Increase In High-density Lipoprotein Levels Research Articles

Pre- and Post-operative Comparative Analysis of Serum Lipid Profile in Patients with Cholelithiasis.

Background:Gallstones have become a major health problem because of their silent manifestation and unclear pathogenesis. Although the association between the disturbed lipid metabolism and formation of gallstones has been elucidated in many studies, the effect of cholecystectomy on lipid profile has not been studied in detail.Aim:The aim of the present study was to study the effect of cholecystectomy on lipid levels in patients with gallstones.Materials and Methods:The study was conducted on 50 patients with gallstones and 30 healthy volunteers for comparison of lipid levels. Subsequently, cholecystectomy was conducted on patients with gallstones and pre- and post-operative lipid levels were compared.Results:There was a significant decrease in total cholesterol, and triglycerides levels and increase in high-density lipoprotein levels after 1 month of surgery, while low-density lipoprotein levels and very low-density lipoprotein were not statistically changed.Conclusion:Cholecystectomy can significantly improve lipid levels in patients with gallstones.

Pilot Mechanistic Study of Insulin Modulation of Somatotrophic Hormones, Inflammation, and Lipid Metabolism During Critical Illness in Children.

To evaluate the mechanism of insulin modulation on somatotrophic response, inflammation, and lipid metabolism in critically ill children. Open-label randomized mechanistic study. Two-center, tertiary PICU study. Thirty critically ill children between 1 month and 14 years old, requiring mechanical ventilation and with evidence of two or more organ system failures. Randomized physiologic design of hyperinsulinemic-euglycemic clamp using continuous insulin infusion at 0.1 U/kg/hr versus conventional management. Thirteen children underwent hyperinsulinemic-euglycemic clamp. Blood samples for somatotrophic, inflammatory, and metabolic evaluation were obtained before randomization, and 24 and 72 hours later. A growth hormone oscillation profile was obtained during the first night. There was no difference between groups at baseline. Growth hormone resistance, increased proinflammatory cytokines, and increased lipolysis with low lipoprotein levels were present in all patients. Hyperinsulinemic-euglycemic clamp did not affect growth hormone, insulin-like growth factor-1 or insulin-like growth factor binding protein-3 levels. By day 2, insulin reduced insulin-like growth factor binding protein-1 levels. Tumor necrosis factor-α and interleukin-1β were similar in both groups, whereas interleukin-6 levels reduced over time only in children receiving hyperinsulinemic-euglycemic clamp. Hyperinsulinemic-euglycemic clamp also decreased free fatty acid levels, which was accompanied by increased low-density lipoprotein cholesterol and relative increase in high-density lipoprotein levels. Total cholesterol and triglycerides were unchanged. Insulin does not reverse most of the somatotrophic changes induced by the stress of critical illness. Rather, it may improve lipid metabolism and down-regulate some markers of the inflammatory response.

Experimental support for the effects of a probiotic/digestive enzyme supplement on serum cholesterol concentrations and the intestinal microbiome.

BackgroundElevated levels of blood cholesterol are associated with cardiovascular disease, a leading cause of morbidity and mortality worldwide. Current therapies for addressing elevated blood cholesterol can be inadequate, ineffective or associated with side effects; therefore, the search for additional therapies is ongoing. This study evaluated Daily Body Restore (DBR), a proprietary blend of 9 probiotic organisms of the genera Lactobacillus and Bifidobacterium, and 10 digestive enzymes, for its effects on cholesterol metabolism using an in vitro system and a mouse model.MethodsWe used a murine model of hypercholesterolemia induced by a high fat diet to evaluate the effects of DBR on blood cholesterol concentrations. Hypercholesterolemic mice were supplemented with DBR in their drinking water for 8 weeks and compared to control mice given low fat diets or unsupplemented high fat diets. To evaluate the effects of DBR on the activity of gut microbiota in vitro, the Shime® system consisting of sequential colon reactors was supplemented with DBR for analysis of short chain fatty acid production.ResultsAnalysis of hypercholesterolemic mice after 4 and 8 weeks of DBR supplementation revealed significant decreases in blood concentrations of low-density lipoprotein (LDL) and increases in high-density lipoprotein (HDL) while triglyceride concentrations were unaltered. Specifically, after 4 weeks of DBR supplementation, there was a 47 % decrease in LDL and a 32 % increase in HDL in peripheral blood compared to unsupplemented, high fat diet-fed mice. After 8 weeks of DBR treatment, LDL concentrations were dramatically reduced by 78 % and HDL was increased by 52 % relative to control mice. Addition of DBR to the Shime® system led to significantly increased production of propionate in colon reactors, indicative of microbial production of short chain fatty acids known to inhibit cholesterol synthesis.ConclusionsDBR, a probiotic and digestive enzyme supplement, lowered harmful LDL and increased HDL levels in a mouse model and also exerted in vitro effects consistent with cholesterol-lowering activity. Given the magnitude of the effects of DBR, these findings are promising for clinical implementation of DBR for treating hypercholesterolemia.

Effects of continuous long-term testosterone therapy (TTh) on anthropometric, endocrine and metabolic parameters for up to 10years in 115 hypogonadal elderly men: real-life experience from an observational registry study.

Subnormal levels of testosterone are associated with significant negative health consequences, with higher risks of all-cause and cardiovascular mortality. The numbers of studies reporting on the benefits of normalisation of testosterone is increasing but longer-term data on (elderly) men receiving testosterone treatment are almost nonexistent. In this single-centre, cumulative, prospective, registry study, 115 hypogonadal men (mean age 59.05years) received injections with testosterone undecanoate in 12-week intervals for up to 10years. Waist circumference, body weight and mean BMI dropped progressively with statistical significance versus previous year for 7years and, respectively, 8years for weight and body mass index. Similarly, fasting glucose displayed a significant decrease after the first year continuing to decrease thereafter. A decline in HbA1c , from 6.4% to 5.6% (mean <6%), was observed from year 2 on, together with a decrease in the ratio of triglycerides:high-density lipoprotein (HDL), a surrogate marker of insulin resistance, with an increase in HDL levels. The total cholesterol:HDL ratio and non-HDL cholesterol declined significantly. A decrease was also observed in systolic and diastolic blood pressure, with a decrease in levels of the inflammation marker C-reactive protein. No major adverse cardiovascular events were observed throughout the study.

HDL in sepsis - risk factor and therapeutic approach.

High-density lipoprotein (HDL) is a key component of circulating blood and plays essential roles in regulation of vascular endothelial function and immunity. Clinical data demonstrate that HDL levels drop by 40–70% in septic patients, which is associated with a poor prognosis. Experimental studies using Apolipoprotein A-I (ApoAI) null mice showed that HDL deficient mice are susceptible to septic death, and overexpressing ApoAI in mice to increase HDL levels protects against septic death. These clinical and animal studies support our hypothesis that a decrease in HDL level is a risk factor for sepsis, and raising circulating HDL levels may provide an efficient therapy for sepsis. In this review, we discuss the roles of HDL in sepsis and summarize the efforts of using synthetic HDL as a potential therapy for sepsis.

Antibodies to high-density lipoproteins are associated with inflammation and cardiovascular disease in rheumatoid arthritis patients

Several lines of evidence suggest that chronic inflammation and immune dysregulation are related to altered lipid profiles in rheumatoid arthritis (RA), but the actual mechanisms are still unclear. We wondered whether the development of antibodies against high-density lipoprotein (HDL) can be found in RA patients linked to clinical and cardiovascular (CV) risk factors. To this end, immunoglobulin G (IgG) anti-HDL antibodies and total IgG serum levels were quantified in 212 RA patients, 131 sex- and age-matched healthy controls (HC), and 52 subjects with traditional CV risk factors (tCVRs). A subgroup of 13 RA patients was prospectively followed on TNFα-blockade. TNFα, interferon (IFN)α, MIP1α, IFNγ, IL-8, VEGF, GM-CSF, IL-17, MCP-1, SDF-1α, resistin, and leptin serum levels were quantified by immunoassays. IgG anti-HDL levels were higher in RA patients compared with HC (P < 0.0001) and tCVR subjects (P = 0.015). Differences with HC remained after correction for total IgG levels (P < 0.003). Anti-HDL/IgG were negatively associated with HDL levels in RA (-1.182 [-1.823 to -0.541], P = 0.0003) after adjusting for demographical, clinical, inflammatory parameters, and treatments. RA patients with high levels of anti-HDL/IgG (n = 40, 18.8%) were more likely to have experienced a CV event (P < 0.0001) and exhibited increased levels of several proinflammatory mediators (C-reactive protein, IFNα, MIP1α, IFNγ, IL-8, GM-CSF, IL-17 and MCP-1). Finally, change in anti-HDL antibodies on TNFα-blockade was independently associated with increasing HDL levels. Overall, IgG anti-HDL antibodies are increased in RA independently of tCVRs and associated with a proinflammatory milieu and impaired lipid blood profile, which may contribute to the increased rate of CV events in these patients.

Serum amyloid A receptor blockade and incorporation into high-density lipoprotein modulates its pro-inflammatory and pro-thrombotic activities on vascular endothelial cells.

The acute phase protein serum amyloid A (SAA), a marker of inflammation, induces expression of pro-inflammatory and pro-thrombotic mediators including ICAM-1, VCAM-1, IL-6, IL-8, MCP-1 and tissue factor (TF) in both monocytes/macrophages and endothelial cells, and induces endothelial dysfunction—a precursor to atherosclerosis. In this study, we determined the effect of pharmacological inhibition of known SAA receptors on pro-inflammatory and pro-thrombotic activities of SAA in human carotid artery endothelial cells (HCtAEC). HCtAEC were pre-treated with inhibitors of formyl peptide receptor-like-1 (FPRL-1), WRW4; receptor for advanced glycation-endproducts (RAGE), (endogenous secretory RAGE; esRAGE) and toll-like receptors-2/4 (TLR2/4) (OxPapC), before stimulation by added SAA. Inhibitor activity was also compared to high-density lipoprotein (HDL), a known inhibitor of SAA-induced effects on endothelial cells. SAA significantly increased gene expression of TF, NFκB and TNF and protein levels of TF and VEGF in HCtAEC. These effects were inhibited to variable extents by WRW4, esRAGE and OxPapC either alone or in combination, suggesting involvement of endothelial cell SAA receptors in pro-atherogenic gene expression. In contrast, HDL consistently showed the greatest inhibitory action, and often abrogated SAA-mediated responses. Increasing HDL levels relative to circulating free SAA may prevent SAA-mediated endothelial dysfunction and ameliorate atherogenesis.

Targeting high-density lipoproteins: increasing de novo production versus decreasing clearance.

Although cardiovascular mortality has been decreasing in industrialized countries, there continues to be a substantial residual risk; thus, novel therapeutic agents and new targets of therapy have been sought. One highly plausible therapeutic target is high-density lipoprotein (HDL). HDL is a key player in reverse cholesterol transport and possesses a slew of other cardioprotective properties; however, recent trials with agents known to increase HDL levels have generally not shown any reduction in cardiovascular events. Further analysis of these trials suggest that fibrates have consistently reduced some cardiovascular outcomes, at least in the subgroup of patients with high serum triglycerides and low HDL cholesterol (HDLc) levels. Since fibrates, unlike niacin or cholesterol ester transfer protein inhibitors, increase HDLc level mostly through the stimulation of apolipoprotein A-I production, it is suggested that the quality and functionality of HDL are enhanced when de novo synthesis rather than inhibition of turnover is the mechanism of increasing HDL level. In this communication, the evidence for and against the cardioprotective properties of HDL is reviewed and the contemporary clinical trials are discussed.

Effect of Ezetimibe on Low‐and High‐Density Lipoprotein Subclasses in Sitosterolemia

Sitosterolemia (STSL) is a rare sterol disease manifested by very high plasma phytosterols (PS) with normal to high total cholesterol (TC) levels and increased atherosclerosis risk. Low density lipoprotein (LDL), intermediate density lipoprotein (IDL) and very lowdensity lipoprotein (VLDL) cholesterols are proatherogenic while high density lipoprotein (HDL) cholesterol is antiatherogenic. Ezetimibe (EZ), a sterol absorption inhibitor, can reduce plasma PS and TC levels in STSL but its effect on lipoprotein subclasses has not been studied. We evaluated the effect of EZ on lipoprotein subclasses in STSL patients (pts, n=8) taken off EZ for 14 wks then placed on EZ (10 mg/d) for 14 wks. Serum total lipids and subfractions were measured enzymatically or with the Lipoprint system. Data (mean±SEM) were analyzed by paired t‐test. EZ reduced serum TC (‐13±4%, p=0.02), VLDL (‐24±4%, p=0.002) and total LDL (‐17±6%, p=0.03) levels vs off EZ. Reduced LDL values were due to decreased IDLB and C (‐22±7 and ‐21±8%, p&lt;0.05), not to large, buoyant LDL subclasses (LDL1: ‐8±8%, p=0.23 and LDL2: +35±55%, p=0.17). LDL size did not change with EZ (275±0 vs 274±1 Å, p=0.18). EZ increased HDL levels (26±8%, p=0.008) due to increased intermediate (34±14%, p=0.02) and large (33±16%, p=0.06) HDL subclasses. These data suggest EZ can favorably affect LDL and HDL subfractions distribution, thus providing potential clinical benefit in STSL beyond reducing TC and PS accrual.Funded by NIH and CIHR

Inhibition of soluble epoxide hydrolase in mice promotes reverse cholesterol transport and regression of atherosclerosis

Adipose tissue is the body largest free cholesterol reservoir and abundantly expresses ATP binding cassette transporter A1 (ABCA1), which maintains plasma high-density lipoprotein (HDL) levels. HDLs have a protective role in atherosclerosis by mediating reverse cholesterol transport (RCT). Soluble epoxide hydrolase (sEH) is a cytosolic enzyme whose inhibition has various beneficial effects on cardiovascular disease. The sEH is highly expressed in adipocytes, and it converts epoxyeicosatrienoic acids (EETs) into less bioactive dihydroxyeicosatrienoic acids. We previously showed that increasing EETs levels with a sEH inhibitor (sEHI) (t-AUCB) resulted in elevated ABCA1 expression and promoted ABCA1-mediated cholesterol efflux from 3T3-L1 adipocytes. The present study investigates the impacts of t-AUCB in mice deficient for the low density lipoprotein (LDL) receptor (Ldlr−/− mice) with established atherosclerotic plaques. The sEH inhibitor delivered in vivo for 4 weeks decreased the activity of sEH in adipose tissue, enhanced ABCA1 expression and cholesterol efflux from adipose depots, and consequently increased HDL levels. Furthermore, t-AUCB enhanced RCT to the plasma, liver, bile and feces. It also showed the reduction of plasma LDL-C levels. Consistently, t-AUCB–treated mice showed reductions in the size of atherosclerotic plaques. These studies establish that raising adipose ABCA1 expression, cholesterol efflux, and plasma HDL levels with t-AUCB treatment promotes RCT, decreasing LDL-C and atherosclerosis regression, suggesting that sEH inhibition may be a promising strategy to treat atherosclerotic vascular disease.

What is the best treatment for low HDL?

Evidence-Based Answer No high-quality evidence is available regarding the impact of a low-fat diet for patients with low high-density lipoprotein (HDL). Moderate alcohol consumption may slightly increase HDL levels by less than 0.1 mmol/L. Medications including fibrates and HMG-CoA reductase inhibitors increase HDL by 3% to 10% (SOR: C, disease-oriented outcomes). In patients with both low HDL and low LDL with cardiovascular risk factors, pravastatin therapy reduces cardiovascular events by 4% over 6 years (SOR: B, RCT).

Abstract 234: Changes in Plasma Nitration of High-Density and Low-Density Lipoproteins in Patients With Chronic Kidney Disease Receiving Kidney Transplants

Background: Functional abnormalities of high-density lipoprotein (HDL) and elevated concentration of low-density lipoprotein (LDL) could contribute to cardiovascular disease (CVD) in chronic kidney disease (CKD) patients. Both qualitative and quantitative changes in HDL have been described in patients with CKD. Specifically, HDL abundance is reduced and HDL acquires a pro-inflammatory properties. In this study, we hypothesized that a functioning kidney transplant reduces serum nitrated apoA-I concentration. Methods: Concentrations of nitrated apoA-I, nitrated apoB, total apoA-I and total apoB were measured using indirect sandwich ELISA on sera collected from each transplant subject pre-transplant and at 1, 3, and 12 months post-transplant. Patients were excluded if they had a history of diabetes, prednisone dose &gt; 15 mg/day, nephrotic range proteinuria, serum creatinine (Cr) &gt; 1.5mg/dL or active inflammatory disease, or were treated with lipid-lowering medication or HIV protease inhibitors. Paired values of percent nitrated Apo A-I or nitrated apoB before and after kidney transplantation were compared using Wilcoxon signed rank sum test. Results: We screened 75 transplant patients, and 14 were found to meet the selection criteria. Amongst these patients, twelve and eight patients had Cr &lt; 1.5 mg/dL at 3 and 12 months post-transplant, respectively. There was a significant reduction in % nitrated apoA-I at 12 months post-transplant compared to pre-transplant values in patients with Cr&lt;1.5 mg/dL (p=0.04) but neither at 3 months post-transplant nor in patients with Cr &gt;1.5. Reduction of nitrated apoA-I was associated with slight increase in HDL levels 12 months post-transplantation. In contrast to apoA-I, there was no significant change in % nitrated apoB at 3 months and 12 months post-transplant. No significant corelation was observed between nitrated lipoproteins and CRP levels. Conclusion: Patients with well functioning grafts had significant reduction in percent nitrated apoA-I without any effect on apoB nitration 12 months after kidney transplantation. Further studies are needed in a large cohort to determine if nitrated apoA-I can be used as a valuable marker for cardiovascular risk stratification in CKD.

HDL Cholesterol

Lowering low-density lipoprotein cholesterol (LDL) has been definitely shown to reduce cardiovascular events and improve clinical outcomes in the literature. As a result, LDL lowering has become the cornerstone of therapeutic approaches to cardiovascular disease prevention. Recently, there has been a focus on targeting other lipid fractions to improve the clinical risk profile of patients. Raising high-density lipoprotein (HDL) has received considerable attention. Low HDL levels are often seen in combination with elevated triglyceride levels. New therapeutic modalities are being developed to increase HDL levels. Recent failure of agents such as cholesteryl ester transferase protein inhibitor torcetrapib has highlighted the importance of measuring functionality of HDL particles and not just focus quantitatively on HDL-C levels. The heterogeneity of HDL within the systemic circulation results from constant remodeling of particles in response to several factors. Established dyslipidemia therapies such as stains, fibrates, and niacin have already been well known in the literature to have a substantial benefit. Lifestyle changes such as smoking cessation and moderate alcohol consumption have also shown to have some benefit. Several novel HDL therapies are currently being developed, but only the cholesteryl ester transferase protein inhibitors have received considerable attention. Although torcetrapib has received some negative attention due to adverse effects, this overall class of therapeutic agents still holds a lot of promise. Newer agents without the concerned toxicities are currently being developed. ApoA-1-related peptides, peroxisome proliferator-activated receptor agonists, endothelial lipase inhibitors, and liver X receptor agonists are some of the other novel agents currently in various stages of development.

Effect of a 6-Month Intervention with Cooking Oils Containing a High Concentration of Monounsaturated Fatty Acids (Olive and Canola Oils) Compared with Control Oil in Male Asian Indians with Nonalcoholic Fatty Liver Disease

We investigated the effects of dietary intervention with canola or olive oil in comparison with commonly used refined oil in Asian Indians with nonalcoholic fatty liver disease (NAFLD). This was a 6-month intervention study including 93 males with NAFLD, matched for age and body mass index (BMI). Subjects were randomized into three groups to receive olive oil (n=30), canola oil (n=33), and commonly used soyabean/safflower oil (control; n=30) as cooking medium (not exceeding 20 g/day) along with counseling for therapeutic lifestyle changes. The BMI, fasting blood glucose (FBG) and insulin levels, lipids, homeostasis model of assessment for insulin resistance (HOMA-IR), HOMA denoting β-cell function (HOMA-βCF), and disposition index (DI) were measured at pre- and post-intervention. Data were analyzed with one-way analysis of variance (ANOVA) and Tukey's Honestly Significant Difference multiple comparison test procedures. Olive oil intervention led to a significant decrease in weight and BMI (ANOVA, P=0.01) compared with the control oil group. In a comparison of olive and canola oil, a significant decrease in fasting insulin level, HOMA-IR, HOMA-βCF, and DI (P<0.001) was observed in the olive oil group. Pre- and post-intervention analysis revealed a significant increase in high-density lipoprotein level (P=0.004) in the olive oil group and a significant decrease in FBG (P=0.03) and triglyceride (P=0.02) levels in the canola oil group. The pre- and post-intervention difference in liver span was significant only in the olive (1.14 ± 2 cm; P<0.05) and canola (0.66 ± 0.33 cm; P<0.05) oil groups. In the olive and canola oil groups, post-intervention grading of fatty liver was reduced significantly (grade I, from 73.3% to 23.3% and from 60.5% to 20%, respectively [P<0.01]; grade II, from 20% to 10% and from 33.4% to 3.3%, respectively [P<0.01]; and grade III, from 6.7% to none and from 6.1% to none, respectively). In contrast, in the control oil group no significant change was observed. Results suggest significant improvements in grading of fatty liver, liver span, measures of insulin resistance, and lipids with use of canola and olive oil compared with control oils in Asian Indians with NAFLD.

Regulation of High-Density Lipoprotein Metabolism

There is compelling evidence from human population studies that plasma levels of high-density lipoprotein (HDL) cholesterol correlate inversely with cardiovascular risk. Identification of this relationship has stimulated research designed to understand how HDL metabolism is regulated. The ultimate goal of these studies has been to develop HDL-raising therapies that have the potential to decrease the morbidity and mortality associated with atherosclerotic cardiovascular disease. However, the situation has turned out to be much more complex than originally envisaged. This is partly because the HDL fraction consists of multiple subpopulations of particles that vary in terms of shape, size, composition, and surface charge, as well as in their potential cardioprotective properties. This heterogeneity is a consequence of the continual remodeling and interconversion of HDL subpopulations by multiple plasma factors. Evidence that the remodeling of HDLs may impact on their cardioprotective properties is beginning to emerge. This serves to highlight the importance of understanding not only how the remodeling and interconversion of HDL subpopulations is regulated but also how these processes are affected by agents that increase HDL levels. This review provides an overview of what is currently understood about HDL metabolism and how the subpopulation distribution of these lipoproteins is regulated.

Impact of Roux-en-Y Gastric Bypass on Metabolic Syndrome and Insulin Resistance Parameters

Metabolic syndrome (MetS) is a complex association of clustering metabolic factors that increase risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. Surgical treatment has become an important tool to achieve its control. The aim of this study was to evaluate the impact of Roux-en-Y gastric bypass (RYGB) on MetS and its individual components, clinical characteristics, and biochemical features. The study is a retrospective cohort of 96 subjects with MetS who underwent RYGB and were evaluated at baseline and after surgery. Clinical and biochemical features were analyzed. After surgery, significant rates of resolution for MetS (88.5%), T2DM (90.6%), hypertension (85.6%), and dyslipidemias (54.2%) were found. Significant decreases in levels of fasting glucose, fasting insulin, hemoglobin A1c, low-density lipoprotein, and triglycerides and an increase in high-density lipoprotein level were also shown. The decrease in insulin resistance evaluated by homeostasis model assessment (HOMA-IR) was consistent. MetS resolution was associated with postoperative glycemic control, decreases in levels of fasting glucose, hemoglobin A1c, HOMA-IR, and triglycerides and in antihypertensive usage, and percentage weight loss. This study found high rates of resolution for MetS, T2DM, hypertension, and dyslipidemias after RYGB in obese patients. This finding was consistent with current literature. Hence RYGB should be largely indicated for this group of subjects as it is a safe and powerful tool to achieve MetS control.

Blend of selected fruit extracts shows antidiabetic effect by enhanced insulin secretion, modulation of β-cell function, and antidyslipidemic activity in type 2 diabetic rats

Over the years, daily consumption of fruits has been associated with reduced risk of cancer, heart disease, premature aging, stress, diabetes, and fatigue. This paper reports the antidiabetic potentials of blends of pawpaw (Carica papaya L.) and grapefruit (Citrus paradissi) with guava (Psidium guajava L.) leaves in male albino rats. Blend of fruit extracts were designed to contain 60 % pawpaw, 20 % grapefruit, and 20 % guava leaves aqueous extracts. Four groups of five rats each were acclimatized on pelletized mouse chow for 7 days, after which diabetes was induced by a single ip injection of alloxan in all groups except group 1, which served as control. Group 2 served as negative control, while groups 3 and 4 were treated with blend of fruit extracts at 2.5 and 5 ml/kg bw, respectively. Food intake, body weight, and blood glucose levels were monitored. They were sacrificed by cervical dislocation after a 2-week treatment. Blood serum was analyzed to evaluate insulin level, beta cell function, insulin resistance, and lipid profile. Histological study was carried out on pancreatic tissues. Treatment with single dose of the blend (2.5 ml/kg bw) led to a significant reduction (p < 0.05) in blood glucose, total cholesterol triglyceride, low-density lipoprotein, and increased high-density lipoprotein (HDL) levels. It also improved serum insulin level, beta cell function, and reduced insulin resistance as well as restoration of pancreatic beta cells compared to the diabetic group. These were, however, the reverse on treatment with double dosing the blend. Single dose of the selected fruit extract blend showed potent antidiabetic property as evident by the reduced blood glucose, improved serum insulin, and increased HDL levels.

Mobile Health Is Worth It! Economic Benefit and Impact on Health of a Population-Based Mobile Screening Program in New Mexico

HABITS for Life was a 3-year initiative to broadly deliver a statewide biometric and retinal screening program via a mobile unit throughout New Mexico at no charge to participants. The program goal-to identify health risk and improve population health status-was tested over a 3-year period. Value to participants and impact to the healthcare system were measured to quantify impact and value of investing in prevention at the community level. We used the Mobile Health Map Return-on-Investment Calculator, a mobile screening unit, biometric screening, retinography, and community coordination. Our systems included satellite, DSL, and 3G connectivity, a Tanita® (Arlington Heights, IL) automated body mass index-measuring scale, the Cholestec® (Alere™, Waltham, MA) system for biomarkers and glycosylated hemoglobin, a Canon (Melville, NY) CR-1 Mark II camera, and the Picture Archiving Communication System. In this report for the fiscal year 2011 time frame, 6,426 individuals received biometric screening, and 5,219 received retinal screening. A 15:1 return on investment was calculated; this excluded retinal screening for the under-65 year olds, estimated at $10 million in quality-adjusted life years saved. Statistically significant improvement in health status evidenced by sequential screening included a decrease in total cholesterol level (p=0.002) (n=308) and an increase in high-density lipoprotein level after the first and second screening (p=0.02 and p=0.01, respectively), but a decrease in mean random glucose level was not statistically significant (p=0.62). Retinal results indicate 28.4% (n=1,482) with a positive/abnormal finding, of which 1.79% (n=93) required immediate referral for sight-threatening retinopathy and 27% (n=1,389) required follow-up of from 3 months to 1 year. Screening programs are cost-effective and provide value in preventive health efforts. Broad use of screening programs should be considered in healthcare redesign efforts. Community-based screening is an effective strategy to identify health risk, improve access, provide motivation to change health habits, and improve physical status while returning significant value.

High-density lipoprotein maintains skeletal muscle function by modulating cellular respiration in mice.

Abnormal glucose metabolism is a central feature of disorders with increased rates of cardiovascular disease. Low levels of high-density lipoprotein (HDL) are a key predictor for cardiovascular disease. We used genetic mouse models with increased HDL levels (apolipoprotein A-I transgenic [apoA-I tg]) and reduced HDL levels (apoA-I-deficient [apoA-I ko]) to investigate whether HDL modulates mitochondrial bioenergetics in skeletal muscle. ApoA-I ko mice exhibited fasting hyperglycemia and impaired glucose tolerance test compared with wild-type mice. Mitochondria isolated from gastrocnemius muscle of apoA-I ko mice displayed markedly blunted ATP synthesis. Endurance capacity during exercise exhaustion test was impaired in apoA-I ko mice. HDL directly enhanced glucose oxidation by increasing glycolysis and mitochondrial respiration rate in C2C12 muscle cells. ApoA-I tg mice exhibited lower fasting glucose levels, improved glucose tolerance test, increased lactate levels, reduced fat mass, associated with protection against age-induced decline of endurance capacity compared with wild-type mice. Circulating levels of fibroblast growth factor 21, a novel biomarker for mitochondrial respiratory chain deficiencies and inhibitor of white adipose lipolysis, were significantly reduced in apoA-I tg mice. Consistent with an increase in glucose utilization of skeletal muscle, genetically increased HDL and apoA-I levels in mice prevented high-fat diet-induced impairment of glucose homeostasis. In view of impaired mitochondrial function and decreased HDL levels in type 2 diabetes mellitus, our findings indicate that HDL-raising therapies may preserve muscle mitochondrial function and address key aspects of type 2 diabetes mellitus beyond cardiovascular disease.

Expanding the Therapeutic Frontier in Atherosclerosis

Expanding the Therapeutic Frontier in Atherosclerosis