Pre‐ to Postoperative Physical Activity Changes in Bariatric Surgery Patients: Self Report vs. Objective Measures

Bariatric surgery patients report significant pre‐ to postoperative increases in physical activity (PA). However, it is unclear whether objective measures would corroborate these changes. The present study compared self‐reported and accelerometer‐based estimates of changes in moderate‐to‐vigorous intensity PA (MVPA) from pre‐ (pre‐op) to 6 months postsurgery (post‐op). Twenty bariatric surgery (65% laparoscopic‐adjustable gastric banding, 35% gastric bypass) patients (46.2 ± 9.8 years, 88% female, pre‐op BMI = 50.8 ± 9.7 kg/m²) wore RT3 accelerometers as an objective measure of MVPA and completed the Paffenbarger Physical Activity Questionnaire (PPAQ) as a subjective measure before and 6 months after bariatric surgery. Time (min/week) spent in MVPA was calculated for the PPAQ and RT3 (≥1‐min and ≥10‐min bouts) at pre‐op and post‐op. Self‐reported MVPA increased fivefold from pre‐op to post‐op (44.6 ± 80.8 to 212.3 ± 212.4 min/week; P < 0.005). By contrast, the RT3 showed nonsignificant decreases in MVPA for both ≥1‐min (186.0 ± 169.0 to 151.2 ± 118.3 min/week) and ≥10‐min (41.3 ± 109.3 to 39.8 ± 71.3 min/week) bouts. At pre‐op, the percentage of participants who accumulated ≥150‐min/week of MVPA in bouts ≥10‐min according to the PPAQ and RT3 was identical (10%). However, at post‐op, 55% of participants reported compliance with the recommendation compared to 5% based on RT3 measurement (P = 0.002). Objectively‐measured changes in MVPA from pre‐op to 6 months post‐op appear to be much smaller than self‐reported changes. Further research involving larger samples is needed to confirm these findings and to determine whether self‐report and objective PA measures are differentially associated with surgical weight loss outcomes.     

Gastric bypass surgery reduces plasma ceramide subspecies and improves insulin sensitivity in severely obese patients

Bariatric surgery is associated with near immediate remission of type 2 diabetes and hyperlipidemia. The mechanisms underlying restoration of normal glucose tolerance postoperatively are poorly understood. Herein, we examined the effect of Roux‐en‐Y gastric bypass surgery (RYGB) on weight loss, insulin sensitivity, plasma ceramides, proinflammatory markers, and cardiovascular risk factors before and at 3 and 6 months after surgery. Thirteen patients (10 female; age 48.5 ± 2.7 years; BMI, 47.4 ± 1.5 kg/m²) were included in the study, all of whom had undergone laparoscopic RYGB surgery. Insulin sensitivity, inflammatory mediators and fasting lipid profiles were measured at baseline, 3 and 6 months postoperatively, using enzymatic analysis. Plasma ceramide subspecies (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. At 3 months postsurgery, body weight was reduced by 25%, fasting total cholesterol, triglycerides, low‐density lipoproteins, and free fatty acids were decreased, and insulin sensitivity was increased compared to presurgery values. These changes were all sustained at 6 months. In addition, total plasma ceramide levels decreased significantly postoperatively (9.3 ± 0.5 nmol/ml at baseline vs. 7.6 ± 0.4 at 3 months, and 7.3 ± 0.3 at 6 months, P < 0.05). At 6 months, the improvement in insulin sensitivity correlated with the change in total ceramide levels (r = ?0.68, P = 0.02), and with plasma tumor necrosis factor‐α (TNF‐α) (r = ?0.62, P = 0.04). We conclude that there is a potential role for ceramide lipids as mediators of the proinflammatory state and improved insulin sensitivity after gastric bypass surgery.     

Weight loss therapy improves pancreatic endocrine function in obese older adults

Objective: Obesity and aging increase the risk of type 2 diabetes (T2D). We evaluated whether weight loss therapy improves pancreatic endocrine function and insulin sensitivity in obese older adults. Methods and Procedures: Twenty‐four obese (BMI: 38 ± 2 kg/m²) older (age: 70 ± 2 years) adults completed a 6‐month randomized, controlled trial. Participants were randomized to diet and exercise (treatment group) or no therapy (control group). β‐Cell function (assessed using the C‐peptide minimal model), α‐cell function (assessed by the glucagon response to an oral glucose load), insulin sensitivity (assessed using the glucose minimal model), and insulin clearance rate were evaluated using a 5‐h modified oral glucose tolerance test. Results: Body weight decreased in the treatment group, but did not change in the control group (?9 ± 1% vs. 0 ± 1%; P < 0.001). Insulin sensitivity doubled in the treatment group and did not change in the control group (116 ± 49% vs. ?11 ± 13%; P < 0.05). Even though indices of β‐cell responsivity to glucose did not change (P > 0.05), the disposition index (DI), which adjusts β‐cell insulin response to changes in insulin sensitivity, improved in the treatment group compared with the control group (100 ± 47% vs. ?22 ± 9%; P < 0.05). The glucagon response decreased in the treatment but not in the control group (?5 ± 2% vs. 4 ± 4%; P < 0.05). Insulin secretion rate did not change (P > 0.05), but insulin clearance rate increased (51 ± 25%; P < 0.05), resulting in lower plasma insulin concentrations. Discussion: Weight loss therapy concomitantly improves β‐cell function, lowers plasma glucagon concentrations, and improves insulin action in obese older adults. These metabolic effects are likely to reduce the risk of developing T2D in this population.     

Altered Intramuscular Lipid Metabolism Relates to Diminished Insulin Action in Men,but Not Women,in Progression to Diabetes

Whether sex differences in intramuscular triglyceride (IMTG) metabolism underlie sex differences in the progression to diabetes are unknown. Therefore, the current study examined IMTG concentration and fractional synthesis rate (FSR) in obese men and women with normal glucose tolerance (NGT) vs. those with prediabetes (PD). PD (n = 13 men and 7 women) and NGT (n = 7 men and 12 women) groups were matched for age and anthropometry. Insulin action was quantified using a hyperinsulinemic‐euglycemic clamp with infusion of [6,6^?2H₂]‐glucose. IMTG concentration was measured by gas chromatography/mass spectrometry (GC/MS) and FSR by GC/combustion isotope ratio MS (C‐IRMS), from muscle biopsies taken after infusion of [U^?13C]palmitate during 4 h of rest. In PD men, the metabolic clearance rate (MCR) of glucose was lower during the clamp (4.71 ± 0.77 vs. 8.62 ± 1.26 ml/kg fat‐free mass (FFM)/min, P = 0.04; with a trend for lower glucose rate of disappearance (Rd), P = 0.07), in addition to higher IMTG concentration (41.2 ± 5.0 vs. 21.2 ± 3.4 µg/mg dry weight, P ≤ 0.01), lower FSR (0.21 ± 0.03 vs. 0.42 ± 0.06 %/h, P ≤ 0.01), and lower oxidative capacity (P = 0.03) compared to NGT men. In contrast, no difference in Rd, IMTG concentration, or FSR was seen in PD vs. NGT women. Surprisingly, glucose Rd during the clamp was not different between NGT men and women (P = 0.25) despite IMTG concentration being higher (42.6 ± 6.1 vs. 21.2 ± 3.4 µg/mg dry weight, P = 0.03) and FSR being lower (0.23 ± 0.04 vs. 0.42 ± 0.06 %/h, P = 0.02) in women. Alterations in IMTG metabolism relate to diminished insulin action in men, but not women, in the progression toward diabetes.     

Sleep apnea modifies the long‐term impact of surgically induced weight loss on cardiac function and inflammation

Objective:

Obesity is frequently associated with obstructive sleep apnea (OSA). Both conditions are proinflammatory and proposed to deteriorate cardiac function. We used a nested cohort study design to evaluate the long‐term impact of bariatric surgery on OSA and how weight loss and OSA relate to inflammation and cardiac performance.

Design and Methods:

At 10‐year follow‐up in the Swedish Obese Subjects (SOS) study, we identified 19 obese subjects (BMI 31.2 ± 5.3 kg m^?2), who following bariatric surgery at SOS‐baseline had displayed sustained weight losses (surgery group), and 20 obese controls (BMI 42.0 ± 6.2 kg m^?2), who during the same time‐period had maintained stable weight (control group). All study participants underwent overnight polysomnography examination, echocardiography and analysis of inflammatory markers.

Results:

The surgery group displayed a lower apnea hypopnea index (AHI) (19.9 ± 21.5 vs. 37.8 ± 27.7 n/h, P = 0.013), lower inflammatory activity (hsCRP 2.3 ± 3.0 vs. 7.2 ± 5.0 mg L^?1, P < 0.001), reduced left ventricular mass (165 ± 22 vs. 207 ± 22 g, P < 0.001) and superior left ventricular diastolic function (E/A ratio 1.24 ± 1.10 vs. 1.05 ± 0.20, P = 0.006) as compared with weight stable obese controls. In multiple regression analyses including all subjects (n = 39) and controlling for BMI, the AHI remained independently associated with hsCRP (β = 0.09, P < 0.001), TNF‐α (β = 0.03, P = 0.031), IL‐6 (β = 0.01, P = 0.007), IL 10 (β = ?0.06; P = 0.018), left ventricular mass (β = 0.64, P < 0.001), left atrial area (β = 0.08, P = 0.002), pulmonary artery pressure (β = 0.08, P = 0.011) and E/E_a ratio (β = 0.04, P = 0.021).

Conclusions:

Patients with sustained weight loss after bariatric surgery display less severe sleep apnea, reduced inflammatory activity, and enhanced cardiac function. Persisting sleep apnea appears to limit the beneficial effect of weight loss on inflammation and cardiac performance.

     

Mediators of Weight Loss and Weight Loss Maintenance in Middle‐aged Women

Long‐term behavioral self‐regulation is the hallmark of successful weight control. We tested mediators of weight loss and weight loss maintenance in middle‐aged women who participated in a randomized controlled 12‐month weight management intervention. Overweight and obese women (N = 225, BMI = 31.3 ± 4.1 kg/m²) were randomly assigned to a control or a 1‐year group intervention designed to promote autonomous self‐regulation of body weight. Key exercise, eating behavior, and body image variables were assessed before and after the program, and tested as mediators of weight loss (12 months, 86% retention) and weight loss maintenance (24 months, 81% retention). Multiple mediation was employed and an intention‐to‐treat analysis conducted. Treatment effects were observed for all putative mediators (Effect size: 0.32–0.79, P < 0.01 vs. controls). Weight change was ?7.3 ± 5.9% (12‐month) and ?5.5 ± 5.0% (24‐month) in the intervention group and ?1.7 ± 5.0% and ?2.2 ± 7.5% in controls. Change in most psychosocial variables was associated with 12‐month weight change, but only flexible cognitive restraint (P < 0.01), disinhibition (P < 0.05), exercise self‐efficacy (P < 0.001), exercise intrinsic motivation (P < 0.01), and body dissatisfaction (P < 0.05) predicted 24‐month weight change. Lower emotional eating, increased flexible cognitive restraint, and fewer exercise barriers mediated 12‐month weight loss (R² = 0.31, P < 0.001; effect ratio: 0.37), but only flexible restraint and exercise self‐efficacy mediated 24‐month weight loss (R² = 0.17, P < 0.001; effect ratio: 0.89). This is the first study to evaluate self‐regulation mediators of weight loss and 2‐year weight loss maintenance, in a large sample of overweight women. Results show that lowering emotional eating and adopting a flexible dietary restraint pattern are critical for sustained weight loss. For long‐term success, interventions must also be effective in promoting exercise intrinsic motivation and self‐efficacy.     

Weight Loss Reduces Liver Fat and Improves Hepatic and Skeletal Muscle Insulin Sensitivity in Obese Adolescents

Obesity in adolescents is associated with metabolic risk factors for type 2 diabetes, particularly insulin resistance and excessive accumulation of intrahepatic triglyceride (IHTG). The purpose of this study was to evaluate the effect of moderate weight loss on IHTG content and insulin sensitivity in obese adolescents who had normal oral glucose tolerance. Insulin sensitivity, assessed by using the hyperinsulinemic–euglycemic clamp technique in conjunction with stable isotopically labeled tracer infusion, and IHTG content, assessed by using magnetic resonance spectroscopy, were evaluated in eight obese adolescents (BMI ≥95th percentile for age and sex; age 15.3 ± 0.6 years) before and after moderate diet‐induced weight loss (8.2 ± 2.0% of initial body weight). Weight loss caused a 61.6 ± 8.5% decrease in IHTG content (P = 0.01), and improved both hepatic (56 ± 18% increase in hepatic insulin sensitivity index, P = 0.01) and skeletal muscle (97 ± 45% increase in insulin‐mediated glucose disposal, P = 0.01) insulin sensitivity. Moderate diet‐induced weight loss decreases IHTG content and improves insulin sensitivity in the liver and skeletal muscle in obese adolescents who have normal glucose tolerance. These results support the benefits of weight loss therapy in obese adolescents who do not have evidence of obesity‐related metabolic complications during a standard medical evaluation.     

Baroreflex sensitivity in obesity: relationship with cardiac autonomic nervous system activity

Objective: The aim of this study was to test the hypothesis that baroreflex sensitivity (BRS), assessed by indirect measurement of aortic pressure, is blunted in obesity. Additionally, the potential effect of cardiac autonomic nervous system (ANS) activity, aortic compliance, and metabolic parameters on BRS of obese subjects was investigated. Research Methods and Procedures: A group of 30 women with BMI >30 kg/m² and a group of 30 controls with BMI <25 kg/m² were examined. BRS was estimated by the sequence technique, cardiac ANS activity by short‐term spectral analysis of heart rate variability (HRV), and aortic compliance by the method of applanation tonometry. Results: BRS was lower in obese women (9.18 ± 3.77 vs. 19.63 ± 9.16 ms/mm Hg, p < 0.001). The median values (interquartile range) of the power of both the high‐frequency and low‐frequency components of the HRV were higher in the lean than in the obese participants [1079.2 (202.7 to 1716.9) vs. 224.1 (72.7 to 539.6) msec², p = 0.001 and 411.8 (199.3 to 798.0) vs. 235.8 (99.4 to 424.5) msec², p = 0.01 respectively]. Low‐to‐high‐frequency ratio values were higher in the obese subjects [0.82 (0.47 to 2.1) vs. 0.57 (0.28 to 0.89), p = 0.02]. Aortic augmentation values were not significantly different between lean and obese subjects. Multivariate analysis demonstrated a significant and independent association between BRS and age (p = 0.003), BMI (p < 0.001), and high‐frequency power of HRV (p < 0.001). These variables explained 72% of the variation of BRS values. Discussion: BRS is severely reduced in obese subjects. BMI, age, and the parasympathetic nervous system activity are the main determinants of BRS. Baroreflex behavior is of clinical relevance because an attenuated BRS represents a negative prognostic factor in cardiovascular diseases, which are common in obesity.     

The Development of Obesity Begins at an Early Age in Captive Common Marmosets (Callithrix jacchus)

Animal models to study the causes and consequences of obesity during infancy in humans would be valuable. In this study, we examine the patterns of fat mass gain from birth to 12 months in common marmosets (Callithrix jacchus). Lean and fat mass was measured by quantitative magnetic resonance at 1, 2, 6, and 12 months for 31 marmosets, 15 considered Normal and 16 considered Fat (>14% body fat) at 12 months. Animals were fed either the regular colony diet mix or a high‐fat variation. Subjects classified as Fat at 12 months already had greater lean mass (198.4 ± 6.2 g vs. 174.0 ± 6.8 g, P = 0.013) and fat mass (45.5 ± 5.0 g vs. 24.9 ± 3.4 g, P = .002) by 6 months. Body mass did not differ between groups prior to 6 months, however, by 1 month, Fat infants had greater percent body fat. Percent body fat decreased between 1 and 12 months in Normal subjects; in Fat subjects, it increased. The high‐fat diet was associated with body fat >14% at 6 months (P = 0.049), but not at 12 months. This shift was due to three subjects on the normal diet changing from Normal to Fat between 6 and 12 months. Although maternal prepregnancy adiposity did not differ, overall, between Normal and Fat subjects, the subjects Normal at 6 and Fat at 12 months all had Fat mothers. Therefore, diet and maternal obesity appear to have potentially independent effects that may also vary with developmental age. Although birth weight did not differ between groups, it was associated with fat mass gain from 1 to 6 months in animals with >14% body fat at 6 months of age (r = 0.612, P = 0.026); but not in 6‐month‐old animals with <14% body fat (r = –0.012, P = 0.964). Excess adiposity in captive marmosets develops by 1 month. Birth weight is associated with adiposity in animals vulnerable to obesity.     

Weight loss on the web: A pilot study comparing a structured behavioral intervention to a commercial program

Objective: Internet weight loss programs have become widely available as alternatives to standard treatment, but few data are available on their efficacy. This study aimed to investigate the effectiveness of a structured behavioral weight loss website (VTrim) vs. a commercial weight loss website ( eDiets.com ). Research Methods and Procedures: A randomized, controlled trial was conducted from February 2003 to March 2005, in 124 overweight and obese subjects ages 18 years and older with a BMI of 25 to 39.9 kg/m² (mean age, 47 ± 9 years; BMI, 32 ± 3 kg/m²; 20% men). Analyses were performed for the 88 subjects who had complete follow‐up data. Participants were randomly assigned to 12‐month VTrim (n = 62) or eDiets.com (n = 62) intervention. VTrim participants had access to a therapist‐led structured behavioral weight loss program delivered on‐line. eDiets.com subjects had access to a self‐help commercial on‐line weight loss program. Body weight, social support, and use of website components were measured at 0, 6, and 12 months. Results: Repeated‐measures analyses showed that the VTrim group lost significantly more weight than the eDiets.com group at 6 months (8.3 ± 7.9 kg vs. 4.1 ± 6.2 kg; p = 0.004) and maintained a greater loss at 12 months (7.8 ± 7.5 kg vs. 3.4 ± 5.8 kg; p = 0.002). More participants in the VTrim group maintained a 5% weight loss goal (65% vs. 37.5%; p = 0.01) at 12 months. Discussion: An on‐line, therapist‐led structured behavioral weight loss website produced greater weight loss than a self‐help commercial website. Because commercial sites have great potential public health impact, future research should investigate the feasibility of incorporating a more structured behavioral program into a commercial application.     

A Pilot Internet‐Based Behavioral Weight Loss Intervention with or without Commercially Available Portion‐Controlled Foods

Objective : To evaluate the short‐term impact of portion‐controlled food provision in combination with an Internet behavioral weight loss program on weight, blood cholesterol, and blood glucose levels. Design and Methods : Fifty participants, mean age 46 ± 10.7 years and mean body mass index 35.1 ± 3.8 kg/m², were randomized to one of two study groups, an Internet behavioral weight loss program (Internet‐alone; n = 25) or an Internet behavioral weight loss program plus a commercially available portion‐controlled diet (Internet + PCD; n = 25) for 12 weeks. Results : An intent‐to‐treat analysis found that the mean weight change in the Internet + PCD group was ?5.7 ± 5.6 kg and in the Internet‐alone group (n = 25) was ?4.1 ± 4.0 kg (P = 0.26). Participants in the Internet + PCD group achieved significantly greater improvements in blood glucose (?2.6 ± 5.7 vs. 1.4 ± 11.0 mg/dl; P = 0.05) and LDL cholesterol (?8.2 ± 18.0 vs. ?0.6 ± 21.0 mg/dl; P = 0.04), compared with Internet‐alone group. Conclusions : These data suggest that there may be short‐term clinical benefit in using a PCD in conjunction with a behavioral Internet‐based weight loss program to enhance weight loss and improve health indicators.     

Impact of surgically induced weight loss on cardiovascular autonomic function: one-year follow-up

Objective: To determine the impact of surgically induced weight loss on cardiovascular autonomic function in subjects with severe obesity and examine whether the effect was comparable for persons with and without diabetes. Research Methods and Procedures: Twenty‐six severely obese individuals (BMI = 48 ± 7 kg/m²) underwent bariatric surgery (laparoscopic Roux‐en‐Y gastric bypass, n = 21; laparoscopic adjustable gastric banding, n = 5). Cardiovascular autonomic function (heart rate variation during deep breathing and the Valsalva maneuver) was assessed before and 6 and 12 months after surgery. Results: Twelve months after bariatric surgery, there was a 28% decrease in BMI. There was an increase in all parasympathetic indices of autonomic function (all assessment modalities, p < 0.05) with weight loss. The amount of improvement from baseline for all measures of autonomic function did not differ for those with or without diabetes. Discussion: Surgically induced weight loss 12 months after surgery has a favorable effect on cardiovascular autonomic function in severely obese individuals with and without diabetes.     

Pioglitazone Increases the Proportion of Small Cells in Human Abdominal Subcutaneous Adipose Tissue

Rodent and in vitro studies suggest that thiazolidinediones promote adipogenesis but there are few studies in humans to corroborate these findings. The purpose of this study was to determine whether pioglitazone stimulates adipogenesis in vivo and whether this process relates to improved insulin sensitivity. To test this hypothesis, 12 overweight/obese nondiabetic, insulin‐resistant individuals underwent biopsy of abdominal subcutaneous adipose tissue at baseline and after 12 weeks of pioglitazone treatment. Cell size distribution was determined via the Multisizer technique. Insulin sensitivity was quantified at baseline and postpioglitazone by the modified insulin suppression test. Regional fat depots were quantified by computed tomography (CT). Insulin resistance (steady‐state plasma insulin and glucose (SSPG)) decreased following pioglitazone (P < 0.001). There was an increase in the ratio of small‐to‐large cells (1.16 ± 0.44 vs. 1.52 ± 0.66, P = 0.03), as well as a 25% increase in the absolute number of small cells (P = 0.03). The distribution of large cell diameters widened (P = 0.009), but diameter did not increase in the case of small cells. The increase in proportion of small cells was associated with the degree to which insulin resistance improved (r = ?0.72, P = 0.012). Visceral abdominal fat decreased (P = 0.04), and subcutaneous abdominal (P = 0.03) and femoral fat (P = 0.004) increased significantly. Changes in fat volume were not associated with SSPG change. These findings demonstrate a clear effect of pioglitazone on human subcutaneous adipose cells, suggestive of adipogenesis in abdominal subcutaneous adipose tissue, as well as redistribution of fat from visceral to subcutaneous depots, highlighting a potential mechanism of action for thiazolidinediones. These findings support the hypothesis that defects in subcutaneous fat storage may underlie obesity‐associated insulin resistance.     

Effect of Lifestyle Modification on Adipokine Levels in Obese Subjects with Insulin Resistance

Objective: To study the effect of weight loss in response to a lifestyle modification program on the circulating levels of adipose tissue derived cytokines (adipokines) in obese individuals with insulin resistance. Research Methods and Procedures: Twenty‐four insulin‐resistant obese subjects with varying degrees of glucose tolerance completed a 6‐month program consisting of combined hypocaloric diet and moderate physical activity. Adipokines [leptin, adiponectin, resistin, tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6)] and highly sensitive C‐reactive protein were measured before and after the intervention. Insulin sensitivity index was evaluated by the frequently sampled intravenous glucose tolerance test. Results: Participants had a 6.9 ± 0.1 kg average weight loss, with a significant improvement in sensitivity index and reduction in plasma leptin (27.8 ± 3 vs. 23.6 ± 3 ng/mL, p = 0.01) and IL‐6 (2.75 ± 1.51 vs. 2.3 ± 0.91 pg/mL, p = 0.012). TNF‐α levels tended to decrease (2.3 ± 0.2 vs. 1.9 ± 0.1 pg/mL, p = 0.059). Adiponectin increased significantly only among diabetic subjects. The reductions in leptin were correlated with the decreases in BMI (r = 0.464, p < 0.05) and with changes in highly sensitive C‐reactive protein (r = 0.466, p < 0.05). Discussion: Weight reduction in obese individuals with insulin resistance was associated with a significant decrease in leptin and IL‐6 and a tendency toward a decrease in circulating TNF‐α, whereas adiponectin was increased only in diabetic subjects. Further studies are needed to elucidate the relationship between changes of adipokines and the health benefits of weight loss.     

Low Plasma Leptin Concentration and Low Rates of Fat Oxidation in Weight‐Stable Post‐Obese Subjects

Objective: A low resting metabolic rate for a given body size and composition, a low rate of fat oxidation, low levels of physical activity, and low plasma leptin concentrations are all risk factors for body weight gain. The aim of the present investigation was to compare resting metabolic rate (RMR), respiratory quotient (RQ), levels of physical activity, and plasma leptin concentrations in eight post‐obese adults (2 males and 6 females; 48.9 ± 12.2 years; body mass index [BMI]: 24.5 ± 1.0 kg/m²; body fat 33 ± 5%; mean ± SD) who lost 27.1 ± 21.3 kg (16 to 79 kg) and had maintained this weight loss for ≥2 months (2 to 9 months) to eight age‐ and BMI‐matched control never‐obese subjects (1 male and 7 females; 49.1 ± 5.2 years; BMI 24.4 ± 1.0 kg/m²; body fat 33 ± 7%). Research Methods and Procedures: Following 3 days of weight maintenance diet (50% carbohydrate and 30% fat), RMR and RQ were measured after a 10‐hour fast using indirect calorimetry and plasma leptin concentrations were measured using radioimmunoassay. Levels of physical activity were estimated using an accelerometer over a 48‐hour period in free living conditions. Results: After adjustment for fat mass and fat‐free mass, post‐obese subjects had, compared with controls, similar levels of physical activity (4185 ± 205 vs. 4295 ± 204 counts) and similar RMR (1383 ± 268 vs. 1430 ± 104 kcal/day) but higher RQ (0.86 ± 0.04 vs. 0.81 ± 0.03, p < 0.05). Leptin concentration correlated positively with percent body fat (r = 0.57, p < 0.05) and, after adjusting for fat mass and fat‐free mass, was lower in post‐obese than in control subjects (4.5 ± 2.1 vs. 11.6 ± 7.9 ng/mL, p < 0.05). Discussion: The low fat oxidation and low plasma leptin concentrations observed in post‐obese individuals may, in part, explain their propensity to relapse.     

Inflexibility in Intramuscular Triglyceride Fractional Synthesis Distinguishes Prediabetes From Obesity in Humans

Whether intramuscular triglyceride (IMTG) concentration or flux is more important in the progression to type 2 diabetes is controversial. Therefore, this study examined IMTG concentration, as well as its fractional synthesis rate (FSR), in obese people with normal glucose tolerance (NGT; n = 20) vs. obese people with prediabetes (PD; n = 19), at rest and during exercise. Insulin action and secretion were assessed using an intravenous glucose tolerance test. [U‐¹³C]palmitate was infused for 4 h before and throughout 1.5 h of treadmill walking at 50% VO_2max. IMTG concentration was measured by gas chromatograph/mass spectrometer, and FSR by gas chromatography–combustion isotope ratio mass spectrometer, from muscle biopsies taken immediately before and after exercise. Basal IMTG concentration was higher (43 ± 5.7 vs. 27 ± 3.9 mg/mg dry weight, P = 0.03) and FSR trended lower (0.23 ± 0.04 vs. 0.32 ± 0.05/h, P = 0.075), as did insulin action (S_i; 2.9 ± 0.43 vs. 3.3 ± 0.35 × 10^?4/mU/ml, P = 0.07), in PD vs. NGT. IMTG concentration did not change significantly during exercise, but was no longer different in PD vs. NGT (45 ± 7.7 vs. 37 ± 5.8 mg/mg dry weight, P = 0.41). IMTG FSR suppressed during exercise in NGT (?81% to 0.06 ± 0.13/h, P = 0.02), but not PD (+4% to 0.24 ± 0.13%/h, P = 0.95). Palmitate oxidation was similar during rest (P = 0.92) and exercise (P = 0.94) between groups, but its source appeared different with more coming from muscle at rest and plasma during exercise in NGT, whereas the converse was true in PD. Altogether, higher basal IMTG concentration that is metabolically inflexible distinguishes obese people with PD from those with NGT.     

Dysregulation of the Autonomic Nervous System Can Be a Link between Visceral Adiposity and Insulin Resistance

Objective: To evaluate the interplay among abdominal adipose tissue distribution, the cortisol axis, the autonomic nervous system, and insulin resistance. Research Methods and Procedures: Two age‐, sex‐, and BMI‐matched groups were studied. Fifteen subjects were first‐degree relatives of patients with type 2 diabetes (R), and 15 had no family history of diabetes (controls, C). A hyperinsulinemic euglycemic clamp, cortisol measurements, and analysis of heart rate variability (HRV) were performed. Computed tomography was performed in a subgroup (n = 9 + 9) to determine abdominal adipose tissue distribution. Results: R tended to be less insulin‐sensitive than C (M value 9.2 ± 1.0 vs 10.3 ± 0.7 mg/kg per minute, not significant). Stimulation with tetracosactin or corticotropin releasing hormone yielded lower peak serum cortisol levels in R (p = 0.03 and p = 0.06, respectively). The amount of visceral abdominal fat (VAT) tended to be greater in R. In all subjects, VAT was negatively correlated to insulin sensitivity (r = ?0.93, p < 0.001). There was a positive association between VAT and resting heart rate (r = 0.70, p = 0.003) and sympathetic/parasympathetic ratio in HRV assessment after tilt (r = 0.53, p = 0.03). Subcutaneous abdominal tissue was not associated with insulin sensitivity or any of the hormonal or HRV assessments. Discussion: Subjects genetically predisposed for type 2 diabetes had a tendency toward a larger amount of VAT and to lower insulin sensitivity compared with control subjects. The amount of visceral fat was strongly associated with insulin resistance and signs of a high ratio of sympathetic vs. parasympathetic reactivity. A large amount of visceral fat may act in concert with sympathetic/parasympathetic imbalance to promote the development of insulin resistance, and this may be partly independent of genetic background.     

Plasma visfatin concentrations in severely obese subjects are increased after intestinal bypass

Objective: Visfatin has shown to be increased in obesity and in type 2 diabetes. The aim of this study was to determine the change in plasma visfatin in severely obese (SO) persons after weight loss following bariatric surgery in relation to glucose concentration. Research Methods and Procedures: Visfatin and leptin were studied in 53 SO persons (BMI, 54.4 ± 6.8 kg/m²) before and 7 months after bariatric surgery and in 28 healthy persons (BMI, 26.8 ± 3.8 kg/m²). All of the patients underwent bariatric surgery with biliopancreatic diversion or gastric bypass. Results: The pre‐surgery levels of visfatin in the SO group were greater than in the control group (55.9 ± 39.9 vs. 42.9 ± 16.6 ng/mL, p = 0.024). This increase was significant in the SO group with impaired fasting glucose (63.4 ± 36.6 ng/mL) and diabetes (60.0 ± 46.0 ng/mL). SO patients with normal fasting glucose had similar levels of visfatin to the controls. Seven months after surgery, visfatin levels were significantly increased (84.8 ± 32.8 ng/mL, p < 0.001). This increase was independent of the pre‐surgical glucose levels. The type of bariatric surgery had no influence on visfatin levels. Post‐surgical visfatin was significantly correlated with the post‐surgery plasma concentrations of leptin (r = 0.39, p = 0.014). Discussion: Plasma levels of visfatin in the SO group were increased but only when accompanied by high glucose levels, even in the range of impaired fasting glucose. Bariatric surgery causes an increase in visfatin, which is correlated mainly with the changes produced in the leptin concentration.     

A losing battle: weight regain does not restore weight loss-induced bone loss in postmenopausal women

Previously, we reported significant bone mineral density (BMD) loss in postmenopausal women after modest weight loss. It remains unclear whether the magnitude of BMD change in response to weight loss is appropriate (i.e., proportional to weight loss) and whether BMD is recovered with weight regain. We now report changes in BMD after a 1‐year follow‐up. Subjects (n = 23) in this secondary analysis were postmenopausal women randomized to placebo as part of a larger trial. They completed a 6‐month exercise‐based weight loss program and returned for follow‐up at 18 months. Dual‐energy X‐ray absorptiometry (DXA) was performed at baseline, 6, and 18 months. At baseline, subjects were aged 56.8 ± 5.4 years (mean ± s.d.), 10.0 ± 9.2 years postmenopausal, and BMI was 29.6 ± 4.0 kg/m². They lost 3.9 ± 3.5 kg during the weight loss intervention. During follow‐up, they regained 2.9 ± 3.9 kg. Six months of weight loss resulted in a significant decrease in lumbar spine (LS) (?1.7 ± 3.5%; P = 0.002) and hip (?0.04 ± 3.5%; P = 0.03) BMD that was accompanied by an increase in a biomarker of bone resorption (serum C‐terminal telopeptide of type I collagen, CTX: 34 ± 54%; P = 0.08). However, weight regain was not associated with LS (0.05 ± 3.8%; P = 0.15) or hip (?0.6 ± 3.0%; P = 0.81) bone regain or decreased bone resorption (CTX: ?3 ± 37%; P = 0.73). The findings suggest that BMD lost during weight reduction may not be fully recovered with weight regain in hormone‐deficient, postmenopausal women. Future studies are needed to identify effective strategies to prevent bone loss during periods of weight loss.