A Newly Developed Indicator of Overeating Saturated Fat Based on Serum Fatty Acids and Amino Acids and Its Association With Incidence of Type 2 Diabetes: Evidence From Two Randomized Controlled Feeding Trials and a Prospective Study

Abstract

Objective: Hyper-caloric intake of saturated fatty acids (SFAs) is common in modern societies, probably contributing to the epidemic of type 2 diabetes mellitus (T2DM). This study conducted two randomized controlled trials (RCTs) for developing a new indicator that can assess the nutritional status and examined its association with incidence of T2DM. Methods: In RCT 1, healthy participants were randomly assigned into three groups, namely, control group (n = 40), overfeeding group 1 (100 g butter per day, n = 37), and overfeeding group 2 (120 g butter per day, n = 37). In RCT 2, healthy subjects were randomly assigned into two groups, namely, control group (n = 52) and high-fat group (300-extra kcal/day from diet that was designed by high-fat diet, n = 58). In the prospective cohort, 4,057 participants aged 20–74 years were enrolled and followed up over 5.3 years. Serum profiles of fatty acids and amino acids were measured. Results: In RCT 1, serum fatty acids, including C14:0 and C18:0, increased, whereas C18:2, C20:4, C22:5, and C22:6 decreased; serum amino acids, including tyrosine, alanine, and aminobutyric acid, increased, whereas histidine and glycine decreased (p < 0.05). Among these serum fatty acids and amino acids, changes in C14:0, C20:4, tyrosine, histidine, and glycine were also observed in RCT 2. An indicator was developed based on the five fatty acids and amino acids, namely, C14:0 × tyrosine × 1,000/[C20:4 × (glycine + histidine)], and it significantly identified participants in the intervention group with area under the curve (AUC) (95% CI) being 0.85 (0.77–0.92). The indicator was significantly associated with incidence of T2DM in the prospective cohort with HRs (95% CIs) from bottom quartile to top quartile being 1,1.21 (0.82–1.77), 1.60 (1.12–2.30), 2.04 (1.42–2.94). Conclusion: The newly developed indicator in RCTs can be used in assessing the nutritional status of hypercaloric intake of SFA and predicting the development of T2DM.