Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
Metabolism. 2013 Jan;62(1):100-8. doi: 10.1016/j.metabol.2012.06.004. Epub 2012 Jul 21.
Evidence from pre-clinical studies suggests inhibition of stearoyl co-A desaturase-1 (SCD-1) activity improves insulin sensitivity. Translation of these findings to humans remains less defined. The purpose of this research was to evaluate the association between different measures of SCD-1 activity and incident diabetes in a large, prospective human study.
In 2738 white participants (aged 45-64 yrs, 47% men) who were free of diabetes at baseline, SCD-1 activity was estimated at baseline by plasma fatty acid ratios in cholesterol esters (SCD16c=16:1n-7/16:0, SCD18c =18:1n-9/18:0) and in phospholipids (SCD16p=16:1n-7/16:0, SCD18p=18:1n-9/18:0). Incident diabetes was ascertained during 3 follow-up visits. Cox proportional hazards regression was used to determine the association between estimated SCD-1 activity and incident diabetes.
During follow-up (mean 8.0±SE 2.1 years), 207 (7.6%) participants developed diabetes. After adjusting for age and sex, higher SCD16c, higher SCD16p, and lower SCD18p were significantly associated with incident diabetes. After additional adjustment for education, parental history of diabetes, smoking, dietary intake (carbohydrate, fiber, saturated/monounsaturated/polyunsaturated fat), alcohol use, physical activity, body mass index (BMI), waist-hip ratio, blood pressure, and lipid composition - only SCD16c remained significantly associated with incident diabetes (Hazard Ratio=1.1 linearly across decreasing quintiles, 95% CI 1.01-1.30; p =0.03) which remained nominally associated after adjusting for insulin resistance (p=0.05).
In a large community-based prospective cohort study, the estimate of SCD-1 activity by SCD16c had the strongest association with incident diabetes. Refinement of SCD-1 measurement and replication of its association with incident diabetes in an independent cohort is recommended.
临床前研究证据表明，硬脂酰辅酶 A 去饱和酶-1（SCD-1）活性抑制可改善胰岛素敏感性。但这些发现转化为人类的研究还不够明确。本研究的目的是在一项大型前瞻性人类研究中评估不同 SCD-1 活性指标与糖尿病发病的相关性。
在 2738 名基线时无糖尿病的白种人参与者（年龄 45-64 岁，47%为男性）中，基线时通过胆固醇酯中的脂肪酸比值（SCD16c=16:1n-7/16:0，SCD18c=18:1n-9/18:0）和磷脂中的 SCD-1 活性（SCD16p=16:1n-7/16:0，SCD18p=18:1n-9/18:0）来估计 SCD-1 活性。在 3 次随访期间确定糖尿病的发病情况。采用 Cox 比例风险回归来确定估计的 SCD-1 活性与新发糖尿病之间的相关性。
在随访期间（平均 8.0±SE 2.1 年），207 名（7.6%）参与者发生了糖尿病。在校正年龄和性别后，SCD16c 升高、SCD16p 升高和 SCD18p 降低与新发糖尿病显著相关。在进一步调整教育程度、父母糖尿病史、吸烟、饮食摄入（碳水化合物、纤维、饱和/单不饱和/多不饱和脂肪）、饮酒、体力活动、体重指数（BMI）、腰臀比、血压和血脂成分后-仅 SCD16c 与新发糖尿病仍显著相关（风险比在递减五分位数中呈 1.1 线性变化，95%CI 1.01-1.30；p=0.03），在调整胰岛素抵抗后，这种关联仍具有名义意义（p=0.05）。
在一项大型社区前瞻性队列研究中，SCD16c 估计的 SCD-1 活性与新发糖尿病的相关性最强。建议进一步细化 SCD-1 的测量，并在独立队列中验证其与新发糖尿病的相关性。
