Ceramide stearic to palmitic acid ratio predicts incident diabetes

Hilvo, M; Salonurmi, T; Havulinna, AS; Kauhanen, D; Pedersen, ER; Tell, GS; Meyer, K; Teeriniemi, AM; Laatikainen, T; Jousilahti, P; Savolainen, MJ; Nygård, O; Salomaa, V; Laaksonen, R

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Date

2018

Author(s)

Hilvo, M

Salonurmi, T

Havulinna, AS

Kauhanen, D

Pedersen, ER

Tell, GS

Meyer, K

Teeriniemi, AM

Laatikainen, T

Jousilahti, P

Savolainen, MJ

Nygård, O

Salomaa, V

Laaksonen, R

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10.1007/s00125-018-4590-6

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Hilvo, M. Salonurmi, T. Havulinna, AS. Kauhanen, D. Pedersen, ER. Tell, GS. Meyer, K. Teeriniemi, AM. Laatikainen, T. Jousilahti, P. Savolainen, MJ. Nygård, O. Salomaa, V. Laaksonen, R. (2018). Ceramide stearic to palmitic acid ratio predicts incident diabetes. DIABETOLOGIA, 61 (6) , 1424–1434. 10.1007/s00125-018-4590-6.

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Abstract

Aims/hypothesis
Ceramide lipids have a role in the development of insulin resistance, diabetes and risk of cardiovascular disease. Here we investigated four ceramides and their ratios to find the best predictors of incident diabetes.

Methods
A validated mass-spectrometric method was applied to measure Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0) and Cer(d18:1/24:1) from serum or plasma samples. These ceramides were analysed in a population-based risk factor study (FINRISK 2002, n = 8045), in a cohort of participants undergoing elective coronary angiography for suspected stable angina pectoris (Western Norway Coronary Angiography Cohort [WECAC], n = 3344) and in an intervention trial investigating improved methods of lifestyle modification for individuals at high risk of the metabolic syndrome (Prevent Metabolic Syndrome [PrevMetSyn], n = 371). Diabetes risk score models were developed to estimate the 10 year risk of incident diabetes.

Results
Analysis in FINRISK 2002 showed that the Cer(d18:1/18:0)/Cer(d18:1/16:0) ceramide ratio was predictive of incident diabetes (HR per SD 2.23, 95% CI 2.05, 2.42), and remained significant after adjustment for several risk factors, including BMI, fasting glucose and HbA1c (HR 1.34, 95% CI 1.14, 1.57). The finding was validated in the WECAC study (unadjusted HR 1.81, 95% CI 1.53, 2.14; adjusted HR 1.39, 95% CI 1.16, 1.66). In the intervention trial, the ceramide ratio and diabetes risk scores significantly decreased in individuals who had 5% or more weight loss.

Conclusions/interpretation
The Cer(d18:1/18:0)/Cer(d18:1/16:0) ratio is an independent predictive biomarker for incident diabetes, and may be modulated by lifestyle intervention.