The association between plasma stearoyl Co-A desaturase-1 (SCD-1) activity and risk of incident Type 2 diabetes from the atherosclerosis risk in communities (ARIC) study

Abstract

Objective: Stearoyl Co-A desaturase (SCD-1), the rate limiting enzyme in monounsaturated fatty acid synthesis, is critical for lipid synthesis, lipid oxidation and possibly type 2 diabetes. This study characterized SCD-1 activity through fatty acids ratios in baseline plasma measurements and established their association with incident diabetes in the Atherosclerosis Risk in Communities (ARIC) study. Research Design & Methods: In 2782 Caucasian adults (age 45-64, 47% men) free of diabetes, baseline SCD-1 activity was approximated by plasma fatty acid ratios in cholesterol esters (SCD16c-16:1/16, SCD18c-18:1/18:0) and plasma phospholipids (SCD16p-16:1/16:0, SCD18p-18:1/18:0). Incident diabetes was ascertained during three follow up visits. The relationship between SCD-1 activity and incident diabetes was evaluated by Cox proportional hazards regression. Results: During follow-up, 208 (7.5%) participants developed diabetes (mean 8 years ± SD 2.1 years). The various SCD-1 ratios correlated with each other (p<0.001). After adjusting for age and gender, higher levels of SCD16c and SCD16p were positively associated with incident diabetes. Higher levels of SCD18p were inversely associated with incident diabetes. After additional adjustment for parental history of diabetes, smoking, blood pressure, activity, carbohydrate intake, fiber intake, saturated fat intake, Waist-hip ratio, education, alcohol, and body-mass-index (BMI), only SCD16c remained positively associated with incident diabetes (RR=1.1: 95%CI 1.01-1.30 ; p=0.03). This association disappeared with additional adjustment for insulin resistance. Conclusions: Approximation of SCD-1 activity by SCD16c was positively associated with incident diabetes but this association was weak, especially when considering common phenotypic measures (i.e. BMI and Waist-hip ratio). Measurements of SCD-1 activity should be further refined.