ANALYSIS OF THE FATTY ACID SPECTRUM OF FREE FATTY ACIDS AND LIPID PROFILE IN TYPE 2 DIABETIC PATIENTS WITH DYSLIPIDEMIA AS A COMPONENT OF METABOLOMIC PROFILING IN DAPAGLIFLOZINE THERAPY
Keywords:type 2 diabetes mellitus, free fatty acids, serum lipid fractions, fatty acid spectrum, dapagliflozin
Background: The spectrum estimation of (FAs) as part of the metabolomic profiling can help predict cardiovascular fatty acids complications of the type 2 diabetes mellitus (DM) even before the onset of clinical symptoms, whilst the quantification of several FAs and the estimation of their relative levels in the dynamics of treating diseases can provide a fuller picture of fatty acid metabolism rather than researching a few individual FA.
The goal of the research was metabolomic profiling of free fatty acids in type 2 diabetes mellitus patients with dyslipidemia, in order to compare the fatty acid profile before and after treatment with dapagliflozin.
Materials and methods: 30 patients, aged 45 or older, with type 2 DM and dyslipidemia, HbA1c levels >7,5%, who took therapy 2000 mg of metformin were examined. Indicators of carbohydrate metabolism and lipid spectrum of blood serum were determined. The fatty acid composition of free FAs (FFA) was also determined by gas-liquid chromatography.
Results. After treating the patients with dapaglifozin for 1 year, the levels of cholesterol, triglycerides and FFA decreased drastically without increasing the dose of statins, however, no significant changes were observed in other lipids. Significant changes in the index of visceral obesity have also been reported, indicating a decrease in the risk of atherogenesis and improved visceral adipose tissue function.
As a result of the treatment, there occurred a significant decrease not only in the amount of FFA, but also changes in their fatty acid spectrum, more specifically the redistribution of saturated and unsaturated FFA towards the reduction of saturation by reducing palmitic, stearic and myristic acids and increasing unsaturation by increasing the proportion monounsaturated palmitoleic and polyunsaturated arachidonic acids.
Conclusions. It was shown that the influence of dapagliflozin therapy in patients with type 2 diabetes and dyslipidemia manifested in an increase in the ratio of the total amount of unsaturated to saturated in the free fatty acids fraction on the background of a general decrease in the levels of cholesterol and triglycerides. In addition to that, the decrease in the content of linoleic acid in the free fatty acids fraction may indicate an improvement in its conversion to arachidonic acid, which itself is a precursor of eicosanoids with anti-inflammatory, vasodilatory, neurotropic properties. Thus, the use of dapagliflozin doesn't just help to correct disorders in the lipid spectrum of serum, but also improves their bioavalibility to β-oxidation in the liver, because of change in the quality of free fatty acids, which indicates the effect of dapagliflozin on a metabolomic level and provides new insights into this medication.
Diabetes Care 2022;45 (1): 144-174. https://doi.org/10.2337/dc22-S010
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