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The latest evidence and guidance in lifestyle and surgical interventions to achieve weight loss in people with overweight or obesity

ABSTRACT
Background
The prevalence of obesity and related co-morbidities has reached epidemic proportions. Effective evidence-based treatment approaches are therefore important. Lifestyle intervention remains the mainstay of the treatment strategy to manage obesity. Increased evidence has also emerged regarding the efficacy of metabolic bariatric surgery (MBS) to induce significant and sustained weight loss while also reducing the progression of obesity-related co-morbidities for people living with obesity.
Aims & Methods
This article aims to bring together current evidence, guidance and best practice for the prevention and management of people living with overweight or obesity by means of lifestyle and behavioural intervention, as well as by MBS.
Result
Lifestyle intervention encompasses dietary strategies, physical activity and behavioural intervention. Discussion on MBS will focus on current indications, comparison between different MBS procedures, novel endoscopic techniques, potential complications and pre-operative management.
Plain Language Summary
The number of people living with excess weight and complications associated with being overweight is alarmingly quite high. Effective treatment approaches that are supported by clinical studies are therefore important. Lifestyle changes remain very important to manage excess weight. Increased evidence has also shown the benefits of weight loss surgery to produce significant weight loss which could be sustained, while also reducing the risk of developing medical conditions associated with excess weight. This article aims to bring together current evidence, guidance and best practice for the prevention and management of people living with excess weight by means of lifestyle and behavioural changes, as well as by weight loss surgery. Lifestyle intervention encompasses dietary strategies, physical activity and behavioural intervention. Discussion on weight loss surgery will focus on current criteria for suitability, comparison between different weight loss surgery procedures, new techniques, possible complications and appropriate management prior to weight loss surgery.

Disparities in heart failure deaths among people with diabetes in the United States: 1999–2020

Abstract
Aims
Heart failure is a leading cause of mortality in the United States, with significant disparities in its burden, particularly among underserved populations. A similar pattern exists for diabetes, but less is known about the mortality impact of these two comorbid conditions. This study aims to examine the risk of death from heart failure among people with diabetes, focusing on socio-demographic disparities.
Materials and Methods
We analysed data from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research Multiple Cause of Death Database, examining patterns of heart failure deaths in which diabetes was a contributing cause. Our analysis was stratified by socio-demographic variables, including race, ethnicity and geography, and we also explored trends over time.
Results
Between 1999 and 2020, there were 82 617 deaths from heart failure in which diabetes was a contributing cause, with an age-adjusted mortality rate of 32.04 deaths per 1 000 000 individuals. The death rate increased by 2.18% during the study period. Death rates were higher among Black Americans compared with White Americans (age-adjusted mortality rate ratio = 1.51, 95% confidence interval: 1.49–1.53), with disparities growing over time (a 10.75% increase for Black Americans vs. a 1.11% increase for White Americans).
Conclusions
Deaths from comorbid heart failure and diabetes are increasing in the United States, with significant and worsening disparities, particularly among minorities. Urgent action is needed to reduce heart failure mortality among people with diabetes, especially in underserved populations.

Carnitine supplementation improves insulin sensitivity and skeletal muscle acetylcarnitine formation in patients with type 2 diabetes

Abstract
Aim/Hypothesis
Recently, we reported that increasing free carnitine availability resulted in elevated skeletal muscle acetylcarnitine concentrations and restored metabolic flexibility in individuals who have impaired glucose tolerance. Metabolic flexibility is defined as the capacity to switch from predominantly fat oxidation while fasted to carbohydrate oxidation while insulin stimulated. Here we investigated if carnitine supplementation enhances the capacity of skeletal muscle to form acetylcarnitine and thereby improves insulin sensitivity and glucose homeostasis in patients with type 2 diabetes (T2DM).
Methods
Thirty-two patients followed a 12-week L-carnitine treatment (2970 mg/day, orally). Insulin sensitivity was assessed by a two-step hyperinsulinemic-euglycemic clamp. In vivo skeletal muscle acetylcarnitine concentrations at rest and post-exercise (30 min, 70% W
max) and intrahepatic lipid content (IHL) were determined by proton magnetic resonance spectroscopy (1H-MRS). All measurements were performed before and after 12 weeks of carnitine supplementation.
Results
Compliance with the carnitine supplementation was good (as indicated by increased plasma-free carnitine levels (p < 0.01) and pill count (97.1 ± 0.7%)). Insulin-induced suppression of endogenous glucose production (31.9 ± 2.9 vs. 39.9 ± 3.2%, p = 0.020) and peripheral insulin sensitivity (Δ rate of glucose disappearance (ΔRd): 10.53 ± 1.85 vs. 13.83 ± 2.02 μmol/kg/min, p = 0.005) improved after supplementation. Resting (1.18 ± 0.13 vs. 1.54 ± 0.17 mmol/kgww, p = 0.008) and post-exercise (3.70 ± 0.22 vs. 4.53 ± 0.30 mmol/kgww, p < 0.001) skeletal muscle acetylcarnitine concentrations were both elevated after carnitine supplementation. Plasma glucose (p = 0.083) and IHL (p = 0.098) tended to be reduced after carnitine supplementation.
Conclusion
Carnitine supplementation improved insulin sensitivity and tended to lower IHL and fasting plasma glucose levels in patients with type 2 diabetes. Furthermore, carnitine supplementation increased acetylcarnitine concentration in muscle, which may underlie the beneficial effect on insulin sensitivity.

Machine learning approach on plasma proteomics identifies signatures associated with obesity in the KORA FF4 cohort

Abstract
Aims
This study investigated the role of plasma proteins in obesity to identify predictive biomarkers and explore underlying biological mechanisms.
Methods
In the Cooperative Health Research in the Region of Augsburg (KORA) FF4 study, 809 proteins were measured in 2045 individuals (564 obese and 1481 non-obese). Multivariate logistic regression adjusted for confounders (basic and full models) was used to identify obesity-associated proteins. Priority-Lasso was applied for feature selection, followed by machine learning models (support vector machine [SVM], random forest [RF], k-nearest neighbour [KNN] and adaptive boosting [Adaboost]) for prediction. Correlation and enrichment analyses were performed to elucidate relationships between protein biomarkers, obesity risk factors and perturbed pathways. Mendelian randomisation (MR) assessed causal links between proteins and obesity.
Results
A total of 16 proteins were identified as significantly associated with obesity through multivariable logistic regression in the basic model and subsequent Priority-Lasso analysis. Enrichment analyses highlighted immune response, lipid metabolism and inflammation regulation were linked to obesity. Machine learning models demonstrated robust predictive performance with area under the curves (AUC) of 0.820 (SVM), 0.805 (RF), 0.791 (KNN) and 0.819 (Adaboost). All 16 proteins correlated with obesity-related risk factors such as blood pressure and lipid levels. MR analysis identified AFM, CRP and CFH as causal and potentially modifiable proteins.
Conclusions
The protein signatures identified in our study showed promising predictive potential for obesity. These findings warrant further investigation to evaluate their clinical applicability, offering insights into obesity prevention and treatment strategies.