Comparative speed of kill provided by lotilaner (Credelio™), sarolaner (Simparica Trio™), and afoxolaner (NexGard™) to control Amblyomma americanum infestations on dogs.

BACKGROUND: Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products. METHODS: Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days - 7, - 2, 21, and 28, and tick counts were performed on day - 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons. RESULTS: On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) (P = 0.002, P < 0.001, respectively). On day 21, at 12 h postinfestation, lotilaner efficacy (59.6%) was significantly different from sarolaner (0.0%) (P < 0.001) and afoxolaner (6.3%) (P < 0.001). At 24 h, lotilaner efficacy (97.4%) was significantly different (P < 0.001) from sarolaner and afoxolaner (13.6% and 14.9%, respectively). On day 28, at 12 h postinfestation, lotilaner efficacy (47.8%) was significantly different from sarolaner (17.1%) (P = 0.020) and afoxolaner (9.0%) (P = 0.006). At 24 h, lotilaner efficacy (92.3%) was significantly different from sarolaner 4.9% (P < 0.001) and afoxolaner (0.0%) (P < 0.001). Speed of kill for sarolaner and afoxolaner, but not lotilaner, significantly declined over the study period. Following reinfestation on day 28, neither sarolaner nor afoxolaner reached 90% efficacy by 48 h. By 72 h, sarolaner efficacy was 97.4% and afoxolaner efficacy was 86.3%. Only lotilaner achieved ≥ 90% efficacy by 24 h post-treatment and 24 h postinfestation on days 21 and 28. Time to ≥ 90% efficacy following new infestations consistently occurred 24-48 h earlier for lotilaner compared with sarolaner or afoxolaner. CONCLUSIONS: Credelio (lotilaner) has a more rapid onset of acaricidal activity against A. americanum than Simparica Trio (sarolaner-moxidectin-pyrantel) and NexGard (afoxolaner). Only lotilaner's speed of tick kill is sustained throughout the dosing period.

Importance of early weight loss and other predictors of lower weight loss in a commercial program: A secondary data analysis.

Objective: There is substantial inter-individual variability in response to weight loss interventions and emerging evidence suggests that weight loss during the early weeks of an intervention may be predictive of longer-term weight loss. This secondary analysis of data from a commercial program therefore examined 1) the associations between early weight loss (i.e., week 4) with final visit weight loss and duration on the program, and 2) other predictors of lower weight loss at final visit. Methods: Client charts of adults with overweight or obesity (N = 748) were analyzed. Clients were stratified into categories of weight loss at the week 4 (< and ≥2%, 3% and 4%) and final visits (< and ≥5% and 10%). Multivariate logistic regression was used to assess predictors of <5% and <10% final visit weight loss. Results: The odds ratios for losing <5% or <10% of weight at the final visit were higher (49.0 (95% CI: 13.84, 173.63) and 20.1 (95% CI: 6.96, 58.06)) for clients who lost <2% or <3% compared to those who lost ≥2% or ≥3% at week 4. Other predictors of not losing a clinically relevant amount of weight included female sex, use of higher calorie meal plans and shorter time in the program, among others. Those who lost ≥2% at week 4 also had a significantly greater percent program completion (109.2 ± 75.2% vs. 82.3 ± 82.4, p < 0.01) compared with those who did not meet the 2% threshold. Conclusions: Lower 4-week weight loss was identified as a strong predictor of not losing a clinically relevant amount of weight. These results may be useful for the early identification of individuals who can be targeted for additional counseling and support to aid in attaining weight loss goals.

The Relationship between Whole Grain Intake and Body Weight: Results of Meta-Analyses of Observational Studies and Randomized Controlled Trials.

Results from some observational studies suggest that higher whole grain (WG) intake is associated with lower risk of weight gain. Ovid Medline was used to conduct a literature search for observational studies and randomized controlled trials (RCTs) assessing WG food intake and weight status in adults. A meta-regression analysis of cross-sectional data from 12 observational studies (136,834 subjects) and a meta-analysis of nine RCTs (973 subjects) was conducted; six prospective cohort publications were qualitatively reviewed. Cross-sectional data meta-regression results indicate a significant, inverse correlation between WG intake and body mass index (BMI): weighted slope, -0.0141 kg/m2 per g/day of WG intake (95% confidence interval (CI): -0.0207, -0.0077; r = -0.526, p = 0.0001). Prospective cohort results generally showed inverse associations between WG intake and weight change with typical follow-up periods of five to 20 years. RCT meta-analysis results show a nonsignificant pooled standardized effect size of -0.049 kg (95% CI -0.297, 0.199, p = 0.698) for mean difference in weight change (WG versus control interventions). Higher WG intake is significantly inversely associated with BMI in observational studies but not RCTs up to 16 weeks in length; RCTs with longer intervention periods are warranted.

Corn Oil Lowers Plasma Cholesterol Compared with Coconut Oil in Adults with Above-Desirable Levels of Cholesterol in a Randomized Crossover Trial.

Background: Few trials have examined the effects of coconut oil consumption in comparison with polyunsaturated fatty acid-rich oils such as corn oil. Objective: This trial assessed the effects of consuming foods made with corn oil compared with coconut oil on lipids, glucose homeostasis, and inflammation. Methods: This was a preliminary randomized crossover study of men (n = 12) and women (n = 13) with a mean age of 45.2 y, mean body mass index (in kg/m2) of 27.7, fasting LDL cholesterol ≥115 mg/dL and <190 mg/dL, and triglycerides (TGs) ≤375 mg/dL. Subjects consumed muffins and rolls providing 4 tablespoons (∼54 g) per day of corn oil or coconut oil as part of their habitual diets for 4 wk, with a 3-wk washout between conditions. Fasting plasma lipids and high-sensitivity C-reactive protein (hs-CRP) and glucose metabolism were assessed via an intravenous glucose tolerance test at baseline and 15 and 29 d of treatment. Responses were compared between treatments by ANCOVA. Results: Median baseline concentrations of LDL cholesterol, non-HDL cholesterol, total cholesterol (total-C), HDL cholesterol, total-C:HDL cholesterol, and TGs were 123, 144, 188, 46.0, 4.21, and 92.5 mg/dL, respectively. Changes from baseline for corn oil and coconut oil conditions, respectively, were: LDL cholesterol (primary outcome; -2.7% compared with +4.6%), non-HDL cholesterol (-3.0% compared with +5.8%), total-C (-0.5% compared with +7.1%), HDL cholesterol (+5.4% compared with +6.5%), total-C:HDL cholesterol (-4.3% compared with -3.3%), and TGs (-2.1% compared with +6.0%). Non-HDL cholesterol responses were significantly different between corn and coconut oil conditions (P = 0.034); differences between conditions in total-C and LDL cholesterol approached significance (both P = 0.06). Responses for hs-CRP and carbohydrate homeostasis parameters did not differ significantly between diet conditions. Conclusions: When incorporated into the habitual diet, consumption of foods providing ∼54 g of corn oil/d produced a more favorable plasma lipid profile than did coconut oil in adults with elevated cholesterol. This trial was registered at clinicaltrials.gov as NCT03202654.

Type-4 Resistant Starch in Substitution for Available Carbohydrate Reduces Postprandial Glycemic Response and Hunger in Acute, Randomized, Double-Blind, Controlled Study.

Resistant starch (RS) is a type of dietary fiber that has been acknowledged for multiple physiological benefits. Resistant starch type 4 (RS4) is a subcategory of RS that has been more intensively studied as new types of RS4 emerge in the food supply. The primary aim of this randomized, double-blind, controlled study was to characterize the postprandial glucose response in healthy adults after consuming a high fiber scone containing a novel RS4 or a low fiber control scone without RS4. Secondary aims included assessment of postprandial insulin response, postprandial satiety, and gastrointestinal tolerance. The fiber scone significantly reduced postprandial glucose and insulin incremental areas under the curves (43-45% reduction, 35-40% reduction, respectively) and postprandial glucose and insulin maximum concentrations (8-10% and 22% reduction, respectively). The fiber scone significantly reduced hunger and desire to eat during the 180 min following consumption and yielded no gastrointestinal side effects compared with the control scone. The results from this study demonstrate that a ready-to-eat baked-good, such as a scone, can be formulated with RS4 replacing refined wheat flour to yield statistically significant and clinically meaningful reductions in blood glucose and insulin excursions. This is the first study to report increased satiety after short-term RS4 intake, which warrants further investigation in long-term feeding studies.

Use of supplemental long-chain omega-3 fatty acids and risk for cardiac death: An updated meta-analysis and review of research gaps.

BACKGROUND: Randomized controlled trials (RCTs) assessing use of long-chain omega-3 polyunsaturated fatty acids (LC-OM3), primarily eicosapentaenoic acid, and/or docosahexaenoic acid have shown mixed results. OBJECTIVE: The objectives of the study were to update and further explore the available RCT data regarding LC-OM3 supplementation and risk for cardiac death and to propose testable hypotheses for the mixed results obtained in RCTs regarding supplemental LC-OM3 use and cardiac risk. METHODS: A literature search was conducted using PubMed and Ovid/MEDLINE for RCTs assessing LC-OM3 supplements or pharmaceuticals with intervention periods of at least 6 months and reporting on the outcome of cardiac death. Meta-analysis was used to compare cumulative frequencies of cardiac death events between the LC-OM3 and control groups, including sensitivity and subset analyses. RESULTS: Fourteen RCTs were identified for the primary analysis (71,899 subjects). In the LC-OM3 arms, 1613 cardiac deaths were recorded (4.48% of subjects), compared with 1746 cardiac deaths in the control groups (4.87% of subjects). The pooled relative risk estimate showed an 8.0% (95% confidence interval 1.6%, 13.9%, P = .015) lower risk in the LC-OM3 arms vs controls. Subset analyses showed numerically larger effects (12.9%-29.1% lower risks, all P < .05) in subsets of RCTs with eicosapentaenoic acid + docosahexaenoic acid dosages >1 g/d and higher risk samples (secondary prevention, baseline mean or median triglycerides ≥150 mg/dL, low-density lipoprotein cholesterol ≥130 mg/dL, statin use <40% of subjects). Heterogeneity was low (I2 ≤ 15.5%, P > .05) for the primary and subset analyses. CONCLUSION: LC-OM3 supplementation is associated with a modest reduction in cardiac death.

Replacement of Refined Starches and Added Sugars with Egg Protein and Unsaturated Fats Increases Insulin Sensitivity and Lowers Triglycerides in Overweight or Obese Adults with Elevated Triglycerides.

Background: Hypertriglyceridemia is a common condition in the United States and is often associated with other metabolic disturbances, including insulin resistance, metabolic syndrome, and a predominance of small dense LDL particles.Objective: The objective of this trial was to evaluate the effects of a combination of egg protein (Epro) and unsaturated fatty acids (UFAs) substituted for refined starches and added sugars on insulin sensitivity (primary outcome) and other cardiometabolic health markers in overweight or obese adults with elevated triglyceride (TG) concentrations.Methods: Subjects with elevated TG concentrations were given test foods prepared by using Epro powder (∼8% of energy) and vegetable oil (∼8% of energy; Epro and UFA condition) or test foods prepared by using refined starch and sugar (∼16% of energy; carbohydrate condition) in a randomized, double-blind, controlled-feeding, crossover trial (3 wk/condition, 2-wk washout). The Matsuda insulin sensitivity index (MISI), fasting lipids, and other cardiometabolic health markers were assessed at baseline and the end of each diet condition. Responses were compared by using repeated-measures ANCOVA.Results: Twenty-five participants [11 men, 14 women; mean ± SEM: age, 46.3 ± 2.4 y; body mass index (in kg/m2), 31.8 ± 1.0] with a median (interquartile range limits) fasting serum TG concentration of 173 mg/dL (159, 228 mg/dL) completed the trial. The MISI value increased 18.1% ± 8.7% from baseline during the Epro and UFA condition and decreased 5.7% ± 6.2% from baseline during the carbohydrate condition (P < 0.001). The disposition index increased 23.8% ± 20.8% during the Epro and UFA condition compared with a decrease of 16.3% ± 18.8% during carbohydrate (P = 0.042) and LDL peak particle size increased 0.12 nm (-0.12, 0.28 nm) with Epro and UFA compared with a decrease of 0.15 nm (-0.33, 0.12 nm) with carbohydrate (P = 0.019). TG and VLDL cholesterol concentrations were lowered by 18.5% (-35.7%, -6.9%) and 18.6% (-34.8%, -7.4%), respectively, after the Epro and UFA condition and by 2.5% (-13.4%, 17.0%) and 3.6% (-12.5%, 16.2%), respectively, after the carbohydrate diet condition (P < 0.002).Conclusions: The replacement of refined carbohydrates with a combination of Epro and UFA increased the MISI value and altered several markers of cardiometabolic health in overweight or obese adults with elevated TG concentrations. This trial was registered at clinicaltrials.gov as NCT02924558.

Predictors of anterior and posterior wall carotid intima media thickness progression in men and women at moderate risk of coronary heart disease.

BACKGROUND: The rate of carotid intima media thickness (CIMT) progression has been widely used in clinical trials as a surrogate marker for subclinical atherosclerosis. OBJECTIVE: The aim of this study was to investigate relationships between coronary heart disease (CHD) risk markers and progression of CIMT in patients at moderate CHD risk. METHODS: Participants included men (45-75 years) and women (55-74 years) in the control arm of a clinical trial. All had at least one major CHD risk factor and baseline posterior wall CIMT 0.7-2.0 mm, without significant stenosis. Posterior (n = 134) and anterior wall (in a subset, n = 72) CIMT were assessed with B-mode ultrasound at baseline and 12 and ∼18 months. Fasting lipoprotein lipid, apolipoprotein (Apo), inflammatory, and oxidative stress markers were evaluated. RESULTS: Baseline CIMT was inversely associated (P < .001) with CIMT progression. After adjustment for baseline CIMT, significant predictors of anterior wall CIMT progression in linear regression analyses included glucose (P = .044), high-density lipoprotein cholesterol (HDL-C, inverse, P = .006), triglycerides (TG, P = .006), and ratios of total cholesterol (TC)/HDL-C (P = .013), TG/HDL-C (P = .005), and Apo B/HDL-C (P = .021). Posterior wall CIMT progressed on average, whereas anterior wall CIMT regressed (0.0078 vs -0.0164 mm/year, P = .014). Significant baseline CIMT-adjusted predictors of posterior wall CIMT progression included TC (P = .028), low-density lipoprotein-C (P = .035), non-HDL-C (P = .004), TG (P = .016), Apo B (P = .005), and ratios of TC/HDL-C (P < .001), TG/HDL-C (P = .015), Apo B/Apo AI (P = .012) and Apo B/HDL-C (P = .004). CONCLUSION: The strongest predictors for CIMT progression in anterior and posterior walls were lower baseline CIMT, increased TG, and elevated ratios, including TC/HDL-C, TG/HDL-C and Apo B/HDL-C.

Fat mass, abdominal fat distribution, and C-reactive protein concentrations in overweight and obese men and women.

BACKGROUND: Previous work suggests a positive correlation between intraabdominal adipose tissue and high-sensitivity C-reactive protein (hsCRP). We sought to further explore the relationships between body fat mass/distribution and hsCRP levels in sedentary overweight and obese men and women. METHODS: Body composition and abdominal fat areas were measured using dual-energy X-ray absorptiometry and abdominal computed tomography, respectively. Concentrations of hsCRP were measured in serum by nephelometry. RESULTS: Values for hsCRP were 3.2 ± 0.3 mg/L and 4.8 ± 0.6 mg/L in men and women, respectively. Fat mass was nonsignificantly (P=0.09) higher in women (38.8 ± 1.0 kg) than men (36.2 ± 1.1 kg). Abdominal visceral adipose tissue (VAT) area was greater in men than women (104.5 ± 5.7 vs. 59.6 ± 4.3 cm(2), P<0.001) whereas women had greater abdominal subcutaneous adipose tissue (SAT) area compared to men (334.6 ± 11.6 vs. 285.0 ± 13.4 cm(2), P<0.01). Significant associations were present between hsCRP concentrations (natural log transformed) and total fat mass (r=0.502, P<0.01), VAT (r=0.241, P<0.05), and SAT (r=0.418, P<0.01) in men, whereas a significant association for women was found only for total fat mass (r=0.359, P<0.01). Multiple regression analyses showed that men and women had similar concentrations of hsCRP for a given age and fat mass. In both men and women, neither VAT nor SAT area independently predicted hsCRP when included individually or separately in models with age and fat mass. CONCLUSIONS: Results suggest that whole body fat mass, but not abdominal fat distribution, is associated with hsCRP concentrations in overweight and obese men and women.

Efficacy and safety of flavocoxid compared with naproxen in subjects with osteoarthritis of the knee- a subset analysis.

OBJECTIVE: twice-daily flavocoxid, a cyclooxygenase and 5-lipoxygenase inhibitor with potent antioxidant activity of botanical origin, was evaluated for 12 weeks in a randomized, double-blind, active-comparator study against naproxen in 220 subjects with moderate-severe osteoarthritis (OA) of the knee. As previously reported, both groups noted a significant reduction in the signs and symptoms of OA with no detectable differences in efficacy between the groups when the entire intent-to-treat population was considered. This post-hoc analysis compares the efficacy of flavocoxid to naproxen in different subsets of patients, specifically those related to age, gender, and disease severity as reported at baseline for individual response parameters. METHODS: in the original randomized, double-blind study, 220 subjects were assigned to receive either flavocoxid (500 mg twice daily) or naproxen (500 mg twice daily) for 12 weeks. In this subgroup analysis, primary outcome measures including the Western Ontario and McMaster Universities OA index and subscales, timed walk, and secondary efficacy variables, including investigator global assessment for disease and global response to treatment, subject visual analog scale for discomfort, overall disease activity, global response to treatment, index joint tenderness and mobility, were evaluated for differing trends between the study groups. RESULTS: subset analyses revealed some statistically significant differences and some notable trends in favor of the flavocoxid group. These trends became stronger the longer the subjects continued on therapy. These observations were specifically noted in older subjects (>60 years), males and in subjects with milder disease, particularly those with lower subject global assessment of disease activity and investigator global assessment for disease and faster walking times at baseline. CONCLUSIONS: initial analysis of the entire intent-to-treat population revealed that flavocoxid was as effective as naproxen in managing the signs and symptoms of OA of the knee. Detailed analyses of subject subsets demonstrated distinct trends in favor of flavocoxid for specific groups of subjects.

Repeatability of indices of insulin sensitivity and secretion from standard liquid meal tests in subjects with type 2 diabetes mellitus or normal or impaired fasting glucose.

BACKGROUND: The objective of this investigation was to evaluate the test-retest repeatability of insulin sensitivity and secretion indices derived from liquid meal tolerance tests (MTTs) in subjects with normal fasting glucose (NFG) (n = 20), impaired fasting glucose (IFG) (n = 20), or type 2 diabetes mellitus (n = 38). METHODS: The Matsuda Index of insulin sensitivity and a Disposition Index (the product of the Matsuda Index and the ratio of the total areas under the curves for glucose and insulin from 0 to 120 min) were assessed in two standard liquid MTTs, separated by approximately 1 week. RESULTS: Mean ±SD Matsuda Index values were 14.2±7.6, 8.8 ± 4.7, and 6.3±4.0, and Disposition Index values were 1,009.6 ±355.5, 671.4± 249.0, and 201.8 ±101.3 for NFG, IFG, and diabetes, respectively (all P < 0.05 except Matsuda Index for IFG vs. diabetes, P = 0.241). Differences between tests in subjects with NFG, IFG, and diabetes, respectively, were -0.2 ± 3.6 (coefficient of variation for the method error, 17.9%), 0.2±3.2 (26.1%), and 0.1±3.0 (34.1%) for the Matsuda Index and 16.5±225.8 (16.1%), 13.3±221.6 (23.1%), and 15.2±79.4 (28.1%) for the Disposition Index. CONCLUSIONS: The Matsuda and Disposition indices derived from liquid MTTs appropriately ranked categories of fasting glucose tolerance and have repeatability profiles suggesting potential usefulness in population studies and moderately sized clinical trials requiring repeated measurements.

Efficacy and safety of flavocoxid, a novel therapeutic, compared with naproxen: a randomized multicenter controlled trial in subjects with osteoarthritis of the knee.

INTRODUCTION: Flavocoxid is a novel flavonoid-based "dual inhibitor" of the 5-lipoxygenase (5-LOX) enzyme and the cyclooxygenase (COX) enzymes. This study was designed to compare the effectiveness and safety of flavocoxid to naproxen in subjects with moderate to severe osteoarthritis (OA) of the knee. METHODS: In this randomized, multicenter, double-blind study, 220 subjects were assigned to receive either flavocoxid (500 mg twice daily) or naproxen (500 mg twice daily) for 12 weeks. The trial was structured to show noninferiority of flavocoxid to naproxen. Primary outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and subscales and a timed walk. RESULTS: More than 90% of the subjects in both groups noted significant reduction in the signs and symptoms of knee OA. There were no statistically significant differences in efficacy between the flavocoxid and naproxen groups when the entire intent-to-treat population was analyzed. The flavocoxid group had significantly fewer upper gastrointestinal (UGI) and renal (edema) adverse events (AEs) as well as a strong trend toward fewer respiratory AEs. CONCLUSION: Flavocoxid, a first-in-class flavonoid-based therapeutic that inhibits COX-1 and COX-2 as well as 5-LOX, was as effective as naproxen in managing the signs and symptoms of OA of the knee. Flavocoxid demonstrated better UGI, renal (edema), and respiratory safety profiles than naproxen.

Effects of consumption of pomegranate juice on carotid intima-media thickness in men and women at moderate risk for coronary heart disease.

This randomized, double-blind, parallel trial assessed the influence of pomegranate juice consumption on anterior and posterior carotid intima-media thickness (CIMT) progression rates in subjects at moderate risk for coronary heart disease. Subjects were men (45 to 74 years old) and women (55 to 74 years old) with > or =1 major coronary heart disease risk factor and baseline posterior wall CIMT 0.7 to 2.0 mm, without significant stenosis. Participants consumed 240 ml/day of pomegranate juice (n = 146) or a control beverage (n = 143) for up to 18 months. No significant difference in overall CIMT progression rate was observed between pomegranate juice and control treatments. In exploratory analyses, in subjects in the most adverse tertiles for baseline serum lipid peroxides, triglycerides (TGs), high-density lipoprotein (HDL) cholesterol, TGs/HDL cholesterol, total cholesterol/HDL cholesterol, and apolipoprotein-B100, those in the pomegranate juice group had significantly less anterior wall and/or composite CIMT progression versus control subjects. In conclusion, these results suggest that in subjects at moderate coronary heart disease risk, pomegranate juice consumption had no significant effect on overall CIMT progression rate but may have slowed CIMT progression in subjects with increased oxidative stress and disturbances in the TG-rich lipoprotein/HDL axis.

Hydroxypropylmethylcellulose and methylcellulose consumption reduce postprandial insulinemia in overweight and obese men and women.

Hydroxypropylmethylcellulose (HPMC) and methylcellulose (MC) are modified cellulose dietary fibers that generate viscous solutions in the gastrointestinal (GI) tract. This study assessed the effects of high viscosity (HV) HPMC, ultra-HV (UHV) HPMC, and medium viscosity MC on postprandial glucose and insulin responses in overweight and obese men and women (n = 50). After overnight fasts, subjects consumed 5 breakfast meals containing 75 g carbohydrate, each of which contained 1 of the following: 1 g HV-HPMC, 2 g HV-HPMC, 2 g UHV-HPMC, 4 g medium-viscosity MC or control (2 g cellulose). Test sequence was randomized and double-blind, except the MC test, which was last and single-blind (46 subjects completed all 5 tests). Glucose and insulin responses were determined pre-meal and for 120 min postprandially. Median (interquartile limits) peak glucose concentration was lower (P = 0.001) after the meal containing 2.0 g UHV-HPMC (7.1, 6.3-8.2 mmol/L) compared with the control meal (7.7, 6.6-8.7 mmol/L). The control did not differ from the other conditions for peak glucose or for any of the HPMC/MC conditions for glucose incremental areas under the curves (IAUC). Peak insulin was reduced (P < 0.05) for all HPMC/MC conditions compared with control. Insulin IAUC was lower than control (P < 0.001) after meals containing 2 g HV-HPMC, 2 g UHV-HPMC, and 4 g MC. GI symptoms did not differ among treatments. These findings indicate that HV-HPMC (1 and 2 g), UHV-HPMC (2 g), and MC (4 g) consumption reduced postprandial insulin excursions consistent with delayed glucose absorption.

Clinical predictors of glycosylated hemoglobin response to thiazolidinedione therapy.

BACKGROUND: The aim of this investigation was to assess clinical predictors of the glycosylated hemoglobin (HbA1C) response after the addition of a thiazolidinedione (TZD) to a biguanide, a sulfonylurea, or both in subjects with type 2 diabetes. METHODS: Chart review (n = 68 physicians) was used to identify consecutive subjects started on a TZD. Qualifying subjects had been treated with pioglitazone (> or = 4 mg/day) or rosiglitazone (> or = 30 mg/day) for > or = 12 weeks. Clinical characteristics and HbA1C responses were assessed for the purpose of creating an initial predictive response model (Study 1). A separate sample from a managed care database was used to independently validate the model (Study 2). RESULTS: Data were collected from 4085 subjects (1365 in Study 1; 2720 in Study 2). In Study 1, baseline HbA1C was 8.2 +/- 0.1%. Forty-five percent (611 of 1365) and 55% (754 of 1365) were prescribed pioglitazone and rosiglitazone, respectively. In multivariate regression, baseline HbA1C (beta = -0.693%), age (beta = -0.006%), and use of multiple agents at baseline (referent = single agent, beta = 0.189%) were significant (P < 0.05) predictors, explaining 49% of the variance in HbA1C response in Study 1 and 44% of the variance in HbA1C response in the Study 2 sample. The model showed no material evidence of bias across the range of baseline HbA1C values. CONCLUSIONS: These results suggest that readily available clinical information, particularly baseline HbA1C, explains a substantial proportion of the variance in the response to TZD therapy.

High-viscosity hydroxypropylmethylcellulose blunts postprandial glucose and insulin responses.

OBJECTIVE: High-viscosity hydroxypropylmethylcellulose (HV-HPMC) is a modified cellulose fiber that produces a viscous gel in the gastrointestinal tract. Clinical trials demonstrate that consumption of HV-HPMC significantly lowers cholesterol, but limited information has been available on the influence of HV-HPMC on postprandial insulin and glucose responses. The objective of this investigation was to assess the influence of HV-HPMC on postprandial glucose and insulin responses in overweight and obese men and women. RESEARCH DESIGN AND METHODS: Participants were 31 overweight or obese men and women without diabetes who underwent three breakfast meal tests in random order, separated by > or = 72 h. Test meals containing 75 g carbohydrate plus 4 or 8 g HV-HPMC or control meals containing 8 g cellulose were delivered in a double-blind fashion. RESULTS: Peak glucose was significantly lower (P < 0.001) after both HV-HPMC-containing meals (7.4 mmol/l [4 g] and 7.4 mmol/l [8 g]) compared with the control meal (8.6 mmol/l). Peak insulin concentrations and the incremental areas for glucose and insulin from 0 to 120 min were also significantly reduced after both HV-HPMC doses versus control (all P < 0.01). CONCLUSIONS: These findings indicate that HV-HPMC consumption reduces postprandial glucose and insulin excursions, which may favorably alter risks for diabetes and cardiovascular disease.

Lipid responses to a dietary docosahexaenoic acid supplement in men and women with below average levels of high density lipoprotein cholesterol.

OBJECTIVE: To assess fasting lipid responses to a docosahexaenoic acid (DHA) supplement in men and women with below-average levels of high-density lipoprotein (HDL) cholesterol. METHODS: This randomized, double-blind, controlled clinical trial included 57 subjects, 21-80 years of age, with fasting HDL cholesterol concentrations < or =44 mg/dL (men) and < or =54 mg/dL (women), but > or =35 mg/dL. Subjects were randomly assigned to receive either 1.52 g/day DHA from capsules containing DHA-rich algal triglycerides or olive oil (control) for six weeks. RESULTS: There were no significant differences between groups in baseline lipid values. The DHA supplemented group showed significant changes [-43 (DHA) vs. -14 (controls) mg/dL, p = 0.015] and percent changes [-21% (DHA) vs. -7% (controls), p = 0.009] in triglycerides, total (12 vs. 3 mg/dL; p = 0.021 and 6% vs. 2%; p = 0.018) and low-density lipoprotein (17 vs. 3 mg/dL; p = 0.001 and 12% vs. 3%; p = 0.001) cholesterol concentrations, and in the triglyceride to HDL cholesterol ratio (-1.33 vs. -0.50, p = 0.010), compared with controls. In addition, there was a significant reduction in the percentage of LDL cholesterol carried by small, dense particles in the DHA supplemented group (changes = -10% vs. -3%, p = 0.025). CONCLUSIONS: Supplementation with 1.52 g/d of DHA in men and women with below-average HDL cholesterol concentrations raised the LDL cholesterol level, but had favorable effects on triglycerides, the triglyceride/HDL cholesterol ratio and the fraction of LDL cholesterol carried by small, dense particles. Further research is warranted to evaluate the net impact of these alterations on cardiovascular risk.

Consumption of diacylglycerol oil as part of a reduced-energy diet enhances loss of body weight and fat in comparison with consumption of a triacylglycerol control oil.

BACKGROUND: Diacylglycerol is a natural component of edible oils that has metabolic characteristics that are distinct from those of triacylglycerol. OBJECTIVE: We assessed the efficacy of an oil containing mainly 1,3-diacylglycerol in reducing body weight and fat mass when incorporated into a reduced-energy diet. DESIGN: The study was a randomized, double-blind, parallel intervention trial that was conducted at an outpatient clinical research center. The subjects (n = 131) were overweight or obese men (waist circumference > or = 90 cm) and women (waist circumference > or = 87 cm). Food products (muffins, crackers, soup, cookies, and granola bars) containing diacylglycerol or triacylglycerol oil and having the same fatty acid composition were incorporated into a reduced-energy diet (2100-3350-kJ/d deficit) for 24 wk. Percentages of change in body weight, fat mass, and intraabdominal fat area were assessed. RESULTS: In an intention-to-treat analysis, body weight and fat mass decreased significantly more in the diacylglycerol group than in the triacylglycerol group (P = 0.025 and 0.037, respectively). By the end of the trial, mean body weight had decreased 3.6% and 2.5% in the diacylglycerol and triacylglycerol groups, respectively. Fat mass decreased 8.3% and 5.6% in the diacylglycerol and triacylglycerol groups, respectively. CONCLUSION: Foods containing diacylglycerol oil promoted weight loss and body fat reduction and may be useful as an adjunct to diet therapy in the management of obesity.