Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-alpha and TNF soluble receptors in women with overweight and obesity

The aims of the present study was to examine how overweight and obesity affect serum concentrations nitric oxide (NO) metabolites and to determine whether there is association between serum concentrations tumor necrosis factor (TNF)-alpha and TNF soluble receptors (sTNF-R) in subjects with overweight and obesity. The study groups involved 154 women: 102 obese (81 obese with body mass index [BMI] 30 to 40 kg/m2 and 21 obese with BMI > 40 kg/m2), 24 overweight patients, and 28 lean controls. Serum concentrations of NO metabolites and of TNF-alpha and its soluble receptors (sTNF-R1, sTNFR-2) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Serum concentration of insulin was measured by radioimmunoassay (RIA). Plasma glucose, cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglicerydes were determined by enzymatic procedure. Body composition was determined by impedance analysis using Bodystat (Douglas, British Isles). Serum concentrations of NO in the overweight group (35.1 +/- 12.1 micromol/L) and the obese groups with BMI 30 to 40 kg/m2 (32.8 +/- 9.3 micromol/L) and with BMI greater than 40 kg/m2 (33.3 +/- 8.5 micromol/L) were significantly higher when compared to controls (28.2 +/- 8.1 micromol/L): P < .05; P < .01, and P < .01, respectively. There was no difference in levels of NO between the overweight group and both obese groups. Serum concentration of TNF-alpha was also significantly higher in the group with overweight (6.5 +/- 3.1 pg/mL), in the obese group with BMI 30 to 40 kg/m2 (6.8 +/- 3.1 pg/mL), and in the obese group with BMI greater than 40 kg/m2 (7.4 +/- 2.6 pg/mL) when compared to controls (2.9 +/- 2.2 pg/mL): P < .00005; P < .00005, and P < .0000001, respectively. However, serum concentrations of sTNF-R1 and -R2 did not differ significantly between the overweight group, both obese groups, and controls. In conclusion, we observed increased serum concentrations of TNF-alpha and NO in overweight and obese women. It seems that there is an association between serum concentrations of TNF-alpha and NO; however, this relationship depends on the degree of obesity.     

Association of subclinical right ventricular dysfunction with obesity.

OBJECTIVES: The purpose of this research was to identify the determinants of right ventricular (RV) dysfunction in overweight and obese subjects. BACKGROUND: Right ventricular dysfunction in obese subjects is usually ascribed to comorbid diseases, especially obstructive sleep apnea. We used tissue Doppler imaging to identify the determinants of RV dysfunction in overweight and obese subjects. METHODS: Standard and tissue Doppler echocardiography was performed in 112 overweight (body mass index [BMI] 25 to 29.9 kg/m2) or obese (BMI >30 kg/m2) subjects and 36 referents (BMI <25 kg/m2), including 22 with obstructive sleep apnea but no obesity. Tissue Doppler was used to measure RV systolic (s(m)) and diastolic (e(m)) velocities and strain indexes. RESULTS: Obese subjects with BMI >35 kg/m2 had reduced RV function compared with referent subjects, evidenced by reduced s(m) (6.5 +/- 2.4 cm/s vs. 10.2 +/- 1.5 cm/s, p < 0.001), peak strain (-21 +/- 4% vs. -28 +/- 4%, p < 0.001), peak strain rate (-1.4 +/- 0.4 s(-1) vs. -2.0 +/- 0.5 s(-1), p < 0.001), and e(m) (-6.8 +/- 2.4 cm/s vs. -10.3 +/- 2.5 cm/s, p < 0.001), irrespective of the presence of sleep apnea. Similar but lesser degrees of reduced systolic function (p < 0.05) were present in overweight (BMI 25 to 29.9 kg/m2) and mildly obese (BMI 30 to 35 kg/m2) groups. Differences in RV e(m), s(m), and strain indexes were demonstrated between the severely versus overweight and mildly obese groups (p < 0.05). Body mass index remained independently related to RV changes after adjusting for age, log insulin, and mean arterial pressures. In obese patients, these changes were associated with reduced exercise capacity but not the duration of obesity and presence of sleep apnea or its severity. CONCLUSIONS: Increasing BMI is associated with increasing severity of RV dysfunction in overweight and obese subjects without overt heart disease, independent of sleep apnea.     

Associations among cardiometabolic risk factor clustering, weight status, and cardiovascular disease in an Appalachian population

It has been suggested that within the traditional body mass index (BMI) categories there is a heterogeneous pattern of cardiometabolic risk factor clustering. The objective of this research was to determine the associations among obesity, cardiometabolic abnormalities, and cardiovascular disease (CVD) in a large population-based study of Appalachian adults. The study comprised a cross-sectional survey of Appalachian adults residing in 6 communities in Ohio and West Virginia, who were aged 18 years and older (n=14,783, 50.9% women). The authors categorized BMI into normal weight (<25kg/m(2) ), overweight (25-29.9kg/m(2) ), and obese (≥30kg/m(2) ). Cardiometabolic abnormalities were defined as the presence of hypertension, elevated triglycerides (≥150mg/dL), decreased high-density lipoprotein cholesterol (<40mg/dL [men], <50mg/dL [women]), elevated fasting glucose (≥100mg/dL)/diabetes, insulin resistance (homeostasis model assessment >5.13), or elevated C-reactive protein (>3mg/L). They found that 25.6% of normal-weight adults displayed clustering of ≥2 cardiometabolic abnormalities; in contrast, 36.8% of overweight/obese adults displayed no clustering. Compared with normal-weight persons without clustering of cardiometabolic abnormalities (referent), the odds ratio of CVD was 1.06 (95% confidence interval [CI], 0.84-1.34) among overweight/obese individuals without cardiometabolic clustering, 2.21 (95% CI, 1.74-2.81) among normal-weight individuals with cardiometabolic clustering, and 2.45 (95% CI, 2.02-2.97) among overweight/obese individuals with cardiometabolic clustering. These results suggest that within the traditional BMI categories, there may be heterogeneity of CVD risk depending on whether there is underlying clustering of cardiometabolic abnormalities.     

Total ghrelin levels during acute insulin infusion in patients with polycystic ovary syndrome

Controversial data were reported concerning fasting ghrelin (decreased, normal or elevated) in polycystic ovary syndrome (PCOS). The aim of our study was to clarify ghrelin levels in non-obese, overweight, and obese PCOS patients; to investigate the effect of acute insulin infusion on ghrelin in PCOS as a chronic insulin-resistant state, with and without the impact of obesity, and to examine ghrelin-androgen interaction. In that order, we evaluated 1) ghrelin levels among 8 nonobese patients with PCOS [body mass index (BMI): 20.52+/-1.31 kg/m2], 8 overweight and obese patients with PCOS (BMI: 34.36+/-6.53 kg/m2) and their respective controls, 2) ghrelin suppression during euglycemic hyperinsulinemic clamp, and 3) ghrelin-androgen interrelationship. After overnight fast, 2-h euglycemic hyperinsulinemic clamp, was performed in all investigated women. Fasting ghrelin was significantly lower in non-obese PCOS than in controls (64.74+/-25.69 vs 108.36+/-52.60; p<0.05) as well as in overweight and obese PCOS in comparison with controls (38.71+/-14.18 vs 98.77+/-40.49; p<0.05). Insulin infusion significantly suppressed ghrelin in all subgroups of investigated women. Analysis of variance for repeatable measures confirmed that there was no significant difference in pattern of response between PCOS and controls. In conclusion, women with PCOS had lower fasting ghrelin and decreased insulin sensitivity independently of their BMI, compared to the controls. In addition, there were no differences between fasting ghrelin levels among non-obese, overweight, and obese women with PCOS. During euglycemic hyperinsulinemic clamp, ghrelin decreased in all studied groups to a similar extent, implying that, compared to chronic hyperinsulinemia, acute hyperinsulinemia reduces ghrelin levels independently of the degree of insulin resistance.     

Effect of increased body mass index on accuracy of two-dimensional echocardiography for measurement of left ventricular volume, ejection fraction, and mass

We used 2- and 3-dimensional echocardiography to determine left ventricular volume, mass, and ejection fraction in overweight (body mass index [BMI] > or = 25 kg/m2), obese (BMI > or = 30 kg/m2), and control (BMI < 25 kg/m2) subjects. Compared with corresponding magnetic resonance imaging measurements, 3-dimensional echocardiography is more accurate than 2-dimensional echocardiography in all patients, but particularly in overweight and obese subjects.     

Impaired response of cardiac autonomic nervous system to glucose load in severe obesity

OBJECTIVE: This study was undertaken to further analyze the response of the cardiovascular autonomic nervous system (ANS) to changes in plasma insulin concentration induced by an oral glucose load. We hypothesized that, as a consequence of insulin resistance, an inability of insulin to increase the sympathetic modulation of heart rate (HR) and blood pressure (BP) would be observed in normotensive obese patients. METHODS: We used spectral analysis to measure simultaneously the short-term variability of HR and BP in 23 never-obese subjects and in 70 normotensive overweight or obese patients subdivided into 3 subgroups: (1) overweight group (body mass index [BMI], 25-29.9 kg/m 2 ), n = 23; (2) class I-II obese group (BMI, 30-39.9 kg/m 2 ), n = 23; (3) class III obese group (BMI, > or =40 kg/m 2 ), n = 23. RESULTS: Oral glucose ingestion and the related increased insulinemia caused significant changes in the indices of sympathetic modulation (low-frequency [LF] power and LF/high-frequency ratio) of both HR and BP in normal weight, overweight, and obese subjects. However, the LF increments gradually decreased with the BMI classes, suggesting that sympathetic nervous system modulation in these subjects may be insulin-resistant. CONCLUSION: Obesity could develop resistance to the sympatho-excitatory effects of insulin that might play a role in the etiology of obesity. Spectral analysis of BP and HR can be used in research to evaluate the reactivity of the sympathetic nervous system in a manner that represents another feature of the obesity/insulin-resistance syndrome.     

Body fat distribution and cardiovascular disease risk factors in pre- and postmenopausal obese women with similar BMI

The aim of this study is to determine the body fat distribution and cardiovascular disease risk factors in pre- and postmenopausal obese women matched for weight, height and body mass index (BMI). Study group consisted of 405 premenopausal overweight/obese (BMI > 27 kg/m2, mean 37.83 +/- 6.91 kg/m2) and 405 postmenopausal overweight/obese (BMI > 27 kg/m2), BMI-matched (mean 37.77 +/- 6.84 kg/m2) women. None of the women were on hormone replacement therapy. Insulin resistance was evaluated by "homeostasis model assessment" (HOMA) formula. Intraabdominal fat volume was calculated according to the following formula: IAF (L) = [(0.370 x abdominal sagittal diameter) - 4.85]. Age, waist circumference, waist to hip ratio (WHR) and intraabdominal fat volume were significantly higher in postmenopausals compared with BMI-matched premenopausal women (p < 0.001). Systolic and diastolic blood pressure, glucose, uric acid, cholesterol and triglyceride were significantly higher (p < 0.001) and HDL-cholesterol was significantly lower (p < 0.05) in postmenopausals. No significant differences were observed with respect to insulin and HOMA. When age-matched pre- and postmenopausal women were compared, only total cholesterol was significantly higher in the postmenopausal group. However, older postmenopausal women (> 50 years) had significantly higher systolic blood pressure, waist circumference, WHR, glucose and uric acid concentrations compared with younger (< or = 50 years) postmenopausals. It is concluded that an increase in abdominal fat accumulation and unfavorable alterations in risk factors disturb postmenopausal obese women even if total body weight and BMI do not change during menopause transition. Ageing, particularly throughout the postmenopausal years, has important effects on the detrimental changes associated with menopause.     

The cardiovascular risk of young women with polycystic ovary syndrome: an observational, analytical, prospective case-control study

To evaluate the cardiovascular risk of polycystic ovary syndrome (PCOS), we investigated lipid profile, metabolic pattern, and echocardiography in 30 young women with PCOS and 30 healthy age- and body mass index (BMI)-matched women. PCOS women had higher fasting glucose and insulin levels, homeostasis model assessment score of insulin sensitivity, total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels, and TC/high density lipoprotein cholesterol (HDL-C) ratio and lower HDL-C levels than controls. Additionally, PCOS women had higher left atrium size (32.0 +/- 4.9 vs. 27.4 +/- 2.1 mm; P < 0.0001) and left ventricular mass index (80.5 +/- 18.1 vs. 56.1 +/- 5.4 g/m(2); P < 0.0001) and lower left ventricular ejection fraction (64.4 +/- 4.1 vs. 67.1 +/- 2.6%; P = 0.003) and early to late mitral flow velocity ratio (1.6 +/- 0.4 vs. 2.1 +/- 0.2; P < 0.0001) than controls. When patients and controls were grouped according to BMI [normal weight (BMI, >18 and <25 kg/m(2)), overweight (BMI, 25.1-30 kg/m(2)), and obese (BMI, >30 kg/m(2))], the differences between PCOS women and controls were maintained in overweight and obese women. In normal weight PCOS women, a significant increase in left ventricular mass index and a decrease in diastolic filling were observed, notwithstanding no change in TC, LDL-C, HDL-C, TC/HDL-C ratio, and TG compared with controls. In conclusion, our data show the detrimental effect of PCOS on the cardiovascular system even in young women asymptomatic for cardiac disease.     

B-type natriuretic peptide levels in obese patients with advanced heart failure.

Although recent studies show that obesity, or elevated body mass index (BMI), is associated with lower levels of B-type natriuretic peptide (BNP), it is unknown whether BMI affects the prognostic value of BNP in heart failure (HF). This study confirms the relationship between high BMI and low BNP in patients with advanced systolic HF. Despite relatively lower levels of BNP in overweight and obesity, BNP predicts worse symptoms, impaired hemodynamics, and higher mortality in HF at all levels of BMI.OBJECTIVES: This study aimed to examine the influence of obesity on the predictive value of the B-type natriuretic peptide (BNP) assay in heart failure (HF). BACKGROUND: Recent studies show that obesity, or elevated body mass index (BMI), is associated with lower circulating levels of BNP both in the general population and in patients with HF. METHODS: We analyzed data from 316 systolic HF (left ventricular ejection fraction [LVEF] < or =40%) patients [age, 53 +/- 13 years; mean LVEF, 24 +/- 7%; 48% ischemic] followed up at a university HF center. Patients were divided into categories of BMI: lean (BMI <25 kg/m2), overweight (BMI = 25 to 29.9 kg/m2), and obese (BMI > or =30 kg/m2). RESULTS: The BNP levels were significantly lower in overweight and obese compared with lean patients (p = 0.0001); median BNP (interquartile range) for the lean (n = 131), overweight (n = 99), and obese (n = 86) groups was 747 (272 to 1,300), 380 (143 to 856), and 332 (118 to 617) pg/ml, respectively. In each BMI category, elevated BNP was significantly associated with worse symptoms and higher pulmonary capillary wedge pressure. Higher BNP was also a significant independent predictor of survival independent of BMI. Optimal BNP cutoff for prediction of death or urgent transplant in lean, overweight, and obese HF patients was 590, 471, and 342 pg/ml, respectively. CONCLUSIONS: Although BNP levels are relatively lower in overweight and obese HF patients, BNP predicts worse symptoms, impaired hemodynamics, and higher mortality at all levels of BMI.     

The relationship of body mass index to outcomes after percutaneous coronary intervention

OBJECTIVES: To evaluate the effect of body mass index (BMI) on in-hospital outcomes in patients undergoing percutaneous coronary intervention (PCI) at a tertiary care hospital center in Ontario, Canada. BACKGROUND: Obesity is present in a large population of patients undergoing revascularization with PCI. METHODS: Retrospective analysis of 4,631 patients aged 62.0 +/- 12 years, stratified by BMI into five groups: nonobese (<25 kg/m2); overweight (25-29.9 kg/m2); class I obese (30-34.9 kg/m2); class II obese (35-39.9 kg/m2); and class III obese (> or =40 kg/m2). RESULTS: A BMI >25 kg/m2 was present in 79% of patients, and 35% were obese (BMI > or =30 kg/m2). Obese patients, particularly the class III obese, were significantly younger and had higher prevalence of diabetes, hypertension, and dyslipidemia (P < 0.0001). After adjustment for several covariates, lower BMI was independently associated with higher risk of major bleeding requiring transfusion (adjusted odds ratio [OR]= 1.40, 95% confidence interval [CI] 1.04-1.88, P = 0.025), and femoral hematoma (adjusted OR = 1.14, 95% CI 1.05-1.25, P = 0.003) in lean (<20 kg/m2) and normal BMI (20-24.9 kg/m2) patients. Obesity was not associated with death, myocardial infarction, repeat PCI, coronary artery bypass grafting, or major adverse cardiac event. CONCLUSIONS: Obesity is not associated with increased risk of adverse postprocedural in-hospital outcomes. These findings, however, do not discount the need for sustained efforts in secondary prevention of obesity and its consequences.     

The impact of obesity and disease on busulfan oral clearance in adults.

The apparent oral clearance (CL/F, mL/min) of busulfan was measured in 279 adolescent and adult patients. Significant (P <.05) determinants of CL/F by linear regression were: actual body weight (BW; r2 = 0.300), body surface area (BSA; r2 = 0.277), adjusted ideal body weight (AIBW; r2 = 0.265), and ideal body weight (IBW; r2 = 0.173); whereas body mass index (BMI), height, age, gender, and disease were less important predictors. CL/F (mL/min) for normal weight patients (BMI, 18 to 27 kg/m2) was 16.2% lower (P <.001) than for obese patients (BMI, 27 to 35 kg/m2). Thus, expressing CL/F relative to BW did not eliminate statistically significant differences between normal and obese patients. However, busulfan CL/F expressed relative to BSA (110 +/- 24 v 110 +/- 24 mL/min/m2, P = 1.0) or AIBW (3.04 +/- 0.65 v 3.19 +/- 0.67 mL/min/kg, P =.597) were similar in normal and obese patients. Non-Hodgkin's lymphoma patients (n = 10) had approximately 32% lower mean busulfan CL/F expressed relative to BW, BSA, or AIBW compared with patients with chronic myelogenous leukemia (n = 73). Routine dosing on the basis of BSA or AIBW in adults and adolescents does not require a specific accommodation for the obese. However, dosing based on BSA may be improved by considering CL/F differences in certain diseases. Adjusting dose for body size or disease does not diminish interpatient variability sufficiently to obviate plasma level monitoring in many indications.     

Elevated body mass index and intermediate-term clinical outcomes after acute coronary syndromes

PURPOSE: Obesity is a coronary disease risk factor, but its independent effect on clinical outcomes following acute coronary syndromes has not been quantified. We evaluated the relationship between elevated body mass index (BMI) and 30-day, 90-day, and 1-year clinical outcomes postacute coronary syndromes. SUBJECTS AND METHODS: Using 15 071 patients (normal weight [BMI = 18.5-24.9 kg/m(2)], overweight [BMI = 25-29.9 kg/m(2)], obese [BMI = 30-34.9 kg/m(2)] or very obese [BMI > or =35 kg/m(2)]) randomized from 1997-1999 in the SYMPHONY (Sibrafiban vs aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes) and 2nd SYMPHONY trials, we evaluated the relationships between BMI and 30-day, 90-day, and 1-year mortality and 30-day and 90-day death or myocardial infarction. RESULTS: Increasing BMI was associated with younger age, multiple comorbidities, and greater cardiac medication and procedure use; however, systolic function and coronary disease extent were similar for all BMI categories. Unadjusted Kaplan-Meier mortality estimates were higher for normal-weight patients than for all other BMI groups. After multivariable adjustment, the 30-day mortality hazard ratios (95% confidence interval [CI]) were: overweight, 0.66 (95% CI: 0.47 to 0.94); obese, 0.61 (95% CI: 0.39 to 0.97); very obese, 0.89 (95% CI: 0.48 to 1.64). Adjusted hazard ratios were similar for 90-day and 1-year mortality. There were no statistically significant differences among BMI groups in 30-day and 90-day death or myocardial infarction (unadjusted or adjusted). CONCLUSION: Overweight and obese BMI classifications were associated with better intermediate-term survival after acute coronary syndromes than normal weight and very obese, but death or myocardial infarction rates were similar. Further study is required to understand the apparent association of overweight and moderate obesity with better intermediate-term outcomes.     

Obesity and suppressed B-type natriuretic peptide levels in heart failure

OBJECTIVES: This investigation evaluated the relationship between obesity and B-type natriuretic peptide (BNP) in heart failure. BACKGROUND: Obesity is a major risk factor for the development of heart failure, but the precise mechanisms remain uncertain. Physiologically, natriuretic peptides and lipolysis are closely linked. METHODS: A total of 318 patients with heart failure were evaluated between June 2001 and June 2002. Levels of BNP were compared in obese (body mass index [BMI] > or =30 kg/m(2)) and nonobese (BMI <30 kg/m(2)) patients with respect to New York Heart Association functional class and lean body weight-adjusted peak aerobic oxygen consumption. In a subset of 36 patients, plasma levels of tumor necrosis factor-alpha, interleukin-6, and soluble intercellular adhesion molecule-1 were measured. RESULTS: The population's BMI was 29.4 +/- 6.6 kg/m(2); 24% were lean (BMI <25 kg/m(2)), 31% overweight (BMI > or =25 to 29.9 kg/m(2)), and 45% obese (BMI > or =30 kg/m(2)). Obese patients were younger, more often African American, and more likely to have a history of antecedent hypertension, but less likely to have coronary artery disease and with only a trend toward diabetes mellitus. Levels of BNP were significantly lower in obese than in nonobese subjects (205 +/- 22 and 335 +/- 39 pg/ml, respectively; p = 0.0007), despite a similar severity of heart failure and cytokine levels. Multivariate regression analysis identified BMI as an independent negative correlate of BNP level. There were no differences in emergency department visits, heart failure hospitalization, or death between the obese and nonobese patients at 12-month follow-up. CONCLUSIONS: Our investigation indicates that a state of reduced natriuretic peptide level exists in the obese individual with heart failure.     

Relation of body mass index to fatal and nonfatal cardiovascular events after cardiac rehabilitation

The aim of the present study was to determine whether body mass index (BMI) influences survival and recurrent cardiovascular events in a cardiac rehabilitation population. We followed 389 consecutive entrants to cardiac rehabilitation for 6.4 +/- 1.8 years. Patients were stratified into 3 groups: normal (BMI 18 to 24.9 kg/m(2)), overweight (BMI 25 to 29.9 kg/m(2)), and obese (BMI > or =30 kg/m(2)). Total and cardiovascular mortality were inversely associated with BMI category in bivariate models. However, only cardiovascular mortality was significant after adjustment for age and gender (p < 0.044), with cardiovascular death rates of 10% in normal, 8% in overweight, and 2% in obese patients. The rates of nonfatal recurrent events were 10% in normal, 24% in overweight, and 25% in obese patients. Our data indicate that BMI is inversely related to cardiovascular mortality but positively related to the risk of nonfatal recurrent events.     

Beta-cell hypersecretion and not reduced hepatic insulin extraction is the main cause of hyperinsulinemia in obese nondiabetic subjects.

Obesity is characterized by peripheral hyperinsulinemia, for which either beta-cell hypersecretion, diminished hepatic insulin extraction, or both may be responsible. To clarify this issue, we investigated insulin secretion and hormone hepatic extraction in 18 nondiabetic obese patients (body mass index [BMI], 39 +/- 1.3 kg/m2) and 18 healthy, lean control subjects (BMI, 21.3 +/- 0.7 kg/m2). Body fat distribution was calculated by measuring the waist to hip ratio (WHR). A highly reduced tissue insulin sensitivity (2.4 +/- 0.5 v 9.5 +/- 1.5 10(4).min-1/[microU/mL], P > .0005) and glucose effectiveness, ie, glucose's ability to stimulate its own disappearance at basal insulin (16 +/- 2 v 30 +/- 3 10(3).min-1, P > .005), were found in the overweight subjects compared with the controls. The basal (76 +/- 14 v 37 +/- 4 pmol/L/min) and total (377,848 +/- 5,562 v 16,864 +/- 1,850 pmol/L) prehepatic insulin secretion and the basal (15 +/- 2 v 7 +/- 0.7 pmol/L/min) and total (8,286 +/- 2,009 v 2,840 +/- 210 pmol/L) posthepatic insulin delivery were significantly higher in the overweight subjects compared with the controls (P < .005), whereas the mean hepatic insulin extraction did not differ (77.8% +/- 2.6% v 79.5% +/- 2.6%). A significant inverse correlation was found between the hepatic insulin extraction and the WHR (r = .5, P > .04), signifying the importance of fat distribution in insulin metabolism. The obese patients were subdivided into two subgroups according to their glucose tolerance; eight patients exhibited a normal tolerance and the remaining 10 were intolerant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Substantial weight gain during adulthood: the road to bariatric surgery

We sought to examine the relationship of body mass index (BMI) at age 18 years with the degree and rate of rise in body weight during adulthood among the morbidly obese. We evaluated 196 patients with a standard medical history form and a structured interview with questions regarding weight at age 18 years. The study included 40 (20.4%) men and 156 (79.6%) women. The mean BMI was 50.2+/-8.0 kg/m2, range 37.0-80.0 kg/m2. Based on self-reported weight, 133 (67.9%) were overweight/obese (BMI >25 kg/m2) and 68 (34.7%) were obese (BMI > or =30 kg/m2) at age 18 years. The distribution of cumulative weight gain was normal with a mean of 60.8+/-23.7 kg. There was a positive relationship (r=0.36, p<0.0001) between BMI at age 18 years and BMI in adulthood at a mean of 44+/-10.6 years. Independent predictors for cumulative adult weight gain were BMI at age 18 years (p<0.0001); women (p<0.0001); African Americans (p=0.05). These data suggest that modestly overweight young adults can have excessive weight gains during adult life, resulting in morbid obesity and high rates of obesity-related comorbidities.     

Obesity is an independent contributor to functional capacity and inflammation in systemic lupus erythematosus

OBJECTIVE: Obesity induces a proinflammatory state and is a major cause of morbidity in the general population. However, little is known about the effects of obesity in patients with chronic inflammatory illnesses such as systemic lupus erythematosus (SLE). METHODS: One hundred consecutive patients with SLE were studied to determine the relationship between body mass index (BMI) and functional capacity, measures of fatigue, quality of life, and the inflammation markers C-reactive protein (CRP), the erythrocyte sedimentation rate, and interleukin-6 (IL-6). The association between BMI and patient characteristics was determined, and multiple logistic regression models were used to adjust for age, sex, disease activity, and disease-related damage. RESULTS: Thirty-three patients had a normal BMI (< 25 kg/m(2)), 28 were overweight (25-29.9 kg/m(2)), and 39 were obese (> or =30 kg/m(2)). Obese patients had worse functional capacity, more fatigue, and higher concentrations of inflammation markers. The mean +/- SD modified Health Assessment Questionnaire (M-HAQ) score was 0.6 +/- 0.4 in obese patients compared with 0.3 +/- 0.4 and 0.2 +/- 0.3 in overweight patients and those with a normal BMI, respectively (P = 0.001). The mean +/- SD concentrations of CRP in obese patients (10.0 +/- 8.6 mg/liter) were higher than those in patients who were overweight (4.7 +/- 5.4 mg/liter) or had a normal BMI (6.2 +/- 9.9 mg/liter) (P < 0.001). Similarly, concentrations of IL-6 were higher in obese patients (P = 0.003). After adjusting for age, sex, disease activity, and damage indices, the associations between BMI and CRP (P < 0.001), M-HAQ scores (P = 0.005), and IL-6 concentrations (P = 0.01) remained significant. CONCLUSION: Obesity is independently associated with impaired functional capacity and inflammation markers in patients with lupus. Thus, weight loss may improve functional capacity and decrease cardiovascular risk factors.     

Impact of body mass index on outcomes following critical care

STUDY OBJECTIVES: To determine the impact of body mass index (BMI) on outcomes in critically ill patients. DESIGN: Retrospective analysis of a large multi-institutional ICU database. MEASUREMENTS: The influence of BMI classification (underweight, < 20 kg/m(2); normal [control subjects], 20 to 25 kg/m(2); overweight, 25 to 30 kg/m(2); obese, 30 to 40 kg/m(2); severe obesity, > 40 kg/m(2)) on hospital survival, functional status at hospital discharge, and ICU/hospital length of stay (LOS) was analyzed via multivariate analysis, adjusting for age, gender, type of hospital admission, and severity score (ie, simplified acute physiologic score [SAPS] II and mortality prediction model [MPM] at time zero). Univariate analysis also was performed according to the quartile of the severity score. All comparisons were to the normal BMI group. RESULTS: Of 63,646 patient datasets, 41,011 were complete for height, weight, and at least one of the two severity scores. We found increased mortality in underweight patients (odds ratio [OR] of death: SAPS group, 1.19; MPM group, 1.26) but not in overweight, obese, or severely obese patients. ICU and hospital LOS were increased in both the severely obese (OR of discharge: ICU, 0.81 and 0.84, respectively; hospital, 0.83 and 0.87, respectively) and underweight groups (OR of discharge: ICU, 0.96 and 0.94, respectively; hospital, 0.91 and 0.90, respectively). Only in the SAPS group did the obese group have increased ICU LOS (OR, 0.96) and hospital LOS (OR, 0.96). Functional status at discharge was impaired in underweight patients (OR of disability: ICU, 1.11; hospital, 1.19). Overweight patients had decreased discharge disability (OR of disability: SAPS, 0.93; MPM, 0.94), while the results in the obese group were discordant between the two severity score groups (SAPS, not significant; MPM, 0.91; p < 0.05 for all ORs). CONCLUSIONS: Low BMI, but not high BMI, is associated with increased mortality and worsened hospital discharge functional status. LOS is increased in severely obese patients and, to a lesser extent, in underweight patients. Patients in the overweight and obese BMI groups may have improved mortality and discharge functional status.     

Clinical profile and outcomes of obese patients in cardiac rehabilitation stratified according to National Heart, Lung, and Blood Institute criteria

PURPOSE: Obesity is a major health problem and must be evaluated and treated in cardiac rehabilitation patients. The purpose of this study was to identify the scope of this problem in an urban-based cardiac rehabilitation program by evaluating the prevalence of obesity, and comparing the clinical and risk factor profiles and outcomes of patients stratified according to National Heart, Lung, and Blood Institute (NHLBI) weight classifications. METHODS: Four hundred forty-nine consecutive cardiac rehabilitation patients, aged 57 +/- 11 years, were stratified according to the NHLBI criteria as: normal (body mass index [BMI] 18-24.9 kg/m2), overweight (BMI 25-29.9 kg/m2), class I/II obese (BMI 30-39.9 kg/m2), and class III morbidly obese (BMI > or = 40 kg/m2). Baseline cardiac risk factors and dietary habits were identified, and both pre- and postexercise training measurements of exercise tolerance, weight, and lipid profile were obtained. RESULTS: Overweight and obesity (BMI > or = 25 kg/m2) were present in 88% of patients. Compared to normal weight patients, obese patients were younger and had a greater adverse risk profile (higher prevalence of diabetes and hypertension, larger waist circumference, lower exercise capacity, lower high-density lipoprotein cholesterol level) at entry. After 10 weeks, all groups had a significant increase in exercise capacity, and on average obese patients in each category lost weight (Class I/II--4 lbs and Class III--12 lbs). Dropout rates were similar among the groups. CONCLUSION: Overweight and obesity are highly prevalent in cardiac rehabilitation. Overweight and obese patients had a greater adverse cardiovascular risk profile, including a lower exercise capacity in the latter. Thus, targeted interventions toward weight management in contemporary cardiac rehabilitation programs are important. Although short-term outcomes appear promising, greater efforts to improve these outcomes and to support long-term management are needed.     

Two polymorphisms in the peroxisome proliferator-activated receptor-gamma gene are associated with severe overweight among obese women.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor that regulates adipocyte differentiation. Variations in the PPARgamma gene may affect the function of the PPARgamma and, therefore, body adipocity. We investigated the frequencies of the Pro12Ala polymorphism in exon B and the silent CAC478CAT polymorphism in exon 6 of the PPARgamma gene and their effects on body weight, body composition, and energy expenditure in obese Finns. One hundred and seventy obese subjects [29 men and 141 women; body mass index (BMI), 35.7 +/- 3.8 kg/m2; age, 43 +/- 8 yr; mean +/- SD) participated in the study. The frequencies of the Ala12 allele in exon B and CAT478 allele in exon 6 were not significantly different between the obese and population-based control subjects (0.14 vs. 0.13 and 0.19 vs. 0.21, respectively). The polymorphisms were associated with increased BMI [Pro12Pro, 34.5 +/- 3.8; Pro12Ala, 34.8 +/- 3.1; Ala12Ala, 39.2 +/- 4.6 kg/m2 (P = 0.011); CAC478CAC, 34.5 +/- 3.8; CAC478CAT, 34.5 +/- 3.3; CAT478CAT, 37.7 +/- 4.1 kg/m2 (P = 0.046)]. In addition, the women with both Ala12Ala and CAT478CAT genotypes (n = 5) were significantly more obese compared with the women having both Pro12Pro and CAC478CAC genotypes (n = 85; BMI, 40.6 +/- 3.3 vs. 34.4 +/- 3.9 kg/m2; P = 0.001), and they had increased fat mass (46.8 +/- 9.1 vs. 36.8 +/- 7.5 kg; P = 0.005). In conclusion, the Pro12Ala and CAC478CAT polymorphisms in the PPARgamma gene are associated with severe overweight and increased fat mass among obese women.