Abstract
Background: Type 2 diabetes (T2D) is characterized by alterations in polyunsaturated fatty acid (PUFA) metabolism
that is dominantly regulated by desaturase enzymes.
Objective: To investigate the association between the FADS cluster variant rs174455 and estimated desaturase
activity in new T2D patients
Methods: 160 participants were chosen for this case-control study (80 new drug-naive T2D patients and 80
matched healthy controls). The rs174455 variant was also genotyped by Sanger sequencing. Serum PUFA was
quantified by gas chromatography (for omega-3) and by enzyme-linked immunosorbent assays for omega-6
pathways. Desaturase activity was checked by product-to-precursor ratios.
Results: There were no significant differences in genotype or allele frequencies between T2D and control cohorts.
However, the heterozygous AG genotype resulted in significantly lower alpha-linolenic acid (ALA) levels and
higher gamma-linolenic acid (GLA) levels in individuals with T2D than in those with the homozygous AA genotype.
AG genotype was significantly associated with high omega-6 Delta-6 desaturase (D6D) activity.
Furthermore, a stepwise multiple linear regression analysis demonstrated that insulin resistance (HOMA-IR) and
systemic inflammation (hs-CRP) were the most significant independent clinical predictors of altered omega-6
Delta-6 desaturase activity.
Conclusion: Furthermore, a stepwise multiple linear regression analysis demonstrated that insulin resistance
(HOMA-IR) and systemic inflammation (hs-CRP) were the most significant independent clinical correlates of
altered omega-6 Delta-6 desaturase activity. However, the key drivers of these altered enzymatic pathways are
driven by major metabolic disturbances, including insulin resistance and inflammation.
| Has the manuscript been published | published |
|---|---|
| Intend to be published in the IJPS ? | NO |
