Percentage Fat in Overweight and Obese Children: Comparison of DXA and Air Displacement Plethysmography**

Objective: To compare percentage body fat (percentage fat) estimates from DXA and air displacement plethysmography (ADP) in overweight and obese children. Research Methods and Procedures: Sixty‐nine children (49 boys and 20 girls) 14.0 ± 1.65 years of age, with a BMI of 31.3 ± 5.6 kg/m² and a percentage fat (DXA) of 42.5 ± 8.4%, participated in the study. ADP body fat content was estimated from body density (D_b) using equations devised by Siri (ADP_Siri) and Lohman (ADP_Loh). Results: ADP estimates of percentage fat were highly correlated with those of DXA in both male and female subjects (r = 0.90 to 0.93, all p < 0.001; standard error of estimate = 2.50% to 3.39%). Compared with DXA estimates, ADP_Siri and ADP_Loh produced significantly (p < 0.01) lower estimates of mean body fat content in boys (?2.85% and ?4.64%, respectively) and girls (?2.95% and ?5.15%, respectively). Agreement between ADP and DXA methods was further examined using the total error and methods of Bland and Altman. Total error ranged from 4.46% to 6.38% in both male and female subjects. The 95% limits of agreement were relatively similar for all percentage fat estimates, ranging from ±6.73% to ±7.94%. Discussion: In this study, conversion of D_b using the Siri equation led to mean percentage fat estimates that agreed better with those determined by DXA compared with the Lohman equations. However, relatively high limits of agreement using either equation resulted in percentage fat estimates that were not interchangeable with percentage fat determined by DXA.     

Obesity Increases the Risk of Spontaneous Abortion during Infertility Treatment

Objective: This study examines the relationship between body mass and the risk of spontaneous abortion in a large cohort of patients who received infertility treatment. Research Methods and Procedures: This is a retrospective study using data on pregnancies (n = 2349) achieved after treatment in a tertiary medical center from 1987 to 1999. One pregnancy per subject was included, and the subjects were stratified into five body mass groups based on body mass index (BMI): underweight, <18.5 kg/m²; normal, 18.5 to 24.9 kg/m²; overweight, 25 to 29.9 kg/m²; obese, 30 to 34.9 kg/m²; and very obese, ≥35 kg/m². Logistical regression analysis was used. Results: The overall incidence of spontaneous abortion was 20% (476 of 2349). The effect of BMI on the risk of spontaneous abortion was significant after adjusting for several independent risk factors. Compared with the reference group (BMI 18.5 to 24.9 kg/m²), underweight women had a similar risk of spontaneous abortion, whereas there was progressive increase of risk in overweight, obese, and very obese groups (p < 0.05, p < 0.01, and p < 0.001, respectively). Discussion: Of all known risk factors for spontaneous abortion, the control of obesity has great significance because it is noninvasive, potentially modifiable, possibly amenable to low cost, and self‐manageable by patients. This study established a positive relationship between BMI and the risk of spontaneous abortion in women who became pregnant after assisted reproductive technology treatment.     

Is There a Role for Gastric Accommodation and Satiety in Asymptomatic Obese People?

Objective: The relationships of gastric accommodation and satiety in moderately obese individuals are unclear. We hypothesized that obese people had increased gastric accommodation and reduced postprandial satiety. The objective of this study was to compare gastric accommodation and satiety between obese and non‐obese asymptomatic subjects. Research Methods and Procedures: In 13 obese (body mass index [BMI] ≥ 30 kg/m²; mean BMI, 37.0 ± 4.9 kg/m²) and 19 non‐obese control subjects (BMI < 30 kg/m²; mean BMI, 26.2 ± 2.9 kg/m²), we used single photon emission computed tomography to measure fasting and postprandial gastric volumes and expressed the accommodation response as the ratio of postprandial/fasting volumes. The satiety test measured maximum tolerable volume of ingestion of liquid nutrient meal (Ensure) and symptoms 30 minutes after cessation of ingestion. Results: Total fasting and postprandial gastric volumes and the ratio of postprandial/fasting gastric volume were not different between asymptomatic obese and control subjects. However, the fasting volume of the distal stomach was greater in obese than in control subjects. Maximum tolerable volume of ingested Ensure and aggregate symptom score 30 minutes later were also not different between obese and control subjects. Discussion: Asymptomatic obese individuals (within the BMI range of 32.6 to 48 kg/m²) did not show either increased postprandial gastric accommodation or reduced satiety. These datasuggest that gastric accommodation is unlikely to provide an important contribution to development of moderate obesity.     

Obesity and Quality of Life: Mediating Effects of Pain and Comorbidities

Objective: To estimate the association between body mass index (BMI) and health‐related quality of life (HRQL) and examine whether joint pain and obesity‐related comorbidities mediate the BMI‐HRQL association. Research Methods and Procedures: Population‐based survey data from the 1999 Behavioral Risk Factor Surveillance Survey. Adults (N = 155, 989) were classified according to BMI as underweight (<18.5 kg/m²), desirable weight (18.5 to 24.9 kg/m²), overweight (25 to 29.9 kg/m²), obese class I (30 to 34.9 kg/m²), obese class II (35 to 39.9 kg/m²), and obese class III (≥40 kg/m²). Data including general health status, unhealthy days in the past 30 caused by physical problems and mental problems, and total unhealthy days in the past 30 were collected. Results: After adjusting for age, sex, race, smoking, education, and income, we observed J‐shaped associations between BMI and HRQL. Compared with desirable weight adults, underweight, overweight, and obesity classes I, II, and III adults [odds ratio (OR) = 1.57, 1.19, 1.95, 2.72, and 4.36, respectively] were significantly (p < 0.001) more likely to report fair/poor general health status. For unhealthy days caused by physical problems, the corresponding ORs were 1.51, 1.15, 1.66, 2.27, and 3.61 (p < 0.001). For unhealthy days caused by mental problems, the ORs were 1.35, 1.14 1.43, 1.57, and 2.25 (p < 0.001). For total unhealthy days, the corresponding ORs were 1.27, 1.09, 1.37, 1.73, and 2.46 (p < 0.01). Adding joint pain and obesity‐related comorbidities into models attenuated BMI‐HRQL associations. Discussion: Associations between BMI and HRQL indices were J‐shaped. Joint pain and comorbidities may mediate BMI‐HRQL associations.     

Prevalence of Uncomplicated Obesity in an Italian Obese Population

Objective: The existence of healthy obese subjects has been suggested but not clearly reported. We sought to address the prevalence of uncomplicated obesity and adverse risk factors in a large Italian obese population. Research Methods and Procedures: This was a cross‐sectional study of a population of consecutive Italian obese subjects. We studied 681 obese subjects (514 women and 167 men), with a mean age of 41.1 ± 13.9 years (range, 16 to 77 years), mean BMI of 40.2 ± 7.6 kg/m² (range, 30 to 89.8 kg/m²), and a history of obesity for 20.5 ± 7 years (range, 10.5 to 30 years). Anthropometric, metabolic, cardiac, and obesity‐related risk factors were evaluated. Results: The prevalence of uncomplicated subjects was 27.5%, independent of BMI and duration of obesity. The youngest group of obese subjects showed a higher, but not statistically significantly higher, prevalence of uncomplicated obesity. No statistical difference for the prevalence of impaired fasting glucose, glucose intolerance, high triglycerides, high total cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol among BMI categories (from mild to extremely severe obesity degree) was found. Obese subjects with BMI >50 kg/m² showed a higher prevalence of high blood pressure only when they were compared with the group with a BMI of 30 to 35 kg/m² (p < 0.01). Obese subjects with BMI >40 kg/m² showed a higher prevalence of hyperinsulinemia than subjects with BMI 30 to 35 kg/m² (p < 0.01). Discussion: This study shows that a substantial part of an Italian obese population has uncomplicated obesity, and the prevalence of adverse risk factors in this sample is unexpectedly low and partially independent of obesity degree. Uncomplicated obesity could represent a well‐defined clinical entity.     

Adapted Changes in Left Ventricular Structure and Function in Severe Uncomplicated Obesity

Objective: A massive amount of fat tissue, as that observed in obese subjects with BMI over 50 kg/m², could affect cardiac morphology and performance, but few data on this issue are available. We sought to evaluate cardiac structure and function in uncomplicated severely obese subjects. Research Methods and Procedures: We studied 55 uncomplicated severely obese patients, 40 women, 15 men, mean age 35.5 ± 10.2 years, BMI 51.2 ± 8.8 kg/m², range 43 to 81 kg/m², with a history of fat excess of at least 10 years, and 55 age‐matched normal‐weight subjects (40 women, 15 men, mean BMI 23.8 ± 1.2 kg/m²) as a control group. Each subject underwent an echocardiogram to evaluate left ventricular (LV) mass and geometry and systolic and diastolic function. Results: Severely obese subjects showed greater LV mass and indexed LV mass than normal‐weight subjects (p < 0.01 for all parameters). Nevertheless, LV mass was appropriate for sex, height^2.7, and stroke work in most (77%) uncomplicated severely obese subjects. In addition, no significant difference in LV mass indices and LV mass appropriateness between obese subjects with BMI ≥ 50 kg/m² and those with BMI ≤ 50 kg/m² was found. Obese subjects also showed higher ejection fraction and midwall shortening than normal‐weight subjects (p = 0.05 and p < 0.01, respectively), suggesting a hyperdynamic systolic function. No significant difference in systolic performance between obese subjects with BMI ≥ 50 kg/m² and those with BMI ≤ 50 kg/m² was seen. Discussion: Our data show that uncomplicated severe obesity, despite the massive fat tissue amount, is associated largely with adapted and appropriate changes in cardiac structure and function.     

Influence of Excess Fat on Cardiac Morphology and Function: Study in Uncomplicated Obesity

Objective: To evaluate whether or not “uncomplicated” obesity (without associated comorbidities) is really associated with cardiac abnormalities. Research Methods and Procedures: We evaluated cardiac parameters in obese subjects with long‐term obesity, normal glucose tolerance, normal blood pressure, and regular plasma lipids. We selected 75 obese patients [body mass index (BMI) >30 kg/m²], who included 58 women and 17 men (mean age, 33.7 ± 11.9 years; BMI, 37.8 ± 5.5 kg/m²) with a ≥10‐year history of excess fat, and 60 age‐matched normal‐weight controls, who included 47 women and 13 men (mean age, 32.7 ± 10.4 years; BMI, 23.1 ± 1.4 kg/m²). Each subject underwent an oral glucose tolerance test to exclude impaired glucose tolerance or diabetes mellitus, bioelectrical impedance analysis to calculate fat mass and fat‐free mass, and echocardiography. Results: Obese patients presented diastolic function impairment, hyperkinetic systole, and greater aortic root and left atrium compared with normal subjects. No statistically significant differences between obese subjects and normal subjects were found in indexed left ventricular mass (LVM/body surface area, LVM/height^2.7, and LVM/fat‐free mass_kg), and no changes in left ventricular geometry were observed. No statistically significant differences in cardiac parameters between extreme (BMI > 40 kg/m²) and mild obesity (BMI < 35 kg/m²) were observed. Discussion: In conclusion, our data showed that obesity, in the absence of glucose intolerance, hypertension, and dyslipidemia, seems to be associated only with an impairment of diastolic function and hyperkinetic systole, and not with left ventricular hypertrophy.     

Association Between the 4 bp Proinsulin Gene Insertion Polymorphism (IVS‐69) and Body Composition in Black South African Women

The objective of the study was to examine the association between a functional 4 bp proinsulin gene insertion polymorphism (IVS‐69), fasting insulin concentrations, and body composition in black South African women. Body composition, body fat distribution, fasting glucose and insulin concentrations, and IVS‐69 genotype were measured in 115 normal‐weight (BMI <25 kg/m²) and 138 obese (BMI ≥30 kg/m²) premenopausal women. The frequency of the insertion allele was significantly higher in the class 2 obese (BMI ≥35kg/m²) compared with the normal‐weight group (P = 0.029). Obese subjects with the insertion allele had greater fat mass (42.3 ± 0.9 vs. 38.9 ± 0.9 kg, P = 0.034) and fat‐free soft tissue mass (47.4 ± 0.6 vs. 45.1 ± 0.6 kg, P = 0.014), and more abdominal subcutaneous adipose tissue (SAT, 595 ± 17 vs. 531 ± 17 cm², P = 0.025) but not visceral fat (P = 0.739), than obese homozygotes for the wild‐type allele. Only SAT was greater in normal‐weight subjects with the insertion allele (P = 0.048). There were no differences in fasting insulin or glucose levels between subjects with the insertion allele or homozygotes for the wild‐type allele in the normal‐weight or obese groups. In conclusion, the 4 bp proinsulin gene insertion allele is associated with extreme obesity, reflected by greater fat‐free soft tissue mass and fat mass, particularly SAT, in obese black South African women.     

Abnormal Signal‐Averaged Electrocardiogram (SAECG) in Obesity

Objective: The occurrence of small high‐frequency electrocardiogram (ECG) potentials (1 to 20 μV) seen at the end of the QRS complex and into the ST segment have been correlated with increased risk for ventricular arrhythmias and sudden cardiac death. Computer‐assisted analysis of these “late potentials” by signal‐averaged electrocardiography (SAECG) has been studied and utilized to predict the likelihood of ventricular arrhythmias in various clinical states. Obesity is associated with significant cardiovascular morbidity and sudden death. Ventricular arrhythmias are postulated causes. We studied the occurrence of late potentials in a randomly selected group of obese patients and healthy volunteers. Research Methods and Procedures: We performed SAECG on 105 subjects. Of these, 62 were obese ambulatory patients with body mass index (BMI) of >30 kg/m², whereas 43 were healthy asymptomatic volunteers with a BMI of <30 kg/m². Patients with a history of clinical heart disease and pulmonary disease, electrolyte abnormalities, recent hospitalizations, or abnormal screening ECG or taking medications known to alter the QRS interval were excluded. At least 250 beats were analyzed with a noise level of <0.50 μV. Criteria of a late potential include QRS duration >114 ms, high‐frequency low amplitude >38 ms, and root‐mean‐square voltage <20 μV. Patients were divided into four subgroups based on BMI values. The prevalence of SAECG abnormalities in each BMI subgroup was studied. We utilized multiple logistic regression analysis to study the effect of obesity, hypertension, and diabetes mellitus on abnormal SAECG results. Results: Compared to age‐ and sex‐matched healthy volunteers with BMI of <30 kg/m², obese patients with BMI of >30 kg/m² had significantly more abnormalities on SAECG (4.6% vs. 55%). In the obese group, the prevalence and number of abnormalities increased with increase in BMI (35% in the BMI 31 to 40 kg/m² subgroup, 86% in the BMI 41 to 50 kg/m² subgroup, and 100% in patients with BMI of >50 kg/m²). Multiple logistic regression analysis shows that BMI is an independent predictor variable of abnormal SAECG results in obese patients (n = 62) with BMI of >30kg/m² as well as in all study subjects (n = 105). BMI also predicts abnormality of each abnormal SAECG criterion in both obese and all subjects. Hypertension was found to influence the QRS duration alone in obese and all subjects. Discussion: Obesity is associated with increased occurrence of abnormal SAECG results. These abnormalities are found both in obese patients with and without hypertension and/or diabetes. Obesity is an independent predictor variable of abnormal SAECG results. A history of hypertension predicts abnormality of QRS duration only.     

Basal Endothelial Nitric Oxide Release Is Preserved in Overweight and Obese Adults

Objective: Impaired basal nitric oxide release is associated with a number of cardiovascular disorders including hypertension, arterial spasm, and myocardial infarction. We determined whether basal endothelial nitric oxide release is reduced in otherwise healthy overweight and obese adult humans. Research Methods and Procedures: Seventy sedentary adults were studied: 32 normal weight (BMI <25 kg/m²), 24 overweight (BMI ≥ 25 < 30 kg/m²), and 14 obese (BMI ≥ 30 kg/m²). Forearm blood flow (FBF) responses to intra‐arterial infusions of N^g‐monomethyl‐l ‐arginine (5 mg/min), a nitric oxide synthase inhibitor, were used as an index of basal nitric oxide release. Results: N^g‐monomethyl‐l ‐arginine elicited significant reductions in FBF in the normal weight (from 4.1 ± 0.2 to 2.7 ± 0.2 mL/100 mL tissue/min), overweight (4.1 ± 0.1 to 2.8 ± 0.2 mL/100 mL tissue/min), and obese (3.9 ± 0.3 to 2.7 ± 0.2 mL/100 mL tissue/min) subjects. Importantly, the magnitude of reduction in FBF (～30%) was similar among the groups. Discussion: These results indicate that the capacity of the endothelium to release nitric oxide under basal conditions is not compromised in overweight and obese adults.     

Effect of circulatory congestion on the components of pulmonary diffusing capacity in morbid obesity

Objective: Obese patients without clinically apparent heart disease may have a high output state and elevated total and central blood volumes. Central circulatory congestion should result in elevated pulmonary diffusing capacity (D_LCO) and capillary blood volume (V_c) reflecting pulmonary capillary recruitment; however, the effect on membrane diffusion (D_m) is uncertain. We examined D_LCO and its partition into V_c and D_m in 13 severely obese subjects (BMI = 51 ± 14 kg/m²) without manifest cardiopulmonary disease before and after surgically induced weight loss. Research Methods and Procedures: D_LCO and its partition into V_c and D_m [referenced to alveolar volume (V_A)] as described by Roughton and Forster, total body water by tritiated water, and fat distribution by waist‐to‐hip ratio were performed. Results: Despite normal D_LCO (mean 98 ± 16% predicted), V_c/V_A was increased (mean 118 ± 30% predicted), and D_m/V_A was reduced (mean 77 ± 34% predicted). Nine of 13 subjects were restudied after weight loss (mean 52 ± 43 kg); V_c/V_A decreased to 89 ± 18% predicted (p = 0.01), and D_m/V_A increased to 139 ± 30% predicted (p < 0.01). Increasing total body water was associated with both increasing V_c (r = 0.74, p = 0.01) and increasing waist‐to‐hip ratio (r = 0.65, p = 0.02), indicating that circulatory congestion increases with increasing central obesity. Discussion: Severely obese subjects without manifest cardiopulmonary disease may have increased V_c indicating central circulatory congestion and reduced D_m suggesting associated alveolar capillary leak, despite normal D_LCO. Reversibility with weight loss is in accord with reversibility of the hemodynamic abnormalities of obesity.     

The influence of weight loss on serum osteoprotegerin concentration in obese perimenopausal women

Objective: To assess the influence of weight reduction therapy on serum osteoprotegerin (OPG) concentration in obese patients and compare these results with normal‐weight controls. Research Methods and Procedures: Forty‐three obese women (BMI, 36.7 ± 4.1 kg/m²; mean age, 50.1 ± 4.5 years) were studied. The control group consisted of 19 normal‐weight women (BMI, 24.2 ± 2.1 kg/m²; mean age, 53.8 ± 5.2 years). In all patients, serum concentrations of OPG, C telopeptide of type I collagen containing the cross‐linking site (CTX), osteocalcin, parathormone, 25‐(OH)‐D₃ (vitamin D), and total calcium and phosphorus were assessed before and after a 3‐month weight reduction therapy. Results: In obese subjects, serum concentrations of OPG, 25‐(OH)‐D₃, osteocalcin, total calcium, and phosphorus were significantly lower, and serum concentration of parathormone was significantly higher, before weight reduction therapy in comparison with normal‐weight controls. After weight reduction, a significantly higher serum concentration of 25‐(OH)‐D₃ and CTX and significantly lower concentration of OPG were found. Discussion: Serum concentration of OPG was significantly lower in obese patients in comparison with normal‐weight controls. Weight reduction therapy resulted in further decrease in OPG serum concentrations. Therefore, OPG cannot be treated as a protective factor from bone loss in obese patients.     

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.     

Comparison of body adiposity index (BAI) and bmi with estimations of % body fat in clinically severe obese women

Objective:

Body adiposity index (BAI), a new surrogate measure of body fat (hip circumference/(height^1.5 – 18)), has been proposed as an alternative to body mass index (BMI). We compared BAI with BMI, and each of them with laboratory measures of body fat‐derived from bioimpedance analysis (BIA), air displacement plethysmography (ADP), and dual‐energy X‐ray absorptiometry (DXA) in clinically severe obese (CSO) participants.

Design and Methods:

Nineteen prebariatric surgery CSO, nondiabetic women were recruited (age = 32.6 ± 7.7 SD; BMI = 46.5 ± 9.0 kg/m²). Anthropometrics and body fat percentage (% fat) were determined from BIA, ADP, and DXA. Scatter plots with lines of equality and Bland–Altman plots were used to compare BAI and BMI with % fat derived from BIA, ADP, and DXA. BAI and BMI correlated highly with each other (r = 0.90, P < 0.001).

Results:

Both BAI and BMI correlated significantly with % fat from BIA and ADP. BAI, however, did not correlate significantly with % fat from DXA (r = 0.42, P = 0.08) whereas BMI did (r = 0.65, P = 0.003). BMI was also the single best predictor of % fat from both BIA (r² = 0.80, P < 0.001) and ADP (r² = 0.65, P < 0.001). The regression analysis showed that the standard error of the estimate (SEE), or residual error around the regression lines, was greater for BAI comparisons than for BMI comparisons with BIA, ADP, and DXA. Consistent with this, the Bland and Altman plots indicated wider 95% confidence intervals for BAI difference comparisons than for BMI difference comparisons for their respective means for BIA, ADP, and DXA.

Conclusions:

Thus, BAI does not appear to be an appropriate proxy for BMI in CSO women.     

Relationship of Insulin Sensitivity and Left Ventricular Mass in Uncomplicated Obesity

Objective: We studied uncomplicated obesity as a model to evaluate the influence of insulin sensitivity per se on left ventricular mass (LVM) and geometry. Research Methods and Procedures: We selected 50 obese subjects (BMI > 30 kg/m²; 38 women and 12 men; mean age, 38.4 ± 10 years; BMI, 36.4 ± 10.5 kg/m²) with normal blood pressure, glucose tolerance, and plasmatic lipid levels. Thirty lean subjects formed the control group. Each subject underwent euglycemic insulin clamp (7 pmol/min per kg) to evaluate whole body glucose use (M index) and echocardiogram to calculate LVM and indexed LVM. Results: Insulin‐resistant obese subjects had higher LVM, LVM/h^2.7, LVM/body surface area, and LVM/fat‐free mass_kg (p = 0.001; p = <0.001 p = 0.001, and p = 0.04, respectively) than obese subjects with normal insulin sensitivity. Multivariate regression analysis showed that M index was the strongest independent correlate of LVM (r² = 0.34; p = 0.03). Discussion: Our findings showed that insulin resistance, in uncomplicated obesity, is associated with an increased LVM and precocious changes of left ventricular geometry, whereas preserved insulin sensitivity is not associated with increased LVM.     

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.     

Obesity Affects Myocardial Vasoreactivity and Coronary Flow Response to Insulin

Objective: Obesity is associated with increased risk for cardiovascular diseases and peripheral endothelial dysfunction. We examined whether myocardial vasoreactivity and coronary‐flow response to insulin stimulation are altered in obesity. Research Methods and Procedures: Myocardial blood flow was quantitated in 10 obese men (body mass index, 33.6 ± 1.9 kg/m²) and 10 healthy matched non‐obese men (body mass index, 24.2 ± 1.9 kg/m²), using positron emission tomography and oxygen‐15‐labeled water. The measurements were performed basally and during adenosine infusion (140 μg/kg per minute), with or without simultaneous physiological (1 mU/kg per minute) and supraphysiological (5 mU/kg per minute) hyperinsulinemia. Results: Basal myocardial blood flow was not significantly different between obese and non‐obese subjects. Adenosine‐stimulated flow was blunted in obese (3.2 ± 0.6 mL/g per minute) when compared with non‐obese subjects (4.0 ± 1.1 mL/g per minute, p < 0.05). Simultaneous physiological hyperinsulinemia increased adenosine‐stimulated myocardial flow significantly in both groups (to 4.03 ± 1.24 and 4.85 ± 1.04 mL/g per minute in obese and non‐obese men, respectively; p < 0.05 vs. adenosine). Supraphysiological hyperinsulinemia further enhanced the adenosine‐stimulated flow in non‐obese subjects (to 5.56 ± 0.98 mL/g per minute; p < 0.05) but not in obese subjects. Discussion: Young obese, healthy men have reduced myocardial vasoreactivity, which may represent an early precursor of future coronary artery disease. Additionally, insulin‐induced enhancement of myocardial blood flow is blunted in obesity. Thus, endothelial dysfunction seems to also characterize myocardial vasculature of obese subjects.     

Association between Low‐Molecular Weight Apolipoprotein(a) Isoforms and Obesity in Italian Women

Objective: Low‐molecular weight (MW) apolipoprotein(a) [apo(a)] isoforms are closely associated with an increased incidence of atherothrombotic disease, prevalence of which is higher in obese individuals, particularly in women. The hypothesis of this study was to assess whether there are differences in the distribution of apo(a) phenotypes between obese patients and healthy controls. Research Methods and Procedures: One hundred three obese Italian women (BMI ≥ 30.0 kg/m²) were enrolled in the study, and apo(a) phenotyping was performed in all subjects. The prevalence of low‐MW apo(a) isoforms, detected in plasma samples of our obese women, was compared with that found in a control group of 84 normal‐weight, never‐obese (BMI < 25.0 kg/m²), age‐matched women. Results: The distribution of apo(a) isoforms in the population of obese women was significantly different from that found in normal‐weight female subjects. In particular, the percentage of subjects in the obese group with at least one apo(a) isoform of low MW was significantly higher than that in the control group (51.4% vs. 32.1%, p = 0.0079). Discussion: Our results seem to suggest the possibility that small‐sized apo(a) isoforms may be used together with other traditional risk factors to better assess the overall predisposition to atherothrombotic disease in obese women.     

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.     

Lipoprotein Oxidation and Plasma Vitamin E in Nondiabetic Normotensive Obese Patients

Objective: To correlate the susceptibility of low‐(LDL) and very‐low‐density lipoprotein to oxidation in vitro and the concentrations of serum antibodies against malondialdehyde‐modified LDL and plasma vitamin E with the anthropometric and laboratory characteristics of obesity. Research Methods and Procedures: A total of 75 nondiabetic, normotensive obese patients were assigned to one of four groups according to their body mass index (BMI): moderately obese (30 ≤ BMI ≤ 34.9 kg/m², n = 11), severely obese (35 ≤ BMI ≤ 39.9 kg/m², n = 20), morbidly obese (40 ≤ BMI ≤ 50 kg/m², n = 29), and very severely obese (BMI > 50 kg/m², n = 15). Results: The oxidation lag time for LDL from patients with a BMI ≥35 kg/m² was shorter than that for LDL from non‐obese controls (n = 13), whereas very‐low‐density lipoprotein oxidation lag times were not significantly different. The serum antibodies against modified LDL were similar in all groups, whereas the plasma vitamin E concentrations of obese patients were decreased (p ≤ 0.01). There was a negative correlation between LDL oxidation lag time and BMI (r = ?0.35, p = 0.0008), and between plasma vitamin E and BMI (r = ?0.53, p < 0.0001) and waist‐to‐hip ratio (r = ?0.40, p = 0.0003). Discussion: The LDL of nondiabetic, normotensive obese patients is more readily oxidized, and plasma vitamin E concentrations are low. These are both risk factors for coronary heart disease.