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High serum osteopontin levels are associated with prevalent fractures and worse lipid profile in post-menopausal women with type 2 diabetes.
Filardi, T, Carnevale, V, Massoud, R, Russo, C, Nieddu, L, Tavaglione, F, Turinese, I, Lenzi, A, Romagnoli, E, Morano, S
Journal of endocrinological investigation. 2019;(3):295-301
Abstract
PURPOSE Patients with type 2 diabetes (T2DM) have increased fracture risk. Osteopontin (OPN) is a protein involved in bone remodeling and inflammation. The aim of this study was to evaluate the association of OPN with fracture prevalence and with metabolic parameters in post-menopausal women with T2DM. METHODS Sixty-four post-menopausal women with T2DM (age 67.0 ± 7.8 years, diabetes duration 8.9 ± 6.7 years), enrolled in a previous study, were followed up (3.6 ± 0.9 years). Previous fragility fractures were recorded. The FRAX score (without BMD) was calculated and biochemical parameters (plasma glucose, HbA1c, lipid profile and renal function) were assessed. Serum 25OH-vitamin D, calcium, PTH and OPN were evaluated at baseline. The association between OPN and fracture prevalence at baseline was evaluated by a logistic model. RESULTS OPN levels were higher in patients with previous fractures (n.25) than in patients without previous fractures at baseline (n.39) (p = 0.006). The odds of having fractures at baseline increased by 6.7 (1.9-31.4, 95% CI, p = 0.007) for each increase of 1 ng/ml in OPN levels, after adjustment for vitamin D and HbA1c levels. Fracture incidence was 4.7%. Higher OPN associated with a decrease in HDL-cholesterol (p = 0.048), after adjustment for age, basal HDL-cholesterol, basal and follow-up HbA1c and follow-up duration. 25OH-vitamin D associated with an increase in FRAX-estimated probability of hip fracture at follow-up (p = 0.029), after adjustment for age, 25OH-vitamin D and time. CONCLUSIONS In post-menopausal women with T2DM, OPN might be a useful marker of fracture and worse lipid profile.
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Liraglutide in combination with metformin may improve the atherogenic lipid profile and decrease C-reactive protein level in statin treated obese patients with coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial.
Anholm, C, Kumarathurai, P, Pedersen, LR, Samkani, A, Walzem, RL, Nielsen, OW, Kristiansen, OP, Fenger, M, Madsbad, S, Sajadieh, A, et al
Atherosclerosis. 2019;:60-66
Abstract
BACKGROUND AND AIMS Atherosclerosis in obesity and type 2 diabetes (T2DM) is associated with low-grade inflammation (LGI) and dyslipidemia, where especially small, dense lipoprotein particles are atherogenic. The glucagon-like peptide-1 receptor agonist, liraglutide, reduces cardiovascular events by poorly understood mechanisms. We investigated the effect of liraglutide combined with metformin on LGI and lipoprotein density profiles in patients with stable coronary artery disease (CAD) and newly diagnosed T2DM. METHODS We conducted a randomized, double-blind, placebo-controlled, cross-over trial over a 12 + 12-week period, with ≥2-week wash-out. INTERVENTION liraglutide/metformin vs. placebo/metformin. Lipoproteins were separated by continuous density gradient ultracentrifugation, and LDL divided into five subfractions between 226 and 270 Å, considering particle size ≤255 Å as the atherogenic pattern. Plasma C-reactive protein and tumor necrosis factor-α were assessed by the enzyme-linked immunosorbent-assay. RESULTS 28 out of 41 randomized patients completed all visits. Intention-to-treat analysis was performed but one patient had statin dosage and was excluded from the analysis. 95% of the patients were on statin therapy. Overall, liraglutide did not affect lipid subfractions or markers of LGI compared to placebo. The combination of liraglutide and metformin reduced the total LDL subfractions, primarily by reducing the most atherogenic subfraction LDL5, and reduced CRP but not TNF-α. Explorative analyses suggested that the subfraction LDL5 during the wash-out period rebounded significantly at least in a per-protocol analysis of the sub-group of patients starting the liraglutide therapy. CONCLUSIONS In patients with CAD and newly diagnosed T2DM on stable statin therapy, liraglutide combined with metformin may improve the atherogenic LDL lipid profile and CRP.
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Effects of 1 year of exercise training versus combined exercise training and weight loss on body composition, low-grade inflammation and lipids in overweight patients with coronary artery disease: a randomized trial.
Pedersen, LR, Olsen, RH, Anholm, C, Astrup, A, Eugen-Olsen, J, Fenger, M, Simonsen, L, Walzem, RL, Haugaard, SB, Prescott, E
Cardiovascular diabetology. 2019;(1):127
Abstract
BACKGROUND Dyslipidaemia and low-grade inflammation are central in atherogenesis and linked to overweight and physical inactivity. Lifestyle changes are important in secondary prevention of coronary artery disease (CAD). We compared the effects of combined weight loss and interval training with interval training alone on physical fitness, body composition, dyslipidaemia and low-grade inflammation in overweight, sedentary participants with CAD. METHODS Seventy CAD patients, BMI 28-40 kg/m2 and age 45-75 years were randomised to (1) 12 weeks' aerobic interval training (AIT) at 90% of peak heart rate three times/week followed by 40 weeks' AIT twice weekly or (2) a low energy diet (LED) (800-1000 kcal/day) for 8-10 weeks followed by 40 weeks' weight maintenance including AIT twice weekly and a high-protein/low-glycaemic load diet. Effects of the intervention were evaluated by physical fitness, body weight and composition. Dyslipidaemia was described using both biochemical analysis of lipid concentrations and lipoprotein particle subclass distribution determined by density profiling. Low-grade inflammation was determined by C-reactive protein, soluble urokinase-type plasminogen activator receptor and tumour necrosis factor α. Effects on continuous outcomes were tested by mixed-models analysis. RESULTS Twenty-six (74%) AIT and 29 (83%) LED + AIT participants completed the study. At baseline subject included 43 (78%) men; subjects averages were: age 63 years (6.2), body weight 95.9 kg (12.2) and VO2peak 20.7 mL O2/kg/min (4.9). Forty-six (84%) had pre-diabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). LED + AIT reduced body weight by 7.2 kg (- 8.4; - 6.1) and waist circumference by 6.6 cm (- 7.7; - 5.5) compared to 1.7 kg (- 0.7; - 2.6) and 3.3 cm (- 5.1; - 1.5) after AIT (within-group p < 0.001, between-group p < 0.001 and p = 0.018, respectively). Treatments caused similar changes in VO2peak and lowering of total cholesterol, triglycerides, non-HDL cholesterol and low-grade inflammation. A shift toward larger HDL particles was seen following LED + AIT while AIT elicited no change. CONCLUSIONS Both interventions were feasible. Both groups obtained improvements in VO2peak, serum-lipids and inflammation with superior weight loss and greater central fat loss following LED + AIT. Combined LED induced weight loss and exercise can be recommended to CAD patients. Trial registration NCT01724567, November 12, 2012, retrospectively registered (enrolment ended in April 2013).
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Plasma lipid concentrations and survival in geriatric population: A retrospective cohort study.
Wang, MC, Hu, HY, Lin, IF, Chuang, JT
Medicine. 2019;(49):e18154
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Abstract
Plasma lipids in mid-life are important predictors for cardiovascular events and deaths. However, the association between plasma lipid concentrations and mortality in late life is controversial. Recent studies showed that older people with extremely low total cholesterol (TC) have poor survival outcome, but this conclusion was drawn mostly from Western cohorts. Our study investigated association between plasma lipid concentrations and mortality in Taiwanese elderly population.A retrospective cohort study was conducted among the 69,824 elderly people who participated in the Taipei City Geriatric Health Examination between 2006 and 2010, with a mean follow-up of 3.6 years. The measurements of TC, high density lipoprotein (HDL) and triglycerides were obtained from the records of the participants. Low density lipoprotein (LDL) was calculated using Friedewald formula in 69,088 participants. All lipid components were categorized into quartiles. Males and females were analyzed separately using multivariate Cox proportional hazards models.The elderly with the lowest quartile of TC (<175 mg/dL), HDL cholesterol (<43 mg/dL) and LDL cholesterol (<100.4 mg/dL) were at higher risk of all-cause mortality. Older females with the lowest quartile of TC and LDL cholesterol had higher cardiovascular mortality. Older females with the lowest quartile of HDL had higher mortality from cardiovascular and cerebrovascular diseases.We concluded that TC, mostly attributed to LDL cholesterol, was inversely related to all-cause mortality. HDL remained to be protective against both cardiovascular and stroke mortality in older females. The target levels of plasma lipids in people older than 65 years should be different from that in younger adults.
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Disentangling the Effects of Monounsaturated Fatty Acids from Other Components of a Mediterranean Diet on Serum Metabolite Profiles: A Randomized Fully Controlled Dietary Intervention in Healthy Subjects at Risk of the Metabolic Syndrome.
Michielsen, CCJR, Hangelbroek, RWJ, Feskens, EJM, Afman, LA
Molecular nutrition & food research. 2019;(9):e1801095
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SCOPE The Mediterranean (MED) diet has been associated with a decreased risk of cardiovascular diseases. It is unclear whether this health effect can be mainly contributed to high intakes of monounsaturated fatty acids (MUFA), characteristic for the MED diet, or whether other components of a MED diet also play an important role. METHODS AND RESULTS A randomized fully controlled parallel trial is performed to examine the effects of the consumption of a saturated fatty acid rich diet, a MUFA-rich diet, or a MED diet for 8 weeks on metabolite profiles, in 47 subjects at risk of the metabolic syndrome. A total of 162 serum metabolites are assessed before and after the intervention by using a targeted NMR platform. Fifty-two metabolites are changed during the intervention (false discovery rate [FDR] p < 0.05). Both the MUFA and MED diet decrease exactly the same fractions of LDL, including particle number, lipid, phospholipid, and free cholesterol fraction (FDR p < 0.05). The MED diet additionally decreases the larger subclasses of very-low-density lipoprotein (VLDL), related VLDL fractions, VLDL-triglycerides, and serum-triglycerides (FDR p < 0.05). CONCLUSION The findings clearly demonstrate that the MUFA component is responsible for reducing LDL subclasses and fractions, and therefore causes an antiatherogenic lipid profile. Interestingly, consumption of the other components in the MED diet show additional health effects.
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Body Weight Reduction of 5% Improved Blood Pressure and Lipid Profiles in Obese Men and Blood Glucose in Obese Women: A Four-Year Follow-up Observational Study.
Hasegawa, Y, Nakagami, T, Oya, J, Takahashi, K, Isago, C, Kurita, M, Tanaka, Y, Ito, A, Kasahara, T, Uchigata, Y
Metabolic syndrome and related disorders. 2019;(5):250-258
Abstract
Background: Body weight reduction (BWR) of at least 3% in obese Japanese individuals through lifestyle interventions has improved the risk factors for cardiovascular disease (CVD). We aimed to assess the relation between body weight change (BWC) and CVD risk change and to identify lifestyle improvement related to BWR in obese Japanese individuals. Methods: Subjects were 2579 health checkup examinees without medicated diabetes, hypertension or dyslipidemia, and a body mass index ≥25 kg/m2 who completed lifestyle questionnaires in 2008 and 2012. The 4-year changes in fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), lipids, and blood pressure (BP) levels were compared across the five groups based on the 4-year BWC, and presented as <-5%, -5% to -3%, -3% to -1%, -1% to 1%, and ≥1%. Multivariable logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) for lifestyle improvement related to BWR. Results: Comparing the groups to the reference group (BWC ranging from -1% to +1%), we observed that FPG and HbA1c levels were lower in women in the <-5% group; BP levels were also lower in the <-5% group; triglyceride levels had improved in the <-3% group, and low-density lipoprotein cholesterol levels in the <-5% group; high-density lipoprotein cholesterol levels had improved in men in the <-5% group. In men, the adjusted OR (95% CI) for BWR related to lifestyle improvement pertaining to "over 30 min exercise" was 2.6 (2.0-3.6). In women, the adjusted ORs for BWR related to "walking or physical activity," "drinking alcohol," and "drinking more than a glass of sake" were 1.7 (1.1-2.7), 1.9 (1.1-3.5), and 1.8 (1.1-3.0), respectively. Conclusions: A 5% BWR improved FPG and HbA1c levels in obese women, and BP and lipid levels in obese men. Improvements in exercise and alcohol consumption habits were associated with BWR in this population.
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Acute Effects of Hibiscus Sabdariffa Calyces on Postprandial Blood Pressure, Vascular Function, Blood Lipids, Biomarkers of Insulin Resistance and Inflammation in Humans.
Abubakar, SM, Ukeyima, MT, Spencer, JPE, Lovegrove, JA
Nutrients. 2019;(2)
Abstract
BACKGROUND/OBJECTIVES The acute impact of Hibiscus sabdariffa calyces (HSC) extract on postprandial vascular function and other cardiometabolic risk factors have not been studied previously. This study investigated the acute impact of HSC extract consumption on blood pressure (BP), vascular function and other cardiometabolic risk markers. SUBJECTS/METHODS Twenty-five men with 1% to 10% cardiovascular disease (CVD) risk (determined by QRISK®2) were randomised to consume either 250 mL of the aqueous extract of HSC or water with breakfast in a randomised, controlled, single-blinded, 2-meal cross-over study (ClinicalTrials.gov, NTC02165553) with a two weeks washout period between study days. BP was measured at baseline and hourly for 4 h. Flow mediated dilatation (FMD) of the branchial artery was measured at baseline, 2 and 4 h post intervention drink consumption. RESULTS Acute consumption of aqueous extract of HSC caused a significant increase in % FMD (p < 0.001), a non-significant decrease in systolic BP (SBP) and diastolic BP (DBP); non-significant increase in urinary and plasma nitric oxide (NOx) and reduced response of serum glucose, plasma insulin, serum triacylglycerol and C-reactive protein (CRP) levels; significant (p = 0.026) improvement in the area under systemic antioxidant response curve (0 to 2 h); no significant changes in arterial stiffness following the acute consumption of the extract of HSC. Gallic acid, 4-O-methylgallic acid, 3-O-methylgallic acid and hippuric acid reached a maximum plasma concentration at 1 to 2 h post consumption of the extract of HSC. CONCLUSION The extract of HSC improved postprandial vascular function and may be a useful dietary strategy to reduce endothelial dysfunction and CVD risk, although this requires confirmation.
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Calcium electroporation and electrochemotherapy for cancer treatment: Importance of cell membrane composition investigated by lipidomics, calorimetry and in vitro efficacy.
Hoejholt, KL, Mužić, T, Jensen, SD, Dalgaard, LT, Bilgin, M, Nylandsted, J, Heimburg, T, Frandsen, SK, Gehl, J
Scientific reports. 2019;(1):4758
Abstract
Calcium electroporation is a novel anti-cancer treatment investigated in clinical trials. We explored cell sensitivity to calcium electroporation and electroporation with bleomycin, using viability assays at different time and temperature points, as well as heat calorimetry, lipidomics, and flow cytometry. Three cell lines: HT29 (colon cancer), MDA-MB231 (breast cancer), and HDF-n (normal fibroblasts) were investigated for; (a) cell survival dependent on time of addition of drug relative to electroporation (1.2 kV/cm, 8 pulses, 99 µs, 1 Hz), at different temperatures (37 °C, 27 °C, 17 °C); (b) heat capacity profiles obtained by differential scanning calorimetry without added calcium; (c) lipid composition by mass spectrometry; (d) phosphatidylserine in the plasma membrane outer leaflet using flow cytometry. Temperature as well as time of drug administration affected treatment efficacy in HT29 and HDF-n cells, but not MDA-MB231 cells. Interestingly the HT29 cell line displayed a higher phase transition temperature (approximately 20 °C) versus 14 °C (HDF-n) and 15 °C (MDA-MB231). Furthermore the HT29 cell membranes had a higher ratio of ethers to esters, and a higher expression of phosphatidylserine in the outer leaflet. In conclusion, lipid composition and heat capacity of the membrane might influence permeabilisation of cells and thereby the effect of calcium electroporation and electrochemotherapy.
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Diets Enriched with Conventional or High-Oleic Acid Canola Oils Lower Atherogenic Lipids and Lipoproteins Compared to a Diet with a Western Fatty Acid Profile in Adults with Central Adiposity.
Bowen, KJ, Kris-Etherton, PM, West, SG, Fleming, JA, Connelly, PW, Lamarche, B, Couture, P, Jenkins, DJA, Taylor, CG, Zahradka, P, et al
The Journal of nutrition. 2019;(3):471-478
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BACKGROUND Novel oils high in monounsaturated fatty acids (MUFAs) and low in saturated fatty acids (SFAs) are an alternative to partially hydrogenated oils high in trans-unsaturated fatty acids. There is widespread use of high-MUFA oils across the food industry; however, limited knowledge of their cardiovascular impact exists. OBJECTIVES We investigated the effects of diets containing canola oil, high-oleic acid canola oil (HOCO), and a control oil blend (diet formulated to emulate a Western fat profile) on lipids, lipoproteins, and apolipoproteins (apos), as secondary outcomes of the trial. METHODS In a multi-center, double-blind, randomized, 3-period crossover, controlled feeding trial, men (n = 44) and women (n = 75) with a mean age of 44 y, mean body mass index (BMI; in kg/m2) of 31.7, and an increased waist circumference plus ≥1 metabolic syndrome criteria consumed prepared, weight-maintenance diets containing canola oil [17.5% MUFAs, 9.2% polyunsaturated fatty acids (PUFAs), 6.6% SFAs], HOCO (19.1% MUFAs, 7.0% PUFAs, 6.4% SFAs), or control oil (10.5% MUFAs, 10.0% PUFAs, 12.3% SFAs) for 6 wk with ≥4-wk washouts. Fasting serum lipids were assessed at baseline and 6 wk. Diet effects were examined using a repeated measures mixed model. RESULTS Compared with the control, canola and HOCO diets resulted in lower endpoint total cholesterol (TC; -4.2% and -3.4%; P < 0.0001), LDL cholesterol (-6.6% and -5.6%; P < 0.0001), apoB (-3.7% and -3.4%; P = 0.002), and non-HDL cholesterol (-4.5% and -4.0%; P = 0.001), with no differences between canola diets. The TC:HDL cholesterol and apoB:apoA1 ratios were lower after the HOCO diet than after the control diet (-3.7% and -3.4%, respectively). There were no diet effects on triglyceride, HDL cholesterol, or apoA1 concentrations. CONCLUSIONS HOCO, with increased MUFAs at the expense of decreased PUFAs, elicited beneficial effects on lipids and lipoproteins comparable to conventional canola oil and consistent with reduced cardiovascular disease risk in adults with central adiposity. This trial was registered at www.clinicaltrials.gov as NCT02029833.
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Does alpha-lipoic acid affect lipid profile? A meta-analysis and systematic review on randomized controlled trials.
Haghighatdoost, F, Hariri, M
European journal of pharmacology. 2019;:1-10
Abstract
Randomized controlled trials (RCTs) have demonstrated that alpha lipoic acid (ALA) may change lipid profile, but their results are contradictory. The aim of this study is to conduct a meta-analysis to assess the effects of ALA on lipid profile. Electronic databases including ISI web of science, Ovid, PubMed/Medline, SCOPUS, and Google Scholar were searched up to February 2018. RCTs which assessed ALA effects on lipid profile were selected. Weighted mean difference (WMD) and 95% confidence intervals (CIs) in serum lipids concentrations were defined as intervention effects. Random effects model was used to estimate the pooled effect. Heterogeneity was measured by using I2 test. The protocol was registered with PROSPERO (No. CRD42017072365). Database search retrieved 12 articles. Serum total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-) levels were significantly lower in subjects supplemented with alpha-lipoic acid compared with controls (WMD=-10.18 mg/dL; 95% CI: -16.16, -4.20 mg/dL; P = 0.001 and WMD=-9.22 mg/dL; 95% CI: -18.28, -0.16 mg/dL; P = 0.001, respectively), but no significant changes were found for high density lipoprotein-cholesterol (HDL-c) (WMD: 3.02 mg/dL; 95% CI: -0.39, 6.43; P = 0.082). The overall effect of ALA on serum triglyceride did not reveal any significant change, but in subgroup analysis based on health status (diabetic vs. non-diabetic), ALA decreased serum triglyceride levels in both diabetic and non-diabetic groups compared with controls. This meta-analysis revealed that ALA might favorably affect lipid profile especially LDL and TC. However, for confirming these results, more studies particularly among hyperlipidemic patients are needed.