Project description:ObjectiveLittle is known about the predictors of response to obesity interventions.MethodsIn 450 participants with obesity, body composition, resting energy expenditure, satiety, satiation, eating behavior, affect, and physical activity were measured by validated studies and questionnaires. These variables were used to classify obesity phenotypes. Subsequently, in a 12-month, pragmatic, real-world trial performed in a weight management center, 312 patients were randomly assigned to phenotype-guided treatment or non-phenotype-guided treatment with antiobesity medications: phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide. The primary outcome was weight loss at 12 months.ResultsFour phenotypes of obesity were identified in 383 of 450 participants (85%): hungry brain (abnormal satiation), emotional hunger (hedonic eating), hungry gut (abnormal satiety), and slow burn (decreased metabolic rate). In 15% of participants, no phenotype was identified. Two or more phenotypes were identified in 27% of patients. In the pragmatic clinical trial, the phenotype-guided approach was associated with 1.75-fold greater weight loss after 12 months with mean weight loss of 15.9% compared with 9.0% in the non-phenotype-guided group (difference -6.9% [95% CI -9.4% to -4.5%], P < 0.001), and the proportion of patients who lost >10% at 12 months was 79% in the phenotype-guided group compared with 34% with non-phenotype-guided treatment group.ConclusionsBiological and behavioral phenotypes elucidate human obesity heterogeneity and can be targeted pharmacologically to enhance weight loss.
Project description:Obesity is a chronic, multifactorial disease associated with a large number of comorbidities. The clinical management of obesity involves a stepwise integrated approach, beginning with behavioral and lifestyle modification, followed by antiobesity medications, endobariatric procedures, and bariatric surgery. Weight gain and subsequent obesity are common side effects of medications, such as prednisone or antipsychotics. In this era of precision medicine, it is essential to identify patients at the highest risk of weight gain as a result of medication use. Pharmacogenomics could play an important role in obesity management by optimizing use of antiobesity medications as well as minimizing adverse weight gain. This review aims to provide a comprehensive analysis of the current literature on the role of pharmacogenomics in obesity and medication-induced weight gain. In summary, there are more robust studies of medication associated with weight gain and pharmacogenomics, and more studies are needed to understand the role of pharmacogenomics in antiobesity medications.
Project description:Purpose of reviewTo highlight the added benefits of approved and upcoming, centrally-acting, anti-obesity drugs, focusing not only on the most common metabolic and cardiovascular effects but also on their less explored clinical benefits and drawbacks, in order to provide clinicians with a tool for more comprehensive, pharmacological management of obesity.Recent findingsObesity is increasingly prevalent worldwide and has become a challenge for healthcare systems and societies. Reduced life expectancy and cardiometabolic complications are some of the consequences of this complex disease. Recent insights into the pathophysiology of obesity have led to the development of several promising pharmacologic targets, so that even more effective drugs are on the horizon. The perspective of having a wider range of treatments increases the chance to personalize therapy. This primarily has the potential to take advantage of the long-term use of anti-obesity medication for safe, effective and sustainable weight loss, and to concomitantly address obesity complications/comorbidities when already established. The evolving scenario of the availability of anti-obesity drugs and the increasing knowledge of their added effects on obesity complications will allow clinicians to move into a new era of precision medicine.
Project description:BackgroundThe prevalence of obesity and related diseases has increased enormously in the last few decades, becoming a very important medical and social issue. Because of the increasing number of people who need weight loss therapies and the high costs associated with these, the search for reliable predictors of success for weight loss and weight maintenance treatments has become a priority.ObjectiveA literature review was undertaken to identify possible predictors of outcome of weight loss and weight maintenance in patients treated with antiobesity drugs.ResultsFor the majority of variables, published data are not sufficient to define their role on final outcomes. Among all considered factors, only early response to treatment appeared to be a reliable positive predictor, and diabetes a negative predictor of weight loss and maintenance.ConclusionTo date, no definitive results have been obtained. Due to the great benefits of reliable predictors of outcome associated to currently available antiobesity drugs and those under development, identifying these predictors has to be supported and encouraged.
Project description:The hypothesis tested in the present study was The effect fo weight loss by dietary intervention with very low calorie diet on colorectal inflammatory genes and genepathways. The study results have shown that a 10% weight loss in obese women down-regulated inflammatory and cancer gene pathways. In addition there was downregulation of transcription factors known to play an important role in colorectal cancer. Total RNA obtained from colorectal mucosal biopsy samples
Project description:IntroductionAlthough people with chronic kidney disease (CKD) and obesity have important motivations to lose weight, weight loss is also associated with health risks. We examined whether patterns of change in systolic blood pressure (SBP), serum albumin level, and fat-free mass (FFM) can help to differentiate between healthy and high-risk weight loss in this population.MethodsUsing data from the Chronic Renal Insufficiency Cohort Study (CRIC), we estimated a joint multivariate latent class model with 6 classes to identify distinct trajectories of body mass index (BMI), albumin, and SBP among participants with obesity (BMI ≥30 kg/m2 at baseline), accounting for informative missingness from death. In a secondary analysis, we fit a 6-class model with BMI and FFM.ResultsAmong 2831 participants (median baseline BMI 35.6, interquartile range [IQR] 32.4-40.0 kg/m2), median follow-up was 6.8 (IQR 4.8-12.9) years, median age was 61 (IQR 54-67) years, 53% were male, 50% were non-Hispanic Black, and 82% were trying to control or lose weight at baseline. Latent classes were associated with mortality risk (5-year cumulative incidence of mortality 6.8% and 1.5% in class 6 and 3, respectively). Class 6 had the highest mortality rate and was characterized by early, steep BMI loss, early serum albumin decline, and late SBP increase. In the secondary analysis, a class characterized by steep BMI and FFM loss was associated with the highest death risk.ConclusionsAmong adults with CKD and obesity, BMI loss with concomitant serum albumin or FFM loss was associated with a high risk of death.
Project description:Most individuals do not maintain weight loss, and weight regain increases cardio-metabolic risk beyond that of obesity. Adipose inflammation directly contributes to insulin resistance; however, immune-related changes that occur with weight loss and weight regain are not well understood. Single cell RNA-sequencing was completed with CITE-sequencing and biological replicates to profile changes in murine immune subpopulations following obesity, weight loss, and weight cycling. Weight loss normalized glucose tolerance, however, type 2 immune cells did not repopulate adipose following weight loss. Many inflammatory populations persisted with weight loss and increased further following weight regain. Obesity drove T cell exhaustion and broad increases in antigen presentation, lipid handing, and inflammation that persisted with weight loss and weight cycling. This work provides critical groundwork for understanding the immunological causes of weight cycling-accelerated metabolic disease.
Project description:Human patients were enrolled in a weight loss clinic and followed. Patients were male and female, normoglycemic,pre-diabetic and diabetic and with and without neuropathy.