Healthy Obese Subjects Research Articles

Potentially prothrombotic abnormalities of coagulation in benign intracranial hypertension.

OBJECTIVE: Benign intracranial hypertension (BIH) may be caused by intracranial venous sinus thrombosis. Cerebral angiograms may, however, be normal in patients with BIH that are associated with conditions with an...

Fasting affects serum insulin-like growth factors (IGFs) and IGF- binding proteins differently in patients with noninsulin-dependent diabetes mellitus versus healthy nonobese and obese subjects

Fasting affects serum insulin-like growth factors (IGFs) and IGF- binding proteins differently in patients with noninsulin-dependent diabetes mellitus versus healthy nonobese and obese subjects

Left ventricular filling in young normotensive obese adults

Obesity is a condition of increased adipose tissue mass. The association between cardiovascular diseases and obesity are well documented. 1,2 An excess of body fat requires a high cardiac output to meet high metabolic demands. If this hemodynamic burden is sustained, cardiac adaptation may cause premature impairment of left ventricular (LV) contractile function. 3–5 No information is known about LV filling in normotensive young obese subjects. The present study analyzes the effect of obesity on LV dimension, wall thickness and diastolic filling in 30 healthy young obese subjects.

Prolonged very low calorie diet in obese subjects reduces factor VII and PAI but not fibrinogen levels

Fibrinogen, factor VII and plasminogen activator inhibitor (PAI) are now considered hematologic risk factors for cardiovascular disease and it is well known that their levels are increased in obesity. 52 obese healthy subjects (31 women), with BMI>30, were investigated to assess: (a) fibrinogen, factor VII and PAI levels in relation to the different types of body fat distribution, and (b) the effect of a prolonged period (3 months) of very low calorie diet (VLCD, 514 and 470 Kcal/day in women and men respectively) on the above mentioned variables. Only significantly higher factor VII and insulin levels were found in the subjects with the highest waist/hip ratio (WHR) values and no significant correlations were found between test results and WHR levels. After 3 months VLCD, body weight and BMI decreased markedly, and factor VII and PAI levels dropped significantly in 32/34 individuals who were compliant with the diet; changes in factor VII and PAI were correlated with decreases in BMI and apolipoprotein Al, but not with changes in insulin values or their sum after glucose load. Fibrinogen did not change significantly after diet. In conclusion, the present study in a group of highly obese subjects shows that a severe dietary restriction associated with marked weight loss consistently lowers factor VII and PAI, but not fibrinogen.

Insulin resistance is an important determinant of left ventricular mass in the obese.

Obesity in adults is associated with increased left ventricular (LV) mass. The mechanism for this is unclear, however. We tested the hypothesis that insulin resistance is an important independent contributing factor to LV mass in the healthy obese population. The study population consisted of 40 normotensive, nondiabetic, otherwise healthy obese subjects with body mass index (BMI) > 25 kg/m2. LV mass was echocardiographically determined according to the Penn convention, using the formula of Devereux and Reichek. Insulin resistance was assessed using indices derived from Intravenous Glucose Tolerance Test (IVGTT): insulin level at baseline, insulin level at 90 minutes of IVGTT (insulin-90), insulin integration over 90 minutes of IVGTT, and rate of glucose disposal (k value). Insulin-90 (r = .61, P = .0001), k value (r = .55, P = .003), insulin integration over 90 minutes (r = .46, P = .003), basal insulin (r = .44, P = .005), and BMI (r = .59, P = .0001) were all strongly correlated with LV mass by univariate analysis. No significant correlation was found with blood pressure or age. In multivariate regression analysis, only insulin-90 and k value correlated significantly with LV mass (P = .03, P = .02, respectively), accounting for 50% of the variance of LV mass, whereas the association with BMI became insignificant (P = .2). LV mass in the normotensive nondiabetic obese population is strongly associated with, and may be mediated by, the degree of insulin resistance and its associated hyperinsulinemia, independent of BMI and blood pressure.

Effects of metoclopramide on the growth hormone response to galanin in normal man.

One of the most prominent metabolic effects of the systemic administration of the synthetic neuropeptide galanin in man is the increase in growth hormone (GH) secretion. This stimulating action of galanin is thought to occur directly at the hypothalamic level through the release of GHRH. Recently, it has been shown that also dopaminergic drugs may elicit GH secretion through an increase in hypothalamic GHRH secretion. The aim of this study was to investigate if the action of galanin on GHRH and consequently on GH release may be mediated via dopaminergic pathways evaluating the effects of a potent central dopaminergic receptor blocker, metoclopramide (MCP), on the galanin-induced growth hormone (GH) secretion in normal subjects. We studied seven young non obese healthy subjects (three females and four males). GH secretion was evaluated after 45 min iv infusion of porcine galanin (0.5 mg in 100 ml of saline) from 0 to 45 min combined with a 60 min iv infusion of a) saline (100 ml) or b) MCP (10 mg in 100 ml of saline) from -15 to 45 min. In all the seven subjects, during galanin infusion, GH values increased with respect to baseline with peaks occurring between 30 and 60 min after the beginning of galanin infusion. Peak GH values ranged between 3.5 and 15.4 micrograms/l (mean 10.4 +/- 1.6 micrograms/l). During MCP infusion no significant differences in the GH response to galanin with respect to saline were observed both when absolute GH levels and GH AUC were examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Visceral fat loss measured by magnetic resonance imaging in relation to changes in serum lipid levels of obese men and women.

The effect of weight reduction on serum lipids in relation to visceral fat accumulation was studied in 78 healthy obese subjects (40 premenopausal women and 38 men) aged 27-51 years and with an initial body mass index of 30.7 +/- 2.2 kg/m2 (mean +/- SD). The subjects received a 4.2 MJ/day energy-deficit diet for 13 weeks. Magnetic resonance imaging was used to assess abdominal fat areas before and after weight loss. Weight reductions of 12.6 +/- 3.2 kg in men and 11.7 +/- 3.8 kg in women resulted in larger reductions in the fasting serum levels of total cholesterol (p < 0.05), low density lipoprotein cholesterol (p = 0.06), and triglycerides (p < 0.01) and a larger increase in the high density lipoprotein cholesterol/low density lipoprotein cholesterol ratio (p = 0.05) in men compared with women. Men also lost more visceral fat (p < 0.0001), whereas the reductions in the total and subcutaneous abdominal fat depots were similar. In women, visceral fat loss was significantly related with an increase of the high density lipoprotein cholesterol level, independent of the degree of total fat loss. In men, however, no significant correlations were observed between changes in visceral fat and any of the serum lipids. Comparisons of average changes in obese men and women suggest that visceral fat loss is associated with an improvement of the serum lipid profile. However, correlation analysis does not support a critical role of visceral fat in determining serum lipid concentrations on an individual level, except for an improvement of the high density lipoprotein cholesterol level with visceral fat loss in obese women.

Visceral fat accumulation in obese subjects: relation to energy expenditure and response to weight loss.

Seventy-eight healthy obese subjects, 40 premenopausal women and 38 men aged 27-51 yr received a 4.2 MJ/day energy-deficit diet for 13 wk. Resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) were measured by indirect calorimetry. Abdominal subcutaneous and visceral fat areas were calculated from magnetic resonance imaging scans before and after weight loss. Before weight loss, visceral fat accumulation was positively correlated with higher levels of RMR (P < 0.05) and DIT (P < 0.01) in women but not in men. The mean weight reduction was 12.2 +/- 3.5 (SD) kg. In men but not in women, an initially large visceral fat depot was associated with a reduced loss of weight and total fat mass (P < 0.05). Within each sex, an initial abundance of visceral fat was significantly related to a larger loss of visceral fat (P < 0.001) and in men to a smaller loss of subcutaneous fat (P < 0.05). These results suggest that there may be gender differences in the associations between visceral fat accumulation and components of energy expenditure (RMR and DIT) in obese subjects. Obese subjects with an initial abundance of visceral fat do not lose more body weight but more visceral fat than subjects with less visceral fat.

Habitual dietary intake and insulin sensitivity in lean and obese adults

Studies in rodents have shown that short-term increases in dietary fat result in fat cell enlargement and insulin resistance. In humans, although high-fat diets have been associated with obesity, little is known about the specific metabolic effects of these diets. In this study we explored possible associations between habitual dietary composition and insulin sensitivity. Twenty-two lean and 23 obese subjects were characterized by dietary history (food frequency questionnaire), anthropometrics, oral glucose tolerance, and insulin sensitivity (SI, from the minimal model). As shown previously, body mass index was positively correlated with percent of energy intake as fat (r = 0.47, P = 0.001). Increasing fat intake was also associated with diminished SI (r = -0.41, P = 0.01). In contrast, SI was positively correlated with fiber intake (r = 0.43, P = 0.007). Multivariate analysis confirmed the importance of dietary fiber for SI. We conclude that habitually low dietary fiber intake, along with elevated dietary fat, correlates with diminished SI in otherwise healthy lean and obese subjects.

Visceral fat accumulation measured by magnetic resonance imaging in relation to serum lipids in obese men and women

In 91 apparently healthy obese subjects (45 premenopausal women and 46 men) the associations between specific fat depots and serum lipids were studied. Magnetic resonance imaging was used to quantify fat depots at abdominal and hip level. In women, an accumulation of visceral fat was associated with a less favourable lipid profile, even after adjustment for age and body fat percentage: higher triglycerides levels ( P < 0.001), lower levels of HDL-cholesterol ( P < 0.01) and a diminished HDL-cholesterol/LDL-cholesterol ratio ( P < 0.01). In men, however, the significant inverse relationship between an abundance of visceral fat and the HDL-cholesterol/LDL-cholesterol ratio and the significant positive correlations with total-, LDL-cholesterol and triglycerides disappeared after adjustment for age and fat percentage. Within each sex, subcutaneous fat neither at abdominal level nor at hip level was significantly related to serum lipids. It is concluded that there are gender differences in the associations between visceral fat accumulation and serum lipids.

Physiological elevations of plasma β-endorphin alter glucose metabolism in obese, but not normal-weight, subjects

The present study was undertaken to evaluate the metabolic and hormonal responses to physiologic elevations of plasma β-endorphin concentrations in both normal-weight and obese healthy subjects. The infusion of synthetic human β-endorphin (4.5 ng/kg/min) produced the following: (1) in normal-weight subjects, no significant change of plasma glucose and pancreatic hormones (insulin, C-peptide, and glucagon), a significant plasma free fatty acids (FFA) increase, and a suppression of glycerol plasma levels; (2) in obese subjects, significant increases of glucose, insulin, C-peptide, and glucagon, a progressive decline of circulating FFA, and no change in glycerol plasma levels. In obese subjects, the intravenous administration of naloxone, given as a bolus (5 mg injected in 5 minutes) before the start of β-endorphin infusion, reduced the plasma glucose response to the opioid by approximately half, annulled the pancreatic hormonal responses, and also reduced the FFA, but not glycerol, response. In normal-weight subjects, naloxone pretreatment did not induce any change of the flat glucose and hormonal responses to β-endorphin, but reversed its effects on circulating FFA and glycerol. These data suggest that physiological elevations of plasma β-endorphin concentrations produce metabolic and hormonal effects in obese subjects significantly different from those occurring in normal-weight subjects; these effects are partially naloxone-sensitive, suggesting the mediation of endogenous opioid receptors.

Effects of Sodium Supplementation during Energy Restriction on Plasma Norepinephrine Levels in Obese Women*

We tested whether sodium restriction would counteract the decrease in sympathetic nervous system activity usually associated with marked energy restriction. The effects of two levels of energy restriction, with different sodium intakes, on plasma norepinephrine (NE) levels while supine and in response to standing were studied. Twenty-two healthy normotensive obese female subjects (body mass index, 34 +/- 1 kg/m2; weight, 90 +/- 2 kg) followed one of three 3-week protocols: 1) total fasting with 80 mmol/day NaCl, 2) a very low energy diet (VLED) containing 1.7 MJ, 93 g protein, and 90 mmol Na/day, with an additional 60 mmol/day NaCl supplement, or 3) total fasting without NaCl (0 Na fast). At the end of the baseline isocaloric diet and of total fasts or VLED, pulse, blood pressure, and plasma NE were measured after 4 h of recumbency and 5 and 10 min after assuming the upright posture. These measurements were repeated after 1 L physiological saline was infused into the 0 Na fast subjects. Cumulative negative sodium balance was observed only in the 0 Na fasting subjects. Supine blood pressure decreased from baseline with fasting, but not with the VLED. The decreases in systolic pressure and increases in heart rate on standing observed with all diets were greatest with the 0 Na fast. Supine plasma NE (vs. baseline value) declined (P less than 0.05) with the VLED, remained unchanged with the Na supplemented fast, but increased with the 0 Na fast (P less than 0.05). The upright plasma NE values were highest in the 0 Na fast subjects, but lower after the saline infusion as well as in the subjects on the VLED. Thus, the decrease in NE due to energy restriction with normal sodium intake was counteracted by moderate sodium restriction, and levels increased with zero sodium intake. Therefore, sodium depletion can override the suppressive effect of energy restriction and, instead, increase the activity of the sympathetic nervous system, as reflected by plasma NE.

Effects of Bicarbonate Supplementation on Urinary Mineral Excretion During Very Low Energy Diets

Metabolic acidosis is associated with increased calciuria and ammoniagenesis. This study evaluated the effects of oral sodium bicarbonate (NaHCO3) or combined potassium bicarbonate-calcium carbonate supplementation on urinary mineral excretion during the ketoacidosis of a very-low-energy protein diet. Seventeen healthy obese subjects (BMI: 37.5 +/- 3.2 kg/m2, weight: 100 +/- 3 kg) were given a 1.72 MJ all protein (93 g) liquid formula and a multivitamin-mineral supplement daily for 3 weeks. Subjects in groups 1 (n = 6) and 2 (n = 5) received 16 mmol KCl. In addition, subjects in group 1 received 60 mmol Na+ daily as sodium chloride, subjects in group 2, 60 mmol Na+ as NaHCO3. The subjects in group 3 (n = 6) were given 32 mmol K+ as bicarbonate and 16 mmol Ca++ as carbonate daily. Metabolic acidosis was prevented in groups 2 and 3 with bicarbonate and bicarbonate-carbonate administration. This was reflected in significant curtailment of the augmented ammonium nitrogen excretion found in group 1. The additional oral K+ in group 3 improved K+ balance and probably also inhibited ammoniagenesis. Urine calcium was greater (p less than 0.04) in group 1 subjects, but similar in groups 2 and 3, despite higher calcium intake in group 3. Urinary phosphorus decreased with time in all groups, but more so in the group 2 subjects who received NaHCO3. Acidosis was associated with the reverse effect on urinary magnesium, which decreased in group 1 subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunobiological Consequence of Regulation of Insulin Receptor on Alloactivated Lymphocytes in Normal and Obese Subjects

Acute manipulations of insulin in vivo regulate the display of insulin receptors induced on activated T lymphocytes after presentation of alloantigen. This study explored the immunobiological consequences of regulation of insulin-receptor display by acute manipulations of insulin achieved during the hyperinsulinemic-euglycemic clamp in healthy normal individuals and obese subjects. T lymphocytes were isolated at 0, 1, and 4 h of hyperinsulinemia from seven normal volunteers and seven obese individuals and studied for their capacity to 1) synthesize a complement of insulin receptors on cell membrane, 2) respond to alloantigen in the mixed-lymphocyte culture (an immunologic activity unrelated to manipulations in insulin concentrations in complete medium), and 3) respond to the lymphocyte-mediated cytotoxicity reaction (an immunologic activity known to be modulated by insulin). In the face of a reduction in receptor numbers to 25% of baseline in normal individuals, alloreactivity in the mixed-lymphocyte culture was not affected (95 +/- 9% of time 0 after 4 h of hyperinsulinemia), whereas lymphocyte-mediated cytotoxicity fell from 14 +/- 4 at time 0 to 2 +/- 2% sp Cr release (P less than 0.02). Hyperinsulinemia achieved by the clamp in seven obese subjects did not alter the synthesis of insulin receptors on cell membrane after presentation of alloantigen. In the absence of further reduction of insulin-receptor membrane display, neither the mixed-lymphocyte culture nor lymphocyte-mediated cytotoxicity reaction was affected. It is concluded that those immunologic activities of lymphocytes that can be modulated by insulin are affected by regulation of insulin-receptor display on activated lymphocytes. Therefore, receptor regulation is not effete but carries significant immunologic consequence.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in sleeping metabolic rate and glucose induced thermogenesis during a diet or a diet/exercise treatment

After 4 weeks of dieting, 4 weeks of frequent exercise training (6h/wk) were added to a low energy diet of 3.0 MJ/day in 6 out of 12 healthy obese female subjects (aged 30–46 years) in order to compare changes in sleeping metabolic rate (SMR) and glucose induced thermogenesis (GIT). On the basis of BMI and percentage of body fat a diet group (D) and a diet-exercise group were formed (DE). SMR and GIT were both measured during a 36-h stay in a respiration chamber. Weight loss and changes in body composition were similar after 4 weeks of dieting. Adding 4 weeks of physical training for the DE group after 4 weeks of dieting did not result in significant differences between D and DE. SMR decreased significantly after 4 weeks of dieting (D 13%; DE 12%, P<0.05), a decrease which was not restored by the addition of 4 weeks of exercise in the DE group. However, compared to the values obtained after 4 weeks of dieting SMR in the DE group tended to increase, which was in agreement with the lower decrease of triiodothyronine (T3) in the DE group (3.5%) compared to the D group (12%). GIT tended to decrease during the first 4 weeks of dieting but a significant decrease in GIT was only demonstrated in the diet-exercise group after 8 weeks. After weight reduction plasma concentrations of glucose and insulin decreased for the D and DE group both during fasting and after a glucose load.

Effects of sodium bicarbonate on nitrogen metabolism and ketone bodies during very low energy protein diets in obese subjects

This study evaluated the effects of oral sodium bicarbonate (NaHCO 3) supplementation on ammonium (NH 4 +) nitrogen (N) and urea N excretion and on ketone bodies during the metabolic acidosis of a very low energy protein diet. Ten healthy obese female subjects (BMI, 38.4 ± 1.5 kg/m 2; weight, 100 ± 4 kg) were given a 1.72 MJ (412 kcal) all protein (16.8 g N) liquid formula, 16 mmol KCl and a multivitamin-mineral supplement daily for 4 weeks. In addition, the five subjects in group 1 received 60 mmol Na + daily as sodium chloride (NaCl) for 3 weeks and as NaHCO 3 during week 4. The subjects in group 2 were given 40 mmol/d NaHCO 3 during the first week, 60 mmol/d during weeks 2 and 3, and 60 mmol/d NaCl during week 4. Nitrogen balance was achieved in both groups by the end of week 3. The subjects in group 1 at week 2 showed an increase in blood [H +] of 0.41 ± 0.06 × 10 −8 mol/L and a decrease in blood bicarbonate from 26.0 ± 0.8 to 23.8 ± 1.2 mmol/L. The subsequent NaHCO 3 curtailed NH 4 + N excretion by one half, without significant change in ketone body levels or excretion. Administration of NaHCO 3 from the start of the diet to the subjects in group 2 prevented both the metabolic acidosis and the increase in NH 4 + N excretion and attenuated the increase in blood and urine 3-hydroxybutyrate. When NaCl replaced NaHCO 3 during week 4, ammonium N excretion doubled. Urea N excretion was comparable in both groups and was unaffected by bicarbonate. Thus, NaHCO 3 supplementation resulted in the sparing of 9.11 g of N in 3 weeks and in the lowering of ketone body levels and excretion, at least in part by the neutralizing effect of HCO 3 − on the diet-induced metabolic acidosis.

Influence of a very low calorie diet on the clearance of oxazepam and antipyrine in man.

A very low calorie diet (Prodi) was administered to eleven otherwise healthy obese subjects for fourteen days. The daily intake of protein was 52.7 g and carbohydrate 25.7 g, corresponding to 360 kcal. The clearance of oxazepam and antipyrine was investigated before and after the diet period. Total oxazepam clearance was 1.04 ml.min-1.kg-1 and it decreased 0.88-fold after the diet. The mean clearance of unbound oxazepam was correspondingly reduced 0.88-fold. The elimination half-life increased to 1.22-times the control value, 7.9 h. No significant change was found in the volume of distribution or protein binding of oxazepam. Antipyrine clearance, estimated by the one-sample technique, was 52.4 and 51.8 ml.min-1, before and after the diet, respectively. It appears that a very low calorie diet with a sufficient protein and a very low carbohydrate content decreases the metabolism of oxazepam by glucuro-conjugation, whereas no effect was seen on the oxidative metabolism of antipyrine.

Sensitivity to β-endorphin as a cause of human obesity

Naloxone, an opiate antagonist, was given as an intravenous bolus (5 mg) in both lean and obese healthy subjects. In lean people, there was a slight trend for insulin and C-peptide concentrations to decrease below baseline values with no glucose change. Obese subjects showed an exaggerated suppression of insulin and C-peptide and a slight decrease of glucose. Glucagon was suppressed in both groups. An infusion of human β-endorphin (0.05 mg/h) produced only minor changes in plasma glucose, insulin, glucagon, and C-peptide concentrations in lean subjects, but caused marked increments in obese. Glucagon rose in both groups, but its response was greater in obese subjects. A ten-day treatment with naloxone (1.2 mg twice a day) did not change the metabolic and hormonal responses to an oral glucose load (75 g) in lean but significantly inhibited the insulin and C-peptide responses to glucose in obese people. These results suggest that an increased opiate drive to the pancreatic beta-cell and an increased responsiveness of insulin to β-endorphin are present in human obesity.

Diet-induced thermogenesis in man: thermic effects of single protein and carbohydrate test meals in lean and obese subjects.

Postprandial thermogenesis of 8 healthy males of normal body weight and 17 healthy obese subjects with a body weight gain of more than 10 kg per year was measured continuously by means of a respiratory chamber over 10 h after test meals of 1 and 2 MJ protein (casein) and 2 MJ carbohydrate (hydrolized starch). The total thermic response to all test meals was reduced by about 50% in the obese subjects. The thermic response was related to body weight, energy intake, resting metabolic rate and weight loss during restricted energy intake. The necessity for a careful characterization of the obese subjects in studies of thermogenesis and of efficiency of energy utilization in obesity is pointed out. It is suggested that thermic response to food can be considered as a suitable indicator for the distinction between people of different metabolic efficiency.

Epinephrine-stimulated glucose production is not diminished by starvation: evidence for an effect on gluconeogenesis.

We infused physiological doses of epinephrine (1.2 microgram/m2 X min) into six healthy obese subjects in the postabsorptive state and after 3-4 days of starvation. During starvation, a reduction in hepatic glycogen stores was demonstrated by the absence of a rise in plasma glucose and glucose production (using [3-3H]glucose) in response to glucagon infusion. The increases in plasma epinephrine and glucose during the epinephrine infusion were comparable before and after starvation. Most importantly, the increase in endogenous glucose production produced by epinephrine was virtually unaffected, i.e. the initial rise in glucose production (59% vs. 49%), the incremental area under the curve (2.6 vs. 3.1 g/m2), and the spike-decline pattern of the response were no different before and after starvation, respectively. Similarly, epinephrine-induced elevations in gluconeogenic precursors (lactate and alanine) were not altered by starvation. However, starvation accentuated the rise in FFA by 200%. We conclude that starvation does not diminish the rise in endogenous glucose production in response to stress-like elevations of epinephrine. This occurs even though the liver fails to respond to high physiological doses of glucagon, possibly because epinephrine enhances the mobilization of gluconeogenic precursors and FFA. These data suggest that epinephrine is a potent stimulator of gluconeogenesis and may be more effective than glucagon in accelerating glucose production in patients with depleted glycogen stores.