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Consensus has not been reached on what constitutes an optimal diet in individuals with prediabetes and type 2 diabetes mellitus (T2DM), especially between low-carbohydrate options.We compared 2 low-carbohydrate diets with 3 key similarities (incorporating nonstarchy vegetables and avoiding added sugars and refined grains) and 3 key differences (incorporating compared with avoiding legumes, fruits, and whole, intact grains) for their effects on glucose control and cardiometabolic risk factors in individuals with prediabetes and T2DM.Keto-Med was a randomized, crossover, interventional trial. Forty participants aged ≥18 years with prediabetes or T2DM followed the well-formulated ketogenic diet (WFKD) and the Mediterranean-plus diet (Med-Plus) for 12 weeks each, in random order. The diets shared the 3 key similarities noted above. The Med-Plus incorporated legumes, fruits, and whole, intact grains, while the WFKD avoided them. The primary outcome was the percentage change in glycated hemoglobin (HbA1c) after 12 weeks on each diet. Secondary and exploratory outcomes included percentage changes in body weight, fasting insulin, glucose, and blood lipids; average glucose from continuous glucose monitor (CGM), and nutrient intake.The primary analysis was of 33 participants with complete data. The HbA1c values did not differ between diets at 12 weeks. Triglycerides decreased more for the WFKD [percentage changes, -16% (SEM, 4%) compared with -5% (SEM, 6%) for the Med-Plus; P = 0.02] and LDL cholesterol was higher for the WFKD [percentage changes, +10% (SEM, 4%) compared with -5% (SEM, 5%) for the Med-Plus; P = 0.01]. Weight decreased 8% (SEM, 1%) compared with 7% (SEM, 1%) and HDL cholesterol increased 11% (SEM, 2%) compared with 7% (SEM, 3%) for the WFKD compared with the Med-Plus, respectively; however, there was a significant interaction of diet × order for both. Participants had lower intakes of fiber and 3 nutrients on the WFKD compared with the Med-Plus. Twelve-week follow-up data suggest the Med-Plus is more sustainable.HbA1c values were not different between diet phases after 12 weeks, but improved from baseline on both diets, likely due to several shared dietary aspects. The WFKD led to a greater decrease in triglycerides, but also had potential untoward risks from elevated LDL cholesterol and lower nutrient intakes from avoiding legumes, fruits, and whole, intact grains, as well as being less sustainable. This trial was registered at clinicaltrials.gov as NCT03810378.

The ketogenic diet (KD) is a low-carbohydrate, high-fat, adequate-protein diet proven to be effective for the reversal of obesity, metabolic syndrome and type 2 diabetes, and holding therapeutic potential for the prevention and treatment of other chronic diseases. Genetic and dynamic markers of KD response may help to identify individuals most likely to benefit from KD and point to individuals at higher risk for adverse health outcomes. Here, we provide a clinician-friendly review of state-of-the-art research on biomarkers of KD response for a variety of outcomes including weight loss, body composition and cognitive performance drawing data from both intervention trials and case reports of rare inborn errors of metabolism. We also present a selection of the most promising candidate genes to evaluate in future studies and discuss key aspects of study design and variant interpretation that may help accelerate the implementation of these biomarkers in clinical practice.

Background/objectives Biological sex factors and sociocultural gender norms affect the physiology and behavior of weight loss. However, most diet intervention studies do not report outcomes by sex, thereby impeding reproducibility. The objectives of this study were to compare 12-month changes in body weight and composition in groups defined by diet and sex, and adherence to a healthy low carbohydrate (HLC) vs. healthy low fat (HLF) diet. Participants/methods This was a secondary analysis of the DIETFITS trial, in which 609 overweight/obese nondiabetic participants (age, 18–50 years) were randomized to a 12-month HLC (n = 304) or HLF (n = 305) diet. Our first aim concerned comparisons in 12-month changes in weight, fat mass, and lean mass by group with appropriate adjustment for potential confounders. The second aim was to assess whether or not adherence differed by diet-sex group (HLC women n = 179, HLC men n = 125, HLF women n = 167, HLF men n = 138). Results 12-month changes in weight (p P p = 0.02). Weight loss estimates within group remained similar after adjusting for adherence, suggesting adherence was not a mediator. Conclusions By reporting outcomes by sex significant weight loss differences were identified between HLC and HLF, which were not recognized in the original primary analysis. These findings highlight the need to consider sex in the design, analysis, and reporting of diet trials.

The working definition of health is often the simple absence of diagnosed disease. This common standard is limiting given that changes in functional health status represent early warning signs of impending health declines. Longitudinal assessment of functional health status may foster prevention of disease occurrence and modify disease progression. The LIFEHOUSE (Lifestyle Intervention and Functional Evaluation-Health Outcomes SurvEy) longitudinal research project explores the impact of personalized lifestyle medicine approaches on functional health determinants. Utilizing an adaptive tent–umbrella–bucket design, the LIFEHOUSE study follows the functional health outcomes of adult participants recruited from a self-insured employee population. Participants were each allocated to the tent of an all-inclusive N-of-one case series. After assessing medical history, nutritional physical exam, baseline functional status (utilizing validated tools to measure metabolic, physical, cognitive, emotional and behavioral functional capacity), serum biomarkers, and genomic and microbiome markers, participants were assigned to applicable umbrellas and buckets. Personalized health programs were developed and implemented using systems biology formalism and functional medicine clinical approaches. The comprehensive database (currently 369 analyzable participants) will yield novel interdisciplinary big-health data and facilitate topological analyses focusing on the interactome among each participant’s genomics, microbiome, diet, lifestyle and environment.

In 2015, the Dietary Guidelines for Americans (DGA) eliminated the historical upper limit of 300 mg of dietary cholesterol/day and shifted to a more general recommendation that cholesterol intake should be limited. The primary aim of this secondary analysis of the Diet Intervention Examining the Factors Interacting With Treatment Success (DIETFITS) weight loss diet trial was to evaluate the associations between 12-month changes in dietary cholesterol intake (mg/day) and changes in plasma lipids, particularly low-density lipoprotein (LDL) cholesterol for those following a healthy low-carbohydrate (HLC) diet. Secondary aims included examining high-density lipoprotein (HDL) cholesterol and triglycerides and changes in refined grains and added sugars. The DIETFITS trial randomized 609 healthy adults aged 18–50 years with body mass indices of 28–40 kg/m2 to an HLC or healthy low-fat (HLF) diet for 12 months. Linear regressions examined the association between 12-month change in dietary cholesterol intake and plasma lipids in 208 HLC participants with complete diet and lipid data, adjusting for potential confounding variables. Baseline dietary cholesterol intake was 322 ± 173 (mean ± SD). At 12 months, participants consumed an average of 460 ± 227 mg/day of dietary cholesterol, 76% consumed over the previously recommended limit of 300 mg/day. Twelve-month changes in cholesterol intake were not significantly associated with 12-month changes in LDL-C, HDL-C, or triglycerides. Diet recall data suggested participants’ increase in dietary cholesterol was partly due to replacing refined grains and sugars with eggs. An increase in daily dietary cholesterol intake to levels substantially above the previous 300 mg upper limit was not associated with a negative impact on lipid profiles in the setting of a healthy, low-carbohydrate weight loss diet.

Background For low-carbohydrate diets, a public health approach has focused on the replacement of carbohydrates with unsaturated fats. However, little research exists on the impacts of saturated fat intake on the lipid profile in the context of whole-food-based low-carbohydrate weight-loss diets.

The goal of the 2018 American Society for Parenteral and Enteral Nutrition (ASPEN) Research Workshop was to explore the influence of nutrition and dietary exposure to xenobiotics on the epigenome during critical periods in development and how these exposures influence both disease incidence and severity transgenerationally. A growing compendium of research indicates that the incidence and severity of common and costly human diseases may be influenced by dietary exposures and deficiencies that modify the epigenome. The greatest periods of vulnerability to these exposures are the periconception period and early childhood. Xenobiotics in the food chain, protein malnutrition, and methyl donor deficiencies could have a profound bearing on the risk of developing heart disease, diabetes, obesity, hypertension, and mental illness over multiple generations. The financial impact and the life burden of these diseases are enormous. These and other aspects of nutrition, epigenetics, and health are explored in this research workshop.

The loading of small interfering RNAs (siRNAs) and microRNAs into Argonaute proteins is enhanced by Hsp90 and ATP in diverse eukaryotes. However, whether this loading also occurs independently of Hsp90 and ATP remains unclear. We show that the Tetrahymena Hsp90 co-chaperone Coi12p promotes siRNA loading into the Argonaute protein Twi1p in both ATP-dependent and ATP-independent manners in vitro. The ATP-dependent activity requires Hsp90 and the tetratricopeptide repeat (TPR) domain of Coi12p, whereas these factors are dispensable for the ATP-independent activity. Both activities facilitate siRNA loading by counteracting the Twi1p-binding protein Giw1p, which is important to specifically sort the 26- to 32-nt siRNAs to Twi1p. Although Coi12p lacking its TPR domain does not bind to Hsp90, it can partially restore the siRNA loading and DNA elimination defects of COI12 knockout cells, suggesting that Hsp90- and ATP-independent loading of siRNA occurs in vivo and plays a physiological role in Tetrahymena.

Aim: Obesity results from the interaction of genetic and environmental factors, which may involve epigenetic mechanisms such as DNA methylation (DNAm). Materials & methods: We have followed the PRISMA protocol to select studies that analyzed DNAm at baseline and end point of a weight loss intervention using either candidate-locus or genome-wide approaches. Results: Six genes displayed weight loss associated DNAm across four out of nine genome-wide studies. Weight loss is associated with significant but small changes in DNAm across the genome, and weight loss outcome is associated with individual differences in baseline DNAm at several genomic locations. Conclusion: The identified weight loss associated DNAm markers, especially those showing reproducibility across different studies, warrant validation by further studies with robust design and adequate power.

Tetrahymena eliminates micronuclear-limited sequences from the developing macronucleus during sexual reproduction. Homology between the sequences to be eliminated and ∼28-nucleotide small RNAs (scnRNAs) associated with an Argonaute family protein Twi1p likely underlies this elimination process. However, the mechanism by which Twi1p–scnRNA complexes identify micronuclear-limited sequences is not well understood. We show that a Twi1p-associated putative RNA helicase Ema1p is required for the interaction between Twi1p and chromatin. This requirement explains the phenotypes of EMA1 KO strains, including loss of selective down-regulation of scnRNAs homologous to macronuclear-destined sequences, loss of H3K9 and K27 methylation in the developing new macronucleus, and failure to eliminate DNA. We further demonstrate that Twi1p interacts with noncoding transcripts derived from parental and developing macronuclei and this interaction is greatly reduced in the absence of Ema1p. We propose that Ema1p functions in DNA elimination by stimulating base-pairing interactions between scnRNAs and noncoding transcripts in both parental and developing new macronuclei.