Persistence of improvement in insulin sensitivity following a dietary weight loss programme

Aim: Short‐term dietary weight loss can improve insulin resistance but long‐term studies are lacking. We sought to quantify the degree to which maintenance of weight loss after a short‐term dietary intervention was associated with persistent metabolic benefits. Methods: Fifty‐seven insulin‐resistant obese subjects had insulin‐mediated glucose disposal quantified through the steady‐state plasma glucose (SSPG) test, and associated metabolic risk markers quantified at baseline, after a 16‐week dietary weight loss intervention, and in 25 subjects, at follow‐up of 28.8 ± 13 months. Changes in metabolic variables over time were analysed and correlation with weight loss ascertained. Those with greatest vs. least long‐term SSPG response (responders vs. non‐responders) were compared. Multivariate analysis was performed for predictors of persistent SSPG response. Results: At follow‐up, the 25 subjects who returned for metabolic testing had, on average, maintained their weight loss. Insulin‐mediated glucose disposal remained significantly improved vs. baseline, as did plasma triglyceride and HDL cholesterol (HDL‐C) concentrations, and improvement correlated with total amount of weight lost. Comparison of SSPG responders to non‐responders showed no difference in amount of weight lost and SSPG change during the 16‐week dietary intervention; however, SSPG non‐responders regained 2.6% of weight lost, whereas responders lost an additional 1.5% at follow‐up (p < 0.05 vs. non‐responders). Non‐responders had baseline characteristics consistent with more severe insulin resistance, including higher fasting plasma glucose (p = 0.03). Long‐term SSPG change was independently predicted by both total weight loss (p = 0.005) and baseline fasting plasma glucose (p = 0.007). Conclusions: Improvement in insulin sensitivity is maintained for 2–3 years following dietary weight loss if weight is not regained. Triglyceride and HDL‐C concentrations also remain improved over time, consistent with improvement in insulin sensitivity. Fasting glucose and weight regain predict less long‐term response in insulin sensitivity. These results highlight the potential long‐term benefits of weight loss and importance of preventing weight regain among high‐risk individuals.     

N-butyldeoxynojirimycin causes weight loss as a result of appetite suppression in lean and obese mice

Aim: To determine the mechanism of weight loss caused by high doses of N‐butyldeoxynojirimycin (NB‐DNJ) in healthy lean and leptin–deficient obese (ob/ob) mice. Methods: Healthy lean and obese mice were treated with NB‐DNJ by the following methods: admixed with their diet, delivered by subcutaneously implanted mini‐pumps or by intraperitoneal or intracerebroventricular (ICV) injection. Daily changes in body weight and food intake were recorded during the experimental period. The effect of NB‐DNJ treatment on subcutaneous adipose tissue and on epididymal fat pads was measured. Results: Lean mice treated with NB‐DNJ, admixed with their diet, lost weight in the form of adipose tissue. This resulted in a 40% reduction in skin thickness (control, 358 ± 11 μm; NB‐DNJ treated 203 ± 6 μm) and a reduction in epididymal fat pad weights after 5 weeks of treatment at 2400 mg/kg/day (control, 0.0154 ± 0.001; NB‐DNJ treated, 0.0026 ± 0.0005 as ratios of fat pad weight to total body weight). Following the depletion of adipose tissue mass, the mice grew normally and did not have any reduction in lean mass. Obese mice treated with NB‐DNJ also lost weight or gained weight at a greatly reduced rate compared with non‐treated controls. Body weights at 6 months of age were: lean control, 29.10 ± 1.15 g; lean NB‐DNJ treated, 22.73 ± 0.29 g; obese control, 63.25 ± 1.5 g; obese NB‐DNJ treated from 5 weeks of age, 35.30 ± 1.68 g; obese NB‐DNJ treated from 12 weeks of age, 38.84 ± 1.26 g. Both the lean and obese groups of mice treated with NB‐DNJ ate up to 30% less than untreated controls. Daily food intake (powder diet) were: lean control, 4.15 ± 0.54 g; obese control, 4.14 ± 0.2 g; lean NB‐DNJ treated 2.9 ± 0.37 g; obese NB‐DNJ treated, 2.88 ± 0.47 g. Mice treated with the N‐substituted galactose imino sugar analogue, N‐butyldeoxygalactonojirimycin (NB‐DGJ) did not lose weight. Mice experienced similar weight loss or lack of weight gain when fed a restricted diet that mimics the drug‐induced level of food consumption. Delivery of 2 nmol NB‐DNJ by ICV injection into lean mice also caused similar reductions in food intake. Food intake: saline vehicle, 4.30 ± 0.12 g; NB‐DNJ, 3.37 ± 0.19 g; NB‐DGJ, 4.03 ± 0.16 g; 2‐deoxyglucose, 4.7 ± 0.15 g. Conclusion: NB‐DNJ causes weight loss as a result of reduced food consumption due to central appetite suppression.     

The effects of weight loss strategies on gastric emptying and appetite control

The gastrointestinal tract plays an important role in the improved appetite control and weight loss in response to bariatric surgery. Other strategies which similarly alter gastrointestinal responses to food intake could contribute to successful weight management. The aim of this review is to discuss the effects of surgical, pharmacological and behavioural weight loss interventions on gastrointestinal targets of appetite control, including gastric emptying. Gastrointestinal peptides are also discussed because of their integrative relationship in appetite control. This review shows that different strategies exert diverse effects and there is no consensus on the optimal strategy for manipulating gastric emptying to improve appetite control. Emerging evidence from surgical procedures (e.g. sleeve gastrectomy and Roux‐en‐Y gastric bypass) suggests a faster emptying rate and earlier delivery of nutrients to the distal small intestine may improve appetite control. Energy restriction slows gastric emptying, while the effect of exercise‐induced weight loss on gastric emptying remains to be established. The limited evidence suggests that chronic exercise is associated with faster gastric emptying, which we hypothesize will impact on appetite control and energy balance. Understanding how behavioural weight loss interventions (e.g. diet and exercise) alter gastrointestinal targets of appetite control may be important to improve their success in weight management.     

A systematic review of the impact of weight loss on cancer incidence and mortality

Obesity is well recognized as a significant risk factor for certain cancers; however, a corresponding risk reduction with weight loss is not yet clearly defined. This review aims to examine the literature investigating the effect of all types of weight loss on cancer incidence and mortality, and to more clearly describe the relationship between these two factors. A literature search identified 34 publications reporting weight loss data in relation to cancer incidence or mortality. All except one were observational studies and the majority used self‐reported weights and did not define intentionality of weight loss. 16/34 studies found a significant inverse association between weight loss and cancer incidence or mortality. The remainder returned null findings. The observed association was more consistently seen in studies that investigated the effect of intentional weight loss (5/6 studies) and the risk reduction was greatest for obesity‐related cancers and in women. In conclusion, intentional weight loss does result in a decreased incidence of cancer, particularly female obesity‐related cancers. However, there is a need for further evaluation of sustained intentional weight loss in the obese with less reliance on self‐reported weight data and more focus on male populations.     

Relative changes in resting energy expenditure during weight loss: a systematic review

A more comprehensive understanding of the effects of weight loss on the changes in resting energy expenditure (EE) is relevant. A MEDLINE search was performed to identify studies with information relevant to this systematic review. From this search, the mean rate of resting EE decrease relative to weight loss was calculated from 90 available publications. A decrease of resting EE relative to weight loss of ?15.4 ± 8.7 kcal kg^?1 was observed from 2996 subjects. No sex differences were noted in the overall resting EE decrease relative to weight loss. However, a significant sex differences was seen with pharmacological interventions, which seemed to depress the resting EE relative to weight loss to a greater extent in men than in women (P < 0.05). A greater drop in resting EE relative to weight loss was observed for short interventions (more than 2 but less than 6 weeks) when compared with long interventions (<6 weeks) (–27.7 ± 6.7 vs. ?12.8 ± 7.1 kcal kg^?1) (P < 0.001). Men and women have a similar decrease in resting EE relative to weight loss except in the case of pharmacological interventions. Short interventions also produced greater resting EE losses relative to weight loss.     

Impact of weight loss on the metabolic syndrome

Aim: Individuals with the metabolic syndrome (MS), a clustering of risk factors [triglycerides, glucose, high-density lipoprotein cholesterol, blood pressure (BP), abdominal obesity] defined by the National Cholesterol Education Program (NCEP), are at high risk for coronary heart disease and type 2 diabetes mellitus, and may benefit from aggressive lifestyle modification.
Methods: We reviewed 1 year of consecutive patients' charts to determine the prevalence of the MS in obese individuals enrolled in a medically supervised rapid weight loss programme, the correlation of weight change with the components of the MS, and response to diet-induced weight loss.
Results: Out of 185 individuals, 125 (68%) met the NCEP definition of the MS. A moderate decrease in weight (6.5%) induced by a very low calorie diet (VLCD) resulted in substantial reductions of systolic (11.1 mmHg) and diastolic (5.8 mmHg) blood pressure (BP), glucose (17 mg/dl), triglycerides (94 mg/dl) and total cholesterol (37 mg/dl) at 4 weeks (all p < 0.001). These improvements were sustained at the end of active weight loss (average 16.7 weeks; total weight loss 15.1%), with further significant reductions in BP and triglycerides. Weight loss was related to the changes in each criterion of the metabolic syndrome.
Conclusions: The MS is prevalent in two-thirds of obese individuals enrolling in a structured weight loss programme. Moderate weight loss with a VLCD markedly improved all aspects of the MS.     

Effectiveness of web‐based interventions in achieving weight loss and weight loss maintenance in overweight and obese adults: a systematic review with meta‐analysis

The objectives of this systematic review are to evaluate the effectiveness of web‐based interventions on weight loss and maintenance and identify which components of web‐based interventions are associated with greater weight change and low attrition rates. A literature search from 1995 to April 2008 was conducted. Studies were eligible for inclusion if: participants were aged ≥18 years with a body mass index ≥25, at least one study arm involved a web‐based intervention with the primary aim of weight loss or maintenance, and reported weight‐related outcomes. Eighteen studies met the inclusion criteria. Thirteen studies aimed to achieve weight loss, and five focused on weight maintenance. Heterogeneity was evident among the studies with seven research questions examined across interventions of varying intensity. Seven studies were assessed for effectiveness based on percentage weight change, with four studies deemed effective. Although the four meta‐analyses suggest meaningful weight change, it is not possible to determine the effectiveness of web‐based interventions in achieving weight loss or maintenance due to heterogeneity of designs and thus the small number of comparable studies. Higher usage of website features may be associated with positive weight change, but we do not know what features improve this effect or reduce attrition.     

A review of web‐based weight loss interventions in adults

Unprecedented obesity rates are changing the burden of disease worldwide and obesity‐related health complications are increasing healthcare costs. In response, researchers, clinicians and public health practitioners are seeking new and effective tools such as the Internet to effect weight loss. This review highlights peer‐reviewed literature on randomized controlled trials that examine Internet‐delivered weight loss and maintenance programmes. The scope of this review is broader than previous reviews, including more males and non‐Caucasian participants. The reviewed studies show intervention results ranging from no weight loss to an average loss of 7.6 kg. It is difficult to draw a definitive conclusion on the potential impact of Internet‐based weight loss as study methods are highly variable between papers, low adherence was recorded and not all studies include a control group. As the demand for low‐cost, efficacious interventions that yield statistically significant and/or clinically relevant results grows, more rigorous, population‐specific research is needed to determine if Internet‐delivered interventions may slow or reverse with weight gain and obesity and the associated health consequences.     

A systematic review with meta‐analyses of text message‐delivered behaviour change interventions for weight loss and weight loss maintenance

Short Message Service (SMS)‐delivered behaviour change interventions are frequently used to support weight management. This systematic review examines the effectiveness of SMS‐delivered behaviour change interventions for weight management. Electronic databases were searched for randomised controlled trials (RCTs) comparing SMS‐delivered adult weight management interventions to control groups, published between 1990 and 2018. Weight change was examined using random effects meta‐analyses at intervention cessation and postintervention follow‐up. Subgroup analyses examined intervention duration, SMS frequency, theory use, SMS interactivity, and SMS tailoring. Fifteen studies met inclusion criteria (2705 participants). For weight loss interventions (n = 12, 1977 participants), the mean difference in weight change was ?2.28 kg (95% confidence interval [CI] ?3.17 to ?1.36 kg). No studies reported postintervention follow‐up. For weight loss maintenance interventions (n = 3, 728 participants), the mean difference in weight change was ?0.68 kg (95% CI, ?1.31 to ?0.05 kg), and postintervention follow‐up (n = 2, 498 participants) effects were ?0.57 kg (95% CI, ?1.67 to 0.53 kg). No subgroup differences were found. SMS‐delivered behaviour change interventions for weight loss led to significant small to moderate weight loss and weight loss maintenance compared with control groups. Evidence on long‐term effects is limited. SMS‐delivered behaviour change interventions are a potentially effective and scalable intervention option for obesity treatment.     

Weight loss and African-American women: a systematic review of the behavioural weight loss intervention literature

The excess burden of obesity among African-American women is well documented. However, the behavioural weight loss intervention literature often does not report results by ethnic group or gender. The purpose of this article is to conduct a systematic review of all behavioural weight loss intervention trials published between 1990 and 2010 that included and reported results separately for African-American women. The criteria for inclusion included (i) participants age ≥18 years; (ii) a behavioural weight loss intervention; (iii) weight as an outcome variable; (iv) inclusion of African-American women; and (v) weight loss results reported separately by ethnicity and gender. The literature search identified 25 studies that met inclusion criteria. Our findings suggest that more intensive randomized behavioural weight loss trials with medically at-risk populations yield better results. Well-designed and more intensive multi-site trials with medically at-risk populations currently offer the most promising results for African-American women. Still, African-American women lose less weight than other subgroups in behavioural weight loss interventions. It is now critical to expand on individual-level approaches and incorporate the biological, social and environmental factors that influence obesity. This will help enable the adoption of healthier behaviours for this group of women disproportionately affected by obesity.     

The impact of Internet use for weight loss

With rising rates of obesity and obesity-related health problems, finding additional means to help reduce obesity is critical. This review examined the impact of the Internet as a medium to deliver weight loss programs. Specifically, the review examined the public's interest, the availability and the known efficacy of Internet-based weight loss programs. Findings showed that the general public is turning to the Internet for diet and fitness information and has reported that information they found online has impacted their behaviour. Little is known about who is interested in using the Internet for weight loss and what their experiences have been. The programs most readily available to the general consumer tend to vary widely in quality, with few efficacy studies. However, researchers have shown that efficacious programs have been delivered via the Internet. Successful online programs included a structured approach to modifying energy balance, the use of cognitive-behavioural strategies such as self-monitoring, and individualized feedback and support. Implications include developing strategies to increase distribution of programs with known efficacy, determining the applicability of effective programs for diverse audiences, conducting media literacy education for the general public, and continued research into understanding who may be best served by online weight loss programming.     

Modulation of nutrient sensing nuclear hormone receptors promotes weight loss through appetite suppression in mice

Aim: Peroxisome proliferator activated receptors (PPARs) are nuclear receptors involved in glucose and lipid metabolism. Three isoforms of PPARs have been identified with different tissue distribution and biological functions. Although the pharmacology of each receptor is well studied, the physiological effect of simultaneous activation of PPARα, γ and δ is only starting to emerge. We sought to determine the biological effects of a novel PPAR pan activator and elucidate the physiological mechanisms involved. Methods: Ob/ob, diet‐induced obese (DIO) or PPARα knockout mice were administered a novel agonist that activates all PPARs to various degrees to determine the effect on body weight, body composition, food intake and energy expenditure. In addition, serum parameters including glucose, insulin, triglycerides and ketone bodies as well as tissue acylcarnitine were evaluated. The effect of the novel agonist on liver and skeletal muscle histopathology was also studied. Results: We report that simultaneous activation of all PPARs resulted in substantial weight loss in ob/ob and DIO mice. Consistent with known PPAR pharmacology, we observed that agonist treatment increased lipid oxidation, although appetite suppression was mainly responsible for the weight loss. Agonist‐induced weight loss was completely absent in PPARα knockout mice suggesting that PPARα pharmacology was the major contributor to weight regulation in mice. Conclusions: Our work provides evidence that simultaneous activation of PPARα, γ and δ decreases body weight by regulating appetite. These effects of the pan agonist were completely absent in PPARα knockout mice, suggesting that PPARα pharmacology was the major contributor to weight loss.     

Problems in identifying predictors and correlates of weight loss and maintenance: implications for weight control therapies based on behaviour change

Weight management is a dynamic process, with a pre‐treatment phase, a treatment (including process) phase and post‐treatment maintenance, and where relapse is possible during both the treatment and maintenance. Variability in the statistical power of the studies concerned, heterogeneity in the definitions, the complexity of obesity and treatment success, the constructs and measures used to predict weight loss and maintenance, and an appreciation of who and how many people achieve it, make prediction difficult. In models of weight loss or maintenance: (i) predictors explain up to 20–30% of the variance; (ii) many predictors are the sum of several small constituent variables, each accounting for a smaller proportion of the variance; (iii) correlational or predictive relationships differ across study populations; (iv) inter‐individual variability in predictors and correlates of outcomes is high and (v) most of the variance remains unexplained. Greater standardization of predictive constructs and outcome measures, in more clearly defined study populations, tracked longitudinally, is needed to better predict who sustains weight loss. Treatments need to develop a more individualized approach that is sensitive to patients' needs and individual differences, which requires measuring and predicting patterns of intra‐individual behaviour variations associated weight loss and its maintenance. This information will help people shape behaviour change solutions to their own lifestyle needs.     

Incremental weight loss improves cardiometabolic risk in extremely obese adults

Objective

Excessively obese adults often acquire many metabolic disorders that put them at high risk for developing type 2 diabetes mellitus and cardiovascular disease. We investigated the hypothesis that cardiometabolic risk in a primary care cohort of 208 excessively obese adults (body mass index 40-60 kg/m², 48 with type 2 diabetes mellitus) would deteriorate with additional weight gain and improve incrementally beginning with 5% weight reduction.

Methods

Further analysis of the Louisiana Obese Subjects Study of excessively obese patients enrolled and followed during 2005-2008 is reported.

Results

Weight loss correlated significantly with improvements in fasting plasma glucose, triglycerides, high- and low-density lipoprotein cholesterol, uric acid, alanine aminotransferase, lactate dehydrogenase, and high-sensitivity C-reactive protein. Most parameters deteriorated with weight gain and progressively improved with 5% or more weight loss. Except for low-density lipoprotein cholesterol, all risk factors significantly improved with ≥ 20% loss of body weight. Among patients who had not been diagnosed with type 2 diabetes mellitus and had normoglycemia at baseline, median fasting plasma glucose increased significantly (13%) with stable or gained weight at 1 year, but did not change significantly with reduced weight. Although glucose levels did not change significantly in patients with type 2 diabetes mellitus who gained weight, a decline beginning after 5% weight reduction culminated in 25% glucose reduction with ≥ 20% weight loss. Resting blood pressure declined independently of weight change.

Conclusion

Very obese adults can improve their cardiometabolic risk under primary care weight management. Incremental success may help motivate further therapeutic weight reduction.     

Effectiveness of male-only weight loss and weight loss maintenance interventions: a systematic review with meta-analysis

The objectives of this systematic review were to investigate the effectiveness of male-only weight loss and weight loss maintenance interventions and to identify intervention characteristics associated with effectiveness. In May 2011, a systematic literature search with no date restrictions was conducted across eight databases. Twenty-four articles describing 23 studies met the eligibility criteria. All studies included a weight loss intervention and four studies included an additional weight loss maintenance intervention. Study quality was mostly poor for weight loss studies (median = 3/10, range = 1-9) and weight loss maintenance studies (median = 3.5/10, range = 1-6). Twenty-three of 31 individual weight loss interventions (74%) from the eligible studies were considered effective. Meta-analysis revealed a significant difference in weight change favouring weight loss interventions over no-intervention controls at the last reported assessment (weighted mean difference -5.66 kg [-6.35, -4.97], Z = 16.04 [P < 0.00001]). Characteristics common to effectiveness were younger sample (mean age ≤ 42.8 years), increased frequency of contact (> 2.7 contacts/month), group face-to-face contact and inclusion of a prescribed energy restriction. Preliminary evidence suggests men-only weight loss programmes may effectively engage and assist men with weight loss. However, more high-quality studies are urgently needed to improve the evidence base, particularly for maintenance studies.     

Evaluating commercial weight loss programmes: an evolution in outcomes research

The increasing prevalence of obesity has been mirrored by a parallel increase in the number of commercial weight loss programmes. Research evaluating these programmes is meagre, however, compared to the numbers treated. Reluctance of commercial weight loss programmes to meaningfully evaluate their weight loss efficacy may arise from fear that competitors will use the results against them. Evaluation of commercial weight loss programmes usually progresses from testimonials, often by famous people who were successful, to uncontrolled studies of past participants evaluated either by the programme itself or by an outside entity. The gold standard, however, is a scientifically rigorous, controlled study of the programme conducted by an independent entity. Such a study, published in a peer-reviewed journal, can gain credibility for a programme, as it did with Slim Fast, if the results are positive, or herald the end of the programme, as it was with Simeons human chorionic gonadotropin injection clinics. This review of the evolution of the evaluation process of commercial weight loss programmes leads us to conclude that consumers are likely to demand greater scientific rigour in the future, a change that will favour informed choice and discourage the practice of unrealistic advertising that raises false hopes.     

Effect of obesity and weight loss on ventricular repolarization: a systematic review and meta‐analysis

We performed a systematic review and meta‐analysis of the effects of obesity ± overweight and weight loss on the corrected QT interval (QTc) and QT or QTc dispersion (indices of ventricular repolarization). Mean difference for both QTc and QT or QTc dispersion with 95% confidence intervals (CIs) was calculated comparing obese ± overweight subjects and normal weight controls and QTc and QT or QTc dispersion before and after weight loss from diet ± exercise or bariatric surgery. A total of 22 studies fulfilled the selection criteria. Compared with normal weight controls, there was a significantly longer QTc in obese ± overweight subjects (mean difference of 21.74 msec, 95% CI: 18.76 to 22.32) and significantly longer QT or QTc dispersion (mean difference of 15.17 msec, 95% CI: 13.59 to 16.74). Weight loss was associated with a significant decrease in QTc (mean difference ?25.77 msec, 95% CI: ?28.33–23.21) and QT or QTc dispersion (mean difference of ?13.46 msec, 95% CI: ?15.60 to ?11.32 in obese ± overweight subjects. Thus, obesity ± overweight is associated with significant prolongation of QTc and QT or QTC dispersion. Weight loss in obese ± overweight subjects produces significant decreases in these variables. © 2016 World Obesity