David Benaiges

Background: Clinical obesity (CO) is a newly proposed and debated multidimensional definition of obesity requiring biological and clinical validation. This study aimed to characterize the prevalence and metabolomic signatures of CO and metabolically unhealthy obesity (MUHO), determine CO remission after metabolic bariatric surgery (MBS), and explore baseline predictors of remission.Methods: A prospective observational study was conducted in patients with severe obesity undergoing MBS. CO was defined according to the 2025 Lancet Diabetes & Endocrinology framework and metabolic status using modified Wildman criteria. Targeted metabolomics was performed on plasma samples using Liquid chromatography–tandem mass spectrometry.Findings: Among 145 patients, 76·6% met criteria for CO and 89·7% for MUHO at baseline. Distinct metabolomic signatures were identified for both phenotypes: CO was mainly associated with microbiota-related metabolites and energetic metabolism intermediates, whereas MUHO showed broader alterations involving amino acid metabolism. At 12 months, CO remission occurred in 30·5% of cases. Baseline clinical variables showed limited predictive ability (AUC 0·66), while a six-metabolite panel related to gut microbiota-derived metabolism, bile acid signaling, energetic metabolism, and tryptophan metabolism improved discrimination (AUC 0·78; p=0·027).Interpretation: MBS was associated with CO remission in approximately one third of patients at 12 months. The association of CO and its remission with distinct metabolomic signatures supports the biological relevance of this construct and suggests that metabolomic profiling may help characterize obesity heterogeneity and treatment response beyond weight loss.

Background/Objectives: The Global Leadership Initiative on Malnutrition (GLIM) recently updated its inflammation criterion through a Delphi consensus to standardize its assessment. This study aimed to assess the impact of these new recommendations on the concurrent and predictive validity of the GLIM criteria in hospitalized medical patients. Methods: This post hoc analysis re-evaluated a previously published cohort of 119 hospitalized patients with acute medical conditions, originally assessed using the GLIM criteria and the Subjective Global Assessment (SGA) as the reference standard. Inflammation was redefined according to the 2024 GLIM Delphi consensus, and the concurrent and predictive validity of the modified GLIM criteria (GLIM-I) were examined. Receiver operating characteristic (ROC) curves were used to compare the discriminative ability of SGA, original GLIM, and GLIM-I to predict prolonged hospital stay. Results: With the updated inflammation definition, all patients met the etiologic criterion, increasing malnutrition prevalence from 41.7% to 52.2%. GLIM-I showed a sensitivity of 78.0% and specificity of 67.7% versus SGA, not reaching the predefined ≥80% threshold for concurrent validity. Predictive validity was maintained (adjusted odds ratio (OR) = 3.40; 95% CI: 1.31–8.83). SGA achieved the highest discriminative ability (area under the curve (AUC) = 0.783; 95% CI: 0.693–0.874), significantly outperforming the original GLIM (AUC = 0.723; 95% CI: 0.616–0.830; p = 0.049). GLIM-I showed similar performance (AUC = 0.731; 95% CI: 0.620–0.843; p = 0.727). Conclusions: SGA should continue to be considered the method of choice for nutritional diagnosis in hospitalized medical patients. Further research is needed to determine how the new inflammation criteria influence the validity of the GLIM framework in other clinical contexts before their widespread implementation.

Background/Objectives: Many patients with obesity require conversion bariatric surgery (CBS) after sleeve gastrectomy (SG). The objective of this study was to assess the evolution of LDL cholesterol and other cardiometabolic parameters in patients who have undergone an SG and require a CBS, as the metabolic effects of such conversion procedures remain insufficiently understood. Methods: A retrospective analysis was conducted in a non-randomized prospective cohort of patients with severe obesity who were previously treated with SG and undergoing CBS. Changes in LDL cholesterol levels after SG were compared to those following CBS using repeated-measures ANOVA. Results: Twenty-eight patients were included (mean age 44.5 ± 7.2 years; 68% female; mean BMI 47.3 ± 7.2 kg/m²). Of these, 57% underwent Roux-en-Y gastric bypass (RYGB), and 43% underwent single-anastomosis duodeno–ileal bypass with sleeve gastrectomy (SADI-S) as conversion procedures. The mean time between SG and CBS was 93.5 ± 45.3 months for RYGB and 31.0 ± 45.2 months for SADI-S. The change in LDL cholesterol pre- vs. post-SG was 3.3 mg/dL (95% CI: −13.6 to 20.1), whereas the change pre- vs. post-CBS was −25.7 mg/dL (95% CI: −37.5 to −13.9) (p < 0.001). Remission of high LDL-C was 18.8% after SG and 73.3% after CBS (p = 0.023). The cardiometabolic profile showed a marked improvement profile during the SG period, followed by maintenance of these improvements during the CBS period. Conclusions: CBS (with either RYGB or SADI-S) results in a reduction in LDL-C, in contrast to the initial surgery with SG. However, CBS does not appear to provide additional benefits over SG in terms of other cardiometabolic parameters.

Background: There has been a substantial increase in the use of laparoscopic sleeve gastrectomy (SG) to treat morbid obesity despite observational evidence demonstrating the superiority of Roux-en-Y gastric bypass (RYGB) for reducing low-density lipoprotein (LDL) cholesterol. The main aim was to ascertain whether high LDL cholesterol levels should be considered when selecting the most appropriate surgical procedure for each patient (RYGB or SG). Methods: In this single-center, randomized clinical trial using intention-to-treat analysis, 38 patients with severe obesity and elevated levels of LDL cholesterol were randomly assigned to undergo RYGB or SG. The primary outcome was LDL cholesterol remission at 12 months, defined as LDL cholesterol < 3.36 nmol/l without lipid-lowering medications. Secondary outcomes included changes in weight, other comorbidities, qualitative lipoprotein traits, cholesterol esters, glycoproteins, cholesterol absorption and synthesis metabolites and complications. Results: Intention-to-treat analysis revealed that LDL cholesterol remission occurred in 66.6% of RYGB patients compared to 27.8% of SG patients (p = 0.019). Among patients completing follow-up, RYGB demonstrated superior remission (80.0% vs. 29.4%, p = 0.005). Exclusive benefits of RYGB included a reduction in large, medium, and small LDL particles. Cholesterol absorption markers showed differential behavior after both techniques: campesterol (Δ −15.2 µg/mg, 95% CI −30.2 to −0.1) decreased after RYGB, and sitosterol (Δ 21.1 µg/mg, 95% CI 0.9 to 41.2), cholestanol (Δ 30.6 µg/mg, 95% CI 14.8 to 57.9) and campesterol (Δ 18.4 µg/mg, 95% CI 4.4 to 32.3) increased after SG. No differences in weight loss, cholesterol esters, glycoproteins, cholesterol synthesis metabolites or postoperative complications were observed between techniques. Conclusion: In conclusion, RYGB is superior to SG in terms of short-term of high LDL cholesterol remission. Furthermore, RYGB also led to a greater improvement in lipoprotein parameters that confer an atherogenic profile. Therefore, the presence of elevated levels of LDL cholesterol should be considered when determining the optimal bariatric surgery procedure for each patient. Trial registration: Clinicaltrials.gov number, NCT03975478). Graphical

Despite elevated low-density lipoprotein (LDL) cholesterol levels, some older subjects with heterozygous familial hypercholesterolemia (HeFH) do not develop atherosclerotic cardiovascular disease (ACVD) during their lifetime. The factors related to this resilient state have not been fully established. The aim of this study was to evaluate differential characteristics between older HeFH subjects with and without ACVD and factors associated with the presence of ACVD. Subjects were part of the Spanish Atherosclerosis Society Dyslipidemia Registry, and those ≥ 70 years old and with HeFH were included. Baseline characteristics of these subjects with and without ACVD were compared. A multivariate analysis was performed to assess factors associated with the presence of ACVD. A total of 2148 subjects with HeFH were included. Resilient subjects were mostly female, younger and presented fewer comorbidities with respect to the ACVD group. Subjects without ACVD had higher baseline high-density lipoprotein (HDL) cholesterol (55.8 ± 17.1 vs. 47.9 ± 15.4 mg/dL; p < 0.001) and lower lipoprotein(a) [Lp(a)] (53.4 ± 67.9 vs. 66.6 ± 85.6 mg/dL; p < 0.001) levels with respect to those in the ACVD group. Lp(a) and the presence of ≥3 risk factors were associated with the presence of ACVD.

Background: The objective was to assess the association between early HbA1c levels and pregnancy complications and whether this relationship is affected when HbA1c thresholds are greater than or less than 39 mmol/mol (5.7%). Methods: Electronic searches of the MEDLINE and EMBASE databases up to October 2022 were conducted. We included retrospective and prospective observational studies. The inclusion criteria were as follows: HbA1c measurements taken at 39 mmol/mol (5.7%). The association between HbA1c levels and premature birth was statistically significant in studies using both higher and lower HbA1c thresholds. Conclusions: Women with high early HbA1c levels below the range of diabetes presented an increased risk of pregnancy complications such as macrosomia, LGA, and pre-eclampsia. An early HbA1c threshold of >39 mmol/mol (5.7%) showed the strongest association with pregnancy complications.

Purpose: To assess the effects of Helicobacter pylori (HP) eradication with an omeprazole, clarithromycin, amoxicillin, and metronidazole (OCAM) regimen on the metabolic profile and weight loss 12 months after bariatric surgery (BS). Methods: Retrospective analysis of a prospective cohort of patients with morbid obesity undergoing BS. HP presence was tested preoperatively by gastric biopsy and treated with OCAM when positive. Short-term metabolic outcomes and weight loss were evaluated. Results: HP infection was detected in 75 (45.7%) of the 164 patients included. OCAM effectiveness was 90.1%. HP-negative patients had a greater reduction in glucose levels at 3 (−14.6 ± 27.5 mg/dL HP-treated vs −22.0 ± 37.1 mg/dL HP-negative, p=0.045) and 6 months (−13.7 ± 29.4 mg/dL HP-treated vs −26.4 ± 42.6 mg/dL HP-negative, p= 0.021) and greater total weight loss (%TWL) at 6 (28.7 ± 6.7% HP-treated vs 30.45 ± 6.48% HP-negative, p= 0.04) and 12 months (32.21 ± 8.11% HP-treated vs 35.14 ± 8.63% HP-negative, p= 0.023). Conclusions: Preoperative treatment with OCAM has been associated to poorer glycemic and weight loss outcomes after BS. More research is needed on the influence of OCAM on gut microbiota, and in turn, the effect of the latter on metabolic and weight loss outcomes after BS. Graphical