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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. [ABSTRACT FROM AUTHOR]

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. This analysis adds to the growing evidence suggesting that weight loss during the early weeks of an intervention may be predictive of longer‐term success. To our knowledge, this analysis is also the first to evaluate the sensitivity and specificity of various weight loss thresholds within the context of a commercial weight loss program. An additional unique aspect of this study, not typically evaluable in clinical trials that have a defined study length or within research trials which incentivize participants for study completion, is the evaluation of the relationship between early weight loss and time spent in the program. [ABSTRACT FROM AUTHOR]

Hydroxypropylmethylcellulose (HPMC) and methytcellulose (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.

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 cm2, 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 cm2, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

High-viscosity hydroxypropylmethylcellulose (HV-HPMC) is a dietary fiber that forms a viscous gel in the gastrointestinal tract after consumption. The aim of the present analysis was to evaluate the influence of glucose tolerance on postprandial responses to HV-HPMC. Subjects were classified into low (LPG) or high (HPG) subgroups based on the median peak glucose concentration (< or ≥147 mg/dL) after a control test meal containing 75 g of carbohydrate. Those with HPG (n=16) did not differ from the LPG subset (n=15) in demographic characteristics or fasting insulin, but had significantly higher fasting glucose (99 vs. 91 mg/dL, p=0.006). Postprandial glucose (7882 vs. 5122 minx mg/dL, p=0.023) and insulin (5184 vs. 2739 min x mU/L, p=0.019) incremental areas under the curves (IAUC, 0-120 min) were higher in the HPG subjects. Adding HV-HPMC (4 or 8 g) to the meal reduced glucose and insulin responses (p<0.001). The degree of blunting of the insulin IAUC did not differ between the HPG and LPG subsets (-47 vs. -43%, p=0.671), but the glucose IAUC was blunted to a larger degree in the HPG subjects (-41 vs. -26%, p=0.034). Thus, slowing the rate of glucose absorption with HV-HPMC had a larger impact on postprandial glycemia in subjects with HPG. These findings may have implications for understanding how slowing carbohydrate absorption may influence diabetes risk. [ABSTRACT FROM AUTHOR]

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., Competing Interests: CDC, JRK, and SSJ are employees of Medifast, Inc. JLU is a member of the Medifast Scientific Advisory Board and receives consulting fees associated with that appointment. Within the prior 24 months, KCM has received consulting fees from entities that provide products or services related to weight management, including Medifast, Eli Lilly, Pharmavite, General Mills, and 89Bio; he also has current research grant funding from the National Dairy Council, Hass Avocado Board, Greenyn, the Indiana University Foundation, Naturmega, Cargill, and National Cattlemen's Beef Association. MLW and LLG are employees of and MB is a contractor for Midwest Biomedical Research, which has received consulting fees from entities that provide products or services related to weight management, including Medifast, Eli Lilly, Pharmavite, General Mills, and 89Bio., (© 2023 Jason Pharmaceuticals, Inc and The Authors. Obesity Science & Practice published by World Obesity and The Obesity Society and John Wiley & Sons Ltd.)

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.

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.

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.