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Short sleep appears to be strongly associated with obesity and altered metabolic function, and sleep and growth hormone (GH) secretion seems interlinked. In obesity, both the GH-insulin-like-growth-factor-I (GH-IGF-I) axis and sleep have been reported to be abnormal, however, no studies have investigated sleep in relation to the GH-IGF-I axis and weight loss in obese subjects. In this study polygraphic sleep recordings, 24-h GH release, 24-h leptin levels, free-IGF-I, total-IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), cortisol and insulin sensitivity were determined in six severely obese subjects (BMI: 41+/-1 kg/m(2), 32+/-2 years of age), cross-sectional at baseline, and longitudinal after a dramatically diet-induced weight loss (36+/-7 kg). Ten age- and gender-matched nonobese subjects served as controls. Sleep duration (360+/-17 vs. 448+/-15 min/night; P<0.01), 24-h GH (55+/-9 vs. 344+/-55 mU/l.24 h; P<0.01), free-IGF-I (2.3+/-0.42 vs. 5.7+/-1.2 microg/l; P<0.01), and total-IGF-I (186+/-21 vs. 301+/-18 microg/l; P<0.01) were significantly decreased and 24-h leptin levels were increased (35+/-5 vs. 12+/-3 microg/l; P<0.01) in obese subjects at pre-weight loss compared with nonobese subjects After diet-induced weight loss the differences in GH, free IGF-I, and leptin were no longer present between previously obese and nonobese subjects, whereas a significant difference in sleep duration and total IGF-I levels persisted. Rapid eye movement (REM) sleep, non-REM sleep, IGFBP-3, ALS, and cortisol levels were similar in obese and nonobese subjects. Sleep duration, 24-h GH, and IGF-I levels were decreased and 24-h leptin levels were increased in obese subjects. We conclude that hyposomatotropism and hyperleptinemia in obesity are transient phenomena reversible with weight loss, whereas short sleep seems to persist after weight has been reduced dramatically.

Objective: It has been hypothesized that increased free insulin-like growth factor (IGF)-I levels generated from an increase in IGF-binding protein (IGFBP) protease activity could be the inhibitory mechanism for the decreased growth hormone (GH) secretion observed in obese subjects., Research Methods and Procedures: In this study, we determined basal and 24-hour levels of free IGF-I and -II, total IGF-I and -II, IGFBP-1, as well as basal IGFBP-2, -3, and -4, acid-labile subunit (ALS), IGFBP-1, -2, and -3 protease activity, and 24-hour GH release in obese women before and after a diet-induced weight loss. Sixteen obese women (age, 29.5+/-1.4 years) participated in a weight loss program and 16 age-matched non-obese women served as controls., Results: Circulating free IGF-I and 24-hour GH release were significantly decreased in obese women at before weight loss compared with non-obese women (1.29+/-0.12 vs. 0.60+/-0.09 microg/L; p<0.001 and 862+/-90 vs. 404+/-77 mU/24 hours; p<0.001, respectively). Free IGF-I and 24-hour GH release were not inversely correlated to each other. IGFBP-1 and -2 levels were decreased, whereas ALS, IGFBP-3 and -4, and IGFBP-1, -2, and -3 protease activity were similar in obese and non-obese women. Eight of the 16 obese women achieved an average weight loss of 30+/-5 kg during 26 to 60 weeks of dieting. After the considerable weight loss, significant differences in free IGF-I, GH release, and IGFBP-1 and -2 levels were no longer present between previously obese and non-obese women., Discussion: We showed that circulating free IGF-I is markedly decreased in severely obese women and does not per se mediate the concomitant hyposomatotropism. The decreased levels of free IGF-I seem to be transient and restored to normal levels after weight loss.

Objective: Decreased levels of GH and total IGF-I have been reported in obesity. It has been hypothesized that increased free (biologically active) IGF-I levels generated from IGF-binding protein (IGFBP) protease activity could be the mechanism for the low GH release in dieting obese subjects. However, no published data exist on free IGF-I levels, acid labile subunit (ALS), or IGFBP protease activity in relation to GH release during a hypocaloric diet. The main purpose of this study was to determine free IGF-I, ALS, IGFBPs-1-4, and IGFBPs-1-3 protease activity in relation to 24-h GH release before and after a short-term very low-calorie diet (VLCD)., Design: Six obese subjects before weight loss, five after an average weight loss of 36.1 kg, and five age-and sex-matched lean controls underwent a 4-day VLCD. All subjects were studied on two occasions, once during normal basic diet and again during the last day of the VLCD (1.6 MJ)., Methods: Free IGF-I was determined by a non-competitive immunoradiometric assay., Results: Free IGF-I levels decreased in concert with increased ALS and unchanged blunted GH release after a VLCD in the obese subjects. IGFBPs-1-3 proteolytic activity was found to be unchanged by hypocaloric diet in all groups., Conclusions: We conclude that free IGF-I decreases after a short-term hypocaloric diet in obese subjects with no concomitant change in 24-h GH release. Circulating free IGF-I per se cannot be the main mechanism of the attenuated GH release in dieting obese subjects.

Background: The success rate of long-term maintenance of weight loss in obese patients is usually low. To improve the success rate, determinants of long-term weight maintenance must be identified., Objective: The objective of the study was to identify determinants of long-term success in weight maintenance in obese subjects who completed the Sibutramine Trial on Obesity Reduction and Maintenance (n = 261), a multicenter European study of weight loss and weight maintenance in obesity that combines sibutramine treatment with dietary restriction and advice on exercise and behavior., Design: We studied weight maintenance over 18 mo in subjects who had completed a 6-mo weight-loss phase. Factors included in the analysis were initial body weight, the percentage of initial body weight lost, dietary intake, various components of physical activity (measured with the Baecke questionnaire), the type of treatment (sibutramine or placebo), age, and sex., Results: Multiple regression analysis identified treatment group (sibutramine or placebo), the percentage of the initial body weight that was lost during the 6-mo weight-loss phase, and the leisure-time physical activity index as significant determinants of weight maintenance. Together, these 3 factors explained 20% of the variation in weight maintenance (P < 0.001). Dietary factors, age, and sex were not significant predictors of weight-maintenance success in this study., Conclusions: Weight-maintenance success after weight loss is positively influenced by sibutramine treatment during weight maintenance, by a greater initial weight loss, and by a higher leisure-time physical activity index, which reflects higher levels of activities such as walking and cycling and lower levels of television viewing.

Background: Plasma tryptophan concentrations and the ratio of tryptophan to other large neutral amino acids (plasma tryptophan ratio) are reportedly low in obese subjects. The plasma tryptophan ratio predicts brain tryptophan uptake and serotonin production. If this ratio is low in obese subjects, serotonin function may also be low. Plasma tryptophan concentrations and ratios have been measured only at single time points in obese subjects; it is not known whether low values for these 2 variables persist throughout a 24-h period., Objective: Our objective was to determine whether plasma tryptophan concentrations and ratios in obese subjects are lower than those in normal-weight subjects throughout a 24-h period and whether they increase when body weight is reduced., Design: Plasma tryptophan concentrations and ratios were examined in obese subjects before and after weight loss and in nonobese control subjects. Blood samples were drawn frequently throughout the 24-h period. An insulin tolerance test was also used to determine whether weight loss altered the ability of insulin to modify plasma concentrations of tryptophan and of the other large neutral amino acids., Results: Plasma tryptophan concentrations and ratios in obese subjects were low at all times; these effects persisted after weight reduction. Plasma concentrations of all the large neutral amino acids decreased during insulin infusion in all the groups., Conclusions: The low 24-h plasma tryptophan ratios in obese and formerly obese subjects suggest that brain tryptophan uptake may be continuously diminished and may remain below normal despite weight reduction.

Aim: To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG)and beta-cell function., Design: Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet., Subjects: Twelve obese patients (11 women, 1 man), age 45.8 +/- 10.5 years, body weight (BW) 99.7 +/- 13.3 kg, BMI 35.3 +/- 2.8 kg/m(2)., Measurements: At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning., Results: The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a19% increase. A significant decrease in both fasting (p = 0.038) and 2 h (p = 0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r = - 0.83,p = 0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in S(I) explaining 67% of the variation. First phase insulin response (AIRg)remained unchanged whereas insulin disposition index increased significantly (p = 0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later., Conclusion: In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor weight loss was able to normalize glucose tolerance.

Background: In this report we assess pre-treatment determinants of weight loss and maintenance outcome in The Sibutramine Trial of Obesity Reduction and Maintenance (STORM), a 2 y randomized, double-blind, placebo-controlled, European multicenter study examining the effect of sibutramine (Sib) on inducing and maintaining weight loss in obese subjects., Material: A total of 605 obese patients (BMI: 30-45 kg/m2) of both gender were included from eight European centers and treated for 24 months. The patients were treated for the initial 6 months by Sib (10 mg/day) and a low-fat low-energy, individualized diet (600 kcal/day deficit). The 467 patients who achieved >5% weight loss after 6 months were randomized 3&ratio;1 to Sib (10 mg/day) (Sib/Sib) and placebo (Sib/Pla) for weight maintenance over a further 18 months. MAIN OUTCOME AND ANALYSES: Pre-treatment individual characteristics were assessed as predictors of 6 months weight loss (kg) and 24 months weight maintenance using simple and multivariate correlation and regression analyses., Results: In univariate analyses, the 6 month weight loss (n=505) was positively associated with pre-treatment body weight (r=0.27), height (r=0.18), fat-free mass (r=0.21) (all P<0.001), fat mass (r=0.13, P<0.03), and resting metabolic rate (r=0.13, P<0.003). However, no relation was found with age, gender, smoking status, age at onset of obesity, or number of previous slimming attempts. The same predictors were found for weight change to endpoint in the Sib/Sib group (n=350), while no predictors were identified in the Sib/Pla (n=114). In the multivariate regression analysis only pre-treatment body weight predicted weight loss at 6 months (P<0.001). Weight change (kg) to 24 month was predicted by: 4.34+0.07*body weight (kg)-4*treatment (Sib=1, Pla=0)-0.06*age (y), (r2=8%, P<0.001)., Conclusion: Only pre-treatment body weight seems to be an important independent predictor of 6 months weight loss and 24 month weight maintenance in this study on diet and Sib. As only 8% of the variation in 24 months weight change could be explained by the predictors, the clinical value of this information is limited.

Background: Sibutramine is a tertiary amine that has been shown to induce dose-dependent weight loss and to enhance the effects of a low-calorie diet for up to a year. We did a randomised, double-blind trial to assess the usefulness of sibutramine in maintaining substantial weight loss over 2 years., Methods: Eight European centres recruited 605 obese patients (body-mass index 30-45 kg/m2) for a 6-month period of weight loss with sibutramine (10 mg/day) and an individualised 600 kcal/day deficit programme based on measured resting metabolic rates. 467 (77%) patients with more than 5% weight loss were then randomly assigned 10 mg/day sibutramine (n=352) or placebo (n=115) for a further 18 months. Sibutramine was increased up to 20 mg/day if weight regain occurred. The primary outcome measure was the number of patients at year 2 maintaining at least 80% of the weight lost between baseline and month 6. Secondary outcomes included changes in uric acid concentrations and glycaemic and lipid variables. Analysis was by intention to treat., Findings: 148 (42%) individuals in the sibutramine group and 58 (50%) in the placebo group dropped out. Of the 204 sibutramine-treated individuals who completed the trial, 89 (43%) maintained 80% or more of their original weight loss, compared with nine (16%) of the 57 individuals in the placebo group (odds ratio 4.64, p<0.001). Patients had substantial decreases over the first 6 months with respect to triglycerides, VLDL cholesterol, insulin, C peptide, and uric acid; these changes were sustained in the sibutramine group but not the placebo group. HDL cholesterol concentrations rose substantially in the second year: overall increases were 20.7% (sibutramine) and 11.7% (placebo, p<0.001). 20 (3%) patients were withdrawn because of increases in blood pressure; in the sibutramine group, systolic blood pressure rose from baseline to 2 years by 0.1 mm Hg (SD 12.9), diastolic blood pressure by 2.3 mm Hg (9.4), and pulse rate by 4.1 beats/min (11.9)., Interpretation: This individualised management programme achieved weight loss in 77% of obese patients and sustained weight loss in most patients continuing therapy for 2 years. Changes in concentrations of HDL cholesterol, VLDL cholesterol, and triglyceride, but not LDL cholesterol, exceed those expected either from weight loss alone or when induced by other selective therapies for low concentrations of HDL cholesterol relating to coronary heart disease.

Objective: To validate the ability of DXA to measure total body composition before and after weight loss and the composition of the lost body mass., Design: Cross sectional and follow-up study of body composition before and after a weight loss of 10.6 +/- 6.8 kg., Subjects: 31 obese subjects with a mean body weight of 105.2 +/- 15.2 kg at baseline, and a mean body weight of 94.6 +/- 16.5 kg at follow-up., Measurements: Body composition was measured by dual X-ray absorptiometry, total body potassium counting, and high precision scales before and after a weight loss., Results: DXA and the scales showed a strong linear relation (r = 1). At baseline, however, DXA underestimated the body weight by a maximum of 3.2 kg because the subjects were too large for the scan table. After weight loss body weight measurements were accurate. Before and after weight loss the linear relations between DXA and TBK for FFM were strong (r = 0.92 and 0.93). Bland and Altman plots showed limits of agreement of +/-9 kg before and after weight loss; DXA underestimated FFM in women and overestimated FFM in men. DXA accounted for 80% of the lost body weight. The composition of the lost body mass did not differ from that estimated by TBK (7.6% FFM and 92.4% FM by TBK; 11% FFM and 89% FM by DXA)., Conclusion: DXA estimates accurately the body composition and the composition of weight loss in groups of obese subjects. However, the scan table may be too small for patients weighing more than 95 kg.

A total of 16 obese women (body mass index (BMI) 30-43 kg m(-2)) participated in a weight reduction study. Before and after a weight loss of 11.7 +/- 7.4 kg (mean +/- SD), body composition was assessed by dual energy X-ray absorptiometry (DXA), and total body potassium counting (TBK). These measurements were compared with bioimpedance analysis (BIA) by applying 11 predictive BIA equations published in the literature. Predictive equations for the present study population were developed, with the use of fat-free mass (FFM) as assessed by TBK and DXA as references in multiple regression analysis. The results of the BIA equations varied widely; FFM was generally overestimated by BIA as compared with DXA and TBK before and after weight loss. During weight loss, the FFM did not change, as estimated by DXA (1.3 +/- 2.3 kg, p > 0.05) and TBK (0.9 +/- 2.9 kg, p > 0.05). The recorded change in impedance (R) was also insignificant. Three BIA equations from the literature, which were not specific for the degree of obesity in the present study group, predicted changes in FFM (from 0.5 + 3.6 to 2.4 +/- 4.4kg, p > 0.05) that were comparable with those estimated by the reference methods. Eight equations from the literature, which included equations specific for the degree of obesity in the study group, and the group specific equations developed for the present population predicted significant changes in FFM during weight loss (from 2.3 +/- 3.0 to 5.0 +/- 3.0 kg, p < 0.05). We conclude that in obesity most predictive equations are unable to predict static body composition and are not reproducible for individuals over time. However, a significant or insignificant change in R (without accompanying predictive equations) may be used to indicate whether FFM is lost or preserved in groups of obese subjects.

GH-binding protein (GHBP) is increased in obesity. It is not known whether the increase in GHBP is reversible with weight loss or modulated by acute changes in nutritional intake. To address these questions, we measured GHBP in 18 obese subjects [body mass index (BMI), 40.9 +/- 1.1 kg/m2 (mean +/-SEM)] before and after an average weight loss of 30.3 +/- 4.6 kg and in 18 age- and sex matched normal subjects (BMI, 23.0 +/- 0.4 kg/m2) and studied the effects of a very low calorie diet over 4 days in 5 normal subjects and a subgroup of obese subjects before (n = 6) and after (n = 5) weight loss. GHBP was elevated in the obese subjects compared to levels in age- and sex-matched normal controls (1.48 +/- 0.1 vs. 0.53 +/- 0.1 nmol/L; P < 0.0001). GHBP was positively correlated to BMI and waist circumference (r = 0.71; P < 0.00001 and r = 0.73; P < 0.00001, respectively). In addition, GHBP was positively correlated to insulin as well as proinsulin levels (r = 0.60; P < 0.001 and r = 0.55; P < 0.001, respectively). After diet-induced massive weight loss, GHBP levels were restored to normal in obese subjects (BMI, 27.8 +/- 1.4 kg/m2). Multiple stepwise regression analysis revealed that changes in waist circumference and abdominal sagittal diameter during weight loss were the major determinants of and accounted for 54% of the fall in GHBP levels. Neither insulin nor proinsulin was an independent predictor. No changes were observed in GHBP in normal, obese, or reduced weight obese subjects after 4 days of a very low calorie diet, although mean insulin levels fell significantly in the normal subgroup as well as in the obese subgroup studied after weight loss. In summary, GHBP levels are elevated in obesity, are restored to normal by massive weight loss, and are unaffected by short term hypocaloric feeding. We conclude that GHBP may be regulated by the same or closely related factors that regulate fat mass and abdominal fat mass in particular, but not by insulin or acute changes in nutrition.

Objective: To investigate the impact of obesity, fat distribution and weight loss on collagen turnover using serum concentrations of the carboxyterminal propeptide of type I procollagen (S-PICP) and the aminoterminal propeptide of type III pro-collagen (S-PIIINP) as markers for collagen turnover., Design: Blood samples were obtained once at baseline, and after 8 and 16 weeks of dietary treatment (5.0 MJ/day diet)., Setting: Outpatient clinic of Hvidovre University Hospital., Main Outcome Measures: S-PICP, S-PIIINP, fat distribution and weight loss., Results: S-PIIINP was associated with body weight (r = 0.37; P = 0.004), height (r = 0.27; P = 0.04), waist circumference (r = 0.35; P = 0.007), as well as with WHR (r = 0.33; P = 0.01) and was inversely correlated to age (r = -0.40; P = 0.002). Compared with randomly selected controls from a large pool of healthy volunteers, the obese patients had elevated S-PIIINP values before as well as during weight loss, whereas S-PICP levels were within the normal range and did not correlate with any anthropometric measures. The average weight loss after 16 weeks dietary treatment was 8.1 kg (s.d. = 0.8). S-PIIINP decreased during the 16 weeks of energy restriction (P < 0.05) and changes in S-PIIINP was correlated to body weight loss (r = 0.32; P < 0.05) and to changes in waist circumference (r = 0.34; P < 0.05) as well as changes in WHR (r = 0.30; P < 0.05)., Conclusion: S-PIIINP is elevated in obesity and associated with body fat distribution, suggesting an increased turnover of type III collagen related to obesity in general and to abdominal obesity in particular. S-PIIINP levels decreases during weight loss in obese subjects, whereas S-PICP levels seems un-related to obesity and weight loss.

In the present study, we 1) determined whether the impaired spontaneous 24-h GH secretion as well as the blunted GH response to provocative testing in obese subjects are persistent disorders or transient defects reversed with weight loss and 2) investigated 24-h urinary GH excretion and basal levels of insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), as well as insulin in obese subjects before and after a massive weight loss. We studied 18 obese subjects (age, 26 +/- 1 yr; body mass index, 40.9 +/- 1.1 kg/m2); 18 normal age-, and sex-matched control subjects; and 9 reduced weight obese subjects after a diet-induced average weight loss of 30.3 +/- 4.6 kg. Twenty-four-hour spontaneous GH secretion was estimated by obtaining 3240 integrated 20-min blood samples using a constant blood withdrawal technique and computerized algorithms. Body composition was determined using anthropometric measurements and dual energy x-ray absorptiometry scanning (DXA). In the obese subjects, 24-h spontaneous GH release profiles and the GH responses to insulin-induced hypoglycemia and L-arginine as well as basal IGF-I levels and the IGF-I/IGFBP-3 molar ratio were decreased, whereas insulin levels were elevated compared to those in normal subjects. In obese subjects, 24-h spontaneous GH secretion and serum IGF-I levels were inversely related to abdominal fat (r = -0.67; P < 0.01) and percent body fat (r = -0.69; P < 0.01), respectively. The decreased 24-h spontaneous GH release profiles, the decreased GH responses to insulin-induced hypoglycemia and L-arginine, the decreased basal IGF-I levels and IGF-I/IGFBP-3 molar ratio, as well as the elevated insulin levels were returned to normal after a massive weight loss in the obese subjects. In conclusion, the present study has shown reversible defects in 24-h spontaneous GH release profiles, basal IGF-I levels, and the IGF-I/IGFBP-3 molar ratio in obese subjects. The recovery of the 24-h GH release points to an acquired transient defect rather than a persistent preexisting disorder.

Obesity is associated with a marked reduction in the spontaneous secretion of GH. To investigate the effect of acute alterations in calorie intake on GH release, 24-hr spontaneous GH release was measured during habitual calorie intake as well as during a short term, very low calorie diet (VLCD) in 6 obese subjects, 5 obese subjects after weight loss, and 5 normal, age- and sex-matched control subjects. Integrated 20-min samples were obtained over 24-h on two occasions in each subject using a constant blood withdrawal technique. In addition, basal levels of serum insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGF-binding protein-3 (IGFBP-3), insulin, pro-insulin, and blood glucose were measured during habitual energy intake as well as during the hypocaloric diet. Twenty-four-hour GH release profiles and IGFBP-1 were decreased, and insulin as well as proinsulin levels were elevated in obese subjects compared to those in normal age- and sex-matched controls. No differences between obese subjects and normal controls were present regarding IGF-I, IGFBP-3, or IGF-I/IGFBP-3 molar ratio. In the last 24 h during the 96-h VLCD, an increase in 24-h GH release and basal IGFBP-1 levels and a decrease in basal insulin levels occurred in the normal controls, whereas no such changes were observed in the obese subjects. After caloric restriction 24-hr GH release, IGFBP-1 levels and insulin levels were similar in control subjects and obese subjects after weight loss. This suggests a reversible defect in GH release, rather than a persistent preexisting disorder. It is hypothesized that enhanced bioavailability of IGF-I, acting in concert with elevated proinsulin and insulin levels, may account for the lack of stimulation of 24-hr GH release by the hypocaloric diet in obese subjects. We conclude that the increase in 24-h spontaneous GH release and IGFBP-1 levels observed in normal subjects during the last 24 h of a 96-h VLCD is abolished in obese subjects. The lack of short term hypocaloric stimulation of spontaneous GH release may promote the retention of body fat and perpetuate the obese state.

The aim of this study was to characterize the association between serum insulin-like growth factor-1 (IGF-1) and obesity, as well as fat distribution, before and during moderate energy restriction (1,200 kcal/d). In 51 females and nine males having a body mass index (BMI) between 27 and 39 kg/m2, relationships between serum IGF-1, IGF-binding protein-3 (IGFBP-3), insulin, growth hormone (GH), blood glucose, and anthropometric measurements of body fat were examined. The patients were studied before treatment and again after 8 and 16 weeks of dieting. Visceral adipose tissue (AT) was estimated by anthropometric computed tomography (CT)-calibrated equations. In females, IGF-1 was inversely associated with the abdominal sagittal diameter (SagD) and with the visceral AT (r = -.41, P = .006). No significant correlations were found between IGF-1 and BMI or other indices of adiposity. Weight loss caused a temporary increase in IGF-1 concentrations (P = .03) and continued decrements in blood glucose levels (P = .0004 at 16 weeks). A statistically significant inverse correlation between IGF-1 and blood glucose levels was present before (r = -.30, P = .02) and after 8 (r = -.37, P = .007) and 16 (r = .02, P = .02) weeks of dietary treatment. Both serum IGF-1 and insulin levels were positively correlated with serum IGFBP-3 levels (r = .34, P = .009 and r = .34, P = .008, respectively). We conclude that IGF-1 levels in obese females reflect the intraabdominal fat mass rather than obesity per se. IGF-1 and blood glucose levels are inversely correlated in obesity before and during energy restriction.

Objective: To study the effect of cimetidine suspension compared with placebo suspension on weight loss in moderately obese patients taking a 5 MJ/day diet supplemented with dietary fibre. To determine the relation between the effectiveness of the blinding and weight loss., Design: Randomised double blind study with an eight week parallel group phase and a subsequent eight week crossover or continuation phase., Setting: Outpatient clinic., Subjects: 60 patients (51 women) aged 18-60., Main Outcome Measure: Weight loss., Results: After eight weeks of treatment the mean weight loss in the cimetidine group (5.7 kg) was similar to that of the placebo group (5.9 kg; p = 0.78, 95% confidence interval -2.0 to 1.5 kg). Body mass index, waist and hip measurements, waist-hip ratio, and systolic and diastolic blood pressures decreased similarly in the two groups. No association was found between weight loss and the patients' ability to guess if they were being given drug or placebo. Correct guesses of current drug were more prevalent than expected by chance (25/37 correct, p = 0.05 for the parallel group phase; 26/30, p = 0.0001 for the crossover phase)., Conclusions: Cimetidine had no effect on weight loss in moderately obese patients. The study underlines the potential problem that blinding of patients to treatment can be compromised.

SUMMARY Aim To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI ), non-insulin mediated glucose disposal, glucose effectiveness (SG ) and β-cell function. Design Glucose metabolism was evaluated before and after participation in a two-year weight loss trial of Orlistat vs. placebo, combined with an energy and fat restricted diet. Subjects Twelve obese patients (11 women, 1 man), age 45.8 ± 10.5 years, body weight (BW) 99.7 ± 13.3 kg, BMI 35.3 ± 2.8 kg/m2 . Measurements At inclusion and 2 years later an oral glucose tolerance test (OGTT) and a frequently sampled intravenous glucose tolerance test (FSIGT) were performed. Body composition was estimated by a dual-energy X-ray absorptiometry (DXA) whole body scanning. Results The patients obtained varying changes in BW ranging from a weight loss of 17.8 kg to a weight gain of 6.0 kg. Corresponding changes in fat mass (FM) varied from a 40% reduction to a 19% increase. A significant decrease in both fasting (p = 0.038) and 2 h (p = 0.047) blood glucose at OGTT was found. The improvement in insulin sensitivity (SI ) estimated by means of Bergmans Minimal Model, was significantly and linearly correlated to change in total FM (r = - 0.83, p = 0.0026). A multiple regression analysis showed that changes in truncal FM was the strongest predictor of change in SI explaining 67% of the variation. First phase insulin response (AIRg) remained unchanged whereas insulin disposition index increased significantly (p = 0.044). At inclusion five patients had impaired glucose tolerance of which four, who lost weight, were normalized at the retest 2 years later. Conclusion In obese subjects long-term minimal or moderate changes in weight were found to be linearly associated with changes in insulin sensitivity. In obese subjects with impaired glucose tolerance even a minor... [ABSTRACT FROM AUTHOR]