William S Yancy’s research while affiliated with Microbiome Core Facility USA and other places

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Publications (187)


Opportunities for General Internal Medicine to Promote Equity in Obesity Care
  • Article

October 2024

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3 Reads

Journal of General Internal Medicine

Ryan M. Kane

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Jacinda M. Nicklas

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Jessica L. Schwartz

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[...]

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The number and complexity of obesity treatments has increased rapidly in recent years. This is driven by the approval of new anti-obesity medications (AOMs) that produce larger degrees of weight loss than previously approved AOMs. Unfortunately, access to these highly effective therapies and to integrated team-based obesity care is limited by intra-/interpersonal patient, institutional/practitioner, community, and policy factors. We contextualized these complexities and the impact of patients’ social drivers of health (SDOH) by adapting the social ecological model for obesity. Without multi-level intervention, these barriers to care will deepen the existing inequities in obesity prevalence and treatment outcomes among historically underserved communities. As General Internal Medicine (GIM) physicians, we can help our patients navigate the complexities of evidence-based obesity treatments. As care team leaders, GIM physicians are well-positioned to (1) improve education for trainees and practitioners, (2) address healthcare-associated weight stigma, (3) advocate for equity in treatment accessibility, and (4) coordinate interdisciplinary teams around non-traditional models of care focused on upstream (e.g., policy changes, insurance coverage, health system culture change, medical education requirements) and downstream (e.g., evidence-based weight management didactics for trainees, using non-stigmatizing language with patients, developing interdisciplinary weight management clinics) strategies to promote optimal obesity care for all patients.


Average number of group classes attended (out of 16) for in‐person versus virtual cohorts. Box and whisker plots indicate the median (solid line), mean (dot), and interquartile range within the dimensions of the boxes.
Retention of weight data over time for in‐person and virtual cohorts.
Estimated daily caloric intake and daily steps for in‐person versus virtual cohorts.
Observed weight across time for in‐person versus virtual cohorts.
A non‐randomized comparison of engagement and outcomes for in‐person versus virtual delivery of the Partner2Lose weight management trial
  • Article
  • Full-text available

July 2024

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14 Reads

Objective Existing behavioral weight management interventions produce clinically meaningful weight loss. The onset of the COVID‐19 pandemic led to the quick transition of such interventions from in‐person to virtual platforms. This provided a unique opportunity to compare engagement and outcomes for an in‐person versus virtually delivered weight management intervention. Methods A non‐randomized comparison of engagement and weight outcomes was performed between two cohorts who participated in a weight management intervention in person (N = 97) versus three who participated virtually via videoconference (N = 134). Various metrics of engagement were examined, including group class and individual phone call attendance and duration, and retention for weight assessments. Behavioral targets of daily caloric intake and step‐counts and the clinical weight outcome were explored. Results Cohorts (mean [standard deviation] age 47.3 (11.5), 67.1% women: 86.8% White) that participated virtually attended more group sessions (p < 0.001) and had maintenance telephone calls that were of a longer duration (p < 0.001). No other engagement or weight outcomes significantly differed by delivery modality. Conclusions Virtual weight management programs are promising and may generate similar outcomes to those delivered in‐person. Future research should seek to understand how best to promote and sustain engagement in virtual interventions.

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Outcomes from Partner2Lose: a randomized controlled trial to evaluate 24-month weight loss in a partner-assisted intervention

July 2024

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15 Reads

BMC Public Health

Background Partner support is associated with better weight loss outcomes in observational studies, but randomized trials show mixed results for including partners. Unclear is whether teaching communication skills to couples will improve weight loss in a person attempting weight loss (index participant). Purpose To compare the efficacy of a partner-assisted intervention versus participant-only weight management program on 24-month weight loss. Methods This community-based study took place in Madison, WI. Index participants were eligible if they met obesity guideline criteria to receive weight loss counseling, were aged 18–74 years, lived with a partner, and had no medical contraindications to weight loss; partners were aged 18–74 years and not underweight. Couples were randomized 1:1 to a partner-assisted or participant-only intervention. Index participants in both arms received an evidence-based weight management program. In the partner-assisted arm, partners attended half of the intervention sessions, and couples were trained in communication skills. The primary outcome was index participant weight at 24 months, assessed by masked personnel; secondary outcomes were 24-month self-reported caloric intake and average daily steps assessed by an activity tracker. General linear mixed models were used to compare group differences in these outcomes following intent-to-treat principles. Results Among couples assigned to partner-assisted (n = 115) or participant-only intervention (n = 116), most index participants identified as female (67%) and non-Hispanic White (87%). Average baseline age was 47.27 years (SD 11.51 years) and weight was 106.55 kg (SD 19.41 kg). The estimated mean 24-month weight loss was similar in the partner-assisted (2.66 kg) and participant-only arms (2.89 kg) (estimated mean difference, 0.23 kg [95% CI, -1.58, 2.04 kg], p=0.80). There were no differences in 24-month average daily caloric intake (estimated mean difference 50 cal [95% CI: -233, 132 cal], p=0.59) or steps (estimated mean difference 806 steps [95% CI: -1675, 64 steps], p=0.07). The percentage of participants reporting an adverse event with at least possible attribution to the intervention did not differ by arm (partner-assisted: 9%, participant-only, 3%, p = 0.11). Conclusions Partner-assisted and individual weight management interventions led to similar outcomes in index participants. Trial registration Clinicaltrials.gov NCT03801174, January 11, 2019.


Metaproteomics and DNA metabarcoding as tools to assess dietary intake in humans

April 2024

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38 Reads

Objective biomarkers of food intake are a sought-after goal in nutrition research. Most biomarker development to date has focused on metabolites detected in blood, urine, skin or hair, but detection of consumed foods in stool has also been shown to be possible via DNA sequencing. An additional food macromolecule in stool that harbors sequence information is protein. However, the use of protein as an intake biomarker has only been explored to a very limited extent. Here, we evaluate and compare measurement of residual food-derived DNA and protein in stool as potential biomarkers of intake. We performed a pilot study of DNA sequencing-based metabarcoding (FoodSeq) and mass spectrometry-based metaproteomics in five individuals’ stool sampled in short, longitudinal bursts accompanied by detailed diet records ( n =27 total samples). Dietary data provided by stool DNA, stool protein, and written diet record independently identified a strong within-person dietary signature, identified similar food taxa, and had significantly similar global structure in two of the three pairwise comparisons between measurement techniques (DNA-to-protein and DNA-to-diet record). Metaproteomics identified proteins including myosin, ovalbumin, and beta-lactoglobulin that differentiated food tissue types like beef from dairy and chicken from egg, distinctions that were not possible by DNA alone. Overall, our results lay the groundwork for development of targeted metaproteomic assays for dietary assessment and demonstrate that diverse molecular components of food can be leveraged to study food intake using stool samples.


Characteristics of participants, overall and by treatment group a
Primary outcomes from Partner2Lose: A randomized controlled trial to evaluate partner involvement on long-term weight loss

February 2024

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26 Reads

Background: Partner support is associated with better weight loss outcomes in observational studies, but randomized trials show mixed results for including partners. Unclear is whether teaching communication skills to couples will improve weight loss in index participants. Purpose: To compare the efficacy of a partner-assisted intervention versus participant-only weight management program on long-term weight loss. Methods: This community-based study took place in Madison, WI. Index participants were eligible if they met obesity guideline criteria to receive weight loss counseling, were aged 74 years or younger, lived with a partner, and had no medical contraindications to weight loss; partners were aged 74 years or younger and not underweight. Couples were randomized 1:1 to a partner-assisted or participant-only intervention. Index participants in both arms received an evidence-based weight management program. In the partner-assisted arm, partners attended half of the intervention sessions, and couples were trained in communication skills. The primary outcome was index participant weight at 24 months, assessed by masked personnel; secondary outcomes were 24-month self-reported caloric intake and average daily steps assessed by an activity tracker. General linear mixed models were used to compare group differences in these outcomes following intent-to-treat principles. Results: Among couples assigned to partner-assisted (n=115) or participant-only intervention (n=116), most index participants identified as female (67%) and non-Hispanic White (87%). Average baseline age was 47.27 years (SD 11.51 years) and weight was 106.55 kg (SD 19.41 kg). The estimated mean 24-month weight loss was similar in the partner-assisted (2.66 kg) and participant-only arms (2.89 kg) (estimated mean difference, 0.23 kg [95% CI, -1.58, 2.04 kg]). There were no differences in 24-month average daily caloric intake (50 cal [95% CI: -233, 132 cal]) or steps (806 steps [95% CI: -1675, 64 steps]). The percentage of participants reporting an adverse event with at least possible attribution to the intervention did not differ by arm (partner-assisted: 9%, participant-only, 3%, p=0.11). Conclusions: Partner-assisted and individual weight management interventions led to similar outcomes in index participants. Trial registration: Clinicaltrials.gov NCT03801174


Consensus definitions and categories of lower-carbohydrate dietary patterns proposed by attendees of the Scientific Forum on Nutrition, Wellness, and Lower-Carbohydrate Diets: An Evidence-and Equity-Based Approach to Dietary Guidance. 1
Expert consensus on nutrition and lower-carbohydrate diets: An evidence- and equity-based approach to dietary guidance

February 2024

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174 Reads

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13 Citations

There is a substantial body of clinical evidence supporting the beneficial effects of lower-carbohydrate dietary patterns on multiple established risk factors associated with insulin resistance and cardiovascular diseases in adult populations. Nutrition and health researchers, clinical practitioners, and stakeholders gathered for, “The Scientific Forum on Nutrition, Wellness, and Lower-Carbohydrate Diets: An Evidence- and Equity-Based Approach to Dietary Guidance” to discuss the evidence base around lower-carbohydrate diets, health outcomes, and dietary guidance. Consensus statements were agreed upon to identify current areas of scientific agreement and spotlight gaps in research, education, and practice to help define and prioritize future pathways. Given the evidence base and considering that most American adults are living with at least one nutrition-related chronic disease, there was consensus that including a lower-carbohydrate dietary pattern as one part of the Dietary Guidelines for Americans could help promote health equity among the general population.



The proposed framework for the Keep It Off data analysis.
Percentage of report days in 1 week. The red line represents the lottery group; the green one represents the group with direct payment; the blue line is the control group.
Daily weight patterns, missing percentage, and 6-month milestone weight change in the first 6 months for three groups (i.e., control group, direct payment group, lottery group). Cells in purple are the daily weights. The first column in red and green is the heat bar to show the percentage of missing daily weight. The cells in grey represent missing values.
Illustration of the pairwise likelihood method idea in the proposed framework Stage II by using a pair of participants as example. K is the total number of observations for each participant.
Quantifying and correcting bias due to outcome dependent self-reported weights in longitudinal study of weight loss interventions

November 2023

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41 Reads

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1 Citation

In response to the escalating global obesity crisis and its associated health and financial burdens, this paper presents a novel methodology for analyzing longitudinal weight loss data and assessing the effectiveness of financial incentives. Drawing from the Keep It Off trial—a three-arm randomized controlled study with 189 participants—we examined the potential impact of financial incentives on weight loss maintenance. Given that some participants choose not to weigh themselves because of small weight change or weight gains, which is a common phenomenon in many weight-loss studies, traditional methods, for example, the Generalized Estimating Equations (GEE) method tends to overestimate the effect size due to the assumption that data are missing completely at random. To address this challenge, we proposed a framework which can identify evidence of missing not at random and conduct bias correction using the estimating equation derived from pairwise composite likelihood. By analyzing the Keep It Off data, we found that the data in this trial are most likely characterized by non-random missingness. Notably, we also found that the enrollment time (i.e., duration time) would be positively associated with the weight loss maintenance after adjusting for the baseline participant characteristics (e.g., age, sex). Moreover, the lottery-based intervention was found to be more effective in weight loss maintenance compared with the direct payment intervention, though the difference was non-statistically significant. This framework's significance extends beyond weight loss research, offering a semi-parametric approach to assess missing data mechanisms and robustly explore associations between exposures (e.g., financial incentives) and key outcomes (e.g., weight loss maintenance). In essence, the proposed methodology provides a powerful toolkit for analyzing real-world longitudinal data, particularly in scenarios with data missing not at random, enriching comprehension of intricate dataset dynamics.


Does Medically Supervised Weight Loss Prior to Total Knee Arthroplasty Improve Patient-Reported Pain and Physical Function?

August 2023

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37 Reads

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3 Citations

The Journal of Arthroplasty

Background: Weight loss is commonly recommended before total knee arthroplasty (TKA) despite inconsistent evidence for better outcomes. This study sought to examine impacts of preoperative weight loss on patient-reported and adverse outcomes among TKA patients supervised by a medical weight management clinic. Methods: This study retrospectively analyzed patients who underwent medical weight management supervision within 18 months before TKA comparing patients who did and did not have clinically relevant weight loss. Preoperative body mass indices, demographics, Patient-Reported Outcomes Measurement Information System (PROMIS) physical function and pain interference scores, pain intensity scores, and adverse outcomes were extracted. Multivariable linear regressions were performed to determine if preoperative weight loss correlated with patient-reported outcomes after controlling for confounders. Results: There were 90 patients, 75.6% women, who had a mean age of 65 years (range, 42-82) were analyzed. There were 51 (56.7%) patients who underwent clinically relevant weight loss with a mean weight loss of 10.4% and experienced no difference in adverse outcomes. Preoperative weight loss predicted significantly improved 3-months postoperative physical function (β = 15.2 [13.0-17.3], P < 0.001), but not pain interference (β = -18.9 [-57.1-19.4], P=0.215) or pain intensity (β = -1.8 [-4.9-1.2], P=0.222) scores. Conclusion: We found that medically supervised preoperative weight loss predicted improvement in physical function 3 months after TKA. This weight loss caused no major adverse effects. Further research is needed to understand the causal relationships between preoperative weight loss, medical supervision, and outcome after TKA and to elucidate potential longer-term benefits in a larger sample.


Fig. 1. Generation and scope of trnL metabarcoding data for dietary plant intake. (A) Conceptual overview of trnL metabarcoding protocol and pMR calculation. Conserved primers (F and R) flank a variable trnL region, allowing amplification of a mixed pool of plant food-derived DNA from stool. Following sequencing and taxonomic identification, data can be analyzed as the presence or count of each plant taxon per sample or metrics like the number of taxa per sample (pMR). (B) The reference trnL sequence database used for taxonomic assignment had broad representation (black and gray tick marks in the outer ring) of food crop species [full phylogenetic tree (21)] and included multiple sequences for 27% of plant taxa, which indicates within-food genetic variation at the trnL-P6 locus. Leaves in the crop tree terminate at the species level, although 70 subspecies-and 52 variety-level taxa were included in the full reference. Plant crops tracked by the FAO ("major") were more likely to be included in the reference than untracked crops ("minor"; Chi-square 188.94, df = 2, P < 10 −15 ). Example plants from each clade are shown in silhouette. Clockwise from legend, these are apple, pumpkin, cucumber, walnut, chickpea, cassava, starfruit, orange, okra, mango, grape, bell pepper, chili pepper, potato, carrot, kiwi, beet, rice, wheat, corn, onion, banana, pineapple, and avocado.
Fig. 2. pMR is associated with independent measures of dietary diversity and quality. (A) Correlation between pMR and number of plant taxa from recorded menus of Weight Loss participants from the 2 d prior to stool collection. The red dotted line denotes a theoretical perfect correspondence between the two measures. (B-D) Correlations between mean pMR (pMR averaged across all available stool samples per participant) and dietary diversity (B) and quality (C and D) indices derived from FFQ data in Adult-1 and Adult-2 participants. (E) Correlations from upper panels of (B-D) retested under candidate sampling schemes with mean pMR derived from a smaller number of stool samples. The "two samples (3 to 10 d apart)" is the current dietary assessment protocol used by the National Health and Nutrition Examination Survey (36). All boxplots represent ~100 random subsamples at each strategy, and color indicates the percentage of iterations reaching the statistical significance threshold of P < 0.05. Spearman correlations are two-tailed. FVS, Food Variety Score; hPDI, healthy plant-based dietary index; HEI-2015, Healthy Eating Index 2015.
Fig. 3. pMR detects known relationships between dietary diversity and demographic, health, and socioeconomic variables. (A) Histogram of pMR across Adolescent samples. (B) Visualization of linear model output, showing effect sizes and 95% CIs of associations of demographic, clinical, and socioeconomic covariates with pMR as a response variable. Coefficient estimates with P ≤ 0.05 are indicated in red, 0.05 < P ≤ 0.1 in yellow, and P > 0.1 in gray. For categorical variables shown, the reference category is as follows: white for race, non-Hispanic ethnicity for ethnicity, control (healthy body weight) for case-control status, self-reported income <$25,000 annually for income, and no occurrence of food running out for food insecurity. (C) Raw data underlying significant or trending covariates from (B).
Diversity of plant DNA in stool is linked to dietary quality, age, and household income

June 2023

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182 Reads

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11 Citations

Proceedings of the National Academy of Sciences

Eating a varied diet is a central tenet of good nutrition. Here, we develop a molecular tool to quantify human dietary plant diversity by applying DNA metabarcoding with the chloroplast trnL-P6 marker to 1,029 fecal samples from 324 participants across two interventional feeding studies and three observational cohorts. The number of plant taxa per sample (plant metabarcoding richness or pMR) correlated with recorded intakes in interventional diets and with indices calculated from a food frequency questionnaire in typical diets (ρ = 0.40 to 0.63). In adolescents unable to collect validated dietary survey data, trnL metabarcoding detected 111 plant taxa, with 86 consumed by more than one individual and four (wheat, chocolate, corn, and potato family) consumed by >70% of individuals. Adolescent pMR was associated with age and household income, replicating prior epidemiologic findings. Overall, trnL metabarcoding promises an objective and accurate measure of the number and types of plants consumed that is applicable to diverse human populations.


Citations (70)


... The Portfolio Moderate-carbohydrate diet (PMCD) is a plant-based diet consisting of 40% carbohydrates, 20% protein, and 40% fat [16].The portfolio diet is designed by excluding all animal products such as meat, fish, poultry, eggs, and dairy products and emphasizing on the consumption of five specific cholesterol-lowering foods and nutrients, including plant protein (mainly from soy products and pulses), viscous fiber (such as oats, barley, and certain fruits), nuts, phytosterols, and monosaturated fats [17,18]. A systematic review has shown that adhering to a low carbohydrate diet (providing less than 45% of total energy from carbohydrates) while maintaining an energy deficit led to positive changes in body measurements, blood sugar levels, fasting insulin levels, insulin response during a 3-h oral glucose tolerance test, and reproductive hormones like FSH, LH, DHEA, SHBG, and free testosterone in women with PCOS [19].The beneficial effect of low-carbohydrate regimens in metabolic outcomes of PCOS is possibly due to the reduced levels of circulating glucose, insulin, insulin-like growth factor-1(IGF-1), and insulin-like growth factor binding protein 1(IGFBP1), which reduces the hyper-androgens among PCOS patients [20]. ...

Reference:

The effects of portfolio moderate-carbohydrate and ketogenic diets on anthropometric indices, metabolic status, and hormonal levels in overweight or obese women with polycystic ovary syndrome: a randomized controlled trial
Expert consensus on nutrition and lower-carbohydrate diets: An evidence- and equity-based approach to dietary guidance

... Patients with a history of other neuropsychiatric disorders, such as depression (OR = 1.688) and psychoses (OR = 1.501), were found to be at higher risk of developing pain following BC surgery. Other comorbidities such as metastatic cancer (OR = 1.293), weight loss (OR = 1.701), and chronic pulmonary disease (OR = 1.340) have previosuly been documented as factors predisposing to postoperative pain [44,45]. Interestingly, patients older than 60 years (OR = 0.638), urban hospital (OR = 0.694), private insurance (OR = 0.688), elective admission (OR = 0.797), and solid tumor without metastasis (OR = 0.675) yielded a protective effect against postoperative pain, although the reasons are unknown and could be multifaceted. ...

Does Medically Supervised Weight Loss Prior to Total Knee Arthroplasty Improve Patient-Reported Pain and Physical Function?
  • Citing Article
  • August 2023

The Journal of Arthroplasty

... However, inter-individual variations in metabolism, storage and excretion mean that in some cases similar biomarker values across individuals may not represent similar dietary intakes, and such biomarkers cannot accurately quantitate exposure but may differentiate between those who are consumers and non-consumers. More recently, the detection of plant DNA in stools has been used as a method to detect the presence of plant food intake 66 . Currently, dietary biomarkers are limited to a finite list of dietary constituents and can be expensive, and the validity and reproducibility sensitivity of some biomarkers remain suboptimal 67 . ...

Diversity of plant DNA in stool is linked to dietary quality, age, and household income

Proceedings of the National Academy of Sciences

... There are few sources in the literature concerning the increased risk of PJI linked to rapid weight loss. The study by Rechenmacher AJ et al. [70] argues that a weight loss of more than 5 per cent of the initial BMI in 6 months may expose one to a greater likelihood of complications than a loss of the same but in 1 year. Further studies will be needed to define a minimum time limit that is safe and does not expose the obese patient to a greater risk of infection. ...

Does Preoperative Weight Loss Within 6 Months or 1 Year Change the Risk of Adverse Outcomes in Total Knee Arthroplasty by Initial Body Mass Index Classification?
  • Citing Article
  • June 2023

The Journal of Arthroplasty

... Another limitation is that our retention rate for the primary outcome was lower than we assumed in our power calculation despite offering multiple methods for participants to provide data, which may be an artifact of conducting the trial during the pandemic. Using a cellular-enabled scale for data capture and transmission may be a more effective approach to enhancing retention [67][68][69]. Finally, although none of our measured variables was associated with retention, retention may have been related to unmeasured variables associated with the experience of the pandemic, such as stress or caregiving responsibilities. ...

Comparison of weight captured via electronic health record and cellular scales to the gold‐standard clinical method

... Accordingly, the VA/ DoD Clinical Practice Guideline for the Management of Adult Overweight and Obesity recommends the use of varied dietary change approaches including low-and very low-carbohydrate diets to expand the menu of preference-sensitive treatment options (12). Our team is currently testing the weight loss and glycemic effectiveness of the VLC-DPP compared to the CDC's standard NDPP in a fully powered randomized controlled trial (42,63). These data may inform future efforts to implement, evaluate, and scale the VLC-DPP within VHA as one alternative to the standard MOVE! ...

Testing a very low-carbohydrate adaption of the Diabetes Prevention Program among adults with prediabetes: study protocol for the Lifestyle Education about prediabetes (LEAP) trial

Trials

... [1] The current debate mainly revolves around whether it is just sugar or also fat that should be avoided for a healthier BMI. [1,4,5] This has led to competing models of the nutritional basis of obesity. [1,[4][5][6] These include the "Carbohydrate Insulin Model" (CIM), the "Energy Balance Model" (EBM), and the more recently proposed "Fructose Survival Hypothesis" (FSH) for obesity. ...

Competing paradigms of obesity pathogenesis: energy balance versus carbohydrate-insulin models

European Journal of Clinical Nutrition

... Culinary ingredients, mainly consisting of fats and oils, formed the smallest portion of the diet for all groups. The KD group exhibited the highest intake of these ingredients, consistent with its low-carbohydrate, healthy-fat principles (Zinn, Rush, and Johnson 2018;Volek, Phinney, and Krauss 2021). In contrast, the vegan group had the lowest intake, aligning with their plantbased dietary preferences and typically lower saturated fat consumption (Bakaloudi et al. 2021;Melina, Craig, and Levin 2016). ...

Alternative Dietary Patterns for Americans: Low-Carbohydrate Diets

... Evidence from interventions involving overweight or obese adults suggests that reducing carbohydrate intake can effectively contribute to weight loss [41]. Despite ongoing debates, the carbohydrateinsulin model revealed that a high-refined carbohydrate diet can cause rapid spikes in blood sugar levels, causing elevated insulin secretion, which may promote fat deposition and inhibit fat breakdown, raising the risk of obesity [42]. Another possible explanation is the excessive consumption of poultry and red meat. ...

The carbohydrate-insulin model: A physiological perspective on the obesity pandemic

American Journal of Clinical Nutrition

... Studies exploring success in managing diabetes often relate it to how well a patient adheres to treatment [16,17] and whether they achieve a desired clinical outcome [1]. This is complicated by many different components that influence weight management over time, including biological factors, family and social culture, and the availability and accessibility of food options [18]. Tying success and failure to an individual's actions, and not the treatment approach or wider context may therefore be problematic. ...

Nutritional basis of type 2 diabetes remission

The BMJ