Markers for the gene ob and serum leptin levels in human morbid obesity

Leptin, the product of the ob gene, reduces body fat in genetically obese animals and circulates in elevated concentrations in the blood of obese patients. Polymorphic markers situated in the proximity of the human ob gene have recently been suggested to be linked to morbid obesity. We have studied the possible association between the microsatellite markers near the ob gene and morbid obesity in 252 morbidly obese patients with a mean body mass index (BMI) of 43 ± 7 kg/m², and 151 lean controls with a mean BMI of 22 ± 2 kg/m², and searched for linkage of these gene markers to obesity in 76 affected sib-pairs (BMI ≥ 32). No significant association was observed between any of the eight microsatellite markers and morbid obesity, and affected-sib-pair analysis failed to show linkage of three selected ob gene markers to obesity in the sibships. There was a strong positive correlation between serum leptin levels and BMI in morbidly obese patients; a carrier status for either of the two most prevalent alleles of the microsatellite marker D7S530 in the vicinity of the ob gene was associated with serum leptin levels in the obese subjects. Two of the markers (D7S2519, D7S649) showed a significant relation to the weight-losing response to a 16-week very-low-calorie dietary intervention. We have thus been able to confirm a tight relationship between serum leptin and body mass but have found no evidence for genetic linkage of the ob gene markers to morbid obesity in a population considered to represent a genetic isolate and to be an ideal model for studies of complex disorders. Received: 25 October 1996 / Revised: 4 December 1996     

Biochemical and Anthropometric Characterization of Morbid Obesity in a Large Utah Pedigree

A Utah family with morbid obesity was extended to include 122 persons in four generations for the purpose of characterizing anthropometric and biochemical variables in family members with and without morbid obesity. Seventy-seven subjects had blood drawn for biochemical analyses. Of the 77 subjects, 12 were morbidly obese (≥44.5 kg or 100 pounds overweight), 20 were between 22.5–45.4 kg (50 and 99 pounds) overweight and 45 were less than 22.5 kg (50 pounds) overweight Sixty-two randomly-ascertained controls were used for comparisons of age- and gender-adjusted study variables. Morbidly obese subjects had mean body mass indices (BMI) of 41.0 kg/m² (62 kg over ideal weight) compared to 25.3 kg/m² (10 kg overweight) in the <22.5 kg family members (p<0.001). The <22.5 kg family members had lower BMI than the random controls (27.6 kg/m², p<0.05), indicating clear bimodality of obesity within the pedigree. Percent body fat from bioelectrical impedance was 35% versus 24% in the morbidly obese and the <22.5 kg subjects, respectively. Ideal body weight was similar among the three pedigree weight groups. Hip and waist circumferences were much larger in the morbidly obese and the waist-to-hip ratio remained significantly greater in the morbidly obese subjects compared to the <22.5 kg group. Morbidly obese subjects had elevated triglycerides and VLDL-C levels, low HDL-levels, and normal LDL-C levels. Fasting insulin was the best predictor of morbid obesity of all biochemical and lipid measurements (odds ratio of 4.5). Fasting insulin levels and the insulin-to-glucose ratio were more than twice as high as control levels. Even after adjusting for differences in BMI, fasting insulin and the insulin to glucose ratio were elevated in the morbidly obese subjects indicating that insulin levels were inappropriately high for their weight compared to this relationship found in the other groups. Adjusted insulin levels for the 22.5–45.4 kg group were similar to controls, indicating insulin level was at the predicted level for their weight. In conclusion, individuals with morbid obesity appeared to have greater insulin resistance than could be explained by their weight. CHD risk from elevated LD L-C was not present, but CHD risk was increased by the so-called multiple metabolic syndrome (insulin resistance, high triglycerides and low HDL-C).     

Cigarette Smoking Is Associated with a Lower Prevalence of Newly Diagnosed Diabetes Screened by OGTT than Non-Smoking in Chinese Men with Normal Weight

Different studies have produced conflicting results regarding the association between smoking and diabetes mellitus, and detailed analysis of this issue in Chinese males based on nationwide samples is lacking. We explored the association between cigarette smoking and newly-diagnosed diabetes mellitus (NDM) in Chinese males using a population-based case-control analysis; 16,286 male participants without previously diagnosed diabetes were included. Prediabetes and NDM were diagnosed using the oral glucose tolerance test. The cohort included 6,913 non-smokers (42.4%), 1,479 ex-smokers (9.1%) and 7,894 current smokers (48.5%). Age-adjusted glucose concentrations (mmol/L) were significantly lower at fasting and 120 min in current smokers than non-smokers (5.25 vs. 5.30, 6.46 vs. 6.55, respectively, both P < 0.01). After adjustment for demographic and behavioral variables (age, region, alcohol consumption status, physical activity, education, and family history of diabetes), logistic regression revealed significant negative associations between smoking and NDM in males of a normal weight (BMI < 25 kg/m²: adjusted odds ratio [AOR] = 0.75, P = 0.007; waist circumference < 90 cm: AOR = 0.71, P = 0.001) and males living in southern China (AOR = 0.75, P = 0.009), but not in males who were overweight/obese, males with central obesity, or males living in northern China. Compared to non-smokers, current smokers were less likely to be centrally obese or have elevated BP (AOR: 0.82 and 0.74, both P < 0.05), and heavy smokers (≥ 20 pack-years) were less likely to have elevated TG (AOR = 0.84, P = 0.012) among males of a normal weight. There were no significant associations between quitting smoking and metabolic disorders either among males of a normal weight or males who were overweight/obese. In conclusion, smokers have a lower likelihood of NDM than non-smokers among Chinese males with a lower BMI/smaller waist.     

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.     

Emotional and Affective Temperaments in Smoking Candidates for Bariatric Surgery

Introduction

The prevalence of smoking habits in severe obesity is higher than in the general population. There is some evidence that smokers have different temperaments compared to non-smokers. The aim of this study is to evaluate the associations between smoking status (smokers, ex-smokers and non-smokers) and temperament characteristics in bariatric surgery candidates.

Methods

We analyzed data on temperament of 420 bariatric surgery candidates, as assessed by the AFECTS scale, in an exploratory cross-sectional survey of bariatric surgery candidates who have been grouped into smokers, ex-smokers and non-smokers.

Results

We detected significant statistical differences in temperament related to the smoking status in this population after controlling the current use of psychiatric medication. Smokers had higher anxiety and lower control than non-smokers. Ex-smokers with BMI >50 kg/m² presented higher coping and control characteristics than smokers.

Conclusions

Smoking in bariatric surgery candidates was associated with lower control and higher anxious temperament, when controlled by current use of psychiatric medication. Smokers with BMI >50 kg/m² presented lower coping and control than ex-smokers. Assessment of temperament in bariatric surgery candidates may help in decisions about smoking cessation treatment and prevention of smoking relapse after surgery.     

Regional body volumes, BMI, waist circumference, and percentage fat in severely obese adults

Objective: This study presents total body volume (TBV) and regional body volume, and their relationships with widely used body composition indices [BMI, waist circumference (WC), and percentage body fat (% fat)] in severely obese adults (BMI ≥35 kg/m²). Research Methods and Procedures: We measured TBV, trunk volume (TV), arm volume (AV), leg volume (LV), and WC and estimated % fat in 32 severely obese persons with BMI 36 to 62 kg/m² (23 women; age, 19 to 65 years; weight, 91 to 182 kg) and in 58 persons with BMI <35 kg/m² (28 women; age, 18 to 83 years; weight, 48 to 102 kg) using a newly validated 3‐day photonic image scanner (3DPS, Model C9036–02, Hamamatsu Co., Japan) and calculated TV/TBV, AV/TBV, and LV/TBV. Results: Men had significantly larger TBV and higher TV/TBV and AV/TBV, but significantly lower LV/TBV than women, independently of BMI. TV/TBV increased while AV/TBV and LV/TBV decreased with increasing BMI, WC, and % fat, and the rate of increase in TV/TBV per % fat was significantly greater in severely obese individuals than in individuals with BMI <35 kg/m². The relationships for TBV with % fat were much lower than with BMI or WC. Conclusion: Body volume gains were mainly in the trunk region in adults, irrespective of sex or BMI. For a given BMI, WC, or % fat, men had a significantly larger TV than women. The implication is that men could have higher health risks due to having higher trunk body weight as a proportion of total body weight compared with severely obese or less severely obese women.     

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.     

Plasma Adiponectin Levels in Overweight and Obese Asians

Objective: Hypoadiponectin has been documented in subjects with obesity, diabetes mellitus, or coronary heart disease, suggesting a potential use of plasma adiponectin in following the clinical progress in subjects with metabolic syndrome (MS). In this study, we investigated the plasma adiponectin levels in relation to the variables of MS among overweight/obese Asian subjects. Research Methods and Procedures: The plasma adiponectin, anthropometric and biochemical measurements, oral glucose tolerance tests (OGTT), and modified insulin suppression tests were performed on 180 overweight/obese Asian subjects [body mass index (BMI) ≥ 23 kg/m²], including 47 subjects with morbid obesity (BMI ≥ 40 kg/m²). Results: The plasma adiponectin levels negatively correlated with BMI, waist-to-hip ratio, fasting plasma glucose, insulin, triglyceride, uric acid levels, hyperinsulinemia, and glucose intolerance in OGTT, but positively with high-density lipoprotein-cholesterol. In contrast, they were not related to blood pressure and total cholesterol. Moreover, insulin sensitivity, measured by quantitative insulin sensitivity check index (QUICKI) or in insulin suppression tests, significantly correlated with the plasma adiponectin levels. Among morbidly obese subjects, only the waist-to-hip ratio correlated with the plasma adiponectin levels. Using multivariate linear regression models, the area under curve of plasma glucose in OGTT and high-density lipoprotein-cholesterol among the overweight/obese subjects and WHR among the morbidly obese subjects were significantly related to the plasma adiponectin levels after adjustment for other variables. Discussion: In overweight/obese Asians, the plasma adiponectin levels significantly correlated with various indices of MS except hypertension. Whether the plasma adiponectin level could be a suitable biomarker for following the clinical progress of MS warrants further investigation.     

The influence of body composition, fat distribution, and sustained weight loss on left ventricular mass and geometry in obesity

Alterations in left ventricular mass and geometry vary along with the degree of obesity, but mechanisms underlying such covariation are not clear. In a case–control study, we examined how body composition and fat distribution relate to left ventricular structure and examine how sustained weight loss affects left ventricular mass and geometry. At the 10‐year follow‐up of the Swedish obese subjects (SOS) study cohort, we identified 44 patients with sustained weight losses after bariatric surgery (surgery group) and 44 matched obese control patients who remained weight stable (obese group). We also recruited 44 matched normal weight subjects (lean group). Dual‐energy X‐ray absorptiometry, computed tomography, and echocardiography were performed to evaluate body composition, fat distribution, and left ventricular structure. BMI was 42.5 kg/m², 31.5 kg/m², and 24.4 kg/m² for the obese, surgery, and lean groups, respectively. Corresponding values for left ventricular mass were 201.4 g, 157.7 g, and 133.9 g (P < 0.001). In multivariate analyses, left ventricular diastolic dimension was predicted by lean body mass (β = 0.03, P < 0.001); left ventricular wall thickness by visceral adipose tissue (β = 0.11, P < 0.001) and systolic blood pressure (β = 0.02, P = 0.019); left ventricular mass by lean body mass (β = 1.23, P < 0.001), total body fat (β = 1.15, P < 0.001) and systolic blood pressure (β = 2.72, P = 0.047); and relative wall thickness by visceral adipose tissue (β = 0.02, P < 0.001). Left ventricular adjustment to body size is dependent on body composition and fat distribution, regardless of blood pressure levels. Obesity is associated with concentric left ventricular remodeling and sustained 10‐year weight loss results in lower cavity size, wall thickness and mass.     

The Systemic Inflammome of Severe Obesity before and after Bariatric Surgery

Introduction

Obesity is associated with low-grade systemic inflammation. The “inflammome” is a network layout of the inflammatory pattern. The systemic inflammome of obesity has not been described as yet. We hypothesized that it can be significantly worsened by smoking and other comorbidities frequently associated with obesity, and ameliorated by bariatric surgery (BS). Besides, whether or not these changes are mirrored in the lungs is unknown, but obesity is often associated with pulmonary inflammation and bronchial hyperresponsiveness.

Objectives

We sought to: (1) describe the systemic inflammome of morbid obesity; (2) investigate the effects of sex, smoking, sleep apnea syndrome, metabolic syndrome and BS upon this systemic inflammome; and, (3) determine their interplay with pulmonary inflammation.

Methods

We studied 129 morbidly obese patients (96 females; age 46±12 years; body mass index [BMI], 46±6 kg/m²) before and one year after BS, and 20 healthy, never-smokers, (43±7 years), with normal BMI and spirometry.

Results

Before BS, compared with controls, all obese subjects displayed a strong and coordinated (inflammome) systemic inflammatory response (adiponectin, C-reactive protein, interleukin (IL)-8, IL-10, leptin, soluble tumor necrosis factor-receptor 1(sTNF-R1), and 8-isoprostane). This inflammome was not modified by sex, smoking, or coexistence of obstructive sleep apnea and/or metabolic syndrome. By contrast, it was significantly ameliorated, albeit not completely abolished, after BS. Finally, obese subjects had evidence of pulmonary inflammation (exhaled condensate) that also decreased after BS.

Conclusions

The systemic inflammome of morbid obesity is independent of sex, smoking status and/or comorbidities, it is significantly reduced by BS and mirrored in the lungs.     

Magnetic Resonance Imaging of Changes in Abdominal Compartments in Obese Diabetics during a Low-Calorie Weight-Loss Program

ObjectivesTo investigate changes in the fat content of abdominal compartments and muscle area during weight loss using confounder-adjusted chemical-shift-encoded magnetic resonance imaging (MRI) in overweight diabetics.MethodsTwenty-nine obese diabetics (10/19 men/women, median age: 59.0 years, median body mass index (BMI): 34.0 kg/m²) prospectively joined a standardized 15-week weight-loss program (six weeks of formula diet exclusively, followed by reintroduction of regular food with gradually increasing energy content over nine weeks) over 15 weeks. All subjects underwent a standardized MRI protocol including a confounder-adjusted chemical-shift-encoded MR sequence with water/fat separation before the program as well at the end of the six weeks of formula diet and at the end of the program at 15 weeks. Fat fractions of abdominal organs and vertebral bone marrow as well as volumes of visceral and subcutaneous fat were determined. Furthermore, muscle area was evaluated using the L4/L5 method. Data were compared using the Wilcoxon signed-rank test for paired samples.ResultsMedian BMI decreased significantly from 34.0 kg/m² to 29.9 kg/m² (p < 0.001) at 15 weeks. Liver fat content was normalized (14.2% to 4.1%, p < 0.001) and vertebral bone marrow fat (57.5% to 53.6%, p = 0.018) decreased significantly throughout the program, while fat content of pancreas (9.0%), spleen (0.0%), and psoas muscle (0.0%) did not (p > 0.15). Visceral fat volume (3.2 L to 1.6 L, p < 0.001) and subcutaneous fat diameter (3.0 cm to 2.2 cm, p < 0.001) also decreased significantly. Muscle area declined by 6.8% from 243.9 cm² to 226.8 cm².ConclusionMRI allows noninvasive monitoring of changes in abdominal compartments during weight loss. In overweight diabetics, weight loss leads to fat reduction in abdominal compartments, such as visceral fat, as well as liver fat and vertebral bone marrow fat while pancreas fat remains unchanged.     

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.     

Determinants of insulin-resistant phenotypes in normal-weight and obese Black African women

Objective: Subsets of metabolically “healthy obese” and “at‐risk” normal‐weight individuals have been previously identified. The aim of this study was to explore the determinants of these phenotypes in black South African (SA) women. Methods and Procedures: From a total of 103 normal‐weight (BMI ≤ 25 kg/m²) and 122 obese (BMI ≥ 30 kg/m²) black SA women, body composition, fat distribution, blood pressure, fasting glucose levels, insulin resistance, and lipid profiles were measured. Questionnaires relating to family history, physical activity energy expenditure (PAEE), and socio‐demographic variables were administered. The subjects were classified as insulin sensitive or insulin resistant according to the homeostasis model assessment of insulin resistance (HOMA‐IR) (≥1.95 insulin resistant). Results: Our study showed that 22% of the normal‐weight women were insulin resistant and 38% of the obese women were insulin sensitive. Increased visceral adipose tissue (VAT) (P = 0.001) and decreased VAT/leg fat mass (P ≤ 0.001), independent of total body fatness, distinguished between the phenotypes. Moreover, the insulin‐sensitive women were of higher socioeconomic status, did more leisure and vigorous PAEE and were less likely to use injectable contraceptives. Using a regression model, body fat distribution, percent body fat, age, log leisure PAEE, and use of injected contraception accounted for 35% of the variance in HOMA‐IR in the normal‐weight women. In the obese women, 34% of the variance in HOMA‐IR was explained by the same variables, excluding PAEE. No differences in smoking status or family history of metabolic disease were found between the phenotypes. Discussion: Central fat distribution, total adiposity, socioeconomic status, leisure PAEE, and use of injectable contraceptives distinguished between insulin‐sensitive and insulin‐resistant black SA women.     

Familial Aggregation of Morbid Obesity

Recent studies have shown major gene effects for obesity in randomly ascertained families. To investigate the familial aggregation of a specific subset of obesity, which is particularly prone to medical complications, families with morbid obesity were studied. This condition occurs in 1%-2%of the population and is defined as 45.5 kg (100 pounds) or more over ideal weight. First-degree relatives of 221 morbidly obese probands (1560 adults) were identified, and height and weight (current and greatest) were obtained from each family member. Morbid obesity occurred in the family members of the probands 8 times more often than in the general population. Of the morbidly obese probands, 48% had one or more first-degree relatives who were also morbidly obese compared to a 6% population estimate. By the ages of 20–24, 12% of the morbidly obese probands were already 45.5 kg or more overweight, and 45% were 22.7 kg (50 pounds) or more overweight. There was little difference in the prevalence of familial morbid obesity by the gender of the probands: 47% of the male probands and 48% of the female probands had another morbidly obese relative, while 67% and 53% of the early onset (before age 25) male and female probands, respectively, had one or more first-degree relatives who were also morbidly obese. In addition to the extreme degree of familial aggregation, the prevalence of morbid obesity in parent-offspring sets was calculated within the morbidly obese families. Morbidly obese families who have one or two morbidly obese parents have a 2.6 times increased risk (p<0.002) of having one or more morbidly obese adult offspring, compared to families who have neither parent morbidly obese. Evidence for trimodality of the body mass index distribution was found for each gender (p = 0.0006 for male relatives and p = 0.075 for female relatives). The strong familial aggregation of morbid obesity indicates the need for further understanding of the genetic determinants of this extreme clinical disorder and how environmental factors affect the genetic expression of the trait. (OBESITY RESEARCH 1993;1:261–270)     

Air Displacement Plethysmography: Validation in Overweight and Obese Subjects

Objective: Patients with moderate and severe obesity, because of their physical size, often cannot be evaluated with conventional body composition measurement systems. The BOD POD air displacement plethysmography (ADP) system can accommodate a large body volume and may provide an opportunity for measuring body density (D_b) in obese subjects. D_b can be used in two‐ or three‐compartment body composition models for estimating total body fat in patients with severe obesity. The purpose of this study was to compare D_b measured by ADP to D_b measured by underwater weighing (UWW) in subjects ranging from normal weight to severely obese. Research Methods and Procedures: D_b was measured with UWW and BOD POD in 123 subjects (89 men and 34 women; age, 46.5 ± 16.9 years; BMI, 31.5 ± 7.3 kg/m²); 15, 70, and 10 subjects were overweight (25 ≤ BMI < 30 kg/m²), obese (30 ≤ BMI < 40 kg/m²), and severely obese (BMI ≥ 40 kg/m²), respectively. Results: There was a strong correlation between D_b(kilograms per liter) measured by UWW and ADP (r = 0.94, standard error of the estimate = 0.0073 kg/L, p < 0.001). Similarly, percent fat estimates from UWW and ADP using the two‐compartment Siri equation were highly correlated (r = 0.94, standard error of the estimate = 3.58%, p < 0.001). Bland‐Altman analysis showed no significant bias between D_b measured by UWW and ADP. After controlling for D_b measured by ADP, no additional between‐subject variation in D_b by UWW was accounted for by subject age, sex, or BMI. Discussion: Body density, an important physical property used in human body composition models, can be accurately measured by ADP in overweight and obese subjects.     

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.     

Lower than predicted resting metabolic rate is associated with severely impaired cardiorespiratory fitness in obese individuals

Obese individuals have reduced cardiorespiratory fitness as compared with leaner counterparts. Regular exercise maintains or increases fitness and lean body mass. Lean body mass, in turn, has a direct impact on resting metabolic rate (RMR). Given these relationships, we sought to evaluate the association between RMR and cardiorespiratory fitness in obese individuals. We evaluated 64 obese individuals (78% female) with direct assessment of RMR and cardiorespiratory fitness via breath‐by‐breath measurement of oxygen consumption and carbon dioxide production at rest and during exercise. The mean age and BMI were 47.4 ± 12.2 years and 47.2 ± 9.2 kg/m², respectively. The majority of subjects, 69%, had a measured RMR above that predicted by the Harris‐Benedict equation. Compared with the higher RMR group, those with a lower than predicted RMR had increased BMI, with values of 52.9 vs. 44.7 kg/m², P = 0.001, respectively. Analysis of those demonstrating significant effort during cardiopulmonary exercise testing (peak respiratory exchange ratio ≥1.10) revealed a significantly higher peak oxygen uptake (VO₂ peak) in the higher RMR group (17.3 ± 3.5 ml/min/kg) compared with the lower RMR group (13.6 ± 1.9 ml/min/kg), P = 0.003. In summary, a lower than predicted RMR was associated with a severely reduced VO₂ peak and a higher BMI in this cohort. These data suggest that morbid obesity may be a vicious cycle of increasing BMI, reduced cardiorespiratory fitness, muscle deconditioning, and lower RMR. Collectively, these responses may, over time, exacerbate the imbalance between energy intake and expenditure, resulting in progressive increases in body weight and fat stores.     

Bariatric Surgery in Morbidly Obese Insulin Resistant Humans Normalises Insulin Signalling but Not Insulin-Stimulated Glucose Disposal

Aims

Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB), and compared this to lean volunteers.

Materials and Methods

The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR) in eight morbidly obese (body mass index, BMI=47.3±2.2 kg/m²) patients, before and after RYGB, and in eight lean volunteers (BMI=20.7±0.7 kg/m²). Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR₅₀) and maximal (GDR₁₀₀) GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity.

Results

Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001). Weight-loss of 29.9±4 kg after surgery significantly improved GDR₅₀ (P=0.004) but not GDR₁₀₀ (P=0.3). These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001). Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA), and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA), and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively).

Conclusions

Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss.     

Relationships Between the Body Mass Index and Body Composition

The aims of this study were to evaluate the Body Mass Index (BMI) (weight/stature²) as a proxy for percent body fat (%BF) and to determine its association with fat-free mass (FFM). Multivariate analysis of variance and partial correlations were used to examine relationships between BMI and %BF and FFM from densitometry for 504 men and 511 women, aged 20 to 45 years. Sensitivity/specificity analyses used cut offs of 28 kg/m² in men and 26 kg/m² in women for BMI, and 25% in men and 33% in women for %BF. Significantly higher associations existed in each gender between BMI and %BF in the upper BMI tertile than in the lower BMI tertiles. In the lower BMI tertiles, correlations between BMI and FFM were approximately twice as large as those between BMI and %BF. The BMI correctly identified about 44% of obese men, and 52% of obese women when obesity was determined from %BF. BMI is an uncertain diagnostic index of obesity. Results of Receiver Operator Characteristic (ROC) analyses using %BF and total body fat, both provided a BMI of 25 kg/m² in men and 23 kg/m² in women as diagnostic screening cut offs for obesity.     

BMI Is the Main Determinant of the Circulating Leptin in Women after Vertical Banded Gastroplasty

Objective: To assess the main determinant of serum leptin concentration changes in morbidly obese patients treated by banded vertical gastroplasty. Research Methods and Procedures: Serum leptin and insulin concentrations, insulin resistance, BMI, body weight, and body fat mass in 18 obese women and 8 obese men treated by vertical banded gastroplasty were studied. Lean women and men subjects were used as controls. Results: Before surgery, serum leptin and insulin concentrations and insulin resistance index were significantly higher in morbidly obese patients than in control subjects. BMI, body fat mass, and serum triacylglycerol concentrations were also significantly higher in obese than in lean subjects. All of these parameters gradually decreased during 50 weeks after surgery. Univariate regression analysis displayed significant correlations between the following: serum leptin concentration and BMI (and body fat mass), serum leptin concentration and serum insulin concentration, and serum leptin concentration and insulin resistance index. Multivariate regression analysis indicated that only BMI was independently correlated with the decrease in serum leptin concentration. Discussion: Obtained data suggest the following: 1) vertical banded gastroplasty causes reduction of body weight, serum leptin and insulin concentration, insulin resistance, and serum triacylglycerol concentration; and 2) BMI is the main determinant of the circulating leptin concentration in morbidly obese women after anti‐obesity surgery.