Physical training in human hyperplastic obesity. IV. Effects on the hormonal status.

Severly obese subjects and sex- and age-matched controls underwnet physical training during a 6-wk period. Evidence of training was shown in all subjects by increased aerobic power. Before training the obese subjects were characterized by the following abberations: decreased glucose tolerance, hyperinsulinemia, elevated blood glycerol and plasma free fatty acids, and a blunted plasma growth hormone response during glucose tolerance. Noradrenaline output was elevated, a finding of potential interest for the explanation of increased lipolysis, blood pressure, and heart size in obesity. With training the following changes were found:In the controls there was evidence for the beginning of a decrease of adipose tissue mass. In the obese, however, body weight, body fat, or fat cell size did not decrease during training. Plasma insulin decreased, and a corresponding increase of plasma glycerol was seen. Glucose tolerance was not changed, and this, together with decreased plasma insulin, indicated an increase insulin sensitivity of the periphery. Changes in noradrenaline or growth hormone during training could not explain this increased sensitivity. Urinary cortisol output was found to decrease after training in the obese; this might be interpreted as a decrease in cortisol secretion allowing a more effective insulin action on the periphery.     

Physical training in human obesity. 3. Effects of long-term physical training on body composition

Eight severely obese patients with adipose tissue hypercellularity, elevated body cell mass, and a juvenile onset of obesity were subjected to physical training during 6 mo without dietary restrictions. The training program was of 35-min duration three times weekly and followed a fixed schedule individualized to the working ability of each subject, so that the heart rate was 10–15 beats below maximal during three 5-min periods of each training session. Body weight, body cell mass, and body fat showed no significant changes after 3 or 6 mo of training. Fasting plasma insulin decreased after 3 mo of training, but fasting blood glucose was not changed. After 6 mo plasma insulin values were still decreased. Now glucose tolerance had also improved, and plasma triglycerides showed a trend to lower values. The results suggest that the lack of body fat decrease after the long training period might be characteristic for subjects with the type of severe obesity studied, because in a previous study¹ a similar, although lighter, training procedure produced a marked body fat decrease in patients without severe obesity.     

Fat cell number,resting metabolic rate,mean heart rate,and insulin elevation while seeing and smelling food as predictors of slimming

The explanatory value of total fat cell number, resting metabolic rate, mean heart rate during sleep, and peripheral insulin while seeing and smelling food were examined in relation to weight reduction in 19 obese women on a 1100-kcal/day diet. The insulin response while seeing and smelling food was expressed as the insulin area (mU · min · 1^?1) over the baseline level. Food was presented in front of the patient for 5 min. Insulin was determined in short intervals 20 min before and 20 min after start of food presentation. Fat cell number, resting metabolic rate, and mean heart rate during sleep were determined with standard techniques. All patients went through a period of weight loss, a plateau phase, and a period of weight regain. Body weight, fat cell number, resting metabolic rate, and/or heart rate correlated significantly with degree and rate of weight loss, duration of plateau phase, and rate of regain. In multiple regression analysis fat cell number and resting metabolic rate explained 81% of the variance for weight loss, 66% for rate of regain, and 29% for duration. For duration, only fat cell number contributed significantly. The variance of rate of weight loss was explained up to 49% by metabolic rate and insulin response while seeing and smelling food. The possibility of predicting weight reduction to a certain target weight is of great practical importance since the patients can obtain a realistic goal for their efforts to reduce body weight. Hopefully systematic investigations of factors associated with the inability of obese subjects to maintain weight reduction will improve treatment in the future.     

Muscle tissue in obesity with different distribution of adipose tissue. Effects of physical training

Obese men and women with the same body fat mass, as well as obese women in another study, were divided into groups with male or female type of body fat distribution, but again with similar body fat mass. The participants were examined with measurements of body composition, including muscle fiber distribution, as well as circulatory and metabolic variables before and after physical training under controlled conditions. Obese men had higher lean body mass, blood pressure, blood glucose and plasma insulin, C-peptide, cholesterol and triglyceride concentrations than age- and body fat-matched obese women. Obese women with male type of adipose tissue distribution showed the same differences (except cholesterol) in comparisons with women with female type of adipose tissue distribution. The women with male type obesity were also more insulin resistant in glucose clamp measurements, and had male type of muscle fiber distribution. Physical training in the group of obese men resulted in a decrease of body fat, a further increase of lean body mass, an increase of fast twitch, aerobic type, muscle fibres as well as lower plasma insulin, cholesterol and triglyceride concentrations and lower blood pressure. Obese women with male type distribution of adipose tissue responded to physical training essentially like men. The insulin sensitivity was improved to the same level as in obese women with female type of adipose tissue distribution. In contrast, the latter women showed an increase of body fat and no metabolic improvements after training. These results show that obese women with male type of body fat distribution also have male characteristics of muscle mass, morphology and function. It is suggested that the obesity complications associated with this condition are improved by physical training because of an adaptation to a negative energy balance, in combination with an improvement of insulin sensitivity of the muscle mass. In contrast, the failure of obese women with female type of adipose tissue distribution to adapt to a negative energy balance during physical training is probably explaining their failure to decrease body fat and to improve metabolism during physical training.     

Effects of physical training on insulin, connecting peptide (C-peptide), gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) levels in obese subjects

Ten severely obese women were subjected to physical training for three months on ad libitum diet. Under metabolic ward conditions oral glucose tolerance test was performed before and after the training period with the same energy intake quantitatively and qualitatively, and glucose, insulin, connecting (C)-peptide, gastric inhibitory polypeptide (GIP) and pancreatic polypeptide (PP) were determined. In confirmation of previous work, physical training caused no decrease in body fat in these severely obese subjects, and no change in body cell mass or glucose tolerance, while insulin and blood pressure decreased. The control of dietary conditions demonstrated that the latter phenomena were not due to quantitative or qualitative changes in the diet. C-peptide concentrations decreased also, indicating effects of physical training in obesity on insulin production. GIP is believed to be a gastrointestinal factor facilitating insulin secretion (Incretin). Previous work has indicated that gastrointestinal factor(s) are involved in the insulin lowering effect seen after physical training. It is possible that GIP is contributing to this phenomenon.     

Lifestyle intervention of hypocaloric dieting and walking reduces abdominal obesity and improves coronary heart disease risk factors in obese,postmenopausal, African-American and Caucasian women

BACKGROUND: There are few empirical data to support the claim that weight loss improves coronary heart disease (CHD) risk factors in postmenopausal women; nor is it known if there are racial differences in changes of body fat distribution, lipids, glucose tolerance, and blood pressure with weight loss. This study determined the efficacy of a lifestyle weight loss intervention in reducing total and abdominal obesity and improving CHD risk factors in obese Caucasian and African-American postmenopausal women. METHODS: Body composition (dual-energy x-ray absorptiometry), abdominal fat areas (computed tomography scan), lipoprotein lipids, insulin, glucose tolerance, and blood pressure were measured before and after 6 months of hypocaloric diet and low-intensity walking in 76 overweight or obese (body mass index > 25 kg/m(2)), Caucasian (72%) or African-American (28%), postmenopausal (age = 60 +/- 5 years) women who completed the study. RESULTS: Absolute amount of body weight lost was similar in Caucasians (-5.4 +/- 3.6 kg) and African Americans (-3.9 +/- 3.6 kg), but Caucasian women lost relatively more fat mass (p <.05). Both groups decreased their subcutaneous abdominal fat, and Caucasian women decreased their visceral fat area, but there were no racial differences in the magnitude of abdominal fat lost. The intervention decreased triglyceride and increased high-density lipoprotein and high-density lipoprotein 2 cholesterol in both races, and it decreased total and low-density lipoprotein cholesterol in Caucasian women (p <.05-.0001). Fasting glucose and glucose area during the oral glucose tolerance test decreased (p <.0001) in Caucasian women, whereas insulin area decreased in both Caucasian (p <.01) and African-American (p <.05) women. Blood pressure decreased the most in women with higher blood pressures at baseline. Changes in lipids, fasting glucose and insulin, their responses during the oral glucose tolerance test, and blood pressure were not different between racial groups. CONCLUSIONS: Weight loss achieved through a lifestyle intervention of energy restriction and increased physical activity is an equally effective therapy in African-American and Caucasian obese, postmenopausal women for improving glucose and lipid CHD risk factors.     

Cyclic glycine-proline normalizes systolic blood pressure in high-fat diet-induced obese male rats

Background and aimsInsulin-like growth factor (IGF)-1 deficiency is associated with a range of metabolic disorders. Cyclic glycine-proline (cGP) is a natural nutrient and regulates the amount of active IGF-1 in plasma. Plasma cGP decreases in hypertensive women whereas increases in obese women, suggesting its involvement in cardio-metabolic function. We therefore examined the effects of cGP on metabolic profiles and blood pressure in high-fat diet (HFD)-induced obese male rats.MethodsMale rats were fed either a HFD or a standard chow diet (STD) ad-libitum from 3 to 15 weeks of age. Rats were administered either saline or cGP from 11 to 15 weeks of age. At 14 weeks of age, systolic-blood pressure (SBP) was measured by tail-cuff plethysmography and body composition quantified by DEXA. Blood and retroperitoneal fat tissues were collected. Plasma concentrations of insulin, IGF-1, IGF binding protein (IGFBP)-3 and cGP were evaluated using ELISA and HPLC-MS respectively.ResultsCompared to STD, HFD feeding increased SBP, total fat mass and fat/lean ratio, retroperitoneal fat weight, fasting plasma insulin and cGP concentrations whereas decreased plasma IGF-1 and IGFBP-3 concentrations. Administration of cGP reduced SBP and retroperitoneal fat weight, but had no effect on body composition and plasma insulin concentrations.ConclusionHFD-associated decreases in IGFBP-3 and increases in cGP represent an autocrine response to normalize IGF-1 function through improving the amount of bioavailable IGF-1 in the circulation of obese male rats. The beneficial effects of cGP on SBP and retroperitoneal fat mass may suggest a therapeutic potential for cGP in HFD-associated cardio-metabolic complications.     

有氧运动防治代谢综合征的实验研究

目的建立与人类代谢综合征相似的大鼠模型，并观察游泳（有氧运动）的干预作用。方法8周龄雄性Wistar大鼠，分别给予普通膳食（对照组）、高脂高盐膳食、普通膳食加游泳和高脂高盐膳食加游泳处理，24周后观测各组的体重、内脏脂肪量、尾动脉血压、空腹血糖、空腹胰岛素和血脂，并进行腹腔葡萄糖耐量试验和正常葡萄糖高胰岛素钳夹试验。结果高脂高盐膳食组出现了典型的代谢综合征特征，其体重、内脏脂肪、血压、胰岛素和甘油三酯均比其他组的各项指标显著增加，而葡萄糖输注率显著降低。结论高脂高盐膳食可诱导大鼠代谢综合征，有氧运动可减少或控制因高脂、高盐饮食引起的体重、腹围增加，改善胰岛素敏感性和血糖调节异常，有效防止代谢综合征的发生。     

The effects of exercise, training on body composition and metabolism in men and women

In order to examine whether there are sex-differences in the response of energy balance to physical training slightly obese men and women participated in the same 3 months physical training program with the same individual relative intensity. The men became somewhat lighter (-2 kg) and leaner (-2.9 kg body fat) and showed decreases in sum of insulin and sum of C-peptide values during an oral glucose tolerance test as well as cholesterol values. The women showed decrease of 2.6 kg body fat, and also increased lean body mass (1.9 kg) and similar metabolic changes. The women had, however, a larger body fat mass at the outset. When women with similar body fat mass as that of men were analysed separately, no change in body weight or body fat had occurred, and the metabolic adaptations were less pronounced. No compensatory increase of energy intake could be discovered in any of the groups, the most obese women actually showed a decrease. Taken together with previous information these results suggest that men, like male rats, become leaner during physical training due to a lack of energy intake compensation. Women with similar body fat mass, however, like female rats, may react with such a compensation, causing a protection of their body fat. Women usually have more body fat than men, however. Obese women in this study showed a decrease of body fat.     

Effects of age, sex, and clinical conditions on adipose tissue cellularity in man

Methods for measurements of fat cell size in man are now available. Total fat cell number is more difficult to measure, and the numbers reported should probably so far be regarded as estimates of fat-containing fat cells. The first years of life seem to be critical for adipose tissue development in man. Nonobese adult women probably have more fat cells than men. Fat cell size increases with age.Obese children and adults show increases in both fat cell size and number. Division of obese subjects into different subgroups according to adipose tissue cellularity must take into consideration the age and sex variations in the nonobese population. Attempts to such subdivision seem to give one group with an increased number of fat cells, early debut of obesity, and increased body cell mass. These patients are difficult to treat successfully by conventional methods. Adult onset obesity seems to be characterized by enlarged fat cells.All data presently available are transsectional and do not allow any definite conclusions about possible fat cell division. Thus, there might well be adult obese subjects who, like certain genetically obese rodents, have fat cells which multiply during an abnormally long period of life.Fat cell size has been found to correlate with plasma insulin and triglyceride concentrations. Patients with endogenous hypertriglyceridemia and possibly adult onset diabetes mellitus before debut of the diabetes have enlarged fat cells, while patients with juvenile, insulin-requiring diabetes mellitus have small fat cells.Thus, the subgrouping of obesity according to the cellularity of adipose tissue has given associations with clinical observations such as age at debut of obesity, disturbances of carbohydrate and lipid metabolism, and with prognosis for treatment. These relationships seem to justify the adipose cellularity measurements as they are now performed, although only a fairly rough estimate of the total cell number is obtained.     

Importance of obesity for the metabolic abnormalities associated with an abdominal fat distribution

Obese people with a high waist/hip ratio (W/H ratio) have an increased risk for cardiovascular disease. The present study was designed to separately analyze the importance of obesity and the regional fat distribution for the metabolic risk factors. Blood pressure, glucose tolerance, insulin, and plasma lipid levels were studied in lean and obese postmenopausal women with a high or low W/H ratio. The individuals within each group were carefully matched for age, lean body mass, and body fat. The risk factors associated with a high W/H ratio (elevated blood pressure, blood lipids, and glucose levels) were found in the obese but not in the lean women. Furthermore, lean women with a high W/H ratio tended to have a lower metabolic risk factor profile than obese women with a low W/H ratio. These findings document the importance of obesity in expressing the metabolic risk factors for cardiovascular disease associated with a high W/H ratio.     

Comparison of a low-fat diet to a low-carbohydrate diet on weight loss, body composition, and risk factors for diabetes and cardiovascular disease in free-living, overweight men and women

Overweight and obese men and women (24-61 yr of age) were recruited into a randomized trial to compare the effects of a low-fat (LF) vs. a low-carbohydrate (LC) diet on weight loss. Thirty-one subjects completed all 10 wk of the diet intervention (retention, 78%). Subjects on the LF diet consumed an average of 17.8% of energy from fat, compared with their habitual intake of 36.4%, and had a resulting energy restriction of 2540 kJ/d. Subjects on the LC diet consumed an average of 15.4% carbohydrate, compared with habitual intakes of about 50% carbohydrate, and had a resulting energy restriction of 3195 kJ/d. Both groups of subjects had significant weight loss over the 10 wk of diet intervention and nearly identical improvements in body weight and fat mass. LF subjects lost an average of 6.8 kg and had a decrease in body mass index of 2.2 kg/m2, compared with a loss of 7.0 kg and decrease in body mass index of 2.1 kg/m2 in the LC subjects. The LF group better preserved lean body mass when compared with the LC group; however, only the LC group had a significant decrease in circulating insulin concentrations. Group results indicated that the diets were equally effective in reducing systolic blood pressure by about 10 mm Hg and diastolic pressure by 5 mm Hg and decreasing plasminogen activator inhibitor-1 bioactivity. Blood beta-hydroxybutyrate concentrations were increased in the LC only, at the 2- and 4-wk time points. These data suggest that energy restriction achieved by a very LC diet is equally effective as a LF diet strategy for weight loss and decreasing body fat in overweight and obese adults.     

Hormonal influences on the relationships between body fatness, body fat distribution, lipids, lipoproteins, glucose and blood pressure in French working women

The independent associations between overall obesity, body fat distribution, lipids, lipoproteins, glucose, blood pressure and some hormonal factors (sex hormone-binding globulin (SHBG), corticosteroid binding globulin (CBG) and fasting insulin) were cross-sectionally examined in 205 French working women. After adjustment for age, overall adiposity assessed by body mass index (BMI) was significantly associated with most metabolic parameters, whereas regional adiposity assessed by the waist-hip ratio (WHR) was significantly associated only with triglyceride, systolic and diastolic blood pressure. Blood pressure, glucose but not triglyceride, were also negatively and significantly correlated with SHBG and positively with fasting insulin. Negative independent associations were found between SHBG and both BMI and WHR, whereas CBG was positively associated only with WHR. Fasting insulin was no longer related to WHR after adjustment for BMI. After controlling for the effect of SHBG or insulin, the associations between triglyceride, blood pressure and both BMI and WHR were not substantially modified. After adjustment for BMI and WHR, fasting insulin was independently associated with both HDL cholesterol and diastolic blood pressure. In conclusion, in these French women, hormonal factors under study appeared to have little influence on the relationships between body fatness, body fat distribution, metabolic variables and blood pressure.     

The effects of weight loss treatments on upper and lower body fat

The intra-abdominal visceral deposition of adipose tissue, which characterises upper body obesity, is a major contributor to the development of hypertension, glucose intolerance and hyperlipidaemia. Conversely, individuals with lower body obesity may have comparable amounts of adipose tissue but remain relatively free from the metabolic consequences of obesity. This raises an obvious question-are there particular weight reducing treatments which specifically target intra-abdominal fat? In theory, surgical removal of upper body fat should be effective. In reality, neither liposuction nor apronectomy ('tummy tuck') have any beneficial metabolic effects, they simply remove subcutaneous adipose tissue which is often rapidly replaced. Vertical banded gastroplasty and gastric bypass operations may be dramatically effective in improving blood pressure, insulin sensitivity and glucose tolerance. However, these benefits result from a parallel reduction in visceral and total body fat. Studies of body fat distribution in postmenopausal women confirm that the marked decrease in adiposity, following a programme of very low calorie diet and exercise, reflects a comparable reduction in visceral and thigh fat. The reduction in waist circumference after a low fat/exercise programme suggests a similar situation in men. Exercise has an important role in treatment but, once again, the fat loss is generalised. Nevertheless, the improved metabolic parameters seen in exercising obese subjects, independent of weight loss, suggest other beneficial actions. Growth hormone (GH) has a marked lipolytic action. GH replacement treatment for GH deficient adults with pronounced abdominal fat deposition, has been shown to reduce intra-abdominal fat by 47% compared to 27% decrease in abdominal subcutaneous fat. Similar beneficial actions on abdominal fat have been reported following treatment with testosterone in obese men. The potential hazards of such treatments make them unsuitable therapy for obesity. Dexfenfluramine is effective in reducing total body fat but the results from a six month randomised controlled trial indicates that it does not specifically influence changes in waist circumference associated with weight loss. In conclusion, any treatment which reduces total body fat will, by its nature, reduce intra-abdominal visceral fat. There are presently no specific treatments which can be recommended for intra-abdominal fat but increasing knowledge of the biochemical aberrations associated with visceral adiposity may lead to more specific therapies for the future.     

Metabolic effects and body fat mass changes in obese subjects on a very-low-calorie diet with and without intensive physical training

During 4 weeks, 40 obese subjects (body mass index 30-45 W/H2) were treated with a 300-kcal mixed diet alone or in combination with exercise training on a bicycle ergometer in a metabolic ward. Exercise had a minor effect on body weight, reflected by an additional fat loss of 1.7 kg (expected loss: 4.0 kg). Hyperinsulinemia was improved by diet and normalized by diet combined with exercise; a similar effect was observed regarding C-peptide levels. Plasma concentrations of epinephrine and norepinephrine decreased in both groups. At maximal work, norepinephrine levels were higher in the group with exercise. Free fatty acids and free glycerol increased at rest as well as during exercise in subjects on both regimens, the difference being more pronounced in the exercise group. Enhanced oxidation of fat was substantiated by lower respiratory quotients during endurance exercise. Working capacity increased and blood pressure decreased considerably as a consequence of physical training. It is concluded that exercise training in addition to a hypocaloric diet lowers body weight and body fat, although to a lower degree than expected. During and following bouts of exercise, fat mobilization and oxidation is enhanced, but these effects are probably counteracted at rest. On the other hand, the diet-induced deterioration of physical performance is overcompensated.     

Influence of menopause on dietary treatment of obesity

Obese women (n = 104) were treated with an energy reduced diet (1100 kcal d-1) in a strictly standardized outpatient regime. Body composition, regional adipose tissue distribution, regional fat cell sizes and metabolic variables were followed before treatment, after 5% weight loss and at the stage when there was no further weight loss. Premenopausal women lost less body fat and relapsed earlier after treatment, compared with menopausal women. Fat loss appeared to be more uniform, and included several adipose tissue regions in postmenopausal women, while younger women seemed to lose fat mainly from the epigastrial fat cells. Higher baseline levels of thyroid hormones were associated with increased fat loss and a tendency to lose less lean body mass. Waist/hip and waist/thigh ratios did not change in response to weight loss. The addition of fibre to the diet did not affect the rate of relapse. These results suggest that obesity treatment by implementation of a negative calorie balance might be more successful in postmenopausal than in younger women, perhaps due to the more uniform availability of body fat in the former.     

Hemorheological disturbances, metabolic parameters and blood pressure in different types of obesity

Body fat distribution characterized by a high waist/hip ratio (WHR) has been described as a risk factor in the incidence of cardiovascular diseases and associated mortality. Hemorheological changes have been shown to accompany several risk factors. Gynoid and android obese women were compared in the present study with respect to hemorheological and metabolic variables and blood pressure. The android obese women had a significantly higher hematocrit and red blood cell count and showed higher blood viscosity at both high and low shear rates than women with the gynoid obesity type. Blood pressure was also higher in the android group. No significant differences were shown in concentration of cholesterol or triglycerides in serum nor in the microrheological properties of the red blood cells. The filterability index, which mirrors the number of rigid erythrocytes in the blood, was found to correlate with the plasma insulin concentration (r = 0.78, P less than 0.05) in the android but not in the gynoid obese women. It is concluded that the pathological changes in blood rheology observed in the android obese women may contribute to the high rate of cardiovascular events and associated mortality reported in this type of obesity.     

Laparoscopic adjustable gastric banding for the treatment of morbid (grade 3) obesity and its metabolic complications: a three-year study

Weight loss ameliorates arterial hypertension and glucose metabolism in obese patients, but the dietary approach is unsatisfactory because obesity relapses. Durable reduction of body weight, obtained through major nonreversible surgical procedures, such as jejunal and gastric bypass, allows improvement of glucose metabolism and arterial blood pressure in morbid (grade 3) obesity. Laparoscopic adjustable gastric banding (LAGB) is a minimally invasive and reversible surgical procedure that yields a significant reduction of gastric volume and hunger sensation. In this study, 143 patients with grade 3 obesity [27 men and 116 women; age, 42.9 +/- 0.83 yr; body mass index (BMI), 44.9 +/- 0.53 kg/m(2); normal glucose tolerance (NGT; n = 77); impaired glucose tolerance (IGT; n = 47); type 2 diabetes mellitus (T2DM; n = 19)] underwent LAGB and a 3-yr follow-up for clinical (BMI, waist circumference, waist to hip ratio, and arterial blood pressure) and metabolic variables (glycosylated hemoglobin, fasting insulin and glucose, insulin and glucose response to oral glucose tolerance test, homeostasis model assessment index, total and high-density lipoprotein cholesterol, triglycerides, uric acid, and transaminases). At baseline and 1 yr after LAGB, patients underwent computerized tomography and ultrasound evaluation of visceral and sc adipose tissue. One-year metabolic results were compared with 120 obese patients (51 men and 69 women; age, 42.9 +/- 1.11 yr; BMI, 43.6 +/- 0.46 kg/m(2); NGT, n = 66; IGT, n = 8; T2DM, n = 46) receiving standard dietary treatment. LAGB induced a significant and persistent weight loss and decrease of blood pressure. Greater metabolic effects were observed in T2DM patients than in NGT and IGT patients, so that at 3 yr glycosylated hemoglobin was no longer different in NGT and T2DM subjects. Clinical and metabolic improvements were proportional to the amount of weight loss. LAGB induced a greater reduction of visceral fat than sc fat. At 1-yr evaluation, weight loss and metabolic improvements were greater in LAGB-treated than diet-treated patients. We conclude that LAGB is an effective treatment of grade 3 obesity in inducing long-lasting reduction of body weight and arterial blood pressure, modifying body fat distribution, and improving glucose and lipid metabolism, especially in T2DM.     

The safety and efficacy of a controlled low-energy ('very-low-calorie') diet in the treatment of non-insulin-dependent diabetes and obesity

We evaluated the safety and efficacy of a highly supplemented controlled low-energy (1764 kJ [420 kcal]) diet in the treatment of non-insulin-dependent diabetes and obesity. Six obese, diabetic women ranging from 143% to 297% of ideal body weight were studied in a metabolic ward for 48 days. The subjects ingested a weight-maintenance diet during an eight-day control period followed by 40 days of an experimental diet containing 1764 kJ (420 kcal) of a mixture of protein (43% of energy intake), carbohydrates (51%), and fat (6%), supplemented with minerals, trace elements, and vitamins. The subjects were monitored for balances of nitrogen and minerals, as well as for the appearance of cardiac arrhythmias by 24-hour electrocardiographic recordings. Weight loss was rapid and sustained and averaged 10.1% +/- 0.8% over 40 days. Fasting plasma glucose levels declined from 16.2 +/- 1.9 mmol/L (293 +/- 36 mg/dL) to 6.9 +/- 0.8 mmol/L (126 +/- 16 mg/dL) by day 35. Similarly, hemoglobin A1c levels fell from 0.11 +/- 0.009 (11.2% +/- 0.9%) to 0.8 +/- 0.001 (8.2% +/- 1.1%). Urinary C-peptide levels declined from 62.2 +/- 15.6 nmol/48 h to 20.0 +/- 5.9 nmol/48 h by days 39 to 40 and paralleled the decline in plasma glucose values, the majority of which occurred in the first seven days. Concentrations of serum cholesterol and triglycerides decreased. Balances for nitrogen, potassium, and magnesium were negative at -1.7 g/24 h, -2.2 mEq/24 h, and -2.9 mg/dL, respectively. Blood pressure decreased without orthostasis. Resting metabolic rate fell a mean of 18% but remained within normal limits. Triiodothyronine levels also declined. Twenty-four-hour ambulatory electrocardiographic readings disclosed no significant bradyarrhythmia or tachyarrhythmia for any patient. These studies, based on a limited number of subjects, demonstrate that a highly supplemented controlled low-energy diet is a safe and efficacious treatment for diabetes and obesity, leading to significant decreases in weight, blood pressure, and levels of plasma glucose and plasma lipids. Such diets may be the optimal initial treatment of moderate to markedly obese patients with non-insulin-dependent diabetes.     

Circulating ghrelin is sensitive to changes in body weight during a diet and exercise program in normal-weight young women

Ghrelin is directly involved with short-term regulation of energy balance. Although circulating levels of ghrelin are elevated in anorexia nervosa and reduced in obesity, the role of ghrelin in regulating long-term energy balance in healthy women has not been investigated. We examined the effects of a 3-month energy deficit-imposing diet and exercise intervention on circulating ghrelin in normal-weight, healthy women. Body composition, resting metabolic rate, and serum ghrelin were measured at pre-, mid-, and postintervention in controls (n = 7), who performed no exercise, and exercising women who remained weight stable (n = 5) or lost weight (n = 10). Exercise training occurred five times per week, and subjects were fed a specific diet. Ghrelin significantly increased over time (770 +/- 296 to 1322 +/- 664 pmol/liter) in the weight-loss group compared with the controls and the weight-stable group (P < 0.05). Changes in ghrelin were negatively correlated with changes in body weight (r = -0.61; P < 0.05). Body fat, body weight, and resting metabolic rate significantly decreased in the weight-loss group before the increase in ghrelin. These findings suggest that ghrelin responds in a compensatory manner to changes in energy homeostasis in healthy young women, and that ghrelin exhibits particular sensitivity to changes in body weight.