Changes In Serum Triglycerides Research Articles

Temporal Changes in Metabolic Syndrome Indices and Factors of Metabolic Syndrome Development in Patients With Rheumatic Disease: A Prospective Cohort Study.

Patients with rheumatic disease have a high prevalence of metabolic syndrome. The purpose of this study was to investigate temporal changes in metabolic syndrome indices and to identify factors influencing metabolic syndrome development. A prospective cohort study design was adopted. The study participants were 68 outpatients with a rheumatic disease at an outpatient clinic of a university hospital. Data on demographics, health-related characteristics, steroid use, serum C-reactive protein levels, and metabolic syndrome indices were collected between December 2017 and March 2021. Temporal changes in body mass indices, serum triglyceride, and cholesterol levels were significant. Body mass indices, diastolic blood pressure, serum triglyceride, high-density lipoprotein, and fasting blood glucose levels at time of diagnosis were found to influence metabolic syndrome development. Temporal changes in serum triglyceride, cholesterol, and fasting blood glucose levels were significantly influenced by inflammatory status. The findings demonstrate the importance of controlling inflammatory activities in the context of inhibiting the progression of metabolic syndrome and rheumatic diseases.

843-P: Effects of Pemafibrate on Glucose Metabolism in Adults with Type 2 Diabetes and Hypertriglyceridemia—Subanalysis of the PARM-T2D Study

Background and Aims: Pemafibrate, a novel selective peroxisome proliferator-activated receptor modulator, has been demonstrated to have potent effects on abnormalities of lipid metabolism in adults with type 2 diabetes (T2DM) and hypertriglyceridemia in real-world clinical practice (PARM-T2D study). However, the effects of pemafibrate on glucose metabolism have not been fully clarified. Materials and Methods: In this multicenter, open-labeled, prospective, observational study, adults with T2DM were treated with pemafibrate (PEMA group) or continued on their current therapy (CTRL group) for dyslipidemia for 52 weeks. This subanalysis consisted of participants who did not change their treatment for diabetes and who did not receive insulin or insulin secretagogues during the study period. Glycemic control, insulin secretion, and insulin resistance were assessed by HbA1c levels, HOMA2-β, and HOMA2-R, respectively. The changes of these parameters between baseline and the end of the study were compared between the groups. Results: In total, 279 of 650 participants met the criteria for this analysis. There were no statistical differences in baseline characteristics between PEMA (n = 141) and CTRL groups (n = 138). There were no significant changes in HbA1c levels and beta-cell function over 52 weeks between the groups, whereas pemafibrate significantly improved insulin resistance assessed by HOMA2-R versus the CTRL group (−0.20 vs. 0.01; estimated treatment difference, −0.23% [95% confidence interval = −0.44, −0.02]; p<0.05). Pemafibrate also ameliorated lipid profiles and liver dysfunction. Changes in serum triglyceride, HDL-cholesterol, γ-GTP, and ALP levels were significantly correlated with those in HOMA2-R (p = 0.024, p = 0.002, p < 0.001, and p = 0.032, respectively). Conclusions: Pemafibrate reduced insulin resistance and improved lipid profiles and liver dysfunction in individuals with T2DM and hypertriglyceridemia. Disclosure H.Nomoto: Speaker's Bureau; Novo Nordisk, Sumitomo Pharma, Co., Ltd. T.Atsumi: Speaker's Bureau; Eli Lilly Japan K.K., Kowa Company, Ltd. H.Miyoshi: Research Support; Abbott, LifeScan Diabetes Institute, Taisho Pharmaceutical Holdings Co., Ltd., Speaker's Bureau; AstraZeneca, Boehringer Ingelheim Japan, Inc., Eli Lilly Japan K.K., Kowa Company, Ltd., MSD Life Science Foundation, Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sanofi K.K., Mitsubishi Tanabe Pharma Corporation. K.Kito: None. A.Nakamura: Research Support; Abbott Japan Co., Ltd., Boehringer Ingelheim Japan, Inc., Daiichi Sankyo, Taisho Pharmaceutical Holdings Co., Ltd., Teijin Pharma Limited, Kowa Company, Ltd., Mitsubishi Tanabe Pharma Corporation. H.Kameda: None. K.Omori: None. S.Yanagiya: None. H.Iesaka: None. Y.Oe: None. S.Kawata: None.

The Mechanism of Kelulut Honey in Reversing Metabolic Changes in Rats Fed with High-Carbohydrate High-Fat Diet.

Metabolic syndrome (MetS) is composed of central obesity, hyperglycemia, dyslipidemia and hypertension that increase an individual's tendency to develop type 2 diabetes mellitus and cardiovascular diseases. Kelulut honey (KH) produced by stingless bee species has a rich phenolic profile. Recent studies have demonstrated that KH could suppress components of MetS, but its mechanisms of action are unknown. A total of 18 male Wistar rats were randomly divided into control rats (C group) (n = 6), MetS rats fed with a high carbohydrate high fat (HCHF) diet (HCHF group) (n = 6), and MetS rats fed with HCHF diet and treated with KH (HCHF + KH group) (n = 6). The HCHF + KH group received 1.0 g/kg/day KH via oral gavage from week 9 to 16 after HCHF diet initiation. Compared to the C group, the MetS group experienced a significant increase in body weight, body mass index, systolic (SBP) and diastolic blood pressure (DBP), serum triglyceride (TG) and leptin, as well as the area and perimeter of adipocyte cells at the end of the study. The MetS group also experienced a significant decrease in serum HDL levels versus the C group. KH supplementation reversed the changes in serum TG, HDL, leptin, adiponectin and corticosterone levels, SBP, DBP, as well as adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) level, area and perimeter at the end of the study. In addition, histological observations also showed that KH administration reduced fat deposition within hepatocytes, and prevented deterioration of pancreatic islet and renal glomerulus. In conclusion, KH is effective in preventing MetS by suppressing leptin, corticosterone and 11βHSD1 levels while elevating adiponectin levels.

To evaluate the safety and efficacy of saroglitazar among pre-diabetes and dyslipidemia

Patients with prediabetes are not only at increased risk of progression to type 2 diabetes, but they are also at high risk of developing cardiovascular (CV) risk compared to normoglycemic people. Further, prediabetes is also often associated with abnormal lipid levels (dyslipidemia). We therefore aimed to evaluate the effect of saroglitazar in patients with prediabetes and dyslipidemia. This was a prospective, single centre, single arm study involving patients with pre-diabetes and dyslipidemia. Subjects with baseline HbA1c 5.7-6.4% and dyslipidemia were enrolled in this study. Subjects with on-going medications affecting blood glucose or lipids were excluded from the study. Saroglitazar 4mg once daily was administered for a period of 24 weeks. The primary outcome was change in serum triglycerides and secondary outcome parameters included changes in other lipid parameters and HbA1c levels at 24 weeks follow-up. Forty patients with prediabetes and dyslipidemia were enrolled in the study. At 24 weeks follow-up, serum triglycerides was significantly reduced from 348 mg/dl to 216 mg/dl (P <0.0001). HbA1c was significantly reduced from 6.3% to 5.5% after 24 weeks of Saroglitazar therapy (P<0.0001).

Curcumin and zinc co-supplementation along with a loss-weight diet can improve lipid profiles in subjects with prediabetes: a multi-arm, parallel-group, randomized, double-blind placebo-controlled phase 2 clinical trial

BackgroundDiabetes is one of the major public health concerns. Prediabetes can increase the risk of developing some non-communicable diseases such as type 2 diabetes. Given the increasing trend of prediabetes, it is critical to control it and prevent its complications. Curcumin is a major bioactive component of turmeric. Zinc is an antioxidant nutrient. The present trial aimed to evaluate the effect of curcumin and zinc co-supplementation along with a loss-weight diet on serum lipid profiles in overweight or obese patients with prediabetes.MethodsEighty-four participants were randomized to four groups (curcumin (500 mg/day), zinc (30 mg/day), “curcumin and zinc”, and placebo) for 90 days. Serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), non-HDL, HDL/LDL ratio, weight, BMI, waist circumstance (WC), hip circumstance (HC), physical activity (PA) and dietary intake were determined pre and post-intervention. This study will be conducted at Yazd Diabetes Research Clinic, Shahid Sadoughi University of Medical Sciences.ResultsTotally, 82 participants were included in the final analysis. After the adjusted PA effect, changes in serum TG (adjusted p = 0.001), LDL (adjusted p = 0.035), non-HDL (adjusted p = 0.003), HDL/LDL ratio (adjusted p = 0.002), and HDL (adjusted p < 0.0001) revealed a significant difference between the groups. However, the changes in weight (adjusted p = 0.004) and BMI (adjusted p = 0.006) were significant but the changes in dietary intake, PA, WC, and HC were non-significant (adjusted p ≥ 0.05). Despite that there was a significant difference for post-intervention HDL levels (adjusted p = 0.016), other lipid profiles showed no significant difference (adjusted p ≥ 0.05).ConclusionThe beneficial effects of “curcumin and zinc” co-supplementation was reported for the changes of some lipid profiles (TG, LDL, HDL, non-HDL, and HDL to LDL ratio), BMI, and weight with no positive effects on TC, dietary intake, PA, WC, and HC. Therefore, it may play a potential role in the prevention of macro and microvascular complications.Trial registration The project is a registered clinical trial (Registration number: IRCT20190902044671N1, Iranian Registry of Clinical Trials (IRCT), registered October 11, 2019.

Assessment of the effect of sub-lethal acute toxicity of Emamectin benzoate in Labeo rohita using multiple biomarker approach

Emamectin benzoate (EMB) is a potent neurotoxin agent, widely used for ectoparasites control in aquaculture, but their detailed toxicological implications in Labeo rohita are unknown. Thus, this study was conceptualized to determine the LC50 and to investigate the effects of two sub-lethal concentrations 1/50th of 96 h LC50 (1.82 μgL−1) and 1/10thof 96 h LC50 (9.1 μgL−1) on hemato-immunological and biochemical responses in L. rohita (mean weight 25.54 ± 2.3 g and length 10.35 ± 2.4 cm) for a period of 24 h, 48 h, and 72 h. LC50 of EMB were 163 μgL-1, 112 μgL-1, 99 μgL-1 and 91 μgL-1 at 24 h, 48 h, 72 h, and 96 h respectively. The safe limit at 96 h LC50 of EMB was 2.30 μgL-1. In EMB treated fish, red blood cells, white blood cells, hemoglobin, and hematocrit counts were reduced (p < 0.05) significantly. Superoxide dismutase (SOD) activity in the liver and kidney declined (p < 0.05) at 72 h while in gill and muscle the activity increased significantly. Glutathione-s-transferase (GST) activity in the liver, gill, and kidney increased (p < 0.05) while muscle decreased significantly. Catalase (CAT) activity in liver, gill, and muscle decreased while in kidney increases. Glutamic-oxaloacetic acid transaminase (GOT) activity and Glutamate pyruvate transaminase (GPT) activity were increased in liver, kidney, and muscle tissue. The change in serum triglycerides, serum protein level was noticed. The level of cortisol, heat shock protein 70 (HSP70), and HSP90 increased (p < 0.05) while the immunological responses like immunoglobulin M (IgM) and complement 3(C3) activity decreased (p < 0.05) in EMB exposed fish. Thus, EMB exposure at two sub-lethal concentrations in L. rohita induces several hemato-immuno, and biochemical alterations in blood, serum, and different organs. The overall result of the present study indicated that EMB is toxic to fish even for a short-term exposure and low doses, and therefore utmost caution should be taken to prevent their drainage into water bodies.

Rapid Decrease and Subsequent Increase in the Serum Triglycerides Accompanied by &amp;lt;i&amp;gt;CD36&amp;lt;/i&amp;gt; Transcript Increase in an Acute Stress Mice Model

In this article, we report the changes in serum triglyceride (TG) levels that occurred during repeated tail blood sampling using a mouse restrainer. We used three groups of mice, namely, “PBS-restrained” “PBS-unrestrained” and “mock-restrained”. The mice in the PBS-restrained and PBS-unrestrained groups were intraperitoneally (i.p.) injected with 100 mL PBS and tail blood sampling was performed at 1, 5, 8, 24, and 48 h after i.p. injection. For the mock-restrained group, no i.p. injection was performed whereas the subsequent tail blood sampling was similarly performed. During the tail blood sampling, the mice of the two “restrained” groups were placed inside the restrainer designed from an open-ended 50 mL conical tube. The blood from the mice in the PBS-unrestrained group mice was sampled from the tail held by the operator’s hands while being allowed to move on a stage. Strikingly, in all of the three groups, the serum TG level initially decreased to remarkably low levels (approximately 30 mg/dL) after several blood samplings were performed over 8 h. This decrease was followed by a 2 - 3-fold increase in the levels relative to that in the control mice in the subsequent 24 - 48 h time period. We concluded that the acute stress associated with blood sampling caused alterations in TG levels. Serum levels of free fatty acid showed only modest changes. Changes in TG levels were not associated with serum corticosterone levels but with a dramatic increase in CD36 transcript levels in the liver. The relevance of this finding to the previously reported release of lipoprotein lipase (LPL) from white fatty tissue into the plasma during acute stress is also discussed.

Effect of a very low-carbohydrate ketogenic diet vs recommended diets in patients with type 2 diabetes: a meta-analysis.

There is renewed interest in using very low-carbohydrate ketogenic (VLCK) diets to manage diabetes. Many clinical trials have been published, often with mixed results. This meta-analysis compares the effect of a VLCK diet on glycemic control, body weight, lipid profile, medication use, and dropouts with that of recommended diets for 12 weeks or longer in people with type 2 diabetes. Ovid MEDLINE, Ovid Embase, CENTRAL, and CINAHL databases were searched (January 1980 through September 2019). Two authors independently reviewed search results to select randomized controlled trials (RCTs) comparing a VLCK diet (carbohydrate intake < 50 g/d or < 10% of total energy) with any recommended diet for type 2 diabetes in adults. Discrepancies were resolved after consulting with the third author. Eight RCTs with 648 participants were identified. Compared with control diets, the VLCK diet resulted in a greater decrease in hemoglobin A1c after 3 months (weighted mean difference[WMD]: -6.7 mmol/mol; 95%CI, -9.0 to -4.4) (WMD: -0.61%; 95%CI, -0.82 to -0.40; P < 0.001; moderate-certainty evidence) and after 6 months (WMD: -6.3 mmol/mol; 95%CI, -9.3 to -3.5) (WMD: -0.58%; 95%CI, -0.85 to -0.32; low-certainty evidence). There was a significantly greater weight loss with the VLCK diet after 3 months (WMD: -2.91 kg; 95%CI, -4.88 to -0.95; low-certainty evidence) and after 6 months (WMD: -2.84 kg; 95%CI, -5.29 to -0.39; low-certainty evidence). The VLCK diet was not better than a control diet after 12 months. It was superior in decreasing triglyceride levels, increasing high-density lipoprotein cholesterol levels, and reducing the use of antidiabetic medications for up to 12 months. The VLCK diet appears to control glycemia and decrease body weight for up to 6 months in people with obesity and diabetes. Beneficial changes in serum triglycerides and high-density lipoprotein cholesterol, along with reductions in antidiabetic medications, continued in the VLCK group until 12 months. However, the quality of currently available evidence is not sufficient to recommend VLCK diets. A major limitation of the VLCK diet is patients' lack of adherence to carbohydrate restriction. PROSPERO registration number CRD42020154700.

Effect of Limb-Specific Resistance Training on Central and Peripheral Artery Stiffness in Young Adults: A Pilot Study

This study aimed to investigate the effect of limb-specific resistance training on arterial stiffness in young adults. Twenty-four participants were randomly assigned to three groups: upper-limb resistance training (n = 8 (URT)), lower-limb resistance training (n = 8 (LRT)), and control group (n = 8 (CON)). Both URT and LRT groups performed the limb-specific resistance training at 70–80% of one-repetition maximum twice a week for 8 weeks. The aortic pulse wave velocity and augmentation index (AIx) were measured by the SphygmoCor XCEL to assess central artery stiffness. Peripheral artery stiffness was evaluated by brachial to radial artery pulse wave velocity (ArmPWV) and femoral to posterior tibial artery pulse wave velocity (LegPWV) using Doppler flowmeters. URT significantly reduced AIx (4.7 ± 3.0 vs. 0.3 ± 2.9%, pre vs. post, P = 0.01), and ArmPWV presented a tendency to decrease following URT (10.4 ± 0.3 vs. 8.6 ± 0.8 m/s, pre vs. post, P = 0.06). LRT showed no negative influence on central and peripheral artery stiffness. Changes in serum triglyceride and leg lean body mass after resistance training were significantly associated with changes in AIx and LegPWV, respectively. URT is beneficial in decreasing central artery wave reflection and may help to improve local peripheral artery stiffness even in healthy young adults.

Dynamic Chronological Changes in Serum Triglycerides Are Associated With the Time Point for Non-alcoholic Fatty Liver Disease Development in the Nationwide Korean Population Cohort.

Background: We investigated the effects of anthropometric, laboratory, and lifestyle factors on the development of non-alcoholic fatty liver disease (NAFLD) in a nationwide, population-based, 4-year retrospective cohort.Methods: The propensity score-matched study and control groups contained 1,474 subjects who had data in the Korean National Health Insurance Service-National Sample Cohort in 2009, 2011, and 2013. NAFLD was defined using medical records of a diagnosis confirmed by primary clinicians and meeting two previously validated fatty liver prediction models. Chronological changes in anthropometric variables, laboratory results, and lifestyle factors during two periods were compared between patient and control groups in order to find out parameters with consistent dynamics in pre-NAFLD stage which was defined as period just before the NAFLD development.Results: Among the 5 anthropometric, 10 laboratory, and 3 lifestyle factors, prominent chronological decremental changes in serum triglycerides were consistently observed during the pre-NAFLD stage, although the degrees of changes were more predominant in men (−9.46 mg/dL) than women (−5.98 mg/dL). Furthermore, weight and waist circumference changes during the pre-NAFLD stage were noticeable only in women (+0.36 kg and +0.9 cm for weight and waist circumference, respectively), which suggest gender difference in NAFLD.Conclusion: Early screening strategies for people with abrupt chronological changes in serum triglycerides to predict NAFLD development before the progression is recommended.

Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice

BackgroundLipoprotein glomerulopathy (LPG) is a rare autosomal dominant kidney disease that is most commonly caused by mutations in ApoE Kyoto (p.R43C) and ApoE Sendai (p.R163P). Differences in phenotype among the various ApoE mutations have been suggested, but the pathogenic role of ApoE Kyoto has not been validated in an animal model. This study intended to establish an ApoE Kyoto murine model and to further compare the pathologic differences between ApoE Kyoto and ApoE Sendai.MethodMale ApoE-deficient mice, 3 months of age, were divided into five groups, including the AD-ApoE Sendai, AD-ApoE Kyoto, AD-ApoE3, AD-eGFP, and ApoE (−/−) groups. The first four groups received recombinant adenovirus that contained the entire coding regions of the human ApoE Sendai and ApoE Kyoto, apoE3, and eGFP genes, respectively. Fasting blood and urine samples were collected at multiple time points. Lipid profiles and urine albumin–creatinine ratio were measured. Renal and aortic histopathologic alterations were analyzed.ResultsAfter virus injection, plasma human ApoE was detected and rapidly reached the maximum level at 4–6 days in the AD-ApoE Kyoto and AD-ApoE Sendai groups (17.4 ± 3.1 µg/mL vs.: 22.2 ± 4.5 µg/mL, respectively) and at 2 days in the AD-ApoE3 group (38.4 µg/mL). The serum total cholesterol decreased by 63%, 65%, and 73% in the AD-ApoE Kyoto, AD-ApoE Sendai and AD-ApoE3 groups, respectively. There were no significant changes in serum triglyceride and urinary albumin–creatinine ratio among the five groups. Typical lipoprotein thrombi with positive ApoE staining were detected in the AD-ApoE Kyoto and AD-ApoE Sendai groups. The Oil-red O-positive glomerular area tended to be higher in the AD-ApoE Kyoto group (9.2%) than in the AD-ApoE Sendai (3.9%), AD-ApoE3 (4.8%), AD-eGFP (2.9%), and ApoE (−/−) (3.6%) groups. The atherosclerotic plaque area in the aorta was lower in the group injected with various ApoE mutations than in the group without injection of ApoE mutation.ConclusionsIn this animal study, we first established an ApoE Kyoto mutation murine model and confirmed its pathogenic role in LPG. Our results suggested that LPG may be more severe with the ApoE Kyoto than with the ApoE Sendai.

Effects of Exercise Intervention on Mitochondrial Stress Biomarkers in Metabolic Syndrome Patients: A Randomized Controlled Trial.

Metabolic syndrome (MetS) pathogenesis involves oxidative stress associated with mitochondrial dysfunction, which triggers integrated stress responses via various compensatory metabolic modulators like mitokines and hepatokines. However, the regulatory mechanisms underlying the exercise-derived benefits with respect to mitokines and hepatokines (potential MetS biomarkers) are unknown. Thus, we investigated the effects of exercise training on MetS biomarkers and their associations with clinical parameters. In this single-center trial, 30 women with MetS were randomly assigned to 12-week supervised exercise or control groups (1:1) and compared with 12 age-matched healthy volunteers. All participants completed the study except one subject in the control group. Expectedly, serum levels of the mitokines, fibroblast growth factor-21 (FGF21), growth differentiation factor-15 (GDF15), and the hepatokine, angiopoietin-like 6 (ANGPTL6), were higher in MetS patients than in healthy volunteers. Moreover, their levels were markedly attenuated in the exercise group. Further, exercise-mediated changes in serum FGF21 and GDF15 correlated with changes in the homeostasis model of assessment of insulin resistance (HOMA-IR) and appendicular lean mass (ALM), respectively. Additionally, changes in serum triglycerides and ANGPTL6 were correlated with changes in leptin. Aberrant mitokine and hepatokine levels can be rectified by relieving metabolic stress burden. Therefore, exercise training may reduce the need for the compensatory upregulation of MetS metabolic modulators by improving gluco-lipid metabolism.

Gene Expression and Histochemical Analyses in the Fatty Livers of Rats Fed a Histidine-Excess Diet.

Triglyceride (TG) and cholesterol accumulation are known to occur in the liver of rats fed a histidine-excess (5%) diet, but there are few studies reporting histochemical and molecular biological analyses of the rat liver. The aim of this study was to elucidate the molecular basis of this lipid-accumulation mechanism. Lipid accumulations, tissue section images, and gene expression levels were compared in the livers of rats fed a control or histidine-excess diet for 5 wk (n=8/group). Serum levels of TGs, free fatty acids, total cholesterol, high-density lipoprotein cholesterol, glucose, albumin, and the enzyme activities of aspartate aminotransferase and alanine aminotransferase were also analyzed. In the livers of rats fed a histidine-excess diet, histochemical analyses showed what appeared to be a preliminary stage of nonalcoholic fatty liver, characterized by lipid accumulation around the central vein area and minor fibrosis. However, there were no changes in serum TG or free fatty acid levels. Quantitative PCR analyses showed the up-regulation of FAT/CD36, which is related to the uptake of fatty acids into cells, and the downregulation of two apolipoprotein genes, ApoC3 and ApoE. The mRNA levels of PPARγ, LXRα, and AMPKα in the liver were also reduced by excess histidine intake. The results of this study suggest that steatosis caused by excess histidine intake may be the result of an imbalance between lipid transport from the liver and the uptake of free fatty acids into hepatocytes.

The influence of parathyroidectomy on cardiometabolic risk factors in patients with primary hyperparathyroidism: a systematic review and meta-analysis.

Primary hyperparathyroidism (PHPT) is associated with increased risk of cardiovascular morbidity and mortality. We aim to determine whether parathyroidectomy (PTX) can change cardiometabolic risk factors including serum lipids, glycemic parameters, systolic and diastolic blood pressure, C reactive protein (CRP), and body mass index (BMI). MEDLINE, Web of Science, Scopus, and Google Scholar were searched for relevant articles published till June 2020. Fixed-effect or random-effects models were used to estimate the weighted mean difference (WMD) and 95% CI for outcomes where applicable. In total, 34 studies were eligible to be included in the current meta-analysis. Our results indicated no favorable change in serum triglyceride (n = 13, WMD = -0.06, 95% CI: -0.15, 0.03 mmol/L), total cholesterol (n = 15, WMD = 0.01, 95% CI: -0.14, 0.16 mmol/L), LDL-C (n = 10, WMD = -0.01, 95% CI: -0.17, 0.19 mmol/L), HDL-C (n = 10, WMD = 0.03, 95% CI: -0.001, 0.06 mmol/L), and CRP (n = 5, WMD = 0.82, 95% CI: -0.01, 1.64 mg/L) after PTX in PHPT patients. However, glucose (n = 24, WMD = -0.16, 95% CI: -0.26, -0.06 mmol/L), serum insulin (n = 12, WMD = -1.11, 95% CI: -1.73, -0.49 µIU/mL), systolic (n = 17, WMD = -10.14, 95% CI: -12.27, -8.01 mmHg), and diastolic (n = 16, WMD = -5.21, 95% CI: -7.0, -3.43 mmHg) blood pressures were decreased after PTX, whilst a significant increase was observed in BMI (n = 13, WMD = 0.35, 95% CI: 0.19, 0.51 kg/m2). PTX could improve glycemic parameters and blood pressure, without any significant change in serum lipoproteins and CRP.

Efficacy and safety of saroglitazar in managing hypertriglyceridemia in type-2 diabetes: A meta-analysis

Background and aimsSaroglitazar is commonly used in India for managing hypertriglyceridemia in diabetes. This meta-analysis evaluated the efficacy and safety of saroglitazar in hypertriglyceridemia. MethodsElectronic databases were searched for RCTs involving diabetes patients receiving saroglitazar in intervention arm, and placebo/lipid/diabetes medication in the control arm. Primary outcome was to evaluate change in serum triglyceride and HbA1c. Secondary outcomes were to evaluate changes in other lipid parameters, glycaemia and adverse effects. Analysis for lipid and glycaemic parameters were done separately for controls receiving anti-lipid medications (statins/fibrates) [active control group (ACG)] and those receiving placebo/diabetes medications [passive control group (PCG)]. ResultsFollowing 12 weeks therapy, individuals receiving saroglitazar had significantly lower triglycerides when compared to PCG [MD -71.67 mg/dl (95% CI: −123.67 to −19.66 mg/dl); P < 0.01; I2 = 91% (considerable heterogeneity); low certainty of evidence (LCE)], but not ACG [MD -37.38 mg/dl (95% CI: −84.55–9.79 mg/dl; P = 0.12; I2 = 98% (considerable heterogeneity); LCE]. Individuals receiving saroglitazar had significantly lower fasting glucose when compared to PCG [MD -24.61 mg/dl (95% CI: −44.13 to −5.09 mg/dl); P = 0.01; I2 = 65% (moderate heterogeneity); LCE], but not ACG [MD -13.5 mg/dl (95% CI: −33.1–6.10 mg/dl; P = 0.18; I2 = 98% (considerable heterogeneity); LCE]. HbA1c, total cholesterol, LDL-C, apolipoprotein-B and HDL-C were not significantly different among study groups. Creatinine was significantly higher in patients receiving saroglitazar as compared to controls [MD 0.12 mg/dl (95% CI: 0.04–0.21 mg/dl); P < 0.01; I2 = 29% (low heterogeneity); high certainty of evidence]. ConclusionThis meta-analysis reinforces the excellent triglyceride lowering of saroglitazar, but highlights significant increase in creatinine.

Effects of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Beverages on Cardiometabolic Risk Factors, Body Composition, and Sweet Taste Preference: A Randomized Controlled Trial.

BackgroundA 2018 American Heart Association science advisory indicated that, pending further research, artificially sweetened beverages (ASBs) may be an appropriate initial replacement for sugar‐sweetened beverages (SSBs) during transition to unsweetened beverages (USBs).Methods and ResultsWe randomly assigned 203 adults (121 males, 82 females; 91.6% retention), who habitually consumed SSBs, to 3 groups and delivered free SSBs, ASBs, or USBs to their homes for 12 months. Outcomes included serum triglyceride to high‐density lipoprotein cholesterol ratio (primary), body weight, and sweet taste preference (experimental assessment, 0%–18% sucrose solutions). Change in serum triglyceride to high‐density lipoprotein cholesterol ratio was not different between groups. Although overall change in weight also was not different between groups, we found effect modification (P=0.006) by central adiposity. Among participants in the highest tertile of baseline trunk fat but not other tertiles, weight gain was greater (P=0.002) for the SSB (4.4±1.0 kg, estimate±SE) compared with ASB (0.5±0.9 kg) or USB (−0.2±0.9 kg) group. Both sweetness threshold (–1.0±0.2% m/v; P=0.005) and favorite concentration (–2.3±0.4% m/v; P<0.0001) decreased in the USB group; neither changed in the SSB group. In the ASB group, sweetness threshold did not change, and favorite concentration decreased (–1.1±0.5% m/v; P=0.02). Pairwise comparison between the ASB and USB groups indicated a difference in sweetness threshold (P=0.015).ConclusionsReplacing SSBs with noncaloric beverages for 12 months did not affect serum triglyceride to high‐density lipoprotein cholesterol ratio. Among individuals with central adiposity, replacing SSBs with either ASBs or USBs lowered body weight. However, USBs may have the most favorable effect on sweet taste preference.RegistrationURL: https://www.clinicaltrials.gov; unique identifier: NCT01295671.

2214-PUB: An Open-Label Study of Gemcabene in Adults with Familial Partial Lipodystrophy

Familial Partial Lipodystrophy (FPLD) is characterized by partial loss of subcutaneous fat accompanied by metabolic abnormalities, not responding well to conventionally available therapies. Gemcabene calcium is a monocalcium salt of a dialkyl ether dicarboxylic acid having 2 terminal gem dimethyl carboxylate moieties. Previous studies have shown that gemcabene has the potential to enhance the clearance of VLDL cholesterol and block the overall production of hepatic triglyceride and cholesterol synthesis. The objective of this study was to assess the overall efficacy and safety of gemcabene in a small number of patients with FPLD who have a fasting triglyceride value ≥ 250 mg/dL and hepatic steatosis ≥10%. Five female patients with FPLD (age range: 39-63; 2 with LMNA R482Q and 3 with no causative genetic variant) were included. Patients received a 300 mg/day dose of gemcabene for the first 12 weeks, with randomization to either 300 mg/day (n=3) or 600 mg/day (n=2) for another 12 weeks. Four patients completed treatment and a fifth one discontinued at 22 weeks (data carried forward). Gemcabene treatment resulted in a median change in serum triglycerides of -19.6% at week 12 (the primary endpoint). The range of triglyceride responses was +40.4% to -52.9%, with 3 patients showing decreases. Liver fat fraction showed a reduction in 2 of the 3 responding patients, although an increase in hepatic fat was observed in 2 patients with LMNA R482Q at the end of the study. Four of 5 patients showed slight reductions in HbA1c at week 12 and one patient had no change. Best responding patients fit the previous profiles of gemcabene responders from previous studies (elevated baseline LDL along with triglycerides). This limited proof-of-concept study provided evidence that gemcabene has the potential to lower triglycerides in certain FPLD patients at 12 weeks. Heterogeneous patient responses observed in this study might be related to different genetic etiologies; however further studies are needed to understand this phenomenon. Disclosure B. Akinci: Advisory Panel; Self; Aegerion Pharmaceuticals, Regeneron Pharmaceuticals. Research Support; Self; Gemphire Therapeutics Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Servier. M. Swaidan: None. M. Foss-Freitas: None. Y. Luo: None. A.H. Neidert: None. R.P. Hench: None. T.L. Chenevert: None. A. Longcore: Consultant; Self; Gemphire Therapeutics Inc., Viacyte, Inc. R. Bakker-Arkema: None. C.L. Bisgaier: Advisory Panel; Self; Imagine Pharma. Board Member; Self; Gemphire Therapeutics Inc., Hygieia. Employee; Self; Gemphire Therapeutics Inc. Stock/Shareholder; Self; Gemphire Therapeutics Inc., Hygieia, Imagine Pharma. E.A. Oral: Consultant; Self; Aegerion Pharmaceuticals, Akcea Therapeutics, Regeneron Pharmaceuticals. Research Support; Self; Aegerion Pharmaceuticals, Akcea Therapeutics, Gemphire Therapeutics Inc., GI Dynamics Inc., Regeneron Pharmaceuticals. Funding Gemphire Therapeutics Inc.

1051-P: Selective Targeting of Angiopoietin-Like 3 (ANGPTL3) via the Second-Generation Antisense Oligonucleotide (ASO) ISIS-703802 (AKCEA-ANGPTL3-LRx) in Subjects with Familial Partial Lipodystrophy (FPLD)

FPLD is an extreme form of metabolic dyslipidemia and diabetes caused by selective loss of peripheral subcutaneous fat. Currently, there are no approved therapies for this rare cause of diabetes in the U.S. Reductions in circulating levels of the hepatokine ANGPTL3 either by mutations in humans or by targeted drugs in rodents are associated with reductions in triglyceride levels and provide protection from atherosclerosis, making it an attractive target for patients with FPLD and metabolic dyslipidemia. The objective of this proof-of concept, Phase 2, open-label study was to assess the early efficacy and safety of a strategy that targets ANGPTL3 via ISIS-703802 (AKCEA-ANGPTL3-LRx) in patients with FPLD. Four patients with FPLD (3F/1M; age range: 38-47; 1 with LMNA R482Q, 1 with LMNA R584H, and 2 with no causative genetic variant) with diabetes (HbA1c&amp;gt;6.5%) and hypertriglyceridemia (≥ 500 mg/dL or ≥ 200 mg/dL for patients meeting genetic or family history criteria) were included. Patients received the study drug at a subcutaneous dose of 20 mg weekly for 26 weeks. Primary endpoint was the percent change in serum triglycerides from baseline to week 27. All other endpoints were also analyzed at week 27. Treatment resulted in a 60±26 (mean±SD) % reduction in triglycerides from a baseline of 818±432 mg/dL. Consistent with antisense reduction of ANGPTL3 mRNA, circulating ANGPTL3 levels were lowered by 55±10%. Treatment was also associated with 51±27% reduction in circulating apoC3 levels, 64±24% reduction in total VLDL and chylomicron triglycerides, and 18±15% reduction in total cholesterol. In addition, HbA1c showed a modest mean absolute reduction of 0.2±1.0 % The drug was well tolerated and there were no new safety signals observed. Although a small study, these results suggest that targeting ANGPTL3 in patients with FPLD could successfully address metabolic dyslipidemia. Disclosure M. Foss-Freitas: None. B. Akinci: Advisory Panel; Self; Aegerion Pharmaceuticals, Regeneron Pharmaceuticals. Research Support; Self; Gemphire Therapeutics Inc. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novartis AG, Novo Nordisk A/S, Sanofi-Aventis, Servier. A.H. Neidert: None. R.P. Hench: None. M. Swaidan: None. E.A. Oral: Consultant; Self; Aegerion Pharmaceuticals, Akcea Therapeutics, Regeneron Pharmaceuticals. Research Support; Self; Aegerion Pharmaceuticals, Akcea Therapeutics, Gemphire Therapeutics Inc., GI Dynamics Inc., Regeneron Pharmaceuticals. Funding Ionis Pharmaceuticals, Inc.; Akcea Therapeutics

Efficacy of letrozole in treatment of male adolescents with idiopathic short stature

ObjectiveTo evaluate the efficacy and safety of aromatase inhibitor letrozole in treatment of male adolescents with idiopathic short stature (ISS). MethodSeventy five boys with height less than 2 standard deviation (SD) below the mean who had entered puberty were enrolled in our study from 2004 to 2017, in the Pediatric Department of the First Affiliated Hospital, Sun Yat-Sen University. Among 75 patients, 28 in letrozole group received letrozole and spironolactone, 30 in gonadotrophin releasing hormone analogue (GnRHa) group received GnRHa injection and 17 had no intervention. Height velocity (HV), increment of bone age/chronological age (ΔBA/ΔCA), the final adult height (FAH) were compared among groups and the safety of letrozole treatment was evaluated. ResultsHV maintained faster during letrozole treatment when compared with other groups. HV during GnRHa treatment showed slightly decline in the first 6 months, but decreased remarkably after 6 months, and was significantly lower than that in letrozole group ( P &lt; 0.05). The maturation of BA slowed down in both letrozole and GnRHa groups. But the ΔBA/ΔCA in letrozole group during the first and the second year of treatment were significantly higher (0.67±0.09, 0.50±0.15, respectively) when compared with GnRHa group (0.59±0.16, 0.44±0.13, respectively) ( t=2.78 and 2.20, all P &lt; 0.05). FAH in letrozole group and GnRHa group were (170±4) cm and (170±6)cm, there was no significant differences between the two groups ( P&gt;0.05), and both were higher than that in no intervention group (162±4 cm, P &lt; 0.01). After 6 months of letrozole treatment, testicular volumes and serum testerone levels increased; 39.2% (11/28) boys had clinical manifestations of hyperandrogenemia, and 82.1% (23/28) boys had decreased serum high-density lipoprotein (HDL) levels. Serum levels of HDL and testerone returned normal and the hyperandrogenemia disappeared after the cessation of letrozole treatment. No significant changes in serum triglyceride, serum low-density lipoprotein (LDL), fating serum levels of insulin and glucose, HOMA-IR were observed. No abnormal liver function, myalgia, scoliosis or aggravations of scoliosis was found. ConclusionsLong term letrozole therapy during puberty in boys with ISS can delay bone maturation without significant decrease of linear growth, and thus can improve the final adult height. No severe adverse reactions were found.

Association of increased hepatic insulin clearance and change in serum triglycerides or β-hydroxybutyrate concentration via the sodium/glucose-cotransporter 2 inhibitor tofogliflozin.

AimsObesity and hepatic fat accumulation diminish hepatic insulin clearance, which can cause hyperinsulinaemia. Sodium/glucose‐cotransporter 2 inhibitors (SGLT2‐is) improve insulin resistance and hyperinsulinaemia by weight loss via increased urinary glucose excretion in type 2 diabetes. However, there are few reports of the influence of SGLT2‐is on hepatic insulin clearance. We examined the impact of an SGLT2‐i on hepatic insulin clearance and explored the clinical influence associated with changes in hepatic insulin clearance via an SGLT2‐i and the mechanism of the effects of SGLT2‐i.Materials and methodsData were analysed from 419 patients with type 2 diabetes controlled by diet and exercise. Patients received a placebo or the SGLT2‐i tofogliflozin (TOFO) (placebo: n = 56; TOFO: n = 363) orally once daily for ≥24 weeks. Hepatic insulin clearance was calculated from the ratio of areas under the curve (AUC) of C‐peptide and insulin levels derived from oral meal tolerance test data (C‐peptide AUC0‐120 min/insulin AUC0‐120 min: HICCIR). The correlation of HICCIR via the SGLT2‐i with other clinical variables was analysed using multivariate analysis.ResultsHICCIR was significantly increased via TOFO at week 24. Furthermore, with TOFO insulin and triglyceride (TG) levels were significantly reduced (P < 0.001) and β‐hydroxybutyrate (BHB) was significantly elevated (P < 0.001). Changes in HICCIR were significantly correlated with changes in TG and BHB via TOFO.ConclusionsIncreased HICCIR was significantly associated with reduced TG via TOFO and contributed to the greater increase in BHB compared with placebo in addition to the correction of hyperinsulinaemia.