Dietary Fat Restriction Research Articles

Weight loss and metabolic effects of an ALDH1A1-specific inhibitor, FSI-TN42, in a diet induced mouse model of obesity.

Retinoic acid (RA) participates in weight regulation and energy metabolism. Mice lacking ALDH1A1, one of the major enzymes responsible for RA biosynthesis, are resistant to diet-induced obesity. Previously, we identified FSI-TN42 (N42) as an ALDH1A1-specific inhibitor and reported its pharmacokinetics and pharmacodynamics as well as its efficacy in weight suppression. In the first study, C57BL/6 J male mice were fed a high fat diet for 8 weeks to induce obesity. Mice were then divided into three groups and fed (1) moderate fat diet (MFD), (2) MFD + WIN 18,446 (1 g/kg diet), or (3) MFD + N42 (1 g/kg diet) for 8 weeks. A control group of mice were fed a low-fat diet for the entire period. Mice were weighed weekly and fasting glucose was determined every 4 weeks. Tissues were examined for potential toxicity using histopathology and complete blood counts. In the second study, we examined influences of N42 on energy balance and/or appetite by determining food intake, activity and energy expenditure in mice with obesity treated with MFD or MFD + N42. Lastly, we tested fertility with a mating study. N42 significantly accelerated weight loss compared to MFD alone in mice with obesity by reducing fat mass without decreasing lean mass. N42 did not alter food intake or activity levels. While mice treated with N42 lost significantly more weight, they maintained a similar level of energy expenditure compared to mice fed MFD only. Mice fed N42 preferentially used fat postprandially, especially under thermoneutral or mild cold challenge. N42 did not affect male fertility. N42 promotes weight loss when used with MFD in mice with diet-induced obesity without causing significant organ toxicity or male infertility. Future studies will determine if N42 can be used to promote further weight loss if combined with current weight loss drugs.

8077 Use of Lovaza for Management of Hypertriglyceridemia in Pregnancy

Abstract Disclosure: J. Segarra-Villafane: None. L.R. Sepulveda-Garcia: None. L. El Musa Penna: None. I.C. Arroyo: None. Z. Maisonet -Feliciano: None. W. Medina-Torres: None. M. Alvarado: None. M. Ramirez: None. L.A. Gonzalez-Rodriguez: None. Severe hypertriglyceridemia in pregnancy increases the risk of health complications to both mother and fetus, including preeclampsia, hyperviscosity syndrome and life-threatening pancreatitis. Several case reports include management of hypertriglyceridemia in pregnancy with medical nutrition therapy, omega fatty acids and gemfibrozil but is controversial. There are no formal clinical guidelines for management of severe hypertriglyceridemia in pregnancy which presents a challenge for physicians. Lovaza is a combination of ethyl esters of omega 3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) indicated as an adjunct to diet to reduce triglycerides (TG) levels in adult patients with severe hypertriglyceridemia. Lovaza is Category C (risk cannot be ruled out) and should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus. Case of a 40 years old female G3P1A1 with IUP 25 WGA with history of hypothyroidism, dyslipidemia and episode of acute pancreatitis in 2016 due to hypertriglyceridemia, who was referred to clinics due to uncontrolled lipids and thyroid disease. Laboratories included fasting serum triglycerides (TG) 4357mg/dL (40-150mg/dL), total cholesterol 525mg/dL (120-200), HDL 56mg/dL, LDL invalid due to elevated TG. Thyroid function test revealed TSH of 161uIU/mL (0.43-2.91) and FT4 of 0.24ng/dL (0.8-1.8). HbA1c, lipase and amylase within range. Vital signs were normal. Patient was asymptomatic, no abdominal complaints or hypothyroidism-related symptoms, but hospital admission was recommended due to high risk of pancreatitis and uncontrolled hypothyroidism. She was started on Synthroid 220 mcg IV daily for hypothyroidism and was placed NPO until nutritionist evaluation. Triglycerides levels improved with conservative interventions and low-fat diet. However, TG persisted above 2000mg/dL and, after discussing risks and benefits with patient, pharmacological therapy with Lovaza was started to reach goal of TG less than 1000 mg/dL and reduce potential risk of pancreatitis. Patient agreed to start Lovaza 2gm AM and 2gm PM. After initiation of Lovaza, in addition to dietary modifications and hypothyroidism management, laboratories showed significant improvement in TG levels from 3569 down to 1778 mg/dL. Patient was discharged on Lovaza 2gm oral BID and Synthroid 200mcg oral daily. One month later, TG had decreased to 557mg/dL (0-150) and thyroid tests showed TSH at 0.305mIU/mL and FT4 at 1.71ng/dL. Patient tolerated medications well without side effects and had an uncomplicated pregnancy and delivery. This case demonstrates that severe hypertriglyceridemia during pregnancy can be managed effectively and, more importantly, in a safe manner with Lovaza, in addition to dietary fat restriction. However, additional research is needed if its use is to be included in future pregnancy management guidelines. Presentation: 6/2/2024

Evaluation of Nutritional Preferences of School-Age Children and Parents Attitudes Towards Child Nutrition: A Cross-Sectional Study

Objective: This study aimed to examine the nutrition of school-age children and the influence of their parents. Method: The study involved 259 school-age children aged 9-12 and their volunteering parents from a province in Türkiye. A questionnaire was administered to the children questioning sociodemographic data and basic nutritional information, anthropometric measurements were taken, and the Parent Mealtime Action Scale was applied to their parents. The obtained data were analyzed in SPSS 26 program. Results: It was found that the snack consumption status of children was related to the income status of the family's daily fruit and vegetable consumption (p<0.01). It has been found that animal fat restricted diet is associated with growth status in children (p<0.01). It has been determined that the children's eating situation is related to the persistent behavior of parents (p<0.05). It has been found that children who do not consume chips at all are also fed restricted animal fats in their daily diet. It was determined that bagel/cereal consumption was also excessive in children in whom rewarding was applied excessively (p<0.05). Conclusion: As a result, it was determined that school-age children's own preferences in food choices, as well as the parent's behavior and educational status, and the family's income level also have a significant impact. It is thought that it will be beneficial to provide nutrition education to parents and children in order to develop the right eating habits in school-age children and to increase the level of nutrition knowledge.

Unraveling cysteine deficiency-associated rapid weight loss.

Forty percent of the US population and 1 in 6 individuals worldwide are obese, and the incidence of this disease is surging globally1,2. Various dietary interventions, including carbohydrate and fat restriction, and more recently amino acid restriction, have been explored to combat this epidemic3-6. We sought to investigate the impact of removing individual amino acids on the weight profiles of mice. Compared to essential amino acid restriction, induction of conditional cysteine restriction resulted in the most dramatic weight loss, amounting to 20% within 3 days and 30% within one week, which was readily reversed. This weight loss occurred despite the presence of substantial cysteine reserves stored in glutathione (GSH) across various tissues7. Further analysis demonstrated that the weight reduction primarily stemmed from an increase in the utilization of fat mass, while locomotion, circadian rhythm and histological appearance of multiple other tissues remained largely unaffected. Cysteine deficiency activated the integrated stress response (ISR) and NRF2-mediated oxidative stress response (OSR), which amplify each other, leading to the induction of GDF15 and FGF21, hormones associated with increased lipolysis, energy homeostasis and food aversion8-10. We additionally observed rapid tissue coenzyme A (CoA) depletion, resulting in energetically inefficient anaerobic glycolysis and TCA cycle, with sustained urinary excretion of pyruvate, orotate, citrate, α-ketoglutarate, nitrogen rich compounds and amino acids. In summary, our investigation highlights that cysteine restriction, by depleting GSH and CoA, exerts a maximal impact on weight loss, metabolism, and stress signaling compared to other amino acid restrictions. These findings may pave the way for innovative strategies for addressing a range of metabolic diseases and the growing obesity crisis.

Lipidome changes due to improved dietary fat quality inform cardiometabolic risk reduction and precision nutrition

Current cardiometabolic disease prevention guidelines recommend increasing dietary unsaturated fat intake while reducing saturated fats. Here we use lipidomics data from a randomized controlled dietary intervention trial to construct a multilipid score (MLS), summarizing the effects of replacing saturated fat with unsaturated fat on 45 lipid metabolite concentrations. In the EPIC-Potsdam cohort, a difference in the MLS, reflecting better dietary fat quality, was associated with a significant reduction in the incidence of cardiovascular disease (−32%; 95% confidence interval (95% CI): −21% to −42%) and type 2 diabetes (−26%; 95% CI: −15% to −35%). We built a closely correlated simplified score, reduced MLS (rMLS), and observed that beneficial rMLS changes, suggesting improved dietary fat quality over 10 years, were associated with lower diabetes risk (odds ratio per standard deviation of 0.76; 95% CI: 0.59 to 0.98) in the Nurses’ Health Study. Furthermore, in the PREDIMED trial, an olive oil-rich Mediterranean diet intervention primarily reduced diabetes incidence among participants with unfavorable preintervention rMLS levels, suggestive of disturbed lipid metabolism before intervention. Our findings indicate that the effects of dietary fat quality on the lipidome can contribute to a more precise understanding and possible prediction of the health outcomes of specific dietary fat modifications.

Early diagnosis and treatment by newborn screening (NBS) or family history is associated with improved visual outcomes for long-chain 3-hydroxyacylCoA dehydrogenase deficiency (LCHADD) chorioretinopathy.

Long chain 3-hydroxyacyl-CoA dehydrogenase (LCHADD) is the only fatty acid oxidation disorder to develop a progressive chorioretinopathy resulting in vision loss; newborn screening (NBS) for this disorder began in the United States around 2004. We compared visual outcomes among 40 participants with LCHADD or trifunctional protein deficiency diagnosed symptomatically to those who were diagnosed via NBS or a family history. Participants completed ophthalmologic testing including measures of visual acuity, electroretinograms (ERG), fundal imaging, contrast sensitivity, and visual fields. Records were reviewed to document medical and treatment history. Twelve participants presented symptomatically with hypoglycemia, failure to thrive, liver dysfunction, cardiac arrest, or rhabdomyolysis. Twenty eight were diagnosed by NBS or due to a family history of LCHADD. Participants diagnosed symptomatically were older but had similar percent males and genotypes as those diagnosed by NBS. Treatment consisted of fasting avoidance, dietary long-chain fat restriction, MCT, C7, and/or carnitine supplementation. Visual acuity, rod- and cone-driven amplitudes on ERG, contrast sensitivity scores, and visual fields were all significantly worse among participants diagnosed symptomatically compared to NBS. In mixed-effects models, both age and presentation (symptomatic vs. NBS) were significant independent factors associated with visual outcomes. This suggests that visual outcomes were improved by NBS, but there was still lower visual function with advancing age in both groups. Early diagnosis and treatment by NBS is associated with improved visual outcomes and retinal function compared to participants who presented symptomatically. Despite the impact of early intervention, chorioretinopathy was greater with advancing age, highlighting the need for novel treatments.

Impact of dietary carbohydrate, fat or protein restriction on the human gut microbiome: a systematic review.

Restriction of dietary carbohydrates, fat and/or protein is often used to reduce body weight and/or treat (metabolic) diseases. Since diet is a key modulator of the human gut microbiome, which plays an important role in health and disease, this review aims to provide an overview of current knowledge of the effects of macronutrient-restricted diets on gut microbial composition and metabolites. A structured search strategy was performed in several databases. After screening for inclusion and exclusion criteria, thirty-six articles could be included. Data are included in the results only when supported by at least three independent studies to enhance the reliability of our conclusions. Low-carbohydrate (<30 energy%) diets tended to induce a decrease in the relative abundance of several health-promoting bacteria, including Bifidobacterium, as well as a reduction in short-chain fatty acid (SCFA) levels in faeces. In contrast, low-fat diets (<30 energy%) increased alpha diversity, faecal SCFA levels and abundance of some beneficial bacteria, including Faecalibacterium prausnitzii. There were insufficient data to draw conclusions concerning the effects of low-protein (<10 energy%) diets on gut microbiota. Although the data of included studies unveil possible benefits of low-fat and potential drawbacks of low-carbohydrate diets for human gut microbiota, the diversity in study designs made it difficult to draw firm conclusions. Using a more uniform methodology in design, sample processing and sharing raw sequence data could foster our understanding of the effects of macronutrient restriction on gut microbiota composition and metabolic dynamics relevant to health. This systematic review was registered at https://www.crd.york.ac.uk/prospero as CRD42020156929.

High-Dose ERT, Rituximab, and Early HSCT in an Infant with Wolman’s Disease

SummaryWolman’s disease, a severe form of lysosomal acid lipase deficiency, leads to pathologic lipid accumulation in the liver and gut that, without treatment, is fatal in infancy. Although continued enzyme-replacement therapy (ERT) in combination with dietary fat restriction prolongs life, its therapeutic effect may wane over time. Allogeneic hematopoietic stem-cell transplantation (HSCT) offers a more definitive solution but carries a high risk of death. Here we describe an infant with Wolman’s disease who received high-dose ERT, together with dietary fat restriction and rituximab-based B-cell depletion, as a bridge to early HSCT. At 32 months, the infant was independent of ERT and disease-free, with 100% donor chimerism in the peripheral blood.

Breaking the chains of lipoprotein lipase deficiency: A pediatric perspective on the efficacy and safety of Volanesorsen

RationaleLipoprotein lipase (LPL) deficiency, a rare inherited metabolic disorder, is characterized by high triglyceride (TG) levels and life-threatening acute pancreatitis. Current treatment for pediatric patients involves a lifelong severely fat-restricted diet, posing adherence challenges. Volanesorsen, an EMA-approved RNA therapy for adults, effectively reduces TG levels by decreasing the production of apolipoprotein C-III. This 96-week observational open-label study explores Volanesorsen's safety and efficacy in a 13-year-old female with LPL deficiency. MethodsThe patient, with a history of severe TG elevations, 53 hospital admissions, and life-threatening recurrent pancreatitis despite dietary restrictions, received weekly subcutaneous Volanesorsen injections. We designed a protocol for this investigator-initiated study, primarily focusing on changes in fasting TG levels and hospital admissions. ResultsWhile the injections caused occasional pain and swelling, no other adverse events were observed. TG levels decreased during treatment, with more measurements below the pancreatitis risk threshold compared to pre-treatment. No hospital admissions occurred in the initial 14 months of treatment, contrasting with 21 admissions in the 96 weeks before. In the past 10 months, two pancreatitis episodes may have been linked to dietary noncompliance. Dietary restrictions were relaxed, increasing fat intake by 65% compared to baseline. While not fully reflected in the PedsQL, both parents and the patient narratively reported an improved quality of life. ConclusionThis study demonstrates, for the first time, that Volanesorsen is tolerated in a pediatric patient with severe LPL deficiency and effectively lowers TG levels, preventing life-threatening complications. This warrants consideration for expanded access in this population.

Modified dietary fat intake for treatment of gallstone disease in people of any age.

The prevalence of gallstones varies between less than 1% and 64% in different populations and is thought to be increasing in response to changes in nutritional intake and increasing obesity. Some people with gallstones have no symptoms but approximately 2% to 4% develop them each year, predominantly including severe abdominal pain. People who experience symptoms have a greater risk of developing complications. The main treatment for symptomatic gallstones is cholecystectomy. Traditionally, a low-fat diet has also been advised to manage gallstone symptoms, but there is uncertainty over the evidence to support this. To evaluate the benefits and harms of modified dietary fat intake in the treatment of gallstone disease in people of any age. We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials in the Cochrane Library, MEDLINE ALL Ovid, Embase Ovid, and three other databases to 17 February 2023 to identify randomised clinical trials in people with gallstones. We also searched online trial registries and pharmaceutical company sources, for ongoing or unpublished trials to March 2023. We included randomised clinical trials (irrespective of language, blinding, or status) in people with gallstones diagnosed using ultrasonography or conclusive imaging methods. We excluded participants diagnosed with another condition that may compromise dietary fat tolerance. We excluded trials where data from participants with gallstones were not reported separately from data from participants who did not have gallstones. We included trials that investigated other interventions (e.g. trials of drugs or other dietary (non-fat) components) providing that the trial groups had received the same proportion of drug or other dietary (non-fat) components in the intervention. We intended to undertake meta-analysis and present the findings according to Cochrane recommendations. However, as we identified only five trials, with data unsuitable and insufficient for analyses, we described the data narratively. We included five trials but only one randomised clinical trial (69 adults), published in 1986, reported outcomes of interest to the review. The trial had four dietary intervention groups, three of which were relevant to this review. We assessed the trial at high risk of bias. The dietary fat modifications included a modified cholesterol intake and medium-chain triglyceride supplementation. The control treatment was a standard diet. The trial did not report on any of the primary outcomes in this review (i.e. all-cause mortality, serious adverse events, and health-related quality of life). The trial reported on gallstone dissolution, one of our secondary outcomes. We were unable to apply the GRADE approach to determine certainty of evidence because the included trial did not provide data that could be used to generate an estimate of the effect on this or any other outcome. The trial expressed its finding as "no significant effect of a low-cholesterol diet in the presence of ursodeoxycholic acid on gallstone dissolution." There were no serious adverse events reported. The included trial reported that they received no funding that could bias the trial results through conflicts of interest. We found no ongoing trials. The evidence about the effects of modifying dietary fat on gallstone disease versus standard diet is scant. We lack results from high-quality randomised clinical trials which investigate the effects of modification of dietary fat and other nutrient intakes with adequate follow-up. There is a need for well-designed trials that should include important clinical outcomes such as mortality, quality of life, impact on dissolution of gallstones, hospital admissions, surgical intervention, and adverse events.

Long-term clinical outcomes and management of hypertriglyceridemia in children with Apo-CII deficiency

Background and aimAPO CII, one of several cofactors which regulate lipoprotein lipase enzyme activity, plays an essential role in lipid metabolism. Deficiency of APO CII is an ultra-rare autosomal recessive cause of familial chylomicronemia syndrome. We present the long-term clinical outcomes of 12 children with APO CII deficiency. Methods and resultsThe data of children with genetically confirmed APO CII deficiency were evaluated retrospectively. Twelve children (8 females) with a mean follow-up of 10.1 years (±3.9) were included. At diagnosis, the median age was 60 days (13 days-10 years). Initial clinical findings included lipemic serum (41.6%), abdominal pain (41.6%), and vomiting (16.6%). At presentation, the median triglyceride (TG) value was 4341 mg/dL (range 1277–14,110). All patients were treated with a restricted fat diet, medium-chain triglyceride (MCT), and omega-3-fatty acids. In addition, seven patients (58.3%) received fibrate. Fibrate was discontinued in two patients due to rhabdomyolysis and in one patient because of cholelithiasis. Seven (58.3%) patients experienced pancreatitis during the follow-up period. One female experienced recurrent pancreatitis and was treated with fresh frozen plasma (FFP). ConclusionsApo CII deficiency is an ultra-rare autosomal recessive condition of hypertriglyceridemia associated with significant morbidity and mortality. Low-fat diet and MCT supplementation are the mainstays of therapy, while the benefit of TG-lowering agents are less well-defined.

PNPLA3 Genotype and Dietary Fat Modify Concentrations of Plasma and Fecal Short Chain Fatty Acids and Plasma Branched-Chain Amino Acids.

The GG genotype of the Patatin-like phosphatase domain-containing 3 (PNPLA3), dietary fat, short-chain fatty acids (SCFA) and branched-chain amino acids (BCAA) are linked with non-alcoholic fatty liver disease. We studied the impact of the quality of dietary fat on plasma (p) and fecal (f) SCFA and p-BCAA in men homozygous for the PNPLA3 rs738409 variant (I148M). Eighty-eight randomly assigned men (age 67.8 ± 4.3 years, body mass index 27.1 ± 2.5 kg/m2) participated in a 12-week diet intervention. The recommended diet (RD) group followed the National and Nordic nutrition recommendations for fat intake. The average diet (AD) group followed the average fat intake in Finland. The intervention resulted in a decrease in total p-SCFAs and iso-butyric acid in the RD group (p = 0.041 and p = 0.002). Valeric acid (p-VA) increased in participants with the GG genotype regardless of the diet (RD, 3.6 ± 0.6 to 7.0 ± 0.6 µmol/g, p = 0.005 and AD, 3.8 ± 0.3 to 9.7 ± 8.5 µmol/g, p = 0.015). Also, genotype relation to p-VA was seen statistically significantly in the RD group (CC: 3.7 ± 0.4 to 4.2 ± 1.7 µmol/g and GG: 3.6 ± 0.6 to 7.0 ± 0.6 µmol/g, p = 0.0026 for time and p = 0.004 for time and genotype). P-VA, unlike any other SCFA, correlated positively with plasma gamma-glutamyl transferase (r = 0.240, p = 0.025). Total p-BCAAs concentration changed in the AD group comparing PNPLA3 CC and GG genotypes (CC: 612 ± 184 to 532 ± 149 µmol/g and GG: 587 ± 182 to 590 ± 130 µmol/g, p = 0.015 for time). Valine decreased in the RD group (p = 0.009), and leucine decreased in the AD group (p = 0.043). RD decreased total fecal SCFA, acetic acid (f-AA), and butyric acid (f-BA) in those with CC genotype (p = 0.006, 0.013 and 0.005, respectively). Our results suggest that the PNPLA3 genotype modifies the effect of dietary fat modification for p-VA, total f-SCFA, f-AA and f-BA, and total p-BCAA.

Dietary "Beigeing" Fat Contains More Phosphatidylserine and Enhances Mitochondrial Function while Counteracting Obesity.

Activation of mitochondrial function and heat production in adipose tissue by the modification of dietary fat is a promising strategy against obesity. However, as an important source of lipids for ketogenic and daily diets, the function of fats extracted from different adipose tissue sites was largely unknown. In this study, we illustrated the function of fats extracted from adipose tissues with different "beigeing" properties in the ketogenic diet and identified lipid profiles of fats that facilitate energy expenditure. We found that the anti-obesity effect of ketogenic diets was potentiated by using "beigeing" fat [porcine subcutaneous adipose tissue (SAT)] as a major energy-providing ingredient. Through lipidomic analyses, phosphatidylserine (PS) was identified as a functional lipid activating thermogenesis in adipose tissue. Moreover, invivo studies showed that PS induces adipose tissue thermogenesis and alleviates diet-induced obesity in mice. Invitro studies showed that PS promotes UCP1 expression and lipolysis of adipocytes. Mechanistically, PS promoted mitochondrial function in adipocytes via the ADCY3-cAMP-PKA-PGC1α pathway. In addition, PS-PGC1a binding may affect the stability of the PGC1α protein, which further augments PS-induced thermogenesis. These results demonstrated the efficacy of dietary SAT fats in diminishing lipid accumulation and the underlying molecular mechanism of PS in enhancing UCP1 expression and mitochondrial function. Thus, our findings suggest that as dietary fat, "beigeing" fat provides more beneficial lipids that contribute to the improvement of mitochondrial function, including PS, which may become a novel, nonpharmacological therapy to increase energy expenditure and counteract obesity and its related diseases.

Hepatic Safety in Rats Fed on Fructose, Glucose, or Sucrose When Combine with A Moderate Fat Diet

Hepatic Safety in Rats Fed on Fructose, Glucose, or Sucrose When Combine with A Moderate Fat Diet

Long-Term Nutritional Counseling for a Patient with Lipoprotein Lipase Deficiency.

A one-year-and-nine-month-old Japanese boy was admitted with hypertriglyceridemia (fasting triglycerides 2548 mg/dL). After close examination, he was diagnosed with lipoprotein lipase (LPL) deficiency (compound heterozygous) and was immediately started on a fat-restricted dietary therapy. He responded well to the regimen (1200 kcal/day, 20 g fat/day) and his triglycerides decreased to 628 mg/dL within 7 days of starting the dietary therapy. It was decided to manage his illness without using any drugs because he was still an infant and responded well to a fat-restricted diet. During his hospital stay, dietitians provided him with nutritional counseling using a food exchange list, which was designed to easily calculate the fat content by including foods that are commonly served. His family quickly learned the skills to prepare a fat-restricted diet. Moreover, since dietary restrictions may have impaired the child's growth and development, the dietitians continued to intervene regularly after the child was discharged from the hospital. The dietitians confirmed that the patient was receiving nutritional intake appropriate for his growth and discussed the dietary concerns in his daily life and how to participate in school events that involved eating and drinking. Nutritional counseling was provided every 3-4 months from disease onset to age 23 years, except for a 14-month break at age 20 years. The patient grew up without developing acute pancreatitis, a serious complication of LPL deficiency. The long-term intervention of dieticians is necessary to achieve a balance between living on a strict diet for disease management and ensuring appropriate nutritional intakes for growth/development.

Greater adherence to the Dietary Guidelines for Americans is associated with lower diet-related greenhouse gas emissions but higher costs.

Few studies have evaluated the sustainability of popular diet patterns in the US, which limits policy action and impedes consumer efficacy to make sustainable dietary changes. This study filled this gap by evaluating the relationship between diet quality, greenhouse gas emissions (GHGE), and diet cost for plant-based, restricted carbohydrate, low grain, low fat, and time restricted diet patterns. Dietary data were retrieved from the National Health and Nutrition Examination Survey (2011-2018, n = 8,146) and linked with data on GHGE and food prices from publicly available databases. Diet quality was measured using the Healthy Eating Index-2015. The present study (1) compared the mean diet quality, GHGE, and diet cost between diet patterns, (2) evaluated the association of diet quality to GHGE and diet cost for each diet pattern, and (3) estimated the contribution of food sources to GHGE and diet cost for each diet pattern. Higher diet quality was associated with lower GHGE for the general population and for most diet patterns (p < 0.01) except for the plant-based and time restricted diet patterns (p > 0.05). Higher diet quality was associated with higher cost for the general population and for all dietary patterns (p < 0.01) except the time restricted diet pattern (p > 0.05). Protein foods, mostly beef, accounted for the largest share of GHGE (29-40%) and diet cost (28-47%) for all diet patterns except plant-based. Higher diet quality was associated with lower GHGE but was often accompanied by higher diet cost. These sustainability trade-offs can help inform major policy discussions in the US and shed light on further research needs in the area of food systems transformation.

Weight, insulin resistance, blood lipids, and diet quality changes associated with ketogenic and ultra low-fat dietary patterns: a secondary analysis of the DIETFITS randomized clinical trial.

The DIETFITS trial reported no significant difference in 12-month weight loss between a healthy low-fat and healthy low-carbohydrate diet. Participants were instructed to restrict fat or carbohydrates to levels consistent with a ketogenic or ultra low-fat diet for 2 months and to subsequently increase intakes until they achieved a comfortable maintenance level. To compare 3- and 12-month changes in body weight and cardiometabolic risk factors between a subsample of participants who reported 3-month fat or carbohydrates intakes consistent with either a ketogenic-like diet (KLD) or ultra low-fat diet (ULF). 3-month and 12-month weight and risk factor outcomes were compared between KLD (n = 18) and ULF (n = 21) sub-groups of DIETFITS participants (selected from n = 609, healthy overweight/obese, aged 18-50 years). Less than 10% of DIETFITS participants met KLD or ULF criteria at 3-months. Both groups achieved similar weight loss and insulin resistance improvements at 3-months and maintained them at 12- months. Significant differences at 3-months included a transient ~12% increase in LDL cholesterol (LDL-C) for KLD with a concomitant greater reduction in log(TG/HDL), a measure of LDL-C's atherogenic potential. The latter was maintained at 12-months, despite substantial diet recidivism for both groups, whereas LDL-C levels were similar for ULF at baseline and 12-months. KLD participants achieved and maintained the greatest reductions in added sugars and refined grains at 3- months and 12-months, whereas ULF participants reported a 50% increase in refined grains intake from baseline to 12-months. Among the ~10% of study participants that achieved the most extreme restriction of dietary fat vs. carbohydrate after 3 months, weight loss and improvement in insulin sensitivity were substantial and similar between groups. At 12 months, after considerable dietary recidivism, the few significant differences in diet quality and blood lipid parameters tended to favor KLD over ULF.

1792-PUB: Predictors of Weight Loss Variability in the COVID-19 Disrupted ACT1ON Diet Pilot in Young Adults with T1D

We reported that young adults with T1D and overweight or obesity lost equivalent weight when randomized to 3 months of a hypocaloric low carb or moderate low fat diet or an ad libitum Mediterranean diet. The remainder of the 9 month study was disrupted by COVID-19. We identified predictors of weight loss variability between study enrollment and completion/dropout, accounting for % of participant study time during COVID-19. Potential predictors of % weight loss were identified a priori and included in multivariate models when univariate correlations had a p-value &amp;lt;0.2. General linear models used backward elimination. We introduced variables in groups (order: demographic and design, clinical, behavioral); the variable with the highest p-value was sequentially removed until those with p&amp;lt;0.2 remained. Crude weight changed by -0.87% (95%CI -2.6, 0.85, p=0.31, n=48) over 12 months (IQR 10.8, 12.9). Accounting for % COVID-19 time and study duration, 26.3% (model p=0.07) of weight loss variability was collectively explained by employment status (full-time lost less weight than unemployed), age at highest weight (weight loss decreased with younger age), education level (more weight loss with bachelor degree or higher than less education), and HbA1c (weight loss decreased with higher HbA1c, Table). Larger studies should confirm these findings and uncover additional predictors of weight loss success in T1D. Disclosure D.Igudesman: None. M.R.Kosorok: None. R.E.Pratley: Other Relationship; Bayer Inc., Corcept Therapeutics, Dexcom, Inc., Gasherbrum Bio, Inc., Hanmi Pharm. Co., Ltd., Hengrui (USA) Ltd., Merck Sharp &amp; Dohme Corp., Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. D.M.Maahs: Advisory Panel; Medtronic, LifeScan Diabetes Institute, MannKind Corporation, Consultant; Abbott, Research Support; Dexcom, Inc. E.J.Mayer-davis: None. A.Addala: None. J.Crandell: None. F.R.Muntis: None. D.P.Zaharieva: Advisory Panel; Dexcom, Inc., Research Support; Hemsley Charitable Trust, International Society for Pediatric and Adolescent Diabetes, Insulet Corporation, Speaker's Bureau; American Diabetes Association, Ascensia Diabetes Care, Medtronic. J.Thomas: None. K.Corbin: None. A.Casu: None. M.Kirkman: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (1DP3DK113358-01)

51-LB: Race Specific Effects of a Carbohydrate-Restricted Diet on Acute and Maximal C Peptide Response to Glucose in Adults with Type 2 Diabetes

Beta-cell response to glucose is compromised in individuals with type 2 diabetes (T2D), possibly due to lipid infiltration of the pancreas from excessive carbohydrate consumption. This study was conducted to determine if a eucaloric carbohydrate restricted diet (~9% energy from carbohydrate, 65% energy from fat), compared to a eucaloric fat restricted diet (~55% energy from carbohydrate, 20%energy from fat), would improve beta-cell response to glucose in participants with T2D. Participants were 43 African American and European American adults with T2D not using insulin. Medications were discontinued 1-2 weeks (depending upon the medication) prior to baseline testing. A hyperglycemic clamp was used to assess the acute (first-phase) and maximal (arginine-stimulated) C-peptide responses to glucose at baseline and after 12 weeks of controlled diet therapy (all food provided). Based on the detection of a race-by-diet interaction (P=0.06), data were analyzed within each race group. At 12 weeks, a significant effect of diet was observed by ANCOVA on acute C-peptide response in African Americans (2-fold greater with the carbohydrate restricted diet, P&amp;lt;0.05), and on maximal C-peptide response in European Americans (50% greater with the carbohydrate restricted diet, P&amp;lt;0.01), after adjusting for change in body weight. Paired t-test revealed an improvement in acute C-peptide response within African Americans on the carbohydrate restricted diet (P&amp;lt;0.01) from baseline to week 12, and an improvement in maximal C-peptide response within European Americans on the carbohydrate restricted diet (P&amp;lt;0.01). No changes in beta-cell function were observed in response to the fat restricted diet. These results suggest that a carbohydrate restricted diet has beneficial effects on beta-cell function that are race-specific and independent of weight loss. Disclosure B. Gower: Consultant; Abbott. A. M. Goss: Advisory Panel; Novo Nordisk, Consultant; Weight Watchers International. W. Garvey: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck &amp; Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Research Support; Novo Nordisk, Eli Lilly and Company, Epitomee, Pfizer Inc., Neurovalens. Funding National Institutes of Health (R01DK116726)

Optimal Fat-Modified Diet Duration for the Treatment of Postoperative Chylothorax in Children

BackgroundDietary modification is the mainstay of treatment for postoperative chylothorax in children. However, optimal fat-modified diet (FMD) duration to prevent recurrence is unknown. Our aim was to determine the association between FMD duration and chylothorax recurrence. MethodsRetrospective cohort study conducted across 6 pediatric cardiac intensive care units within the United States. Patients aged <18 years who developed chylothorax within 30 days after cardiac surgery between January 2020 and April 2022 were included. Patients with a Fontan palliation, who died, or were lost to follow-up or within 30 days of resuming a regular diet were excluded. FMD duration was defined as the first day of a FMD when chest tube output was <10 mL/kg/d without increasing until the resumption of a regular diet. Patients were classified into 3 groups (<3 weeks, 3-5 weeks, >5 weeks) based on FMD duration. ResultsA total of 105 patients were included: <3 weeks (n = 61) 3-5 weeks (n = 18), and >5 weeks (n = 26). Demographic, surgical, and hospitalization characteristics were not different across groups. In the >5 weeks group, chest tube duration was longer compared with the <3 weeks and 3-5 weeks groups (median, 17.5 days [interquartile range, 9-31] vs 10 and 10.5 days; P = .04). There was no recurrence of chylothorax within 30 days once chylothorax was resolving regardless of FMD duration. ConclusionsFMD duration was not associated with recurrence of chylothorax, suggesting that FMD duration can safely be shortened to at least <3 weeks from time of resolving chylothorax.