Fasting Triglyceride Concentrations Research Articles

Genome-Wide Association Study of Habitual Exercise-Induced Improvement of Arterial Stiffness in Japanese Adults

An increase in arterial stiffness is causal factor of cardiovascular diseases. Habitual exercise improves arterial stiffness and has a protective effect against these diseases. However, not all individuals may benefit equally from exercise. These genetic variations in association with the regular exercise-induced improvement of arterial stiffness remain unclear. PURPOSE: To identify genetic variants, which influence individuals respond to regular exercise-induced improvement of arterial stiffness, using genome-wide association studies (GWAS) in Japanese adults. METHODS: 285 Japanese adults aged from 25 to 70, who were recruited from Nutrition and EXercise Intervention Study (NEXIS) totally enrolled 838 persons, participated in this study. Mean daily amount of physical activity for 14 days at >3 METs was measured by using triaxial accelerometry at both baseline and 1 year later. Also, arterial stiffness was assessed by carotid beta-stiffness with ultrasonography and tonometry. Active subjects (n=45), which has kept more than 5.1 METs*h/day (the highest quintile at baseline) at both baseline and 1 year measurements, were divided into two groups; high values of beta-stiffness (High-Stif) and low values of beta-stiffness (Low-Stif) based on the median value of beta-stiffness in each sex and decade. A GWAS between two groups was performed by Human660W-Quad BeadChip (illumina). RESULTS: There were no significant differences in age, sex, BMI, blood pressure and fasting blood glucose, triglyceride, and HDL-C concentrations between High-Stif and Low-Stif groups, whereas there was a significant difference in beta-stiffness (13.2±1.2 vs 7.0±0.4 AU, P<0.0001). The >550,000 genetic polymorphisms were analyzed by using JMP Genetics (SAS Institute), then 10 and 27 SNPs were significantly associated with the individual variation of regular exercise-induced improvement of arterial stiffness (genotype and allele frequency respectively, P<0.0001). These polymorphisms were located on gene locus involved in the cadherin superfamily, cGMP, and endothelial progenitor cell, and lipoprotein related protein, etc. CONCLUSIONS: These genetic variations may be associated with the regular exercise-induced improvement of arterial stiffness. Supported by grant in KAKENHI 22650166

Serum concentrations of insulin-like growth factor-I, insulin-like growth factor binding protein-3 and cardiovascular risk factors in adolescents

The risk association between the insulin like growth factor-I (IGF-I) system and cardiovascular risk is inconclusive in adults and under-explored in adolescents. We aimed to investigate the associations between serum concentrations of IGF-I and IGF binding protein-3 (IGFBP-3) and cardiovascular risk factors in adolescents. This was a cross-sectional, population-based, observational study in a school setting with 2102 Hong Kong Chinese adolescents aged 12-19 years. Serum IGF-I and IGFBP-3 concentrations were measured by chemiluminescence immunoassays. Anthropometric indices and traditional cardiovascular risk factors were assessed. After excluding participants with abnormal thyroid and liver test results, 765 boys and 877 girls, mean (±SD) age of 15.3 (±2.0) and 15.7 (±2.0) years, respectively, were included in the analysis. Multivariable regression analyses revealed that both IGF-I and IGFBP-3 concentrations were independently associated with waist circumference, fasting insulin and haemoglobin concentrations in boys (all P < 0.05), systolic blood pressure, serum creatinine, fasting insulin and haemoglobin concentrations in girls (all P < 0.05). In girls, IGF-I was also associated with C-reactive protein concentration (P < 0.001) and IGFBP-3 was associated with fasting triglyceride concentration (P < 0.001). Compared with adolescents with the lowest tertile, the top tertile of both IGF-I and IGFBP-3 concentrations were associated with increased odds of having overweight/obesity, top tertiles of insulin and haemoglobin in both boys and girls (P for trend, all <0.05). The associations between serum IGF-I, IGFBP-3, obesity, cardiovascular risk factors, insulin and haemoglobin suggest that dysregulation of the IGF system may play a linking role for the clustering of cardiovascular risk factors.

Whither the Lipid Profile: Feast, Famine, or No Free Lunch?

A lipid profile (LP)3 is used in clinical practice to assess risk of cardiovascular disease (CVD) and to guide therapy. The standard LP includes a direct measurement of plasma total cholesterol, triglyceride, and HDL cholesterol concentrations, and derived estimates of LDL cholesterol, non–HDL cholesterol, and lipid ratios (1). Expert guidelines recommend that accurate assessment of the LP requires a fast of 9 to 12 h (2). The principal reason is to diminish the biological variation in the plasma triglyceride concentration after ingestion of a fatty meal. Another reason is to compare plasma lipid levels with fasting data from healthy individuals. A fasting triglyceride concentration is also required for accurate estimation by the Friedewald formula of the cholesterol in LDL (3), the principal atherogenic lipoprotein. The established practice of fasting has been challenged by population studies that have shown that components of the LP, including triglycerides, do not change greatly when measured at different times during the day in nonfasting individuals (4). Compelling epidemiology data also show that nonfasting concentrations of triglycerides, LDL cholesterol, non–HDL cholesterol, and HDL cholesterol, as well as the lipid ratios, are significant predictors of cardiovascular (CV) events (5), possibly more than in the fasting state (6). Can these findings be extended to patients with type 2 diabetes, a group with a high prevalence of hypertriglyceridemia and perturbed cholesterol-rich lipoprotein metabolism (7)? Investigators from the Copenhagen General Population Study have assessed the plasma concentrations of lipids, lipoproteins, apolipoproteins, and albumin in 58 434 individuals, 2270 of whom had diabetes (8). Participants were asked the time since their last meal, and nonfasting blood samples were categorized accordingly. In individuals with and without diabetes, the plasma triglyceride concentration remained increased for up to 7 h after the last meal. A mean postprandial reduction of 0.6 mmol/L (23 …

Effects of meals rich in either monounsaturated or saturated fat on lipid concentrations and on insulin secretion and action in subjects with high fasting triglyceride concentrations

The nature of dietary fats and fasting concentrations of triglycerides affect postprandial hypertriglyceridemia and glucose homeostasis. The objectives were to examine the effects of meals enriched in monounsaturated fatty acids (MUFAs) or saturated fatty acids (SFAs) on postprandial lipid, glucose, and insulin concentrations and to examine the extent of β cell function and insulin sensitivity in subjects with high fasting triglyceride concentrations. Fourteen men with fasting hypertriglyceridemia and normal glucose tolerance were given meals (≈10 kcal/kg body weight) containing MUFAs, SFAs, or no fat. Blood samples were collected at baseline and hourly over 8 h for analysis. The high-fat meals significantly increased postprandial concentrations of triglycerides, nonesterified fatty acids, and insulin and postprandial indexes of β cell function. However, postprandial indexes of insulin sensitivity decreased significantly. These effects were significantly attenuated with MUFAs relative to SFAs. MUFAs postprandially buffered β cell hyperactivity and insulin intolerance relative to SFAs in subjects with high fasting triglyceride concentrations. These data suggest that, in contrast with SFAs, MUFA-based strategies may provide cardiovascular benefits to persons at risk by limiting lipid and insulin excursions and may contribute to optimal glycemic control after meal challenges.

Changes in body weight, body composition and cardiovascular risk factors after long-term nutritional intervention in patients with severe mental illness: an observational study

BackgroundCompared with the general population, individuals with severe mental illness (SMI) have increased prevalence rates of obesity and greater risk for cardiovascular disease. This study aimed to investigate the effects of a long term nutritional intervention on body weight, body fat and cardiovascular risk factors in a large number of patients with SMI.MethodsNine hundred and eighty-nine patients with a mean ± S.D age of 40 ± 11.7 yrs participated in a 9 mo nutritional intervention which provided personalised dietetic treatment and lifestyle counselling every two weeks. Patients had an average body mass index (BMI) of 34.3 ± 7.1 kg.m-2 and body weight (BW) of 94.9 ± 21.7 kg. Fasted blood samples were collected for the measurement of glucose, total cholesterol, triglycerides and HDL- cholesterol. All measurements were undertaken at baseline and at 3 mo, 6 mo and 9 mo of the nutritional intervention.ResultsFour hundred and twenty-three patients of 989 total patients' cases (42.8%) dropped out within the first 3 months. Two hundred eighty-five completed 6 months of the program and 145 completed the entire 9 month nutritional intervention. There were progressive statistically significant reductions in mean weight, fat mass, waist and BMI throughout the duration of monitoring (p < 0.001). The mean final weight loss was 9.7 kg and BMI decreased to 30.7 kg.m-2 (p < 0.001). The mean final fat mass loss was 8.0 kg and the mean final waist circumference reduction was 10.3 cm (p < 0.001) compared to baseline. Significant and continual reductions were observed in fasting plasma glucose, total cholesterol and triglycerides concentrations throughout the study (p < 0.001).ConclusionThe nutritional intervention produced significant reductions in body weight, body fat and improved the cardiometabolic profile in patients with SMI. These findings indicate the importance of weight-reducing nutritional intervention in decreasing the cardiovascular risk in patients with SMI.

Insulin Resistance and the Relationship of a Dyslipidemia to Coronary Heart Disease

The goal of this study was to examine the effect of insulin resistance (IR) in subjects without diabetes on the relationship of a dyslipidemia with high triglycerides and low high-density lipoprotein cholesterol (HDL-C) to the development of coronary heart disease (CHD). Lower and higher fasting plasma HDL-C and triglyceride concentrations (defined at the study population median) and presence or absence of IR (defined by upper quartile Homeostatic Model Assessment values) were related to the development of myocardial infarction or CHD death in Framingham Heart Study participants without diabetes or a history of CHD (n=2910) attending the 1991 to 1995 examination. During follow-up (mean, 14 years), 128 participants experienced an incident CHD event. With Kaplan-Meier plots, the incidence of CHD was significantly greater with than without IR at either the lowest HDL-C or the highest triglycerides (P<0.001). In multivariable Cox models adjusted for major CHD risk factors, including waist circumference, only subgroups with IR had a significantly higher incidence of CHD. Compared with a reference group without IR and with higher-than-median HDL-C or lower-than-median triglycerides, the hazard ratio (HR) for incident events was significant with only IR and a lower HDL-C (HR 2.83, P<0.001) or higher triglycerides (HR 2.50, P<0.001). These findings were similar in men and women. In this community-based sample exclusive of diabetes, incident CHD risk associated with plasma HDL-C or triglycerides was significantly increased only in the presence of IR.

Use of a meal challenge test to estimate peak postprandial triglyceride concentrations in dogs

To develop a standardized meal challenge test by assessing associations between food-withheld preprandial (ie, fasting) and postprandial triglyceride concentrations, determining the most appropriate sampling time to detect the peak concentration (highest postprandial concentration), and estimating reference intervals for fasting and postprandial concentrations in healthy dogs. 12 lean healthy mixed-breed dogs. Dogs were fed a dry commercially available diet (fat, 31% metabolizable energy) for 3 weeks. After food was withheld for 23 to 24 hours, plasma triglyceride concentrations were measured 1 and 0.083 hours before and 1, 2, 3, 4, 5, 6, 9, and 12 hours after feeding of a standardized challenge meal (median amount eaten, 63 kcal/kg [127 kcal/kg⁰.⁷⁵]). Correlation and agreement between concentrations at peak and other time points were assessed by use of correlation coefficients and Bland-Altman limits of agreement. Reference intervals were calculated by use of a robust method. Fasting and peak triglyceride concentrations were not closely associated. The highest concentration among samples obtained 2, 5, and 6 hours after meal consumption had closest agreement with peak concentration. In 5 of 12 dogs, concentrations 12 hours after eating were still significantly above baseline concentration (mean of each dog's fasting concentrations). Fasting triglyceride concentration could not be used to accurately predict peak concentration. When estimating peak concentration, multiple samples should be collected 2, 5, and 6 hours after consumption of a standardized meal. Food may need to be withheld for > 12 hours when assessing fasting concentrations in healthy dogs.

Letter by Singh et al Regarding Article, “Apolipoprotein E Polymorphisms and Postprandial Triglyceridemia Before and After Fenofibrate Treatment in the GOLDN Study”

HomeCirculation: Cardiovascular GeneticsVol. 4, No. 1Letter by Singh et al Regarding Article, “Apolipoprotein E Polymorphisms and Postprandial Triglyceridemia Before and After Fenofibrate Treatment in the GOLDN Study” Free AccessLetterPDF/EPUBAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBLetter by Singh et al Regarding Article, “Apolipoprotein E Polymorphisms and Postprandial Triglyceridemia Before and After Fenofibrate Treatment in the GOLDN Study” Puneetpal Singh, MSc, PhD Mario Di Napoli, MD Monica Singh, MSc, PhD Puneetpal SinghPuneetpal Singh Molecular Genetics LabDepartment of Human BiologyPunjabi UniversityPatiala, India (Singh) Search for more papers by this author Mario Di NapoliMario Di Napoli Neurological ServiceSan Camillo de'Lellis General HospitalRieti, Italy (Di Napoli) Search for more papers by this author Monica SinghMonica Singh Molecular Genetics LabDepartment of Human BiologyPunjabi UniversityPatiala, India (Singh) Search for more papers by this author Originally published1 Feb 2011https://doi.org/10.1161/CIRCGENETICS.110.958660Circulation: Cardiovascular Genetics. 2011;4:e5To the Editor:We read with interest the article by Irvin et al1 on the significance of APOE polymorphism on triglyceride response to fenofibrate which revealed that ε2 carriers have higher fasting triglyceride concentrations and greater postprandial response to high-fat meals than ε3 homozygotes both before and after finofibrate treatment.Alterations of serum apolipoprotein E (apoE) levels significantly modify the relationship between APOE polymorphism and triglycerides.2 This study has not observed any significant change according to APOE genotypes in fasting triglyceride after fenofibrate treatment, which may have been missed as a consequence of unforeseen interaction of apoE levels with APOE polymorphism. The study has overlooked the adjustment of models with apoE levels, which modulate triglyceride levels, confer 2-fold higher risk of cardiovascular disease mortality and account for 34.6% of the triglyceride variance3 independent of APOE polymorphism.Individual response to fibrates is highly variable and multiple genes have been associated with the efficacy of finofibrate treatment.4 The mediating effect of individual APOE polymorphism on postprandial response to finofibrate treatment may vary, if other single-nucleotide polymorphisms (SNPs) are also participating especially when they are non randomly associated with each other, consequences of which have been oversimplified in the present study. For instance, SNP rs440446 in the regulatory region of APOE influences transcriptional efficacy and has significant effect on gene function. Interactions of this with rs429358 or rs7412 may mediate the triglyceride response to fenofibrate. Moreover, the domain interactions between 2 terminals (N- and C-terminals) of APOE are responsible for the preferential association of apoE4 with very low-density lipoprotein and attenuate the lipolysis products of triglyceride rich lipoproteins as a postprandial response.5 In the light of these interactions, we assume that SNP-SNP interactions within APOE gene (tagged SNPs) would clarify the effect on triglyceride response to fenofibrate, which will strengthen the reliability of targeting individuals with diet interventions.Puneetpal Singh, MSc, PhD Molecular Genetics Lab Department of Human Biology Punjabi University Patiala, IndiaMario Di Napoli, MD Neurological Service San Camillo de'Lellis General Hospital Rieti, ItalyMonica Singh, MSc, PhD Molecular Genetics Lab Department of Human Biology Punjabi University Patiala, IndiaDisclosuresNone.

Fenofibrate, a peroxisome proliferator-activated receptor α agonist, alters triglyceride metabolism in enterocytes of mice

Fenofibrate, a drug in the fibrate class of amphiphathic carboxylic acids, has multiple blood lipid modifying actions, which are beneficial to the prevention of atherosclerosis. One of its benefits is in lowering fasting and postprandial blood triglyceride (TG) concentrations. The goal of this study was to determine whether the hypotriglyceridemic actions of fenofibrate in the postprandial state include alterations in TG and fatty acid metabolism in the small intestine. We found that the hypotriglyceridemic actions of fenofibrate in the postprandial state of high-fat (HF) fed mice include a decrease in supply of TG for secretion by the small intestine. A decreased supply of TG for secretion was due in part to the decreased dietary fat absorption and increased intestinal fatty acid oxidation in fenofibrate compared to vehicle treated HF fed mice. These results suggest that the effects of fenofibrate on the small intestine play a critical role in the hypotriglyceridemic effects of fenofibrate.

Abdominal adiposity depots are correlates of adverse cardiometabolic risk factors in Caucasian and African-American adults

Objective:Accumulation of adipose tissue is associated with cardiometabolic risks. Although visceral adipose tissue (VAT) has been strongly implicated in this relationship, there is still some debate regarding the contribution of abdominal subcutaneous adipose tissue (SAT). The purpose of this study was to determine the contribution of abdominal SAT to cardiometabolic risk factors, independent of total and visceral adiposity. These relationships were assessed in Caucasian and African Americans.Design:It is a cross-sectional analysis of the Pennington Center Longitudinal Study.Subjects:Data were extracted from 1246 participants. Total body fat mass (FM) was measured by dual-energy X-ray absorptiometry, whereas abdominal VAT and SAT areas (cm2) were measured with computed tomography. The cardiometabolic risk factors included resting blood pressure (BP), fasting blood glucose and triglyceride concentrations and high-density lipoprotein cholesterol (HDL-C).Results:Positive relationships across tertiles of VAT were seen for the participants with high glucose, high BP and low HDL-C (P<0.043). There was also a significant increase in the percentage of participants with two or more cardiometabolic risk factors across most tertiles of abdominal SAT (P<0.042). Logistic regression analysis showed that in univariate models, all adiposity measures were significantly associated with increased odds of having all risk factors in men and women. In multivariate models, VAT was significantly associated with most risk factors across gender. Abdominal SAT and FM (odds ratios (ORs) 1.3–2.1; all P<0.05) were associated with fewer risk factors after accounting for VAT. VAT (OR=5.9 and 5.3) and SAT (OR=2.0 and 1.8) were both associated with higher odds of the presence of two or more cardiometabolic risk factors in both males and females (P<0.001).Conclusion:The data suggest that abdominal SAT is not protective against unfavorable cardiometabolic risk profiles. These conclusions were consistent across ethnic groups.

Treatment of high fat diet induced type 2 diabetes in C57BL/6J mice by two medicinal plants used in traditional treatment of diabetes in the east of Algeria

Hydro-alcoholic extracts of Centaurium erythraea Rafn (CE), Gentianaceae and Artemisia herba-alba Asso (AHA), Asteraceae, medicinal plants used in traditional treatment of diabetes in north-eastern Algeria, were tested in established type 2 diabetes induced with a standardized high fat diet (HFD) in mice. After confirmation of diabetes (17th week), plant extracts were administered orally by gavage at a dose of 2 g/kg daily for 18 weeks to male C57BL/6J mice fed HFD. Animals were weighed, food intake and plasma glucose measured weekly, insulin and lipid profile at study end. At 35 weeks, groups treated with AHA or CE vs. HFD control had a significant reduction in mean (±SD) fasting blood glucose concentrations (143.8±23.9 and 139.5±14.2 vs. 229.0±20.8 mg/dL, p<0.05, respectively), triglyceride (18.9±11.1 and 16.0±6.5 vs. 62.8±18.3 mg/dL, p<0.05), total cholesterol (1.2±0.1 and 1.2±0.3 vs. 1.8±1.1 g/L, p<0.05) and serum insulin concentrations (1.7±0.7 and 0.9±0.7 vs. 3.3±14.3 ng/mL, p<0.05). Plant extracts also markedly reduced insulin resistance as compared to HFD controls (AHA: 15.6±9.1, CE: 9.0±7.7 vs. HFD control 38.5±30.3, p<0.05). The plant extracts decreased calorie intake and had little effect on body weight or HDL-cholesterol. AHA has already been shown to have a antihyperglycaemic and antihyperlipidemic effect but this is the first demonstration of an effect of AHA and CE on established HFD-induced diabetes.

The role of fasting versus non-fasting triglycerides in ischemic stroke: a systematic review.

Objective: To synthesize results from pertinent studies and determine if fasting and/or non-fasting triglycerides are a risk factor for ischemic stroke. Method: We performed two independent systematic literature searches using the PubMed and ScienceDirect databases to identify studies examining the relationship between fasting and non-fasting triglyceride concentrations and ischemic stroke risk. A meta-analysis was performed using ischemic stroke as a primary endpoint. Results: Twenty-five reports were identified, including 13 prospective cohort and 12 case–control studies. Baseline characteristics, study samples, methods, and primary outcomes varied. Of 13 prospective cohort studies, nine assessed triglyceride concentrations in the fasting state. Seven of these identified triglycerides as an independent risk factor for ischemic stroke risk (n = 1624 ischemic cases). Three prospective cohort studies identified a positive association between elevated non-fasting triglyceride concentrations and ischemic stroke risk (n = 2050 ischemic cases). One prospective cohort study that compared fasting and non-fasting triglycerides identified only non-fasting triglycerides as an independent risk factor for ischemic stroke. Of 12 case–control studies identified, five identified a positive relationship between ischemic stroke risk and elevated fasting triglycerides (n = 838 cases). Seven case–control studies were included in the meta-analysis (n = 1996 ischemic stroke cases), revealing an odds ratio of 1.15 (95% CI, 1.08–1.21). Conclusions: The available data are inconsistent. The relationship between triglyceride levels and ischemic stroke needs further investigation under standardized conditions. We recommend a standardized triglyceride tolerance test to further investigate the associations between fasting versus non-fasting triglyceride levels and ischemic stroke.

Apolipoprotein E Polymorphisms and Postprandial Triglyceridemia Before and After Fenofibrate Treatment in the Genetics of Lipid Lowering and Diet Network (GOLDN) Study

Although much is known about the effect of Apolipoprotein E (APOE) alleles on fasting lipid concentrations, less is known about the effect of APOE alleles on postprandial triglyceridemia or the triglyceride response to fenofibrate. We evaluated the effects of the APOE locus on fasting and postprandial triglyceride concentrations as part of the Genetics of Lipid Lowering and Diet Network (GOLDN) study. Participants were evaluated after a high-fat meal challenge before (n=1072) and after 3 weeks of daily treatment with 160 mg of fenofibrate (n=738). Mixed models adjusted for sex, age, waist circumference, and family relationship were used to examine the association of the ε4 carrier and ε2 carrier status versus ε3 homozygotes with fasting triglycerides and the area under the curve (AUC) for triglycerides during the high-fat meal challenge. Compared with the ε3/ε3 genotype, ε2 carriers had on average higher fasting triglyceride concentrations (130.5 mg/dL versus 109.3 mg/dL, P<0.001). After fenofibrate treatment, the APOE genotype differences persisted in the fasting state (ε2 carriers: 85.1 mg/dL versus ε3/ε3: 75.9 mg/dL, P<0.05). Carriers of the ε4 allele had significantly higher fasting triglyceride concentrations only prefenofibrate (120.9 mg/dL versus 109.3 mg/dL, P=0.008). APOE alleles did not have an effect on response to fenofibrate. Postprandial triglycerides were significantly higher for ε2 carriers versus ε3 homozygotes (but not ε4 carriers) both before and after fenofibrate treatment (P=0.01 and P=0.005, respectively). APOE polymorphisms are important determinants of triglyceride concentrations, especially in the fasting state.

Impact of acarbose on carotid intima-media thickness in patients with newly diagnosed impaired glucose tolerance or mild type 2 diabetes mellitus: A one-year, prospective, randomized, open-label, parallel-group study in Japanese adults with established coronary artery disease

Objective: This study examined the effect of acarbose therapy on carotid intima-media thickness (IMT) in patients with established coronary artery disease (CAD) who had been newly diagnosed with impaired glucose tolerance (IGT) or mild type 2 diabetes mellitus (T2DM). Methods: This was a 1-year, prospective, randomized, open-label, parallel-group study in patients with established CAD (≥50% stenosis on quantitative coronary angiography) who were newly diagnosed with IGT or mild T2DM. IGT was defined as 2-hour glucose concentrations of 140 to 199 mg/dL on the 75-g oral glucose tolerance test (OGTT). Mild T2DM was defined as a fasting plasma glucose concentration <126 mg/dL, 2-hour plasma glucose concentration on OGTT >200 mg/dL, and glycosylated hemoglobin (HbA 1c) <6.5%. On the day after undergoing coronary angiography, patients were randomly allocated to receive either acarbose 150 mg/d or control (no treatment). Carotid IMT was measured by ultrasonography at baseline and at 12 months of follow-up. The changes in glucose profiles (75-g OGTT), HbA 1c, and lipid profiles were also compared between baseline and follow-up. At visits every 2 months, data on adverse events, drug adherence, and changes in medication were collected. Adverse events were recorded based on spontaneous reports and questioning by the investigator. Clinical follow-up data on outcomes of interest were obtained from patients' hospital charts or from telephone interviews; these outcomes were the incidence of mortality, nonfatal myocardial infarction, repeat percutaneous coronary intervention for a treated coronary artery, and stroke. Results: Ninety Japanese patients were enrolled in the study (45 in each group). Two patients in the acarbose group discontinued therapy due to drug-related diarrhea, and 1 patient in each group was discontinued because of a newly diagnosed malignancy. Three patients in the control group were discontinued because they initiated treatment with fibrates, and 2 patients in the control group were lost to follow-up. Thus, complete baseline and follow-up data were available for 42 patients in the acarbose group and 39 in the control group. These 81 patients were predominantly male (74 [91.4%]), with a mean (SD) age of 66.3 (9.0) years, mean body weight of 65.9 (10.5) kg, and mean HbA 1c of 5.57% (0.38%). Baseline characteristics appeared to be comparable between the 2 groups. In the acarbose group, IMT increased from a mean of 1.28 (0.53) mm at baseline to 1.30 (0.52) mm at 12-month follow-up (mean change, 0.02 [0.29] mm; P = NS), whereas in the control group, it increased from a mean of 1.15 (0.37) mm to 1.32 (0.46) mm (mean change, 0.17 [0.25] mm; P < 0.001 ). The difference between groups was statistically significant ( P = 0.01). In addition, the acarbose group had significant reductions from baseline in 2-hour glucose concentrations on the 75-g OGTT (mean change, −24.8 [45.2] mg/dL; P = 0.001), fasting total cholesterol (mean change, −11.26 [26.1] mg/dL; P = 0.009), and fasting triglyceride concentrations (mean change, −30.4 [62.7] mg/dL; P = 0.003), whereas the corresponding changes were not significant in the control group (mean change, −8.5 [39.4], −6.22 [26.7], and −1.05 [74.2] mg/dL, respectively). Cardiovascular events requiring hospitalization occurred in 4 patients (9.5%) in the acarbose group and 4 patients (10.3%) in the control group. No deaths, nonfatal myocardial infarctions, or strokes occurred in either group over the follow-up period. Conclusion: In this small, open-label study in patients with established CAD who were newly diagnosed with IGT or mild T2DM, 12 months of treatment with acarbose was associated with a beneficial effect in terms of preventing the progression of carotid IMT compared with control, although it was not associated with a significant decrease in IMT from baseline. UMIN (University Hospital Medical Information Network) Clinical Trials Registry identifier: UMIN000000544.

Insulin resistance relates to microvascular reactivity 23 years after preeclampsia

Preeclampsia, an endothelial disorder of pregnancy, is associated with an increased risk on cardiovascular diseases. Cardiovascular risk factors may mediate vascular dysfunction both during pregnancy but also later in life. This study aims to investigate microvascular reactivity, and its relationship with several cardiovascular risk factors, in women with a history of preeclampsia and controls. In this cross-sectional study we compared women with a history of preeclampsia (PE, n = 22) with women with uneventful pregnancies only (CON, n = 29) 23 years after their first delivery. Participants were matched for BMI, age and date of delivery. We assessed blood concentrations of fasting glucose, HbA1c, insulin, (total, HDL-, LDL-) cholesterol, triglycerides and CRP. Endothelial function was assessed by measurement of skin microcirculatory blood flow by Laser Doppler flowmetry at the dorsal and ventral site of the finger during post-occlusive reactive hyperemia (PORH). PE had higher fasting insulin levels and HOMA-IR compared with CON. The PORH response was similar in both groups. The area under the curve of PORH correlated with insulin and HOMA-IR at both sites, with BMI, triglycerides at the dorsal site and with CRP at the ventral site of the finger in PE and not in CON. In conclusion, 23 years after pregnancy we did not observe a difference in the microvascular hyperemic response between women with a history of preeclampsia and controls. Meanwhile, the results of our study suggest that insulin resistance and other cardiovascular risk factors are related to microvascular reactivity in middle-aged women with a history of preeclampsia.

Acute resistance exercise attenuates fasting and postprandial triglyceridemia in women by reducing triglyceride concentrations in triglyceride-rich lipoproteins

A single bout of endurance exercise lowers fasting and postprandial triglyceride (TG) concentrations in both men and women, by reducing TG in triglyceride-rich lipoproteins (TRLs). The effect of resistance exercise on TRL-TG metabolism is not known; previous studies only measured total plasma TG concentrations and provide conflicting results. Furthermore, none has specifically examined women. We therefore sought to evaluate the effect of a single bout of resistance exercise on TRL-TG metabolism in women. We measured the concentrations of TG in total plasma and TRLs in the fasting state and during an oral fat tolerance test in five healthy untrained women (age: 32 ± 5 years; body mass index: 21.5 ± 1.7 kg/m(2); peak oxygen consumption: 31 ± 4 mL/kg min) in the morning, on two separate occasions: once after a single ~95-min bout of moderate-intensity whole-body resistance exercise (energy expenditure: 2.9 ± 0.1 MJ) and once after an equivalent period of rest, on the preceding afternoon. Fasting plasma TG and TRL-TG concentrations were 22 ± 12 and 40 ± 21% lower, respectively, and postprandial plasma TG and TRL-TG areas-under-the-curve were 24 ± 13 and 27 ± 10% lower, respectively, after exercise than rest (all P values <0.05). Effect sizes ranged from -0.52 to -0.90. Non-TRL-TG concentrations in the fasting and postprandial states were not different between trials (P > 0.60). We conclude that a single bout of resistance exercise attenuates fasting and postprandial triglyceridemia in women by reducing TRL-TG concentrations.

Fasting glucose and triglycerides as biomarkers of mTOR inhibition, evidence of a categorical response.

3091 Background: Hyperglycemia and hypertriglyceridemia are mechanism-based toxicities of mammalian target of rapamycin (mTOR) inhibitors, but have not been intensively studied as potential pharmacodynamic biomarkers. Methods: Changes in fasting serum glucose and triglyceride concentrations were determined in 127 patients (pts) before, and 4 weeks after treatment with the mTOR inhibitor sirolimus/rapamycin (S). Pts were enrolled in three different trials of S administered to achieve AUC of 1,000-6,000 ng-hr/ml. Results: Of these pts (67 male; 60 female; median age 62 y [range of 27-82], 72 had fasting measures for both glucose and triglycerides. Twelve pts had Type II diabetes. Mean/median change: in glucose = 17/8 mg/dL (SD=32, 95% CI 10-25, p< 0.0001), in triglycerides = 51/31 mg/dL (SD= 76, 95% CI 33-69, p< 0.0001) (p values for paired T-test). Changes were not associated with sex, S dose, baseline triglycerides, or use of lipid lowering agents. Change in glucose was significantly associated with a history of diabetes (larger increases in pts with a history, p<0.001) and baseline glucose levels (smaller increases in pts with higher baseline levels, p= 0.002). The Table features a striking observation. Of 72 pts, only 7 had no increase in glucose or triglyceride concentrations, and 9 had S- related increases in both glucose(>20 mg/dL) and triglycerides(>50 mg/dL). Meanwhile, 17 pts increased triglycerides of >50 mg/dL and 14 increased glucose of > 20 mg/dL without a change in the other marker. There was no evidence for association between changes in glucose and triglycerides (p = 0.72 by McNemar's test). Conclusions: Fasting blood glucose and triglyceride changes might be independent effects of mTOR inhibition. This would explain the absence of correlation between glucose and triglyceride changes and, excepting history of diabetes and changes in glucose, lack of association with clinically relevant covariates. These data suggest a new approach for developing these inexpensive validated laboratory measurements for qualification as clinically useful pharmacodynamic markers of mTOR inhibition. Δ glucose≤ 20 mg/dL Δglucose>20 mg/dL Δtriglycerides ≤ 50 mg/dL 32 14 Δtriglycerides > 50 mg/dL 17 9 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories, Amgen, Astellas Pharma, Biomarin, Daiichi Sankyo, Gilead, Millennium, Novartis, Pfizer, Takeda, Wyeth Actelion, Bayer, Bristol-Myers Squibb, EMD Serono, Genentech, Gilead, Lilly, Novartis, Pfizer, Roche patent pending for use of sorafenib in pulmonary hypertension

Orally Disintegrating and Oral Standard Olanzapine Tablets Similarly Elevate the Homeostasis Model Assessment of Insulin Resistance Index and Plasma Triglyceride Levels in 12 Healthy Men

Treatment with olanzapine is associated with obesity, diabetes mellitus, and dyslipidemia. Reports have indicated that orally disintegrating tablets (ODT) cause less weight gain than oral standard tablets (OST). The aim of this study was to compare the effect of short-term treatment with these 2 distinct olanzapine formulations on glucose and lipid metabolism in healthy men. Twelve healthy men (mean ± SEM age: 25.1 ± 5.5 years) received olanzapine ODT (10 mg od, 8 days), olanzapine OST (10 mg od, 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, glucose, insulin, free fatty acids (FFA), and triglyceride concentrations were measured at 10-minute intervals from 30 minutes prior to 2 hours after ingestion of standard meals. Leptin and adiponectin concentrations were measured at 20- and 30-minute intervals, respectively, between 0000h-1200h. Physical activity was assessed with an accelerometer. Fuel oxidation was measured in fasting condition by indirect calorimetry. The study was conducted from April 2006 through September 2006. Treatment with olanzapine ODT and OST equally elevated the homeostasis model assessment of insulin resistance (HOMA-IR) (P = .005). At breakfast, both formulations equally increased fasting and postprandial triglyceride concentrations (P = .013 and P = .005, respectively) while decreasing fasting and postprandial FFA concentrations (P = .004 and P = .009, respectively). Body weight, body composition, physical activity, or fuel oxidation did not differ between treatment modalities. Eight days of treatment with both olanzapine formulations similarly increased HOMA-IR and triglyceride concentrations and decreased FFA concentrations in response to standard meals without affecting anthropometrics or physical activity. These data suggest that olanzapine hampers insulin action via mechanistic routes other than body adiposity or physical inactivity. controlled-trials.com. Identifier: ISRCTN17632637.

All-cause and cardiovascular mortality in treated patients with severe hypertriglyceridaemia: A long-term prospective registry study

Objective To examine all-cause and cardiovascular mortality in patients with severe hypertriglyceridaemia. Methods 337 patients aged less than 80 years (47 with diabetes, 75 women) with a fasting triglyceride concentration on at least two occasions of >5.0 mmol/l were registered by 21 lipid clinics in the United Kingdom and followed prospectively between 1980 and 2008 for 4353 person-years. The standardised mortality ratio (SMR) was calculated by comparison with the general population. Results The mean untreated total cholesterol concentration was 9.8 (SD 3.6) mmol/l for men and 11.9 (7.2) mmol/l for women and the corresponding geometric mean triglyceride concentration was 12.6 (inter-quartile range 7.3, 21.6) and 15.7 (8.2, 29.2) mmol/l. There were 70 deaths, including 35 from CHD and 7 from stroke. The SMR for CHD was raised at 327 (95% confidence intervals 228, 455; p < 0.0001) and remained elevated after excluding patients with diabetes at registration (SMR = 287, 95% CI 190, 419; p < 0.0001), and after excluding patients with CHD at registration (SMR = 259, 95% CI 158, 400; p = 0.0003). The increased SMR was most marked in younger men aged 40–59 years (SMR = 544, 95% CI 304, 897; p < 0.0001). The SMR for stroke for patients aged 20–79 years was raised at 262 (95% CI 105, 540; p = 0.04), as was all-cause mortality at 164 (95% CI 129, 208; p < 0.001). Conclusion Severe hypertriglyceridaemia is associated with a substantially increased mortality from cardiovascular disease, even in the absence of diabetes. In addition to lowering triglyceride concentrations to reduce the risk of pancreatitis, treatment should aim to reduce the overall cardiovascular risk.

Modulatory Effect of Psidium Guajava Linn and Ocimum Gratissimum Linn on Lipid Profile and Selected Biochemical Indices in Rabbits Fed High Cholesterol Diet

The effect of aqueous leaf extracts of Psidium guajava(PG) and Ocimum gratissimum(OG) on fasting plasma glucose (FPG), total protein (TP), albumin (ALB), globulin (GLB), total cholesterol (TC), triglyceride (TG), HDL-cholesterol (HDL), LDL-cholesterol (LDL) and lactate dehydrogenase (LDH) concentrations in rabbits fed high-cholesterol diet was investigated. Four groups of animals were used (n = 6). Animals in group A were fed normal laboratory pellet and water ad libitum; those in group B were fed the high-cholesterol diet (normal diet + 1% w/w cholesterol + 1% w/w vegetable oil) while those in groups C and D received a daily oral administration of 250 mg/kg body weight of the extract of Psidium guajava and Ocimum gratissimum, respectively, in addition to the high-cholesterol diet for a period of six weeks. Hypercholesterolemia, associated with hyperglycemia was induced significantly in animals in group B compared to normal control group (A) (P&lt;0.01). There were also significant increases in the levels of LDL (P&lt;0.05) and HDL (P&lt;0.01). Treatments with PG and OG reduced the plasma cholesterol level by 15% and 28%, respectively, compared to animals in Group B. PG caused a remarkable increase in HDL (69%) but a decrease in LDL (74%) levels. OG on the other hand reduced the levels of both HDL and LDL by 50% and 26%, respectively, compared to animals in Group B. While the level of HDL in the OG group was similar to that of normal controls, the LDL level was significantly higher (71%). Furthermore, both extracts reduced the associated hyperglycemia significantly (P&lt;0.05). This decrease was more pronounced in PG treated rabbits (PG; 43%, OG; 19%). In addition, OG stimulated a significant increase in the concentrations of LDH and serum protein, particularly albumin. These results show that aqueous extracts of both plants especially PG ameliorated the hypercholesterolemic and associated hyperglycemic effects of high cholesterol diet. However, OG shows possible contraindications and the safety of its ethnomedical usage warrants further investigation.