Obesity-related Comorbidities Research Articles

The Impact of Metabolic and Bariatric Surgery on Apo B100 Levels in Individuals with high BMI: A Multi-Centric Prospective Cohort Study.

Metabolic and Bariatric surgery (MBS) leads to significant weight loss and improvements in obesity-related comorbidities. However, the impact of MBS on Apolipoprotein B100 (Apo-B100) regulation is unclear. Apo-B100 is essential for the assembly and secretion of serum lipoprotein particles. Elevated levels of these factors can accelerate the development of atherosclerotic plaques in blood vessels. This study aimed to evaluate changes in Apo-B100 levels following MBS. 121 participants from the Iranian National Obesity and Metabolic Surgery Database (INOSD) underwent Laparoscopic Sleeve Gastrectomy (LSG) (n = 43), One-Anastomosis Gastric Bypass (OAGB) (n = 70) or Roux-en-Y Gastric Bypass (RYGB) (n = 8). Serum Apo-B100, lipid profiles, liver enzymes, and fasting glucose were measured preoperatively and six months postoperatively. Apo-B100 levels significantly decreased from 94.63 ± 14.35 mg/dL preoperatively to 62.97 ± 19.97 mg/dL after six months (p < 0.01), alongside reductions in total cholesterol, triglycerides, LDL, VLDL, AST, and ALT (p < 0.05). Greater Apo-B100 reductions occurred in non-diabetics versus people with diabetes (p = 0.012) and strongly correlated with baseline Apo-B100 (r = 0.455, p < 0.01) and LDL levels (r = 0.413, p < 0.01). However, surgery type did not impact Apo-B100 changes in multivariate analysis (p > 0.05). Bariatric surgery leads to a significant reduction in Apo-B100 levels and improvements in lipid profiles and liver enzymes, indicating a positive impact on dyslipidemia and cardiovascular risk in individuals with high BMI.

Defining Overweight and Obesity by Percent Body Fat instead of Body Mass Index.

Thresholds for overweight and obesity are currently defined by body mass index (BMI), a poor surrogate marker of actual adiposity (percent body fat, %BF). Practical modern technologies provide estimates of %BF but medical providers need outcome-based %BF thresholds to guide patients. This analysis determines %BF thresholds based on key obesity-related comorbidities, exhibited as metabolic syndrome (MetSyn). These limits were compared to existing BMI thresholds of overweight and obesity. Correlational analysis of data from cross sectional sampling of 16,918 adults (8,734 men and 8,184 women) from the US population, accessed by the National Health and Nutrition Examination Survey (NHANES) public use datasets. Individuals measured by BMI as overweight (BMI>25 kg/m2) and with obesity (BMI>30 kg/m2) included 5% and 35% of individuals with MetSyn, respectively. For men, there were no cases of MetSyn below 18%BF, %BF equivalence to "overweight" (i.e., 5% of MetSyn individuals) occurred at 25%BF, and "obesity" (i.e., 35% of MetSyn individuals) corresponded to 30%BF. For women, there were no cases of MetSyn below 30%BF, "overweight" occurred at 36%BF, and "obesity" corresponded to 42%BF. Comparison of BMI to %BF illustrates the wide range of variability in BMI prediction of %BF, highlighting the potential importance of using more direct measures of adiposity to manage obesity-related disease. Practical methods of body composition estimation can now replace the indirect BMI assessment for obesity management, using threshold values provided from this study. Clinically relevant "overweight" can be defined as 25 and 36% BF for men and women, respectively, and "obesity" is defined as 30 and 42% BF for men and women.

Obesity-related comorbidities as potential factors influencing features of premature ageing in severely obese patients

Obesity-related comorbidities as potential factors influencing features of premature ageing in severely obese patients

Pro- and anti-inflammatory cytokines are the game-changers in childhood obesity-associated metabolic disorders (diabetes and non-alcoholic fatty liver diseases).

Childhood obesity is a chronic inflammatory epidemic that affects children worldwide. Obesity affects approximately 1 in 5 children worldwide. Obesity in children can worsen weight gain and raise the risk of obesity-related comorbidities like diabetes and non-alcoholic fatty liver disease (NAFLD). It can also negatively impact the quality of life for these children. Obesity disrupts immune system function, influencing cytokine (interleukins) balance and expression levels, adipokines, and innate and adaptive immune cells. The altered expression of immune system mediators, including interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-17 (IL-17), interleukin-18 (IL-18), transforming growth factor (TGF), tumor necrosis factor (TNF), and others, caused inflammation, progression, and the development of pediatric obesity and linked illnesses such as diabetes and NAFLD. Furthermore, anti-inflammatory cytokines, including interleukin-2 (IL-2), have been shown to have anti-diabetes and IL-1 receptor antagonist (IL-1Ra) anti-diabetic and pro-NAFLFD properties, and interleukin-10 (IL-10) has been shown to have a dual role in managing diabetes and anti-NAFLD. In light of the substantial increase in childhood obesity-associated disorders such as diabetes and NAFLD and the absence of an effective pharmaceutical intervention to inhibit immune modulation factors, it is critical to consider the alteration of immune system components as a preventive and therapeutic approach. Thus, the current review focuses on the most recent information regarding the influence of pro- and anti-inflammatory cytokines (interleukins) and their molecular mechanisms on pediatric obesity-associated disorders (diabetes and NAFLD). Furthermore, we discussed the current therapeutic clinical trials in childhood obesity-associated diseases, diabetes, and NAFLD.

Cost-effectiveness of semaglutide 2.4 mg in chronic weight management in Portugal

BackgroundObesity and overweight are a significant public health concern. Subcutaneous semaglutide 2.4 mg injection is a glucagon-like peptide-1 (GLP-1) analogue approved by the European Medicines Agency as an adjunct to a reduced calorie diet and increased physical activity (diet and exercise, D&E) for the treatment obesity and overweight in the presence of at least one weight related comorbidity. This study aimed to assess the cost-effectiveness of semaglutide 2.4 mg in combination with D&E compared to D&E alone for the Portuguese setting.MethodsAnalysis were conducted using the Core Obesity Model (COM) version 18, a Markov state transition cohort model, to predict the health outcomes and costs of weight related complications based on changes in surrogate endpoints. Efficacy and safety data were sourced from the STEP trials (Body Mass Index, systolic blood pressure and glycemic status) from a cohort of adults aged on average 48 years with obesity (BMI ≥ 30 kg/m2) and ≥ 1 obesity-related comorbidities, over a time horizon of 40 years. Costs were estimated from the perspective of the Portuguese National Health Service. Sensitivity analyses were conducted to test the robustness of results across a range of assumptions.ResultsOn a patient level, Semaglutide 2.4 mg in addition to D&E compared to D&E alone, improved QALYs by 0.098 and yielded higher costs by 1,325 EUR over a 40-year time horizon, with an ICER of 13,459 EUR per QALY gained and 100% probability of cost-effectiveness at the given WTP. Semaglutide 2.4 mg remained cost-effective across all different scenarios and sensitivity analysis at a WTP of 20,000 EUR per QALY. Among the subpopulations examined, Semaglutide 2.4 mg yielded ICERs of 18,459 EUR for patients with BMI ≥ 30 kg/m2 and of 22,657 EUR for patients with BMI ≥ 35 kg/m2.ConclusionsSemaglutide 2.4 mg was cost-effective compared to D&E alone for patients with obesity (BMI ≥ 30 kg/m2) and weight related comorbidities in Portugal, over a 40-year time horizon.

Weight loss benefits on HDL cholesterol persist even after weight regaining.

Obesity-related comorbidities may relapse in patients with weight regain after bariatric surgery. However, HDL cholesterol (HDLc) levels increase after surgery and seem to remain stable despite a gradual increase in BMI. The aim of this study is to analyze the effects of weight regain after bariatric surgery on HDL cholesterol. This is a retrospective, observational, cohort study in patients who underwent bariatric surgery in the Hospital de la Santa Creu i Sant Pau (Barcelona) between 2007 and 2015. Patients without at least 5 years of follow-up after surgery, under fibrate treatment, and those who required revisional surgery were excluded from the analysis. Data were collected at baseline, 3 and 6 months after surgery, and then annually until 5 years post-surgery. One hundred fifty patients were analyzed. 93.3% of patients reached > 20% of total weight loss after surgery. At 5th year, 37% of patients had regained > 15% of nadir weight, 60% had regained > 10%, and 22% had regained < 5% of nadir weight. No differences were found in HDLc levels between the different groups of weight regain, nor in the % of change in HDLc levels between nadir weight and 5 years, or in the proportion of patients with normal HDLc concentrations either. HDLc remains stable regardless of weight regain after bariatric surgery.

Prediction of resting energy expenditure for adolescents with severe obesity: A multi-centre analysis.

Resting energy expenditure (REE) assessments can help inform clinical treatment decisions in adolescents with elevated body mass index (BMI), but current equations are suboptimal for severe obesity. We developed a predictive REE equation for youth with severe obesity and obesity-related comorbidities and compared results to previously published predictive equations. Data from indirect calorimetry, clinical measures, and body composition per Dual x-ray absorptiometry (DXA) were collected from five sites. Data were randomly divided into development (N = 438) and validation (N = 118) cohorts. A predictive equation was developed using Elastic Net regression, using sex, race, ethnicity, weight, height, BMI percent of the 95th%ile (BMIp95), waist circumference, hip circumference, waist/hip ratio, age, Tanner stage, fat and fat-free mass. This equation was verified in the validation cohort and compared with 11 prior equations. Data from the total cohort (n = 556, age 15 ± 1.7 years, 77% female, BMIp95 3.3 ± 0.94) were utilized. The best fit equation was REE = -2048 + 18.17 × (Height in cm) - 2.57 × (Weight in kg) + 7.88 × (BMIp95) + 189 × (1 = male, 0 = female), R2 = 0.466, and mean bias of 23 kcal/day. This new equation provides an updated REE prediction that accounts for severe obesity and metabolic complications frequently observed in contemporary youth.

American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity.

This joint ASGE-ESGE guideline provides an evidence-based summary and recommendations regarding the role of endoscopic bariatric and metabolic therapies (EBMTs) in the management of obesity. The document was developed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework. It evaluates the efficacy and safety of EBMT devices and procedures that currently have CE mark or FDA-clearance/approval, or that had been approved within five years of document development. The guideline suggests the use of EBMTs plus lifestyle modification in patients with a BMI of ≥30 kg/m2, or with a BMI of 27.0-29.9 kg/m2 with at least 1 obesity-related comorbidity. Furthermore, it suggests the utilization of intragastric balloons and devices for endoscopic gastric remodeling (EGR) in conjunction with lifestyle modification for this patient population.

Metabolic outcomes in obese mice undergoing one-anastomosis gastric bypass (OAGB) with a long or a short biliopancreatic limb.

One-anastomosis gastric bypass (OAGB) has gained importance as a safe and effective operation to treat morbid obesity. It is not known whether a long biliopancreatic limb (BPL) in OAGB surgery compared to a short BPL results in beneficial metabolic outcomes. 5-week-old male C57BL/6J mice fed a high-fat diet for 8 weeks underwent OAGB surgery with defined short and long BPL lengths, or sham surgery combined with caloric restriction. Weight loss, glucose tolerance, obesity-related comorbidities, endocrine effects, gut microbiota and bile acids were assessed. Total weight loss was independent of the length of the BPL after OAGB surgery. However, a long BPL was associated with lower glucose-stimulated insulin on day 14, and an improved glucose tolerance on day 35 after surgery. A long BPL resulted in reduced total cholesterol. There were no differences in the resolution of metabolic dysfunction-associated steatotic liver disease and adipose tissue inflammation. Tendencies of an attenuated hypothalamic-pituitary-adrenal axis and aldosterone were present in the long BPL group. In OAGB-operated mice, we found an increase in primary conjugated bile acids (pronounced in long BPL) along with a loss in bacterial Desulfovibrionaceae and Erysipelotrichaceae and simultaneous increase in Akkermansiaceae, Sutterellaceae and Enterobacteriaceae. In sum, OAGB surgery with a long compared to a short BPL led to similar weight loss, but improved glucose metabolism, lipid and endocrine outcomes in obese mice, potentially mediated through changes in gut microbiota and related bile acids. Tailoring the BPL length in humans might help to optimize metabolic outcomes after bariatric surgery.

Perceptions of an acceptance-based weight management treatment among adults living in rural areas.

Obesity and obesity-related comorbidities disproportionately affect rural communities. Research has emerged in support of a novel acceptance-based behavioural weight management treatment (ABT) that integrates the principles and procedures of acceptance-commitment therapy (ACT) with traditional components of standard behavioural treatment (SBT). The current study assessed the perceptions of community stakeholders in rural areas to session materials of a commercially available ABT program. Surveys and focus groups were used to solicit feedback from three former interventionists with experience delivering SBTs in rural counties and from 17 former participants in these programs. Qualitative responses encompassed four overarching themes: (1) recommendations to support participant engagement, (2) comments about preferences for specific ABT and SBT strategies, (3) concerns about specific aspects of treatment delivery, and (4) requests for aesthetic changes to session materials to enhance clarity and engagement. Overall, participants viewed ABT materials and concepts favourably but believed it would be important to begin the intervention with rapport building and training in traditional SBT strategies prior to delving into ACT strategies. Future studies should investigate the efficacy of ABT for weight loss in adults with obesity living in rural communities and continue to solicit feedback from rural community stakeholders.

Intussusception and Gut Dysmotility: A Systematic Review Assessing Unexpected Complications of Bariatric Surgery.

Bariatric surgery, although effective in treating obesity-related comorbidities, rarely results in intussusception, which is a severe complication. This study aimed to enhance clinical practice and establish early diagnosis by elucidating risk factors and management strategies associated with intussusception. We conducted this systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analysis2020 criteria. We looked through PubMed, PubMed Central, ScienceDirect, ScienceOpen, MyScienceWork, Hyper Articles en Ligne (HAL), Google Scholar, and the Medical Literature Analysis and Retrieval System Online for relevant studies and research. Articles were screened according to inclusion and exclusion criteria, and relevance. We employed pertinent quality appraisal instruments to look for bias. Initially, we discovered 2,833 items. We eliminated redundant and unnecessary publications. After reviewing all the articles, we selected 30 studies based on their titles and abstracts. Out of the 30 studies reviewed, 12 papers were included in this review, with the remaining 18being eliminated due to low quality. Medical practitioners and surgeons have a responsibility to meticulously monitor and provide postoperative surveillance, with a particular emphasis placed on individuals exhibiting symptoms of abdominal pain and vomiting, as there is a clinical imperative to consider the possibility of intussusception. The management approach, whether conservative or surgical, remains contingent upon the clinical context.

Adipose-derived miRNAs as potential biomarkers for predicting adulthood obesity and its complications: A systematic review and bioinformatic analysis.

Adipose tissue is the first and primary target organ of obesity and the main source of circulating miRNAs in patients with obesity. This systematic review aimed to analyze and summarize the generation and mechanisms of adipose-derived miRNAs and their role as early predictors of various obesity-related complications. Literature searches in the PubMed and Web of Science databases using terms related to miRNAs, obesity, and adipose tissue. Pre-miRNAs from the Human MicroRNA Disease Database, known to regulate obesity-related metabolic disorders, were combined for intersection processing. Validated miRNA targets were sorted through literature review, and enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes via the KOBAS online tool, disease analysis, and miRNA transcription factor prediction using the TransmiR v. 2.0 database were also performed. Thirty miRNAs were identified using both obesity and adipose secretion as criteria. Seventy-nine functionally validated targets associated with 30 comorbidities of these miRNAs were identified, implicating pathways such as autophagy, p53 pathways, and inflammation. The miRNA precursors were analyzed to predict their transcription factors and explore their biosynthesis mechanisms. Our findings offer potential insights into the epigenetic changes related to adipose-driven obesity-related comorbidities.

Novel subtype of obesity influencing the outcomes of sleeve gastrectomy: Familial aggregation of obesity.

Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy (SG) between patients with familial aggregation of obesity (FAO) and patients with sporadic obesity (SO) have not been elucidated. To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO. A total of 193 patients with obesity who underwent SG were selected. Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity (1SO vs 1FAO, 2SO vs 2FAO). The baseline characteristics, weight loss outcomes, prevalence of obesity-related comorbidities and incidence of major surgery-related complications were compared between groups. We defined FAO as the presence of two or more first-degree relatives with obesity. Patients with FAO did not initially show significant differences in baseline data, short-term postoperative weight loss, or obesity-related comorbidities when compared to patients with SO preoperatively. However, distinctions between the two groups became evident at the two-year mark, with statistically significant differences in both percentage of total weight loss (P = 0.006) and percentage of excess weight loss (P < 0.001). The FAO group exhibited weaker remission of type 2 diabetes mellitus (T2DM) (P = 0.031), hyperlipidemia (P = 0.012), and non-alcoholic fatty liver disease (NAFLD) (P = 0.003) as well as a lower incidence of acid reflux (P = 0.038). FAO patients is associated with decreased mid-to-long-term weight loss outcomes; the alleviation of T2DM, hyperlipidemia and NAFLD; and decreased incidence of acid reflux postoperatively.

Predictors of Chronic Pain 6 Months and 1 Year After Bariatric Surgery.

Obesity and chronic pain (CP) represent serious, interrelated global public health concerns that have a profound impact on individuals and society. Bariatric surgery is increasing in popularity and has been proven safe and efficacious, providing long-term weight loss and improvements in many obesity-related co-morbidities. A decrease in CP is often a motivation for bariatric surgery. The purpose of this study was to investigate the changes in CP postoperatively and to examine the relationship between psychosocial measures and pain. A total of 155 adult bariatric surgery patients were recruited and completed self-report measures for CP severity and interference, neuropathic pain, anxiety, depression, emotion regulation and perceived social support at three timepoints preoperative and 6 and 12months postoperative. Pain significantly decreased between preoperative and postoperative timepoints, and preoperative pain was the most significant predictor of postoperative pain. Preoperative CP was correlated with anxiety (p < 0.05) and depression (p < 0.01) at 6months postoperatively and perceived social support (p < 0.01) at 1year postoperatively. However, regression analyses with psychological variables were not significant. CP decreases after bariatric surgery, but further research with larger sample sizes is needed to establish whether psychosocial characteristics impact this outcome.

Metabolic surgery results in greater metabolic benefits in patients who achieve healthy weight

BackgroundA percentage of total weight loss >20% as the expected weight loss target after metabolic surgery might be insufficient to produce adequate metabolic benefits. ObjectivesThis study identified the optimal weight loss target to achieve substantial benefits from metabolic surgery. SettingUniversity-affiliated tertiary care center MethodsIn this retrospective study, participants were categorized into healthy weight (18.5 kg/m2≤ body mass index [BMI] <24 kg/m2), overweight (24 kg/m2≤ BMI <28 kg/m2), and obesity groups (BMI ≥28 kg/m2) according to their BMI 1 year after metabolic surgery. The weight loss and remission of obesity-related comorbidities were evaluated. Ordinal logistic regression analysis was used to identify predictors for achieving healthy weight 1 year postoperatively. ResultsOverall, 125 patients (112 sleeve gastrectomies, 13 Roux-en-Y gastric bypasses) were recruited in this study. Forty-two participants achieved healthy weight, 38 were overweight, and 45 had obesity. Type 2 diabetes mellitus and obstructive sleep apnea were relieved in all groups. Individuals who achieved healthy weight showed more improvements in non-alcoholic fatty liver disease, hypertension, and hyperuricemia than those who did not. Preoperative BMI was an independent predictor for the BMI achieved postoperatively, and the optimal cut-off point for achieving healthy weight was 34.9 kg/m2. ConclusionsHealthy weight was a more stringent target for patients who underwent metabolic surgery than the percentage of total weight loss. Populations with a preoperative BMI of <34.9 kg/m2 were prone to realize the goal. Additional weight loss interventions could be considered for those with higher preoperative BMIs and enforced within 1 year postoperatively.

The effect of quercetin on adipogenesis, lipolysis, and apoptosis in 3T3-L1 adipocytes: The role of SIRT1 pathways.

Lipotoxicity, caused by adipocyte triglyceride over-accumulation, contributes to obesity-related comorbidities such as hypertension, type 2 diabetes, coronary heart disease, respiratory dysfunction, and osteoarthritis. This study focuses on determining how sirtuin-1 (SIRT-1) mediates quercetin's (QCT) effect on 3T3-L1 adipocytes. Key aspects of this study include preventing adipogenesis, inducing lipolysis, and stimulating adipocyte apoptosis. 3T3-L1 adipocytes underwent treatment with varying QCT doses, lipopolysaccharide (LPS), and the SIRT-1 inhibitor EX-527, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide [MTT] assay for cell viability assessment. Furthermore, quantitative real-time polymerase chain reaction measured mRNA expression levels of adipogenesis markers (fatty acid synthase [FASN] and peroxisome proliferator-activated receptor gamma [PPARγ]), lipolysis markers (adipose triglyceride lipase [ATGL] and hormone-sensitive lipase [HSL]), and apoptosis markers (B-cell lymphoma2 [Bcl-2], Bcl-2 Associated -X-protein [BAX] and Caspase-3). The data showed that LPS+QCT significantly reduced cell viability in a dose- and time-dependent manner, unaffected by LPS+QCT+EX-527. Treatment with LPS+QCT did not affect FASN and PPARγ expression but significantly increased ATGL and HSL mRNA expression compared with LPS alone. Interestingly, EX-527 reversed the effects of LPS+QCT on lipogenesis and lipolysis markers completely. QCT enhanced apoptosis in a SIRT-1 independent pattern. The data suggest that QCT suppresses adipogenesis while increasing lipolysis via SIRT-1. However, QCT's effects on apoptosis appear to be independent of SIRT-1. These findings provide further evidence for QCT's effects on adipocytes, particularly its interaction with SIRT-1.

Portuguese observational cross-sectional clinical imaging study protocol to investigate central dopaminergic mechanisms of successful weight loss through bariatric surgery

IntroductionBariatric surgery (BS) is the treatment of choice for refractory obesity. Although weight loss (WL) reduces the prevalence of obesity-related comorbidities, not all patients maintain it. It has been suggested...

Obesity and Gastrointestinal Regulation of Food Intake

The aim in this review is to explain the role of the gastrointestinal system in obesity and related complications by focusing on the biological mechanisms between obesity and the gastrointestinal system, based on the latest evidence in the literature. A systematic search of the literatures in the PubMed and ScienceDirect databases was conducted. Factors such as inflammation, mechanical space-occupying effect, microbiota, and adipocyte peptides are involved the development of obesity-related gastrointestinal system comorbidities. However, obesity occurs when the connection between the gastrointestinal tract and the brain changes. Signaling dysfunction disrupts the brain-gut axis, leading to increased frequency of food intake and excessive fat accumulation. Obesity increases the risk of developing gastrointestinal system disorders. However, the gastrointestinal tract and its pathophysiology play a key role the regulation of food intake and subsequent progression to obesity.

Geriatric Bariatric Surgery: Outcomes at a Single Institution.

Obesity, especially in those over the age of 65, is associated with multiple comorbidities and decreased quality of life. Bariatric surgery is an effective method of weight loss and management of comorbidities and is increasingly utilized in younger and middle-aged populations. A retrospective review was performed of patients ≥65 years old who underwent bariatric surgery between 2018 and 2021 at a single institution to evaluate the safety and efficacy of bariatric surgery in older populations. A total of 11 patients were identified with a mean age of 67.5, ranging from 65 to 78. All patients had obesity-related comorbidities including hypertension (90.9%), obstructive sleep apnea (72.7%), diabetes mellitus (54.5%), hyperlipidemia (45.5%), and others. The mean %EWL at 12 months was 26.1% with improvement in comorbidities and no post-operative complications. Our results demonstrate that bariatric surgery can be safe for the geriatric population with improvement in weight loss and comorbidities.

Glycomacropeptide-Based Protein Substitutes for Children with Phenylketonuria in Italy: A Nutritional Comparison.

Advancements in food science technology have allowed the development of new products for the therapeutic management of inherited metabolic diseases such as phenylketonuria (PKU). Glycomacropeptide (GMP), a peptide derived from casein, is naturally low in phenylalanine (Phe) and, thus, adequate for protein substitutes (PSs) for the management of PKU in children. This review aims primarily to analyse the differences in the nutritional composition of GMP-based protein substitutes in different formulations (ready to drink, powdered, and bars), and secondarily to assess the quality of these products, comparing their nutritional composition with that of standard amino acid (L-AA) mixtures. Thirty-five GMP-based PSs produced by six different companies were included in this review: twenty-one powdered PSs, eight ready to drink, and six bars. The analysis revealed great heterogeneity not only among the different formulations (powdered, ready to drink, and bars) but also within the same group, in terms of energy content and nutritional composition. GMP-based PSs were shown to have higher contents of sugars and saturated fatty acids compared to L-AA PSs, especially in ready-to-drink formulations and bars. The latter also provided the highest amounts of energy among the GMP-based products. This finding may be related to a higher risk of developing overweight and obesity. The greater palatability of these GMP-based PSs, combined with improved nutritional quality, could not only improve adherence to diet therapy but also reduce the incidence of obesity-related comorbidities in PKU.