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

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.

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Omega-3 Polyunsaturated Fatty Acid Biomarkers and Risk of Type 2 Diabetes, Cardiovascular Disease, Cancer, and Mortality: A Systematic Review and Meta-analysis

10.21203/rs.3.rs-362088/v1 ◽

2021 ◽

Author(s):

Hong Jiang ◽

Lina Wang ◽

Duolao Wang ◽

Ni Yan ◽

Chao Li ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Fatty Acids ◽

Fatty Acid ◽

Lower Risk ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Dietary Recommendations ◽

Marine Origin

Abstract Background: Considerable attention has focused on omega-3 polyunsaturated fatty acids (PUFA) role in protect against the development of cardiometabolic diseases, which has led to dietary recommendations to increase omega-3 fatty acid intake.Methods: MEDLINE, EMBASE, ISI Web of Science, Cochrane Library, and reference lists were searched for articles from inception to May 2020. Random-effects model was used to estimate the pooled relative risk (RR) and 95% confidence intervals (CIs) for the association of omega-3 PUFAs, including α-linoleic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA), with risk of developing type 2 diabetes (T2D), cardiovascular disease (CVD), including coronary heart disease (CHD) and stroke, cancer, and mortality.Results: 66 prospective studies comprised of 211,600 participants were identified. Individual omega-3 PUFAs showed divergent associations with the study outcomes of interest. An inverse association with risk of T2D was observed comparing extreme categories of ALA concentration (RR,0.91;95%CI,0.83-0.99), but not for the marine-origin omega-3 fatty acids biomarkers. The marine-origin omega-3 fatty acids biomarkers, but not ALA, were significantly associated with lower risks of total CVD, CHD, and overall mortality, with RRs ranging from 0.70 for DHA-CHD association to 0.85 for EPA-CHD association. Lower risk of colorectal cancer was observed at higher levels of DPA (RR,0.76;95%CI:0.59-0.98) and DHA (RR,0.80;95%CI:0.65-0.99). In dose-response analyses, inverse linear associations were observed between EPA, DPA, and DHA biomarkers and CVD or CHD risk, except for DHA-CVD association which showed a nonlinearity association.Conclusion: Higher concentrations of marine-derived omega-3 PUFA biomarkers were associated with a significantly reduced risk of total CVD, CHD, certain types of cancer, and total mortality. Levels of ALA were inversely with a lower risk of T2D but not CVD-related outcomes. These data support the dietary recommendations advocating the role of omega-3 PUFAs in maintaining an overall lower risk of developing cardiovascular disease and premature deaths.

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Faculty Opinions recommendation of Effect of Vitamin D and Omega-3 Fatty Acid Supplementation on Kidney Function in Patients With Type 2 Diabetes: A Randomized Clinical Trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.736875953.793568166 ◽

2019 ◽

Author(s):

Wilbert Aronow

Keyword(s):

Type 2 Diabetes ◽

Clinical Trial ◽

Vitamin D ◽

Fatty Acid ◽

Randomized Clinical Trial ◽

Kidney Function ◽

Omega 3 ◽

Fatty Acid Supplementation ◽

Omega 3 Fatty Acid

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Abstract P120: Omega-3 Fatty Acid Supplementation in Middle-Aged Adults Reduces Cardiometabolic Risk in Men but not Women

Circulation ◽

10.1161/circ.129.suppl_1.p120 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Claire Newlon ◽

Matthew Muldoon ◽

Susan Sereika ◽

Dora Kuan

Keyword(s):

Blood Pressure ◽

Gender Differences ◽

Fatty Acids ◽

Fatty Acid ◽

Cardiometabolic Risk ◽

Acid Metabolism ◽

Hdl Cholesterol ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Middle Aged Adults

Background: Greater consumption of omega-3 fatty acids has been associated with lower cardiovascular disease risk. Randomized controlled trials indicate direct, albeit small, beneficial effects of omega-3 fatty acids on plasma triglycerides and blood pressure, yet few studies have tested their impact on insulin resistance and the clustered risk factors comprising the metabolic syndrome. Hypothesis: Short-term supplementation with marine omega-3 polyunsaturated fatty acids, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) will improve aggregated cardiometabolic risk (CMR) in healthy middle-aged adults Methods: We conducted a double-blind, placebo-controlled, parallel group clinical trial. Subjects were 30-54 year-old adults free of atherosclerotic disease and diabetes whose intake of EPA and DHA totaled <300 mg/day. Each was randomly assigned to daily fish oil supplements (2g/day containing 1000 mg EPA and 400mg DHA) or matching soybean oil placebo for 18 weeks. Aggregate CMR at baseline and post-intervention was calculated as the standardized sum of standardized distributions of blood pressure, BMI, and fasting serum triglycerides, glucose, and HDL (reverse scored). Missing data due to dropouts (n=17) and outliers (1-6 per variable) were replaced by multivariate imputation. Outcome analyses were conducted with linear regressions of all randomized subjects based on intention-to-treat. Results: Participants were 272 healthy adult (57% (154 out of 272) women; 17% (47 out of 272) minority; mean age 42) Pittsburgh-area residents. At baseline, demographics, health parameters, physical activity and EPA and DHA consumption did not differ significantly between treatment groups. No overall treatment effect was found, whereas gender moderated the effects of treatment on CMR risk (gender, p=.001 and gender*treatment interaction term p=.011). In gender-specific analyses, supplementation lowered CMR risk relative to placebo in men(p=.036, effect size=.629, standard error (SE) =.282) but not women (p=.168, effect size .261, SE=.222). Of the individual CMR variables, only HDL-cholesterol in men revealed a significant improvement (p=.012). In men receiving placebo, HDL-cholesterol fell by 1.1 mg/dl, whereas in those receiving fish oil, HDL rose by 1.7 mg/dl. As has been noted in other samples, compared to women men had greater CMR and lower HDL-cholesterol. Conclusions: Increased intake of n-3 fatty acids over 4 months reduced CMR in healthy, mid-life men but not women. This finding may be due to poorer baseline CMR and HDL characteristic of men, or to gender differences in fatty acid metabolism. Further study of gender differences in cardiometabolic risk and fatty acid metabolism may lead to gender-tailored preventive interventions.

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