Weight regain after a diet-induced loss is predicted by higher baseline leptin and lower ghrelin plasma levels

CONTEXT: Appetite-related hormones may play an important role in weight regain after obesity therapy. OBJECTIVE: Our objective was to investigate the potential involvement of ghrelin, leptin, and insulin plasma levels in weight regain after a therapeutic hypocaloric diet. DESIGN: A group of obese/overweight volunteers (49 women and 55 men; 35 ± 7 yr; 30.7 ± 2.4 kg/m(2)) followed an 8-wk hypocaloric diet (-30% energy expenditure) and were evaluated again 32 wk after treatment. Body weight as well as plasma fasting ghrelin, leptin, and insulin concentrations were measured at three points (wk 0, 8, and 32). RESULTS: After the 8-wk hypocaloric diet, the average weight loss was -5.0 ± 2.2% (P < 0.001). Plasma leptin and insulin concentrations decreased significantly, whereas ghrelin levels did not markedly change. In the group regaining more than 10% of the weight loss, leptin levels were higher (P < 0.01), whereas ghrelin levels were lower (P < 0.05). No differences were observed in insulin levels. Weight regain at wk 32 was negatively correlated with ghrelin and positively associated with leptin levels at baseline (wk 0) and endpoint (wk 8). These outcomes showed a gender-specific influence, being statistically significant among men for ghrelin and between women for leptin. Moreover, a decrease in ghrelin after an 8-wk hypocaloric diet was related to an increased risk for weight regain (odds ratio = 3.109; P = 0.008) whereas a greater reduction in leptin (odds ratio = 0.141; P = 0.001) was related to weight-loss maintenance. CONCLUSIONS: Subjects with higher plasma leptin and lower ghrelin levels at baseline could be more prone to regain lost weight, and hormones levels could be proposed as biomarkers for predicting obesity-treatment outcomes

Standards of care for medical management of acromegaly in pituitary tumor centers of excellence (PTCOE)

Purpose: A series of consensus guidelines on medical treatment of acromegaly have been produced in the last two decades. However, little information is available on their application in clinical practice. Furthermore, international standards of acromegaly care have not been published. The aim of our study was to report current standards of care for medical therapy of acromegaly, using results collected through an audit performed to validate criteria for definition of Pituitary Tumor Centers of Excellence (PTCOE). Methods: Details of medical treatment approaches to acromegaly were voluntarily provided by nine renowned international centers that participated in this audit. For the period 2018–2020, we assessed overall number of acromegaly patients under medical treatment, distribution of patients on different treatment modalities, overall biochemical control rate with medical therapy, and specific control rates for different medical treatment options. Results: Median number of total patients and median number of new patients with acromegaly managed annually in the endocrinology units of the centers were 206 and 16.3, respectively. Median percentage of acromegaly patients on medical treatment was 48.9%. Among the patients on medical treatment, first-generation somatostatin receptor ligand (SRL) monotherapy was used with a median rate of 48.7%, followed by combination therapies with a median rate of 29.3%. Cabergoline monotherapy was used in 6.9% of patients. Pegvisomant monotherapy was used in 7 centers and pasireotide monotherapy in 5 centers, with median rates of 7.9% and 6.3%, respectively. Conclusions: Current standards of care in PTCOEs include use of first-generation SRLs as the first medical option in about 50% of patients, as recommended by consensus guidelines. However, some patients are kept on this treatment despite inadequate control suggesting that cost-effectiveness, availability, patient preference, side effects, and therapeutic inertia may play a possible role also in PTCOE. Moreover, at odds with consensus guidelines, other monotherapies for acromegaly appear to have a marginal role as compared to combination therapies as extrapolated from PTCOE practice data. Presence of uncontrolled patients in each treatment category suggest that further optimization of medical therapy, as well as use of other therapeutic tools such as radiosurgery may be needed

ANGPTL-4 is associated with obesity and lipid profile in children and adolescents

Angiopoietin-like protein 4 (ANGPTL-4) regulates lipidic metabolism and a_ects energy homeostasis. However, its function in children with obesity remains unknown. We investigated plasma ANGPTL-4 levels in children and its relationship with body mass index (BMI) and di_erent lipidic parameters such as free fatty acids (FFA). Plasma ANGPTL-4 levels were analyzed in two di_erent cohorts. In the first cohort (n = 150, age 3-17 years), which included children with normal weight or obesity, we performed a cross-sectional study. In the second cohort, which included only children with obesity (n = 20, age 5-18 years) followed up for two years after an intervention for weight loss, in which we performed a longitudinal study measuring ANGPTL-4 before and after BMI-loss. In the cross-sectional study, circulating ANGPTL-4 levels were lower in children with obesity than in those with normal weight. Moreover, ANGPTL-4 presented a negative correlation with BMI, waist circumference, weight, insulin, homeostasis model assessment of insulin resistance index (HOMA index), triglycerides, and leptin, and a positive correlation with FFA and vitamin-D. In the longitudinal study, the percent change in plasma ANGPTL-4 was correlated with the percent change in FFA, total-cholesterol and high-density lipoprotein cholesterol. This study reveals a significant association of ANGPTL-4 with pediatric obesity and plasma lipid profile

Effect of a Very-Low-Calorie Ketogenic Diet on Circulating Myokine Levels Compared with the Effect of Bariatric Surgery or a Low-Calorie Diet in Patients with Obesity

The preservation of muscle mass and muscle function after weight loss therapy is currently a considerable challenge in the fight against obesity. Muscle mass secretes proteins called myokines that have relevant functions in the regulation of metabolism and health. This study was aimed to evaluate whether a very low-calorie ketogenic (VLCK) diet may modulate myokine levels, in addition to changes in body composition, compared to a standard, balanced low-calorie (LC) diet or bariatric surgery in patients with obesity. Body composition, ketosis, insulin sensitivity and myokines were evaluated in 79 patients with overweight/obesity after a therapy to lose weight with a VLCK diet, a LC diet or bariatric surgery. The follow-up was 6 months. The weight loss therapies induced changes in myokine levels in association with changes in body composition and biochemical parameters. The effects on circulating myokine levels compared to those at baseline were stronger after the VLCK diet than LC diet or bariatric surgery. Differences reached statistical significance for IL-8, MMP2 and irisin. In conclusion, nutritional interventions or bariatric surgery to lose weight induces changes in circulating myokine levels, being this effect potentially most notable after following a VLCK diet

Interplay of atherogenic factors, protein intake and betatrophin levels in obese–metabolic syndrome patients treated with hypocaloric diets

The present research evaluated circulating betatrophin levels in obese patients with metabolic syndrome features under energy-restricted weight-loss programs and in normal weight in order to stablish the putative interplay between the levels of this hormone, diet and metabolic risk factors linked to obesity and associated comorbidities

Higher baseline irisin concentrations are associated with greater reductions in glycemia and insulinemia after weight loss in obese subjects

Irisin is assumed to be a relevant link between muscle and weight maintenance as well as to mediate exercise benefits on health. The aim of this study was to assess the possible associations between irisin levels and glucose homeostasis in obese subjects with metabolic syndrome (MetS) following an energy-restricted treatment. Ninety-six adults with excessive body weight and MetS features underwent a hypocaloric dietary pattern for 8 weeks, within the RESMENA randomized controlled trial (www.clinicaltrials.gov; NCT01087086). After the intervention, dietary restriction significantly reduced body weight and evidenced a dietary-induced decrease in circulating levels of irisin in parallel with improvements on glucose homeostasis markers. Interestingly, participants with higher irisin values at baseline (above the median) showed a greater reduction on glucose (P=0.022) and insulin (P=0.021) concentrations as well as on the homeostasis model assessment index (P=0.008) and triglycerides (P=0.006) after the dietary intervention, compared with those presenting low-irisin baseline values (below the median). Interestingly, a positive correlation between irisin and carbohydrate intake was found at the end of the experimental period. In conclusion, irisin appears to be involved in glucose metabolism regulation after a dietary-induced weight loss

Association between circulating irisin levels and the promotion of insulin resistance during the weight maintenance period after a dietary weight-lowering program in obese patients

Objective. Weight regain is associated with the promotion of insulin resistance. The newly discovered myokine irisin, which was proposed to be involved in the management of insulin sensitivity, could play a role in this process. This study aimed to investigate the association between irisin and reduced insulin sensitivity induced by weight regain. Materials/Methods. Insulin sensitivity was evaluated according to the homeostasis model assessment of insulin resistance (HOMA-IR) in 136 obese patients who followed an eight-week hypocaloric diet (30% reduced energy expenditure) to lose weight and were re-evaluated four or six months after treatment. Irisin plasma levels, as well as the levels of leptin, adiponectin, ghrelin and TNF-α, were quantified in a sub-cohort (n=73) from the initially studied patients at baseline (T0), at the diet endpoint (T1) and after the follow-up period (T2). Results. After a successful dietary intervention to lose weight, 50% of the patients who regained the lost weight during the follow-up period were categorized as insulin resistant (HOMA-IR≥2.5) compared with only 25% of patients who maintained the weight loss (p=0.018). Importantly, in addition to the well-studied hormones leptin and adiponectin, irisin plasma levels were statistically associated with several risk factors for insulin resistance. Indeed, the increased risk of insulin resistance during the follow-up period was related to high irisin levels at baseline (odds ratio=4.2; p=0.039). Conclusions. Circulating irisin predicts the insulin resistance onset in association with weight regain. Therefore, irisin could be secreted as an adaptive response to counteract the deleterious effect of excess adiposity on glucose homeostasis

DNA methylation map in circulating leukocytes mirrors subcutaneous adipose tissue methylation pattern: a genome-wide analysis from non-obese and obese patients

The characterization of the epigenetic changes within the obesity-related adipose tissue will provide new insights to understand this metabolic disorder, but adipose tissue is not easy to sample in population-based studies. We aimed to evaluate the capacity of circulating leukocytes to reflect the adipose tissue-specific DNA methylation status of obesity susceptibility. DNA samples isolated from subcutaneous adipose tissue and circulating leukocytes were hybridized in the Infinium HumanMethylation 450 BeadChip. Data were compared between samples from obese (n = 45) and non-obese (n = 8-10) patients by Wilcoxon-rank test, unadjusted for cell type distributions. A global hypomethylation of the differentially methylated CpG sites (DMCpGs) was observed in the obese subcutaneous adipose tissue and leukocytes. The overlap analysis yielded a number of genes mapped by the common DMCpGs that were identified to reflect the obesity state in the leukocytes. Specifically, the methylation levels of FGFRL1, NCAPH2, PNKD and SMAD3 exhibited excellent and statistically significant efficiencies in the discrimination of obesity from non-obesity status (AUC > 0.80; p < 0.05) and a great correlation between both tissues. Therefore, the current study provided new and valuable DNA methylation biomarkers of obesity-related adipose tissue pathogenesis through peripheral blood analysis, an easily accessible and minimally invasive biological material instead of adipose tissue

Growth Hormone Research Society perspective on biomarkers of GH action in children and adults

Objective The Growth Hormone Research Society (GRS) convened a Workshop in 2017 to evaluate clinical endpoints, surrogate endpoints and biomarkers during GH treatment of children and adults and in patients with acromegaly. Participants GRS invited 34 international experts including clinicians, basic scientists, a regulatory scientist and physicians from the pharmaceutical industry. Evidence Current literature was reviewed and expert opinion was utilized to establish the state of the art and identify current gaps and unmet needs. Consensus process Following plenary presentations, breakout groups discussed questions framed by the planning committee. The attendees re-convened after each breakout session to share the group reports. A writing team compiled the breakout session reports into a document that was subsequently discussed and revised by participants. This was edited further and circulated for final review after the meeting. Participants from pharmaceutical companies were not part of the writing process. Conclusions The clinical endpoint in paediatric GH treatment is adult height with height velocity as a surrogate endpoint. Increased life expectancy is the ideal but unfeasible clinical endpoint of GH treatment in adult GH-deficient patients (GHDA) and in patients with acromegaly. The pragmatic clinical endpoints in GHDA include normalization of body composition and quality of life, whereas symptom relief and reversal of comorbidities are used in acromegaly. Serum IGF-I is widely used as a biomarker, even though it correlates weakly with clinical endpoints in GH treatment, whereas in acromegaly, normalization of IGF-I may be related to improvement in mortality. There is an unmet need for novel biomarkers that capture the pleiotropic actions of GH in relation to GH treatment and in patients with acromegaly

Repositioning of the global epicentre of non-optimal cholesterol

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.</p