Couch Sarah C, Crandell Jamie, King Irena, Peairs Abigail, Shah Amy S, Dolan Lawrence M, Tooze Janet, Crume Tessa, Mayer-Davis Elizabeth
3202 Eden Avenue, French Building East, Room 364, University of Cincinnati Medical Center, Cincinnati, OH 45267-0394.
Carrington Hall #7460, School of Nursing and Department of Biostatistics, UNC, Chapel Hill, NC 27599.
J Diabetes Complications. 2017 Jan;31(1):67-73. doi: 10.1016/j.jdiacomp.2016.10.002. Epub 2016 Oct 5.
In this longitudinal study we explored the relationships between plasma n-3 and n-6 polyunsaturated fatty acids (PUFAs) and Δ5 and Δ6 desaturase activities (D5D and D6D, respectively) and fasting lipids in youth with type 1 diabetes (T1D).
Incident cases of T1D in youth <20years of age who were seen for a baseline study visit (N=914) and a 1-year follow-up visit (N=416) were included. Fasting blood samples were obtained at each visit and plasma phospholipid n-6 PUFAs were measured, which included linoleic acid (LA), dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA); n-3 PUFAs included α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Estimated D5D and D6D were calculated as FA product-to-precursor ratios, where D5D=AA/DGLA and D6D=DGLA/LA. To examine the longitudinal relationships between long chain PUFAs, desaturase activities and fasting plasma lipids in youth with T1D mixed effects models were used for each individual PUFAs, D5D and D6D, adjusted for demographics, clinic site, diabetes duration, insulin regimen, insulin dose/kg, HbA1c, insulin sensitivity score, and body mass index with random effects to account for the repeated measurements.
Favorable lipid associations were found between LA and low-density lipoprotein (LDL) cholesterol (β=-0.58, p<0.05); AA, plasma triglycerides (TG) (β=-0.04, p<0.05) and TG/high-density lipoprotein (HDL)-C ratio (β=-0.04, p<0.05); and D5D, plasma TG (β=-0.2, p<0.05) and TG/HDL-cholesterol ratio (β=-0.23, p<0.05). Findings were mixed for the n-3 PUFAs and DGLA: ALA was positively associated with plasma TG (β=0.33, p<0.05) and HDL cholesterol (β=9.86, p<0.05); EPA was positively associated with total cholesterol (β=8.17, p<0.05), LDL cholesterol (β=5.74, p<0.01) and HDL cholesterol (β=2.27, p<0.01); and DGLA was positively associated with TG/HDL-cholesterol ratio (β=0.05, P<0.05).
Findings suggest that the most abundant PUFA, LA as well as its metabolic bi-product AA, may be important targets for CVD lipid risk factor reduction in youth with T1D.
在这项纵向研究中,我们探讨了1型糖尿病(T1D)青少年血浆n-3和n-6多不饱和脂肪酸(PUFA)、Δ5和Δ6去饱和酶活性(分别为D5D和D6D)与空腹血脂之间的关系。
纳入年龄小于20岁的T1D初发病例,这些病例接受了基线研究访视(N = 914)和1年随访访视(N = 416)。每次访视时采集空腹血样,测量血浆磷脂n-6 PUFA,包括亚油酸(LA)、二高-γ-亚麻酸(DGLA)和花生四烯酸(AA);n-3 PUFA包括α-亚麻酸(ALA)、二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)。估计的D5D和D6D通过脂肪酸产物与前体的比率计算,其中D5D = AA/DGLA,D6D = DGLA/LA。为了研究T1D青少年中长链PUFA、去饱和酶活性与空腹血脂之间的纵向关系,对每个个体的PUFA、D5D和D6D使用混合效应模型,并对人口统计学、诊所地点、糖尿病病程、胰岛素治疗方案、胰岛素剂量/千克、糖化血红蛋白、胰岛素敏感性评分和体重指数进行调整,采用随机效应来考虑重复测量。
发现LA与低密度脂蛋白(LDL)胆固醇之间存在有利的脂质关联(β = -0.58,p < 0.05);AA与血浆甘油三酯(TG)(β = -0.04,p < 0.05)和TG/高密度脂蛋白(HDL)-C比率(β = -0.04,p < 0.05);D5D与血浆TG(β = -0.2,p < 0.05)和TG/HDL胆固醇比率(β = -0.23,p < 0.05)。n-3 PUFA和DGLA的结果不一:ALA与血浆TG(β = 0.33,p < 0.05)和HDL胆固醇(β = 9.86,p < 0.05)呈正相关;EPA与总胆固醇(β = 8.17,p < 0.05)、LDL胆固醇(β = 5.74,p < 0.01)和HDL胆固醇(β = 2.27,p < 0.01)呈正相关;DGLA与TG/HDL胆固醇比率(β = 0.05,P < 0.05)呈正相关。
研究结果表明,最丰富的PUFA,即LA及其代谢副产物AA,可能是降低T1D青少年心血管疾病脂质危险因素的重要靶点。