Lipid Profile Modulates Cardiometabolic Risk Biomarkers Including Hypertension in People with Type-2 Diabetes: A Focus on Unbalanced Ratio of Plasma Polyunsaturated/Saturated Fatty Acids

Abstract

Type 2 diabetes mellitus (T2DM) is associated with lipid metabolism disorder, particularly elevated plasma levels of non-esterified free fatty acids (NEFFA) and an increased cardiovascular disease risk, such as essential hypertension (H). The plasma unbalance of saturated fatty acid (SFA)/polyunsaturated fatty acid (PUFA) ratio is a likely contributor, but the mechanisms involved are not clearly elucidated. The aim of this study is to explore the association between plasma SFA/PUFA ratio and the clusters of cardiometabolic syndrome (CMS), including the atherogenic biomarkers, inflammatory status, feeding patterns, and physical activity in people with T2DM with or without essential hypertension. The study was conducted on 784 adult male and female participants, aged between 30 and 50 years, and divided into 3 groups: 100 T2DM without hypertension (D); 368 T2DM with hypertension (DM); and 316 hypertensive participants without T2DM (H). All Participants were phenotyped regarding CMS clusters according to the NCEP/ATPIII criteria. Insulin resistance was assessed by Homeostasis model assessment (HOMA model). Metabolic, atherogenic, and inflammatory parameters were analyzed by biochemical methods; NEFFA by microfluorimetry; SFA, PUFA-n6 and PUFA-n3 by gas phase chromatography. Dietary lipids and physical activity were analyzed through the use of validated questionnaires. The clusters of CMS were found in all groups. Dyslipidemia was correlated with accretion NEFFA levels in all groups, but more accentuated in the DH group (r = +0.77; p < 0.001). Similarly, plasma PUFA/SFA ratio and PUFA-3 level was lower, concomitantly with a higher plasma ApoB100/ApoA1 (p < 0.001), lipoprotein (a), homocysteine (p < 0.001), and pro-inflammatory cytokines (TNFα, IL-6, IL1-β) in the DH group. Likewise, the depletion of PUFA-n3/PUFA-n6 ratio is associated with the decrease of omega 3-DHA (docosahexaenoic acid) and omega 3-EPA (eicosapentaenoic acid) (p < 0.001). It appears that the PUFAs-n3 ratio modulates cardiometabolic risk, inflammatory state and atherogenic biomarkers. The plasma unbalanced ratio of SFA/PUFA reflects dietary fatty acids intake. The contribution of dietary lipids is undisputed. Nutritional recommendations are required to determine the fatty acids ratio (saturated and unsaturated) provided in the diet.

Preventing the Increase in Lysophosphatidic Acids: A New Therapeutic Target in Pulmonary Hypertension?

“…Furthermore, it is now well known that reducing intake of saturated fatty acids may reduce LDL-c and CVD risks [28,29]. SFA possessed numerous deleterious effects such as inflammation, apoptosis, mitochondrial dysfunction and oxidative stress [30] but their impact has mainly been evaluated as non-esterified fatty acids [31]. Thus, the role of esterified SFA in LPA and LPL needs further investigations.…”

Effects of Three-Month Administration of High-Saturated Fat Diet and High-Polyunsaturated Fat Diets with Different Linoleic Acid (LA, C18:2n–6) to α-Linolenic Acid (ALA, C18:3n–3) Ratio on the Mouse Liver Proteome

“…According to Gouaref et al, increased pro-inflammatory cytokine concentrations (TNFα, IL-6, IL1β) were associated with elevated levels of saturated non-esterified fatty acids (NEFAs) and decreased plasma PUFAs. A positive correlation was also found between the plasma PUFA/SFA and HDL-c/LDL-c ratios (r = +66, p < 0.01) in the group of patients with type 2 diabetes mellitus (T2DM) and hypertension [ 12 ]. Additionally, female mortality caused by breast cancer was the highest in the group characterized by high saturated fat intake [ 1 , 13 ].…”

Comparative Analysis of Biomarkers in Type 2 Diabetes Patients with and without Comorbidities: Insights into the Role of Hypertension and Cardiovascular Disease

“…As for the patients with HT only, the importance of C5a, 8-OHdG, GSH/GSSG, IGF-1, became significant in the model in addition to the well documented role of cholesterol. Gouaref et al 76 reported similar results between a control group and patients with T2DM, hypertension, and hypertension. In contrast patients with CVD differed significantly only in TC, HDL, LDL, 8-OHdG, GSH, GSSG, and IL-10 indicating the much more prominent role of cholesterol in cardiovascular disease.…”