Associations between long chain polyunsaturated fatty acids and cardiovascular lipid risk factors in youth with type 1 diabetes: SEARCH Nutrition Ancillary Study

Abstract

Purpose: 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).

Methods: 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.

Findings: 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).

Conclusion: 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.

Keywords: Cardiovascular disease; Desaturase; Lipids; Polyunsaturated fatty acids; Type 1 diabetes.

Figure 1

The n-3 and n-6 polyunsaturated fatty acid (PUFA) metabolic pathways where LA = Linoleic Acid; DGLA = Dihomo-γ-linolenic acid; AA = Arachidonic acid; ALA =α-linolenic acid; EPA = Eicosapentaenoic acid; DHA = Docosahexaenoic acid; D5D = delta 5 desaturation; D6D = delta 6 desaturation; the highlighted PUFAs were those measured in plasma phospholipids in the present study.