Massively Obese Research Articles

Release of mitogenic factors by cultured preadipocytes from massively obese human subjects.

In this study, possible paracrine factors in adipose tissue from lean and obese subjects were sought. Conditioned media were prepared by incubation in alpha minimum essential medium of adipocyte precursors derived from lean and massively obese subjects. Adipocyte-precursor-derived conditioned media from the obese stimulated replication of cultured rat perirenal adipocyte precursors by about fourfold over control. The effect of media conditioned by precursors derived from lean subjects was much less evident. The mitogenicity of conditioned media was abolished by trypsin, indicating the protein nature of the mitogenic factor(s). Sephacryl S-200 chromatography of adipocyte-precursor-derived conditioned media from obese subjects revealed one major active fraction with molecular masses in the range of 25,000-40,000. Our results demonstrate that adipocyte precursors derived from massively obese subjects release factors mitogenic on cultured rat adipocyte precursors. These principles may act as paracrine factors contributing to the development of the adipocyte hyperplasia characteristic of massive obesity.

Sex steroid, gonadotropin, cortisol, and prolactin levels in healthy, massively obese women: correlation with abdominal fat cell size and effect of weight reduction.

To examine hormonal status in obese, gynecologically normal women we studied 25 regularly menstruating, massively obese (mean weight, 120 kg) women participating in a weight reduction program and 25 age-matched normal weight (mean weight, 60 kg) women. Serum 17 beta-estradiol (E2), estrone (E1), androstenedione (A), dehydroepiandrosterone sulfate, testosterone, LH, FSH, PRL, and cortisol concentrations were measured during the follicular phase of the menstrual cycle. Waist to hip ratio and abdominal fat cell size were measured at the beginning of the study. The serum levels of E2 (P less than 0.04) as well as those of A, SHBG, and LH (P less than 0.002) were lower in the obese group. Consequently, the testosterone to SHBG ratio and the E1 to A ratio were higher and the LH to FSH ratio was lower in this group. Waist to hip ratio did not correlate with the levels of circulating hormones or SHBG, but an inverse correlation was found between abdominal fat cell size and A as well as the LH to FSH ratio in the nonhirsute women of the obese group. Subsequent to moderate weight reduction (13.2 kg), serum A and E1 levels (P less than 0.01) increased, and serum cortisol levels decreased (P less than 0.001). Thus, massive obesity is associated with abnormalities in hormonal balance in gynecologically symptomless women, there being an association between E1, E2, A, LH, cortisol, and relative weight and/or abdominal fat cell size.

Renal Disease in Patients With Massive Obesity

During a four-year period, 17 massively obese patients without clinically apparent systemic disease underwent renal biopsy for marked proteinuria. Clinical information and biopsy results were compared with those in 34 normal-body-weight controls matched for age, sex, and similar presentation. Histopathologic changes characteristic of focal glomerulosclerosis were found in nine (53%) of the obese patients and two (6%) of the controls. In addition, five (29%) of the obese patients had occult diabetic nephropathy, while no diabetic changes were seen in controls. Clinically, obese patients resembled controls in most respects. Serum albumin level, however, was higher than in controls (3.5 +/- 0.2 vs 2.5 +/- 0.1 g/dL). Indeed, obese patients with focal glomerulosclerosis had normal serum albumin levels (4.0 +/- 0.1 g/dL). Thus, primary renal disease in massively obese patients with marked proteinuria differed in several important respects from that seen in normal-body-weight patients with a similar degree of proteinuria.

Effects of massive obesity on insulin sensitivity and insulin clearance and the metabolic response to insulin as assessed by the euglycemic clamp technique

Insulin sensitivity was studied in nine nondiabetic massively obese patients (one male and eight females ages 39.0 ± 2.7 years, body mass index 47.1 ± 1) by the euglycemic clamp technique (40 mU/m 2/min) and compared to seven lean control subjects (three males and three females, ages 34.8 ± 2.5 years, body mass index 23 ± 1.1). Fasting plasma glucose, immunoreactive insulin, and C-peptide concentrations were higher in the massively obese patients than in the controls ( P < 0.025). Following exogenous insulin infusion, immunoreactive glucagon and C-peptide concentrations decreased similarly in the massively obese patients and controls, indicating normal sensitivity of the alpha and beta cell to insulin. Glucose uptake (M) expressed either as mg · min −1 of fat free mass was significantly reduced in the massively obese patients compared to the controls ( P < 0.001). Similarly, the M I ratio (glucose uptake per unit of insulin) was significantly reduced in the massively obese patients ( P < 0.001). Free fatty acids and glycerol concentrations measured in the fasting state were significantly elevated in the massively obese patients (free fatty acids 678 ± 51 v 467 ± 55 μmol/L, P < 0.05; glycerol 97 ± 9 v 59 ± 11 μmol/L, P < 0.02). The effects of insulin on antilipolysis was assessed by measuring the reductions in free fatty acids and glycerol concentration during the glucose clamp study. Although the absolute levels remained higher in the massively obese patients, inhibition of lipolysis was similar in both groups. Alanine, lactate, and 3-hydroxybutyrate displayed similar responses in the massively obese patients and controls during the study. The metabolic clearance rate of insulin (MCR 1) was significantly lower in the massively obese patients compared to the controls when expressed per kg of total body weight but not when calculated per kg of fat free mass. In conclusion, massively obese patients showed marked insulin insensitivity on glucose disposal reflecting primarily muscle insensitivity to insulin action. In contrast to decreased glucose disposal, other metabolic effects of insulin were not markedly impaired. The antilipolytic, antiketogenic, and inhibitory effects on insulin and glucagon production remained essentially intact.

The heart in massive (more than 300 pounds or 136 kilograms) obesity: Analysis of 12 patients studied at necropsy

Observations are described in 12 massively obese patients (5 women, 7 men), aged 25 to 59 years (mean 37), who weighed 312 to more than 500 pounds (mean 381). Seven patients had had systemic hypertension, 4 hypersomnia or sleep apnea, 2 diabetes mellitus, and 1 patient symptomatic coronary artery disease. Five patients died suddenly from undetermined causes, 2 from right-sided congestive heart failure, 1 patient from acute myocardial infarction; 1 from aortic dissection; 1 from intracerebral hemorrhage; 1 from a drug overdose, and 1 soon after an ileal bypass. The heart weight was increased in all 12 patients. The heart weight to body weight ratio expressed as a percent ranged from 0.22 to 0.61 (mean 0.37) (normal for men 0.42 to 0.46 [mean 0.43], normal for women 0.38 to 0.46 [mean 0.40]). The left ventricular cavity was dilated in 11 patients and the right ventricular cavity in all 12. Only 2 patients (aged 42 and 59 years) had 1 or more major epicardial coronary arteries narrowed greater than 75% in cross-sectional area by atherosclerotic plaque, 1 of whom had no symptoms of myocardial ischemia. Of 664 five-millimeter segments from the 4 major epicardial coronary arteries from 11 patients (mean 60 per patient), 431 (65%) were narrowed 0 to 25% in XSA, 143 (21%) were narrowed 26 to 50%, 73 (11%) were narrowed 51 to 75%, and 17 (3%) were narrowed 76 to 100%.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for existence of two types of massive obesity.

The responses of growth hormone, cortisol, and prolactin to symptomatic hypoglycaemia during an intravenous insulin tolerance test were measured in 20 massively obese subjects and six lean volunteers. In 11 subjects, who had been obese since early childhood, an impaired growth-hormone response and an absent prolactin response were found. In the nine other obese subjects, however, the growth-hormone and prolactin responses were not significantly impaired. Seven of these subjects had become obese either as a teenager or during adult life. These findings suggest the existence of two types of human obesity similar to those found in rodent models. In one the disorder of hypothalamic function may be due to a basic, possibly genetic abnormality, while in the other it is acquired.

Treatment of massive obesity by prolonged jaw immobilization for edentulous patients

Twenty massively obese patients who were edentulous in one or both jaws were treated by prolonged jaw immobilization. Dentures were secured under general anaesthesia to the edentulous jaws by various direct wiring methods and the jaws immobilized by interdental wires, where teeth were present, and intermaxillary wires. The wired-in dentures were generally well tolerated with minimal mucosal reaction but with a high incidence of infection around the attachment wires. Patients edentulous in one jaw alone, (11 maxilla, two mandible), managed well and 11 achieved a satisfactory weight loss. The seven patients edentulous in both jaws had considerable difficulty with pain and infection, three having the fixation appliances removed in the immediate post-operative period and only one achieved a satisfactory weight loss. Thus prolonged jaw immobilization is an effective means of treating massively obese patients if they are edentulous in one jaw alone but less so if they are completely edentulous.

IMPAIRED HYPOTHALAMIC CONTROL OF PROLACTIN SECRETION IN MASSIVE OBESITY

Intravenous insulin tolerance tests and thyrotropin-releasing hormone (T.R.H.) stimulation tests were performed in nine massively obese women and six lean female controls and the prolactin, growth hormone, and cortisol responses were measured. A combined pituitary function test (insulin, T.R.H., and gonadotropin-releasing hormone) was performed in eleven other massively obese women. In the obese women to whom insulin was given separately there was no prolactin release, and growth hormone and cortisol responses were impaired. T.R.H. stimulation produced a prolactin response which was subnormal. These changes were not apparent in the obese women in whom a combined pituitary function test was performed. The results suggest an alteration of hypothalamic function in massive obesity.

Jejunoileal bypass for the treatment of massive obesity. Prevalence, morbidity, and short- and long-term consequences

The jejunoileal bypass for patients 125 lb or more above their ideal body weight as an experimental procedure exchnages almost certain weight loss for many known and many yet undescribed problems. Study of the known complications has led to altered operative procedures and management techniques that lessen the impact of nearly all of the complications. All patients need occasional advice on potential complications, and most experience episodes of depletions or diarrhea that require hospital intervention. The improved versions of this surgery have not been present sufficiently long to indicate the real nature of long term changes, and careful evaluation is essential for at least small groups of these patients in order for all interested physicians to provide proper advice to the 10,000 or so patients who have already had this procedure. Careful selection of patients to identify those who will accept follow-up and seek help when needed, and to identify those with sufficient social adaptability to adjust to a change in body image, and a competent, experienced acute and chronic team for management lead to the majority of patients having a very satisfactory result. Many specific complications of massive obesity are specifically helped by this procedure. In America, this is the only treatment effective more than half of the time in the massively obese.

Treatment of Massive Obesity With Rice/Reduction Diet Program

One hundred six massively obese patients, who each lost at least 45 kg, were treated as outpatients with the rice/reduction diet, exercise, and motivational enhancement under daily supervision. Average weight loss was 63.9 kg. Forty-three patients achieved normal weight. Men lost weight at a greater rate than women. Concomitant with weight reduction, there were significant decrements in blood pressure; fasting and two-hour postprandial blood glucose, serum triglyceride, and serum uric acid levels, and heart-chest ratio as evidenced on chest x-ray film. Electrocardiographic and retinal venous changes improved. Serum cholesterol level did not change significantly. This study demonstrates that massively obese persons can achieve marked weight reduction, even normalization of weight, without hospitalization, surgery, or pharmacologic intervention. Accompanying cardiovascular risk factors show great decrements concomitant with weight loss.

Some psychological and social implications of massive obesity: A study of some psychosocial accompaniments of major fat loss occurring without dietary restriction in massively obese patients

THE CONTRIBUTION that experiential influences including their psychological and social aspects make to the development and maintenance of obesity is complex and probably highly variable. Few general population studies have been done. In the downtown Manhattan Study little association was found between obesity and psychiatric status (Moore et nl. [l]) although there has for long been a clinical view that the pyknic shape is associated with an increased tendency to develop manic depressive psychosis. Meanwhile McCance [2] and Silverstone and Solomon [3] have reported that obese patients attending medical clinics were characterised by normal levels of neuroticism as measured by the Cornell Medical Index. However, Silverstone [4] also reported that male subjects, 45 per cent or more above ‘ideal’ weight and sampled from the general population reported lesser amounts of such neuroticism than others, and Simon [5] had earlier found significantly less depression amongst a group of obese service personnel than amongst their non-obese colleagues. Moreover, Crisp and McGuinness [a, examining alternate middle-aged subjects within a 10,000 general practice population in southwest London (Crisp and Priest [7]) found massive obesity to be associated with significantly less anxiety and depression. It has often been suggested that the massively obese state might be ‘protective’ against such experiences. Clinic subjects grossly obese since childhood also show major disturbance of body image in terms of feelings, attitudes and cognition. For instance, they feel their bodies to be ‘grotesque and loathsome and that others view it with hostility and contempt’ and this is combined with an excessive general self-consciousness particularly in relation to the opposite sex (Stunkard and Mendelson [8]). Furthermore they strikingly and persistently overestimate their body width (Glucksman and Hirsch [9]). Massively obese clinic patients have been found to have disturbances of behaviour in the realms of eating and sex. Eating is related more to the availability of food than to internal experiences of hunger (Nisbett [lo], Penick and Stunkard [ll]) whilst sexual behaviour is significantly diminished (Crisp [12]).

Psychosocial effects of intestinal bypass surgery for severe obesity.

Abstract The psychosocial consequences of intestinal bypass surgery and weight loss were observed in 29 massively obese patients. The response to weight loss, as assessed by both semistructured psychiatric interviews and a series of self-administered questionnaires, was an improvement in mood, self-esteem, interpersonal and vocational effectiveness, body image and activity levels, as well as a notable decrease in the use of denial. The decrease in depression and improvements in ego strength, body image and global clinical rating of psychologic status were directly proportional to the magnitude of weight loss. The most important psychologic change responsible for improved functioning was the loss of a pervasive sense of entrapment, helplessness and failure associated with massive obesity. There is evidence that the relative unresponsiveness of obese patients to the internal cues associated with satiety is reversible with weight loss. Symptom substitution did not occur. The reversibility of many of the psyc...

Quantitative and qualitative effects of l-triiodothyronine in massive obesity

Seventeen massively obese patients were treated with either l-triiodothyronine (75 μg. three times a day) plus an 800-calorie diet or by diet plus placebo in a randomized double blind protocol. Weight loss data in hospitalized patients at eight weeks revealed a significantly greater mean weight loss of 29.1 pounds in the l-triiodothyronine group as compared with 17.2 pounds in the controls ( p < .025). At 12 weeks there was no longer a significant difference in hospitalized patients with a mean weight loss of 37.0 pounds in the l-triiodothyronine group compared with 23.3 pounds in the controls ( p < 0.15). Weight loss was unfavorably altered by hospital discharge and at 24 weeks the average weight loss of 48.1 pounds in the l-triiodothyroine group versus 29.4 pounds in the controls was not statistically significant. Subjective side effects were negligible, but one patient on l-triiodothyronine developed atrial fibrillation and was removed from the study. Gas chromatographic analysis of fat biopsies from the left buttock and dorsal cervical hump revealed a lower concentration of 16:1 and higher concentration of 16:0 and 18:0 fatty acids in the latter. Neither form of treatment altered this pattern significantly. Hyperuricemia in both groups returned to normal but the decline in serum urate was more striking in the patients treated with l-triiodothyronine. Treatment of obesity with l-triiodothyronine significantly accelerates weight loss in hospitalized patients for eight weeks but is recommended only in healthy, well motivated, massively obese (over 100 pounds above ideal weight) subjects who are agreeable to prolonged hospitalization, concomitant diet therapy, and long-term follow-up.

Clinical appraisal of jejunoileal shunt in patients with morbid obesity

The cause of morbid obesity remains obscure. No specific endocrinopathy has been implicated and although various explanations have been advanced, no uniformly practical medical or psychiatric program of effective treatment has evolved. The basic factor of gluttony with enormous caloric intake, coupled with indolent or absent exercise activity, appears to be the common denominator in most massively obese patients. Although no precise definition for this syndrome is generally accepted, we identify morbid obesity as existing in any person whose weight has reached a level two to three or more times his ideal weight and who has maintained this level of obesity for five years or more despite efforts by himself, family, friends, and physicians to bring about effective and sustained reduction of weight to medically acceptable standards. In the last fifteen years several groups of investigators have attempted to cope with the problem of massive intractable obesity by surgical operation. The basis for a surgical approach to the problem is the dual concept that massive obesity of the “fat man in the circus” variety is a serious disease of life-shortening severity and that long-term dietary control is usually unsatisfactory. The record of accomplishment in medical treatment of such persons by dietary restriction, including rigid inhospital dietary programs of 800 to 0 calories per day for periods up to 300 days, has been marred by the extremely high rate of recurrence of obesity once rigid conditions of dietary control are relinquished.

The possible significance of some behavioural correlates of weight and carbohydrate intake.

of 82 patients with primary anorexia nervosa and a pilot study of 16 patients with massive obesity. The anorexia nervosa patients-G male and 76 female-have all been seen at length by myself, and the majority have been treated as in-patients. Many of them have been referred to in previous reports [l-5]. In particular the view has been expressed that many patients with anorexia nervosa come from an obese or otherwise nutritionally disordered population so far as family and personal constitutional factors are concerned. Not all patients with anorexia nervosa develop this illness in their teens. The majority of the remainder in the present series have been women who developed the illness in their twenties, often having first become more obese during their teens. The majority of the massively obese patients, one male and 15 female, were admitted routinely and successively under a general physician and later seen by me, initially as a collaborative exercise. Only two of these patients were referred directly to me by their general practitioners, one patient because of her high amphetamine intake, the other because his general practitioner wanted psychiatric treatment for the patient’s complaint of being overweight. Five of these patients have subsequently been treated as in-patients in a psychiatric unit, each for about 6-8 consecutive months during which time they have all lost between 8-10 st. in weight. Another two of these patients provided a history of anorexia nervosa during their teens. The discovery of such relationships, between marked underweight and gross overweight, has led to the present study: in particular, to the examination of such psychosomatic factors as sexual behaviour and level of activity in the two groups, also to the consideration of such concepts and descriptive features as ‘denial’, ‘compulsion’ and ‘addiction’, seemingly applicable to and shared by both groups. Firstly I want to restate my view [2, 61 that primary anorexia nervosa is almost invariably a state of weight phobia, hingeing on and pivoting round puberty. This central phobia, no longer only of excess weight as part of a feeding disorder, but of normal (functioning) adolescent weight, is usually evident and fearfully admitted to by the patient. There are some few patients who vigorously deny such a fear. They only come to reveal it in a treatment situation in which they are being pressed to gain weight up to a ‘normal’ amount. I do not therefore take the view that the psychopathological disorder in anorexia nervosa is any longer primarily a feeding disorder akin [7] to the feeding disorders of childhood in which food more often seems to represent and stand for the (absent) mother and for her (absent) love. The intervening factor separating off these feeding disorders and anorexia nervosa, and giving a