Very-low Calorie Research Articles

A multiphase very-low calorie ketogenic diet improves serum redox balance by reducing oxidative status in obese patients

The very-low calorie ketogenic diet (VLCKD) is recommended as an effective dietary approach for the management of obesity. This study investigated changes in circulating biomarkers of redox homeostasis induced by a multiphase VLCKD in obese individuals.A total of 40 obese subjects were prescribed a multiphasic VLCKD for eleven weeks. Anthropometric measurements, body composition parameters, calorimetric measures, and standard laboratory markers of glucose and lipid metabolism were evaluated at baseline (T0) and at the end of the dietary intervention (T1). Additionally, circulating markers of oxidative damage and antioxidant status were analyzed in serum and erythrocytes.Compared to T0, at T1 the multiphase VLCKD induced significant weight loss and reduction of waist circumference, with beneficial effects on body composition parameters and the glucose/lipid biochemical profile. Moreover, a decrease in serum markers of oxidative damage was reported at T1, while no changes in serum markers of antioxidant status and in erythrocyte redox markers were observed. In addition, a significant association was found between variations in anthropometric measurements, body composition, glucose metabolism parameters, and changes in circulating markers of oxidative damage. Regression models showed that variation in lipofuscin was significant predictor of changes in body mass index, fat mass, visceral adiposity, and insulin sensitivity.In conclusion, this study demonstrated that the multiphase VLCKD improves serum redox balance by reducing markers of oxidative damage in obese individuals, highlighting the interplay between adiposity, glucose metabolism, and redox homeostasis in the pathogenesis of obesity. Furthermore, these data provide a rationale for future investigations aimed at testing serum lipofuscin as a reliable redox marker in obesity.

Metabolic effects of very-low calorie diet, Semaglutide, or combination of the two, in individuals with type 2 diabetes mellitus

Background & AimsVery-low calorie diets (VLCD) and the glucagon-like peptide-1 receptor agonist (GLP1RA) Semaglutide induce significant weight loss and improve glycaemic control in individuals with type 2 diabetes (T2D). This pilot study was conducted to explore the comparative short-term effects of these interventions individually, and in combination, on weight, body composition and metabolic outcomes. MethodsThirty individuals with T2D (age 18-75 years, BMI 27-50kg.m-2) were randomly assigned to receive Semaglutide (SEM), 800 kilocalorie/day VLCD (VLCD), or both in combination (COMB) for 12 weeks. Measurement of weight and glycated haemoglobin (HbA1c), dual energy X-ray absorptiometry, and intravenous glucose tolerance tests (IVGTT) were performed at baseline and post-intervention. Diet diaries were utilised to assess compliance. Insulin first phase response during IVGTT provided a marker of pancreatic beta-cell function, and insulin sensitivity was estimated using HOMA-IR. ResultsSignificantly greater reductions in body weight and fat mass were observed in VLCD and COMB, than SEM (p<0.01 v both). VLCD and COMB resulted in a 5.4 and 7 percentage-point greater weight loss than SEM, respectively. HbA1c and fasting glucose reduced significantly in all groups, however fasting insulin and HOMA-IR improved in VLCD and COMB only. Insulin first phase response during IVGTT increased in SEM and COMB, and this increase was significantly greater in COMB than VLCD (p<0.01). ConclusionVLCD elicited greater short-term losses of weight and fat mass than Semaglutide. Adding VLCD to Semaglutide stimulated further weight loss than Semaglutide alone. The combination did not yield any additive effects on weight and body composition above VLCD alone, but did provoke greater improvements in pancreatic beta-cell function. Thus, combination of Semaglutide and VLCD warrants further exploration as a novel approach to T2D management.

A very-low-calorie diet (VLCD) intervention for the management of prediabetes and early Type 2 diabetes mellitus in a multi-ethnic cohort in Aotearoa New Zealand: The PROGRESS NZ feasibility study.

Very-low calorie diets (VLCD) achieve weight loss and remission of Type 2 diabetes (T2DM), but efficacy and acceptability in non-European populations is less clear. This feasibility study examines the impact of 10% weight loss through VLCD on metabolic and body composition outcomes in a multi-ethnic cohort of Aotearoa New Zealand (AoNZ) men with prediabetes/early T2DM, and VLCD tolerability/cultural acceptability. Participants followed a VLCD intervention (mean energy 3033kJ/day) until achievement of 10% weight loss. An oral glucose tolerance test (OGTT), hyperinsulinaemic isoglycaemic clamp with stable isotopes, hood calorimetry and dual-energy Xray absorptiometry (DXA) were undertaken before and after intervention. Qualitative data on VLCD tolerability/cultural acceptability were collected. Fifteen participants were enrolled; nine achieved 10% weight loss. In this group, mean HbA1c reduced by 4.8mmol/mol (2.4-7.1) and reverted to normoglycaemia in n=5/9; mean body weight reduced by 12.0 kg (11.0-13.1) and whole-body glucose disposal improved by 1.5 mg kgFFM-1 min-1 (0.7-2.2). Blood pressure and fasting triglycerides improved significantly. No changes in hepatic glu-cose metabolism were found. In all participants who attended completion testing, HbA1c reduced by 3.4mmol/mol (SD 3.5) and total weight by 9.0kg (SD 5.7). The intervention was highly tolerable/culturally acceptable however challenges with fulfilment of cultural obligations were described. Results support VLCD use in AoNZ however further work to investigate ethnic differences in physiological response to VLCDs and to optimise protocols for multi-ethnic populations are required.

Real world evidence on the characteristics of regular and intermittent users of a very-low calorie diet program and associations with measures of program success, health, and quality of life.

Very low-calorie diet (VLCD) programs are readily available in Australia. However, there is a lack of real-world evidence describing the characteristics related to positive outcomes. To examine the demographic, eating, self-efficacy and program engagement characteristics of VLCD users in Australia, and the associations between user characteristics and program success, weight loss, quality of life (QOL) and health. Cross-sectional data from Australian adults: regular users (n=189: VLCD user ≥4days/week for >4weeks) and intermittent users (n=111, VLCD user <4weeks and/or <4days/week). Self-reported data on demographics, VLCD program use, support, eating behavior, weight-related QOL, mental health, physical health, self-efficacy, and physical activity. Descriptive and inferential statistics were performed in R. Compared to regular users, intermittent users reported lower percentage weight loss (15.1%±SD 9.8 vs. 9.9%±SD 6.8, relative to starting weight), fewer reported their VLCD program as very successful (44% vs. 35%), higher depressive symptom scores (8.7±SD 2.8 vs. 6.7±SD 5.1), and lower general self-efficacy (23.9±SD 4.7 vs. 29.4±SD 5.7), nutrition self-efficacy (11.9±SD 2.0 vs. 14.5±SD 3.1) and weight-related QOL scores (60.9±SD 22.2 vs. 65.0±SD 11.8; p<0.001 for all). In regular users, older age and longer program duration were associated with greater total weight loss, support, and program success (p<0.001 for all). In intermittent users, program success was greater when dietitian support was used (odds ratio [OR] 6.50) and for those with higher BMIs (OR 1.08, p<0.001 for all). In both groups, more frequent support was associated with better weight-related QOL (p<0.001). This study provides real-world evidence that regular VLCD users had greater success and weight loss than intermittent program users. These findings may be used to tailor and improve the delivery of VLCD programs in Australia and other countries with retail access to VLCDs.

1691-P: Weight Status, Longitudinal Weight Change, and Weight Loss Treatment Utilization among Primary Care Patients with Obesity

Background: Effective weight management treatments (WMTs) include nutrition counseling, very low-calorie (VLC) meal replacement, anti-obesity medications (AOMs), and bariatric surgery. Little is known about how these WMTs influence weight change among individual primary care patients and populations. Methods: This was a retrospective cohort study using medical record data from one academic health system. Participants were adults with primary care between October 2015 and March 2020. We used serial cross-sections to examine obesity prevalence and WMT use. We used a multistate model to investigate weight trajectories for patients with obesity and no WMT use prior to baseline. This is a time-to-event model with events representing transitions between 5 successive categories of weight change relative to baseline (i.e., ≥10% weight loss, 5-10% weight loss, baseline weight +/-5%, 5-10% weight gain, or ≥10% weight gain). The primary exposures were WMTs; controls were baseline age, BMI, and prior year primary care. Patients with WMT use were propensity matched 1:1 to controls. The primary outcome was the model-based probability of ≥5% weight loss at 1 year. Results: Among primary patients, the prevalence of obesity increased from 39.2% in 2017 to 40.7% in 2019 (n=138,632); WMT use increased from 2.8% to 8.9% (difference: 6.1%, 95% CI: 5.8-6.4%). In the multistate model (n=10,296), the one-year probability of ≥5% weight loss among patients without WMT exposure was 15.5% [95% CI: 14.8-16.1%]. In contrast, ≥5% weight loss was more likely for patients with year-long exposures to any WMT (nutrition counseling: 23.4%, 95% CI: 21.5-25.3%; VLC meal replacement: 56.4%, 95% CI: 48.7-62.8%; AOMs: 27.8%, 95% CI: 25.1-30.5%; bariatric surgery: 94.4%, 95% CI: 91.1-96.4%). Conclusions: Use of all WMTs increased the probability of achieving ≥5% weight loss at the individual-patient level but underutilization limits their ability to reduce weight at the population-level. Disclosure D.H.Griauzde: None. C.R.Richardson: Other Relationship; Annals of Family Medicine, JMIR Diabetes, Research Support; Dexcom, Inc., Blue Cross Blue Shield of Michigan, Neilson Foundation. J.M.Lee: Advisory Panel; GoodRx, Consultant; Tandem Diabetes Care, Inc. J.Henderson: None. A.P.Ehlers: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (K23DK123416)

278-LB: The Effect of Combining Very-Low-Calorie Diet with Semaglutide on Beta-Cell Function in Individuals with Type 2 Diabetes

Type 2 diabetes (T2D) is characterised by the loss of the first phase response of insulin-producing pancreatic beta cells. Recently, Very-low calorie diets (VLCD - defined as less than 800 kilocalories per day) have been shown to restore this first phase response to induce remission of T2D, while Glucagon-like peptide-1 agonists also improve the first phase response by enhancing postprandial insulin secretion. Here, we present interim results of an investigation exploring the effect of combining these two interventions on beta cell function, in individuals with T2D. Eighteen individuals with T2D and body mass index &amp;gt;27kg.m-2 were randomly allocated into 3 groups: i) Semaglutide (S), ii) VLCD (V), and iii) Semaglutide-plus-VLCD (SV). Semaglutide was administered once weekly gradually up titrated to a maximum dose of 1mg and VLCD regime was provided by LighterLife® total meal replacement. Beta cell function was assessed using intravenous glucose tolerance tests (IVGTT) performed at baseline and 12 weeks. First-phase insulin response was calculated as the incremental area under the suprabasal plasma insulin concentration curve during 0-10 minutes of the IVGTT (µU.min.ml-1). Data were analysed using GraphPad Prism 9.5.0 (La Jolla, USA). All groups were equally matched at baseline. Mean weight loss was 6.4, 14.1 and 14.9 kg in S, V and SV, respectively. A significant improvement in first phase response was observed in all groups (S: +398.5; V: +88.4; SV: +547.8 µU.min.ml-1, all p&amp;lt;0.05 vs. baseline). At 12 weeks, first phase response in SV was significantly higher than in V (583.9 vs. 169.2 µU.min.ml-1 respectively, p&amp;lt;0.05). These data suggest that combination of VLCD and Semaglutide results in a significantly greater improvement in first phase response than VLCD alone. This approach could result in a more robust remission of T2D in the longer-term, and may have important implications for the future design of interventions for the clinical management of T2D. Disclosure O. Anyiam: None. B. E. Phillips: None. D. J. Wilkinson: None. K. Smith: None. P. J. Atherton: None. I. R. Idris: None. Funding Medical Research Council Confidence in Concept Scheme

Efficacy of the Very Low-Calorie Ketogenic Diet (VLCKD) in postmenopausal women with obesity: better to be “owls” or “larks”?

Nutritional approaches (NA) are the cornerstone of obesity therapy, but their optimal design for postmenopausal women, a population with a high prevalence of obesity, is debated. In addition, recent studies have reported that chronotype (reflecting an individual's preference for sleep, eating and activity times over a 24h period) plays a role in both the development of metabolic comorbidities and in determining eating habits in obesity. However, little is known whether the chronotype can predict the efficacy of (NA) in postmenopausal women with obesity (PWO). The aim of this study was to investigate whether chronotype categories may play a role in determining the efficacy of the Very-Low Calorie Ketogenic Diet (VLCKD) in terms of weight loss (WL) and body composition change in PWO.

The Application of Spearman Partial Correlation for Screening Predictors of Weight Loss in a Multiomics Dataset.

Obesity has reached epidemic proportions in the United States, but little is known about the mechanisms of weight gain and weight loss. Integration of omics data is becoming a popular tool to increase understanding in such complex phenotypes. Biomarkers come in abundance, but small sample size remains a serious limitation in clinical trials. In the present study, we developed a strategy to screen predictors from a multiomics, high-dimensional, and longitudinal dataset from a small cohort of 10 women with obesity who were provided an identical very-low calorie diet. Our proposal explores the combinatorial space of potential predictors from transcriptomics, microbiome, metabolome, fecal bile acids, and clinical data with the application of the first-order Spearman partial correlation coefficient. Two statistics are proposed for screening predictors, the partial association score, and the persistent significance. We applied our strategy to predict rates of weight loss in our sample of participants in a hospital metabolic facility. Our method reduced an initial set of 42,000 biomarker candidates to 61 robust predictors. The results show baseline fecal bile acids and regulation in RT-polymerase chain reaction as the most predictive data sources in forecasting the rate of weight-loss. In summary, the present study proposes a strategy based on nonparametric statistics for ranking and screening predictors of weight loss from a multiomics study. The proposed biomarker screening strategy warrants further translational clinical investigation in obesity and other complex clinical phenotypes.

Caloric restriction improves glycaemic control without reducing plasma branched-chain amino acids or keto-acids in obese men

Higher plasma leucine, isoleucine and valine (BCAA) concentrations are associated with diabetes, obesity and insulin resistance (IR). Here, we evaluated the effects of 6-weeks very-low calorie diet (VLCD) upon fasting BCAA in overweight (OW) non-diabetic men, to explore associations between circulating BCAA and IR, before and after a weight loss intervention. Fasting plasma BCAAs were quantified in an OW (n = 26; BMI 32.4 ± 3 kg/m2; mean age 44 ± 9 y) and a normal-weight (NW) group (n = 26; BMI 24 ± 3.1 kg/m2; mean age 32 ± 12.3 y). Ten of the OW group (BMI 32.2 ± 4 kg/m2; 46 ± 8 y) then underwent 6-weeks of VLCD (600–800 kcal/day). Fasting plasma BCAA (gas chromatography-mass spectrometry), insulin sensitivity (HOMA-IR) and body-composition (DXA) were assessed before and after VLCD. Total BCAA were higher in OW individuals (sum leucine/isoleucine/valine: 457 ± 85 µM) compared to NW control individuals (365 ± 78 µM, p < 0.001). Despite significant weight loss (baseline 103.9 ± 12.3 to 93 ± 9.6 kg and BMI 32.2 ± 4 to 28.9 ± 3.6 kg/m2), no changes were observed in BCAAs after 6-weeks of VLCD. Moreover, although VLCD resulted in a significant reduction in HOMA-IR (baseline 1.19 ± 0.62 to 0.51 ± 0.21 post-VLCD; p < 0.001), Pearson’s r revealed no relationships between BCAA and HOMA-IR, either before (leucine R2: 2.49e−005, p = 0.98; isoleucine R2: 1.211−e006, p = 0.9; valine R2: 0.004, p = 0.85) or after VLCD (leucine R2: 0.003, p = 0.86; isoleucine R2: 0.006, p = 0.82; valine R2: 0.002, p = 0.65). Plasma BCAA are higher in OW compared to NW individuals. However, while 6-weeks VLCD reduced body weight and IR in OW individuals, this was not associated with reductions in BCAA. This suggests that studies demonstrating links between BCAA and insulin resistance in OW individuals, are complex and are not normalised by simply losing weight.

RF24 | PSUN126 A Very-Low Calorie Diet Can Reduce Insulin Resistance and Cause Remission of Diabetes Mellitus and Hypertriglyceridemia in a Patient With Familial Partial Lipodystrophy Type 2

Abstract Background Lipodystrophy syndromes are associated with inadequate adipocyte capacity that results in an earlier threshold for ectopic deposition and metabolic dysfunction. We have previously reported that patients with familial partial lipodystrophy (FPLD) present with metabolic severity equivalent to what is observed at 8-12 BMI points higher in a population with common obesity. Currently, there is no strong evidence that any specific diet is the preferred treatment, but bariatric surgery has been reported to improve metabolic outcomes in a few patients. Here, we report the effect of an aggressive calorie-restricted diet in a patient with FPLD who showed remarkable benefit after 16 weeks of the intervention. Clinical Case This is a 38-year-old female diagnosed with FPLD type 2, with LMNA p. R482Q mutation who had a history of recurrent pancreatitis, NAFLD, impaired ovulation, and diabetes mellitus. She had a short-term goal of improving her metabolic state rapidly to achieve pregnancy by IVF. Upon presentation, body weight was 81.6kg, BMI 23.2kg/m2, HbA1c 7.7% and triglycerides 215mg/dL. She was started on very-low calorie diet (VLCD) (800 kcal/day) employing a formula total liquid diet meal replacement: 160 kcal per shake (18g total carbohydrates, 15g net carbohydrates, 3.5g fat, and 16g protein) with the goal to reduce body weight by 15% as has been described for patients in the University of Michigan Weight Management Program. After 1 week on diet, she discontinued glucose and lipid lowering therapies. After 12-weeks of VLCD followed by 4 weeks of transition to low-calorie diet (incorporating 3 meal replacements, one meal, and ad libitum non-starchy vegetables), we observed 12.3kg of body weight and a 1.4% decrease in HbA1c. Insulin resistance was reduced by 66.7 and 61.5% (HOMA-IR and ADIPO-IR, respectively). Fasting insulinemia was reduced by 64.2%. We also performed an OGTT with 75g of glucose for 180 min and observed a decrease in the area under the curve of insulin (-33.2%), triglycerides (-40.7%), and free fatty acids (-34%). DEXA scan showed a reduction in total body fat of 16%. Liver fat via the chemical shift MRI method was reduced from 10±2% to 2±1%. She did not experience any adverse events during the intervention. More importantly, her egg retrieval rate and egg quality during IVF were far superior to past attempts. Conclusion This case illustrates the strong effect and safety of a VLCD intervention in a patient with lipodystrophy. We observed rapid reduction in body weight, and in insulin resistance leading to the remission of diabetes mellitus, hypertriglyceridemia and fatty liver disease. Moreover, there was improved response to ovulation induction. Our data encourage the use of this medical approach for other patients with similar metabolic and reproductive abnormalities due to adipose tissue distribution abnormalities. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m., Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m.

Association of Short-Term Changes in Menstrual Frequency, Medication Use, Weight and Exercise on Bone Mineral Density in College-Aged Women.

To evaluate if experiencing a short-term exposure (18-months) to factors such as menstrual irregularities, dieting, changes in exercise or body weight, and medication usage is associated with bone mineral density (BMD) in college-aged females. A retrospective survey assessing health behaviors during a recent 18-month time period and a DXA scan were completed in 641 females. A total of 45.5% of participants reported amenorrhea during the 18-month time period. Those who experienced amenorrhea had lower femoral neck BMD (p = 0.018), trochanter (p = 0.018) and spine BMD (p = 0.022) compared to eumenorrheic women. Lifetime oral contraceptive usage longer than six months was negatively associated with BMD at femoral neck (p = 0.018) and total hip (p = 0.021). Women who lost weight trended towards having the lowest BMD at all sites compared to women who gained weight. Following a very-low calorie diet during the time period was negatively correlated with spine BMD (p = 0.001). Time spent in vigorous and very vigorous activity was weakly correlated with some hip BMD sites but time spent in extremely vigorous activity was not. In conclusion, females who experienced weight loss, amenorrhea, or a very low-calorie diet within an 18-month period of time in young adulthood had lower BMD. Additionally, oral contraceptive usage for longer than six months during their lifetime was associated with lower BMD.

Adding liraglutide to diet and exercise to maintain weight loss – is it worth it?

Introduction Obesity is a major risk factor for cardiovascular disease, diabetes, osteoarthritis, and some cancers. Weight loss is an obvious management for this, but a major problem is that after weight loss, many people regain weight. Areas Covered In the following evaluation of S-LITE (NCT04122716, Combined effects of GLP-1 analogue and exercise on maintenance of weight loss after very-low calorie diet), the author gives emphasis to the prevention of weight regain by liraglutide, not the effects of exercise. In S-LITE, liraglutide (with or without exercise) was effective in reducing weight regain in subjects with obesity. Expert opinion The subjects with obesity in S-LITE were limited by the enrolment criteria, and the findings of S-LITE cannot be generalised. The increased heart rate with liraglutide did not occur when liraglutide was combined with exercise, and this suggests that liraglutide should probably not be used alone, but only with exercise to maintain weight loss. As the only presently available medicine to have been shown to be effective against weight regain, liraglutide should probably be preferred to other weight-loss medicines in this circumstance. However, without clear evidence that liraglutide treatment for obesity prevents diabetes and/or reduces cardiovascular risk, it is difficult to justify using it.

Ketogenic Diet for Obese COVID-19 Patients: Is Respiratory Disease a Contraindication? A Narrative Review of the Literature on Ketogenic Diet and Respiratory Function.

Morbid obese people are more likely to contract SARS-CoV-2 infection and its most severe complications, as need for mechanical ventilation. Ketogenic Diet (KD) is able to induce a fast weight loss preserving lean mass and is particularly interesting as a preventive measure in obese patients. Moreover, KD has anti-inflammatory and immune-modulating properties, which may help in preventing the cytokine storm in infected patients. Respiratory failure is actually considered a contraindication for VLCKD, a very-low calorie form of KD, but in the literature there are some data reporting beneficial effects on respiratory parameters from ketogenic and low-carbohydrate high-fat diets. KD may be helpful in reducing ventilatory requirements in respiratory patients, so it should be considered in specifically addressed clinical trials as an adjuvant therapy for obese patients infected with SARS-CoV-2.

Effects of intermittent very-low calorie diet on glycemic control and cardiovascular risk factors in obese patients with type 2 diabetes mellitus: A randomized controlled trial.

Aims/IntroductionVery few studies assess the effectiveness of different protocols of intermittent very‐low calorie diet (VLCD) in patients with diabetes. This study was designed to compare the effects of 2 days/week and 4 days/week of intermittent VLCD on glycemic control, diabetes remission, metabolic parameters and quality of life in patients with type 2 diabetes and obesity.Materials and MethodsParticipants with obesity and type 2 diabetes were recruited and randomly assigned to three groups, consisting of control, 2 days/week and 4 days/week of intermittent VLCD. In the intermittent VLCD groups, participants received a 600‐kcal diet per day on restricted days and ad libitum food consumption on non‐restricted days. Glycemic control, rate of diabetes remission, metabolic parameters and quality of life were evaluated at baseline, weeks 2, 10 and 20.ResultsA total of 40 participants were enrolled. The mean body mass index was 30.1 ± 5.9 kg/m2, and the mean glycated hemoglobin was 7.4 ± 1.2%. At week 20, there was an improvement in glycemic control in both intermittent VLCD groups with significant decreases in glycated hemoglobin levels and insulin resistance index throughout the study periods. Diabetes remission without the need for medications was equally found in 29% of participants in both intermittent VLCD groups. Serum triglyceride, bodyweight, body mass index and fat mass were also significantly decreased in both VLCD groups. No serious adverse events were encountered.ConclusionIntermittent VLCD was highly effective in achieving optimal glycemic control. The effects of 2 days/week and 4 days/week of intermittent VLCD on diabetes remission were relatively similar.

Effect of weight loss on early left atrial myopathy in obese patients without known cardiovascular disease

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): BHF &amp; NIHR BRC Introduction Obesity is strongly associated with increased risk of heart failure and ischaemic stroke independently of associated co-morbidities. Left atrial (LA) reservoir dysfunction, a marker of atrial distensibility and compliance, is an early pathophysiological change which precedes the onset of cardiovascular disease in patients with obesity. It is unclear whether a weight loss intervention may be sufficient to reverse LA reservoir dysfunction. Purpose To longitudinally assess whether a weight loss intervention normalizes LA reservoir function by cardiac magnetic resonance (CMR) feature-tracking in patients with obesity and only subclinical cardiovascular disease and compared this age and sex matched non-obese normal weight controls. Methods A total of 45 patients with severe obese (age = 45 ± 11 years, body mass index = 39.1 ± 6.7 kg/m2, 51 ± 18 kg of excess body weight [EBW], 67% female) underwent CMR for quantification of LA and left ventricular (LV) size and function before and a median of 373 days following weight loss intervention. Weight loss was achieved by means of a very-low calorie diet (N = 28; 800 kcal/day) or by bariatric surgery (N = 17). A total of N = 27 non-obese healthy controls (age = 41 ± 12 years, body mass index = 22.3 ± 2.4 kg/m2, 75% female) underwent the same CMR protocol once. Results At baseline, patients with obesity displayed signs of atrial myopathy with increased LA volume and reduced LA reservoir function as compared to normal-weight controls (both P &amp;lt; 0.05, Figure 1) alongside increased LV mass and hyper-normal LV ejection fraction [LVEF] (both p &amp;lt; 0.01). As expected, weight loss led to a significant reduction of LA volume and LV mass with normalization of LVEF regardless of the degree of weight loss achieved (all P &amp;lt; 0.05, Figure 2). By contrast, only a large weight loss (&amp;gt;46.6% EBW, in red in Figure 2) was sufficient to improve and normalize the LA reservoir function (P &amp;lt; 0.05, Figure 2). On the other hand, moderate or milder weight loss (in orange and red) had no significant effect on LA reservoir function (both P &amp;gt; 0.05). Conclusion Successful weight loss can completely revert early LA myopathic phenotype in obese patients without known cardiovascular disease although this can be achieved only with larger weight loss targets.

Reduction of Cardio-Metabolic Risk and Body Weight through a Multiphasic Very-Low Calorie Ketogenic Diet Program in Women with Overweight/Obesity: A Study in a Real-World Setting.

Background: The prevention and treatment of obesity and its cardio-metabolic complications are relevant issues worldwide. Among lifestyle approaches, very low-calorie ketogenic diets (VLCKD) have been shown to lead to rapid initial weight loss, resulting in better long-term weight loss maintenance. As no information on VLCKD studies carried on in a real-world setting are available, we conducted this multi-centre study in a real-world setting, aiming at assessing the efficacy and the safety of a specific multiphasic VLCKD program in women with overweight or obesity. Methods: A multi-center, prospective, uncontrolled trial was conducted in 33 outpatient women (age range 27–60 y) with overweight or obesity (BMI: 30.9 ± 2.7 kg/m2; waist circumference: 96.0 ± 9.4 cm) who started a VLCKD dietary program (duration: 24 weeks), divided into four phases. The efficacy of VLCKD was assessed by evaluating anthropometric measures and cardiometabolic markers; liver and kidney function biomarkers were assessed as safety parameters. Results: The VLCKD program resulted in a significant decrease of body weight and BMI (−14.6%) and waist circumference (−12.4%). At the end of the protocol, 33.3% of the participants reached a normal weight and the subjects in the obesity range were reduced from 70% to 16.7%. HOMA-IR was markedly reduced from 3.17 ± 2.67 to 1.73 ± 1.23 already after phase 2 and was unchanged thereafter. Systolic blood pressure decreased after phase 1 (−3.5 mmHg) and remained unchanged until the end of the program. Total and LDL cholesterol and triglycerides were significantly reduced by VLCKD along with a significant HDL cholesterol increase. Liver, kidney and thyroid function markers did not change and remained within the reference range. Conclusions: The findings of a multi-center VLCKD program conducted in a real-world setting in a cohort of overweight/obese women indicate that it is safe and effective, as it results in a major improvement of cardiometabolic parameters, thus leading to benefits that span well beyond the mere body weight/adiposity reduction.

Epigenetic landscape in blood leukocytes following ketosis and weight loss induced by a very low calorie ketogenic diet (VLCKD) in patients with obesity

The molecular mechanisms underlying the potential health benefits of a ketogenic diet are unknown and could be mediated by epigenetic mechanisms. To identify the changes in the obesity-related methylome that are mediated by the induced weight loss or are dependent on ketosis in subjects with obesity underwent a very-low calorie ketogenic diet (VLCKD). Twenty-one patients with obesity (n=12 women, 47.9±1.02yr, 33.0±0.2kg/m2) after 6 months on a VLCKD and 12 normal weight volunteers (n=6 women, 50.3±6.2yrs, 22.7±1.5kg/m2) were studied. Data from the Infinium MethylationEPIC BeadChip methylomes of blood leukocytes were obtained at time points of ketotic phases (basal, maximum ketosis, and out of ketosis) during VLCKD (n=10) and at baseline in volunteers (n=12). Results were further validated by pyrosequencing in representative cohort of patients on a VLCKD (n=18) and correlated with gene expression. After weight reduction by VLCKD, differences were found at 988 CpG sites (786 unique genes). The VLCKD altered methylation levels in patients with obesity had high resemblance with those from normal weight volunteers and was concomitant with a downregulation of DNA methyltransferases (DNMT)1, 3a and 3b. Most of the encoded genes were involved in metabolic processes, protein metabolism, and muscle, organ, and skeletal system development. Novel genes representing the top scoring associated events were identified, including ZNF331, FGFRL1 (VLCKD-induced weight loss) and CBFA2T3, C3orf38, JSRP1, and LRFN4 (VLCKD-induced ketosis). Interestingly, ZNF331 and FGFRL1 were validated in an independent cohort and inversely correlated with gene expression. The beneficial effects of VLCKD therapy on obesity involve a methylome more suggestive of normal weight that could be mainly mediated by the VLCKD-induced ketosis rather than weight loss.

Effect of various weight loss interventions on serum NT-proBNP concentration in severe obese subjects without clinical manifest heart failure

Obesity is associated with a “natriuretic handicap” indicated by reduced N-terminal fragment of proBNP (NT-proBNP) concentration. While gastric bypass surgery improves the natriuretic handicap, it is presently unclear if sleeve gastrectomy exhibits similar effects. We examined NT-proBNP serum concentration in n = 72 obese participants without heart failure before and 6 months after sleeve gastrectomy (n = 28), gastric bypass surgery (n = 19), and 3-month 800 kcal/day very-low calorie diet (n = 25). A significant weight loss was observed in all intervention groups. Within 6 months, NT-proBNP concentration tended to increase by a median of 44.3 pg/mL in the sleeve gastrectomy group (p = 0.07), while it remained unchanged in the other groups (all p ≥ 0.50). To gain insights into potential effectors, we additionally analyzed NT-proBNP serum concentration in n = 387 individuals with different metabolic phenotypes. Here, higher NT-proBNP levels were associated with lower nutritional fat and protein but not with carbohydrate intake. Of interest, NT-proBNP serum concentrations were inversely correlated with fasting glucose concentration in euglycemic individuals but not in individuals with prediabetes or type 2 diabetes. In conclusion, sleeve gastrectomy tended to increase NT-proBNP levels in obese individuals and might improve the obesity-associated “natriuretic handicap”. Thereby, nutritional fat and protein intake and the individual glucose homeostasis might be metabolic determinants of NT-proBNP serum concentration.

Neuroendocrine and Metabolic Effects of Low-Calorie and Non-Calorie Sweeteners.

Since excessive sugar consumption has been related to the development of chronic metabolic diseases prevalent in the western world, the use of sweeteners has gradually increased worldwide over the last few years. Although low- and non-calorie sweeteners may represent a valuable tool to reduce calorie intake and prevent weight gain, studies investigating the safety and efficacy of these compounds in the short- and long-term period are scarce and controversial. Therefore, future studies will need to elucidate the potential beneficial and/or detrimental effects of different types of sweeteners on metabolic health (energy balance, appetite, body weight, cardiometabolic risk factors) in healthy subjects and patients with diabetes, obesity and metabolic syndrome. In this regard, the impact of different sweeteners on central nervous system, gut hormones and gut microbiota is important, given the strong implications that changes in such systems may have for human health. The aim of this narrative review is to summarize the current evidence for the neuroendocrine and metabolic effects of sweeteners, as well as their impact on gut microbiota. Finally, we briefly discuss the advantages of the use of sweeteners in the context of very-low calorie ketogenic diets.

Suppression of enteroendocrine cell glucagon-like peptide (GLP)-1 release by fat-induced small intestinal ketogenesis: a mechanism targeted by Roux-en-Y gastric bypass surgery but not by preoperative very-low-calorie diet

ObjectiveFood intake normally stimulates release of satiety and insulin-stimulating intestinal hormones, such as glucagon-like peptide (GLP)-1. This response is blunted in obese insulin resistant subjects, but is rapidly restored following...