APPLICATION OF NON-TARGETED METABOLIC PROFILING TO REVEAL POTENTIAL BIOMARKERS LINKING EGG INTAKE AND PREVIOUSLY OBSERVED LOWER RISK OF DEVELOPING TYPE 2 DIABETES IN MIDDLE-AGED MEN

Dietary cholesterol has been suggested to impair glucose metabolism and promote inflammation, thereby potentially increasing the risk of type 2 diabetes (T2D). Due to its high cholesterol content, high consumption of eggs has traditionally been discouraged. In middle-aged men from the prospective, population-based cohort Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) from Eastern Finland, higher egg intake was associated with a lower risk of T2D though the mechanism remains unclear. Here we present the application of non-targeted metabolite profiling to reveal potential biomarkers linking egg intake and the risk of T2D. From the KIHD study we collected 239 baseline plasma samples in 4 groups: 1) subjects with high egg intake who developed T2D within the average follow-up of 19.3 years (cases), 2) cases with low egg intake, 3) subjects with high egg intake who remained free of T2D within the follow-up period (controls), and 4) controls with low egg intake. Non-targeted metabolite profiling was performed with high performance liquid chromatography coupled with tandem mass spectrometry. The comparison of metabolite profile between cases and controls showed that some lysophosphatidylcholine species were higher in controls, whereas phosphatidylcholine species were mostly more abundant in cases. Although eggs are a major dietary source of choline, plasma choline level was not significantly different between high egg and low egg intake groups (p-value 0.389). Interestingly, plasma choline (odds ratio (OR) 0.69; 95% CI 0.53, 0.90; p-value 0.006) and phosphocholine (OR 0.74; 95% CI 0.56, 0.95; p-value 0.021) indicated lower OR of T2D. These results suggest that the inverse association of high egg intake with the risk of T2D in this study population of middle-aged men may be mediated by alterations of choline and its phospholipid-bound metabolites. Further studies are required to investigate the molecular and cellular mechanisms linking egg intake with the development of T2D.