The Relationship of Health Outcomes to Improvement in BMI in Children and Adolescents

Objective: To evaluate the clinical outcomes of patients participating in an outpatient program for managing childhood and adolescent obesity. Research Methods and Procedures: Based on a retrospective chart review, 394 physician‐referred obese youth (BMI > 95th percentile), 5 to 19 years of age, were treated in an interdisciplinary, family‐centered, behavioral weight management program in a hospital‐based outpatient setting. Treatment included group exercise, parent education, and behavioral intervention therapies to improve diet and physical activity. Results: A total of 177 (45%) completed the initial phase of treatment (mean duration = 5.6 months). For the completion group, there were significant improvements (all p < 0.001) in weight (?2.0 ± 4.9 kg), BMI (?1.7 ± 1.9 kg/m²), and BMI z score (?0.15 ± 0.15), without interfering with growth (height, 2.2 ± 1.3 cm; p < 0.001). Significant improvement was also found for blood pressure, total cholesterol, low‐density lipoprotein (LDL)‐cholesterol, triglycerides, insulin, and aerobic fitness. At onset of treatment, 134 (84%) patients had abnormal fasting insulin concentration, 88 (50%) had abnormal total cholesterol, 14 (8%) had abnormal diastolic blood pressure, and 69 (40%) had abnormal LDL‐cholesterol. At the end of treatment, a significant proportion of patients with baseline abnormal blood pressure, total cholesterol, and LDL‐cholesterol had normal values (p < 0.001). A decrease in BMI z score was associated with significant improvements in insulin and lipid values (all p < 0.05). Discussion: We have demonstrated that a modest decrease in BMI in an ongoing clinical pediatric weight management program is accompanied by significant improvements in related health measures. These results may be helpful in counseling families with overweight children and adolescents.     

Transient Increase in HDL‐Cholesterol During Weight Gain by Hyperalimentation in Healthy Subjects

Determination of lipid levels is fundamental in cardiovascular risk assessment. We studied the short‐term effects of fast food‐based hyperalimentation on lipid levels in healthy subjects. Twelve healthy men and six healthy women with a mean age of 26 ± 6.6 years and an aged‐matched control group were recruited for this prospective interventional study. Subjects in the intervention group aimed for a body weight increase of 5–15% by doubling the baseline caloric intake by eating at least two fast food‐based meals a day in combination with adoption of a sedentary lifestyle for 4 weeks. This protocol induced a weight gain from 67.6 ± 9.1 kg to 74.0 ± 11 kg (P < 0.001). A numerical increase in the levels of high‐density lipoprotein (HDL)‐cholesterol occurred in all subjects during the study and this was apparent already at the first week in 16/18 subjects (mean increase at week 1: +22.0 ± 16%, range from ?7 to +50%), whereas the highest level of HDL during the study as compared with baseline values varied from +6% to +58% (mean +31.6 ± 15%). The intake of saturated fat in the early phase of the trial related positively with the HDL‐cholesterol‐increase in the second week (r = 0.53, P = 0.028). Although the levels of insulin doubled at week 2, the increase in low‐density lipoprotein (LDL)‐cholesterol was only +12 ± 17%, and there was no statistically significant changes in fasting serum triglycerides. We conclude that hyperalimentation can induce a fast but transient increase in HDL‐cholesterol that is of clinical interest when estimating cardiovascular risk based on serum lipid levels.     

Improvements in Coronary Heart Disease Risk Indicators by Alternate‐Day Fasting Involve Adipose Tissue Modulations

The ability of alternate‐day fasting (ADF) to modulate adipocyte parameters in a way that is protective against coronary heart disease (CHD) has yet to be tested. Accordingly, we examined the effects of ADF on adipokine profile, body composition, and CHD risk indicators in obese adults. Sixteen obese subjects (12 women/4 men) participated in a 10‐week trial with three consecutive dietary intervention phases: (i) 2‐week baseline control phase, (ii) 4‐week ADF controlled feeding phase, and (iii) 4‐week ADF self‐selected feeding phase. After 8 weeks of treatment, body weight and waist circumference were reduced (P < 0.05) by 5.7 ± 0.9 kg, and 4.0 ± 0.9 cm, respectively. Fat mass decreased (P < 0.05) by 5.4 ± 0.8 kg, whereas fat‐free mass did not change. Plasma adiponectin was augmented (P < 0.05) by 30% from baseline. Leptin and resistin concentrations were reduced (P < 0.05) by 21 and 23%, respectively, post treatment. Low‐density lipoprotein cholesterol (LDL‐C) and triacylglycerol concentrations were 25% and 32% lower (P < 0.05), respectively, after 8 weeks of ADF. High‐density lipoprotein cholesterol (HDL‐C), C‐reactive protein, and homocysteine concentrations did not change. Decreases in LDL‐C were related to increased adiponectin (r = ?0.61, P = 0.01) and reduced waist circumference (r = 0.39, P = 0.04). Lower triacylglycerol concentrations were associated with augmented adiponectin (r = ?0.39, P = 0.04) and reduced leptin concentrations (r = 0.45, P = 0.03) post‐treatment. These findings suggest that adipose tissue parameters may play an important role in mediating the cardioprotective effects of ADF in obese humans.     

Cholesterol lowering action of HOE 402 in the normolipidemic and hypercholesterolemic Golden Syrian hamster

The potent hypolipidemic activity of HOE 402 (4-amino-2-(4,4-dimethyl-2-oxo-l-imidazolidinyl)pyrimidine-5-N-(trifluoromethylphenyl)carboxamide monohydrochloride), which was previously demonstrated in rat and rabbit, was investigated in noncholesterol and cholesterol fed male hamsters. In normolipidemic hamsters fed a low cholesterol chow diet containing 0.10% or 0.15% HOE 402 for 3 weeks, the plasma total cholesterol level fell by 13% and 20% respectively, but no effect on hepatic total cholesterol content was detected. Hepatic sterol synthesis was increased 3-fold in hamsters fed 0.15% HOE 402. In hamsters fed a chow diet containing 0.25% cholesterol for 3 weeks, the plasma cholesterol level increased to 226 mg/dl (compared to 123 mg/dl in their chow fed controls) and the liver cholesterol content was 26.2 mg/g compared to 2.3 mg/g in the control group. However, 0.15% HOE 402 led to a 48% reduction and 0.20% HOE 402 to a 80% reduction, in total hepatic cholesterol concentration. There was a 43% fall in plasma cholesterol level being observed with the higher HOE 402 dose. Using the dual isotope plasma ratio method, no inhibition of intestinal cholesterol absorption by HOE 402 was found, either in the noncholesterol fed or in the cholesterol fed hamsters. Cholesterol feeding diminished the whole LDL animal clearance to 393 ± 17 μl/h per 100 g animal (control 666 ± 81 μl/h per 100 g). When treated with 0.20% HOE 402, the whole animal LDL clearance rate was enhanced 2.3-fold to 824 ± 66 μl/h per 100 g. In the hamsters fed 0.25% cholesterol alone whole liver LDL receptor activity was suppressed to 63 ± 5%, compared to that in the untreated controls (100%). The addition of 0.20% HOE 402 to the cholesterol enriched diet not only reversed this suppression, but resulted in a marked stimulation of liver receptor activity to 165 ± 15% (whole body LDL receptor activity 141 ± 10%). These results indicate that HOE 402 exerts its lipid lowering effect by a more direct activation on hepatic LDL receptor activity rather than by an indirect intestinal effect on cholesterol absorption.     

Weight Loss and Leptin Changes in Individuals with Type 2 Diabetes

WILLIAMS, KATHERINE V., MONICA MULLEN, WE1 LANG, ROBERT V. CONSIDINE, AND RENA R. WING. Weight loss and leptin changes in individuals with type 2 diabetes. Obes Res. Objective To identify variables associated with leptin change in subjects with type 2 diabetes after 3 weeks and 20 weeks of weight loss. Research Methods and Procedures Subjects with type 2 diabetes treated with diet or sulfonylureas (n = 54) were enrolled in a 20-week behavioral weight control program. Sulfonylureas were stopped ≥2 weeks before study entry. Seven subjects who restarted sulfonylureas after week 3 had their data analyzed separately after this point. Results Leptin, fasting plasma glucose, and insulin levels were measured at baseline and at 3, 10, and 20 weeks. After 3 weeks, subjects lost 2.7±2.0 kg (p<0.001), and had significant decreases in leptin (5.2±7.0 ng/mL, p<0.001), fasting plasma glucose (1.8±1.8 mmol/L, p<0.001), and insulin (23±60 pmol/L, p<0.03). Between week 3 and week 20, subjects lost an additional 6.3±4.4 kg (P<0.001), but had no further changes in leptin. The primary determinants of leptin change at all time-points were weight loss and initial leptin level. Changes in insulin were not related to changes in leptin after controlling for the effects of weight loss. At week 20, more recent weight loss (week 10 to week 20) was as strong a predictor of overall change in leptin as overall weight loss (baseline to 20 week). Subjects who restarted sulfonylureas had an increase in both leptin levels (+1.9±9.0 ng/mL, p<0.05) and insulin levels (+23±65 pmol/L, p<0.05), despite significant overall weight loss (-7.4±4.0 kg, p<0.01). Initial changes in leptin (0 weeks to 3 weeks) did not affect subsequent ability to lose weight. Discussion Both short- and long-term changes in weight had an effect on leptin changes in individuals with type 2 diabetes. Although physiological insulin changes did not independently influence changes in leptin concentration with weight loss, increases in insulin levels with sulfonyl-urea therapy were associated with increases in leptin levels despite weight loss.     

The effect of tesofensine on appetite sensations

Tesofensine (TE), an inhibitor of monoamine presynaptic reuptake, has produced twice the weight loss seen with currently marketed drugs. However, its long term effect on appetite in humans has not been studied. A multicentre phase II trial was divided into two parts (24 weeks each). Part 1 had a randomized, double‐blind, placebo‐controlled design and Part 2, an open‐labeled, single‐group, uncontrolled design. A drug‐free period (12 ± 3 weeks) separated them. In Part 1, participants (n = 158) were assigned to 0.25, 0.5 or 1.0 mg TE, or placebo. Completers of Part 1 were invited to participate in Part 2 (n = 113), during which they all received 0.5 or 1.0 mg TE. Appetite sensations and a composite satiety score (CSS = satiety + fullness + (100 − hunger) + (100 − prospective food consumption) were assessed. In Part 1 TE induced a dose‐dependent increase in CSS at week 12 that correlated with weight loss during the 24 weeks (r = 0.36, P < 0.0001). However, CSS diminished over time as weight loss progressed (e.g., for 1.0 mg; 52 ± 17 mm; 64 ± 13 mm; 55 ± 13 mm at baseline, week 12 and week 24, respectively). After drug withdrawal CSS returned to baseline values (50 ± 17 mm, in the whole sample.), despite the participants' reduced‐weight state (−7.2 ± 6.7 kg, P < 0.0001). The reintroduction of TE in Part 2 increased CSS again (56 ± 17 mm at week 60), regardless of initial treatment/weight loss. We postulate that enhanced satiety is involved in early weight loss. Whether the attenuated effect on appetite seen after 24 weeks is due to a counteracting effect in the weight reduced state or whether the appetite suppressing effect of TE per se diminishes over time is, however, still unclear.     

Bupropion for Weight Loss: An Investigation of Efficacy and Tolerability in Overweight and Obese Women

Objective: On the basis of the clinical observations that bupropion facilitated weight loss, we investigated the efficacy and tolerability of this drug in overweight and obese adult women. Research Methods and Procedures: A total of 50 overweight and obese (body mass index: 28.0 to 52.6 kg/m²) women were included. The core component of the study was a randomized, double‐blind, placebo‐controlled comparison for 8 weeks. Bupropion or placebo was started at 100 mg/d with gradual dose increase to a maximum of 200 mg twice daily. All subjects were prescribed a 1600 kcal/d balanced diet and compliance was monitored with food diaries. Responders continued the same treatment in a double‐blind manner for an additional 16 weeks to a total of 24 weeks. There was additional single‐blind follow‐up treatment for a total of 2 years. Results: Subjects receiving bupropion achieved greater mean weight loss (last‐observation‐carried‐forward analysis) over the first 8 weeks of the study (p = 0.0001): 4.9% ± 3.4% (n = 25) for bupropion treatment compared with 1.3% ± 2.4% (n = 25) for placebo treatment. For those who completed the 8 weeks, the comparison was 6.2% ± 3.1% (n = 18) vs. 1.6% ± 2.9% (n = 13), respectively(p = 0.0002), with 12 of 18 of the bupropion subjects (67%) losing over 5% of baseline body weight compared with 2 of 13 in the placebo group (15%; p = 0.0094). In the continuation phase, 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9% ± 5.6% with fat accounting for 73.5% ± 3.7% of the weight lost and no change in bone mineral density as assessed by DXA. Bupropion was generally well‐tolerated in this sample. Discussion: Bupropion was more effective than placebo in achieving weight loss at 8 weeks in overweight and obese adult women in this preliminary study. Initial responders to bupropion benefited further in the continuation phase.     

Antioxidant supplementation lowers exercise-induced oxidative stress in young overweight adults

Objective: To determine whether antioxidant (AOX) supplementation attenuates post‐exercise oxidative stress and contributors to oxidative stress (inflammation, blood lipids) in overweight young adults. Research Methods and Procedures: This was a randomized, double‐blind, controlled study. Overweight (BMI, 33.2 ± 1.9 kg/m²) and comparative normal‐weight (BMI, 21.9 ± 0.5 kg/m²) adults 18 to 30 years old (total N = 48) were enrolled. Participants received either daily antioxidant (AOX) treatment (800 IU of vitamin E, 500 mg of vitamin C, 10 mg of β‐carotene) or placebo (PL) for 8 weeks for a total of four groups. All participants completed a standardized 30‐minute cycle exercise bout at baseline and 8 weeks. Exercise‐induced changes in lipid hydroperoxide (ΔPEROX), C‐reactive protein (ΔCRP), interleukin‐6 (ΔIL‐6), cholesterol subfractions, triglycerides, total AOX status (ΔTAS), and adiponectin were assessed. Results: Exercise‐induced ΔPEROX was lower in the overweight‐AOX group (0.09 nM/kg per min) compared with PL‐treated overweight and normal‐weight groups (0.98, 0.53 nM/kg per min) by 8 weeks (p < 0.05). Adiponectin was increased in both overweight and normal‐weight AOX groups (22.1% vs. 3.1%; p < 0.05) but reduced in PL groups. ΔIL‐6, Δtotal cholesterol, and Δlow‐density lipoprotein‐cholesterol concentrations during exercise were lower in the AOX‐treated groups compared with PL groups (all p < 0.05). After controlling for BMI, the Δtotal cholesterol, Δlow‐density lipoprotein‐cholesterol, Δadiponectin, and ΔTAS explained 59.1% of the variance of the regression model of the ΔPEROX by 8 weeks (total model R² = 0.600; p = 0.015). Discussion: AOX lowers exercise‐induced oxidative stress in overweight adults. Inflammatory and lipid markers may also be attenuated with AOX. Further studies are needed to determine whether AOX may be used in cardiovascular disease prevention in the overweight population.     

A new serum lipoprotein found in many rhesus monkeys.

A new serum lipoprotein was found in about 10 out of 30 rhesus monkeys ($\text{Macaca}\text{mulatta}$) which contained 28% by weight of protein, 42% total cholesterol, 22% phospholipid, and 8% triglyceride. This is in contrast to LDL (which the ten monkeys also contained) which had 24% protein, 46% total cholesterol, 24% phospholipid and 7% triglyceride. An S_{f, 1.063} in KBr of 3.0 to 3.7 and molecular weight of 3.5 – 3.7 million were observed compared to means of 8.1 and 3.0 million for normal rhesus LDL. The lower S_f was caused by its higher density. This new lipoprotein was most easily demonstrated and isolated by preparative ultracentrifugation of all serum lipoproteins at density 1.22 g/ml, followed by 6% agarose gel filtration at 6°. The new lipoprotein appeared as a distinct peak eluting before LDL.     

Liver Volume and Visceral Obesity in Women with Hepatic Steatosis Undergoing Gastric Banding

Objective: To investigate the relationships between visceral obesity and hepatic steatosis in obese patients undergoing adjustable silicone gastric banding with the LAP‐BAND. Research Methods and Procedures: Six premenopausal, morbidly obese women with an ultrasonographic diagnosis of liver steatosis were evaluated before surgery and 8 and 24 weeks after surgery. Liver volume and body fat distribution were simultaneously analyzed by total‐body multislices magnetic resonance imaging. Results: Before surgery, the only variable found to be correlated with liver volume was visceral adipose tissue volume (r = 0.91; p < 0.01). Weight loss was 9.9 ± 3.8 kg in the period from 0 to 8 weeks (p < 0.01) and 7.1 ± 4.9 kg in the the period from 8 to 24 weeks (p < 0.05). Total fat showed a statistically significant reduction of 6.2 ± 4.0 liters in the 0‐ to 8‐week period and a further significant reduction of 7.7 ± 3.9 liters in the 8‐ to 24‐week period. Visceral adipose tissue showed a statistically significant reduction of 1.0 ± 0.9 liters in the 0‐ to 8‐week period (p < 0.05) but only a further, not significant reduction of 0.6 ± 0.7 liters in the 8‐ to 24‐week period. The relative reduction of visceral fat in the 0‐to 8‐week period was higher than the relative reduction of total fat. Liver volume also showed a statistically significant reduction of 0.24 ± 0.26 liters in the first phase of weight loss (p < 0.05), corresponding to a relative reduction of 12.3 ± 10.6%. During the 8‐ to 24‐week period, liver volume was substantially stable. Discussion: Hepatomegaly was associated with visceral obesity in morbidly obese women with liver steatosis. In the phase of rapid weight loss after gastric surgery, a preferential mobilization of visceral fat, compared with total adipose tissue, occurred. This preferential visceral fat loss was associated with a significant reduction in liver volume.     

Cholesteryl ester transfer protein in metabolic syndrome

Objective: Low high‐density lipoprotein cholesterol (HDL‐C), hypertriglyceridemia, and small dense‐low density lipoprotein (LDL) are key components of metabolic syndrome (MS). Cholesteryl ester transfer protein (CETP) mediates the transfer of triglycerides (TGs) from TG‐rich lipoproteins to HDL and LDL particles in exchange for cholesteryl esters, leading to low HDL‐C and small dense‐LDL. The aim of this study was to investigate the role of CETP in subjects with MS. Research Methods and Procedures: In a cross‐sectional cohort of 234 middle‐aged men and 252 women randomly selected from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study, MS was diagnosed according to the National Cholesterol Education Program guidelines. CETP mass was determined by enzyme‐linked immunosorbent assay and LDL size‐by‐gradient polyacrylamide gel electrophoresis. Results: Men and women with MS had lower HDL‐C (45 ± 7 vs. 58 ± 13 and 48 ± 10 vs. 71 ± 14 mg/dL for men and women, respectively; p < 0.001 for all) and higher TG levels (222 ± 71 vs. 98 ± 54 and 167 ± 67 vs. 90 ± 35 mg/dL for men and women, respectively; p < 0.001 for all) than healthy subjects. LDL size was lower in subjects with MS (256 ± 11 Å vs. 267 ± 11 Å and 262 ± 10 Å vs. 273 ± 8 Å for men and women, respectively; p < 0.001 for all). CETP mass was higher in men with MS (1.87 ± 0.78 vs. 1.40 ± 0.65 μg/mL; p < 0.001) but not in women (1.74 ± 0.79 vs. 1.62 ± 0.62 μg/mL). CETP mass correlated inversely with LDL size in both men and women (r = ?0.19, p < 0.01 and r = ?0.13, p < 0.05 in men and women, respectively). Discussion: MS is associated with increased CETP mass in men. Increased CETP mass may be responsible for reduced HDL‐C and reduced LDL particle diameter in MS.     

Decreased bodyweight without rebound and regulated lipoprotein metabolism by gymnemate in genetic multifactor syndrome animal

Objective: The aim of this work was to find obesity control method without rebound. In our previous studies, gymnemate extracted from Gymnema sylvestre, inhibited oleic acid absorption. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a genetic multifactor syndrome model, exhibits progressive overweight, hyperlipidemia and hyperglycemia. The effect of gymnemate on obesity in OLETF was investigated. Methods: Three groups were divided (n = 4–8): (1) OLETF-gymnemate, gymnema water extract (containing gymnemate) diet (62.5 g/kg) and water (2.5 g/kg) were supplied 2 weeks from 26–28 weeks, following it general diet and water were fed 3 weeks to observe if it rebound, (2) OLETF-control and (3) the counterpart Long-Evans Tokushima Otsuka rats as normal-control. Results: With gymnemate treatment, the food and water intake were decreased about 1/3 and 2/3, along with body weight reduced 57.2± 6.4 and 75.5± 6.3 g during 1 and 2 weeks respectively. In the end of experiment (3 weeks after gymnemate withdrawal), the body weight was decreased to no significant difference with normal-control. The total cholesterol was decreased about 1/3, moreover LDL+VLDL (low-density and very-low-density lipoprotein) cholesterol decreased about 1/2. The proportion of HDL (high-density lipoprotein) cholesterol to the total cholesterol was increased. The serum triglyceride was decreased to the 1/4 of OLETF control. The level of serum cholesterol and triglyceride was no significant difference in gymnemate group with normal group. Conclusion: Supplementation with gymnemate promotled weight loss by its ability to reduce hyperlipidemia, which was no withdrawal rebound: an important discovery. Supplementation with gymnemate is a novel therapeutic tool for weight management, especially in multifactor syndrome.     

Serum Fructosamine Levels in Dairy Cows Related to Metabolic Status in Early Lactation

Serum levels of fructosamine were assayed in 57 samples from 23 Norwegian Red Cattle dairy cows in early lactation. The animals were assigned to a 22 factorial feeding experiment. The groups differed in energy and protein supply. All samples were collected before morning feeding. The relationship between fructosamine levels and the plasma concentrations of glucose, acetoacetate, free fatty acids, total cholesterol, lipoproteins, triglycerides, total proteins, progesterone and to weight and energy balance was studied. The overall mean fructosamine level was 1.41 ± 0.20 mmol/1 ranging from 0.92–1.92 mmol/1. Significant relationships were recorded between fructosamine and the concentrations of glucose, acetoacetate, free fatty acids, triglyceride, total cholesterol and energy and weight balance. Free fatty acids and cholesterol showed the best correlation with fructosamine (rs =–0.67 and 0.70, respectively, p < 0.001). The levels of fructosamine increased significantly between 2 and 4 weeks and between 4 and 8 weeks after calving. Animals with a weight gain during 3 weeks prior to fructosamine measurement had higher fructosamine levels than those showing a weight loss (<–7 kg/week) (p < 0.05). The results indicate that serum fructosamine levels in cows may be of interest as an indicator of metabolic status in the early stages of lactation.     

Changes in Skeletal Muscle Vascular Resistance with Weight Gain: Associations with Insulin and Sympathetic Activity

BORNE, AGATHA T., ALYCIA A. TRUETT, MICHELLE P. MONTEIRO, JULIA VOLAUFOVA, AND DAVID B. WEST. Changes in skeletal muscle vascular resistance with weight gain: associations with insulin and sympathetic activity. Obes Res. 1999;7:68–75. Objective : This study was designed to characterize changes in peripheral vascular resistance with weight gain, and whether these changes are correlated with insulin and/or sympathetic activity. Research Methods and Procedures : Femoral vascular resistance (FVR), mean arterial pressure, heart rate, and plasma insulin were measured before and during overfeeding in seven dogs with unilateral lumbar ganglionectomy (L₃ to L₆). Measurements were taken standing and while walking on a treadmill. Results : There was a significant main effect of weight gain to increase mean arterial pressure (16.5±8.4 mmHg and 12.5±6.8 mmHg increase for standing and walking baseline, respectively) and heart rate (increase from week 1 of 31.6±10.6 beats/minute standing and 38.3±9.1 walking beat/minute). FVR increased immediately with overfeeding/ weight gain [standing: denervated (DNX):1.32±0.3 to 2.34±0.5; intact: 0.88±0.17 to 1.9±0.33 mmHg/mL-min^?1], but returned to baseline with continued weight gain. Return of FVR to baseline occurred between weeks 2 and 3 of overfeeding in the DNX limb, but did not return to baseline until week 6 in the innervated limb. These changes were not correlated with plasma insulin levels. Discussion : These data suggest that vascular resistance may be normal in the obese, but increases in vascular resistance occur early with weight gain (before changes in arterial pressure). This initial increase in vascular resistance could initiate the series of events leading to obesity-associated hypertension. Additionally, changing vascular resistance during weight gain may be influenced by sympathetic activity, because DNX limb FVR returned to baseline ?3 weeks earlier than the innervated limb.     

Water Consumption Increases Weight Loss During a Hypocaloric Diet Intervention in Middle‐aged and Older Adults

Water consumption acutely reduces meal energy intake (EI) among middle‐aged and older adults. Our objectives were to determine if premeal water consumption facilitates weight loss among overweight/obese middle‐aged and older adults, and to determine if the ability of premeal water consumption to reduce meal EI is sustained after a 12‐week period of increased water consumption. Adults (n = 48; 55–75 years, BMI 25–40 kg/m²) were assigned to one of two groups: (i) hypocaloric diet + 500 ml water prior to each daily meal (water group), or (ii) hypocaloric diet alone (nonwater group). At baseline and week 12, each participant underwent two ad libitum test meals: (i) no preload (NP), and (ii) 500 ml water preload (WP). Meal EI was assessed at each test meal and body weight was assessed weekly for 12 weeks. Weight loss was ～2 kg greater in the water group than in the nonwater group, and the water group (β = ?0.87, P < 0.001) showed a 44% greater decline in weight over the 12 weeks than the nonwater group (β = ?0.60, P < 0.001). Test meal EI was lower in the WP than NP condition at baseline, but not at week 12 (baseline: WP 498 ± 25 kcal, NP 541 ± 27 kcal, P = 0.009; 12‐week: WP 480 ± 25 kcal, NP 506 ± 25 kcal, P = 0.069). Thus, when combined with a hypocaloric diet, consuming 500 ml water prior to each main meal leads to greater weight loss than a hypocaloric diet alone in middle‐aged and older adults. This may be due in part to an acute reduction in meal EI following water ingestion.     

A Randomized Controlled Trial of a Commercial Internet Weight Loss Program

Objective: To assess, in a 1‐year randomized controlled trial, the efficacy of eDiets.com (a commercial Internet weight loss program) in improving weight, cardiovascular health, and quality of life. Research Methods and Procedures: Participants were 47 women with a mean age of 43.7 ± 10.2 (SD) years and a mean BMI of 33.5 ± 3.1 kg/m². They were randomly assigned to either: 1) eDiets.com , a commercial Internet‐based program available to the public; or 2) a weight loss manual (i.e., LEARN Program for Weight Control 2000). At baseline, participants in both groups met briefly with a psychologist who instructed them to follow the components of their program as closely as possible. Additional brief visits were provided at weeks 8, 16, 26, and 52 to review their progress. Change in weight was the main outcome measure. Results: At week 16, participants in eDiets.com lost 0.9 ± 3.2% of initial weight compared with 3.6 ± 4.0% for women assigned to the weight loss manual. At week 52, losses increased to 1.1 ± 4.0% and 4.0 ± 5.1%, respectively. Results of a last‐observation‐carried‐forward analysis found that women in the manual group lost significantly (p < 0.05) more weight (at both times) than those treated by eDiets.com . (Results, however, of baseline‐carried‐forward and completers analyses did not reach statistical significance.) There were no significant differences between groups in changes in cardiovascular risk factors or quality of life. Discussion: This study provides consumers with important information about the probable benefits they can expect from participating in a popular Internet‐based weight loss program.     

Using facebook and text messaging to deliver a weight loss program to college students

Objective:

Between 31 and 35% of the college‐aged population is overweight or obese, yet few weight loss trials for this population have been conducted. This study examined the feasibility, acceptability, and initial efficacy of a technology‐based 8‐week weight loss intervention among college students.

Design and Methods:

Students (N = 52) were randomly assigned to one of the three arms: Facebook (n = 17); Facebook Plus text messaging and personalized feedback (n = 18); Waiting List control (n = 17), with assessments at 4 weeks and 8 weeks (post‐treatment). Participants were 20.47 ± 2.19 years old, 86.45 ± 17.11 kg, with a body mass index of 31.36 ± 5.3 kg/m². Participants were primarily female (86.5%), and the sample was racially diverse (57.7% Caucasian, 30.8% African American, 5.8% Hispanic, and 5.7% other races).

Results:

The primary outcome was weight loss after 8 weeks (post‐treatment); 96.0% of the participants completed this assessment. At 8 weeks, the Facebook Plus group had significantly greater weight loss (?2.4 ± 2.5 kg) than the Facebook (?0.63 ± 2.4 kg) and Waiting List (?0.24 ± 2.6 kg) (both Ps < 0.05). Weight change at 8 weeks was not significantly different between the Facebook and Waiting List groups.

Conclusions:

Results show preliminary efficacy and acceptability of the two active intervention arms (97.0% found the program helpful, 81.3% found the videos/handouts helpful, and 100% would recommend the program to others). Results indicate the potential for an innovative weight loss intervention that uses technology platforms (Facebook and text messaging) that are frequently used and already integrated into the cultural life of college students.

     

Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins

Mipomersen, an antisense oligonucleotide that reduces hepatic production of apoB, has been shown in phase 2 studies to decrease plasma apoB, LDL cholesterol (LDL-C), and triglycerides. ApoC-III inhibits VLDL and LDL clearance, and it stimulates inflammatory responses in vascular cells. Concentrations of VLDL or LDL with apoC-III independently predict cardiovascular disease. We performed an exploratory posthoc analysis on a subset of hypercholesterolemic subjects obtained from a randomized controlled dose-ranging phase 2 study of mipomersen receiving 100, 200, or 300 mg/wk, or placebo for 13 wk (n = 8 each). ApoC-III-containing lipoproteins were isolated by immuno-affinity chromatography and ultracentrifugation. Mipomersen 200 and 300 mg/wk reduced total apoC-III from baseline by 6 mg/dl (38-42%) compared with placebo group (P < 0.01), and it reduced apoC-III in both apoB lipoproteins and HDL. Mipomersen 100, 200, and 300 mg doses reduced apoB concentration of LDL with apoC-III (27%, 38%, and 46%; P < 0.05). Mipomersen reduced apoC-III concentration in HDL. The drug had no effect on apoE concentration in total plasma and in apoB lipoproteins. In summary, antisense inhibition of apoB synthesis reduced plasma concentrations of apoC-III and apoC-III-containing lipoproteins. Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors.     

The beneficial effects of α-cyclodextrin on blood lipids and weight loss in healthy humans

α‐Cyclodextrin (α‐CD) is a soluble fiber derived from corn. It has previously been reported that early intervention with Mirafit fbcx, a trademarked name for α‐CD, has beneficial effects on weight management in obese individuals with type 2 diabetes, and that it preferentially reduces blood levels of saturated and trans fats in the LDL receptor knockout mice. The current investigation involves overweight but not obese nondiabetic individuals and was intended to confirm the effects of α‐CD on both weight management and improving blood lipid levels. Forty‐one healthy adults (age: 41.4 ± 13.6 years) participated in this 2‐month, double‐blinded, crossover study. In 28 compliant participants (8 males and 20 females), when the active phase was compared to the control phase, there were significant decreases in body weight (?0.4 ± 0.2 kg, P < 0.05), serum total cholesterol (mean ± s.e.m., ?0.295 ± 0.10 mmol/l, 5.3%, P < 0.02) and low‐density lipoprotein (LDL) cholesterol (?0.23 ± 0.11 mmol/l, ?6.7%, P < 0.05). Apolipoprotein B (Apo B) (?0.0404 ± 0.02 g/l, ?5.6%, P = 0.06) and insulin levels also decreased by 9.5% (?0.16 ± 0.08 pmol/l, P = 0.06) while blood glucose and leptin levels did not change. These results suggest that α‐CD exerts its beneficial health effects on body weight and blood lipid profile in healthy nonobese individuals, as previously reported in obese individuals with type 2 diabetes.     

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.