Despite consuming similar calories and protein during resistance training, daily supplementation with whey was more effective than soy protein or isocaloric carbohydrate control treatment conditions in promoting gains in lean body mass. These results highlight the importance of protein quality as an important determinant of lean body mass responses to resistance training.

BackgroundCardiovascular disease (CVD) is a leading cause of death among adults with type 2 diabetes mellitus (T2D). We recently reported that glycemic control in patients with T2D can be significantly improved through a continuous care intervention (CCI) including nutritional ketosis. The purpose of this study was to examine CVD risk factors in this cohort.MethodsWe investigated CVD risk factors in patients with T2D who participated in a 1 year open label, non-randomized, controlled study. The CCI group (n = 262) received treatment from a health coach and medical provider. A usual care (UC) group (n = 87) was independently recruited to track customary T2D progression. Circulating biomarkers of cholesterol metabolism and inflammation, blood pressure (BP), carotid intima media thickness (cIMT), multi-factorial risk scores and medication use were examined. A significance level of P < 0.0019 ensured two-tailed significance at the 5% level when Bonferroni adjusted for multiple comparisons.ResultsThe CCI group consisted of 262 participants (baseline mean (SD): age 54 (8) year, BMI 40.4 (8.8) kg m−2). Intention-to-treat analysis (% change) revealed the following at 1-year: total LDL-particles (LDL-P) (− 4.9%, P = 0.02), small LDL-P (− 20.8%, P = 1.2 × 10−12), LDL-P size (+ 1.1%, P = 6.0 × 10−10), ApoB (− 1.6%, P = 0.37), ApoA1 (+ 9.8%, P < 10−16), ApoB/ApoA1 ratio (− 9.5%, P = 1.9 × 10−7), triglyceride/HDL-C ratio (− 29.1%, P < 10−16), large VLDL-P (− 38.9%, P = 4.2 × 10−15), and LDL-C (+ 9.9%, P = 4.9 × 10−5). Additional effects were reductions in blood pressure, high sensitivity C-reactive protein, and white blood cell count (all P < 1 × 10−7) while cIMT was unchanged. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk score decreased − 11.9% (P = 4.9 × 10−5). Antihypertensive medication use was discontinued in 11.4% of CCI participants (P = 5.3 × 10−5). The UC group of 87 participants [baseline mean (SD): age 52 (10) year, BMI 36.7 (7.2) kg m−2] showed no significant changes. After adjusting for baseline differences when comparing CCI and UC groups, significant improvements for the CCI group included small LDL-P, ApoA1, triglyceride/HDL-C ratio, HDL-C, hsCRP, and LP-IR score in addition to other biomarkers that were previously reported. The CCI group showed a greater rise in LDL-C.ConclusionsA continuous care treatment including nutritional ketosis in patients with T2D improved most biomarkers of CVD risk after 1 year. The increase in LDL-cholesterol appeared limited to the large LDL subfraction. LDL particle size increased, total LDL-P and ApoB were unchanged, and inflammation and blood pressure decreased.Trial registration Clinicaltrials.gov: NCT02519309. Registered 10 August 2015Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0698-8) contains supplementary material, which is available to authorized users.

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Postprandial hyperglycemia induces vascular endothelial dysfunction (VED) and increases future cardiovascular disease risk. We hypothesized that postprandial hyperglycemia would decrease vascular function in healthy men by inducing oxidative stress and proinflammatory responses and increasing asymmetric dimethylarginine:arginine (ADMA:arginine), a biomarker that is predictive of reduced NO biosynthesis. In a randomized, cross-over design, healthy men (n = 16; 21.6 ± 0.8 y) ingested glucose or fructose (75 g) after an overnight fast. Brachial artery flow-mediated dilation (FMD), plasma glucose and insulin, antioxidants, malondialdehyde (MDA), inflammatory proteins, arginine, and ADMA were measured at regular intervals during the 3-h postprandial period. Baseline FMD did not differ between trials (P > 0.05). Postprandial FMD was reduced following the ingestion of glucose only. Postprandial MDA concentrations increased to a greater extent following the ingestion of glucose compared to fructose. Plasma arginine decreased and the ratio of ADMA:arginine increased to a greater extent following the ingestion of glucose. Inflammatory cytokines and cellular adhesion molecules were unaffected by the ingestion of either sugar. Postprandial AUC(0-3 h) for FMD and MDA were inversely related (r = -0.80; P < 0.05), suggesting that hyperglycemia-induced lipid peroxidation suppresses postprandial vascular function. Collectively, these findings suggest that postprandial hyperglycemia in healthy men reduces endothelium-dependent vasodilation by increasing lipid peroxidation independent of inflammation. Postprandial alterations in arginine and ADMA:arginine also suggest that acute hyperglycemia may induce VED by decreasing NO bioavailability through an oxidative stress-dependent mechanism. Additional work is warranted to define whether inhibiting lipid peroxidation and restoring arginine metabolism would mitigate hyperglycemia-mediated decreases in vascular function.

LTC 4 -converting activity has a tissue distribution different from GGT with highest activity in spleen followed by small intestine, kidney, and pancreas and lower activity in liver and lung. The activity is membrane-bound and is inhibited by acivicin, a known inhibitor of GGT. The enzyme was partially purified from the small intestine of GGT-deficient mice by papain treatment and gel filtration chromatography. The partially purified fragment released by papain has an apparent molecular mass of 65-70 kDa and the same substrate specificity as the tissue homogenate. In addition to LTC 4 , S-decyl-GSH is also cleaved. GSH itself, oxidized GSH, and the synthetic substrates used to analyze GGT activity (␥-glutamyl-p-nitroanilide and ␥-glutamyl-4-methoxy-2-naphthylamide) are not substrates for this newly discovered enzyme. These data demonstrate that in addition to GGT at least one other enzyme cleaves LTC 4 in mice. To reflect this enzyme's preferred substrate, we suggest that it be named ␥-glutamyl leukotrienase.Peptidyl leukotrienes, cysteine-containing derivatives of arachidonic acid, are potent inducers of airway constriction, vasoconstriction, smooth muscle contraction, edema, and inflammation (1-4). LTC 4 1 is formed by conjugation of leukotriene A 4 with GSH (5) and is known to be cleaved by GGT, which removes the glutamyl moiety to form LTD 4 (6). LTC 4 conversion to LTD 4 has long been thought to be mediated solely by GGT (7,8). Recently, however, the existence of an activity termed GGT-rel has been identified in humans (9). GGT-rel shares an overall 40% amino acid sequence identity with human GGT and is capable of cleaving the ␥-glutamyl linkage of LTC 4 , but it is unable to hydrolyze synthetic substrates that are commonly used for assaying GGT. This activity has been reported to be absent in mice (9).The role of GGT in leukotriene metabolism is of interest because of the great potency of these compounds in responses to injury. However, the distribution of GGT activity and the sites of peptidyl leukotriene actions are not concordant. In the mouse, GGT tends to be expressed at very high levels in epithelia concerned with catabolism of GSH and reabsorption of its constituent amino acids (kidney and small intestine) and other ductular and secretory epithelia (pancreas and seminal vesicles) (7, 10 -12). It is characteristically low in organs in which leukotrienes may play a role in responses to injury (e.g. lung, heart, and lymphoid tissue (spleen)). In addition, the types of responses mediated by the peptidyl leukotrienes (vasoconstriction, bronchoconstriction, increases in vascular permeability, and mucus formation) do not occur in close proximity to sites where GGT is most abundant (13). Although there are reports of GGT activity in endothelium (14 -16), the discordance between peptidyl leukotriene targets and GGT activity raises the possibility that there are other LTC 4 -cleaving enzymes in the mouse.We have recently used homologous recombination to inactivate GGT in the mouse (12). Mice homozygous for th...