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1.
The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans.
Borén, J, Packard, CJ, Taskinen, MR
Frontiers in endocrinology. 2020;:474
Abstract
Cardiovascular disease (CVD) is the leading cause of death globally. It is well-established based on evidence accrued during the last three decades that high plasma concentrations of cholesterol-rich atherogenic lipoproteins are causatively linked to CVD, and that lowering these reduces atherosclerotic cardiovascular events in humans (1-9). Historically, most attention has been on low-density lipoproteins (LDL) since these are the most abundant atherogenic lipoproteins in the circulation, and thus the main carrier of cholesterol into the artery wall. However, with the rise of obesity and insulin resistance in many populations, there is increasing interest in the role of triglyceride-rich lipoproteins (TRLs) and their metabolic remnants, with accumulating evidence showing they too are causatively linked to CVD. Plasma triglyceride, measured either in the fasting or non-fasting state, is a useful index of the abundance of TRLs and recent research into the biology and genetics of triglyceride heritability has provided new insight into the causal relationship of TRLs with CVD. Of the genetic factors known to influence plasma triglyceride levels variation in APOC3- the gene for apolipoprotein (apo) C-III - has emerged as being particularly important as a regulator of triglyceride transport and a novel therapeutic target to reduce dyslipidaemia and CVD risk (10).
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2.
Risk factors associated with progression to referable retinopathy: a type 2 diabetes mellitus cohort study in the Republic of Ireland.
Smith, JJ, Wright, DM, Scanlon, P, Lois, N
Diabetic medicine : a journal of the British Diabetic Association. 2020;(6):1000-1007
Abstract
AIM: To determine factors associated with progression to referable diabetic retinopathy in people with type 2 diabetes in the Republic of Ireland. RESEARCH DESIGN AND METHODS The study was conducted in a dynamic cohort of 2770 people with type 2 diabetes, recruited between April 2005 and July 2013. Systemic factors (systolic and diastolic blood pressure, HbA1c , lipid levels, BMI) and baseline diabetic retinopathy grading results were evaluated at 4-monthly and yearly intervals, respectively. Associations between risk factors (most recently recorded value, and rate of change in value between pairs of consecutive systemic evaluations) and development of referable diabetic retinopathy were estimated using Cox proportional hazards models. RESULTS There was a fourfold increased risk of progression to referral when retinopathy was present at baseline vs no retinopathy at baseline (hazard ratio 4.02, 95% CI 2.80-5.78; P<0.001). Higher current values of HbA1c (hazard ratio 1.22, 95% CI 1.11-1.34; P<0.001), systolic blood pressure (hazard ratio 1.29, 95% CI 1.15-1.45; P<0.001) and triglycerides (hazard ratio 1.10, 95% CI 1.03-1.18; P=0.004) were associated with increased risk of referral. Higher current BMI (hazard ratio 0.83, 95% CI 0.73-0.95; P=0.007) and diastolic blood pressure (hazard ratio 0.91, 95% CI 0.85-0.97; P=0.006) were associated with reduced risk of referral. CONCLUSIONS Presence of retinopathy at baseline was strongly associated with increased risk of referral. Modest associations between systemic factors and risk of progression to referable retinopathy were detected.
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3.
Effect of dietary intervention with a legume-based food product on malondialdehyde levels, HOMA index, and lipid profile.
Ruiz Esparza Cisneros, J, Vasconcelos-Ulloa, JJ, González-Mendoza, D, Beltrán-González, G, Díaz-Molina, R
Endocrinologia, diabetes y nutricion. 2020;(4):235-244
Abstract
INTRODUCTION Prevalence of overweight and obesity, a condition that promotes development of chronic degenerative diseases, has increased in Mexico in recent years. Implementation of strategies to increase daily consumption of vegetables, legumes, whole grain cereals, and fruits by the population will result in an adequate intake of soluble fiber, antioxidants, protein of vegetable origin, and vitamins. OBJECTIVE To assess the effect of a commercial food product prepared using 6 legumes on some anthropometric and biochemical parameters in apparently healthy subjects. METHODS A randomized dietary intervention trial where subjects in the study group received for three months 15g of the product, administered daily in periods of five days with two days of rest. Before and after intervention, anthropometric and dietary assessments were performed, and serum glucose, lipid profile, insulin, ultrasensitive C-reactive protein, malondialdehyde (MDA) and insulin resistance (HOMA index) were measured. A Mann-Whitney U test was used and values of P<0.05 were considered statistically significant. RESULTS Sixty university students were included in the study (53% males). At the end of the intervention, decreases were seen in serum glucose levels (P=0.001), MDA (P=0.001) and HOMA index (P=0.017), but there were no significant changes in all other parameters. CONCLUSIONS Daily intake of 15g of the legume-based food product improved serum glucose and malondialdehyde levels in the study group, as well as insulin resistance; which could be attributed to the presence of polyphenols and isoflavones such as genistein in legumes.
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4.
Familial chylomicronemia syndrome: A rare but devastating autosomal recessive disorder characterized by refractory hypertriglyceridemia and recurrent pancreatitis.
Chyzhyk, V, Brown, AS
Trends in cardiovascular medicine. 2020;(2):80-85
Abstract
Familial Chylomicronemia Syndrome (FCS) is a rare autosomal recessive lipid disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis. Because the disorder is often misdiagnosed or not diagnosed and because traditional triglyceride lowering medications are often ineffective, the disease leads to a tremendous physical, social and emotional burden on afflicted patients and their caretakers. Mutations in 5 different genes have been implicated in the development of FCS, all of which have an effect on the activity of lipoprotein lipase. Lipoprotein lipase(LPL) is responsible for removing triglycerides from chylomicrons and other triglyceride rich lipoproteins in the circulation, breaking them down into free fatty acids for use as energy. Patients with FCS have loss of function of their LPL leading to severely elevated chylomicrons in the circulation and hence, severe hypertriglyceridemia. The principle treatment for FCS is to reduce chylomicron formation in the gut by placing the patient on an extremely low fat diet. New medications in development hold significant promise for improving the quality of life for FCS patients.
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5.
The Effects of Different Degrees of Carbohydrate Restriction and Carbohydrate Replacement on Cardiometabolic Risk Markers in Humans-A Systematic Review and Meta-Analysis.
Fechner, E, Smeets, ETHC, Schrauwen, P, Mensink, RP
Nutrients. 2020;(4)
Abstract
Low-carbohydrate diets (LCDs) often differ in their diet composition, which may lead to conflicting results between randomized controlled trials. Therefore, we aimed to compare the effects of different degrees of carbohydrate (CHO) restriction on cardiometabolic risk markers in humans. The experimental LCDs of 37 human trials were classified as (1) moderate-low CHO diets (<45-40 E%, n = 13), (2) low CHO diets (<40-30 E%, n = 16), and (3) very-low CHO diets (<30-3 E%; n = 8). Summary estimates of weighted mean differences (WMDs) in selected risk markers were calculated using random-effect meta-analyses. Differences between the LCD groups were assessed with univariate meta-regression analyses. Overall, the LCDs resulted in significant weight loss, reduced diastolic blood pressure BP, and increased total cholesterol and high-density lipoprotein cholesterol (HDL-C), without significant differences between the three LCD groups. Higher low-density lipoprotein cholesterol (LDL-C) concentrations were found with the very-low CHO diets compared to the moderate-low CHO diets. Decreases in triacylglycerol (TAG) concentrations were more pronounced with the low and very-low CHO diets, compared to the moderate-low CHO diets. Substitution of CHO by mainly saturated fatty acids (SFAs) increased total cholesterol, LDL-C, and HDL-C concentrations. Except for LDL-C and TAGs, effects were not related to the degree of CHO restriction. Potential effects of nutrient exchanges should be considered when following LCDs.
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6.
Incorporating Milk Protein Isolate into an Energy-Restricted Western-Style Eating Pattern Augments Improvements in Blood Pressure and Triglycerides, but Not Body Composition Changes in Adults Classified as Overweight or Obese: A Randomized Controlled Trial.
Hudson, JL, Zhou, J, Kim, JE, Campbell, WW
Nutrients. 2020;(3)
Abstract
Unhealthy Western-style eating patterns (WSEP) predominate, adversely affecting health. Resistance to improving dietary patterns prompts interest to incorporate a potentially health-promoting ingredient into typical WSEP foods and beverages. We assessed the effect of incorporating isocalorically matched carbohydrates versus milk protein isolate (MPI) into a WSEP on weight loss-induced changes in cardiometabolic health and body composition. In a randomized, double-blind, parallel-design study, 44 participants (age 52 ± 1 years, body mass index (BMI) 31.4 ± 0.5 kg/m2, mean ± standard error) consumed a weight maintenance WSEP (0.8 g total protein/kg/day) for 3 weeks (baseline). After, participants consumed an energy-restricted (750 kcal/day below estimated requirement) WSEP for 16 weeks, randomly assigned to contain either an additional 0.7 g carbohydrate/kg/d (CON: n = 23, 0.8 g total protein/kg/day) or 0.7 g protein/kg/d from MPI (MPI: n = 21, 1.5 g total protein/kg/day) incorporated into foods and beverages. Compared to CON, the MPI favored reductions in average 24 h and sleeping systolic and diastolic blood pressures (BP), waking hours systolic BP, and fasting plasma triglyceride concentrations. Reductions in fasting plasma insulin, glucose, total cholesterol, and low-density lipoprotein cholesterol concentrations were not different between groups. Among all participants, whole body mass, lean mass, fat mass, and thigh muscle area, each decreased over time. For adults finding it difficult to deviate from a WSEP, replacing a portion of their carbohydrate with foods and beverages containing MPI may be an effective dietary strategy to reduce BP after weight loss.
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7.
Short-Term Efficacy (at 12 Weeks) and Long-Term Safety (up to 52 Weeks) of Omega-3 Free Fatty Acids (AZD0585) for the Treatment of Japanese Patients With Dyslipidemia - A Randomized, Double-Blind, Placebo-Controlled, Phase III Study.
Yokote, K, Niwa, K, Hakoda, T, Oh, F, Kajimoto, Y, Fukui, T, Kim, H, Noda, Y, Lundström, T, Yajima, T
Circulation journal : official journal of the Japanese Circulation Society. 2020;(6):994-1003
Abstract
BACKGROUND This study is the first to evaluate the short-term efficacy and long-term safety of AZD0585, a mixture of omega-3 free fatty acids, in Japanese patients with dyslipidemia.Methods and Results:In this randomized double-blind placebo-controlled Phase III study, 383 patients were randomized to 2 g AZD0585, 4 g AZD0585, or placebo once daily for 52 weeks. Eligible patients had low-density lipoprotein cholesterol (LDL-C) levels controlled regardless of statin use, and triglyceride levels between 150 and 499 mg/dL. The least-squares (LS) mean percentage changes in triglyceride concentrations from baseline to the 12-week endpoint (mean of measurements at Weeks 10 and 12) in the 2 and 4 g AZD0585 and placebo groups were -15.57%, -21.75%, and 11.15% respectively (P<0.0001 for both AZD0585 doses vs. placebo). No clinically significant changes from baseline to the 12-week endpoint in total cholesterol, LDL-C, and LDL-C/apolipoprotein (Apo) B were found with AZD0585. High-density lipoprotein cholesterol (HDL-C) was slightly increased and very low-density lipoprotein cholesterol, non-HDL-C, ApoC-II, and ApoC-III were decreased with AZD0585 compared with placebo at the 12-week endpoint. Lipid profiles up to Week 52 were consistent with those up to the 12-week endpoint. No clinically important safety concerns were raised. CONCLUSIONS AZD0585 significantly decreased serum triglyceride levels compared with placebo at the 12-week endpoint and was generally safe and well tolerated in Japanese patients with dyslipidemia.
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8.
Effects of Evening-Only Low-Carbohydrate Meal on Healthy Volunteers.
Yaegashi, A, Suzuki, J
Journal of nutritional science and vitaminology. 2020;(3):229-236
Abstract
We performed a pre/post-interventional study with participants as self-controls to evaluate the effects of consuming an evening-only low-carbohydrate meal (LCM) at 1800 h on biochemical measures of glucose and lipid metabolism. Study participants comprised 14 healthy men (age range, 20-29 y) who, consumed standard test meals (STMs) or LCM at 1800 h. Blood samples were collected at fasting, and at 60-, 120-, and 240 min after the start of the meals. The 60-min postprandial levels and the area under the curve (AUC) 0-120 min for plasma glucose were significantly lower after the LCM than after the STMs. The 60- and 120-min postprandial levels and the AUC 0-240 min for plasma insulin were significantly lower after the LCM than after the STMs (p<0.01). Postprandial triglyceride (TG) levels at 120- and 240 min and the AUC 0-240 min were significantly higher after the LCM than after the STMs (p<0.05, p<0.01, and p<0.05, respectively). The interleukin-6 levels were significantly higher 240 min after the STMs than before the meals (p<0.05), but not after the LCM. In these healthy volunteers, consuming an LCM at 1800 h suppressed postprandial hyperglycemia and insulin secretion; however, postprandial TG increased. Consuming an LCM at 1800 h was beneficial as it inhibited elevation of blood glucose; however, it may also increase the risk of arteriosclerosis through increasing TG levels.
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9.
High triglyceride-glucose index is associated with subclinical cerebral small vessel disease in a healthy population: a cross-sectional study.
Nam, KW, Kwon, HM, Jeong, HY, Park, JH, Kwon, H, Jeong, SM
Cardiovascular diabetology. 2020;(1):53
Abstract
BACKGROUND The triglyceride-glucose (TyG) index is a marker of insulin resistance (IR) and has been associated with various metabolic syndromes, cardiovascular diseases, and cerebrovascular diseases. However, limited information is available regarding its association with subclinical cerebral small vessel disease (cSVD). In this study, we evaluated the relationship between the TyG index and cSVD, including silent brain infarcts (SBIs) and white matter hyperintensity (WMH). METHODS We assessed health check-up participants aged 40-79 years from 2006 to 2013. The TyG index was calculated using the log scale of fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2. The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was also calculated. This was compared with two insulin surrogates and cSVD as another IR indicator and compared the association between two insulin surrogates and cSVD. SBI was measured for both prevalence and burden. The WMH volume was quantitatively rated using a computer-assisted semi-automated technique. RESULTS A total of 2615 participants were evaluated (median age: 56 years, male sex: 53%). In the multivariable logistic regression analysis, the TyG index was seen to be associated with SBI prevalence (adjusted odds ratio: 1.39; 95% confidence interval [CI] = 1.06-1.81). Further quantitative analyses showed a positive dose-response relationship between the TyG index and SBI burden (P for trend = 0.006). In multivariable linear regression analysis, the TyG index was also found to be related to the volume of WMH (β = 0.084; 95% CI = 0.013 to 0.154). Additionally, the TyG index showed a similar or slightly stronger association with the prevalence of SBI and the volume of WMH than did HOMA-IR. CONCLUSIONS A high TyG index was associated with a higher prevalence and burden of cSVD in a neurologically healthy population. This marker of IR could be a convenient and useful predictor of cSVD.
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10.
Cardiorespiratory Fitness is Associated with Glycated Hemoglobin and Triglyceride Levels in Severely Obese Men: A Retrospective Clinical Data Analysis.
Wilms, B, Keppler, R, Ernst, B, Schmid, SM, Thurnheer, M, Schultes, B
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2020;(1):15-19
Abstract
BACKGROUND Even subjects with severe obesity show a wide range of metabolic health states, with some showing marked alterations in glucose and lipid metabolism whereas others do not. In severely obese women, we could recently show that the degree of cardiorespiratory fitness is, independently of body mass and age, associated with several markers of glucose and lipid metabolism. AIMS In our retrospective study on a clinical data set, we questioned whether such an association also exists in severely obese men. METHODS Cardiorespiratory fitness, i. e. workload (Wpeak) and oxygen uptake (V̇O2,peak) at peak exercise, was assessed by a bicycle spiroergometry in 133 severely obese men (all BMI>35 kg m-2). The following metabolic blood markers were also measured: Fasting serum glucose, insulin, triglycerides (TG), total, low-, high-density cholesterol (Chol, LDL, HDL), uric acid, and whole blood glycated hemoglobin (HbA1c). The Chol/HDL ratio and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were also calculated. RESULTS Multiple stepwise linear regression models including age, body mass, and smoking status as independent variables revealed that Wpeak and V̇O2,peak, explained 4.5 to 10.7% of variance in HbA1c and TG (all beta<- 0.22; all p<0.02). Including fat free mass instead of body mass in respective models revealed that both Wpeak and V̇O2,peak were predictors of HbA1c and TG (all beta<- 0.265; all p<0.013), respectively, while Wpeak also accounted for variance in glucose and Chol (both beta<- 0.259; both p<0.023). CONCLUSIONS Similar to previous observations in women, our data indicate that cardiorespiratory fitness assessed by bicycle ergospirometry test is associated with glucose and lipid metabolism in severely obese men. The strength of the found associations suggest a mild to moderate influence of cardiorespiratory fitness on metabolic health in severe obesity.