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.     

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.     

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.     

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.     

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.     

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.     

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.     

Does weight loss prognosis depend on genetic make‐up?

The prevalence of obesity is rising throughout the world. Indeed, obesity has reached epidemic proportions in many developed and transition countries. Obesity is a complex disease with multifactorial origin, which in many cases appears as a polygenic condition affected by environmental factors. Treatment or prevention of obesity is necessary to reverse or avoid the onset of type 2 diabetes and other obesity-related diseases. Weight loss is a complex trait that depends on many environmental, behavioural and genetic influences. An effective programme for the management of overweight and obesity must take into account all of these factors. Individual responses to weight loss interventions vary widely and reliable predictors of successful slimming are poorly understood. The individual genetic make-up participating in energy expenditure regulation, appetite control, lipid metabolism and adipogenesis, have been reported to affect the risk of treatment failure in some subjects. In addition, the genotype could also help to predict the changes in lipid profile, cardiovascular risk factors and insulin sensitivity in response to weight loss. Herein, the current evidence from human studies that support the existence of a genetic component and the participation of different polymorphisms in the prognosis of weight loss induced by interventions leading to a negative energy balance are reviewed.     

Increased vegetable and fruit consumption during weight loss effort correlates with increased weight and fat loss

Background:

Individuals who focused on calorie counting lost more weight than those who focused on increasing vegetable and fruit (V&F) intake in a weight loss program. We now present serum carotenoid data (biomarkers of V&F intake) from both groups and test whether these biomarkers correlate with changes in weight and body fat.

Design:

Sixty obese volunteers were randomized to one of the following weight loss programs: 500 kcal per day reduction (Reduction) or a focus on consuming eight vegetables per day and 2–3 fruits per day (HiVeg). Volunteers in the Reduction group were 36.8±10.3 years with a body mass index of 33.5; 83% were white, 17% chose not to report race; 70% were not Hispanic or Latino, 13% were Hispanic or Latino and 17% chose not to report ethnicity. Volunteers in the HiVeg group were 30.4±6.6 years with a body mass index of 33.2: 74% white, 11% Asian, 5% black or African American, 5% multiracial and 5% chose not to report race; 89% were not Hispanic or Latino, 5% were Hispanic or Latino and 5% chose not to report ethnicity. Subjects were taught basic nutrition principles, received breakfast and lunch 5 days per week for 3 months, meals 2 days per week during month 4, then regular phone calls to month 12.

Results:

Total serum carotenoid concentrations increased from baseline to 3 months and remained elevated at 12 months, but there was no difference between groups. Changes in weight, fat and % fat correlated negatively with serum carotenoid concentrations.

Conclusion:

Increased serum carotenoids (a biomarker for V&F intake) correlated with improved weight and fat loss indicating that increased V&F consumption is an appropriate strategy for weight loss. However, in light of the fact that the Reduction group lost more weight, the consumption of increased V&F for the purpose of weight loss should happen within the context of reducing total caloric intake.     

降低体质量对阻塞性睡眠呼吸暂停低通气综合征治疗的研究

目的探讨降低体质量对阻塞性睡眠呼吸暂停低通气综合征（OSAHS）伴超重或肥胖者治疗的影响及临床意义。方法采用低热量饮食（84～105kJ／kg）和（或）运动减重后，观察治疗组与对照组自体症状、睡眠监测及血液生化等各项指标的变化情况，并对年龄、性别、治疗前体质量指数（BMI）、呼吸暂停低通气指数（AHI）、吸烟、高血压、糖尿病、高血脂、脑梗死、服药多因素进行Logistic回归分析。结果治疗组与对照组前后差值比较，鼾声、嗜睡评分、憋气、憋醒、记忆力下降、全身不适、胸闷、心悸症状均有改善；颈围、腰围、臀围较对照组有明显差异；呼吸暂停次数、AHI、呼吸暂停指数（AI）也较对照组有明显差异；低通气次数及低通气指数（Hl）无明显差异。血氧饱和度（SaO2低于95％、低于85％及低于80％所占的时间百分比较对照组有明显差异；最低血氧饱和度（LSaO2）及最长呼吸暂停时间较对照组有显著性差异。红细胞（RBC）、血红蛋白（Hb）、红细胞压积（HCT）也有明显差异。Logistic回归分析表明BMI、体质量减少、脑梗死、高脂血症影响OSAHS伴超重或肥胖者的治疗效果。结论减重对OSAHS伴超重或肥胖者的治疗是有效的，可使OSAHS者的严重程度得到改善，并使部分轻度OSAHS者治愈。减重后缺氧、RBC的改善对预防心脑血管病有着重要的意义。     

Factors that may impede the weight loss response to exercise-based interventions

The results of exercise programmes designed to reduce body fat are disappointing. However, the reporting of weight loss as mean values disguises those individuals who do lose significant amounts of fat. Why some participants produce significant exercise-induced fat loss whereas others lose little or increase fat stores is likely to be an outcome of a range of behavioural (e.g. sleep deprivation, caloric intake), inherited (e.g. muscle fibre type, gender) and physiological (e.g. hyperinsulinaemia, hypothyroidism) factors. The following review highlights possible factors involved in weight loss and discusses how individual differences may determine the extent of weight loss after an exercise intervention. Finally, implications for the treatment and prevention of obesity are discussed.     

Effects of lifestyle interventions and long‐term weight loss on lipid outcomes – a systematic review

Weight and lipids are critical components of the metabolic syndrome, diabetes and cardiovascular disease. Past reviews considering weight loss on lipid profiles have been for ≤1 year follow‐up and/or were for very overweight, obese or morbidly obese participants. This systematic review includes lifestyle interventions for adults (18–65 years), with a mean baseline BMI < 35 kg/m², with weight and lipid differences over 2 years. Between 1990 and 2010, 14 studies were identified. Mean differences for weight and lipids were modest. However, weight loss at 2–3 years follow‐up, produced significant beneficial lipid profile changes. These were similar to previous reviews conducted on heavier target groups and/or over shorter follow‐up periods; cholesterol (1.3% decrease per kg lost) and triglycerides (1.6% fall per kg). Weight loss sustained longer than 3 years was not associated with beneficial lipid changes, suggesting that other lifestyle changes not just weight loss needs maintaining. Evidence linking lifestyle induced sustained weight loss with lipid profile changes in the long‐term for this group is limited. Probable within‐group differences (treatment vs prevention), would make further group separation prudent. Individual patient data analysis would facilitate this, uncover baseline, medication and confounding effects, and may identify successful program components enabling more effective obesity prevention and treatment strategies.     

Weight loss in obese men by caloric restriction and high-dose diazoxide-mediated insulin suppression

Objective: To examine the concept whether high‐dose diazoxide (DZX)–mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men. Design: Open, uncontrolled, 6‐month pilot study. Energy intake was reduced by 30%, and walking for at least 30 min a day was strongly recommended. DZX treatment was started at 50 mg t.i.d. and increased by 50 mg per dose every 4 weeks to a maximum of 300 mg t.i.d., unless hyperglycaemia or other side‐effects occurred. Subjects and Methods: Eighteen obese hyperinsulinaemic men with a body mass index of 30–35 kg/m². Measurements included body weight, body composition, blood pressure, glycaemic control, insulin response, adiponectin and serum lipids. Results: Body weight decreased by 9.4 kg (95% CI: 5.6–13.2 kg, p < 0.001), waist circumference reduced by 9.2 cm (95% CI: 5.3–12.9 cm, p < 0.001) and total body fat mass decreased by 23.3% (95% CI: 13.7–32.9%, p < 0.001), without a concomitant change in soft tissue lean body mass or bone mass. Fat loss was inversely related to fasting insulin levels achieved at 6 months (r = ?0.76, p < 0.002). Diastolic blood pressure decreased by 10.9 mmHg (95% CI: 6.5–15.4 mmHg, p < 0.002). Fasting and postmeal peak insulin levels were reduced by about 65% (p < 0.001) and decreased to the normal range for non‐obese men. Fasting and postmeal peak glucose levels increased by 0.8 ± 0.3 mmol/l (p = 0.01) and 1.4 ± 0.7 mmol/l (p = 0.06) respectively. Haemoglobin A1c rose by 0.5% to 5.9 ± 0.2%. Conclusion: High‐dose DZX–mediated insulin suppression, in combination with moderate caloric restriction and lifestyle advice, is associated with a clinically relevant degree of weight reduction. A more extensive exploration is warranted to optimize this mode of treatment and to further clarify its risks and benefits.     

Effects of weight loss on pulmonary function in obese men with obstructive sleep apnoea syndrome

Abstract. The effects of long-term behaviour modification of obesity on pulmonary function was studied in eight men with obstructive sleep apnoea syndrome (initial mean body mass index [BMI] 41.8 kg m^?2) before and after a mean weight loss of 20 ± 7 (SD) kg. Mean arterial Pco₂ fell from 6.3 ± 1.2 to 5.5 ± 0.6 kPa (P < 0.05) and concomitant significant improvements were found in vital capacity, total lung capacity, functional residual capacity and forced expired volume (FEV 1.0). The study suggests that weight loss per se, rather than the method of choice to achieve weight loss, results in clinically significant improvement of pulmonary function in obese men.     

Risk factors for gallstone formation during rapid loss of weight

Risk factors for the development of gallstones during rapid weight loss were assessed in 457 subjects who entered a weight control program (520 kcal/day). Absence of gallstones in these subjects was documented by ultrasonography prior to entry into the study. Ultrasonography was performed again at 16 weeks on the subjects who remained in the study (N=248). The incidence of gallstones by 16 weeks of rapid weight loss was 10.9% (27/248). Most factors associated with gallstones in the general population, eg, older age, female gender, parity, positive family history, etc, were not associated with gallstones in this population. The risk factors for developing gallstones included increased initial body mass index [weight (kg)/height (m)²], amount of body mass index loss, and serum triglyceride levels. The positive predictive value of these risk factors was 75%, but the sensitivity was only 12%. These observations indicate that risk factors for the development of gallstones during rapid weight loss are probably different from those in the general population. The factors identified by this study are useful in predicting patients at high risk for gallstones. However, since only a minority of gallstones that form can be predicted, further study is needed to identify additional factors that will improve our ability to predict gallstone formation.This study was supported by grants from NIH-NIDDK R01 DK-37080, Ciba-Geigy, and the Stuart Foundations.     

Sleep duration and weight loss among overweight/obese women enrolled in a behavioral weight loss program

Objective:

The purpose of this study was to examine whether baseline sleep duration predicts weight loss outcomes in a randomized controlled trial examining a behavioral weight loss (BWL) intervention among overweight and obese (OW/OB) women with urinary incontinence; and whether participation in the BWL intervention is associated with changes in sleep duration.

Design:

Longitudinal, clinical intervention study of a 6-month BWL program.

Subjects:

Three hundred sixteen OW/OB women, with urinary incontinence (age: 30–81 years, body mass index (BMI; 25–50 kg m⁻²) enrolled from July 2004–April 2006.

Measurements:

Measured height and weight, self-report measures of demographics, sleep and physical activity.

Results:

Neither self-reported total sleep time (TST) nor time in bed (TIB) at baseline significantly predicted weight loss outcomes among OW/OB women in a BWL treatment. BWL treatment was successful regardless of how much subjects reported sleeping at baseline, with an average weight loss of 8.19 kg for OW/OB women receiving BWL treatment, versus a weight loss of 1.44 kg in the control condition. Similarly, changes in weight, BMI and incontinence episodes did not significantly predict changes in sleep duration or TIB across the treatment period.

Conclusion:

Although epidemiological and cross-sectional studies support a relationship between short sleep and increased BMI, the present study found no significant relationship between TST or TIB and weight loss for OW/OB women participating in a BWL treatment.