Ceramide stearic to palmitic acid ratio predicts incident diabetes
Hilvo, Mika; Salonurmi, Tuire; Havulinna, Aki S.; Kauhanen, Dimple; Pedersen, Eva Ringdal; Tell, Grethe S.; Meyer, Klaus; Teeriniemi, Anna-Maria; Laatikainen, Tiina; Jousilahti, Pekka; Savolainen, Markku J.; Nygård, Ottar; Salomaa, Veikko; Laaksonen, Reijo
Peer reviewed, Journal article
Published version

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https://hdl.handle.net/1956/22448Utgivelsesdato
2018-03-15Metadata
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Originalversjon
https://doi.org/10.1007/s00125-018-4590-6Sammendrag
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.