, USA.
6
Agios Pharmaceuticals, Cambridge, MA, USA.
7
Cardiometabolic Disease, Merck & Co., Inc., Kenilworth, NJ, USA.
8
Genetics, Merck & Co., Inc., Kenilworth, NJ, USA.
9
Waters Corporation, Milford, MA, USA.
10
McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA.
11
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
12
Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA.

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

PMID:
30159588
PMCID:
PMC6219923
[Available on 2019-12-01]
DOI:
10.1007/s00125-018-4720-1
[Indexed for MEDLINE]

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