Type 2 diabetes is a major risk factor for fragility fractures, yet the contributors to skeletal fragility remain unclear. Through integrated clinical metabolomics, in vivo, and in vitro analyses, we identify maltol—a widely used food additive—as a previously unrecognized risk factor for hyperglycemia-associated bone fragility. Metabolomic profiling of femoral neck tissue from individuals with fragility fractures showed diabetes-associated maltol accumulation, and elevated circulating maltol levels correlated with increased fracture incidence. Mechanistically, maltol inhibits osteoblast differentiation via Wnt/β-catenin and promotes osteoclast maturation through nuclear factor κB (NF-κB) signaling, disrupting bone remodeling. These effects are amplified under hyperglycemia, while insulin reversal of glucose levels mitigates maltol-induced skeletal deterioration in mouse models. Given the widespread use of maltol in processed foods, these findings suggest that food additive safety should consider metabolic context and call for disease-specific dietary exposure guidelines to reduce fracture risk in diabetes.

OBJECTIVE:To assess the effect of dapagliflozin plus calorie restriction on remission of type 2 diabetes. DESIGN:Multicentre, double blind, randomised, placebo controlled trial. SETTING:16 centres in mainland China from 12 June 2020 to 31 January 2023. PARTICIPANTS:328 patients with type 2 diabetes aged 20-70 years, with body mass index >25 and diabetes duration of <6 years. INTERVENTIONS:Calorie restriction with dapagliflozin 10 mg/day or placebo. MAIN OUTCOME MEASURES:Primary outcome: incidence of diabetes remission (defined as glycated haemoglobin <6.5% and fasting plasma glucose <126 mg/dL in the absence of all antidiabetic drugs for at least 2 months); secondary outcomes: changes in body weight, waist circumference, body fat, blood pressure, glucose homoeostasis parameters, and serum lipids over 12 months. RESULTS:Remission of diabetes was achieved in 44% (73/165) of patients in the dapagliflozin group and 28% (46/163) of patients in the placebo group (risk ratio 1.56, 95% confidence interval (CI) 1.17 to 2.09; P=0.002) over 12 months, meeting the predefined primary endpoint. Changes in body weight (difference -1.3 (95% CI -1.9 to -0.7) kg) and homoeostasis model assessment of insulin resistance (difference -0.8, -1.1 to -0.4) were significantly greater in the dapagliflozin group than in the placebo group. Likewise, body fat, systolic blood pressure, and metabolic risk factors were significantly more improved in the dapagliflozin group than in the placebo group. In addition, no significant differences were seen between the two groups in the occurrence of adverse events. CONCLUSION:The regimen of dapagliflozin plus regular calorie restriction achieved a much higher rate of remission of diabetes compared with calorie restriction alone in overweight or obese patients with type 2 diabetes. TRIAL REGISTRATION:ClinicalTrials.gov NCT04004793.

Our study investigated trends in osteoporosis management in Xiamen from 2012 to 2021, revealing improvements in screening and treatment, although medication use remained low. Additionally, we identified factors that may influence medication use and emphasized the importance of effective osteoporosis management strategies. Purpose The goal of the current study is to explore trends in assessment, diagnosis after fragility fractures, and osteoporosis treatment among hospitalized patients in Xiamen, China, between 2012 and 2021. Methods We conducted a retrospective cross-sectional study, using the Cochran-Armitage trend test to describe trends. Logistic regression was performed to identify the influencing factors of anti-osteoporosis medication (AOM) treatment. We performed a sensitivity analysis to verify the robustness of our findings. Results From 2012 to 2021, the rates of dual-energy X-ray absorptiometry (DXA) scans and bone turnover marker (BTM) examinations increased from 0 to 37% and 36.5%, respectively. 29.3% of patients with fragility fractures were diagnosed with osteoporosis. The use rate of AOM was only 22.7%. There was an upward trend in the prescription of bisphosphonates, increasing from 1% in 2012 to 16.8% in 2021. The use of calcitonin ranged from 4.1% (2014) to 32.7% (2021). Calcium and vitamin D supplementation prescribing increased significantly from 5.6% in 2012 to 78.7% in 2021. Logistic regression analysis showed that old age, female sex, history of fractures, DXA scans, and osteoporosis diagnosis were significantly associated with increased AOM use. Tobacco use, hypertension, diabetes, congestive heart failure, cerebral vascular accidents, and severe liver diseases were associated with a reduced likelihood of AOM treatment. Conclusions Although assessment, diagnosis after fragility fractures, and osteoporosis treatment have increased over the past decade, there are still deficiencies in the management of osteoporosis. In the future, it will be necessary to further strengthen management of osteoporosis.

AIMS:Type 2 diabetes mellitus (T2DM) arises from a complex interplay of genetic and environmental factors. Patients with T2DM are susceptible to hyperglycemia-related complications that can impair organ function, underscoring the need to explore the metabolic profiles of affected organs. METHODS:In this study, a comprehensive metabolomic analysis was conducted on the serum, kidney, and heart tissues from a rat model of diabetic complications (DC). Pattern recognition and multivariate statistical analyses were applied to identify the potential biomarkers of DC, and metabolic network analysis served to understand the specific metabolic pathways associated with DC. RESULTS:Fourteen significantly altered metabolites were identified in serum, 20 in the kidney, and 14 in the heart. The corresponding metabolic pathways included mineral absorption, mTOR signaling pathway, taurine and hypotaurine metabolism, glycine, serine and threonine metabolism, ABC transporters, glucagon signaling pathway, protein degradation and uptake, galactose metabolism, purine metabolism, nicotinic acid and nicotinamide metabolism, and glycolysis and gluconeogenesis. Differential metabolite network analysis revealed instinct metabolic patterns among the serum, kidney, and heart. Notably, the serum's metabolic correlation patterns were found to be somewhat similar to those observed in the kidney, whereas the heart exhibited less pronounced metabolite correlations compared to the other two biological matrices. CONCLUSIONS:These findings provide insights into the mechanism underlying the development of diabetic complications. The integration of metabolomics and biological network analyses into diabetes research can potentially revolutionize the field by revealing novel biomarkers for early detection and personalized treatment of diabetes and its associated complications.

Objective: This study was undertaken to investigate the relationship between amino acids (AAs) and nonalcoholic fatty liver disease (NAFLD), and how AAs changed following long-term exercise training under different exercise intensities. Methods: NAFLD participants (n = 220) were recruited and randomly assigned to control, moderate exercise and vigorous exercise groups with a 6-month follow-up. Clinical characteristics were carefully calculated and plasma AAs concentrations were determined using a validated ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results: At baseline, AAs concentrations were closely associated with clinical characteristics in NAFLD, particularly, the sum of branched chain amino acids (BCAAs) positively associated with intrahepatic triglyceride (IHTG) content (r = 0.18, p = 0.007). After 6-month exercise intervention, several AAs concentrations altered, and different exercise intensities exerted inverse effects on histidine, serine, glutamine, valine, tyrosine, and tryptophan concentrations changes, particularly, moderate exercise was much more efficient on decreasing BCAAs than vigorous exercise with a significant difference (p = 0.0008). Conclusion: Several AAs was closely associated with IHTG content in NAFLD patients, and 6-month moderate exercise more strongly reduced AAs concentrations, particularly BCAAs, compared to vigorous exercise. These findings suggest that exercise intensity optimization could enhance the metabolic benefits of exercise therapy in NAFLD.

AIM:This trial assessed the efficacy and safety of 2.24 g intragastric expandable capsules twice per day versus placebo for weight management in adults with overweight or obesity. METHODS:This double-blind, placebo-controlled study included adults with a body mass index of at least 24 kg/m2 and no more than 40 kg/m2 . In total, 280 participants were recruited from six hospitals in China and were assigned in a 1:1 ratio to receive 2.24 g oral intragastric expandable capsules or placebo for 24 weeks. Coprimary endpoints were the percentage change in body weight from baseline and the rate of weight reduction of ≥5%, assessed using both the full analysis set and per protocol set. RESULTS:At baseline, the mean body weight was 81.8 kg, and the mean body mass index was 29.4 kg/m2 . The mean body weight change at week 24 was -4.9% with intragastric expandable capsules versus -1.9% with placebo [estimated treatment difference (ETD) -3.0%, 95% confidence interval (CI) -4.1 to -1.9; p < .001] using the full analysis set and -6.1% versus -2.5% (ETD -3.6%, 95% CI -5.0 to -2.3; p < .001), respectively, using the per protocol set. The percentage of participants who had weight loss exceeding 5% was 45.0% in the intragastric expandable capsule group versus 19.7% in the placebo group (ETD 25.3%, 95% CI 14.7-35.9; p < .001) in the full analysis set and 55.9% versus 26.2% (ETD 29.6%, 95% CI 17.1-42.2; p < .001), respectively, in the per protocol set. Waist circumference significantly decreased at week 24 (intragastric expandable capsules vs. placebo: -5.6 ± 8.3 cm vs. -2.9 ± 4.8 cm; p = .003). The most common adverse events associated with the use of intragastric expandable capsules were gastrointestinal disorders (intragastric expandable capsule vs. placebo, 25.0% vs. 21.9%), and most were mild and transient. CONCLUSIONS:In this 24-week trial including participants with overweight or obesity, 2.24 g of intragastric expandable capsules twice daily led to a clinically meaningful reduction in body weight compared with placebo.

BackgroundAge-related visceral obesity could contribute to the development of cardiometabolic complications. The pathogenesis of visceral fat mass accumulation during the aging process remains complex and largely unknown. Interleukin-6 (IL-6) has emerged as one of the prominent inflammaging markers which are elevated in circulation during aging. However, the precise role of IL-6 in regulating age-related visceral adipose tissue accumulation remains uncertain.ResultsA cross-sectional study including 77 older adults (≥65 years of age) was initially conducted. There was a significant positive association between serum IL-6 levels and visceral fat mass. We subsequently validated a modest but significant elevation in serum IL-6 levels in aged mice. Furthermore, we demonstrated that compared to wildtype control, IL-6 deficiency (IL-6 KO) significantly attenuated the accumulation of visceral adipose tissue during aging. Further metabolic characterization suggested that IL-6 deficiency resulted in improved lipid metabolism parameters and energy expenditure in aged mice. Moreover, histological examinations of adipose depots revealed that the absence of IL-6 ameliorated adipocyte hypertrophy in visceral adipose tissue of aged mice. Mechanically, the ablation of IL-6 could promote the PKA-mediated lipolysis and consequently mitigate lipid accumulation in adipose tissue in aged mice.ConclusionOur findings identify a detrimental role of IL-6 during the aging process by promoting visceral adipose tissue accumulation through inhibition of lipolysis. Therefore, strategies aimed at preventing or reducing IL-6 levels may potentially ameliorate age-related obesity and improve metabolism during aging.

Purpose: To investigate the association between blood pressure (BP) time in range (TIR) and composite cardiovascular disease (CVD) in patients with primary aldosteronism (PA). Methods : Between January 2019 and December 2021, 47 patients with PA were recruited from the First Affiliated Hospital of Xiamen University. Twenty-four-hour ambulatory BP monitoring (ABPM) and composite CVD events were assessed in all patients. Results: The mean age of the patients was 48.8 ± 11.4 years. Compared to PA without composite CVD events, the nighttime systolic BP TIR [31.2% (6.2%, 81.2%) vs. 11.5% (0.0%, 29.7%), p = 0.02] and DDDs of antihypertensive medication [2.0 (1.0, 2.8) vs. 1.0 (1.0, 2.0), p = 0.03] were lower in PA patients with composite CVD events, while higher glucose (5.0 ± 1.0 mmol/L vs. 5.9 ± 1.5 mmol/L) and prevalence of a history of alcohol intake was higher in PA patients with composite CVD events. There were no differences in age, sex, BMI, smoking, duration of hypertension, lipid levels, aldosteronism, clinic BP, 24-hour mean BP, daytime or nighttime BP, percentage of nocturnal SBP or DBP decline, 24-hour BP TIR, daytime BP TIR, or nighttime DBP TIR between the two groups. After adjusting for confounding factors, nighttime systolic BP TIR was significantly associated with composite CVD events (adjusted OR = 0.92 [95% CI 0.86, 0.99]) in multiple logistic regression analysis. Conclusion : Patients with PA and composite CVD events had lower nighttime SBP TIR, suggesting that nighttime BP TIR may be a significant predictor of the prognosis of composite CVD events.

Retinal pericytes are mural cells surrounding capillaries to maintain the integrity of blood-retina barrier and regulate vascular behaviors. Pericyte loss has been considered as the hallmark of diabetic retinopathy (DR), which is a major complication of diabetes and the leading cause of blindness in adults. However, the precise function of pericytes in regulating the retinal microenvironment and the underlying mechanism remains largely unknown. In this study, we observed a secretory phenotype of pericytes with elevated inflammatory cytokines in response to Interleukin-1β (IL-1β), a canonical inflammatory cytokine which significantly increases during the initial stages of diabetic retinopathy. This phenotype is also accompanied by reduced expression of adherent junction proteins and contractile proteins. Paracrine cytokines derived from pericytes further induce the chemotaxis of microglia cells and trigger detrimental changes in endothelial cells, including reduced expression of tight junction protein Occludin and increased apoptosis. Mechanically, the secretion potential in pericytes is partially mediated by Hes1/STAT3 signaling pathway. Moreover, co-injection of stattic, an inhibitor targeting STAT3 activation, could effectively attenuate IL-1β-induced retinal inflammation and microglial activation in retina tissues. Collectively, these findings demonstrate the potential of retinal pericytes as an initial inflammatory sensor prior to their anatomical pathological loss, via undergoing phenotypic changes and secreting paracrine factors to amplify local inflammation and damage endothelial cells in vitro. Furthermore, inhibition of STAT3 activation by inhibitors significantly ameliorates IL-1β-induced retinal inflammation, suggesting STAT3 in retinal pericytes as a promising target for alleviating DR and other IL-1β-induced ocular diseases.

Purpose Proper management of subcentimeter thyroid nodules remains challenging for both clinicians and patients. Conducting extensive sonographic research using a safe and inexpensive tool for identifying thyroid nodules is necessary. This study aimed to identify whether having a highest ultrasound (US) risk characteristic suggests that US-guided fine-needle aspiration (FNA) biopsy in subcentimeter nodules is more appropriate for the identification of malignancy than active surveillance (AS) or surgery. Methods The data of patients with highly suspicious subcentimeter thyroid nodules with US characteristics who underwent surgery were retrospectively examined. Results Among a total of 556 subcentimeter nodules, 223 (40.1%) were benign and 333 (59.9%) were malignant, with a mean maximal nodule size of 8.1 mm. The US features that were significantly associated with malignancy were age below 45 years, irregular margin, presence of microcalcification, and a taller-than-wide shape (P < 0.001). Multivariate analysis also identified a taller-than-wide shape (OR = 8.988, P = 0.0015) as an independent factor associated with malignancy in subcentimeter thyroid nodules. The diagnostic performance of the preoperative FNA was classified as a malignancy, with a sensitivity of 98.4%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 76.9%. Conclusions This study is one of the few reports based on actual data of highest suspicious US features in thyroid subcentimeter nodules. A taller-than-wide shape is the US feature most significantly associated with malignancy. FNA is a simple, accurate, and reliable preoperative method for diagnosing malignant subcentimeter thyroid nodules with highly suspicious US characteristics. AS was less appropriate than FNA for subcentimeter nodules with a taller-than-wide shape, especially in patients ≤ 45 years.

AIM:The prevalence of the coexistence of low muscle mass and obesity is increasing, particularly with a rising trend observed in patients diagnosed with type 2 diabetes mellitus (T2DM). However, the association between the coexistence of low muscle mass and obesity and diabetic complications remains unclear. This study aimed to investigate these associations in patients with T2D. MATERIALS AND METHODS:A retrospective study was conducted, including 2387 hospitalized patients with T2DM. Data on demographic characteristics, biochemical parameters, diabetic complications and body composition was from electronic health records. The participants were categorized as control, low muscle mass, obesity and the coexistence of the low muscle mass and obesity groups according to the body compositions evaluated by dual-energy X-ray absorptiometry. Multiple logistic regression models were applied to assess the associations between the pattern of body composition and complications of diabetes. RESULTS:After adjustment for potential confounders, compared with patients in the control group, the odds ratios [95% confidence intervals (CIs)] of macrovascular complications of diabetes were 0.62 (95% CI, 0.27-1.39) for those in the low muscle mass group, 1.12 (95% CI, 0.59-2.11) in the obesity group, and 2.43 (95% CI, 1.16-5.07) in the coexistence of the low muscle mass and obesity group, respectively; the odds ratios (95% CIs) of microvascular complications of diabetes were 0.86 (95% CI, 0.52-1.43) for those in the low muscle mass group, 0.82 (95% CI, 0.53-1.26) in the obesity group, and 1.21 (95% CI, 0.69-2.15) in the coexistence of the low muscle mass and obesity group, respectively. CONCLUSION:According to our findings, the coexistence of low muscle mass and obesity, rather than low muscle mass or obesity alone, was significantly associated with a higher prevalence of macrovascular complications in hospitalized patients with T2DM. This association was not observed for diabetic microvascular complications.

Abstract Objective: The prevalence of Sarcopenic obesity (SO) is increasing, particularly with a rising trend observed in patients diagnosed with Type 2 diabetes (T2D). However, the association between SO and diabetic complications remains unclear when compared to sarcopenia or obesity alone. This study aimed to investigate the associations between sarcopenia, obesity, SO, and diabetes complications in patients with T2D. Methods: A retrospective study was conducted including 2387 hospitalized patients with T2D. Data associated with demographic characteristics, biochemical parameters, diabetic complications, and body composition from electronic health records were collected. The participants were categorized as normal (nonsarcopenia nonobesity), sarcopenia, obesity, and SO groups according to the body compositions evaluated by dual-energy X-ray absorptiometry. Multiple logistic regression models were applied to assess the associations between body composition and complications of diabetes. Results: After adjustment for potential confounders, compared with patients in normal group, the odds ratios (95% CIs) of macrovascular complications of diabetes were 0.64 (95% CI, 0.29-1.42) for those in sarcopenia group, 1.05 (95% CI, 0.56-1.97) in obesity group, and 2.45 (95% CI, 1.18-5.09) in SO group, respectively; the odds ratios (95% CIs) of microvascular complications of diabetes was 0.95 (95% CI, 0.58-1.55) for those in sarcopenia group, 0.80 (95% CI, 0.53-1.22) in obesity group, and 1.21 (95% CI, 0.69-2.11) in SO group, respectively. Conclusion: According to our findings, SO, rather than sarcopenia or obesity alone, was significantly associated with a higher prevalence of macrovascular complications, in hospitalized patients with T2DM. This association was not observed for diabetic microvascular complications.

This randomized clinical trial assesses the long-term effect of vigorous and moderate exercise on incident diabetes over a 10-year follow-up after a 12-month exercise intervention.

BackgroundProviding comprehensive and individualized diabetes care remains a significant challenge in the face of the increasing complexity of diabetes management and a lack of specialized endocrinologists to support diabetes care. Clinical decision support systems (CDSSs) are progressively being used to improve diabetes care, while many health care providers lack awareness and knowledge about CDSSs in diabetes care. A comprehensive analysis of the applications of CDSSs in diabetes care is still lacking. ObjectiveThis review aimed to summarize the research landscape, clinical applications, and impact on both patients and physicians of CDSSs in diabetes care. MethodsWe conducted a scoping review following the Arksey and O’Malley framework. A search was conducted in 7 electronic databases to identify the clinical applications of CDSSs in diabetes care up to June 30, 2022. Additional searches were conducted for conference abstracts from the period of 2021-2022. Two researchers independently performed the screening and data charting processes. ResultsOf 11,569 retrieved studies, 85 (0.7%) were included for analysis. Research interest is growing in this field, with 45 (53%) of the 85 studies published in the past 5 years. Among the 58 (68%) out of 85 studies disclosing the underlying decision-making mechanism, most CDSSs (44/58, 76%) were knowledge based, while the number of non-knowledge-based systems has been increasing in recent years. Among the 81 (95%) out of 85 studies disclosing application scenarios, the majority of CDSSs were used for treatment recommendation (63/81, 78%). Among the 39 (46%) out of 85 studies disclosing physician user types, primary care physicians (20/39, 51%) were the most common, followed by endocrinologists (15/39, 39%) and nonendocrinology specialists (8/39, 21%). CDSSs significantly improved patients’ blood glucose, blood pressure, and lipid profiles in 71% (45/63), 67% (12/18), and 38% (8/21) of the studies, respectively, with no increase in the risk of hypoglycemia. ConclusionsCDSSs are both effective and safe in improving diabetes care, implying that they could be a potentially reliable assistant in diabetes care, especially for physicians with limited experience and patients with limited access to medical resources. International Registered Report Identifier (IRRID)RR2-10.37766/inplasy2022.9.0061

There are emerging studies suggesting that non-alcoholic fatty liver disease (NAFLD) is a heterogeneous disease with multiple etiologies and molecular phenotypes. Fibrosis is the key process in NAFLD progression. In this study, we aimed to explore molecular phenotypes of NAFLD with a particular focus on the fibrosis phenotype and also aimed to explore the changes of macrophage subsets in the fibrosis subset of NAFLD. To assess the transcriptomic alterations of key factors in NAFLD and fibrosis progression, we included 14 different transcriptomic datasets of liver tissues. In addition, two single-cell RNA sequencing (scRNA-seq) datasets were included to construct transcriptomic signatures that could represent specific cells. To explore the molecular subsets of fibrosis in NAFLD based on the transcriptomic features, we used a high-quality RNA-sequencing (RNA-seq) dataset of liver tissues from patients with NAFLD. Non-negative matrix factorization (NMF) was used to analyze the molecular subsets of NAFLD based on the gene set variation analysis (GSVA) enrichment scores of key molecule features in liver tissues. The key transcriptomic signatures on NAFLD including non-alcoholic steatohepatitis (NASH) signature, fibrosis signature, non-alcoholic fatty liver (NAFL) signature, liver aging signature and TGF-β signature were constructed by liver transcriptome datasets. We analyzed two liver scRNA-seq datasets and constructed cell type-specific transcriptomic signatures based on the genes that were highly expressed in each cell subset. We analyzed the molecular subsets of NAFLD by NMF and categorized four main subsets of NAFLD. Cluster 4 subset is mainly characterized by liver fibrosis. Patients with Cluster 4 subset have more advanced liver fibrosis than patients with other subsets, or may have a high risk of liver fibrosis progression. Furthermore, we identified two key monocyte-macrophage subsets which were both significantly correlated with the progression of liver fibrosis in NAFLD patients. Our study revealed the molecular subtypes of NAFLD by integrating key information from transcriptomic expression profiling and liver microenvironment, and identified a novel and distinct fibrosis subset of NAFLD. The fibrosis subset is significantly correlated with the profibrotic macrophages and M2 macrophage subset. These two liver macrophage subsets may be important players in the progression of liver fibrosis of NAFLD patients.

Background:Fibrosis is an important pathological process in the development of non-alcoholic steatohepatitis (NASH), and the activation of hepatic stellate cell (HSC) is a central event in liver fibrosis. However, the transcriptomic change of activated HSCs (aHSCs) and resting HSCs (rHSCs) in NASH patients has not been assessed. This study aimed to identify transcriptomic signature of HSCs during the development of NASH and the underlying key functional pathways.Methods:NASH-associated transcriptomic change of HSCs was defined by single-cell RNA-sequencing (scRNA-seq) analysis, and those top upregulated genes were identified as NASH-associated transcriptomic signatures. Those functional pathways involved in the NASH-associated transcriptomic change of aHSCs were explored by weighted gene co-expression network analysis (WGCNA) and functional enrichment analyses. Key regulators were explored by upstream regulator analysis and transcription factor enrichment analysis.Results:scRNA-seq analysis identified numerous differentially expressed genes in both rHSCs and aHSCs between NASH patients and healthy controls. Both scRNA-seq analysis and in-vivo experiments showed the existence of rHSCs (mainly expressing a-SMA) in the normal liver and the increased aHSCs (mainly expressing collagen 1) in the fibrosis liver tissues. NASH-associated transcriptomic signature of rHSC (NASHrHSCsignature) and NASH-associated transcriptomic signature of aHSC (NASHaHSCsignature) were identified. WGCNA revealed the main pathways correlated with the transcriptomic change of aHSCs. Several key upstream regulators and transcription factors for determining the functional change of aHSCs in NASH were identified.Conclusion:This study developed a useful transcriptomic signature with the potential in assessing fibrosis severity in the development of NASH. This study also identified the main pathways in the activation of HSCs during the development of NASH.

This article introduced the research design and main results of the article " Effect of Moderate and Vigorous Aerobic Exercise on Incident Diabetes in Adults with Obesity: A 10-Year Follow-up of a Randomized Clinical Trial" recently published in JAMA Internal Medicine, and addressed the scientific significance of the study. The importance of obesity management has been well discussed recently. This study investigated obesity management strategies for obese individuals and their long-term metabolic benefits.