Increase In Triglycerides Research Articles

Sex Hormone-Binding Globulin Is Associated with Obesity and Dyslipidemia in Prepubertal Children.

Sex hormone-binding globulin (SHBG) is associated with age, sex, and puberty. The association of SHBG with various diseases has been suggested nowadays, however, the relationships in prepubertal children have not been sufficiently investigated. This study analyzed the relationship of SHBG with body mass index (BMI) and plasma lipid levels in prepubertal children. We evaluated the association of SHBG with BMI among the 693 prepubertal children subdivided into normal, overweight, and obese groups, with plasma lipid levels among the children subdivided into normal and dyslipidemia groups. The obese and overweight group had lower SHBG levels than the normal BMI group in both sexes. The dyslipidemia group included subjects with low high-density lipoprotein cholesterol (HDL-C), high triglycerides (TG), or a high atherogenic index of plasma (AIP); this group had lower SHBG than the normal lipid group. SHBG was positively correlated with HDL-C, and negatively correlated with TG and AIP. After adjusting for BMI, SHBG was positively correlated with HDL-C and negatively correlated with TG and AIP in all groups. In conclusion, SHBG levels are closely correlated with BMI in prepubertal children. SHBG may play a meaningful role in the decrease in HDL-C and increase in TG during prepubertal age.

Therapeutic effects of different drug regimens and metabolic markers in children with bipolar affective disorder: a comparative analysis

OBJECTIVE To study the changes in metabolic markers and clinical outcome after treatment with different drug regimens in children with bipolar affective disorder. METHODS A retrospective analysis was performed on the medical data of 220 children with bipolar affective disorder who attended the hospital from January 2017 to January 2020. According to the treatment method, 112 children treated with atypical antipsychotic drugs alone were enrolled as the control group, and 108 children treated with atypical antipsychotic drugs combined with mood stabilizer were enrolled as the study group. The two groups were compared in terms of baseline data, changes in related metabolic markers[fasting insulin (FIN), glycosylated hemoglobin (HbAlc), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)] after treatment, incidence rate of metabolic syndrome, and clinical outcome. RESULTS There were no significant differences in the baseline data including age, sex, and course of disease between the two groups (P > 0.05). The study group had a significantly higher overall response than the control group (92.6% vs 82.1%, P 0.05). After treatment, the control group had a significant increase in the level of FIN and a significantly higher level of FIN than the study group (P 0.05). There was no significant difference in the level of HbAlc between the two groups before and after treatment (P > 0.05). Before treatment, there were no significant differences in the levels of TC, TG, HDL-C, and LDL-C between the two groups (P > 0.05), and after treatment, the control group had significant increases in TC and TG and significantly higher levels of TC and TG than the study group (P 0.05). There were no significant differences in the levels of HDL-C and LDL-C between the two groups before and after treatment (P > 0.05). The study group had a significantly lower incidence rate of metabolic syndrome than the control group (2.8% vs 9.8%, P < 0.05). CONCLUSIONS Atypical antipsychotic drugs combined with mood stabilizer in the treatment of bipolar disorder in children have little effect on the level of metabolic markers, and the curative effect is significant.

Abstract 16851: Lipid Profile Differences Among Premenopausal and Postmenopausal African American Women and Implications for Treatment Per Guideline

Introduction: Postmenopausal women have an increased cardiovascular disease (CVD) risk compared to premenopausal women. Though literature demonstrates a relationship between abnormal CVD risk factor patterns, namely lipids, and menopause, less is known about this association in minority racial and ethnic groups. Examining this association in African Americans (AA) is important because they experience disproportionate CVD outcomes. Moreover, recent studies have shown that AA eligible for statin therapy were less likely to receive treatment. Hypothesis: Postmenopausal women are more likely to have a more abnormal lipid profile compared to premenopausal women. Methods: A cohort of 962 women (mean age 50 ± 14 years) from the 10,000 Women Project were categorized into self-declared premenopausal (n = 475, mean age 40 ± 9.8 years) and postmenopausal (n= 487, mean age 61 ± 9.1 years) groups. Data was obtained at community health screening events through self-declared health history surveys. Lipid profiles were obtained through a non-fasting point-of-care cholesterol test. Several CVD risk factors were compared among these groups that include serum total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides (TG), pooled cohort Atherosclerotic Cardiovascular Disease (ASCVD) 10-year risk of heart disease or stroke score, BMI, waist circumference, and blood pressure. Student’s T test was utilized for statistical analysis. Results: Cholesterol testing revealed a significant increase in serum TC (p &lt; 0.0001), LDL (p = 0.0001), and TG (p = 0.001) in the postmenopausal group compared to the premenopausal group. Interestingly, there was also a significant increase in serum HDL in the postmenopausal group (p = 0.0081). Additionally, the ASCVD risk score, which is heavily weighted on age, was significantly higher in the postmenopausal group compared to the premenopausal group (p &lt; 0.0001). Conclusion: Menopause is associated with a more abnormal lipid profile and an elevated ASCVD risk score in AA women which places this group at a higher risk of CVD. Prioritizing lipid management, by adhering to cholesterol treatment guidelines, may assist with CVD risk reduction in this high-risk group.

The effect of elevated triglycerides and purified eicosapentaenoic acid ethyl ester (EPA) for cardiovascular risk reduction in the UK Biobank population

Abstract Elevated plasma triglycerides (TG) are associated with insulin resistance, metabolic syndrome and major adverse cardiovascular events (MACE). Elevated plasma TG (&amp;gt;150 and 200–499 mg/dL) were recently reported to be a predictor of heart failure in patients with coronary heart disease on statin therapy with a respective 19% and 24% risk increase compared to normal TG levels. REDUCE-IT was a major double-blind randomised controlled trial that tested a novel formulation of highly purified eicosapentaenoic acid ethyl ester (EPA) in 8179 patients with elevated TG on statin therapy. In the trial, daily 4g of EPA lowered MACE by an absolute rate of 4.8% compared to a placebo over a median 4.9-year follow-up. This reflected a 25% risk reduction in MACE and a number needed to treat of 21. EPA recently received significant public attention in late 2019 as the FDA has approved it for secondary prevention and high-risk primary prevention of cardiovascular disease (CVD) in patients with elevated TG that match the trial criteria in the USA. We aimed to investigate the risk reduction in MACE from using EPA in the UK population. We used the UK BioBank, a panomic resource following 500,000 participants over &amp;gt;10 years, with similar age and sex adjusted rates of CVD as the UK population. We first calculated the hazard ratios and Kaplan-Meier survival curves by deciles of increasing TG for incidence of combined CV outcomes: stroke, coronary heart disease, and atherosclerosis. Non-linear CoxPH and DeepSurvival models were trained using different variables from &amp;gt;200,000 UK BioBank participants' data. C-index with standard error and confidence interval estimated with bootstrap sampling ensured quality control. We then matched the UK Biobank population with the REDUCE-IT inclusion criteria and estimated the reduction of combined cardiovascular outcomes if EPA was approved in this population. Hazard ratios increased for TG levels to 5.44 between the 10th decile, and the 1st decile TG level, which was used as baseline. 3563 UK Biobank participants matched with the REDUCE-IT criteria. With the assumption that EPA would have the same effect on the UK Biobank population, we estimate that if the participants were taking EPA, only 29% of the risk group versus actual 37% would have suffered an outcome within the UK Biobank follow-up period. This means that 289 less individuals would have suffered an event instead of the recorded 1318, for a total of 1037. That means according to the number needed to treat analysis, 13 patients would need to be treated to prevent 1 patient from experiencing an event. Elevated TG increase risk for CV events in the UK Biobank population. Purified EPA might become an important tool in our arsenal for CVD secondary and primary prevention. Survival Curves &amp; CI of TG for CVD Funding Acknowledgement Type of funding source: None

Comparison the Effect of Niacin Treatment with and without Atorvastatin on Lipid Profile in Type 2 Diabetic Patients

Objective: The risk of cardiovascular disease increased in diabetic patients due to lipoprotein metabolism disorder and insulin resistance. There is different type of dyslipidemia in diabetic patient. The nicotinic acid (niacin) is categorized as vitamin B family and decreases low-density lipoproteins (LDL) and triglyceride (TG) level and increases high-density lipoproteins (HDL). The aim of this study was to compare the effect of niacin treatment with and without atorvastatin on lipid profile on diabetic patient. Materials and Methods: This study is cross over clinical trial on 30 diabetic patients (9 men, 21women) referred to diabetes research center of Yazd (IRAN). At initiation of study administered atorvastatin alone (20 mg/day) for 6 weeks (protocol A), and after 3 weeks washout period, started atorvastatin (20 mg/day) with niacin (50 mg/day) for 6 weeks (protocol B). Statistical analysis was accomplished by using SPSS for windows, version 11.50 and kappa and paired T-test. Results: Patients on protocol B had statistically significant more increase of HDL-C (P-value= 0.08) and decrease of TG than profile A (P-value= 0.024). Also, 2 hours post prandial blood sugar and HbA1c changes in two groups were not significant A (P-value= 0.226), B (P-value= 0.918). Patient in group B had statistically significant decrease in systolic blood pressure and diastolic blood pressure than group A (P-value= 0.010, P-value= 0.015). Conclusion: This study showed decrease of TG, LDL-C and total cholesterol and increase of HDL in both groups. There are significant changes in HDL-C and TG in group B that used niacin with atorvastatin than group A.

Methionine- and Choline-Deficient Diet Enhances Adipose Lipolysis and Leptin Release in aP2-Cre Fatp4-Knockout Mice.

Inadequate intake of choline commonly leads to liver diseases. Methionine- and choline-deficient diets (MCDD) induce fatty liver in mice which is partly mediated by triglyceride (TG) lipolysis in white adipose tissues (WATs). Because Fatp4 knockdown has been shown to increase adipocyte lipolysis in vitro, here, the effects of MCDD on WAT lipolysis in aP2-Cre Fatp4-knockout (Fatp4A-/- ) mice are determined. Isolated WATs of Fatp4A-/- mice exposed to MCD medium show an increase in lipolysis, and the strongest effect is noted on glycerol release from subcutaneous fat. Fatp4A-/- mice fed with MCDD for 4 weeks show an increase in serum glycerol, TG, and leptin levels associated with the activation of hormone-sensitive lipase in subcutaneous fat. Chow-fed Fatp4A-/- mice also show an increase in serum leptin and very-low-density lipoproteins as well as liver phosphatidylcholine and sphingomyelin levels. Both chow- and MCDD-fed Fatp4A-/- mice show a decrease in serum ketone and WAT sphingomyelin levels which supports a metabolic shift to TG for subsequent WAT lipolysis CONCLUSIONS: Adipose Fatp4 deficiency leads to TG lipolysis and leptin release, which are exaggerated by MCDD. The data imply hyperlipidemia risk by a low dietary choline intake and gene mutations that increase adipose TG levels.

Protective effect of celastrol on type 2 diabetes mellitus with nonalcoholic fatty liver disease in mice.

To investigate the protective effects of celastrol on mice with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), and to explore its underlying mechanism. The levels of low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), total cholesterol (TC), and triglyceride (TG) in serum were tested. Malondialdehyde (MDA) and superoxide dismutase (SOD), GOT, and GPT in serum were also detected. The histopathological changes of liver tissues were observed by HE staining. The apoptosis cell number of liver tissues was measured by TUNEL staining. Nrf‐2 and HO‐1 protein and mRNA expression were evaluated by IHC, WB, and RT‐PCR assay. Celastrol had effects to depress TG, TC, LDL‐C, GPT, GOT, and MDA concentration and increase HDL‐C and SOD concentration (p < .05, respectively) with dose‐dependent. Compared with model group, apoptosis cell number was significantly depressed in Cel‐treated groups with dose‐dependent (p < .05, respectively). Nrf‐2 and HO‐1 mRNA and protein expressions were significantly improved in Cel‐treated groups with dose‐dependent (p < .05, respectively). Celastrol can inhibit the oxidative stress reaction and liver cell apoptosis via regulation Nrf2/HO‐1 pathway in T2DM mice with NAFLD.

Study of Lipid Profiles levels in Iraqi children with GH Deficiency Before and after 6 Months GH Replacement Therapy

This present study aimed to quantify serum lipid levels [Total cholesterol (TC), Triglyceride (TG), LowDensity Lipoprotein –cholesterol (LDL-c), Very Low Density Lipoprotein –cholesterol( VLDL-c), HighDensity Lipoprotein–cholesterol (HDL–c) ] quantified before and after 6 months of treatment in Iraqichildren with HGH deficiencyThis study was conducted at the National Center for Diabetes Treatment and Research of the MustansiriyaUniversity in Baghdad and for the period from, (October 2016 to July 2017). The study included 200 samplesdivided into two groups. The patient group included 100 children with short stature including 52 males and48 females with their age ranged from 5 to 12 years . For comparison, 100 samples (50 females and 50males) of healthy children corresponding to patients with sex, age were selected as control group.The results of the study showed Serum (TC), (TG), (LDL-C) and (VLDL) levels had a highly significantlyincreased in children GHD group when compared with controls group (P&lt;0.001).Regarding serum (HDL-C) levels there was a highly significantly decreased in children GHD group whencompared with healthy children (P&lt;0.001) before treatment, and after 6 months of treatment a decrease infat levels was observed in patients [ (TC), (TG) and (LDL-C), (VLDL), very significantly (p &lt;0.001), whiletheir HDL-C level was higher than before treatment .To distinguish between GHD patients and the control group, the Receiver Operator Curve (ROC) analysisshowed a descending order of significance for the indicators that showed significant differences beforetreatment. The serum level of LDL-C was 0.77, followed by (TG) (0.637 ) ,(VLDL-C) (0.637),( TC) (0.626),and ( HDL-C) (0.614) respectively [this means that all variables managed to occupy a significant region ofROCIt was concluded from this study that there was a significant increase (P &lt;0.001) in serum TG, TC, LDL-Cand VLDL-C, while the level of HDL-C in the blood decreased significantly in GHD children comparedwith healthy children. After 6 months of treatment rhGH has improved the lipid profile of children withgrowth hormone deficiency.

The Relationship between Leisure-Time Sedentary Behaviors and Metabolic Risks in Middle-Aged Chinese Women.

The prevalence of metabolic diseases has increased over the past few decades, and epidemiological studies suggest that metabolic diseases may be associated with lifestyle. The purpose of the present study was to investigate the relationship between leisure-time sedentary behaviors (LTSBs) and metabolic risks in middle-aged women in China. Data came from the China National Nutrition and Health Surveillance (CNNHS) in 2010–2012. A total of 2643 women aged 46 to 53 years were involved. Multiple linear regression was used to examine the association of leisure-time sedentary duration (LTSD) with total cholesterol (TC), triglyceride (TG), waist circumference (WC), and body mass index (BMI). Restrictive cubic splines (RCS) were used to plot the curves between LTSD and the risk of metabolic diseases. Region, education, income, alcohol consumption, exercise, daily energy intake, and fat energy ratio were adjusted for all models. After adjusting for potential influencing factors, the results of multiple linear regression showed that for each additional hour increase in LTSD, TC and TG increased by 0.03 mmol/L and 0.04 mmol/L, respectively. The results of RCS curves showed that the risks of MetS (p for trend = 0.0276), obesity (p for trend = 0.0369), hypertension (p for trend = 0.0062), and hypercholesteremia (p for trend = 0.0033) increased with the increase in LTSD. LTSB was associated with the risks of MetS, obesity, hypertension, and hypercholesteremia in middle-aged women. Reducing LTSD may be an effective way of preventing metabolic diseases in middle-aged women.

Diabetic Cardiovascular Autonomic Neuropathy: Insulin Resistance, Lipids and Simvastatin

Background: Treatment of diabetic cardiac autonomic neuropathy (CAN) is a complex process, that includes: lifestyle modification; reducing of insulin resistance (IR); optimal glycemic control; management of diabetic dyslipidemia; antioxidants; vitamins; treatment of myocardial metabolic abnormalities; thrombosis and others. The aim of study was to investigate the effects of simvastatin on insulin resistance and blood lipid profile parameters in patients with type 2 diabetes mellitus (DM) and the definite stage of cardiac autonomic neuropathy. Methods: The study involved 107 patients with type 2 DM among them 16 patients without CAN, 19 with subclinical stage of CAN and 72 with definite CAN. Median age of patients was 53.6±0.41 years, disease duration - 4.12±0.24 years and median glycated hemoglobin (HbA1c) - 7.01%±0.09%. The control group included 14 almost healthy people without DM. Patients with definite CAN were allocated into two treatment groups: 1st group - 22 patients received standard hypoglycemic therapy and simvastatin 20 mg/day; 2nd group - control (n = 15). The duration of the study was 3 mos. The concentrations of glucose, HbA1c, immunoreactive insulin (IRI) in the blood were determined. Lipid metabolism was assessed by the concentration of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) measurements. The IR index (HOMA-IR), atherogenic coefficient (AC), TG/HDL-C parameters, and TG-glucose (TyG) index were calculated. Result: It was established that in patients with type 2 DM with subclinical stage of CAN there was statistically significant increase in the parameters of HbA1c, IRI, TC, TG and HOMA-IR, AC, TyG indices and decrease of TG/HDL-C and HDL-C compared to control; increase of IRI, TG, TG/HDL-C and TyG indices compared to patients with type 2 DM without CAN. The definite stage of CAN is characterized by an increase of HbA1c, IRI, TC, LDL-C levels and HOMA-IR, AC indices and a significant decrease in the concentration of HDL-C (compared to patients with subclinical CAN). As a result of our study, we found out that prescription of simvastatin to patients with definite stage of CAN was accompanied by a statistically significant decrease in the concentration of TC, LDL-C, TG and an increase in the content of HDL-C (compared to 2nd, control group). Conclusion: Obtained results justify the appropriateness of statins prescription to patients with type 2 DM and the definite stage of CAN.

Effects of Lactobacillus fermentum CQPC04 on Lipid Reduction in C57BL/6J Mice.

Probiotics are functional foods that can effectively regulate lipid reduction and maintain body health. In this study, a strain of Lactobacillus fermentum CQPC04 (LF-CQPC04) isolated from traditional naturally fermented vegetables (Sichuan pickles) was studied, and its effects on lipid reduction in mice, as well as its mechanism of action, were observed. The results of this experiment show that LF-CQPC04 can reduce the abnormal weight gain and abnormal visceral index of mice caused by a high-fat diet. LF-CQPC04 can decrease TG (triglycerides), TC (total cholesterol), LDL-c (low-density lipoprotein cholesterol), AST (aspartate transaminase), ALT (alanine aminotransferase), and AKP (alkaline phosphatase) levels and increase HDL-c (high-density lipoprotein cholesterol) levels in the serum of high-fat mice. LF-CQPC04 can also decrease the levels of inflammatory cytokines, such as IL-6 (interleukin-6), IL-1β (interleukin-1 beta), TNF-α (tumor necrosis factor alpha), and IFN-γ (interferon gamma), and increase IL-4 and IL-10 levels in the serum of high-fat mice. The results of RT-qPCR (real-time quantitative polymerase chain reaction) and western blot experiments show that LF-CQPC04 can also down-regulate the expression of PPAR-γ (peroxisome proliferator-activated receptor gamma), C/EBP-α (CCAAT/enhances binding protein alpha) mRNA, and protein in the liver tissue of high-fat mice, while up-regulating the expression of Cu/Zn-SOD (copper/zinc superoxide dismutase), Mn-SOD (manganese superoxide dismutase), CAT (catalase), CYP7A1 (cholesterol 7 alpha hydroxylase), PPAR-α (peroxisome proliferator-activated receptor alpha), CPT1 (carnitine palmitoyl transferase 1), LPL (lipoprotein lipase), and ABCA1 (ATP-binding cassette transporter A1). Moreover, LF-CQPC04 shows stronger effects in regulating lipid reduction in mice than L-carnitine and commercial LB (Lactobacillus delbrueckii subsp. Bulgaricus) bacteria. LF-CQPC04 is beneficial for lipid reduction in animals and has good probiotic potential.

Triglycerides are related to left ventricular mass in hypertensive patients independently of other cardiometabolic risk factors: the effect of gender

Given the inconsistent results on the prognostic significance of triglycerides (TGs), the purpose of the present study was to investigate the association of plasma TGs with left ventricular mass (LVM) in hypertensive patients. We studied 760 never treated, non diabetic, hypertensive patients. Τransthoracic echocardiography was performed and LVMI was calculated according to the Devereux formula, adjusted to body surface area. Triglycerides were associated with LVMI after adjustment for age, gender, systolic blood pressure (SBP), smoking and fasting glucose (b = 0.08, p = 0.009). This relationship remained significant even after adjustment for BMI, LDL-C and ApoB/ApoA1 ratio (b = 0.07, p = 0.04). Gender-stratified analysis indicated that TGs were related to LVMI in men (p = 0.001) but not in women (p = NS). In addition, TGs were related with LV hypertrophy (LVH) in men, increasing the odds by 7% to present LVMI over 115 g/m2 (OR = 1.07 per 10 mg/dl increase in TGs, p = 0.01). In conclusion, TGs are associated with LVMI in hypertensive patients, independently of other risk factors, including LDL-C. Given the prognostic significance of LVH, it might be suggested that TGs may serve as a useful marker for indentifying hypertensive patients at high risk. The gender discrepancy may suggest a possible gender-specific modulatory effect of TGs on LV structure.

Characterisation and Hypolipidaemic Activity of Phenylquinoline, and Narceine Isolated from Ficus polita Leaf

Aim: To evaluate hypolipidaemic potentials of column chromatography fractions (F1 to F6) of the chloroform leaf extract of Ficus polita and to detect the bioactive compounds present in the most active fraction using spectroscopic techniques.&#x0D; Study Design: Fourty-five (45) wistar rats were grouped into nine groups of five rats each: normal control, hyperlipidaemic control, hyperlipidaemic administered with standard drug control/ atorvastatin (10 mg/kg body weight), and hyperlipidaemic administered groups administered with 50 mg/kg body weight of column chromatography fractions (F1, F2, F3, F4, F5, and F6) for a period of two weeks.&#x0D; Place and Duration of Study: Department of Biochemistry Laboratory, Faculty of Basic Medical Sciences, Bayero University Kano, Nigeria, from May 2018 to April 2019.&#x0D; Methodology: Chloroform leaf extract of F. polita was fractionated by using column chromatography, and the resulting fractions were pooled, based on their retention factor (Rf), into six (6) fractions by using analytical thin layer chromatography. The resulting six (6) fractions were screened for hypolipidaemic activity. Serum total cholesterol (TC), triglycerides (TG), high density lipoprotein-cholesterol (HDL), and low density lipoprotein cholesterol (LDL) were determined. The rats treated with the best fraction in terms hypolipidaemic activity (fraction 3) were screened for serum HMG Co A reductase, lactate dehydrogenase (LDH), creatine kinase (CK) activities, as well as troponin I level. Oxidative stress markers such as malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) were determined in the heart tissue homogenate of the rats treated with fraction 3.&#x0D; Results: Fraction 3 treated hyperlipidaemic group showed significant (p&lt;0.05) decrease in the levels of serum TC, TG, and LDL, but significant (p&lt;0.05) increase in the level of serum HDL. Fraction 3 (F3) treated hyperlipidaemic groups showed significant (p&lt;0.05) decrease in the activity of serum LDH and the level of troponin I, but significant (p&lt;0.05) increase in the activity of serum HMG Co A reductase. After high fat diet administration, the level of heart tissue antioxidant markers such as GSH, SOD and catalase were decreased whereas the level of heart tissue MDA was elevated. The level of these antioxidant markers were brought to normalcy by fraction 3 (F3). Histological studies of the heart corroborated the biochemical findings, and treatment with fraction 3 (F3) was found to be effective in restoring dietary-induced myocardiac toxicity in rats. FTIR and GCMS analyses were carried out for the detection of bioactive compound(s) in fraction 3 (F3), and the result revealed the presence of "8-methoxy-4-phenylquinoline, and narceine.&#x0D; Conclusion: The study concludes that; the hypolipidaemic property of the leaf of F. polita is mediated by the bioactive compounds "8-methoxy-4-phenylquinoline, and narceine." via their antioxidant properties.

Association of Lipid Profile with Type 2 Diabetes in First-Degree Relatives: A 14-Year Follow-Up Study in Iran.

PurposeDyslipidemia is claimed to be associated with an increased risk of type 2 diabetes mellitus (T2DM). However, first-degree relatives (FDRs) of patients with T2DM are reported to be at higher risk. The aim of this study was to evaluate the association between serum lipid profile and T2DM incidence in FDRs.Patients and methodsInformation on 1222 T2DM FDRs during 14 years of follow-up was retrieved. All individuals were examined for diabetes status and dyslipidemia once a year. We used a Bayesian joint longitudinal-survival model to assess the association.ResultsOur data showed that a 10 mg/dL increase in triglycerides (TG), very-low-density lipoprotein (VLDL), and non-high-density lipoprotein (non-HDL) cholesterol levels during the follow-up period was associated with an increased risk of diabetes by 5%, 29%, and 6.6%, respectively. Moreover, for every one-unit increase in the TG to HDL ratio, the T2DM incidence increased by 35%. Subgroup analysis also showed that the increased risk of diabetes was significant only in female FDRs, so that a 10 mg/dL increase in TG and VLDL cholesterol level and a one-unit increase in TG to HDL ratio in female FDRs resulted in an increased risk of diabetes by 7.8%, 46%, and 64%, respectively. However, analysis of HDL, low-density lipoprotein (LDL), total cholesterol (TC), TC to HDL, and LDL to HDL cholesterol levels/ratios did not find any statistically significant associations.ConclusionIncreases in TG, VLDL, non-HDL cholesterol level, and TG to HDL ratio are associated with an increased risk of T2DM in FDRs, especially in female FDRs.

A novel method for controlling unobserved confounding using double confounders

BackgroundControlling unobserved confounding still remains a great challenge in observational studies, and a series of strict assumptions of the existing methods usually may be violated in practice. Therefore, it is urgent to put forward a novel method.MethodsWe are interested in the causal effect of an exposure on the outcome, which is always confounded by unobserved confounding. We show that, the causal effect of an exposure on a continuous or categorical outcome is nonparametrically identified through only two independent or correlated available confounders satisfying a non-linear condition on the exposure. Asymptotic theory and variance estimators are developed for each case. We also discuss an extension for more than two binary confounders.ResultsThe simulations show better estimation performance by our approach in contrast to the traditional regression approach adjusting for observed confounders. A real application is separately applied to assess the effects of Body Mass Index (BMI) on Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Fasting Blood Glucose (FBG), Triglyceride (TG), Total Cholesterol (TC), High Density Lipoprotein (HDL) and Low Density Lipoprotein (LDL) with individuals in Shandong Province, China. Our results suggest that SBP increased 1.60 (95% CI: 0.99–2.93) mmol/L with per 1- kg/m2 higher BMI and DBP increased 0.37 (95% CI: 0.03–0.76) mmol/L with per 1- kg/m2 higher BMI. Moreover, 1- kg/m2 increase in BMI was causally associated with a 1.61 (95% CI: 0.96–2.97) mmol/L increase in TC, a 1.66 (95% CI: 0.91–55.30) mmol/L increase in TG and a 2.01 (95% CI: 1.09–4.31) mmol/L increase in LDL. However, BMI was not causally associated with HDL with effect value − 0.20 (95% CI: − 1.71–1.44). And, the effect value of FBG per 1- kg/m2 higher BMI was 0.56 (95% CI: − 0.24–2.18).ConclusionsWe propose a novel method to control unobserved confounders through double binary confounders satisfying a non-linear condition on the exposure which is easy to access.

Blood clearance kinetics and organ delivery of medium-chain triglyceride and fish oil-containing lipid emulsions: Comparing different animal species

Medium-chain triglycerides (TG) (MCT) and fish oil (FO) TG are incorporated as the core TG component into intravenous (IV) lipid emulsions for infusion in parenteral nutrition. Bolus injections of IV emulsions, on the other hand, have emerged as a novel therapeutic approach to treat various acute disorders. However, intravascular metabolism and organ delivery of acute IV injection of emulsions containing both MCT and FO are not fully defined, nor have they been characterized across common experimental animal models. We characterized and compared blood clearance kinetics and organ distribution of bolus injections of MCT/FO emulsions among different animal species. We also examined whether sex differences or feeding status can affect catabolic properties of MCT/FO lipid emulsions. Blood clearance rates of lipid emulsions with specific TG composition were compared in rats IV injected with [3H]cholesteryl hexadecyl ether labeled pure n-6 long-chain (LCT) and n-3 FO TG lipid emulsions, or emulsions containing MCT and FO at different ratios (wt/wt), which include 8:2 (80% MCT: 20% FO), 5:4:1 (50% MCT: 40% LCT: 10% FO) and SMOF (30% LCT: 30% MCT: 25% olive oil: 10% FO). Dose-response effects (0.016mg-1.6mgTG/g body weight) of the MCT/FO 8:2 emulsions on blood clearance properties and organ delivery were determined in both mice and rats. Blood clearance kinetics and organ uptake of MCT/FO 8:2 emulsions were compared between male and female rats and between fed and fasted rats. Changes in plasma lipid profiles after acute injections of MCT/FO 8:2 lipid emulsion at different doses (0.043, 0.133, and 0.4mgTG/g body weight) were characterized in non-human primates (Cynomolgus monkeys). MCT/FO 8:2 emulsion was cleared faster in rats when compared with other emulsions with different TG contents. Mice had faster blood clearance and higher fractional catabolic rates (FCR) when compared with the rats injected with MCT/FO 8:2 emulsions regardless of the injected doses. Mice and rats had similar plasma TG and free fatty acid (FFA) levels after low- or high-dose injections of the MCT/FO emulsion. Tissue distribution of the MCT/FO 8:2 lipid emulsion are comparable between mice and rats, where liver had the highest uptake per recovered dose among all organs (>60%). Feeding status and sex differences did not alter the blood clearance rate of the MCT/FO 8:2 emulsion in rats. In a nonhuman primate model, dose-response increases in plasma TG and FFA were observed after IV injection of MCT/FO 8:2 emulsions within the 1st 10min. A lipid emulsion containing both MCT and FO TG is cleared rapidly in blood and readily available for organ uptake in rodent and primate animal models. Characterization of the blood clearance properties of the MCT/FO 8:2 emulsion administered in various animal models may provide further insight into the safety and efficacy profiles for future therapeutic use of bolus injections of MCT/FO emulsions in humans.

Lack of collagen XVIII leads to lipodystrophy and perturbs hepatic glucose and lipid homeostasis.

Lack of collagen XVIII leads to lipodystrophy and perturbs hepatic glucose and lipid homeostasis.

Dietary Glucose Increases Glucose Absorption and Lipid Deposition via SGLT1/2 Signaling and Acetylated ChREBP in the Intestine and Isolated Intestinal Epithelial Cells of Yellow Catfish

Dietary carbohydrate affects intestinal glucose absorption and lipid deposition, but the underlying mechanisms are unknown. We used yellow catfish and their isolated intestinal epithelial cells (IECs) to test the hypothesis that sodium/glucose cotransporters (SGLTs) 1/2 and acetylated carbohydrate response element binding protein (ChREBP) mediated glucose-induced changes in glucose absorption and lipid metabolism. Yellow catfish (mean±SEM weight: 4.68±0.02g, 3mo old, mixed sex) were fed diets containing 250g carbohydrates/kg from glucose (G, control), corn starch (CS), sucrose (S), potato starch (PS), or dextrin (D) for 10 wk. IECs were isolated from different yellow catfish and incubated for 24h in a control or glucose (15mM) solution with or without a 2-h pretreatment with an inhibitor [sotagliflozin (LX-4211) or tubastatin A (TBSA)]. Human embryonic kidney cells (HEK293T cells) were transfected with a Flag-ChREBP plasmid to explore ChREBP acetylation. Triglyceride (TG) and glucose concentrations and enzymatic activities were measured in the intestine and IECs of yellow catfish. They also were subjected to immunofluorescence, immunoprecipitation, qPCR, and immunoblotting. Immunoblotting and immunoprecipitation were performed with HEK293T cells. The G group had greater intestine TGs (0.99- to 2.30-fold); activities of glucose 6-phospate dehydrogenase, 6-phosphogluconate dehydrogenase, and isocitrate dehydrogenase (0.12- to 2.10-fold); and expression of lipogenic genes (0.32- to 2.34-fold) thanthe CS,PS,andDgroups. The G group had greater intestine sglt1/2 mRNA and protein expression than the CS, Sand Dgroups (0.35- to 1.12-fold and 0.40- to 4.67-fold, respectively), but lower mRNA amounts of lipolytic genes(48.6%-65.8%) than the CS and PS groups. LX-4211 alleviated the glucose-induced increase in sglt1/2 mRNA (38.2%-47.4%) and SGLT1 protein (48.0%) expression, TGs (29.3%), and lipogenic enzyme activities (27.7%-42.1%) and gene expression (38.0%-55.5%) in the IECs. TBSA promoted the glucose-induced increase in TGs (11.3%), fatty acid synthase activity (32.6%), and lipogenic gene expression (21.6%-34.4%) in the IECs and acetylated ChREBP (10.5%) in HEK293T cells. SGLT1/2 signaling and acetylated ChREBP mediated glucose-induced changes in glucose absorption and lipid metabolism in the intestine and IECs of yellow catfish.

Influence Of Maternal Exercise And DHA Levels During Pregnancy On Maternal Lipids

Elevated levels of Total Cholesterol (TC), low-density lipoprotein (LDL) and triglycerides (TG) during pregnancy have been associated with risks of gestational diabetes, preeclampsia, fetal macrosomia and cardiovascular disease. Exercise is known to decrease TC, LDL and TG, while increasing HDL within normal ranges. Similarly, Supplementation of polyunsaturated fatty acids (PUFA), such as DHA, help control and mitigate excessive triglycerides, while increasing HDL. Research has not investigated the potential relationship of maternal exercise and PUFA levels on maternal lipid profiles. PURPOSE: To determine the relationship between maternal exercise and plasma levels of DHA on maternal lipid levels at 16 and 36 weeks. METHODS: 22 women with a singleton pregnancy (<16 weeks) were randomized to either aerobic (n=9) or non-exercising control (n=4) group. Participants exercised 3x50 minutes per week at moderate intensity for ~24 weeks, with average weekly METmins/wk calculated based on standard MET values*average minutes. Maternal plasma was collected at 16 and 36 weeks of gestation and analyzed for DHA and lipid levels. Multiple linear regression and Spearman correlation models were performed to determine relationships between maternal METmins/wk, DHA levels, and lipid levels. RESULTS: There is a significant negative correlation between DHA levels on HDL (-0.692, p=0.01) at 36 weeks. There are trends of significance with METmins/wk with DHA (0.500; p=0.08) and TG (-0.440, p=0.13) at 36 wks. There was not a significant regression equation found for TC (F=0.690, p=0.52) and TG (F=2.092, p=0.174), however METmins/wk showed a negative relationship to TC (-0.094, p=0.307) and trended to significantly predict TG (-0.185, p=0.081) while DHA Levels showed a positive relationship with TC (0.059, p=0.331) and TG (0.105, p=0.125). CONCLUSION: The current suggests a potential relationship between exercise and DHA levels during pregnancy on maternal lipids. These findings showed a negative and stronger relationship with METmins/wk compared to DHA levels, thus suggesting exercise may be more important to control excessive increases in TC and TG during pregnancy.

582-P: Triglycerides, Uric Acid, and Incidence of Type 2 Diabetes Mellitus in Northwest China: The Jinchang Cohort Study

Objective: To study the association of triglycerides(TG), uric acid and incidence of type 2 diabetes mellitus(T2DM), evaluate whether there would be an additive interaction between two factors. Methods: Based on the follow-up population of Jinchang cohort, an ongoing occupational-based prospective cohort study of 48,001 participants at baseline, the nested-case control study was used to explore the relationship of TG, uric acid and incidence of T2DM, and calculate the odds ratio(OR) and 95% confidence intervals(CI). The interaction additive model was used to evaluate whether there would be an additive interaction between two factors. Results: Among 18,195 participants with normal fasting plasma glucose(FPG) at baseline, there were 267 incident diabetes cases during a median of 2.2 years of follow-up. With the increase of serum TG and uric acid, the cumulative incidences of diabetes in people with normal FPG at baseline were all rising (P for trend&amp;lt;0.05). After multivariable adjustments, the risk factors of diabetes were overweight/obesity(OR=2.30, 95%CI:1.72-3.08), hypertension(OR=2.42, 95%CI:1.78-3.29),hypertriglyceridemia(OR=1.49,95%CI:1.11-2.00), hyperuricemia(OR=2.32,95%CI:1.62-3.30), hypo high density lipoprotein cholesterolemia(OR=2.35, 95%CI:1.60-3.46). There was a positive additive interaction between hypertriglyceridemia and hyperuricemia on the development of diabetes from normal FPG. When they were co-existing, the risk of diabetes(OR, 95%CI) in the total, male and female population were 7.13 (4.70-10.83), 8.42 (5.13-13.83) and 7.09 (2.94-17.14),respectively. Conclusion: Increased triglycerides and uric acid were strong risk factors of diabetes. Furthermore, there was a positive additive interaction between hypertriglyceridemia and hyperuricemia on the development of diabetes from normal fasting plasma glucose. Disclosure W. Huang: None. J. Yang: None. N. Liu: None. P. Huang: None. R. Zhang: None. R. Wang: None. Z. Bai: None. N. Cheng: None. M. Wang: None. S. Zheng: None. Y. Bai: None. Funding National Institutes of Health (1R01ES02908201A1); Lanzhou University (2018LDBRZD008)