A Diet Rich in Medium-Chain Fatty Acids Improves Systolic Function and Alters the Lipidomic Profile in Patients With Type 2 Diabetes: A Pilot Study

Abstract

Context: Excessive cardiac long-chain fatty acid (LCFA) metabolism/storage causes cardiomyopathy in animal models of type 2 diabetes. Medium-chain fatty acids (MCFAs) are absorbed and oxidized efficiently. Data in animal models of diabetes suggest MCFAs may benefit the heart.

Objective: Our objective was to test the effects of an MCFA-rich diet vs an LCFA-rich diet on plasma lipids, cardiac steatosis, and function in patients with type 2 diabetes.

Design: This was a double-blind, randomized, 2-week matched-feeding study.

Setting: The study included ambulatory patients in the general community.

Patients: Sixteen patients, ages 37-65 years, with type 2 diabetes, an ejection fraction greater than 45%, and no other systemic disease were included.

Intervention: Fourteen days of a diet rich in MCFAs or LCFAs, containing 38% as fat in total, was undertaken.

Main outcome measures: Cardiac steatosis and function were the main outcome measures, with lipidomic changes considered a secondary outcome.

Results: The relatively load-independent measure of cardiac contractility, S', improved in the MCFA group (P < .05). Weight-adjusted stroke volume and cardiac output decreased in the LCFA group (both P < .05). The MCFA, but not the LCFA, diet decreased several plasma sphingolipids, ceramide, and acylcarnitines implicated in diabetic cardiomyopathy, and changes in several sphingolipids correlated with improved fasting insulins.

Conclusions: Although a diet high in MCFAs does not change cardiac steatosis, our findings suggest that the MCFA-rich diet alters the plasma lipidome and may benefit or at least not harm cardiac function and fasting insulin levels in humans with type 2 diabetes. Larger, long-term studies are needed to further evaluate these effects in less-controlled settings.

Trial registration: ClinicalTrials.gov NCT01373814.

Figure 1.

Stroke volume and cardiac output are decreased following an LCFA-enriched diet. Stroke volume (A) and cardiac output (B) are shown for subjects assigned to the LCFA- (black bars) or MCFA-enriched (open bars) diets. Values are weight-adjusted and reported are means ± SEM. *P < .05 for pre vs postdiet values. The interactions between time and group were not significant.

Figure 2.

Systolic function improves following MCFA-enriched diet. Tissue Doppler-derived movement of the mitral valve annulus toward the transducer in systole (S′) was quantified during transthoracic echocardiography in subjects assigned to LCFA (black bars) or MCFA (open bars) dietary intervention. Values are weight-adjusted and reported are means ± SEM. *P = .01 for pre vs postintervention measure in the MCFA treatment group; †P < .05 for the difference between the post-MCFA S′ and the post-LCFA S′. (As a point of reference, a nonweight-adjusted S′ value in a healthy 50-year-old man is approximately 9 cm/s; range, 7–12 cm/s) (39). The interactions between time and group were not significant (P = .13).

Figure 3.

An example of tissue Doppler-derived systolic function (S′) pre- and post-MCFA diet intervention in one subject.

Figure 4.

Lipidomic changes with dietary intervention. This “heat map” depicts the changes in acylcarnitine (AC), Cer, and SM species that were statistically significantly different from pre- to postintervention in the MCFA diet intervention group (as a whole) after FDR correction (*P < .05, †P < .01, ‡P < .001, §P < .005). For preparation of heat maps, we calculated the % change for a given analyte for each subject: [(post values − pre values)/pre values] × 100%. For each lipid species, we calculated the mean and SD of the % change for all MCFA and LCFA subjects. To generate the Z-score transformations, [(%change-mean % change)/SD] was calculated for each analyte for each subject. Data are shown for each subject in the MCFA and LCFA intervention group and the average value for each group, with green and red shades representing decreases or increases, respectively, for each lipid. Among the LCFA diet group, there were no significant changes in these or other lipid species.