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Triglyceride/High-Density Lipoprotein Cholesterol Ratio: A Clue to Metabolic Syndrome, Insulin Resistance, and Severe Atherosclerosis.
Azarpazhooh, MR, Najafi, F, Darbandi, M, Kiarasi, S, Oduyemi, T, Spence, JD
Lipids. 2021;(4):405-412
Abstract
High serum levels of triglycerides (Tg) and low levels of high-density lipoprotein cholesterol (HDL-C) are characteristic of the Metabolic Syndrome (MetS). We assessed the ratio of Tg to HDL-C as a way to identify MetS and insulin resistance. We also evaluated its association with severity of carotid atherosclerosis. Data were analyzed from three cohorts totaling 13,908 participants. MetS was defined according to the International Diabetes Federation criteria. Optimal cut-off for Tg/HDL-C ratio was obtained using Youden's index in receiver-operating characteristic (ROC) curve analyses. The risk of MetS and IR in those with a Tg/HDL-C ratio above the optimum cutoff was evaluated by logistic regression analysis. A Tg/HDL-C ratio above the optimal cutoff level significantly increased the odds ratio for MetS in the three cohorts (OR 6.00, 4.04, and 3.50, least in the healthy population), identified insulin resistance defined by the homeostatic model of insulin resistance (HOMA-IR) (p < 0.0001), and was strongly associated with atherosclerosis severity (p = 0.0001). Tg/HDL-C ratio identifies persons with MetS, insulin resistance, and severe atherosclerosis. It should be used more widely to identify patients at high risk. This is clinically important because insulin resistance is treatable.
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Capillary Triglycerides in Late Pregnancy-Challenging to Measure, Hard to Interpret: A Cohort Study of Practicality.
Barrett, HL, Dekker Nitert, M, D'Emden, M, Lingwood, B, de Jersey, S, McIntyre, HD, Callaway, LK
Nutrients. 2021;(4)
Abstract
BACKGROUND Maternal triglycerides are increasingly recognised as important predictors of infant growth and fat mass. The variability of triglyceride patterns during the day and their relationship to dietary intake in women in late pregnancy have not been explored. This prospective cohort study aimed to examine the utility of monitoring capillary triglycerides in women in late pregnancy. METHODS Twenty-nine women (22 with gestational diabetes (GDM) and 7 without) measured capillary glucose and triglycerides using standard meters at home for four days. On two of those days, they consumed one of two standard isocaloric breakfast meals: a high-fat/low-carbohydrate meal (66% fat) or low fat/high carbohydrate meal (10% fat). Following the standard meals, glucose and triglyceride levels were monitored. RESULTS Median capillary triglycerides were highly variable between women but did not differ between GDM and normoglycaemic women. There was variability in capillary triglycerides over four days of home monitoring and a difference in incremental area under the curve for capillary triglycerides and glucose between the two standard meals. The high-fat standard meal lowered the incremental area under the curve for capillary glucose (p < 0.0001). Fasting (rho 0.66, p = 0.0002) and postpradial capillary triglycerides measured at home correlated with venous triglyceride levels. CONCLUSIONS The lack of differences in response to dietary fat intake and the correlation between capillary and venous triglycerides suggest that monitoring of capillary triglycerides before and after meals in pregnancy is unlikely to be useful in the routine clinical practice management of women with gestational diabetes mellitus.
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Effect of vitamin D supplementation on markers of cardiometabolic risk in children and adolescents: A meta-analysis of randomized clinical trials.
Cai, B, Luo, X, Zhang, P, Luan, Y, Cai, X, He, X
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(10):2800-2814
Abstract
BACKGROUND AND AIMS An increasing attention to the effect of vitamin D supplementation on cardiometabolic risk markers in children and adolescents has been gained recently. However, the results are inconsistent. Therefore, we conducted a meta-analysis to examine the effect of vitamin D supplementation on cardiometabolic risk markers in children and adolescents. METHODS AND RESULTS Eligible randomized controlled trials (RCTs) were identified by searching PubMed, EMBASE and Web of Science. The results of this study are synthetized and reported in accordance with the PRISMA statement. GRADE system was used to assess the certainty of evidence. A total of 9 RCTs were identified and included in the meta-analysis. We found that vitamin D supplementation did not affect the changes of cardiometabolic risk markers including high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), body mass index (BMI), waist circumferences, systolic blood pressure (SDP) and diastolic blood pressure (DBP). However, vitamin D supplementation showed a beneficial effect on fasting glucose (MD, -1.54 mg/dl, 95% CI -2.98 to -0.10) and TG (MD, -24.76 mg/dl, 95% CI -37.66 to -11.86) in the sub-group analysis of total vitamin D supplementation ≥ 200,000 IU. CONCLUSIONS Vitamin D supplementation appeared to have a beneficial effect on reducing fasting glucose and TG level when total vitamin D supplementation ≥200,000 IU but not HDL-C, LDL-C TC, blood pressure and waist circumferences levels in children and adolescents. Further studies are needed to address this issue.
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Triglycerides and Residual Atherosclerotic Risk.
Raposeiras-Roubin, S, Rosselló, X, Oliva, B, Fernández-Friera, L, Mendiguren, JM, Andrés, V, Bueno, H, Sanz, J, Martínez de Vega, V, Abu-Assi, E, et al
Journal of the American College of Cardiology. 2021;(24):3031-3041
Abstract
BACKGROUND Even when low-density lipoprotein-cholesterol (LDL-C) levels are lower than guideline thresholds, a residual risk of atherosclerosis remains. It is unknown whether triglyceride (TG) levels are associated with subclinical atherosclerosis and vascular inflammation regardless of LDL-C. OBJECTIVES This study sought to assess the association between serum TG levels and early atherosclerosis and vascular inflammation in apparently healthy individuals. METHODS An observational, longitudinal, and prospective cohort study, including 3,754 middle-aged individuals with low to moderate cardiovascular risk from the PESA (Progression of Early Subclinical Atherosclerosis) study who were consecutively recruited between June 2010 and February 2014, was conducted. Peripheral atherosclerotic plaques were assessed by 2-dimensional vascular ultrasound, and coronary artery calcification (CAC) was assessed by noncontrast computed tomography, whereas vascular inflammation was assessed by fluorine-18 fluorodeoxyglucose uptake on positron emission tomography. RESULTS Atherosclerotic plaques and CAC were observed in 58.0% and 16.8% of participants, respectively, whereas vascular inflammation was evident in 46.7% of evaluated participants. After multivariate adjustment, TG levels ≥150 mg/dl showed an association with subclinical noncoronary atherosclerosis (odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.08 to 1.68; p = 0.008). This association was significant for groups with high LDL-C (OR: 1.42; 95% CI: 1.11 to 1.80; p = 0.005) and normal LDL-C (OR: 1.85; 95% CI: 1.08 to 3.18; p = 0.008). No association was found between TG level and CAC score. TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation (OR: 2.09; 95% CI: 1.29 to 3.40; p = 0.003). CONCLUSIONS In individuals with low to moderate cardiovascular risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in participants with normal LDL-C levels. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).
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Effects of endogenous GIP in patients with type 2 diabetes.
Stensen, S, Gasbjerg, LS, Krogh, LL, Skov-Jeppesen, K, Sparre-Ulrich, AH, Jensen, MH, Dela, F, Hartmann, B, Vilsbøll, T, Holst, JJ, et al
European journal of endocrinology. 2021;(1):33-45
Abstract
OBJECTIVE The insulinotropic effect of exogenous, intravenously infused glucose-dependent insulinotropic polypeptide (GIP) is impaired in patients with type 2 diabetes. We evaluated the effects of endogenous GIP in relation to glucose and bone metabolism in patients with type 2 diabetes using a selective GIP receptor antagonist and hypothesized that the effects of endogenous GIP were preserved. DESIGN A randomized, double-blinded, placebo-controlled, crossover study. METHODS Ten patients with overweight/obesity and type 2 diabetes (mean±s.d.; HbA1c 52 ± 11 mmol/mol; BMI 32.5 ± 4.8 kg/m2) were included. We infused a selective GIP receptor antagonist, GIP(3-30)NH2 (1200 pmol/kg/min), or placebo (saline) during two separate, 230-min, standardized, liquid mixed meal tests followed by a meal ad libitum. Subcutaneous adipose tissue biopsies were analyzed. RESULTS Compared with placebo, GIP(3-30)NH2 reduced postprandial insulin secretion (Δbaseline-subtracted area under the curve (bsAUC)C-peptide% ± s.e.m.; -14 ± 6%, P = 0.021) and peak glucagon (Δ% ± s.e.m.; -11 ± 6%, P = 0.046) but had no effect on plasma glucose (P = 0.692). Suppression of bone resorption (assessed by circulating carboxy-terminal collagen crosslinks (CTX)) was impaired during GIP(3-30)NH2 infusion compared with placebo (ΔbsAUCCTX; ±s.e.m.; -4.9 ± 2 ng/mL × min, P = 0.005) corresponding to a ~50% reduction. Compared with placebo, GIP(3-30)NH2 did not affect plasma lipids, meal consumption ad libitum or adipose tissue triglyceride content. CONCLUSIONS Using a selective GIP receptor antagonist during a meal, we show that endogenous GIP increases postprandial insulin secretion with little effect on postprandial glycaemia but is important for postprandial bone homeostasis in patients with type 2 diabetes.
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Relationship between triglyceride glucose index, retinopathy and nephropathy in Type 2 diabetes.
Srinivasan, S, Singh, P, Kulothungan, V, Sharma, T, Raman, R
Endocrinology, diabetes & metabolism. 2021;(1):e00151
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Abstract
AIMS: To explore the relationship between TyG index, diabetic retinopathy (DR) and nephropathy. METHODS This was a cross-sectional observational study that examined 1413 subjects with type 2 diabetes (both known and newly diagnosed). Subjects underwent a detailed standard evaluation to detect diabetic retinopathy (fundus photography) and nephropathy (defined as urinary albumin excretion ≥ 30 mg/24 h). The TyG index was calculated as ln (fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2) and stratified into 4 quartiles (TyG-Q). The baseline characteristics of the study population in the four TyG-Q (Q1 (≤7.3) n = 349, Q2 (>7.3 to ≤ 7.5) n = 358, Q3 (>7.5 to ≤ 8.0) n = 354, and Q4 (>8.0) n = 352) were analysed. Variables associated with the presence of DR and nephropathy were assessed using a stepwise binary logistic regression analysis. RESULTS The presence of DR was associated with higher TyG index (OR = 1.453, P =.001) and longer duration of diabetes (OR = 1.085, P < .001). The presence of nephropathy was associated with a higher TyG index (OR = 1.703, P < .001), greater age (OR = 1.031, P < .001), use of insulin (OR = 1.842, P = .033), higher systolic BP (OR = 1.015, P < .001), and the presence of DR (OR = 3.052, P < .001). Higher TyG-Q correlated with the severity of DR (P = .024), presence of nephropathy (P = .001), age (P < .001) and diastolic blood pressure (P = .006). CONCLUSIONS A higher TyG index is associated with the presence of retinopathy and nephropathy in individuals with diabetes and could be used for monitoring metabolic status in clinical settings.
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The Pharmacokinetics of Triheptanoin and Its Metabolites in Healthy Subjects and Patients With Long-Chain Fatty Acid Oxidation Disorders.
Lee, SK, Gupta, M, Shi, J, McKeever, K
Clinical pharmacology in drug development. 2021;(11):1325-1334
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Abstract
Long-chain fatty acid oxidation disorders (LC-FAODs) are a group of life-threatening autosomal recessive disorders caused by defects in nuclear genes encoding mitochondrial enzymes involved in the conversion of dietary long-chain fatty acids into energy. Triheptanoin is an odd-carbon, medium-chain triglyceride consisting of 3 fatty acids with 7 carbons each on a glycerol backbone developed to treat adult and pediatric patients with LC-FAODs. The pharmacokinetics of triheptanoin and circulating metabolites were explored in healthy subjects and patients with LC-FAODs using noncompartmental analyses. Systemic exposure to triheptanoin following an oral administration was negligible, as triheptanoin is extensively hydrolyzed to glycerol and heptanoate in the gastrointestinal tract. Multiple peaks for triheptanoin metabolites were observed in the plasma following oral administration of triheptanoin, generally coinciding with the time that meals were served. Heptanoate, the pharmacologically active metabolite of triheptanoin supplementing energy sources in patients with LC-FAODs, showed the greatest exposure among the metabolites of triheptanoin in human plasma following oral administration of triheptanoin. The exposure of heptanoate was approximately 10-fold greater than that of beta-hydroxypentoate, a downstream metabolite of heptanoate. Exposure to triheptanoin metabolites appeared to increase following multiple doses as compared with the single dose, and with the increase in triheptanoin dose levels.
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Association of "hypertriglyceridemic waist" with increased 5-year risk of subclinical atherosclerosis in a multi-ethnic population: a prospective cohort study.
Namdarimoghaddam, P, Fowokan, A, Humphries, KH, Mancini, GBJ, Lear, S
BMC cardiovascular disorders. 2021;(1):63
Abstract
BACKGROUND Hypertriglyceridemic waist (HTGW), which incorporates measures of waist circumference and levels of triglyceride in blood, could act as an early-stage predictor to identify the individuals at high-risk for subclinical atherosclerosis. Previous studies have explored the cross-sectional association between HTGW and atherosclerosis; however, understanding how this association might change over time is necessary. This study will assess the association between HTGW with 5-year subclinical carotid atherosclerosis. METHODS 517 participants of Aboriginal, Chinese, European, and South Asian ethnicities were examined for baseline HTGW and 5-year indices of subclinical atherosclerosis (intima media thickness (mm), total area (mm2), and plaque presence). Family history of cardiovascular disease, sociodemographic measures (age, sex, ethnicity, income level, maximum education), and traditional risk factors (systolic blood pressure, smoking status, total cholesterol, high-density lipoprotein cholesterol, body mass index) were incorporated into the models of association. These models used multiple linear regression and logistic regression. RESULTS Baseline HTGW phenotype is a statistically significant and clinically meaningful predictor of 5-year intima media thickness (β = 0.08 [0.04, 0.11], p < 0.001), total area (β = 0.20 [0.07, 0.33], p = 0.002), and plaque presence (OR = 2.17 [1.13, 4.19], p = 0.02) compared to the non-HTGW group independent of sociodemographic factors and family history. However, this association is no longer significant after adjusting for the traditional risk factors of atherosclerosis (p = 0.27, p = 0.45, p = 0.66, respectively). Moreover, change in status of HTGW phenotype does not correlate with change in indices of atherosclerosis over 5 years. CONCLUSIONS Our results suggest that when the traditional risk factors of atherosclerosis are known, HTGW may not offer additional value as a predictor of subclinical atherosclerosis progression over 5 years.
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Prevalence and clinical outcomes of triglyceride deposit cardiomyovasculopathy among haemodialysis patients.
Onishi, T, Nakano, Y, Hirano, KI, Nagasawa, Y, Niwa, T, Tajima, A, Ishii, H, Takahashi, H, Sakurai, S, Ando, H, et al
Heart (British Cardiac Society). 2021;(2):127-134
Abstract
OBJECTIVE To evaluate the effect of triglyceride deposit cardiomyovasculopathy (TGCV) on the cardiovascular outcomes in haemodialysis (HD) patients with suspected coronary artery disease (CAD). METHODS This retrospective single-centre observational study included data from the cardiac catheter database of Narita Memorial Hospital between April 2011 and March 2017. Among 654 consecutive patients on HD, the data for 83 patients with suspected CAD who underwent both [123I]-β-methyl-iodophenyl-pentadecanoic acid scintigraphy and coronary angiography were analysed. Patients were divided into three groups: definite TGCV (17 patients), probable TGCV (22 patients) and non-TGCV control group (44 patients). The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke assessed for up to 5 years of follow-up. RESULTS The prevalence of definite TGCV was approximately 20% and 2.6% among consecutive HD patients with suspected CAD and among all HD patients, respectively. At the end of the median follow-up period of 4.7 years, the primary endpoint was achieved in 52.9% of the definite TGCV patients (HR, 7.45; 95% CI: 2.28 to 24.3; p<0.001) and 27.3% of the probable TGCV patients (HR, 3.28; 95% CI: 0.93 to 11.6; p=0.066), compared with that in 9.1% of the non-TGCV control patients. Definite TGCV was significantly and independently associated with cardiovascular mortality and outcomes among HD patients in all multivariate models. CONCLUSIONS TGCV is not uncommon in HD patients and is associated with an increased risk of cardiovascular events including cardiovascular death. Thus, TGCV might be a potential therapeutic target.
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Daily Step Count and Postprandial Fat Metabolism.
Burton, HM, Coyle, EF
Medicine and science in sports and exercise. 2021;(2):333-340
Abstract
INTRODUCTION Two benefits of acute exercise are the next day's lowering of the postprandial plasma triglyceride response to a high-fat meal and increased fat oxidation. However, if activity levels (daily steps) are very low, these acute adaptations to exercise do not occur. This phenomenon has been termed "exercise resistance." This study sought to systematically reduce daily step number and identify the range of step counts that elicit "exercise resistance." METHODS Ten participants completed three, 5-d trials in a randomized, crossover design with differing levels of step reduction. After 2 d of controlled activity, participants completed 2 d of LOW, LIMITED, or NORMAL steps (2675 ± 314, 4759 ± 276, and 8481 ± 581 steps per day, respectively). Participants completed a 1-h bout of running on the evening of the second day. High-fat tolerance tests were performed on the next morning, and postprandial responses were compared. RESULTS After LOW and LIMITED, postprandial incremental area under the curve (AUC) of plasma triglyceride was elevated 22%-23% compared with NORMAL (P < 0.05). Whole body fat oxidation was also significantly lower (16%-19%, P < 0.05, respectively) in LOW and LIMITED compared with NORMAL. No significant differences were found between LOW and LIMITED. CONCLUSION Two days of step reduction to approximately 2500-5000 steps per day in young healthy individuals impairs the ability of an acute bout of exercise to increase fat oxidation and attenuate postprandial increases in plasma triglycerides. This suggests that "exercise resistance" occurs in individuals taking approximately 5000 or fewer steps per day, whereas 8500 steps per day protects against exercise resistance in fat metabolism. It seems that fat metabolism is influenced more by the inhibitory effects of inactivity than by the stimulating effects derived from 1 h of moderate-intensity running.