Serum Selenoprotein P Levels in Patients with Type 2 Diabetes and Prediabetes: Implications for Insulin Resistance, Inflammation, and Atherosclerosis

Abstract

CONTEXT AND OBJECTIVE: The dysregulation of hepatokines may be associated with the pathogenesis of insulin resistance and type 2 diabetes. A recent study has suggested that selenoprotein P (SeP), a novel hepatokine, may play a role in the regulation of glucose metabolism and insulin sensitivity. We examined the relationship between circulating SeP levels and clinical parameters associated with insulin resistance in humans. PARTICIPANTS AND METHODS: We compared serum SeP concentrations in 100 subjects with diverse glucose tolerance statuses. Furthermore, we evaluated the relationship between SeP and cardiometabolic risk factors including insulin resistance, high-sensitivity C-reactive protein, and carotid intima-media thickness. RESULTS: Serum SeP concentrations were significantly higher in patients with type 2 diabetes or prediabetes than those with normal glucose tolerance (all P < 0.01) and decreased in a stepwise manner [1032.4 (495.9-2149.4) vs. 867.3 (516.3-1582.7) vs. 362.0 (252.5-694.5), P = 0.004]. In addition, overweight and obese subjects had significantly increased SeP levels compared with lean subjects (P = 0.002). Spearman's partial correlation analysis adjusted for age and gender showed a significant relationship between SeP and cardiometabolic factors including body mass index, waist circumference, systolic blood pressure, triglycerides, glucose, hemoglobin A1c, aspartate aminotransferase, and insulin resistance. Furthermore, in multiple regression analyses, SeP showed an independent association with carotid intima-media thickness as well as high-sensitivity C-reactive protein, even after adjustment for other confounding factors. CONCLUSIONS: Circulating SeP concentrations were elevated in patients with glucose metabolism dysregulation and were related to various cardiometabolic parameters including insulin resistance, inflammation, and atherosclerosis.