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.     

Combined Dietary and Pharmacological Weight Management in Obese Hypopituitary Patients

Objective: The high prevalence of obesity and cardiovascular risk factors in hypopituitarism affirms the need for effective weight loss intervention. In this study, we investigated the combined effect of sibutramine, diet, and exercise in obese hypopituitary patients (HPs). Research Methods and Procedures: In an open‐label prospective intervention trial, 14 obese well‐substituted nondiabetic HPs and 14 matched simple obese controls were allocated to 11‐month treatment with sibutramine (10 to 15 mg), diet (600 kcal/d deficit), and exercise. Anthropometric indices and body composition (obtained from DXA scan) were assessed monthly for the first 5 months and thereafter every second month for the next 6 months. Results: Mean (±SD) weight loss at 11 months was 11.3 ± 4.8 kg in patients vs. 10.7 ± 4.7 kg in controls. The HPs exhibited the same improvements in body composition, waist circumference, blood lipids, and fasting glucose as the simple obese. In a multivariate model, baseline weight, duration of growth hormone replacement therapy, and duration of pituitary disease explained 79% (p = 0.001) of the variation in weight loss at 4 months in the HPs. Only baseline weight and waist circumference could predict weight loss at 11 months. Discussion: HPs are not resistant to weight loss therapy. Almost all will achieve at least 5% weight loss, and 60% can lose >10% weight within 11 months. However, the long‐term effect on risk factors associated with type 2 diabetes and cardiovascular disease as well as on mortality needs to be established.     

Economic Impact of the Clinical Benefits of Bariatric Surgery in Diabetes Patients With BMI ≥35 kg/m2

The medical costs for a type 2 diabetes patient are two to four times greater than the costs for a patient without diabetes. Bariatric surgery is the most effective weight‐loss therapy and has marked therapeutic effects on diabetes. We estimate the economic effect of the clinical benefits of bariatric surgery for diabetes patients with BMI ≥35 kg/m². Using an administrative claims database of privately insured patients covering 8.5 million lives 1999–2007, we identify obese patients with diabetes, aged 18–65 years, who were treated with bariatric surgery identified using Healthcare Common Procedure Coding System codes. These patients were matched with nonsurgery control patients on demographic factors, comorbidities, and health‐care costs. The overall return on investment (RoI) associated with bariatric surgery was calculated using multivariate analysis. Surgery and control patients were compared postindex with respect to diagnostic claims for diabetes, diabetes medication claims, and adjusted diabetes medication and supply costs. Surgery costs were fully recovered after 26 months for laparoscopic surgery. At month 6, 28% of surgery patients had a diabetes diagnosis, compared to 74% of control patients (P < 0.001). Among preindex insulin users, insulin use dropped to 43% by month 3 for surgery patients, vs. 84% for controls (P < 0.001). By month 1, medication and supply costs were significantly lower for surgery patients (P < 0.001). The therapeutic benefits of bariatric surgery on diabetes translate into considerable economic benefits. These data suggest that surgical therapy is clinically more effective and ultimately less expensive than standard therapy for diabetes patients with BMI ≥35 kg/m².     

Adipogenic and Antiapoptotic Protein Levels in Human Adipose Stromal Cells after Weight Loss

Objective: Obesity is a major risk factor for type 2 diabetes and cardiovascular disease. However, current strategies to achieve sustained weight loss are often unsuccessful. Fat reaccumulation might be favored by enhanced adipose cell differentiation or survival in the postreduced state. Research Methods and Procedures: We measured adipogenic and apoptotic protein expression in subcutaneous abdominal adipose stromal‐vascular cells from 10 obese patients (7 women and 3 men) that were obtained before and after a 16% weight loss in a medically supervised weight loss program. Results: After weight loss, protein expression was 2.4‐fold higher (p < 0.005) for p42 C/CAAT enhancer binding protein α, but there was no change for peroxisome proliferator‐activated receptor γ1; both of these are adipogenic regulators. For neuronal apoptosis inhibitory protein, a protein associated with adipose cell apoptotic resistance, there was a rise of 1.7‐fold (p < 0.02). Discussion: Alterations in C/CAAT enhancer binding protein α and neuronal apoptosis inhibitory protein expression occurred in human adipose stromal‐vascular cells after weight loss in a pilot study of 10 patients. It will be important for future studies to directly examine whether the adipogenic and antiapoptotic capacity of these cells is changed after weight loss.     

Sympathovagal Balance,Nighttime Blood Pressure,and QT Intervals in Normotensive Obese Women

Objective : We describe associations among the heart‐rate‐corrected QT (QTc) interval, QTc dispersion (QTc‐d), circadian BP variation, and autonomic function in obese normotensive women and the effect of sustained weight loss. Research Methods and Procedures : In 71 obese (BMI = 37.14 ± 2.6 kg/m²) women, 25 to 44 years of age, circadian BP variations (24‐hour ambulatory BP monitoring), autonomic function (power spectral analysis of RR interval oscillations), and cardiac repolarization times (QTc‐d and QTc interval) were recorded at baseline and after 1 year of a multidisciplinary program of weight reduction. Results : Compared with nonobese age‐matched women (n = 28, BMI = 23 ± 2.0 kg/m²), obese women had higher values of QTc‐d (p < 0.05) and QTc (p < 0.05), an altered sympathovagal balance (ratio of low‐frequency/high‐frequency power, p < 0.01), and a blunted nocturnal drop in BP (p < 0.01). In obese women, QTc‐d and the QTc interval correlated with diastolic nighttime BP (p < 0.01) and sympathovagal balance (p < 0.01). Waist‐to‐hip ratio, free fatty acids, and plasma insulin levels correlated with QT intervals and reduced nocturnal drops in both systolic and diastolic BP and sympathovagal balance (p < 0.01). After 1 year, obese women lost at least 10% of their original weight, which was associated with decrements of QTc‐d (p < 0.02), the QTc interval (p < 0.05), nighttime BP (p < 0.01), and sympathovagal balance (p < 0.02). Discussion : Sustained weight loss is a safe method to ameliorate diastolic nighttime BP drop and sympathetic overactivity, which may reduce the cardiovascular risk in obese women.     

Short‐Term Effects of Weight Loss on the Cardiovascular Risk Factors in Morbidly Obese Patients

Objective: To analyze the short‐term effects of weight loss on the cardiovascular risk factors in morbidly obese patients. Research Methods and Procedures: Five metabolic cardiovascular risk factors (blood glucose, blood pressure, total cholesterol, high‐density lipoprotein (HDL)‐cholesterol, and triglycerides) were determined before and 15.3 ± 2.1 months after laparoscopic gastric banding in 650 morbidly obese patients. Global cardiovascular risk was calculated according to the Prospective Cardiovascular Münster (PROCAM) scoring system. Results: Mean weight loss was 22.7 ± 20.4 kg. Normalization of the metabolic alteration was observed in 67.3% of patients with diabetes, 38.3% of patients with hypercholesterolemia, 72.5% of patients with low HDL‐cholesterol, 72.3% of patients with hypertriglyceridemia, and 46.7% of patients with hypertension. PROCAM score fell from 31.4 ± 11.6 to 28.0 ± 12.0 points (p < 0.001). The modifications of total cholesterol and blood pressure were unrelated to percentage weight loss. Percentage weight loss was significantly related to the reductions of fasting blood glucose, triglyceride level, and the PROCAM score and to the increase of HDL‐cholesterol concentrations observed after surgery. However, the strength of these four relationships was generally low. The variations of HDL‐cholesterol concentrations and blood pressure levels were more influenced by actual energy balance than by the extent of weight loss. Discussion: Weight loss observed in the first 12 to 18 months after gastric banding was associated with a significant improvement of single cardiovascular risk factors and global risk. On the other hand, the extent of weight loss was poorly related to the magnitude of improvement in cardiovascular risk.     

Effect of Pramlintide on Weight in Overweight and Obese Insulin‐Treated Type 2 Diabetes Patients

Objective: Several randomized, placebo‐controlled, double‐blind trials in insulin‐treated patients with type 2 diabetes have shown that adjunctive therapy with pramlintide reduces hemoglobin (Hb)A_1c with concomitant weight loss. This analysis further characterizes the weight‐lowering effect of pramlintide in this patient population. Research Methods and Procedures: This pooled post hoc analysis of two long‐term trials included all patients who were overweight/obese at baseline (BMI > 25 kg/m²), and who were treated with either 120 μg pramlintide BID (n = 254; HbA_1c 9.2%; weight, 96.1 kg) or placebo (n = 244; HbA_1c 9.4%; weight, 95.0 kg). Statistical endpoints included changes from baseline to week 26 in HbA_1c, body weight, and insulin use. Results: Pramlintide treatment resulted in significant reductions from baseline to week 26, compared with placebo, in HbA_1c and body weight (both, p < 0.0001), for placebo‐corrected reductions of ?0.41% and ?1.8 kg, respectively. Approximately three times the number of patients using pramlintide experienced a ≥5% reduction of body weight than with placebo (9% vs. 3%, p = 0.0005). Patients using pramlintide also experienced a proportionate decrease in total daily insulin use (r = 0.39, p < 0.0001). The greatest placebo‐corrected reductions in weight at week 26 were observed in pramlintide‐treated patients with a BMI >40 kg/m² and in those concomitantly treated with metformin (both, p < 0.001), for placebo‐corrected reductions of ?3.2 kg and ?2.5 kg, respectively. Discussion: These findings support further evaluation of the weight‐lowering potential of pramlintide in obese patients with type 2 diabetes.     

Short‐Term Effects of Gastric Bypass Surgery on Circulating Ghrelin Levels

Objective: To prospectively evaluate the short‐term effects of Roux‐en‐Y gastric bypass (RYGBP) on ghrelin secretion and its relevance on food intake and body weight changes. Research Methods and Procedures: Ghrelin response to a standardized test meal was evaluated in eight obese patients (BMI, 43.5 to 59.1 kg/m²) before and 6 weeks after RYGBP. Ghrelin response was compared with that of an age‐matched group of six normal weight individuals (BMI, 19.6 to 24.9 kg/m²). Results: Fasting serum ghrelin levels were lower in obese subjects compared with controls (p < 0.05). Meal ingestion significantly suppressed ghrelin concentration in controls (p < 0.05) and obese subjects (p < 0.05), albeit to a lesser degree in the latter group (p < 0.05). Despite a 10.3 ± 1.5% weight loss, fasting serum ghrelin levels were paradoxically further decreased in obese subjects 6 weeks after RYGBP (p < 0.05). Moreover, at this time‐point, food intake did not elicit a significant ghrelin suppression. The changes in ghrelin secretion after RYGBP correlated with changes in insulin sensitivity (p < 0.05) and caloric intake (p < 0.05). Discussion: This study showed that the adaptive response of ghrelin to body weight loss was already impaired 6 weeks after RYGBP. Our study provides circumstantial evidence for the potential role of ghrelin in the negative energy balance in RYGBP‐operated patients.     

Echocardiographic Abnormalities in Normotensive Obese Patients: Relationship with Visceral Fat

Objective: To evaluate the relationship of echocardiographic characteristics and visceral adipose tissue (VAT) distribution in normotensive obese patients. Research Methods and Procedures: Echocardiographic parameters were assessed in 28 normotensive obese patients [7 men, 21 women, mean age, 43.2 years; mean body mass index (BMI), 37.2 kg/m²; 10 with impaired glucose tolerance (IGT); 6 with type 2 diabetes] and 18 sex‐ and age‐matched healthy, normal‐weight controls (4 men, 14 women; mean age, 45.8 years; mean BMI, 22.4 kg/m²) by an M‐mode, color‐doppler videofluoroscope. VAT in the obese patients was assessed by computed tomography (at L4 level). Results: The obese patients had a significantly larger internal diastolic left ventricular (LV) diameter (p < 0.05), a thicker end‐diastolic septum (p < 0.001) and posterior wall (p < 0.001), a greater indexed (g/m^2.7) LV mass (p < 0.001), a higher atrial diastolic filling wave velocity (p < 0.001), a lower ratio between early and atrial diastolic filling wave velocities (p < 0.01), and a prolonged isovolumic relaxation time (p < 0.05). End‐diastolic septum and posterior wall thickness and the LV mass were significantly greater in patients with a VAT area >130 cm² than with <130 cm². In the multivariate regression analysis, only VAT (p < 0.0001), waist‐to‐hip ratio (p < 0.001), and sex (p < 0.001) were associated with the most important echocardiographic alterations. Discussion: The morphological and functional echocardiographic alterations usually found in normotensive obese patients closely correlate with the amount of intra‐abdominal fat deposition, even in the presence of diabetes or IGT.     

Insulin Resistance in Nondiabetic Morbidly Obese Patients: Effect of Bariatric Surgery

Objective: To evaluate insulin action on substrate use and insulinemia in nondiabetic class III obese patients before and after weight loss induced by bariatric surgery. Research Methods and Procedures: Thirteen obese patients (four men/nine women; BMI = 56.3 ± 2.7 kg/m²) and 13 lean subjects (five men/eight women; BMI = 22.4 ± 0.5 kg/m²) underwent euglycemic clamp, oral glucose tolerance test, and indirect calorimetry. The study was carried out before (Study I) and after (～40% relative to initial body weight; Study II) weight loss induced by Roux‐en‐Y Gastric bypass with silastic ring surgery. Results: The obese patients were insulin resistant (whole‐body glucose use = 19.7 ± 1.5 vs. 51.5 ± 2.4 μmol/min per kilogram fat‐free mass, p < 0.0001) and hyperinsulinemic in the fasting state (332 ± 86 vs. 85 ± 5 pM, p < 0.0001) and during the oral glucose tolerance test compared with the lean subjects. Fasting plasma insulin normalized after weight loss, whereas whole‐body glucose use increased (35.5 ± 3.7 μmol/min per kilogram fat‐free mass, p < 0.05 vs. Study I). The higher insulin clearance of obese did not change during the follow‐up period. Insulin‐induced glucose oxidation and nonoxidative glucose disposal were lower in the obese compared with the lean group (all p < 0.05). In Study II, the former increased slightly, whereas nonoxidative glucose disposal reached values similar to those of the control group. Fasting lipid oxidation was higher in the obese than in the control group and did not change significantly in Study II. The insulin effect on lipid oxidation was slightly improved (p = 0.01 vs. Study I). Discussion: The rapid weight loss after surgery in obese class III patients normalized insulinemia and improved insulin sensitivity almost entirely due to glucose storage, whereas fasting lipid oxidation remained high.     

Exercise‐Induced Reduction in Obesity and Insulin Resistance in Women: a Randomized Controlled Trial

Objectives : To determine the effects of equivalent diet‐ or exercise‐induced weight loss and exercise without weight loss on subcutaneous fat, visceral fat, and insulin sensitivity in obese women. Research Methods and Procedures : Fifty‐four premenopausal women with abdominal obesity [waist circumference 110.1 ± 5.8 cm (mean ± SD)] (BMI 31.3 ± 2.0 kg/m²) were randomly assigned to one of four groups: diet weight loss (n = 15), exercise weight loss (n = 17), exercise without weight loss (n = 12), and a weight‐stable control group (n = 10). All groups underwent a 14‐week intervention. Results : Body weight decreased by ～6.5% within both weight loss groups and was unchanged in the exercise without weight loss and control groups. In comparison with controls, cardiorespiratory fitness improved within the exercise groups only (p < 0.01). Reduction in total, abdominal, and abdominal subcutaneous fat within the exercise weight loss group was greater (p < 0.001) than within all other groups. The reduction in total and abdominal fat within the diet weight loss and exercise without weight loss groups was greater than within controls (p < 0.001) but not different from each other (p > 0.05). Visceral fat decreased within all treatment groups (p < 0.008), and these changes were not different from each other. In comparison with the control group, insulin sensitivity improved within the exercise weight loss group alone (p < 0.001). Discussion : Daily exercise without caloric restriction was associated with substantial reductions in total fat, abdominal fat, visceral fat, and insulin resistance in women. Exercise without weight loss was also associated with a substantial reduction in total and abdominal obesity.     

Obesity‐related Comorbidities in Obese African Americans in an Outpatient Weight Loss Program

Objective: To identify, among obese African‐American enrollees in an outpatient weight loss program, differences between those with and without obesity‐related comorbidities (ORCMs). Research Methods and Procedures: Data were from 237 obese African Americans (BMI, 30 to 50 kg/m²; 90% women) who enrolled in a 10‐week lifestyle weight loss program. Analyses compared subgroups defined by ORCM status (from medical history) on baseline characteristics, program attendance, and postprogram weight change. Results: Most participants (76%) had one or more ORCMs. Those with versus without ORCMs, respectively, were older (mean age, 45.6 vs. 37.1 years; p < 0.001), were less educated (59.2% vs. 76.6% with >12 years; p = 0.031), were more likely to perceive a physical limitation affecting activity (22.2% vs. 1.8%; p < 0.001), and had higher waist circumference (mean, 113.7 vs. 106.9 cm; p < 0.001) but not BMI (38.3 vs. 37.0 kg/m²; p = 0.095). Logistic regression analyses confirmed the independence of these associations. Having ORCMs was not associated with class attendance or return for data collection after the 10‐week program. Postprogram weight change (n = 134) was unrelated to ORCMs, but better weight loss was seen among those without perceived physical limitations (1.9 vs. 0.4 kg in those without versus with limitations; p = 0.069). Conclusion: Data from this clinical sample of obese African Americans suggest that waist circumference is relevant to ORCM status at BMI levels up to 50 kg/m². Clear indications for tailoring of treatment based on ORCM status were not identified, although the possible influence of ORCM‐related activity limitations warrants further study.     

Sustained Weight Loss in Obese Subjects Has Benefits That Are Independent of Attained Weight

Objective: To explore the hypothesis that sustained weight loss in severely obese patients may have benefits that are independent of their attained BMI. Research Methods and Procedures: We conducted a comparison of two weight‐stable groups with BMI in the 30 to 35 kg/m² range. Subjects (n = 79) were selected obese patients 3 years after laparoscopic adjustable gastric band surgery, and controls (n = 79) were obese patients seeking weight loss therapy. Subjects were selected in a de‐identified manner from our database to best match the control group. A range of clinical, biochemical, and questionnaire measures were obtained to assess obesity‐related health status Results: Subjects maintained a mean weight loss of 32.8 ± 18 kg after surgery. The weight loss subjects had significantly lower fasting plasma glucose, insulin, and triglyceride concentrations, along with higher high‐density lipoprotein‐cholesterol levels and better indirect measures of insulin sensitivity when compared with controls (p < 0.05 for all). In addition, aminotransferase levels, neutrophil counts, and globulin levels were also significantly lower in weight loss subjects. All differences in laboratory variables remained significant after controlling for BMI. The subjects also reported better health‐related quality of life, fewer symptoms of depression, and greater satisfaction with their appearance than controls. Discussion: These findings suggest that the post‐weight loss state conveys benefits that are greater than predicted by the attained BMI. These findings may have important implications regarding the expectations of weight loss therapy, and mechanisms for this effect should be carefully sought.     

Leptin Levels Are Associated with Fat Oxidation and Dietary‐Induced Weight Loss in Obesity

Objective: To examine the relationship between fasting plasma leptin and 24‐hour energy expenditure (EE), substrate oxidation, and spontaneous physical activity (SPA) in obese subjects before and after a major weight reduction compared with normal weight controls. To test fasting plasma leptin, substrate oxidations, and SPA as predictive markers of success during a standardized weight loss intervention. Research Methods and Procedures: Twenty‐one nondiabetic obese (body mass index: 33.9 to 43.8 kg/m²) and 13 lean (body mass index: 20.4 to 24.7 kg/m²) men matched for age and height were included in the study. All obese subjects were reexamined after a mean weight loss of 19.2 kg (95% confidence interval: 15.1–23.4 kg) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability. Twenty‐four‐hour EE and substrate oxidations were measured by whole‐body indirect calorimetry. SPA was assessed by microwave radar. Results: In lean subjects, leptin adjusted for fat mass (FM) was correlated to 24‐hour EE before (r = ?0.56, p < 0.05) but not after adjustment for fat free mass. In obese subjects, leptin correlated inversely with 24‐hour and resting nonprotein respiratory quotient (r = ?0.47, p < 0.05 and r = ?0.50, p < 0.05) both before and after adjustments for energy balance. Baseline plasma leptin concentration, adjusted for differences in FM, was inversely related to the size of weight loss after 8 weeks (r = ?0.41, p = 0.07), 16 weeks (r = ?0.51, p < 0.05), and 24 weeks (r = ?0.50, p < 0.05). Discussion: The present study suggests that leptin may have a stimulating effect on fat oxidation in obese subjects. A low leptin level for a given FM was associated with a greater weight loss, suggesting that obese subjects with greater leptin sensitivities are more successful in reducing weight.     

Longitudinal Analyses among Overweight,Insulin Resistance,and Cardiovascular Risk Factors in Children

Objective: It has been questioned whether insulin resistance or obesity is the central abnormality contributing to the cardiovascular risk factors dyslipidemia and hypertension in obesity. Research Methods and Procedures: We studied weight status [SD score (SDS)‐BMI], lipids (triglycerides, low‐density lipoprotein‐ and high‐density lipoprotein‐cholesterol), blood pressure, and insulin resistance index [as homeostasis model assessment (HOMA) model] over a 1‐year period in 229 obese white children (median age 12 years). Results: Any degree of decrease in HOMA was associated with significant decreases in triglycerides (p < 0.001), systolic blood pressure (p < 0.001), and diastolic blood pressure (p < 0.001), whereas the children with different changes in HOMA did not differ significantly in their weight changes. Only the children in the highest quartile of weight reduction (decrease in SDS‐BMI > 0.5) demonstrated a significant decrease in systolic blood pressure (p < 0.001), diastolic blood pressure (p < 0.001), and triglycerides (p = 0.012), and an increase in high‐density lipoprotein‐cholesterol (p = 0.023), whereas with a lower degree of weight loss, there were no significant changes in cardiovascular risk factors. In contrast with a lower degree of weight loss, a reduction of >0.5 SDS‐BMI was associated with a significant decrease in HOMA (p < 0.001). Discussion: Because blood pressure and triglycerides decreased with any degree of decrease in HOMA, independently of changes in weight status, these findings support the hypothesis that insulin resistance is the central abnormality contributing to these cardiovascular risk factors. Therefore, improving insulin resistance seems more important than reducing overweight to prevent or treat hypertension and dyslipidemia in obese children.     

Lipoprotein Subpopulation Distributions in Lean,Obese, and Type 2 Diabetic Women: A Comparison of African and White Americans

Objective: Abnormal subpopulation distributions of plasma lipoproteins have been reported in white American (WA) women with obesity and type 2 diabetes that explain part of the elevated rate of cardiovascular disease in these patients. This study examined if these perturbations also occur in obese and diabetic African American (AA) women and compared the lipoprotein profiles with WA counterparts. Research Methods and Procedures: We determined the lipoprotein subpopulation distribution in the plasma of 51 lean women (29 WA, 22 AA, body mass index [BMI] < 30), 50 obese women (27 WA, 23 AA, BMI > 30), and 43 obese women with type 2 diabetes (27 WA, 16 AA), by nuclear magnetic resonance spectroscopy. Results: AA diabetic women, like WA diabetic women, had a larger average very low density lipoprotein (VLDL) size, elevated levels of small low density lipoprotein cholesterol (LDL‐C), and lower levels of small high density lipoprotein cholesterol (HDL‐C), when compared to lean controls (p < 0.05). These differences were accompanied by higher VLDL‐triglycerides (TG) and LDL‐C in WA (p < 0.05), but not in AA. Although the effects of obesity and diabetes on lipoprotein subpopulation were fairly similar for AA and WA, some racial differences, particularly with respect to HDL, were observed. Discussion: The atherogenic perturbations in lipoprotein profiles of obese AA women, particularly those with diabetes, were relatively similar to those found in WA women and may be contributing to the increased rate of cardiovascular disease (CVD) in AA with obesity and diabetes. The parameters of subpopulation distribution may provide better markers for CVD than lipid concentrations alone, particularly in AA women. Furthermore, subtle racial differences in lipoprotein profiles suggest that race‐specific criteria may be needed to screen patients for CVD.     

Leptin Responses to Weight Loss in Postmenopausal Women: Relationship to Sex‐Hormone Binding Globulin and Visceral Obesity

Objective: Leptin concentrations increase with obesity and tend to decrease with weight loss. However, there is large variation in the response of serum leptin levels to decreases in body weight. This study examines which endocrine and body composition factors are related to changes in leptin concentrations following weight loss in obese, postmenopausal women. Research Methods and Procedures: Body composition (DXA), visceral obesity (computed tomography), leptin, cortisol, insulin, and sex hormone‐binding globulin (SHBG) concentrations were measured in 54 obese (body mass index [BMI] = 32.0 ± 4.5 kg/m²; mean ± SD), women (60 ± 6 years) before and after a 6‐month hypocaloric diet (250 to 350 kcal/day deficit). Results: Body weight decreased by 5.8 ± 3.4 kg (7.1%) and leptin levels decreased by 6.6 ± 11.9 ng/mL (14.5%) after the 6‐month treatment. Insulin levels decreased 10% (p < 0.05), but mean SHBG and cortisol levels did not change significantly. Relative changes in leptin with weight loss correlated positively with relative changes in body weight (r = 0.50, p < 0.0001), fat mass (r = 0.38, p < 0.01), subcutaneous fat area (r = 0.52, p < 0.0001), and with baseline values of SHBG (r = 0.38, p < 0.01) and baseline intra‐abdominal fat area (r = ?0.27, p < 0.06). Stepwise multiple regression analysis showed that baseline SHBG levels (r² = 0.24, p < 0.01), relative changes in body weight (cumulative r² = 0.40, p < 0.05), and baseline intra‐abdominal fat area (cumulative r² = 0.48, p < 0.05) were the only independent predictors of the relative change in leptin, accounting for 48% of the variance. Discussion: These results suggest that obese, postmenopausal women with a lower initial SHBG and more visceral obesity have a greater decrease in leptin with weight loss, independent of the amount of weight lost.     

Blood Pressure and Pulse Pressure during Long‐Term Weight Loss in the Obese: The Swedish Obese Subjects (SOS) Intervention Study

Objective: Recently we reported a complete relapse in the blood pressure (BP) of obese subjects despite a maintained 16% weight loss over 8 years. This relapse is now analyzed as a function of several variables. Pulse pressure (PP) is an independent risk factor of cardiovascular mortality. We now examine the development of PP in the obese and whether it can be modified by weight‐reducing gastric surgery. Research Methods and Procedures: A total of 1157 patients treated with gastric surgery and 1031 obese controls (body mass index of 41.0 ± 4.6 kg/m² [mean ± SD], age 48 ± 6 years) were followed for 5.5 ± 2.1 (range 3 to 10) years. To separate the effect of weight change from effect of time on BP, the patients were divided in cohorts based on follow‐up time. Results: Gastric surgery resulted in a maximum weight loss after 1 year that was followed by a moderate relapse. After 5.5 years, weight loss in the intervention group was 18 ± 11% of initial body weight. Very little weight change was seen in controls. Systolic BP decreased in the intervention group during the first 6 months but had relapsed to control values at last examination. The adjusted change in PP was +4.7 mm Hg in obese controls but +2.9 mm Hg in the intervention group (p < 0.001). Final BP values were more closely related to follow‐up time and ongoing weight increase than to initial body weight or initial weight loss. Discussion: Effects of time (aging) and weight change per year on BP can be separated. An early increase in PP could be observed in the obese. This increase could be modified by weight‐reducing gastric surgery.     

Sibutramine plus meal replacement therapy for body weight loss and maintenance in obese patients

Objective: Our objective was to assess the efficacy and safety of sibutramine with a low‐calorie diet (LCD) and commercial meal‐replacement product in achieving weight loss and weight‐loss maintenance in obese patients. Research Methods and Procedures: Eight U.S. centers recruited 148 obese patients for a 3‐month comprehensive weight‐loss therapy (Phase I) comprising daily sibutramine 10 mg + LCD (two Slim‐Fast meal‐replacement shakes, one low‐calorie meal; total kcal/d = 1200–1500). Patients (N = 113) who lost ≥5% of initial body weight during Phase I were randomized for a 9‐month period (Phase II) to daily sibutramine 15 mg + LCD (one meal‐replacement shake; two low‐calorie meals: total kcal/d ～1200–1500) or daily placebo + three low‐calorie meals (total kcal/d ～1200–1500). Both phases included behavior modification. Efficacy was assessed by body weight change during each phase and by the number of patients at endpoint maintaining ≥80% of the weight they had lost by the end of Phase I. Other outcomes included changes in cardiovascular and metabolic risk factors, adverse events, and vital signs. Results: Mean body weight change during Phase I was ?8.3 kg (p < 0.001). Patients randomized to sibutramine in Phase II had an additional ?2.5 kg mean weight loss vs. a 2.8‐kg increase in the placebo group (p < 0.001). More sibutramine patients maintained ≥80% of their Phase I weight loss at the end of Phase II (85.5% vs. placebo 36.7%, p < 0.001). Most adverse events were mild or moderate in severity, and all serious adverse events were unrelated to sibutramine. Discussion: Sibutramine plus LCD with meal replacements and behavior modification is a safe and effective strategy for achieving and sustaining weight loss in obese patients.     

Weight Loss Reduces Tissue Factor in Morbidly Obese Patients

Objective: To investigate the tissue factor (TF) pathway in clinical obesity and associated metabolic syndrome. Research Methods and Procedures: Thirty‐seven morbidly obese patients (4 men; BMI, 48 ± 7 kg/m²; range, 42 to 53 kg/m²), undergoing elective gastroplasty for the induction of weight loss, were examined for hemostatic, metabolic, and inflammatory parameters at baseline and 14 ± 5 months postoperatively. Results: Weight loss significantly reduced circulating plasma TF (314 ± 181 vs. 235 ± 113 pg/mL, p = 0.04), coagulation factor VII (130 ± 22% vs. 113 ± 19%, p = 0.023), and prothrombin fragment F1.2 (2.4 ± 3.4 vs. 1.14 ± 1.1 nM, p = 0.04) and normalized glucose metabolism in 50% of obese patients preoperatively classified as diabetic or of impaired glucose tolerance. The postoperative decrease in plasma TF correlated with the decrease of F1.2 (r = 0.56; p = 0.005), a marker of in vivo thrombin formation. In subgroup analysis stratified by preoperative glucose tolerance, baseline circulating TF (402.6 ± 141.6 vs. 176.2 ± 58.2, p < 0.001) and TF decrease after gastroplasty (ΔTF: 164.7 ± 51.4 vs. ?81 ± 31 pg/mL, p = 0.02) were significantly higher in obese patients with impaired glucose tolerance than in patients with normal glucose tolerance. Discussion: Procoagulant TF is significantly reduced with weight loss and may contribute to a reduction in cardiovascular risk associated with obesity.