Similar Reductions In Body Weight Research Articles

One-year changes in body composition and musculoskeletal health following metabolic/bariatric surgery.

There are limited comparative studies between one anastomosis gastric bypass (OAGB) versus Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on body composition and musculoskeletal health. To compare changes in body composition, areal bone mineral density (aBMD), muscle strength, and physical function in the first year following OAGB, RYGB and SG within a UK-based healthcare setting. This is a secondary analysis of the BARI-LIFESTYLE trial in 119 adults (77% women; mean±SD, age: 45.9±10.3 years; BMI: 43.6±5.5 kg/m2) who underwent OAGB (n=19), RYGB (n=39) and SG (n=61). Body composition and aBMD by dual energy x-ray absorptiometry, handgrip strength, sit-to-stand (STS) test and 6-minute walking test (6MWT) were assessed pre-surgery and at 12 months post-surgery. OAGB, RYGB, and SG exhibited similar reductions in body weight, body fat and lean mass (within-group comparisons, p<0.001). All surgery types were associated with reductions in aBMD at the total hip, femoral neck, and lumbar spine, which were more pronounced after OAGB and RYGB compared to SG (all p<0.03), though no difference between OAGB and RYGB. Despite reductions in absolute handgrip strength, relative handgrip strength, STS test and 6MWT improved post-surgery (all p<0.02), with no differences by surgical procedure. OAGB, RYGB, and SG resulted in comparable weight loss, changes in body composition and improvements in relative muscle strength and physical function. OAGB and RYGB, compared with SG, led to greater BMD reductions at clinically relevant sites. Future long-term studies should explore whether these BMD reductions translate into a greater fracture risk.

Short-term effects of obesity surgery versus low-energy diet on body composition and tissue-specific glucose uptake: a randomised clinical study using whole-body integrated 18F-FDG-PET/MRI

Aims/hypothesisObesity surgery (OS) and diet-induced weight loss rapidly improve insulin resistance. We aim to investigate the impact of either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with a diet low in energy (low-calorie diet; LCD) on body composition, glucose control and insulin sensitivity, assessed both at the global and tissue-specific level in individuals with obesity but not diabetes.MethodsIn this parallel group randomised controlled trial, patients on a waiting list for OS were randomised (no blinding, sealed envelopes) to either undergo surgery directly or undergo an LCD before surgery. At baseline and 4 weeks after surgery (n=15, 11 RYGB and 4 SG) or 4 weeks after the start of LCD (n=9), investigations were carried out, including an OGTT and hyperinsulinaemic–euglycaemic clamps during which concomitant simultaneous whole-body [18F]fluorodeoxyglucose-positron emission tomography (PET)/MRI was performed. The primary outcome was HOMA-IR change.ResultsOne month after bariatric surgery and initiation of LCD, both treatments induced similar reductions in body weight (mean ± SD: −7.7±1.4 kg and −7.4±2.2 kg, respectively), adipose tissue volume (7%) and liver fat content (2% units). HOMA-IR, a main endpoint, was significantly reduced following OS (−26.3% [95% CI −49.5, −3.0], p=0.009) and non-significantly following LCD (−20.9% [95% CI −58.2, 16.5). For both groups, there were similar reductions in triglycerides and LDL-cholesterol. Fasting plasma glucose and insulin were also significantly reduced only following OS. There was an increase in glucose AUC in response to an OGTT in the OS group (by 20%) but not in the LCD group. During hyperinsulinaemia, only the OS group showed a significantly increased PET-derived glucose uptake rate in skeletal muscle but a reduced uptake in the heart and abdominal adipose tissue. Both liver and brain glucose uptake rates were unchanged after surgery or LCD. Whole-body glucose disposal and endogenous glucose production were not significantly affected.Conclusions/interpretationThe short-term metabolic effects seen 4 weeks after OS are not explained by loss of body fat alone. Thus OS, but not LCD, led to reductions in fasting plasma glucose and insulin resistance as well as to distinct changes in insulin-stimulated glucose fluxes to different tissues. Such effects may contribute to the prevention or reversal of type 2 diabetes following OS. Moreover, the full effects on whole-body insulin resistance and plasma glucose require a longer time than 4 weeks.Trial registrationClinicalTrials.gov NCT02988011FundingThis work was supported by AstraZeneca R&D, the Swedish Diabetes Foundation, the European Union’s Horizon Europe Research project PAS GRAS, the European Commission via the Marie Sklodowska Curie Innovative Training Network TREATMENT, EXODIAB, the Family Ernfors Foundation, the P.O. Zetterling Foundation, Novo Nordisk Foundation, the Agnes and Mac Rudberg Foundation and the Uppsala University Hospital ALF grantsGraphical

Early time-restricted carbohydrate consumption vs conventional dieting in type 2 diabetes: a randomised controlled trial

Aims/hypothesisEarly time-restricted carbohydrate consumption (eTRC) is a novel dietary strategy that involves restricting carbohydrate-rich food intake to the morning and early afternoon to align with circadian variations in glucose tolerance. We examined the efficacy, feasibility and safety of eTRC in individuals with type 2 diabetes under free-living conditions.MethodsIn this randomised, parallel-arm, open label, controlled trial, participants with type 2 diabetes and overweight/obesity (age 67.2±7.9 years, 47.8% women, BMI 29.4±3.7 kg/m2, HbA1c 49±5 mmol/mol [6.6±0.5%]) were randomised, using computer-generated random numbers, to a 12 week eTRC diet or a Mediterranean-style control diet with matched energy restriction and macronutrient distribution (50% carbohydrate, 30% fat and 20% protein). The primary outcome was the between-group difference in HbA1c at 12 weeks. Body composition, 14 day flash glucose monitoring and food diary analysis were performed every 4 weeks. Mixed meal tolerance tests with mathematical beta cell function modelling were performed at baseline and after 12 weeks.ResultsTwelve (85.7%) participants in the eTRC arm and 11 (84.6%) participants in the control arm completed the study, achieving similar reductions in body weight and fat mass. The two groups experienced comparable improvements in HbA1c (−3 [−6, −0.3] mmol/mol vs −4 [−6, −2] mmol/mol, corresponding to −0.2 [−0.5, 0]% and −0.3 [−0.5, −0.1]%, respectively, p=0.386), fasting plasma glucose, flash glucose monitoring-derived glucose variability and mixed meal tolerance test-derived glucose tolerance, insulin resistance, insulin clearance and plasma glucagon levels, without changes in model-derived beta cell function parameters, glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide and non-esterified fatty acid levels. The two diets similarly reduced liver function markers and triglyceride levels, being neutral on other cardiometabolic and safety variables. In exploratory analyses, diet-induced changes in body weight and glucometabolic variables were not related to the timing of carbohydrate intake.Conclusions/interpretationThe proposed eTRC diet provides a feasible and effective alternative option for glucose and body weight management in individuals with type 2 diabetes, with no additional metabolic benefits compared with conventional dieting.Trial registrationClinicalTrials.gov NCT05713058FundingThis study was supported by the European Society for Clinical Nutrition and Metabolism (ESPEN) and the Italian Society of Diabetology (SID).Graphical

Comparison of Protein- or Amino Acid-Based Supplements in the Rehabilitation of Men with Severe Obesity: A Randomized Controlled Pilot Study.

Weight loss is associated with a reduction in all body compartments, including muscle mass (MM), and this effect produces a decrease in function and muscle strength. Our objective was to assess the impact of protein or amino acid supplements on MM loss in middle-aged men (age < 65 years) with severe obesity (BMI > 35 kg/m2) during weight loss. We conducted a single-site randomized controlled trial (Clinicaltrials.gov NCT05143398) with 40 in-patient male subjects with severe obesity. Participants underwent an intervention program consisting of a low-calorie balanced diet and structured physical activity. They were randomly assigned to 4-week treatment groups: (1) control (CTR, N = 10), (2) protein (P, N = 10), (3) branched-chain amino acid (BCAA, N = 10), and (4) essential amino acid mixture with tricarboxylic acid cycle intermediates (PD-E07, N = 10) supplementation. Following 4 weeks of intervention, all groups showed similar reductions in body weight compared to baseline. When examining the delta values, a notable increase in muscle mass (MM) was observed in the PD-E07 intervention group [MM (kg): 2.84 ± 3.57; MM (%): 3.63 ± 3.14], in contrast to the CTR group [MM (kg): -2.46 ± 3.04; MM (%): -0.47 ± 2.28], with a statistical significance of p = 0.045 and p = 0.023, respectively. However, the MM values for the P group [MM (kg): -2.75 ± 5.98, p = 0.734; MM (%): -0.44 ± 4.02, p = 0.990] and the BCAA group [MM (kg): -1 ± 3.3, p = 0.734; MM (%): 0.34 ± 2.85, p = 0.956] did not exhibit a statistically significant difference when compared to the CTR group. Amino acid-based supplements may effectively mitigate the loss of MM typically observed during weight reduction. Further validation through large-scale studies is necessary.

Treatment sequencing using the dual amylin and calcitonin receptor agonist KBP-336 and semaglutide results in durable weight loss

ObjectiveLong-acting dual amylin and calcitonin receptor agonists (DACRAs) hold great promise as potential treatments for obesity and its associated comorbidities. These agents have demonstrated beneficial effects on body weight, glucose control, and insulin action mirroring the effects observed with glucagon-like peptide-1 (GLP-1) agonist treatment. Strategies aimed at enhancing and prolonging treatment efficacy include treatment sequencing and combination therapy. Here, we sought to investigate the impact of switching between or combining treatment with the DACRA KBP-336 and the GLP-1 analog semaglutide in fed rats with obesity induced by a high-fat diet (HFD). MethodsTwo studies were performed in which HFD-induced obese Sprague Dawley rats were switched between treatment with KBP-336 (4.5 nmol/kg, Q3D) and semaglutide (50 nmol/kg, Q3D) or a combination of the two. Treatment efficacy on weight loss and food intake was evaluated, and glucose tolerance was assessed by oral glucose tolerance tests. ResultsKBP-336 and semaglutide monotherapy resulted in a similar reduction in body weight and food intake. Treatment sequencing resulted in continuous weight loss and all monotherapies resulted in similar weight loss independent of the treatment regimen (P < 0.001 compared to vehicle). The combination of KBP-336 and semaglutide significantly improved the weight loss compared to either monotherapy alone (P < 0.001), which was evident in the adiposity at the study end. All treatments improved glucose tolerance, with the KBP-effect on insulin sensitivity as the dominant response. ConclusionsThese findings highlight KBP-336 as a promising anti-obesity therapy both alone, in treatment sequencing, and in combination with semaglutide or other incretin-based therapies.

From the Editor’s Desk…

From the Editor’s Desk…

Gastric mucosal devitalization improves blood pressure, renin and cardiovascular lipid deposition in a rat model of obesity.

Background and study aims In lieu of the drawbacks of metabolic surgery, a method of mimicking resection of the gastric mucosa could be of value to those with obesity-related cardiovascular disease (CVD). Our study aims to investigate the effect of gastric mucosal devitalization (GMD) on blood pressure (BP) and cardiovascular lipid deposition in a rat model of obesity. Methods GMD of 70 % of the stomach was achieved by argon plasma coagulation. GMD was compared to sleeve gastrectomy (SG) and sham (SH) in a high-fat-diet-induced rat model of obesity (48 rats). At 8 weeks, we measured noninvasive BP, renin, vessel relaxation and ghrelin receptor regulation in the aorta. In addition, we quantified cardiac lipid deposition and lipid droplet deposition in cardiac muscle and aorta. Results GMD and SG were observed to have similar reductions in body weight, visceral adiposity, and serum lipid profile compared to SH rats. GMD resulted in a significant reduction in arterial BP compared to SH. Furthermore, there were significant reductions in plasma renin activity and percentage of phenylnephrine constriction to acetylcholine at the aortic ring in GMD rats compared to SH, providing insights into the mechanisms behind the reduced BP. Interestingly, the reduced BP occurred despite a reduction in endothelial ghrelin recteptor activation. Cardiac lipid content was significantly reduced in GMD rats. Lipid deposition, as illustrated by Nile Red stain, was reduced in cardiac muscle and the aorta. Conclusion GMD resulted in a significant improvement in BP, renin and cardiovascular lipid deposition. GMD deserves further attention as a method of treating obesity-related CVD.

Prenatal undernutrition attenuates fasting-induced reproductive dysfunction in pre-pubertal male rats

Prenatal undernutrition affects various physiological functions, such as metabolic and reproductive functions, after birth, and such changes are associated with the pathogeneses of certain diseases. It has been hypothesized that these changes are predictive adaptive responses that help individuals to endure similar conditions in the postnatal period. Thus, we evaluated the effects of prenatal undernutrition on the responses of the body weight (BW) regulation system and reproductive functions to fasting in the pre-pubertal period in male rats. Prenatally normally nourished and undernourished rats exhibited similar reductions in BW and visceral fat after 48 h fasting in the pre-pubertal period. Furthermore, these two groups displayed similar fasting-induced patterns of change in their hypothalamic levels of appetite regulatory factors; i.e., neuropeptide Y and pro-opiomelanocortin. These results indicate that prenatal undernutrition had no marked effects on BW regulation in male rats. On the other hand, serum luteinizing hormone and testosterone levels were decreased by 48 h fasting in the prenatally normally nourished rats, whereas the levels of these hormones did not change in the prenatally undernourished rats. However, the hypothalamic mRNA level of kisspeptin 1 (Kiss1), which is a positive regulator of gonadotropin-releasing hormone/gonadotropins, was reduced by fasting in both groups. These results indicate that prenatal undernutrition might attenuate fasting-induced reproductive dysfunction in the postnatal period; however, these changes might not be induced by alterations in the hypothalamic Kiss1 system. Further studies are needed to clarify the mechanisms involved in these changes in reproductive function.

Glycemic Benefits of Liraglutide 1.2 mg daily in Overweight Pre-diabetic Compared to Overweight Normoglycemic Individuals

Objective: The aim was to compare the ability of liraglutide 1.2 mg daily to improve glucose control in overweight prediabetic compared to overweight normoglycemic subjects. Research design and Methods: We followed 100 overweight individuals (mean age, 44 ± 12 years) treated with liraglutide 1.2 mg daily over a period of 18 months. Based on their HbA1c, they were divided in two groups: prediabetes group (A) and normoglycemic group (B). All subjects were advised to decrease calorie intake by 500 kcal/day. Weight, BMI, waist circumference, blood pressure, HbA1c, lipid profile and TSH were assessed. Results: Six of 45 individuals (13%) in group A discontinued the study during the 18 months period compared with 8 out of 55(14%) in group B (P=0.46). Subjects in group A (n=39) lost the same percentage weight as those in group B (n=47; 5.8 vs. 7.3%; P=0.26). The percentage change in BMI was similar in both groups A and B (5.8 vs. 7.7%; P=0.19). The percentage drop in waist circumference was less in group A compared to group B (5.1 vs. 8.1%; P=0.04). The drop in HbA1c was higher in group A compared to group B (0.3 vs. 0.1%; P=0.04). The percentage of patients that regressed to normoglycemia in group A was 15% whereas the percentage of patients that progressed to prediabetes in group B was 8%. Only two subjects progressed to diabetes in group A and none in group B. There were no differences between the two groups with respect to percent changes in BP; triglycerides; total, LDL and HDL cholesterols; and TSH. Pre-diabetic subjects with any of the metabolic syndrome components (group A1) lost more percentage weight compared to those without any of the metabolic components (group A2) (7.3 vs. 4.8%; P=0.05). The percentage change in BMI was more in A1 compared to A2 (7.4 vs. 5.0%; P=0.03). The percentage drop in waist circumference was similar in A1 compared to A2 (7.0 vs. 6.2%; P=0.4). The drop in HbA1c was higher in A1 compared to A2 (0.4 vs. 0.08%; P=0.04). Conclusion: The addition of liraglutide 1.2 mg daily to calorie restriction to both pre-diabetic and normoglycemic overweight subjects resulted in a significantly more beneficial glycemic control in the pre-diabetic group despite a lower reduction in waist circumference and a similar reduction in body weight. Liraglutide resulted in normalization of glycemia in 15% of these pre-diabetic subjects and in this group, the presence of any of the metabolic syndrome component results in further weight loss and a better glycemic control.

Anti-obesity and anti-hepatosteatosis effects of dietary scopoletin in high-fat diet fed mice

The effects of scopoletin on non-alcoholic fatty liver in obese mice were investigated. Mice were fed high-fat diet (HF) with or without two doses of scopoletin (0.01 and 0.05%, w/w) for 16 weeks. Both doses of scopoletin led to similar reductions in body weight, visceral fat, serum levels of leptin, lipid, TNFα, IL-6, IFNγ and MCP-1, insulin resistance and hepatic lipid accumulation, whereas they increased serum adiponectin and faecal lipid levels. Ingenuity pathway analysis revealed that hepatic gene networks related to lipid concentrations, inflammation of organs, quantity of adipose tissue, proliferation of cell and necrosis were down-regulated in the scopoletin group. The top up- or down-regulated genes were Cidea, Apoa4, Cyp7a1, Errfi1, Col1a1, Mmp13, Cdkn1a, Gdf15 and Saa1, which emerged as associated genes related to hepatic steatosis and inflammation. These results indicate that scopoletin may ameliorate HF-induced hepatic dysfunction via regulation of lipid metabolic and inflammatory genes.

Addition of Exercise Increases Plasma Adiponectin and Release from Adipose Tissue.

Adiponectin is an adipose tissue-derived anti-inflammatory protein that is down-regulated in obesity. The effects of caloric restriction and exercise-induced weight loss on adiponectin are not clear. To determine whether addition of aerobic exercise training to caloric restriction has additive effects over caloric restriction alone on circulating adiponectin concentrations and adiponectin release from abdominal and gluteal adipose tissue. Overweight or obese (body mass index, 25-40 kg·m(-2); waist >88 cm) postmenopausal women were randomized to 20-wk caloric restriction with and without aerobic exercise (CR + EX, n = 48; and CR, n = 22). Blood samples were collected for measuring plasma adiponectin concentration, and abdominal and gluteal subcutaneous adipose tissue biopsies were performed in a subgroup to determine in vitro adiponectin release, before and after the interventions. The interventions elicited similar amounts of weight loss (CR + EX, -11.3 ± 4.6 kg; CR,-11.2 ± 3.4 kg) and fat loss (CR + EX, -8.0 ± 3.5 kg; CR, -7.4 ± 2.7 kg). The two groups had differential changes in plasma adiponectin concentrations (for interaction, P = 0.014); CR + EX increased (6.9 ± 3.9 to 8.5 ± 4.9 μg·mL(-1); P = 0.0001), whereas CR did not alter (6.4 ± 4.4 to 6.5 ± 4.5 μg·mL(-1); P = 0.42) plasma adiponectin. Likewise, adiponectin release from abdominal and gluteal subcutaneous adipose tissue increased with CR + EX (P = 0.0076 and P = 0.089, respectively) but did not change with CR (P = 0.13 and P = 0.95, respectively). Despite similar reductions in body weight and fat mass, the addition of aerobic exercise to caloric restriction increased plasma adiponectin concentrations, which may be partly explained by increased adiponectin release from abdominal and gluteal subcutaneous adipose tissue.

Deletion of Protein Tyrosine Phosphatase 1B (PTP1B) Enhances Endothelial Cyclooxygenase 2 Expression and Protects Mice from Type 1 Diabetes-Induced Endothelial Dysfunction.

Protein tyrosine phosphatase 1B (PTP1B) dephosphorylates receptors tyrosine kinase and acts as a molecular brake on insulin signaling pathway. Conditions of metabolic dysfunction increase PTP1B, when deletion of PTP1B protects against metabolic disorders by increasing insulin signaling. Although vascular insulin signaling contributes to the control of glucose disposal, little is known regarding the direct role of PTP1B in the control of endothelial function. We hypothesized that metabolic dysfunctions increase PTP1B expression in endothelial cells and that PTP1B deletion prevents endothelial dysfunction in situation of diminished insulin secretion. Type I diabetes (T1DM) was induced in wild-type (WT) and PTP1B-deficient mice (KO) with streptozotocin (STZ) injection. After 28 days of T1DM, KO mice exhibited a similar reduction in body weight and plasma insulin levels and a comparable increase in glycemia (WT: 384±20 vs. Ko: 432±29 mg/dL), cholesterol and triglycerides, as WT mice. T1DM increased PTP1B expression and impaired endothelial NO-dependent relaxation, in mouse aorta. PTP1B deletion did not affect baseline endothelial function, but preserved endothelium-dependent relaxation, in T1DM mice. NO synthase inhibition with L-NAME abolished endothelial relaxation in control and T1DM WT mice, whereas L-NAME and the cyclooxygenases inhibitor indomethacin were required to abolish endothelium relaxation in T1DM KO mice. PTP1B deletion increased COX-2 expression and PGI2 levels, in mouse aorta and plasma respectively, in T1DM mice. In parallel, simulation of diabetic conditions increased PTP1B expression and knockdown of PTP1B increased COX-2 but not COX-1 expression, in primary human aortic endothelial cells. Taken together these data indicate that deletion of PTP1B protected endothelial function by compensating the reduction in NO bioavailability by increasing COX-2-mediated release of the vasodilator prostanoid PGI2, in T1DM mice.

Abstract 477: Adipocyte Twist-1 Deficiency Exacerbates Weight Gain, Glucose Intolerance and Adipose Tissue Inflammation in Females

Twist1 is a transcription factor abundantly expressed by adipocytes, immune and vascular cells in adipose tissue (AT) in humans and rodents. Low twist1 expression in human AT is correlated with insulin resistance and obesity. However the role of twist-1 in different cell types component of AT is not clear. The objective of this study was to determine the role of adipocyte (Adp) twist-1 in obesity and insulin resistance. Adp-specific twist1 knock out mice ( AdiponectinCreTwistflox ) (n=6) on the C57Bl6/J background were maintained on 60%kcal fat diet for 12 weeks. Compared to littermate controls (n=6), the female mutant mice, but not the males, showed a 3- and 1.5- fold increase in visceral and subcutaneous adiposity, respectively. Similarly, only the mutant females had significantly impaired glucose tolerance (P&lt;0.05) compared to the littermate controls. Peri-gonadal AT in mutant females showed increased CD11b+F4/80+ and CD3+CD8+ numbers compared to controls, however no differences were found between the male mice. The female mutant mice had more hypertrophied Adp and displayed a 2-4-fold increase in gene expression of IFN γ, TNF α, CD3e and Jak2 compared to controls. Also, expression of the lipogenic enzymes Acaca and Acls4 were significantly reduced by 2.2-fold in the mutant females. Interestingly expression of Nampt (visfatin) gene was significantly increased in mutant females compared to both controls and mutant males. Importantly, twist1 expression in visceral Adp of obese human females (n=15) and males (n=8) at the time of bariatric surgery was significantly higher in females (p&lt;0.01). Also, in a longitudinal cohort at ~1.2 years following surgical weight loss, twist1 expression was significantly increased in visceral AT of males (n=3) (p&lt;0.05) but not in females (n=6) despite a similar reduction in body weight. Collectively the rodent data suggest that twist1 deficiency in Adp increases AT inflammation and exacerbates adiposity and glucose intolerance only in females and identifies visfatin as a metabolically relevant gene potentially regulated by twist1 in females. Also, obese human females may be protected by constitutively higher expression of twist1 in visceral Adp and surgical weight loss leads to increased twist1 expression in males.

Randomization to a low-carbohydrate diet advice improves health related quality of life compared with a low-fat diet at similar weight-loss in Type 2 diabetes mellitus

AimsTo compare the effects on health-related quality of life (HRQoL) of a 2-year intervention with a low-fat diet (LFD) or a low-carbohydrate diet (LCD) based on four group-meetings to achieve compliance. To describe different aspects of taking part in the intervention following the LFD or LCD. MethodsProspective, randomized trial of 61 adults with Type 2 diabetes mellitus. The SF-36 questionnaire was used at baseline, 6, 12 and 24 months. Patients on LFD aimed for 55–60 energy percent (E%) and those on LCD for 20 E% from carbohydrates. The patients were interviewed about their experiences of the intervention. ResultsMean body-mass-index was 32.7±5.4kg/m2 at baseline. Weight-loss did not differ between groups and was maximal at 6 months, LFD: −3.99±4.1kg, LCD: −4.31±3.6kg (p<0.001 within groups). There was an increase in the physical component score of SF-36 from 44.1 (10.0) to 46.7 (10.5) at 12 months in the LCD group (p<0.009) while no change occurred in the LFD group (p<0.03 between groups). At 12 months the physical function, bodily pain and general health scores improved within the LCD group (p values 0.042–0.009) while there was no change within the LFD group. ConclusionsWeight-changes did not differ between the diet groups while improvements in HRQoL only occurred after one year during treatment with LCD. No changes of HRQoL occurred in the LFD group in spite of a similar reduction in body weight.

Advice to follow a low-carbohydrate diet has a favourable impact on low-grade inflammation in type 2 diabetes compared with advice to follow a low-fat diet

Background. Inflammation may play an important role in type 2 diabetes. It has been proposed that dietary strategies can modulate inflammatory activity.Methods. We investigated the effects of diet on inflammation in type 2 diabetes by comparing a traditional low-fat diet (LFD) with a low-carbohydrate diet (LCD). Patients with type 2 diabetes were randomized to follow either LFD aiming for 55–60 energy per cent (E%) from carbohydrates (n = 30) or LCD aiming for 20 E% from carbohydrates (n = 29). Plasma was collected at baseline and after 6 months. C-reactive protein (CRP), interleukin-1 receptor antagonist (IL-1Ra), IL-6, tumour necrosis factor receptor (TNFR) 1 and TNFR2 were determined.Results. Both LFD and LCD led to similar reductions in body weight, while beneficial effects on glycaemic control were observed in the LCD group only. After 6 months, the levels of IL-1Ra and IL-6 were significantly lower in the LCD group than in the LFD group, 978 (664–1385) versus 1216 (974–1822) pg/mL and 2.15 (1.65–4.27) versus 3.39 (2.25–4.79) pg/mL, both P < 0.05.Conclusions. To conclude, advice to follow LCD or LFD had similar effects on weight reduction while effects on inflammation differed. Only LCD was found significantly to improve the subclinical inflammatory state in type 2 diabetes.Trial registration: ClinicalTrials.gov identifier: NCT01005498.

Comparison of the effects of 52 weeks weight loss with either a high-protein or high-carbohydrate diet on body composition and cardiometabolic risk factors in overweight and obese males

Background:A high-protein (HP), low-fat weight-loss diet may be advantageous for improving cardiometabolic health outcomes and body composition. To date, only limited research has been conducted in male participants.Objective:To evaluate the medium to long-term effects of two, low-fat, hypocaloric diets differing in carbohydrate:protein ratio on body composition and cardiometabolic health outcomes in overweight and obese males.Design:One hundred and twenty males (age 50.8±9.3 (s.d.) years, body mass index 33.0±3.9 kg m−2) were randomly assigned and consumed a low-fat, isocaloric, energy-restricted diet (7 MJ per day) with either HP (protein:carbohydrate:fat %energy, 35:40:25) or high carbohydrate (HC; 17:58:25). Body weight, body composition and cardiometabolic risk factors were assessed at baseline and after 12 and 52 weeks.Results:Sixty-eight participants completed the study (HP, n=33; HC, n=35). At 1 year both the groups experienced similar reductions in body weight (HP, −12.3±8.0 kg (−12%); HC, −10.9±8.6 kg (−11%); P=0.83 time × group interaction) and fat mass (−9.9±6.0 kg (−27%) vs −7.3±5.8 kg (−22%); P=0.11). Participants who consumed the HP diet lost less fat-free mass (−2.6±3.7 kg (−4%) vs −3.8±4.7 kg (−6%); P<0.01). Both groups experienced similar increases in high-density lipoprotein cholesterol (8%) and reductions in total cholesterol (−7%), low-density lipoprotein cholesterol (−9%), triglycerides (−24%), glucose (−3%), insulin (−38%), blood pressure (−7/−12%) and C-reactive protein (−29%), (P⩾0.14).Conclusion:In overweight and obese men, both a HP and HC diet reduced body weight and improved cardiometabolic risk factors. Consumption of a HP diet was more effective for improving body composition compared with an HC diet.

Comparison of the effects of weight loss from a high-protein versus standard-protein energy-restricted diet on strength and aerobic capacity in overweight and obese men

To compare the effects of two low-fat, hypoenergetic diets differing in carbohydrate-to-protein ratio, on strength and aerobic capacity measures in overweight and obese men. In a parallel design, 56 men (age, 45.5 ± 8.7 years; BMI, 33.6 ± 3.9 kg/m(2)) were randomly assigned to a low-fat, energy-restricted diet (7,000 kJ/day) with either high protein (HP: protein/carbohydrate/fat % energy, 35:40:25) or standard protein (SP, 17:58:25). Body weight, body composition, muscle strength and aerobic capacity were assessed at baseline and after 12 weeks. Forty-two participants completed the study (HP, n = 21; SP, n = 21). Both groups experienced similar reductions in body weight (HP, -10.7 ± 5.3 kg [-9.8%]; SP, -8.7 ± 3.5 kg [-8.4%]) and fat-free mass (HP, -2.8 ± 3.6 kg; SP, -3.2 ± 2.7 kg; P < 0.001 time; P > 0.14 time × group interaction). There was a trend for a greater reduction in fat mass in the HP diet group, (-7.7 ± 4.3 kg [-21.2%] vs. -5.4 ± 3.3 kg [-15.1%]; P < 0.001 time; P = 0.06 time × group interaction). Absolute peak oxygen uptake did not change in either group (P = 0.39 time; P = 0.50 time × group interaction). Overall, in both groups, relative peak oxygen uptake increased (2.9 ± 2.8 ml kg(-1) min(-1) [8.9%]), peak isometric knee extensor strength increased (14.1 ± 35.7 Nm [7.1%]) and peak handgrip strength decreased (-1.6 ± 4.1 kg [-3%]) (P ≤ 0.02 time for all), with no diet effect (P ≤ 0.23 time × group interaction). In overweight and obese men, both a HP and SP diet reduced body weight and improved body composition with similar effects on strength and aerobic capacity.

Efficacy and Safety of Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Compared with Exenatide Twice Daily and Sitagliptin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Long-acting glucagon-like peptide-1 receptor agonists (LA-GLP-1RAs) may deliver additional therapeutic benefits over other available incretin-based therapies. To pool results of randomized controlled trials comparing the efficacy and safety of maximum dose LA-GLP-1RAs (liraglutide, exenatide once weekly) with exenatide twice daily and dipeptidyl-peptidase-IV inhibitors in patients with type 2 diabetes. We searched PubMed, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE (all from inception-December 2010), and abstracts presented at the American Diabetes Association Scientific Sessions in 2009 and 2010 to identify English-language reports of studies of at least 24 weeks' duration. The primary endpoint was mean change in hemoglobin A(1c) (A1C) from baseline to study endpoint. Weighted mean differences or odds ratios and their 95% confidence intervals for each outcome relative to control were calculated as appropriate. A1C was reduced favoring LA-GLP-1RAs compared with exenatide twice daily and sitagliptin (weighted mean difference [WMD] -0.47% [95% CI -0.69 to -0.25] and WMD -0.60% [95% CI -0.75 to -0.45], respectively). Odds ratios greater than 1 favored LA-GLP-1RAs for reaching the A1C target goal of less than 7%. Fasting plasma glucose (FPG) was reduced and favored the LA-GLP-1RA-based regimens. Exenatide demonstrated significantly greater reductions in postprandial glucose (PPG) after the morning and evening meals, compared with LA-GLP-1RAs. Body weight was reduced similarly between LA-GLP-1RAs and exenatide, but favored LA-GLP-1RAs in the sitagliptin comparator trials. LA-GLP-1RA therapy was not associated with severe hypoglycemia or acute pancreatitis. Compared with exenatide twice daily, vomiting was reduced significantly with LA-GLP-1RAs (OR 0.55; 95% CI 0.34 to 0.89); there was a trend toward decreased nausea (OR 0.58; 95% CI 0.32 to 1.06) and no difference in the incidence of diarrhea (OR 1.03; 95% CI 0.67 to 1.58). Compared with other incretin-based therapies, LA-GLP-1RAs produce greater improvement in A1C and FPG. They provide lesser effect on PPG, similar reduction in body weight, and result in a potentially favorable adverse event profile compared with exenatide twice daily.

Early Response to Sibutramine in Patients Not Meeting Current Label Criteria: Preliminary Analysis of SCOUT Lead‐in Period

The Sibutramine Cardiovascular Outcomes (SCOUT) trial protocol defines a patient population predominantly outside current European Union label criteria. This article explores responses to sibutramine during the 6-week, single-blind, lead-in period between patients who conformed to the label requirements ("conformers") and those who did not ("nonconformers"). SCOUT is an ongoing, randomized, double-blind, placebo-controlled outcome trial in overweight/obese patients at high risk of a cardiovascular event. In total, 10,742 patients received sibutramine and weight management during the lead-in period. Initial responses were assessed post hoc in label conformers and nonconformers. Of that 8.1% patients met label criteria; 91.9%, the majority with cardiovascular disease and/or blood pressure >145/90 mm Hg, were nonconformers. Conformers and nonconformers had similar reductions in body weight (median change -2.2 kg) and waist circumference (women: -2.0 cm for both groups; men: -1.5 cm vs. -2.0 cm for conformers and nonconformers, respectively) over the 6-week period. Greater blood pressure falls were evident in nonconformers (median change -3.5/-1.0 vs. -1.0/0.0 mm Hg). Both groups had small pulse rate increases; median 1.5 bpm (nonconformers) vs. 3.0 bpm (conformers). There was a low incidence of serious adverse events (conformers: 1.0%; nonconformers: 2.8%) and ~93% of patients in both groups completed the 6-week period. The SCOUT lead-in period evaluating weight management with sibutramine confirms its good tolerability and efficacy in patients who meet current label criteria. Preliminary data from high-risk patients for whom sibutramine is currently contraindicated suggest a low discontinuation rate and few serious adverse events but confirmation from the SCOUT outcome data is needed.

Long‐term effects of weight loss with a very low carbohydrate and low fat diet on vascular function in overweight and obese patients

To compare the effects of an energy reduced very low carbohydrate, high saturated fat diet (LC) and an isocaloric high carbohydrate, low fat diet (LF) on endothelial function after 12 months. Forty-nine overweight or obese patients (age 50.0 +/- 1.1 years, BMI 33.7 +/- 0.6 kg m(-2)) were randomized to either an energy restricted ( approximately 6-7 MJ), planned isocaloric LC or LF for 52 weeks. Body weight, endothelium-derived factors, flow-mediated dilatation (FMD), adiponectin, augmentation index (AIx) and pulse wave velocity (PWV) were assessed. All data are mean +/- SEM. Weight loss was similar in both groups (LC -14.9 +/- 2.1 kg, LF -11.5 +/- 1.5 kg; P = 0.20). There was a significant time x diet effect for FMD (P = 0.045); FMD decreased in LC (5.7 +/- 0.7% to 3.7 +/- 0.5%) but remained unchanged in LF (5.9 +/- 0.5% to 5.5 +/- 0.7%). PWV improved in both groups (LC -1.4 +/- 0.6 m s(-1), LF -1.5 +/- 0.6 m s(-1); P = 0.001 for time) with no diet effect (P = 0.80). AIx and VCAM-1 did not change in either group. Adiponectin, eSelectin, tPA and PAI-1 improved similarly in both groups (P < 0.01 for time). Both LC and LF hypoenergetic diets achieved similar reductions in body weight and were associated with improvements in PWV and a number of endothelium-derived factors. However, the LC diet impaired FMD suggesting chronic consumption of a LC diet may have detrimental effects on endothelial function.