Dietary Fats Lower Diabetes & Cardiometabolic Risk

lA recent study published in Nature Medicine used lipidomics data to create a multilipid score (MLS). It used reduced MLS (rMLS) to evaluate the effect of dietary fat quality on lipid metabolites and its relationship to lower cardiometabolic disease risk.

Background

Cardiovascular diseases (CVDs) (heart and blood vessel disorders such as heart attacks and strokes) account for 20 million deaths worldwide each year, and type 2 diabetes (T2D) (a chronic condition with high blood sugar caused by insulin issues) contributes significantly to the noncommunicable disease burden. Reducing CVD and T2D incidence has significant social advantages.

To prevent cardiometabolic diseases, the World Health Organization (WHO) and national guidelines advocate eating more unsaturated fats and less saturated fat. However, the function of dietary fat in cardiometabolic health is still contested, particularly in terms of high-fat, low-carbohydrate diets (LCDs) vs lowering saturated fats.

It’s unclear how replacing animal-based saturated fats with plant-based unsaturated fats affects cardiometabolic risk. More research is needed to explain these effects and better understand how genetics, physiology, and food interact in lipid metabolism.

About the study – Diabetes & Cardiometabolic Risk

Lipidomics analysis was performed on 113 participants from the 16-week Dietary Intervention and VAScular Function (DIVAS) experiment, which included people aged 21 to 60 with moderate CVD risk. Participants were randomly assigned to one of three isoenergetic diets: saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), or mixed unsaturated fatty acids (UFAs).

In the European Prospective Investigation into Cancer and Nutrition – Potsdam (EPIC-Potsdam) cohort, 27,548 people were recruited to research incident CVD and T2D using a nested case-cohort strategy.

Anthropometric, blood pressure, and lifestyle information were gathered to assess illness risk connections. Lipidomics profiling discovered lipid markers associated with dietary fat intake and illness outcomes.

The Nurses’ Health Study (NHS) and NHSII cohorts included female nurses who gave blood samples and food data over several years, with CVD and T2D validated via medical records and questionnaires. Lipidomics data were utilized to develop a rMLS that linked dietary fat quality to illness risk.

The Prevention with Mediterranean Diet (PREDIMED) experiment found that following a Mediterranean diet reduced cardiometabolic risk.

The LIPOGAIN-2 experiment randomized overweight people to polyunsaturated fatty acid (PUFA) or SFA-rich diets and tracked their weight and lipid profiles.

Study results

The current investigation largely verified the DIVAS dietary effects on circulating lipid metabolites in the LIPOGAIN-2 experiment, an 8-week overfeeding Randomised Controlled experiment (RCT) with SFA and UFA-enriched diet arms.

The NHS and NHSII cohorts, as well as the PREDIMED experiment, were analyzed using Broad Institute lipidomics data to determine the relative abundances of a subset of lipid metabolites included in the original MLS.

A rMLS was created utilizing 42 lower-resolution lipid variables that highly correlated with the original MLS. In the NHS/NHSII cohorts, relationships between food, disease, and 10-year increases in rMLS levels (indicating increased dietary fat quality) were investigated, and a link was found with lower T2D risk.

The PREDIMED trial also looked into whether people with low pre-intervention rMLS levels benefited more from a Mediterranean diet rich in plant-based UFAs, particularly nuts and olive oil.

The DIVAS experiment included isoenergetic meals that provided 36% of total energy from fats, a control diet high in SFAs, and two intervention arms in which 8% of SFA energy was substituted with UFAs. Extensive sensitivity analyses revealed consistent outcomes across intervention arms.

A total of 113 participants underwent lipidomics profiling, assessing 987 molecular lipid species and 111 lipid class-specific fatty acid concentrations.

A UFA-rich diet significantly lowered circulation concentrations of 45 class-specific fatty acids, notably those with medium- or long-chain fatty acids and minimal or few unsaturations.

In the EPIC-Potsdam cohort, the MLS, when standardized to the postintervention comparison in the DIVAS trial, was linked with 32% reduced CVD and 26% lower T2D incidences.

Adjustments for various biomarkers had no significant effect on these relationships, implying that the MLS reflects the cardiometabolic health impact of changed dietary fat quality better than existing surrogate biomarkers.

The MLS correlations with diet and disease were verified by replication in the NHS/NHSII cohorts as well as the LIPOGAIN-2 experiment. The PREDIMED trial found that a Mediterranean diet lowered T2D risk, especially in participants with high pre-intervention rMLS levels.

Network analysis in the EPIC-Potsdam cohort revealed lipid clusters and direct linkages between metabolites and disease risk, shedding light on the biological processes that underpin MLS-disease relationships.

Conclusion

To summarize, this study discovered that lipidomics-based MLSs, which substitute SFAs with UFAs, are linked with significantly decreased risks of CVD and T2D. Results from the DIVAS study and the EPIC-Potsdam cohort revealed that MLSs predicted better cardiometabolic risk reductions than conventional indicators.

Consistent correlations between food, lipid metabolites, and cardiometabolic risk were found in multiple cohorts.

Furthermore, improved lipid scores over ten years were associated with lower T2D risk, implying that lipidomics-based ratings can assist target dietary treatments for better cardiometabolic health.

For more information: Eichelmann, F., Prada, M., Sellem, L. et al. (2024) Lipidome changes due to improved dietary fat quality inform cardiometabolic risk reduction and precision nutrition. Nat Med. doi: https://doi.org/10.1038/s41591-024-03124-1.