[Show abstract][Hide abstract] 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.
To test the effects of a MCFA-rich diet versus an LCFA-rich diet on plasma lipids, cardiac steatosis and function in patients with type 2 diabetes.
Double-blind, randomized 2-wk matched feeding study.
Ambulatory patients in the general community.
Sixteen, ages 37 to 65 y old, with type 2 diabetes, an ejection fraction >45%, and no other systemic disease.
14 d of a diet rich in MCFAs or LCFA, containing 38% as fat in total.
Main outcome measure:
Cardiac steatosis and function. Lipidomic changes were a secondary outcome.
The relatively load-independent measure of cardiac contractility, S`, improved in the MCFA group (P<0.05). Weight-adjusted stroke volume and cardiac output decreased in the LCFA group (both P <0.05). 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.
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.
Full-text · Article · Dec 2015 · Journal of Clinical Endocrinology & Metabolism
[Show abstract][Hide abstract] ABSTRACT: -Skeletal muscle strength, velocity, and power are markedly reduced in heart failure (HF) patients, which contributes to their impaired exercise capacity and lower quality of life. This muscle dysfunction may be partially due to decreased nitric oxide (NO) bioavailability. We therefore sought to determine whether ingestion of inorganic nitrate (NO3 (-)) would increase NO production and improve muscle function in patients with HF due to systolic dysfunction.
-Using a double-blind, placebo-controlled, randomized crossover design, we determined the effects of dietary NO3 (-) in nine HF patients. After fasting overnight, subjects drank beetroot juice containing or devoid of 11.2 mmol NO3 (-). Two hours later, muscle function was assessed using isokinetic dynamometry. Dietary NO3 (-) increased (P<0.05-0.001) breath NO by 35-50%. This was accompanied by 9% (P=0.07) and 11% (P<0.05) increases in peak knee extensor power at the two highest movement velocities tested (i.e., 4.71 and 6.28 rad/s). Maximal power (calculated by fitting peak power data with a parabola) was therefore greater (i.e., 4.74±0.41 vs. 4.20±0.33 W/kg; P<0.05) after dietary NO3 (-) intake. Calculated maximal velocity of knee extension was also higher following NO3 (-) ingestion (i.e., 12.48±0.95 vs. 11.11±0.53 rad/s; P<0.05). Blood pressure was unchanged, and no adverse clinical events occurred.
-In this pilot study, acute dietary NO3 (-) intake was well-tolerated and enhanced NO bioavailability and muscle power in patients with systolic HF. Larger-scale studies should be conducted to determine whether the latter translates into an improved quality of life in this population. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01682356.
[Show abstract][Hide abstract] ABSTRACT: Nitric oxide (NO) has been demonstrated to enhance the maximal shortening velocity and maximal power of rodent muscle. Dietary nitrate (NO3−) intake has been demonstrated to increase NO bioavailability in humans. We therefore hypothesized that acute dietary NO3− intake (in the form of a concentrated beetroot juice (BRJ) supplement) would improve muscle speed and power in humans. To test this hypothesis, healthy men and women (n = 12; age = 22–50 y) were studied using a randomized, double-blind, placebo-controlled crossover design. After an overnight fast, subjects ingested 140 mL of BRJ either containing or devoid of 11.2 mmol of NO3−. After 2 h, knee extensor contractile function was assessed using a Biodex 4 isokinetic dynamometer. Breath NO levels were also measured periodically using a Niox Mino analyzer as a biomarker of whole-body NO production. No significant changes in breath NO were observed in the placebo trial, whereas breath NO rose by 61% (P < 0.001; effect size = 1.19) after dietary NO3− intake. This was accompanied by a 4% (P < 0.01; effect size = 0.74) increase in peak knee extensor power at the highest angular velocity tested (i.e., 6.28 rad/s). Calculated maximal knee extensor power was therefore greater (i.e., 7.90 ± 0.59 vs. 7.44 ± 0.53 W/kg; P < 0.05; effect size = 0.63) after dietary NO3− intake, as was the calculated maximal velocity (i.e., 14.5 ± 0.9 vs. 13.1 ± 0.8 rad/s; P < 0.05; effect size = 0.67). No differences in muscle function were observed during 50 consecutive knee extensions performed at 3.14 rad/s. We conclude that acute dietary NO3− intake increases whole-body NO production and muscle speed and power in healthy men and women.
[Show abstract][Hide abstract] ABSTRACT: Ceramide is a key metabolite in both anabolic and catabolic pathways of sphingolipids. The very long fatty acyl chain ceramides N-(docosanoyl)-sphing-4-enine (Cer(22:0)) and N-(tetracosanoyl)-sphing-4-enine (Cer(24:0)) are associated with multiple biological functions. Elevated levels of these sphingolipids in tissues and in the circulation have been associated with insulin resistance and diabetes. To facilitate quantification of these very long chain ceramides in clinical samples from human subjects, we have developed a sensitive, accurate, and high-throughput assay for determination of Cer(22:0) and Cer(24:0) in human plasma. Cer(22:0) and Cer(24:0) and their deuterated internal standards were extracted by protein precipitation and chromatographically separated by HPLC. The analytes and their internal standards were ionized using positive-ion electrospray mass spectrometry, then detected by multiple-reaction monitoring with a tandem mass spectrometer. Total liquid chromatography–tandem mass spectrometry (LC-MS/MS) runtime was 5 min. The assay exhibited a linear dynamic range of 0.02–4 and 0.08–16 μg/ml for Cer(22:0) and Cer(24:0), respectively, in human plasma with corresponding absolute recoveries from plasma at 109 and 114 %, respectively. The lower limit of quantifications were 0.02 and 0.08 μg/ml for Cer(22:0) and Cer(24:0), respectively. Acceptable precision and accuracy were obtained for concentrations over the calibration curve ranges. With the semi-automated format and short LC runtime for the assay, a throughput of ∼200 samples/day can easily be achieved.
LC-MS/MS chromatograms for Cer(22:0) and Cer(24:0) in LLOQ, in which the analyte and internal standard are shown in blue and red, respectively
[Show abstract][Hide abstract] ABSTRACT: Early detection of diabetic patients at high risk for developing diabetic cardiomyopathy may permit effective intervention. The goal of this work is to determine whether measurements of the magnitude and time delay of cyclic variation of myocardial backscatter, individually and in combination, can be used to discriminate between subgroups of individuals including normal controls and asymptomatic type 2 diabetes subjects. Two-dimensional parasternal long-axis echocardiographic images of 104 type 2 diabetic patients and 44 normal volunteers were acquired. Cyclic variation data were produced by measuring the mean myocardial backscatter level within a region-of-interest in the posterior wall, and characterized in terms of the magnitude and normalized time delay. The cyclic variation parameters were analyzed using Bayes classification and a nonparametric estimate of the area under the receiver operating characteristic (ROC) curve to illustrate the relative effectiveness of using one or two features to segregate subgroups of individuals. The subjects were grouped based on glycated hemoglobin (HbA1c), the homeostasis model assessment for insulin resistance (HOMA-IR) and the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL-C). Analyses comparing the cyclic variation measurements of subjects in the highest and lowest quartiles of HbA1c, HOMA-IR and TG/HDL-C showed substantial differences in the mean magnitude and normalized time delay of cyclic variation. Results show that analyses of the cyclic variation of backscatter in young asymptomatic type 2 diabetics may be an early indicator for the development of diabetic cardiomyopathy. (E-mail: [email protected]
Full-text · Article · Aug 2009 · Ultrasound in medicine & biology