Strategies for minimizing muscle loss during use of incretin-mimetic drugs for treatment of obesity.

The rapid and widespread clinical adoption of highly effective incretin-mimetic drugs (IMDs), particularly semaglutide and tirzepatide, for the treatment of obesity has outpaced the updating of clinical practice guidelines. Consequently, many patients may be at risk for adverse effects and uncertain long-term outcomes related to the use of these drugs. Of emerging concern is the loss of skeletal muscle mass and function that can accompany rapid substantial weight reduction; such losses can lead to reduced functional and metabolic health, weight cycling, compromised quality of life, and other adverse outcomes.

Changes of Branched-Chain Amino Acids and Ectopic Fat in Response to Weight-loss Diets: the POUNDS Lost Trial.

Context: Recent evidence has related circulating branch-chained amino acids (BCAAs) to ectopic fat distribution.

Objective: To investigate the associations of changes in plasma BCAAs induced by weight-loss diet interventions with hepatic fat and abdominal fat, and potential modification by different diets.

Design, Setting, And Participants: The current study included 184 participants from the 2-year Preventing Overweight and Using Novel Dietary Strategies (POUNDS Lost) trial with repeated measurements on plasma BCAAs, hepatic fat, and abdominal fat over 2 years.

Pretreatment Fasting Glucose and Insulin as Determinants of Weight Loss on Diets Varying in Macronutrients and Dietary Fibers-The POUNDS LOST Study.

Efforts to identify a preferable diet for weight management based on macronutrient composition have largely failed, but recent evidence suggests that satiety effects of carbohydrates may depend on the individual's insulin-mediated cellular glucose uptake. Therefore, using data from the POUNDS LOST trial, pre-treatment fasting plasma glucose (FPG), fasting insulin (FI), and homeostatic model assessment of insulin resistance (HOMA-IR) were studied as prognostic markers of long-term weight loss in four diets differing in carbohydrate, fat, and protein content, while assessing the role of dietary fiber intake. Subjects with FPG <100 mg/dL lost 2.

A Randomized, Double-Blind, Placebo-Controlled Study of Gelesis100: A Novel Nonsystemic Oral Hydrogel for Weight Loss.

Objective: This study aims to assess the efficacy and safety of Gelesis100, a novel, nonsystemic, superabsorbent hydrogel to treat overweight or obesity.

Methods: The Gelesis Loss Of Weight (GLOW) study was a 24-week, multicenter, randomized, double-blind, placebo-controlled study in patients with BMI ≥  27 and ≤ 40 kg/m and fasting plasma glucose ≥ 90 and ≤ 145 mg/dL. The co-primary end points were placebo-adjusted weight loss (superiority and 3% margin super-superiority) and at least 35% of patients in the Gelesis100 group achieving ≥ 5% weight loss.

HNF1A variant, energy-reduced diets and insulin resistance improvement during weight loss: The POUNDS Lost trial and DIRECT.

Aim: To determine whether weight-loss diets varying in macronutrients modulate the genetic effect of hepatocyte nuclear factor 1α (HNF1A) rs7957197 on weight loss and improvement of insulin resistance.

Materials And Methods: We analysed the interaction between HNF1A rs7957197 and weight-loss diets with regard to weight loss and insulin resistance improvement among 722 overweight/obese adults from a 2-year randomized weight-loss trial, the POUNDS Lost trial. The findings were replicated in another independent 2-year weight-loss trial, the Dietary Intervention Randomized Controlled Trial (DIRECT), in 280 overweight/obese adults.

Plasma fatty acyl-carnitines during 8 weeks of overfeeding: relation to diet energy expenditure and body composition: the PROOF study.

Objective: Overfeeding is a strategy for evaluating the effects of excess energy intake. In this secondary analysis we tested the possibility that different levels of dietary protein might differentially modify the response of fatty acyl-carnitines to overfeeding.

Methods: Twenty-three healthy adult men and women were overfed by 40% for 8 weeks while in-patients with diets containing 5% (LPD), 15% (NPD) or 25% (HPD) protein.

Relative Validity of Nutrient Intakes Assessed by Questionnaire, 24-Hour Recalls, and Diet Records as Compared With Urinary Recovery and Plasma Concentration Biomarkers: Findings for Women.

We evaluated the performance of a semiquantitative food frequency questionnaire (SFFQ), the Automated Self-Administered 24-Hour Dietary Recall (ASA24), and 7-day dietary records (7DDRs), in comparison with biomarkers, in the estimation of nutrient intakes among 627 women in the Women's Lifestyle Validation Study (United States, 2010-2012). Two paper SFFQs, 1 Web-based SFFQ, 4 ASA24s (beta version), 2 7DDRs, 4 24-hour urine samples, 1 doubly labeled water measurement (repeated among 76 participants), and 2 fasting blood samples were collected over a 15-month period. The dietary variables evaluated were energy, energy-adjusted intakes of protein, sodium, potassium, and specific fatty acids, carotenoids, α-tocopherol, retinol, and folate.

Genetic variation of habitual coffee consumption and glycemic changes in response to weight-loss diet intervention: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.

Coffee consumption has been associated with glucose metabolism and risk of type 2 diabetes. We examined whether the genetic variation determining habitual coffee consumption affected glycemic changes in response to weight-loss dietary intervention. A genetic risk score (GRS) was calculated based on 8 habitual coffee consumption-associated single nucleotide polymorphisms.

Dietary Protein Modifies the Effect of the Genotype on 2-Year Changes in Appetite and Food Craving: The POUNDS Lost Trial.

The melanocortin-4 receptor (MC4R) plays a pivotal role in the regulation of appetite and eating behavior. Variants in the gene have been related to appetite and obesity. We aimed to examine whether weight-loss diets modified the effect of the "obesity-predisposing" genotype on appetite-related measures in a randomized controlled trial.

Genetic Variations of Circulating Adiponectin Levels Modulate Changes in Appetite in Response to Weight-Loss Diets.

Context: Adiponectin plays key roles in regulating appetite and food intake.

Objective: To investigate interactions between the genetic risk score (GRS) for adiponectin levels and weight-loss diets varying in macronutrient intake on long-term changes in appetite and adiponectin levels.

Design, Setting, And Participants: A GRS was calculated based on 5 adiponectin-associated variants in 692 overweight adults from the 2-year Preventing Overweight Using Novel Dietary Strategies trial.

Two-year changes in circulating adiponectin, ectopic fat distribution and body composition in response to weight-loss diets: the POUNDS Lost Trial.

Background/objectives: Adiponectin has a pivotal role in linking fat distribution with cardiometabolic disorders. We investigated the associations of long-term changes in circulating adiponectin with body composition and fat distribution at different abdominal depots in response to weight-loss dietary interventions, as well as the modification effect of sex.

Subjects/methods: In the 2-year Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) Trial, 811 overweight or obese adults were randomly assigned to one of four diets varying in macronutrient intakes.

Genetic susceptibility to diabetes and long-term improvement of insulin resistance and β cell function during weight loss: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.

Background: Diet interventions have shown effectiveness in improving diabetes risk factors; however, little is known about whether the effects of diet intervention are different according to genetic susceptibility.

Objective: We examined interactions between weight-loss diets and the genetic risk score (GRS) for diabetes on 2-y changes in markers of insulin resistance and β cell function in a randomized controlled trial.

Design: Data from the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial were analyzed.

Effect of Three Levels of Dietary Protein on Metabolic Phenotype of Healthy Individuals With 8 Weeks of Overfeeding.

Context: Obesity is associated with insulin resistance and other metabolic changes that might be modified by overfeeding diets with different protein levels.

Objective: The objective of the study was to determine the effect of overfeeding diets with 5%, 15%, or 25% energy from protein on insulin sensitivity and compartments of body fat in healthy men and women.

Methods: Fifteen men and five women were overfed by approximately 40% for 56 days with 5% (low protein), 15% (normal protein), or 25% (high protein) protein diets.

Genetic variation of fasting glucose and changes in glycemia in response to 2-year weight-loss diet intervention: the POUNDS LOST trial.

Objective: Weight-loss intervention through diet modification has been widely used to improve obesity-related hyperglycemia; however, little is known about whether genetic variation modifies the intervention effect. We examined the interaction between weight-loss diets and genetic variation of fasting glucose on changes in glycemic traits in a dietary intervention trial.

Research Design And Methods: The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial is a randomized, controlled 2-year weight-loss trial.

Weight-Loss Diets, Adiponectin, and Changes in Cardiometabolic Risk in the 2-Year POUNDS Lost Trial.

Context: Compelling evidence suggests that the beneficial effects of weight-loss diet interventions on improvement of cardiometabolic risk factors may be partly through modulating secretion of adiponectin from adipose tissue.

Objective: To investigate the effects of long-term weight-loss diets with different compositions of macronutrients on longitudinal changes in circulating adiponectin concentrations and how such changes, if they exist, affect cardiometabolic risk.

Design, Setting, And Participants: In the 2-year Preventing Overweight Using Novel Dietary Strategies trial, 811 overweight or obese adults were randomly assigned to 1 of 4 diets varying in macronutrient intakes.

Weight-loss diets and 2-y changes in circulating amino acids in 2 randomized intervention trials.

Background: Circulating amino acids, such as branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs), have been associated with diabetes risk; however, little is known about how a long-term dietary intervention for weight loss affects circulating amino acids.

Objectives: We examined the effects of weight-loss diets on long-term changes in plasma amino acids and the associations of these changes with weight loss and the improvement of insulin resistance.

Design: We repeatedly measured plasma amino acid profiles over 2 y in overweight or obese participants from 2 randomized, dietary intervention, weight-loss trials [774 subjects from the POUNDS LOST (Preventing Overweight Using Novel Dietary Strategies Trial) and 318 subjects from the DIRECT (Dietary Intervention Randomized Controlled Trial)].

Neuropeptide Y genotype, central obesity, and abdominal fat distribution: the POUNDS LOST trial.

Background: Neuropeptide Y is a key peptide affecting adiposity and has been related to obesity risk. However, little is known about the role of NPY variations in diet-induced change in adiposity.

Objective: The objective was to examine the effects of NPY variant rs16147 on central obesity and abdominal fat distribution in response to dietary interventions.

Sex Differences in the Effects of Weight Loss Diets on Bone Mineral Density and Body Composition: POUNDS LOST Trial.

Context: Weight loss is associated with reduction in bone mineral density (BMD).

Objective: The objective was to address the role of changes in fat mass (FM) and lean mass (LM) in BMD decline in both sexes.

Design: A 2-year randomized controlled trial, the Preventing Overweight Using Novel Dietary Strategies (POUNDS-LOST).

Dietary Fat Modifies the Effects of FTO Genotype on Changes in Insulin Sensitivity.

Background: The common variants in the fat mass and obesity-associated (FTO) gene have been associated with obesity and insulin resistance. Recently, studies also linked FTO variants with macronutrient intakes.

Objective: We aimed to investigate whether diet interventions varying in macronutrients modified the effects of FTO genotypes on changes in insulin resistance.

CETP genotype and changes in lipid levels in response to weight-loss diet intervention in the POUNDS LOST and DIRECT randomized trials.

Little is known about whether cholesteryl ester transfer protein (CETP) genetic variation may modify the effect of weight-loss diets varying in fat content on changes in lipid levels. We analyzed the interaction between the CETP variant rs3764261 and dietary interventions on changes in lipid levels among 732 overweight/obese adults from a 2 year randomized weight-loss trial [Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST)], and replicated the findings in 171 overweight/obese adults from an independent 2 year weight-loss trial [Dietary Intervention Randomized Controlled Trial (DIRECT)]. In the POUNDS LOST, participants with the CETP rs3764261 CC genotype on the high-fat diet had larger increases in HDL cholesterol (P = 0.

FTO genotype, dietary protein, and change in appetite: the Preventing Overweight Using Novel Dietary Strategies trial.

Background: A common obesity-risk variant rs9939609 in the fat mass- and obesity-associated (FTO) gene was recently shown to affect appetite, and the gene is sensitive to the regulation of amino acids.

Objective: We examined the interaction between FTO genotype and protein intake on the long-term changes in appetite in a randomized controlled trial.

Design: We genotyped FTO rs9939609 in 737 overweight adults in the 2-y Preventing Overweight Using Novel Dietary Strategies trial and assessed 4 appetite-related traits including cravings, fullness, hunger, and prospective consumption.

Variants in glucose- and circadian rhythm-related genes affect the response of energy expenditure to weight-loss diets: the POUNDS LOST Trial.

Background: Circadian rhythm has been shown to be related to glucose metabolism and risk of diabetes, probably through effects on energy balance. Recent genome-wide association studies identified variants in circadian rhythm-related genes (CRY2 and MTNR1B) associated with glucose homeostasis.

Objective: We tested whether CRY2 and MTNR1B genotypes affected changes in measures of energy expenditure in response to a weight-loss diet intervention in a 2-y randomized clinical trial, the POUNDS (Preventing Overweight Using Novel Dietary Strategies) LOST Trial.

Addiction potential of phentermine prescribed during long-term treatment of obesity.

Objective: To investigate if phentermine treatment induces phentermine abuse, psychological dependence (addiction) or phentermine drug craving in overweight, obese and weight loss maintenance patients. To investigate whether amphetamine-like withdrawal occurs after abrupt cessation of long-term phentermine treatment.

Design: Clinical intervention trial with interruption of phentermine treatment in long-term patients.

Body image changes associated with participation in an intensive lifestyle weight loss intervention.

The primary aim of this study was to test for changes in body image in men and women enrolled in the Look AHEAD trial. Look AHEAD (Action for Health in Diabetes) is a multicenter, randomized controlled trial designed to test whether intentional weight loss reduces cardiovascular morbidity and mortality in overweight individuals with type 2 diabetes. Participants included 157 adults at one site (Pennington Biomedical Research Center (PBRC), Baton Rouge, LA) of the Look AHEAD study.