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Psychoanalytic treatment of the obese person. Part III.

This paper is an attempt to clarify some of the issues which face the psychiatrist in his efforts at treating the obese patient through analytic means. A thoroughgoing bias in Western culture impairs the psychiatric and non-psychiatric medical care of the obese person. Inconclusive evidence concerning the causal relation between obesity and chronic disease does not deter this cultural bias from exaggerating the role that obesity is thought to play in disease process. Whatever contribution it makes to physical illness, obesity remains a substantial social disability that is frequently associated with self-hate and feelings of ineffectiveness. Scientific investigations indicate that adiposity is determined by interactions of genetic and environmental influences acting at different levels of complexity within the organism. Hence, the adipocyte itself may influence existing fatness and retard weight reduction. Constitutional factors affecting the hypothalamus may contribute to obesity in certain individuals. Also, cortical effects determine maladaptive eating behavior and excessive adiposity. Poor eating habits which are associated with emotional conflict seem to strongly affect the development and continuance of obesity in most fat persons. The interaction among adipocyte, hypothalamus, and cerebral cortex remains unclear. The various treatments of obesity have been shown to be of little impact in helping overweight persons to sustain weight loss. Diet control, exercise, group psychotherapy, and behavior modification show slight benefit. Recent controlled studies dispute earlier claims that behavior modification is effective in achieving meaningful and lasting weight loss. Claims that intestinal bypass procedures are a useful treatment also require further supporting evidence. Psychoanalytic or intensive sustained psychotherapeutic treatment of the obese person emphasizes exploration of the entire personality. As long-neglected constructive forces are stregthened, weight loss may proceed. Psychoanalytic treatment is not indicated for obesity uncomplicated by neurotic distortions. In the presence of interpersonal problems and personal ineffectiveness, psychoanalysis has real utility. It is not clear that obesity is a major determinant of impaired physical or emotional health. Rather, the medical indictment of obesity seems to stem from the need to justify an intensely negative cultural bias. Casual disregard of this fact and of the complexity involving issues of etiology and treatment may signify inadequate appreciation in the psychoanalyst of the extent to which he participates in this cultural bias. The continuing failure of medical science to devise a means to help fat persons sustain weight loss to any meaningful degree has prevented the development of studies which would show if weight reduction truly does provide uniformly enhanced physical and emotional well-being...

Dreams↗

Lessons in obesity from transgenic animals.

Many genetic manipulations have created models of obesity, leanness or resistance to dietary obesity in mice, often providing insights into molecular mechanisms that affect energy balance, and new targets for anti-obesity drugs. Since many genes can affect energy balance in mice, polymorphisms in many genes may also contribute to obesity in humans, and there may be many causes of primary leptin resistance. Secondary leptin resistance (due to high leptin levels) can be investigated by combining the ob mutation with other obesity genes. Some transgenic mice have failed to display the expected phenotype, or have even been obese when leanness was expected. Compensatory changes in the expression of other genes during development, or opposing influences of the gene on energy balance, especially in global knockout mice, may offer explanations for such findings. Obesity has been separated from insulin resistance in some transgenic strains, providing new insights into the mechanisms that usually link these phenotypes. It has also been shown that in some transgenic mice, obesity develops without hyperphagia, or leanness without hypophagia, demonstrating that generalised physiological explanations for obesity in individual humans may be inappropriate. Possibly the most important transgenic model of obesity so far created is the Type 1 11beta-hydroxysteroid dehydrogenase over-expressing mouse, since this models the metabolic syndrome in humans. The perspectives into obesity offered by transgenic mouse models should assist clinical researchers in the design and interpretation of their studies in human obesity.

Adipose Tissue↗

Erectile dysfunction associates with endothelial dysfunction and raised proinflammatory cytokine levels in obese men.

Erectile and endothelial dysfunction may have some shared pathways through a defect in nitric oxide activity. We evaluated associations between erectile function, endothelial function and markers of systemic vascular inflammation in 80 obese men, aged 35-55 yr, divided into two equal groups according to the presence/absence of erectile dysfunction. Compared with non-obese age-matched men [no.=50, body mass index (BMI)=24 +/- 1], obese men (all) had impaired indices of endothelial function as suggested by the reduced mean blood pressure and platelet aggregation responses to L-arginine, and higher circulating concentrations of the proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-18 (IL-18), as well as C-reactive protein (CRP). The mean erectile function score was 14 +/- 4 (range 7-19) in obese men with erectile dysfunction and 23.5 +/- 1 (range 22-25) in obese men without erectile dysfunction. Endothelial function showed a greater impairment in impotent obese men as compared with potent obese men. The mean blood pressure and platelet aggregation decreases following L-arginine were -1.5 +/- 1.1 mmHg and -1.1 +/- 1.2%, respectively, in obese men with erectile dysfunction, and -3.4 +/- 1.2 mmHg and -5.6 +/- 2.1%, respectively, in obese men without erectile dysfunction (p < 0.01). Circulating CRP levels were significantly higher in obese men with erectile dysfunction as compared with obese men without erectile dysfunction (p < 0.05). Erectile function score was positively associated with mean blood pressure responses to L-arginine and negatively associated with BMI, waist-to-hip ratio (WHR), and CRR Erectile and endothelial dysfunction associate in obese men and may contribute to their raised cardiovascular risk through impaired nitric oxide availability elicited by a low-grade inflammatory state.

Adult↗

Association of polymorphisms in the beta2-adrenergic receptor gene with obesity, hypertriglyceridaemia, and diabetes mellitus.

To assess the role of polymorphisms in the beta2-adrenergic receptor gene in the development of obesity and obesity-related metabolic disorders, we analysed Arg16Gly, Gln27Glu, and Thr164Ile polymorphisms in 400 non-obese subjects (body mass index < 27 kg/m2) and 108 obese subjects (body mass index> or =27 kg/m2). The Gln27Glu substitution was twice as common in obese subjects as in non-obese subjects (0.14 vs 0.07, p = 0.001, odds ratio 2.14, 95 % confidence interval 1.35-3.41). The frequency of the Glu27 allele was also higher in patients with Type II (non-insulin-dependent) diabetes mellitus than nondiabetic subjects (0.14 vs 0.07, p = 0.001, odds ratio 2.13, 95% confidence interval 1.34-3.41). Analysis of variance of multiple variables showed an association between 2-h post-load glucose concentrations and body mass index but not with the Glu27 variant, suggesting that the association with diabetes could be secondary to obesity. Obese subjects carrying the variant allele had higher concentrations of serum triglyceride than obese subjects homozygous for the wild type allele (2.68+/-1.90 vs 1.18+/-1.15 mmol/l, p = 0.02). Conversely, the frequency of Gly16 homozygotes was lower in obese women when compared with non-obese women (11% vs 28%, p = 0.01, odds ratio 0.30, 95% confidence interval 0.12-0.75), although the association was not present in male subjects. Thr164Ile substitution was not detected in the subjects of this study. These observations suggest that the amino-terminal polymorphisms of the beta2-adrenergic receptor gene could be involved in the molecular pathogenesis of obesity and hypertriglyceridaemia, and thereby the development of Type II diabetes mellitus.

Amino Acid Substitution↗

A potential role for angiotensin II in obesity induced cardiac hypertrophy and ischaemic/reperfusion injury.

BACKGROUND: The mechanisms for obesity induced myocardial remodelling and subsequent mechanical dysfunction are poorly understood. There is good evidence that angiotensin II and TNFalpha have strong growth promoting properties and are elevated with obesity. In addition, these two peptides may interact to exacerbate myocardial ischaemic/reperfusion injury. HYPOTHESIS: Obesity increases systemic and myocardial renin-angiotensin system (RAS) activity and TNFalpha levels and contributes to obesity induced cardiac remodelling and ischaemic/reperfusion injury. METHODS: Male Wistar rats were placed on a standard rat chow diet or cafeteria diet for 16 weeks. Two additional groups of rats received the respective diets and losartan (30 mg/ kg/d) in their drinking water. Hearts were perfused on the isolated working rat heart perfusion system and mechanical function was documented before and after 15 min normothermic total global ischaemia. Blood and myocardial samples were collected for angiotensin II, TNFalpha and NADPH oxidase activity determinations. RESULTS: The rats on the cafeteria diet became obese compared to rats on the standard rat chow (438 +/- 5.9 g vs 393 +/- 7.3 g for control, p < 0.05). Obesity was associated with elevated serum angiotensin II (0.050 +/- 0.015 pmol/ml vs. 0.035 +/- 0.003 pmol/ml, p < 0.05) and TNFalpha levels (42.8 +/- 5.93 pg/ml vs. 13.18 +/- 2.50 pg/ml, p < 0.05), and increased heart to body weight ratios (3.1 +/- 0.04 mg/g vs. 2.8 +/- 0.03 mg/g, p < 0.05). Losartan had no effect on body weight but decreased basal myocardial angiotensin II and TNFAlpha levels as well as heart to body weight ratio in the obese and lean controls (2.5 +/- 0.05 mg/g and 2.6 +/- 0.04 mg/g relative to their controls, p < 0.05). Hearts from obese rats had lower reperfusion aortic outputs (AO) than their concurrent controls (18.42 +/- 1.17 ml/min vs. 27.8 +/- 0.83 ml/min, p < 0.05). Losartan improved aortic output recoveries in obese rats (23.0 +/- 1.71 ml/min, p < 0.05). CONCLUSIONS: Obesity increased serum angiotensin II and TNFalpha levels, blood pressure, and heart weight to body weight ratios. These changes were associated with decreased basal and post-ischaemic myocardial mechanical function. Chronic AT(1) receptor antagonism prevented the adverse changes in heart weight, mechanical function and susceptibility to ischaemic/reperfusion injury. Although current data do not exclude additional mechanisms for obesity induced cardiac remodelling, they suggest that angiotensin II may contribute to obesity induced cardiac remodelling and ischaemic/reperfusion injury.

Angiotensin II↗

Duration of obesity is a risk factor for non-insulin-dependent diabetes mellitus, not for arterial hypertension or for hyperlipidaemia.

Obesity is often accompanied by non-insulin-dependent diabetes mellitus (type 2), arterial hypertension, and hyperlipidaemia. The aim of this study was to evaluate whether duration of obesity is a risk factor for the appearance of type 2 diabetes, hypertension, and hyperlipidaemia. We studied 760 obese subjects, 207 of whom had normal glucose tolerance, 125 impaired glucose tolerance, and 428 type 2 diabetes; in addition, 560 had hypertension and 315 had hyperlipidaemia. At univariate analysis, passing from normal through impaired glucose tolerance to type 2 diabetes there was a progressive increase of age and of duration of obesity, hypertension and hyperlipidaemia. Compared to subjects without hypertension, hypertensive subjects were older, had a longer duration of obesity, a greater body mass index (BMI, kg/m2), and more frequently a family history of hypertension; they also more frequently showed impaired glucose tolerance and type 2 diabetes and hyperlipidaemia. Compared to subjects without hyperlipidaemia, hyperlipidaemic subjects were older, had a longer duration of obesity, and more frequently showed impaired glucose tolerance and type 2 diabetes, and hypertension. Diabetes, hypertension, and hyperlipidaemia were highly associated, as up to 80% of subjects with type 2 diabetes had hypertension, and more than 80% of hyperlipidaemic subjects had hypertension. Type 2 diabetes was less frequent than hypertension and hyperlipidaemia during the first 10 years of obesity, and progressively increased thereafter; in contrast the frequency of hypertension and of hyperlipidaemia increased only after 30 years of obesity. In 359 subjects undergoing an oral glucose tolerance test (168 with simultaneous determination of insulin release), increasing durations of obesity were accompanied by an increasing prevalence of type 2 diabetes, and in deterioration of glucose response, with no decrease in insulin release. At logistic regression analysis, age was a common risk factor for diabetes, hypertension, and hyperlipidaemia; duration of obesity and hyperlipidaemia were additional risk factors for diabetes; family history of hypertension, BMI and hyperlipidaemia were additional risk factors for hypertension, as were impaired glucose tolerance or diabetes, and hypertension for hyperlipidaemia. These data indicate that duration of obesity is a risk factor for type 2 diabetes, and emphasize the importance of preventing obesity in young subjects.

Adult↗

Polyunsaturated fatty acids in plasma lipids of obese children with and without metabolic cardiovascular syndrome.

Previously we reported significantly higher values of gamma-linolenic acid (GLA, 18:3n-6), dihomo-gamma-linolenic acid (DHGLA, 20:3n-6), and arachidonic acid (20:4n-6) in plasma lipid classes in obese children than in nonobese controls. In the present study, fatty acid composition of plasma phospholipids (PL) and sterol esters (STE) was determined by high-resolution capillary gas-liquid chromatography in obese children with and without metabolic cardiovascular syndrome [MCS: defined as simultaneous presence of (i) dyslipidemia, (ii) hyperinsulinemia, (iii) hypertension, and.(iv) impaired glucose tolerance] and in nonobese controls. Fatty acid composition of PL and STE lipids did not differ between obese children without MCS and controls. Obese children with MCS exhibited significantly lower linoleic acid (LA, 18:2n-6) values in PL (17.43 [2.36], % wt/wt, median [range from the first to the third quartile]) than obese children without MCS (19.14 [3.49]) and controls (20.28 13.80]). In contrast, PL GLA values were significantly higher in obese children with (0.13 [0.08]) than in those without MCS (0.08 [0.04]), whereas STE GLA values were higher in obese children with MCS (1.04 [0.72]) than in controls (0.62 [0.48]). DHGLA values in PL were significantly higher in obese children with MCS (4.06 [0.74]) than in controls (2.69 [1.60]). The GLA/LA ratio was significantly higher, whereas the AA/DHGLA ratio was significantly lower in obese children with MCS than in obese children without MCS and in controls. In this study, LA metabolism was affected only in obese children with but not in those without MCS. In obese children with MCS, delta6-desaturase activity appeared to be stimulated, whereas delta5-desaturase activity appeared to be inhibited. Disturbances in LA metabolism may represent an additional health hazard within the multifaceted clinical picture of MCS.

Adolescent↗

Regulation of lipid synthesis in hepatocytes from lean and obese Zucker rats.

Fatty acid synthesis and CO2 production were evaluated in hepatocytes from lean and obese Zucker rats in the presence of 3H2O, and several carbon precursors. The incorporation of 3H2O into fatty acids was greater in obese compared to lean rats in both the isolated hepatocyte and in vivo. The rates of incorporation of 3H2O into fatty acids and cholesterol in hepatocytes of both lean and obese rats were linear for 2 hr, in the absence or presence of 16.7 mM glucose. Rates of fatty acid synthesis were higher in the presence of 16.7 mM glucose compared to the absence of glucose in both lean and obese while rates of cholesterol synthesis were similar. The incorporation of 3H2O into fatty acids, but not into cholesterol, was correlated with increasing glucose concentration and was 2 to three-fold higher in hepatocytes of obese compared to lean rats in the presence of several carbon precursors. Differences in CO2 production between lean and obese rats suggested increased pentose phosphate shunt activity, decreased pyruvate dehydrogenase activity, and lower tricarboxylic acid cycle activity in obese rats. Fatty acid synthesis and CO2 production from 3H2O and [U-14C]glucose in hepatocytes of lean and obese rats was similarly elevated by insulin and depressed by glucagon at several concentrations, suggesting that hepatocytes of obese animals respond to these hormones. These data indicate that rates of hepatic fatty acid synthesis although higher in obese rats respond to modulation in a fashion which is similar to the response in lean rats. The present studies suggest that the oxidation of several carbon precursors in the tricarboxylic acid cycle is diminished in obese compared to lean rats, but pentose phosphate shunt activity is greater in the obese Zucker rats.

Animals↗

In vitro insensitivity of glucose transport and antilipolysis to insulin due to receptor and postreceptor abnormalities in obese Pima Indians with normal glucose tolerance.

The in vitro sensitivities of glucose transport and antilipolysis to insulin and insulin binding were measured in adipocytes isolated from three groups of normal glycemic male Pima Indians--10 lean (11% to 22% body fat), 11 moderately obese (26% to 34% body fat), and 7 severely obese (37% to 40% body fat) subjects. Both a half-maximum concentration of insulin for the stimulation of glucose transport (ED50 [transport]) and a half-maximum concentration of insulin for the suppression of 25 nmol/L isoproterenol-stimulated lipolysis (ED50 [antilipolysis]) were significantly (P less than 0.05) greater in the moderately obese subjects than in the lean subjects as well as greater in the severely obese group than in the moderately obese group. Mono 125I-(Tyr A14)-insulin binding per cell in the presence of 25, 100, and 200 pm insulin was similar among lean, mildly obese, and severely obese subjects. 125I-insulin binding per cell surface area of adipocytes isolated from either moderately or severely obese Indians was significantly lower (P less than 0.005) than that of lean Indians. However, there was a similar insulin binding per cell surface area between mildly and severely obese subjects. These results indicate that diminished insulin binding per cell surface area may explain decreased sensitivity of transport and antilipolysis to insulin in moderately obese subjects relative to lean subjects. In contrast, these diminished sensitivities in the severely obese subjects relative to moderate obese subjects are not explained by a change in insulin binding and, therefore, are presumably induced by an abnormality of a postbinding step of insulin action.

Adipose Tissue↗

Serum cholesterol, lecithin-cholesterol acyltransferase, and hepatic hydroxymethylglutaryl coenzyme A reductase activities of lean and obese Zucker rats.

Serum cholesterol concentrations, lecithin-cholesterol acyltransferase (LCAT), and hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activities of lean and obese Zucker rats were compared. The excess serum cholesterol of the female obese rat is found to be mainly free cholesterol associated with very low-density lipoproteins, whereas that of the male obese rat is carried as cholesterol esters associated with high-density lipoproteins. The high level of serum free cholesterol in the female obese rat is not due to a deficiency in lecithin-cholesterol acyltransferase activity. This enzyme activity is found to be elevated in the male obese rat. Hepatic HMG-CoA reductase activity declines as rats mature; this observation is most apparent in obese male rats. Lean rats exhibit the normal diurnal rhythm, but mature obese rats show little diurnal variation in HMG-CoA reductase activity. Obese female rats maintain high reductase activities, but the activities of obese male rats remain low at all times. Starvation suppresses liver HMG-CoA reductase and serum cholesterol in both lean and obese female rats. Thus, an increase in hepatic cholesterol synthesis may contribute to hypercholesterolemia in the obese female Zucker rat. On the other hand, factors such as nonhepatic synthesis or a decreased cholesterol catabolism may play more important roles in maintaining high serum cholesterol in the obese male Zucker rat.

Animals↗

Metabolic and sympatho-adrenal abnormalities in the obese Zucker rat: effect of chronic phenoxybenzamine treatment.

The obese Zucker rat manifests a number of physiologic and metabolic abnormalities which are controlled or modulated by the sympatho-adrenal system. The interrelationship of these was examined by subjecting 3-4 month old male, homozygous lean and obese Zucker rats to various stresses which are known to activate the sympatho-adrenal system, and by chronic (16-19 days) phenoxybenzamine (PBZ) treatment to block alpha-adrenergic receptors. Both obese and lean PBZ treated rats gained only 1% and 10% of the body weight of their respective control rats during the treatment period, while only the lean rats had a significant reduction (20%) in food intake. Control obese rats failed to maintain rectal temperature after 4 hr at 7 degrees C and their relative output of plasma catecholamines (CA) to cold stress, as measured from indwelling atrial cannulae, was decreased. PBZ treatment did not alter this rectal temperature response although it was associated with increased baseline norepinephrine levels (at ambient temperature 21-22 degrees C) and relative output of CA in the obese rats, suggesting tat sympathetic neural activity was increased under these circumstances. No abnormalities of sympatho-adrenal function, as reflected in plasma CA levels, were found in treated or control obese rats immobilization for 1 hr followed by decapitation. Simultaneously obtained baseline plasma glucose levels were similar in untreated lean and obese rats, but insulin and glycerol levels in the obese rat were 1350% and 213% of lean values, respectively. During sequential stresses, the obese rats became markedly hyperglycemic and hyperglycerolemic compared to the lean rats, while insulin levels were decreased more in the obese than lean rats (12-15% versus 34-35% of controls, respectively). PBZ affected insulin levels only in the obese rats, reducing their baseline levels by 4-fold and stressed induced levels to those seen in the lean control rats. These results suggest that some of the metabolic and physiologic abnormalities of the obese Zucker rat which are modulated by the sympatho-adrenal system can be normalized by procedures which increase sympatho-adrenal activity.

Animals↗

The effects of gender and age on associations between blood lipid levels and obesity in Danish men and women aged 35-65 years.

The purpose of the study was to assess the influence of gender and age on the associations between different measures of obesity, and blood lipid levels. Overall obesity (body fat, body fat percentage and body mass index) or abdominal obesity (waist/hip-ratio, waist/thigh-ratio and waist-circumference) and lipid levels [high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), total cholesterol and triglyceride level] were measured in 1987/88 in a random Danish population sample of men and women (N = 2987), aged 35, 45, 55 and 65 yr. All lipid levels were dependent on gender and age. The associations between most measures of obesity and HDL or LDL were independent of gender and age, whereas, with a few exceptions, associations between measures of obesity and total cholesterol, VLDL or triglycerides were dependent on gender and/or age. Compared to levels of HDL, LDL and total cholesterol, abdominal obesity specifically affected levels of VLDL or triglycerides, whereas overall obesity affected HDL, LDL, VLDL, total cholesterol and triglyceride levels more evenly. When men and women were compared, associations between the measures of obesity and blood lipids were stronger in men than in women of the same age, except for the associations between measures of abdominal obesity and VLDL or triglycerides in 45-year-old women. No age trend was found for associations between the measures of obesity and VLDL or triglycerides, whereas young age-groups showed stronger associations between obesity and total cholesterol than older age-groups. Failure to consider age/gender effects induces bias and may lead to misleading conclusions regarding the bivariate association between obesity and lipids, and further may make results from population studies incomparable.

Adult↗

Multiple defects occur in the guanine nucleotide regulatory protein system in liver plasma membranes of obese (fa/fa) but not lean (Fa/Fa) Zucker rats: loss of functional Gi and abnormal Gs function.

Hepatocyte membranes from both lean and obese Zucker rats exhibited adenylate cyclase activity that could be stimulated by glucagon, forskolin, NaF and elevated concentrations of p[NH]ppG. In membranes from lean animals, functional Gi was detected by the ability of low concentrations of p[NH]ppG to inhibit forskolin-activated adenylate cyclase. This activity was abolished by treatment of hepatocytes with either pertussis toxin or the phorbol ester TPA, prior to making membranes for assay of adenylate cyclase activity. In hepatocyte membranes from obese animals no functional Gi activity was detected. Quantitative immunoblotting, using an antibody able to detect the alpha subunit of Gi, showed that hepatocyte plasma membranes from both lean and obese Zucker rats had similar amounts of Gi-alpha subunit. This was 6.2 pmol/mg plasma membrane for lean and 6.5 pmol/mg plasma membrane for obese animals. Using thiol pre-activated pertussis toxin and [32P]-NAD+, similar degrees of labelling of the 40 kDa alpha subunit of Gi were found using plasma membranes of both lean and obese Zucker rats. We suggest that liver plasma membranes from obese Zucker rats express an inactive Gi alpha subunit. Thus lesions in liver Gi functioning are seen in insulin-resistant obese rats and in alloxan- and streptozotocin-induced diabetic rats which also show resistance as regards the acute actions of insulin. Liver plasma membranes of obese animals also showed an impairment in the coupling of glucagon receptors to Gs-controlled adenylate cyclase, with the Kd values for activation by glucagon being 17.3 and 126 nM for lean and obese animals respectively. Membranes from obese animals also showed a reduced ability for high concentration of p[NH]ppG to activate adenylate cyclase. The use of [32P]-NAD+ and thiol-preactivated cholera toxin to label the 43 kDa and 52 kDa forms of the alpha-subunit of Gs showed that a reduced labelling occurred using liver plasma membranes from obese animals. It is suggested that abnormalities in the levels of expression of primarily the 52 kDa form of alpha-Gs may give rise to the abnormal coupling between glucagon receptors and adenylate cyclase in liver membranes from obese (fa/fa) Zucker rats.

Adenosine Diphosphate Ribose↗

Obesity and clinical restenosis after coronary stent placement.

BACKGROUND: Obesity has been associated with improved clinical outcomes after percutaneous coronary intervention--"obesity paradox." METHODS: We studied 6186 patients pooled from 6 major coronary stent clinical trials. Clinical restenosis was defined as target lesion revascularization (TLR) at 1 year. Body mass index was classified according to World Health Organization criteria as underweight (< 18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), obesity class I (30-34.9 kg/m2), and obesity class II/III (> or = 35 kg/m2). Multivariable logistic regression analysis was used to evaluate the effect of obesity class on TLR. RESULTS: Compared with normal-weight patients, there was a trend to more frequent TLR in patients of obesity class II/III (13.6% vs 10.9%, P = .08). After adjustment for previously defined predictors of TLR, other than the obesity-related intermediate states of diabetes and hypertension, obesity class II/III was associated with 1.33-fold (95% CI 1.00-1.78) higher odds of TLR. In an analysis restricted to patients without diabetes or hypertension, obesity class II/III was also associated with significantly higher odds of undergoing TLR (odd ratio [OR] 2.14, 95% CI 1.21-3.77). CONCLUSION: After coronary stenting, the odds of undergoing TLR were higher in patients with obesity class II/III compared with normal-weight patients. The significant association of severe obesity in nondiabetic and normotensive patients suggests that other obesity-associated mechanisms such as insulin resistance and inflammation should be further explored.

Aged↗

A comprehensive examination of health conditions associated with obesity in older adults.

BACKGROUND: Over 70% of older adults in the United States are overweight or obese. To examine the overall health burden of obesity in older adults, the Vitamins and Lifestyle cohort study of western Washington State recruited 73,003 adults aged 50 to 76 who completed a self-administered questionnaire on current height and weight, medical history, and risk factors. METHODS: Cross-sectional analysis of body mass index (BMI) and health conditions was performed using data collected in 2000 to 2002. Participants were categorized as normal weight, overweight, obese I, or obese II/III using BMI cut-points. Health conditions included 7 serious diseases, 2 conditions associated with cardiovascular disease risk, 23 medical conditions, and 11 health complaints. Odds ratios (ORs) from logistic regression models were used to examine associations of the four BMI categories with each health condition. Analyses were gender stratified and adjusted for age, education, race/ethnicity, and smoking status. RESULTS: Among women, 34% were overweight, 16% in the obese I category, and 10% in obese categories II/III. Among men, 49% were overweight, 18% in the obese I category, and 6% in obese categories II/III. Overall, 37 of 41 conditions examined for women and 29 of 41 conditions examined for men were associated with increased levels of BMI (trend p <0.05 for all models). For women and men, respectively, the highest ORs comparing obese II/III to normal weight were diabetes (OR=12.5 and 8.3), knee replacement (OR=11.7 and 6.1), and hypertension (OR=5.4 and 5.6). Obesity also increased the odds of several rare diseases such as pancreatitis (OR=1.9 and 1.5) and health complaints such as chronic fatigue (OR=3.7 and 3.5) and insomnia (OR=3.5 and 3.1). CONCLUSIONS: A broad range of diseases and health complaints are associated with obesity. Clinicians should be aware of the diverse ways in which being overweight or obese may affect the health of their patients when counseling them about weight loss.

Age Distribution↗

Plasma leptin and its relationship with lipid peroxidation and nitric oxide in obese female patients with or without hypertension.

BACKGROUND: Recent evidence suggested that leptin-induced oxidative stress in human endothelial cells in vivo and increased oxidative stress in human essential hypertension may further contribute to both the development of atherosclerosis and other cardiovascular diseases. We investigated the association of plasma leptin levels with plasma lipid peroxidation and nitric oxide metabolites (NOx) in obese hypertensive atherosclerosis model. METHODS: Plasma leptin, lipid peroxidation and NOx levels were determined in age-matched non-obese normotensive female subjects (n = 30), obese normotensive female subjects (n = 45), and obese hypertensive female subjects (n = 50). Plasma leptin levels were determined by immunoradiometric method. Lipid peroxidation was determined as thiobarbituric acid reactive substances (TBARS) using spectrophotometric method. NOx levels were determined using enzymatic method. RESULTS: We found that plasma leptin and TBARS levels were increased in obesity, and obese hypertensives have significantly higher plasma leptin and TBARS levels than obese normotensives (p <0.001 and p <0.001). Obese hypertensives have significantly lower plasma NOx levels than obese normotensives (p <0.001). In univariate and multivariate regression analysis, plasma leptin levels were significantly correlated with TBARS (p <0.01 and p <0.01) in obese subjects. Plasma TBARS were also inversely correlated with NOx in hypertensive obese subjects (r = -0.412, p <0.01). CONCLUSIONS: Our results have shown that elevated leptin levels may be associated with increased oxidative stress and free-radical-induced decreased NOx levels. Therefore, hyperleptinemia may be an important contributor to the generation of hypertension in obesity.

Atherosclerosis↗

Obesity increases the risk for persisting obstructive sleep apnea after treatment in children.

OBJECTIVE: To evaluate the impact of obesity at diagnosis on treatment outcomes in paediatric obstructive sleep apnea (OSA). METHODS: Children were included if they had both diagnostic and follow-up studies for OSA. Anthropological and polysomnographic data were collected at the time of both studies. Polysomnograms were scored using standard criteria and OSA was defined as a respiratory disturbance index (RDI) >or=5. Obesity was defined as a body mass index standard deviation (z-)score (BMIsds) greater than 2, adjusted for age and gender. RESULTS: For 69 children (49 males), mean age was 7.1+/-4.2 years and 29 (42%) children were obese. There was no significant difference in RDI between obese and non-obese children at diagnostic study. Following adenotonsillectomy the obese children had a significantly higher mean RDI (10.7+/-15.6 versus 3.7+/-4.3; p=0.01). Disease resolution occurred in 77.5% of non-obese compared to 45% of obese children (p=0.011). The odds ratio (OR) for persistent OSA in obese compared to non-obese children was 4.2 (95% CI: 1.5-11.9; p=0.005). Using initial RDI as a covariate, these data show that obesity in children has an adjusted OR for persistent OSA after adenotonsillectomy 3.7 (95% CI: 1.3-10.8, p=0.016). CONCLUSION: For children, obesity at the time of diagnosis is a major risk for persisting OSA after treatment, regardless of the severity of initial disease.

Adenoidectomy↗

Alterations in left ventricular structure and function in young healthy obese women: assessment by echocardiography and tissue Doppler imaging.

OBJECTIVES: This study was designed to determine the effects of obesity on left ventricular (LV) structure and function in young obese women. BACKGROUND: Severe prolonged obesity in older adults results in increased plasma volume, eccentric LV hypertrophy, and systolic and diastolic dysfunction. Obese women are at increased risk for the development of heart failure. However, the effects of the obesity on cardiac structure and function in young, otherwise-healthy women are controversial. METHODS: Fifty-one women were evaluated: 20 were obese (body mass index [BMI] > or =30 kg/m(2)) and 31 were non-obese (BMI <30 kg/m(2)). Left ventricular structure and systolic and diastolic function were assessed by two-dimensional echocardiography and tissue Doppler imaging, including the load-independent systolic myocardial velocity (Sm global) and early diastolic myocardial velocity (Em global), respectively. The effects of BMI on LV structure and function were assessed using multivariate regression analyses. RESULTS: Obese women had higher end-diastolic septal and posterior wall thickness, LV mass, and relative wall thickness than non-obese women; BMI values showed significant correlations with these variables (r = 0.58, p < 0.0001; r = 0.50, p < 0.0002; r = 0.52, p < 0.0001, and r = 0.40, p < 0.005, respectively). The Sm global and Em global were lower in obese women, suggesting systolic and diastolic function are decreased; both were negatively correlated with BMI (r = -0.43, p <. 002 and r = -0.61, p < 0.0001, respectively). Multivariate analysis showed BMI was the only independent predictor of relative wall thickness, Sm global, and Em global. CONCLUSIONS: Obesity in young otherwise-healthy women is associated with concentric LV remodeling and decreased systolic and diastolic function. These early abnormalities in LV structure and function may have important implications for explaining the myocardial dysfunction that is associated with increased cardiovascular morbidity and mortality caused by obesity.

Adult↗