Fasting Serum Triglyceride Research Articles

Low Risk for Developing Diabetes Among the Offspring of Individuals With Exceptional Longevity and Their Spouses.

Little is known about the risk of type 2 diabetes (T2D) among the offspring of individuals with exceptional longevity. We determined the incidence of and potential risk and protective factors for T2D among the offspring of probands and offspring's spouses (mean age=60 years, range 32-88 years) in the Long Life Family Study (LLFS), a multicenter cohort study of 583 two-generation families with a clustering of healthy aging and exceptional longevity. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.5%, or self-reported with doctor diagnosis of T2D, or the use of anti-diabetic medication during a mean follow-up 7.9 ± 1.1 years. Among offspring (n=1105) and spouses (n=328) aged 45-64 years without T2D at baseline visit, the annual incident rate of T2D was 3.6 and 3.0 per 1000 person-years, respectively, while among offspring (n=444) and spouses (n=153) aged 65+ years without T2D at baseline, the annual incident rate of T2D was 7.2 and 7.4 per 1000 person-years, respectively. By comparison, the annual incident rate of T2D per 1000 person-years in the U.S. general population was 9.9 among those aged 45-64, and 8.8 among those aged 65+ years (2018 National Health Interview Survey). Baseline BMI, waist circumference, and fasting serum triglycerides were positively associated with incident T2D, whereas fasting serum HDL-C, adiponectin, and sex hormone binding globulin were protective against incident T2D among the offspring (all P<0.05). Similar associations were observed among their spouses (all P<0.05, except sex hormone binding globulin). In addition, we observed that among spouses, but not offspring, fasting serum interleukin 6 and insulin-like growth factor 1 were positively associated with incident T2D (P<0.05 for both). Our study suggests that both offspring of long-living individuals and their spouses, especially middle-aged, share a similar low risk for developing T2D as compared with the general population. Our findings also raise the possibility that distinct biological risk and protective factors may contribute to T2D risk among offspring of long-lived individuals when compared with their spouses. Future studies are needed to identify the mechanisms underlying low T2D risk among the offspring of individuals with exceptional longevity, and also among their spouses.

Impairment of endometrial decidual reaction in early pregnant mice fed with high fat diet.

To investigate the effect of obesity induced by high fat diet on decidual reaction of endometrium in mice, and the effect of high fat treatment on decidual reaction of endometrial stromal cells. Twelve 4-week-old healthy C57BL/6J female mice were randomly divided into high fat diet group and control group with 6 mice in each group. They were fed with high fat diet (22 kJ/g) or normal diet (16 kJ/g) for 12 weeks, respectively. The body weight of mice was measured every week. After feeding for 12 weeks, the body length and width of mice were measured, and the levels of fasting serum triglyceride and total cholesterol were determined. Then the mice were mated with healthy C57BL/6J male mice, and the uterine tissues were collected on the seventh day of pregnancy. The decidual cells and collagen fibers in mouse endometrium was observed by HE staining and Masson staining respectively. The expression of decidual reaction related proteins in mouse endometrium were detected by immunohistochemistry and Western blotting. Mouse endometrial stromal cells (mESCs) were isolated and treated with the oleic acid and palmitic acid in vitro, and the decidual reaction was induced with estradiol and progesterone. The accumulation of lipid droplets in mESCs was observed by oil red O and Bodipy staining. The cytoskeleton of mESCs was observed by phalloidin staining. The levels of decidual reaction related genes and proteins were detected by real-time fluorescence quantitative PCR and Western blotting. After feeding for 12 weeks, the body weight of mice in the high fat group was significantly higher than that in the control group ( P<0.01), and there was no significant difference in body length between two groups ( P>0.05), but the body width of mice in the high fat group was significantly larger than that in the control group ( P<0.01), and the levels of serum triglyceride and total cholesterol were significantly higher than those in the control group (Both P<0.05). The number of embryo implantation in the high fat group was significantly less than that in the control group ( P<0.01). The differentiation of mESCs to decidual cells in high fat group was slow and abnormal. The expression levels of decidual reaction markers bone morphogenetic protein (BMP)2 and homeobox A10 (HOXA10) were lower than those in the control group, and there was significant difference in the expression level of HOXA10 ( P<0.01). The results of oil red O and Bodipy staining in mESCs showed that after high fat treatment, the accumulation of lipid droplets increased significantly, phalloidin staining showed abnormal cytoskeleton morphology. The expression levels of decidual reaction related genes dtprp, HOXA10 and proteins BMP2, HOXA10 and cyclooxygenase (COX)2 were significantly lower than those in the control group ( P<0.05). Obesity induced by high fat diet and high fat treatment can impair the decidual reaction of endometrium and endometrial stromal cells in mice.

Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk.

AimsHypertriglyceridaemia is associated with increased risk of cardiovascular events. This clinical trial evaluated olezarsen, an N-acetyl-galactosamine-conjugated antisense oligonucleotide targeted to hepatic APOC3 mRNA to inhibit apolipoprotein C-III (apoC-III) production, in lowering triglyceride levels in patients at high risk for or with established cardiovascular disease.Methods and resultsA randomized, double-blind, placebo-controlled, dose-ranging study was conducted in 114 patients with fasting serum triglycerides 200–500 mg/dL (2.26–5.65 mmol/L). Patients received olezarsen (10 or 50 mg every 4 weeks, 15 mg every 2 weeks, or 10 mg every week) or saline placebo subcutaneously for 6–12 months. The primary endpoint was the percent change in fasting triglyceride levels from baseline to Month 6 of exposure. Baseline median (interquartile range) fasting triglyceride levels were 262 (222–329) mg/dL [2.96 (2.51–3.71) mmol/L]. Treatment with olezarsen resulted in mean percent triglyceride reductions of 23% with 10 mg every 4 weeks, 56% with 15 mg every 2 weeks, 60% with 10 mg every week, and 60% with 50 mg every 4 weeks, compared with increase by 6% for the pooled placebo group (P-values ranged from 0.0042 to <0.0001 compared with placebo). Significant decreases in apoC-III, very low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B were also observed. There were no platelet count, liver, or renal function changes in any of the olezarsen groups. The most common adverse event was mild erythema at the injection site.ConclusionOlezarsen significantly reduced apoC-III, triglycerides, and atherogenic lipoproteins in patients with moderate hypertriglyceridaemia and at high risk for or with established cardiovascular disease.Trial registration numberNCT03385239.

Clinico-investigative Study of Facial Acanthosis Nigricans.

Background:Facial acanthosis nigricans (FAN) is an underrecognized and underdiagnosed entity. The typical presentation of acanthosis nigricans (AN) seen elsewhere on the body like axillae and groins is not seen on the face, making it mimic other pigmentary disorders. Moreover, FAN is seldom not accompanied with AN on the classical sites making the diagnosis challenging. The aims of this study were to determine clinical, dermoscopic, and histopathological features of FAN and to estimate the prevalence of obesity and insulin resistance (IR) in FAN.Methods:Forty cases of FAN and forty healthy nonobese individuals with comparable ages and gender were included in the study. Body mass index, waist circumference, hip circumference, waist to hip ratio, and serum fasting lipid levels were used to evaluate obesity, whereas serum fasting insulin and Homeostatic Model of Assessment of Insulin Resistance (HOMA-IR) were used to evaluate IR. Dermoscopy was performed in all cases. Histopathological features of the skin biopsies were reviewed.Results:Out of the 40 cases, 24 were male and 16 were female. The patterns of facial pigmentation in addition to the classic pattern were a hyperpigmented band over forehead (55%), periorbital darkening (25%), perioral (10%), and generalized darkening (10%). Dermoscopy in all cases revealed linear crista cutis, sulcus cutis, and hyperpigmented dots in crista cutis. Biopsy of 20 cases showed mild hyperkeratosis, acanthosis, papillomatosis, and increase in basal melanin. Clinico-dermoscopic-histological correlation showed that milder (light brown) variants of FAN had follicular plugging and subtle sulci pattern with irregular brown globules and perifollicular pigmentation on dermoscopy and mild hyperkeratosis and hypermelanization of the basal layer with minimal acanthosis and papillomatosis on histopathology. On the other hand, chronic variants (dark brown and black) showed prominent sulci, larger brown globules, and perifollicular hyperpigmentation on dermoscopy and moderate hyperkeratosis and hypermelanization of the basal layer with moderate to severe acanthosis and papillomatosis on histopathology. Fasting blood glucose, insulin, HOMA-IR, fasting serum triglyceride, and total cholesterol were statistically significantly high in cases in comparison with controls (P-value <0.05).Conclusions:Varied clinical presentations of FAN were observed. Dermoscopy and histopathology provide a good aid. FAN may be considered as a cutaneous marker of obesity and IR. Thus, FAN should be suspected in patients presenting with facial melanosis who are obese and have AN over other sites, although FAN can also present de novo.

Effect of night shift on development of metabolic syndrome among health care workers.

ABSTRACTCircadian desynchronization, sleep deprivation, changes in eating habit, and lack of physical activity resulting in an increase in pro-inflammatory markers in night shift health care workers is associated with various risk factors for the development of metabolic syndrome. This study aimed to estimate the pro-inflammatory markers in night shift work and find its relationship with different criteria of metabolic syndrome.Materials and Methods:A total of 303 participants were recruited for the study. Demographic data and parameters pertaining to the development of metabolic syndrome were taken. Highly sensitive C-reactive protein (Hs CRP) as proinflammatory marker was analyzed. Fasting blood sugar (FBS), serum triglyceride (TG), and high-density lipoprotein (HDL) were estimated. Criteria for metabolic syndrome were taken according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines.Results:Night shift workers had higher hs CRP compared to day shift workers. TG and FBS were increased significantly (P < 0.001). A total of 6.5% of the night shift workers had a waist circumference greater than 40 inches. It was observed that night shift workers with higher hsCRP had significantly high waist circumference (P < 0.001) and FBS (P < 0.05). A total of 3.57% of the night shift workers were diagnosed with metabolic syndrome with three criteria positive.Conclusion:Night shift work is associated with an increase in pro-inflammatory markers and the development of risk factors leading to metabolic syndrome. Thus, early screening and management of risk factors among night shift health care workers may improve their health status and prevent the development of MS.

Study of Platelet Indices in Patients with Metabolic Syndromes: A Study Protocol

Background: Metabolic syndrome is a syndrome of unified metabolic disorder which includes abdominal obesity (AO), hypertension, hypertriglyceridemia (HTG), hyperglycemia and decreased high-density lipoprotein (HDL). Metabolic syndrome subjects are exposed to greater chances to have insulin resistance, visceral fat accumulation, atherogenic changes to the vessels, abnormal lipid levels and abnormal functioning of endothelium. Platelets play a key role in hemostasis. The mean platelet volume (MPV) and platelet’s proportion are indicators of platelet function. This study aims to find the correlation between various platelet indices in patients with Metabolic syndromes.&#x0D; Methods: This prospective study is planned to be conducted in AVBRH, Wardha. Patients anthropometric parameters like height, weight, blood pressure, waist circumference, hip circumference and biochemical parameters such as fasting blood glucose, serum triglycerides, serum HDL, and mean platelet volumes will be assessed. Total 130 subjects will be assessed and data will be analyzed to estimate a correlation between platelet indices and metabolic syndromes.&#x0D; Expected Results: A significant correlation is expected between various platelet indices in patients of different metabolic syndromes.

Dyslipidaemia in Schizophrenia

Background: Lipid neurochemistry is an important focus in schizophrenia research. Disorder of fatty acid metabolism within the brain tissue play an important role in the pathophysiology of schizophrenia.&#x0D; Material &amp; Methods: To evaluate the association of dyslipidaemia with Schizophrenia and compare the serum lipid profile with healthy individuals, a cross sectional analytical study was conducted between July 2011 and June 2012 in the Department of Biochemistry, Dhaka Medical College, following approval of a protocol. As per criteria, total 100 cases were included in this study and divided into two groups: Group-I (Diagnosed cases of schizophrenia) and Group-II (Healthy individuals). Written informed consent was taken from all cases. Serum lipid profile (Total Cholesterol, Triglycerides, HDL and LDL) was estimated from both groups by enzymatic determination.&#x0D; Result: Fasting serum triglyceride (p&lt;0.03), HDL cholesterol (p&lt;0.001) and LDL cholesterol (p&lt;0.001) between the groups are significantly related. In group-I mean serum HDL cholesterol is reduced, but LDL cholesterol and Triglyceride were elevated in comparison with group-II. No significant relationship was observed in fasting serum total cholesterol in between groups (p&gt;0.05). Result indicates strong association between schizophrenia and dyslipidaemia. That association would increase the risk of developing coronary heart disease in those patients with schizophrenia compared with healthy individual.&#x0D; AKMMC J 2022; 13(1) : 8-13

Cynanchum atratum Alleviates Non-Alcoholic Fatty Liver by Balancing Lipogenesis and Fatty Acid Oxidation in a High-Fat, High-Fructose Diet Mice Model.

Cynanchum atratum, a medicinal herb, is traditionally used as an antidote, diuretic, and antipyretic in eastern Asia. The current study aimed to investigate the anti-fatty liver capacity of the ethanol extract of Cynanchum atratum (CAE) using a 10-week high-fat, high-fructose diet mouse model. A six-week treatment of CAE (from the fifth week) significantly attenuated the weights of the body, liver, and mesenteric fat without a change in diet intake. CAE also considerably restored the alterations of serum aminotransferases and free fatty acid, fasting blood glucose, serum and hepatic triglyceride, and total cholesterol, as well as platelet and leukocyte counts. Meanwhile, CAE ameliorated hepatic injury and lipid accumulation, as evidenced by histopathological and immunofluorescence observations. Additionally, CAE significantly lowered the elevation of hepatic TNF-α, the TNF-α/IL-10 ratio, fecal endotoxins, and the abundance of Gram-negative bacteria. Hepatic lipogenesis and β-oxidation-related proteins and gene expression, including PPAR-α, SREBP-1, SIRT1, FAS, CTP1, etc., were normalized markedly by CAE. In particular, the AMPK, a central regulator of energy metabolism, was phosphorylated by CAE at an even higher rate than metformin. Overall, CAE exerts anti-hepatic steatosis effects by reducing lipogenesis and enhancing fatty acid oxidation. Consequently, Cynanchum atratum is expected to be a promising candidate for treating chronic metabolic diseases.

Association between aortic calcification and the presence of kidney stones: calcium oxalate calculi in focus

PurposeThe current research is aimed at analyzing the relationship between kidney stone (KS) and abdominal aortic calcification (AAC) and the relationship between KS components and AAC.MethodsThis is a retrospective, case–control study. Kidney stone formers (KSFs) were treated at the Department of Urology, West China Hospital, Sichuan University for urological calculus disease from January 2014 to January 2020. Matched non-stone formers (non-SFs) were drawn from the same hospital for routine health examination from January 2018 to February 2019. Research-related information was collected and reviewed retrospectively from the hospital’s computerized records. AAC were evaluated using available results of computed tomography imaging and abdominal vascular ultrasound. The relationships of AAC between KSFs and non-SFs were compared. The composition of renal calculi was analyzed by Fourier-transform infrared spectrophotometer. KSFs were divided into AAC groups and non-AAC based on AAC. The relationship of the composition of renal calculi between AAC and non-AAC were compared. The independent-sample t test, the chi-squared test and binary logistics regression were performed.ResultsAltogether, 4516 people were included, with 1027 KSFs and 3489 non-SFs. There were no significant differences in the laboratory parameters between KSFs and non-SFs. The association between the presence of AAC and KS was significant in multivariable model 2 [adjusting hypertension, diabetes mellitus, fasting blood glucose, uric acid, serum triglyceride (TG), serum calcium, and urine pH] (OR 5.756, 95% CI 4.616–7.177, p < 0.001). The result of KSFs showed that calcium oxalate calculi (CaOx) was significantly associated with AAC in multivariable model 3 (adjusting age, hypertension, diabetes mellitus, drinking history, smoking history, and TG) (OR 1.351, 95% CI 1.002–1.822, p = 0.048).ConclusionsThe current study pioneered the revelation of the relationship between CaOx and AAC. Through an elimination of the confounding factors, the study demonstrated that KS and AAC were connected.

Abstract 11174: Effect of APOCIII-L Rx on Lipoprotein Size and Particle Numbers Measured by NMR in Patients with Hypertriglyceridemia: Results of the AKCEA-APOCIII-L Rx Trial

Background: APOCIII-L Rx is a hepatocyte-targeted, GalNAc-modified antisense oligonucleotide that decreases plasma levels of apoC-III and triglyceride-rich lipoproteins (TRLs). We examined the effect of APOCIII-L Rx on a variety of lipoprotein fractions measured by nuclear magnetic resonance (NMR) spectroscopy. Methods: The AKCEA-APOCIII-L Rx trial was a dose-ranging study in 114 patients with, or at risk for, ASCVD and fasting serum triglycerides 200-500 mg/dL. Patients (n=114) received AKCEA-APOCIII-L Rx (10 or 50 mg every 4 weeks, 15 mg every 2 weeks, or 10 mg every week) or saline placebo subcutaneously for 6-12 months. Comprehensive NMR LipoProfile ® analysis was performed by LipoScience/LabCorp in frozen EDTA plasma samples collected at baseline and at the primary analysis timepoint (PAT) at 6 months. Results: Results are reported as change from baseline to PAT for the 50 mg every 4 weeks dose versus placebo. APOCIII-L Rx resulted in a significant reduction in total TRL particle (TRLP) concentration by 51% (P&lt;0.0001) with largest reductions in large-size (by 68%, P&lt;0.0001) and medium-size (by 63%, P&lt;0.0001) TRLPs. Total LDL particle (LDLP) concentration was not changed, small LDLP numerically decreased by 39% (P= 0.0713) while medium LDLP increased by 187% (P=0.0119), accompanied by an increase in average LDL size by xx 2% (p=0.0039xx). Total HDL particle (HDLP) concentration increased by 15% (P=0.0006), represented primarily by an increase in small HDL subspecies (particle diameters &lt;8.3 mm) of 32% (P=0.0008). Lower cumulative doses of APOCIII-L Rx generally reflected a dose-dependent relationship in the above parameters. Conclusion: APOCIII-L Rx results in favorable changes in lipoprotein concentration and particle size, primarily manifested by reduction in TRLs, remodeling to larger LDL particles, and increase in small HDLP. These findings suggest an improvement in overall atherogenic risk profile.

Protective Potential of Ginseng and/or Coenzyme Q10 on Doxorubicin-induced Testicular and Hepatic Toxicity in Rats

Introduction: Although doxorubicin (DOX) is a successful cancer chemotherapeutic, side effects limit the clinical utility of DOX-based therapy, including male infertility and hepatotoxicity.&#x0D; Objective: To evaluate the testicular and hepatoprotective effect of ginseng and/or coenzyme Q10 (CoQ10) in rats exposed to DOX and the possible underlying mechanisms.&#x0D; Materials and Methods: Fifty adult male albino rats were divided into (10/group), control, DOX group, DOX/Gin group, DOX/CoQ10 group and DOX/Gin+CoQ10 group. Serum testosterone, serum liver enzymes, fasting serum cholesterol and triglyceride (TG), tissue malondialdehyde (MDA), tissue superoxide dismutase (SOD), serum tumor necrosis factor-alpha (TNF-α), serum interleukin 6, serum interleukin 10, nuclear factor E2‐related factor 2 (Nrf2) gene expression in liver and testis and organ indices were measured. Histopathological and immunohistochemical assessments of apoptotic marker kaspase3 in testis and liver were also performed.&#x0D; Results DOX-induced toxicity is associated with a significant decrease in serum testosterone, testis and liver index values, testicular and hepatic SOD, testicular and hepatic Nrf2 gene expression and serum interleukin 10. However, there was a significant increase in serum liver enzymes, serum cholesterol and TG, testicular and hepatic MDA, serum TNF-α and serum interleukin 6 when compared with the control group. The combination of ginseng and CoQ10 resulted in significant improvement of DOX-induced changes when compared with other treated groups.&#x0D; Conclusion: Ginseng and CoQ10 have valuable therapeutic effects on DOX-induced testicular and hepatic toxicity via up-regulation of Nrf2 gene expression, inhibition of apoptosis, anti-oxidant, anti-inflammatory and hypolipidemic effects.

109 Diet-induced Clinical Responsiveness of Translational Dog Model for Human Western Diet (WD)-related Disease Research

Abstract Human consumption of Western diets (WD) has been strongly associated with increased central obesity, adipocyte hypertrophy, intestinal epithelial stemness/proliferation, dyslipidemia, and blood pressure. These changes reflect metabolic dysfunction and contribute to increased risk of type 2 diabetes mellitus and colorectal cancer. As comprehensive molecular/clinical comparisons have not been performed, the objective of this study was to evaluate diet-induced changes in dogs as a clinically-responsive model for human WD-related disease research. Methods: In a crossover design, 10 dogs were fed either a 1.) control diet (CON) formulated based on the Acceptable Macronutrient Distribution Ranges and fiber recommendations for humans; or 2.) Western diet (WD) formulated based on National Health and Nutrition Examination Survey dataset parameters. Diets were prepared cooked with the same ingredients and formulated to meet/exceed nutrient/energy requirements for both humans/dogs and fed isocalorically based on calculated metabolizable energy (ME). Following each period (~7–8 weeks), experimental parameters were measured. Results/Conclusions: Mean body weights were 8.83 and 9.28kg for CON and WD diets, respectively (P = 0.0018). Fasted (10-hour) blood samples differed significantly (P &amp;lt; 0.01) for mean fasting bile acids (CON=0.79, WD=8.94μmol/L), serum triglycerides (CON=45.70, WD=67.80mg/dL), and serum cholesterol (CON=140.10, WD=175.40mg/dL) demonstrating diet-dependent alterations in lipid profiles. Mean systolic blood pressures were 131.66 and 140.02mmHg for CON and WD, respectively (P &amp;lt; 0.0001). Histological analysis revealed diet-dependent changes in colonic epithelial villus height (CON=182, WD=207μm) and villus:crypt ratio (CON=2.61, WD=3.89). Preliminary RNA-ISH analysis (n = 3 dogs) showed increased LGR5+ expression (intestinal stem-cell marker) in WD compared to CON group (P = 0.0019) suggesting an increased “stemnness” of colonic epithelium. Further, mean adipocyte diameters were increased in omental fat biopsies (CON=58.6, WD=62.5μm; P &amp;lt; 0.0001) but not subcutaneous fat biopsies (P &amp;gt;0.05) following WD feeding, consistent with centralized obesity. Collectively, these results demonstrate effects of diet-induced changes in dogs as a clinically-responsive model for human WD-related disease research.

Influence of high-protein and high-carbohydrate diets on serum lipid and fructosamine concentrations in healthy cats.

The aim of this study was to determine whether high-protein and high-carbohydrate diets exert differential effects on serum cholesterol, triglyceride and fructosamine concentrations in healthy cats. A randomised, crossover diet trial was performed in 35 healthy shelter cats. Following baseline health assessments, cats were randomised into groups receiving either a high-protein or high-carbohydrate diet for 4 weeks. The cats were then fed a washout diet for 4 weeks before being transitioned to whichever of the two studied diets they had not yet received. Fasting serum cholesterol, triglyceride and fructosamine concentrations were determined at the end of each 4-week diet period. Cats on the high-carbohydrate diet had significantly lower serum cholesterol (P <0.001) concentrations compared with baseline measurements. Cats on the high-protein diet had significantly higher serum cholesterol (P <0.001) and triglyceride (P <0.001) concentrations, yet lower fructosamine (P <0.001) concentrations compared with baseline measurements. In contrast, overweight cats (body condition score [BCS] >5) had lower cholesterol (P = 0.007) and triglyceride (P = 0.032) concentrations on the high-protein diet than cats within other BCS groups. Diets higher in protein and lower in carbohydrates appear beneficial for short-term glucose control in healthy cats. A high-protein diet was associated with significantly elevated cholesterol and triglyceride concentrations in healthy cats, even though the increase was significantly less pronounced in cats with a BCS >5. This finding suggests that overweight cats process high-protein diets, cholesterol and triglycerides differently than leaner cats.

The ameliorative effect of bromelain on STZ-induced type 1 diabetes in rats through Oxi-LDL/LPA/LPAR1 pathway

AimsDiabetes, a serious worldwide problem, is modulated via inflammation and oxidative stress. Bromelain, a natural compound, recently attracts interest due to its anti-inflammatory effects, while its mode of action remains not properly understood. Thus, investigating the antidiabetic effect of bromelain is promising. Materials and methodsRats were randomized into normal group, STZ group (were administrated single intraperitoneal (i.p) injection of 55 mg/kg streptozotocin (STZ)) and STZ + Bro group (were administrated single i.p injection of STZ, 72 h later were i.p administrated 10 mg/kg/day bromelain for 15 days). Wound healing ability was investigated for different groups. Spectrophotometry, ELISA, histopathological and immunohistochemical techniques were applied. Key findingsBromelain significantly decreased fasting blood glucose, serum triglycerides and cholesterol and hepatic malondialdehyde levels compared with STZ group. Moreover, Bromelain significantly increased serum albumin and total protein levels and percentage of wound healing compared with STZ group. These results were confirmed through the histopathological examination of liver, pancreas, and skin tissues. Investigating the molecular mechanism underlying these effects, STZ injection caused significant increase in hepatic oxidized-LDL (Oxi-LDL) and lysophosphatidic acid (LPA) levels and hepatic lysophosphatidic acid receptor 1 (LPAR1), and beta secretase (BACE1) protein tissue expressions, while bromelain significantly aborted these effects. Thus, STZ caused upregulation of Oxi-LDL/LPA/LPAR1/BACE1 pathway, while bromelain significantly ameliorated these effects. SignificanceTo our best knowledge, this study represents the 1st study investigating Oxi-LDL/LPA/LPAR1/BACE1 pathway in STZ-induced diabetes in rats, in addition to the promising ameliorative effect of bromelain in STZ-induced diabetes in rats.

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use

Objective To evaluate the effects of metreleptin in distinct subgroups of patients with generalized lipodystrophy (GL) and partial lipodystrophy (PL), using multivariate linear regression modeling to account for the role of patients’ baseline usage of concomitant glucose and lipid-lowering medications and other covariates on their outcomes. Materials and methods A post-hoc statistical analysis of two published single-arm, interventional, phase 2 clinical trials at NIH was conducted. Concomitant medication use was assessed for the clinical trial population using prescription fill data, measured at baseline and the post-one year following metreleptin initiation. Pre-specified co-primary efficacy endpoints measured were change from baseline in HbA1c at month 12, and the percent change from baseline in fasting serum triglycerides (TG) at month 12. Descriptive and statistical analyses were conducted for the overall population, the separate populations with GL and PL, and additional PL subgroups defined by baseline metabolic markers of elevated HbA1c and elevated fasting TG. Results As previously reported, improvement in HbA1c and fasting TG from baseline to 12 months on metreleptin were observed in the overall population (mean change −1.57 percentage points and median change −37.9%, respectively) and subgroups. For both HbA1c and TG, baseline levels were significant predictors of changes after metreleptin. After considering baseline characteristics such as disease type, age, sex, and baseline HbA1c, baseline insulin use was not found to be a significant predictor of HbA1c improvement following metreleptin initiation. Similar results were seen for TG levels, with the use of any lipid-lowering medications at baseline not found to be a significant predictor of reductions in fasting TG levels. Conclusions Patients treated with metreleptin experienced statistically significant improvement in metabolic markers of glycemic and hypertriglyceridemic control—e.g. HbA1c and triglyceride levels—across various subgroups after controlling for baseline characteristics and concomitant medication usage.

Sitagliptin attenuates arterial calcification by downregulating oxidative stress-induced receptor for advanced glycation end products in LDLR knockout mice

Diabetes is a complex disease characterized by hyperglycemia, dyslipidemia, and insulin resistance. Plasma advanced glycation end products (AGEs) activated the receptor for advanced glycation end products (RAGE) and the activation of RAGE is implicated to be the pathogenesis of type 2 diabetic mellitus (T2DM) patient vascular complications. Sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, is a new oral hypoglycemic agent for the treatment of T2DM. However, the beneficial effects on vascular calcification remain unclear. In this study, we used a high-fat diet (HFD)-fed low-density lipoprotein receptor deficiency (LDLR−/−) mice model to investigate the potential effects of sitagliptin on HFD-induced arterial calcification. Mice were randomly divided into 3 groups: (1) normal diet group, (2) HFD group and (3) HFD + sitagliptin group. After 24 weeks treatment, we collected the blood for chemistry parameters and DPP4 activity measurement, and harvested the aorta to evaluate calcification using immunohistochemistry and calcium content. To determine the effects of sitagliptin, tumor necrosis factor (TNF)-α combined with S100A12 was used to induce oxidative stress, activation of nicotinamide adenine dinucleotide phosphate (NADPH), up-regulation of bone markers and RAGE expression, and cell calcium deposition on human aortic smooth muscle cells (HASMCs). We found that sitagliptin effectively blunted the HFD-induced artery calcification and significantly lowered the levels of fasting serum glucose, triglyceride (TG), nitrotyrosine and TNF-α, decreased the calcium deposits, and reduced arterial calcification. In an in-vitro study, both S100A12 and TNF-α stimulated RAGE expression and cellular calcium deposits in HASMCs. The potency of S100A12 on HASMCs was amplified by the presence of TNF-α. Sitagliptin and Apocynin (APO), an NADPH oxidase inhibitor, inhibited the TNF-α + S100A12-induced NADPH oxidase and nuclear factor (NF)-κB activation, cellular oxidative stress, RAGE expression, osteo transcription factors expression and calcium deposition. In addition, treatment with sitagliptin, knockdown of RAGE or TNF-α receptor blunted the TNF-α + S100A12-induced RAGE expression. Our findings suggest that sitagliptin may suppress the initiation and progression of arterial calcification by inhibiting the activation of NADPH oxidase and NF-κB, followed by decreasing the expression of RAGE.

Relation between Acne Vulgaris and Metabolic Syndrome in Males

Abstract Background: Acne is a multifactorial and inflammatory disease of pilosebaceous follicles, which affects most adoles-cents. Metabolic Syndrome (MetS) is a multiplex syndrome and has been reported to be associated with many dermatologic diseases, such as acne vulgaris. Aim of Study: Study the prevalence of MetS in post-adolescent male patients with AV (aged >!20 years), and assess the relation between MetS and severity of AV in these patients. Patients and Methods: A randomized case control study was conducted on 52 post adolescent male patients with acne and 52 patients (age and sex matched) as control. All patients were subjected to clinical assessment including: Evaluation of MetS components: (Body Mass Index (BMI) calculation: [Weight (kg) / height (m)2] & waist circumference) and estimation of biochemical parameters (fasting serum triglyc-erides, HDL and fasting blood glucose). Dermatological evaluation was done for assessment of acne severity. Results: MetS prevalence was statistically significant higher in AV patients (19.2%) compared to controls (5.8%). (x2=4.37, p=0.037). There was a statistical significant relation between AV and risk of developing MetS as odds ratio was 3.9 (1.003 to 15.07), p=0.049. There was statisti-cally insignificant relation between the severity of AV and MetS prevalence. Conclusion: MetS prevalence was higher in AV patients than in control and was more common in patients with severe acne. There was a statistical significant relation between AV and risk of developing MetS.

Treatment of Chinese Patients with Hypertriglyceridemia with a Pharmaceutical-Grade Preparation of Highly Purified Omega-3 Polyunsaturated Fatty Acid Ethyl Esters: Main Results of a Randomized, Double-Blind, Controlled Trial

IntroductionThe lipid-modifying potential of omega-3 polyunsaturated fatty acids in Chinese patients is under-researched. We conducted a multicenter, randomized, placebo-controlled, double-blind, parallel-group study of twice-daily treatment with OMACOR (OM3EE), a prescription-only formulation of highly purified ethyl esters of omega-3 polyunsaturated fatty acids in Chinese adult patients (≥18 years) who had elevated baseline fasting serum triglycerides (TG).MethodsPatients were stratified according to the severity of their hypertriglyceridemia (severe HTG, with baseline TG ≥500 and <1000 mg/dL or moderate HTG, with baseline TG >200 and <500 mg/dL) or use of statins. Patients randomized to OM3EE therapy received 2 g/day for 4 weeks, then 4 g/day for 8 weeks. The primary efficacy endpoint was the percentage change in fasting serum TG between baseline and the end of treatment in patients with severe HTG. The study was concluded after a planned interim analysis demonstrated a significant TG-lowering effect of OM3EE in that contingent (p=0.0019).ResultsThe mean TG end-of-treatment effect of OM3EE was –29.46% (standard deviation 40.60%) in the severe HTG contingent compared with +0.26% (standard deviation 54.68%) in the placebo group. Corresponding changes were –12.12% and –23.25% in the moderate HTG and combination cohorts (vs +55.45% and +6.24% in relevant placebo groups). A dose-dependent reduction in TG was evident in all patient contingents. Safety and tolerability of OM3EE were in line with previous experience.DiscussionThese data indicate that OMACOR therapy at a dose of 2–4 g/day is an effective treatment for Chinese patients with raised TG levels and is well tolerated.

Very severe hypertriglyceridemia in a subject with poor glycemic control: a case report with general consideration

Hypertriglyceridemia is defined as a value of fasting serum triglyceride over 150 mg/dl. The classification of hypertriglyceridemia according to the Endocrine Society includes mild and moderate hypertriglyceridemia, severe hypertriglyceridemia and very severe hypertriglyceridemia. Mild and moderate hypertriglyceridemia increases the risk for cardiovascular events while severe and very severe hypertriglyceridemia is a risk factor for acute pancreatitis. Conventional pharmacological therapy of hypertriglyceridemia includes fibrates, niacin, statins, ezetimibe, and omega-3 fatty acid. Other triglyceride-lowering therapies are represented by plasmapheresis and lipoprotein lipase gene therapy. The present work refers to a 55-year-old man without a history of family diabetes mellitus (DM), dyslipidemia, premature coronary artery disease, diagnosed with type 2 DM in 2016, from 2018 on insulin treatment; he was hospitalized for endocrine evaluation. The patient had a history of high blood pressure for approximately 15 years, chronic kidney disease, very severe hypertriglyceridemia, and chronic obstructive pulmonary disease. The patient followed treatment with hypoglycemic, hypolipemic, low-salt diet, fibrates, statins, omega-3 fatty acid.

Ajwa seeds (Phoenix dactylifera L.) suspension exerted antidiabetic and antihyperlipidemic effects against streptozotocin-induced diabetes in rats by downregulating insulin expression in the pancreatic beta islets

Objectives: This study investigated the antidiabetic and antihyperlipidemic effects of the powdered seeds of Ajwa Al-Madina in streptozotocin (STZ)-induced diabetes in rats. Besides investigating the possible underlying mechanisms. Methods: Rats were assigned to one of six groups (n = 5) as follows: normal control, vehicle control, Ajwa seeds control, diabetic control, Diabetic + Metformin, and Diabetic + Ajwa seeds. Metformin and Ajwa seeds were injected into rats orally via oral gavage 6 days/week along 4 weeks period Results: Ajwa seeds decreased fasting serum glucose, increased fasting serum insulin and decreased fasting serum triglycerides cholesterol, low-density lipoprotein, and increased fasting serum high-density lipoprotein. Besides, it upregulated insulin protein immunoexpression in the beta cells of Langerhans islets. Ajwa seed also preserved the normal histological structure of the pancreatic beta cells tissue. Conclusion: Ajwa seeds produced significant hypoglycemic and hypolipidemic effects in diabetic rats mainly through enhancement of insulin secretion. The plant is a promising adjunctive therapy in diabetes mellitus treatment.