Department of Basic Sciences, Center for Environmental Health Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS, USA.
Diabetes Metab Res Rev. 2018 Mar;34(3). doi: 10.1002/dmrr.2967. Epub 2017 Dec 14.
A longitudinal study assessed serum paraoxonase 1 (PON1) activity and concentration as affected by age and as associated with the development of type 2 diabetes (T2D). PON1's recently established physiological function is the hydrolysis of lipolactones in oxidized LDL particles.
Serum samples and clinical data collected and stored at different time points over a 20-year interval in the Air Force Health Study were analysed. PON1 activity and concentration and C-reactive protein concentration in samples from the same individuals 20 years apart were compared using a paired t test (n = 159). A case-control study design and multivariable logistic regression analysis assessed the association of PON1's activity and concentration with the subsequent development of T2D (n = 222 and α = 0.10).
No difference with age was found in PON1 activity assessed using 3 substrates, paraoxon (P = 0.897), phenyl acetate (P = 0.994), and dihydrocoumarin (P = 0.505), or PON1 serum concentration (P = 0.357). C-reactive protein concentration increased 0.7 mg/L (P = 0.004) over the 20-year interval. Lower PON1 activity assayed with phenyl acetate (P = 0.015, OR = 1.25 per 1000 U/L decrease) was associated with an increased risk of developing T2D as was a lower PON1 serum concentration (P = 0.004, OR = 1.72 per 2 μmol/L decrease). PON1 activity assayed with paraoxon (P = 0.681) or dihydrocoumarin (P = 0.136) was not associated with the development of T2D.
Lower PON1 activity and concentration were associated with an increased risk of developing T2D when adjusted for many of the common risk markers for T2D previously identified. Thus, PON1 may have merit as a biomarker for the development of T2D.
一项纵向研究评估了血清对氧磷酶 1(PON1)活性和浓度随年龄的变化,并与 2 型糖尿病(T2D)的发展相关联。PON1 最近确立的生理功能是水解氧化型 LDL 颗粒中的脂乳酮。
分析了空军卫生研究中在 20 年的时间间隔内不同时间点收集和储存的血清样本和临床数据。使用配对 t 检验比较了相隔 20 年的同一个体样本中的 PON1 活性和浓度以及 C-反应蛋白浓度(n=159)。病例对照研究设计和多变量逻辑回归分析评估了 PON1 的活性和浓度与随后发生的 T2D 的关联(n=222,α=0.10)。
使用 3 种底物(对氧磷、苯乙酸和二氢香豆素)评估 PON1 活性时,未发现年龄差异(P=0.897、P=0.994 和 P=0.505),或 PON1 血清浓度(P=0.357)有差异。在 20 年的时间间隔内,C-反应蛋白浓度增加了 0.7mg/L(P=0.004)。用苯乙酸测定的 PON1 活性较低(P=0.015,OR=每降低 1000U/L 增加 1.25)与 T2D 发病风险增加相关,PON1 血清浓度较低(P=0.004,OR=每降低 2μmol/L 增加 1.72)。用对氧磷(P=0.681)或二氢香豆素(P=0.136)测定的 PON1 活性与 T2D 的发生无关。
在调整了许多先前确定的 T2D 的常见风险标志物后,PON1 活性和浓度较低与 T2D 发病风险增加相关。因此,PON1 作为 T2D 发病的生物标志物可能具有一定价值。