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OBJECTIVE:--Associated with insulin resistance in type 2 diabetes are increased serum triglycerides, decreased HDL cholesterol, and a predominance of large VLDL, small LDL, and small HDL particles. The comparative effects of thiazolidinedione insulin sensitizers on serum lipoprotein particle concentrations and sizes in type 2 diabetes are not known. We studied the effects of pioglitazone (PIO) and rosiglitazone (ROSI) treatments on serum lipoprotein particle concentrations and sizes in type 2 diabetic patients with dyslipidemia. RESEARCH DESIGN AND METHODS--This is a prospective, randomized, double-blind, multicenter, parallel-group study. After a 4-week placebo washout period, patients randomized to PIO (n = 369) were treated with 30 mg q.d. for 12 weeks followed by 45 mg q.d. for another 12 weeks, while patients randomized to ROSI (n = 366) were treated with 4 mg q.d. followed by 4 mg b.i.d. for the same intervals. Lipoprotein subclass particle concentrations and sizes were determined by proton nuclear magnetic resonance spectroscopy at baseline and end point (PIO [n = 333] and ROSI [n = 325] patients). RESULTS:--PIO treatment increased total VLDL particle concentration less than ROSI treatment and decreased VLDL particle size more than ROSI. PIO treatment reduced total LDL particle concentration, whereas ROSI treatment increased it. Both treatments increased LDL particle size, with PIO treatment having a greater effect. Whereas PIO treatment increased total HDL particle concentration and size, ROSI treatment decreased them; both increased HDL cholesterol levels. CONCLUSIONS:--PIO and ROSI treatments have different effects on serum lipoprotein subclass particle concentrations and sizes in patients with type 2 diabetes and dyslipidemia.

There are limited data on the efficacy and safety of triglyceride (TG)-lowering agents in women. We conducted subgroup analyses of the effects of icosapent ethyl (a high-purity prescription form of the ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid) on TG levels (primary efficacy variable) and other atherogenic and inflammatory parameters in a total of 215 women with a broad range of TG levels (200–2000 mg/dl) enrolled in two 12-week placebo-controlled trials: MARINE (n = 18; placebo, n = 18) and ANCHOR (n = 91; placebo, n = 88). Icosapent ethyl 4 g/day significantly reduced TG levels from baseline to week 12 versus placebo in both MARINE (−22.7%; p = 0.0327) and ANCHOR (−21.5%; p <0.0001) without increasing low-density lipoprotein cholesterol levels. Significant improvements were also observed in non–high-density lipoprotein cholesterol levels in MARINE (−15.7%; p = 0.0082) and ANCHOR (−14.2%; p <0.0001) and total cholesterol levels in MARINE (−14.9%; p = 0.0023) and ANCHOR (−12.1%; p <0.0001), along with significant increases of >500% in eicosapentaenoic acid levels in plasma and red blood cells (all p <0.001). Icosapent ethyl was well tolerated, with adverse-event profiles comparable with findings in the overall studies. In conclusion, icosapent ethyl 4 g/day significantly reduced TG levels and other atherogenic parameters in women without increasing low-density lipoprotein cholesterol levels compared with placebo; the clinical implications of these findings are being evaluated in the REDUCtion of Cardiovascular Events With Eicosapentaenoic Acid [EPA]–Intervention Trial (REDUCE-IT) cardiovascular outcomes study.

To characterize via NMR spectroscopy the full spectrum of metabolic changes in umbilical vein blood plasma of newborns diagnosed with different clinical forms of intrauterine growth restriction (IUGR). 23 early IUGR cases and matched 23 adequate-for-gestational-age (AGA) controls and 56 late IUGR cases with 56 matched AGAs were included in this study. Early IUGR was defined as a birth weight <10(th) centile, abnormal umbilical artery (UA) Doppler and delivery <35 weeks. Late IUGR was defined as a birth weight <10(th) centile with normal UA Doppler and delivery >35 weeks. This group was subdivided in 18 vasodilated (VD) and 38 non-VD late IUGR fetuses. All AGA patients had a birth weight >10(th) centile. (1)H nuclear magnetic resonance (NMR) metabolomics of the blood samples collected from the umbilical vein at delivery was obtained. Multivariate statistical analysis identified several metabolites that allowed the discrimination between the different IUGR subgroups, and their comparative levels were quantified from the NMR data. The NMR-based analysis showed increased unsaturated lipids and VLDL levels in both early and late IUGR samples, decreased glucose and increased acetone levels in early IUGR. Non-significant trends for decreased glucose and increased acetone levels were present in late IUGR, which followed a severity gradient when the VD and non-VD subgroups were considered. Regarding amino acids and derivatives, early IUGR showed significantly increased glutamine and creatine levels, whereas the amounts of phenylalanine and tyrosine were decreased in early and late-VD IUGR samples. Valine and leucine were decreased in late IUGR samples. Choline levels were decreased in all clinical subforms of IUGR. IUGR is not associated with a unique metabolic profile, but important changes are present in different clinical subsets used in research and clinical practice. These results may help in characterizing comprehensively specific alterations underlying different IUGR subsets.

Ingestion of pure fructose stimulates de novo lipogenesis and gluconeogenesis. This may however not be relevant to typical nutritional situations, where fructose is invariably ingested with glucose. We therefore assessed the metabolic fate of fructose incorporated in a mixed meal without or with glucose in eight healthy volunteers. Each participant was studied over six hours after the ingestion of liquid meals containing either 13C-labelled fructose, unlabeled glucose, lipids and protein (Fr + G) or 13C-labelled fructose, lipids and protein, but without glucose (Fr), or protein and lipids alone (ProLip). After Fr + G, plasma 13C-glucose production accounted for 19.0% ± 1.5% and 13CO2 production for 32.2% ± 1.3% of 13C-fructose carbons. After Fr, 13C-glucose production (26.5% ± 1.4%) and 13CO2 production (36.6% ± 1.9%) were higher (p < 0.05) than with Fr + G. 13C-lactate concentration and very low density lipoprotein VLDL 13C-palmitate concentrations increased to the same extent with Fr + G and Fr, while chylomicron 13C-palmitate tended to increase more with Fr + G. These data indicate that gluconeogenesis, lactic acid production and both intestinal and hepatic de novo lipogenesis contributed to the disposal of fructose carbons ingested together with a mixed meal. Co-ingestion of glucose decreased fructose oxidation and gluconeogenesis and tended to increase 13C-pamitate concentration in gut-derived chylomicrons, but not in hepatic-borne VLDL-triacylglycerol (TG). This trial was approved by clinicaltrial. gov. Identifier is NCT01792089.

Background Magnesium and vitamin E are known to exert multiple beneficial effects, such as anti-glycemic and anti-lipidemic properties. The aim of this study was to determine the effects of magnesium and vitamin E co-supplementation on metabolic status of women with gestational diabetes (GDM). Methods This randomized, double-blinded, placebo-controlled trial was conducted among 60 subjects diagnosed with GDM, aged 18–40 years. Subjects were randomly allocated into two groups to receive 250 mg/day magnesium oxide plus 400 IU/day vitamin E supplements or placebo ( n  = 30 each group) for 6 weeks. Participants’ blood samples were taken to determine their metabolic profiles. Results Subjects who received magnesium plus vitamin E supplements had significantly lower fasting plasma glucose (β − 5.20 mg/dL; 95% CI, − 7.88, − 2.52; P  = 0.002), serum insulin levels (β − 2.93 μIU/mL; 95% CI, − 5.68, − 0.18; P  = 0.02) and homeostasis model of assessment-insulin resistance (β − 0.78; 95% CI, − 1.42, − 0.14; P  = 0.01), and higher quantitative insulin sensitivity check index (β 0.01; 95% CI, 0.005, 0.02; P  = 0.002) compared with placebo. In addition, magnesium plus vitamin E supplementation resulted in a significant reduction in serum triglycerides (β − 50.31 mg/dL; 95% CI, − 67.58, − 33.04; P  < 0.001), VLDL- (β − 10.06 mg/dL; 95% CI, − 13.51, − 6.60; P  < 0.001), total- (β − 26.10 mg/dL; 95% CI, − 41.88, − 10.33; P  = 0.004), LDL- (β − 15.20 mg/dL; 95% CI, − 29.50, − 0.91; P  = 0.03) and total-/HDL-cholesterol ratio (β − 0.46; 95% CI, − 0.72, − 0.19; P  < 0.001) compared with placebo. Magnesium and vitamin E co-supplementation did not affect HDL-cholesterol levels. Conclusions Overall, magnesium and vitamin E co-supplementation for 6 weeks in women with GDM significantly improved glycemic control and lipid profiles, except for HDL-cholesterol levels. Clinical trial registration number http://www.irct.ir : IRCT20170513033941N24.

Omega-3 long chain polyunsaturated fatty acid (n-3 LCPUFA) supplementation has been shown to improve plasma lipid profiles in men and post-menopausal women, however, data for pre-menopausal women are lacking. The benefits of intakes less than 1 g/day have not been well studied, and dose–response data is limited. The aim of this study was to determine the effect of low doses of docosahexaenoic acid (DHA)-rich tuna oil on plasma triglyceride (TG) lowering in pre-menopausal women, and investigate if low dose DHA-rich tuna oil supplementation would increase the low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particle sizes. A randomized, double-blind, placebo-controlled trial was conducted, in which 53 healthy pre-menopausal women with mildly elevated plasma TG levels consumed 0, 0.35, 0.7, or 1 g/day n-3 LCPUFA as HiDHA™ tuna oil or placebo (Sunola oil) capsules for 8 weeks. Supplementation with 1 g/day n-3 LCPUFA, but not lower doses, reduced plasma TG by 23% in pre-menopausal women. This was reflected in a dose-dependent reduction in very-low-density lipoprotein (VLDL)-TG (R2 = 0.20, p = 0.003). A weak dose-dependent shift in HDL (but not LDL) particle size was identified (R2 = 0.05, p = 0.04). The results of this study indicate that DHA-rich n-3 LCPUFA supplementation at a dose of 1 g/day is an effective TG-lowering agent and increases HDL particle size in pre-menopausal women.

Recent studies point out that not only the daily intake of energy and nutrients but the time of day when they are ingested notably regulates lipid metabolism and cardiovascular risk (CVR). Therefore, the aim of the study was to assess if the type of fat ingested at breakfast can modify lipid metabolism in women with CVR. A randomized, crossover clinical trial was performed. Sixty volunteers were randomly assigned to a (A) polyunsaturated fatty acid (PUFA)-rich breakfast, (B) saturated fatty acid (SFA)-rich breakfast, or (C) monounsaturated fatty acid (MUFA)-rich breakfast. Plasma lipoprotein and apolipoprotein subfractions were determined. Our data showed that the PUFA-rich breakfast decreased lipoprotein (a) (Lp(a)), very low-density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL), and increased high-density lipoproteins (HDL). A similar trend was observed for the MUFA-rich breakfast, whereas the SFA-rich breakfast, although it decreased VLDL, also increased IDL and reduced HDL. The PUFA-rich breakfast also decreased β-lipoproteins and apolipoprotein-B. In summary, varying the type of fat eaten at breakfast is enough to significantly modify the lipid metabolism of women with CVR, which can be of great relevance to establish new therapeutic strategies for the treatment of these subjects.

Low testosterone (T) levels in men have been shown to predict development of the metabolic syndrome, but the effects of T on lipid metabolism are incompletely understood. In a randomized, double-blind, placebo-controlled, crossover study, 12 healthy, young males received gonadotropin-releasing hormone agonist treatment 1 month prior to 3 of 4 trial days to induce castrate levels of T. On trial days, T gel was applied to the body containing either high or low physiological T dose or placebo. On the 4th trial day, participants constituted their own eugonadal controls. Each study comprised a 5-h basal period and a 3-h hyperinsulinemic-euglycemic clamp. Short-term hypogonadism did not affect VLDL triglyceride (TG) secretion, nor did it affect VLDL-TG concentrations. It was, however, characterized by lower total lipid oxidation. In addition, acute rescue with high physiological T increased VLDL-TG secretion during both basal and clamp conditions. These data show that T can act through fast nongenomic pathways in the liver. In addition, the early hypogonadal state is characterized by decreased total lipid oxidation, but whether these changes represent early hypogonadal metabolic dysfunction warrants further investigations. T is not a major determinant of resting VLDL-TG kinetics in men.

Background The prevalence of obesity in pediatric population is increasing at an accelerated rate in many countries, and has become a major public health concern. Physical activity, particularly exercise training, remains to be a cornerstone of pediatric obesity interventions. The purpose of our current randomized intervention trial was to compare the effects of two types of training matched for training volume, aerobic and concurrent, on body composition and metabolic profile in obese adolescents. Thus the aim of the study was compare the effects of two types of training matched for training volume, aerobic and concurrent, on body composition and metabolic profile in obese adolescents. Methods 32 obese adolescents participated in two randomized training groups, concurrent or aerobic, for 20 weeks (50 mins x 3 per week, supervised), and were compared to a 16-subject control group. We measured the percentage body fat (%BF, primary outcome), fat-free mass, percentage of android fat by dual energy x-ray absorptiometry, and others metabolic profiles at baseline and after interventions, and compared them between groups using the Intent-to-treat design. Results In 20 weeks, both exercise training groups significantly reduced %BF by 2.9-3.6 % as compare to no change in the control group ( p  = 0.042). There were also positive changes in lipid levels in exercise groups. No noticeable changes were found between aerobic and concurrent training groups. Conclusions The benefits of exercise in reducing body fat and metabolic risk profiles can be achieved by performing either type of training in obese adolescents. Trial registration Registration number: RBR-4HN597 .

Background Almonds have been shown to lower LDL cholesterol but there is limited information regarding their effects on the dyslipidemia characterized by increased levels of very low density lipoproteins (VLDL) and small, dense low-density lipoprotein (LDL) particles that is associated with abdominal adiposity and high carbohydrate intake. The objective of the present study was to test whether substitution of almonds for other foods attenuates carbohydrate-induced increases in small, dense LDL in individuals with increased abdominal adiposity. Methods This was a randomized cross-over study of three 3wk diets, separated by 2wk washouts: a higher-carbohydrate (CHO) reference diet (CHO high ), a higher-CHO diet with isocaloric substitution of 20% kcal (E) from almonds (CHO high + almonds ), and a lower-CHO reference diet (CHO low ) in 9 men and 15 women who were overweight or obese. The two CHO high diets contained 50% carbohydrate, 15% protein, 35% fat (6% saturated, 21% monounsaturated, 8% polyunsaturated), while the CHO low diet contained 25% carbohydrate, 28% protein, 47% fat (8% saturated, 28% monounsaturated, 8% polyunsaturated). Lipoprotein subfraction concentrations were measured by ion mobility. Results Relative to the CHO low diet: 1) the CHO high + almonds diet significantly increased small, dense LDLIIIa (mean difference ± SE: 28.6 ± 10.4 nmol/L, P  = 0.008), and reduced LDL-peak diameter (− 1.7 ± 0.6 Å, P = 0.008); 2) the CHO high diet significantly increased medium-sized LDLIIb (24.8 ± 11.4 nmol/L, P  = 0.04) and large VLDL (3.7 ± 1.8 nmol/L, P  = 0.05). Relative to CHO low , the effects of CHO high on LDLIIIa (17.7 ± 10.6 nmol/L) and LDL-peak diameter (− 1.1 ± 0.6 Å) were consistent with those of CHO high + almonds , and the effects of CHO high + almonds on LDLIIb (21.0 ± 11.2 nmol/L) and large VLDL (2.8 ± 1.8 nmol/L) were consistent with those of CHO high , but did not achieve statistical significance ( P  > 0.05). None of the variables examined showed a significant difference between the CHO high + almonds and CHO high diets ( P  > 0.05). Conclusion Our analyses provided no evidence that deriving 20% E from almonds significantly modifies increases in levels of small, dense LDL or other plasma lipoprotein changes induced by a higher carbohydrate low saturated fat diet in individuals with increased abdominal adiposity. Trial registration Clinicaltrials.gov NCT01792648 .