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PubMed1997

Familial risk ratios for extreme obesity: implications for mapping human obesity genes.

OBJECTIVE: To determine familial risk ratios for extreme obesity to aid in the design of obesity linkage studies. DESIGN: Family study of obesity. SUBJECTS: 2349 first-degree relatives (parents and siblings) of 840 probands who are members of the National Association to Advance Fat Acceptance (NAAFA) and 5851 participants of the first phase of the National Health and Nutrition Examination Survey III. METHODS: Computed age-gender standardized risk ratios (SRRs) for obesity in relatives categorized by the level of obesity in the index case (proband). MEASUREMENT: Body mass index (BMI) (kg/m2). RESULTS: The risk of extreme obesity (BMI > or = 40) in relatives of extremely obese women (BMI > or = 40) was more than five times greater than in the population; furthermore, the risk of obesity in relatives was approximately linearly associated with the degree of obesity in the proband. The risk of thinness in relatives of obese individuals was substantially lower than in the general population. CONCLUSION: Because the familial risk ratio for extreme obesity is higher than for moderate levels of obesity, the number of families required to achieve adequate statistical power in gene mapping studies of obesity can be reduced substantially by focusing on family members of extremely obese individuals (BMI > or = 40).

Adult↗
PubMed2006

Glomerular volume and renal histology in obese and non-obese living kidney donors.

The link between obesity and renal disease is unclear, and there is no consensus as to whether obese individuals are at increased risk for kidney disease after living kidney donation if they otherwise meet acceptance criteria. We retrospectively studied time-zero (implantation) biopsies in 49 obese (body mass index (BMI) > or = 30 kg/m2) and 41 non-obese (BMI < 30 kg/m2) renal donors that met acceptance criteria. We found that our obese donor population had higher systolic blood pressure (P < 0.001 vs non-obese) and higher absolute iothalamate clearance (P = 0.001 vs non-obese) before donation. The obese donors had larger glomerular planar surface area compared to non-obese controls (P = 0.017), and this parameter correlated with patient weight and urinary microalbumin excretion. Detailed examination of the biopsies revealed that although most histologic findings were similar between groups, the obese donors had more tubular dilation (P = 0.01), but less tubular vacuolization (P = 0.02) than the non-obese controls. There was also a trend toward more arterial hyalinosis in the obese patients than controls (P = 0.08). From these data, our studies detected subtle differences in donor organs obtained from obese compared to non-obese individuals. Further studies should be carried out to quantify the long-term impact of these findings.

Adult↗
PubMed2005

Relationship of body fat distribution by waist circumference, dual-energy X-ray absorptiometry and ultrasonography to insulin resistance by homeostasis model assessment and lipid profile in obese and non-obese postmenopausal women.

OBJECTIVE: To correlate body fat distribution evaluated by waist circumference, dual-energy X-ray absorptiometry and ultrasonography to insulin resistance and lipid profile in obese and non-obese postmenopausal women. METHODS: We studied 40 obese and 47 non-obese postmenopausal women, assessing obesity by measuring waist circumference and fat tissue using dual-energy X-ray absorptiometry and ultrasonography, and examining their correlation with metabolic parameters: insulin resistance as determined by the homeostasis model assessment technique (HOMA-IR) and lipid profile including triglycerides (TG), total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), very-low-density lipoprotein, lipoprotein(a) (Lp(a)) and apoplipoprotein A-I (Apo A-I). RESULTS: There was no difference in lipid profile between the two groups. Insulin resistance was the metabolic disturbance of highest prevalence in the obese group, evaluated by HOMA-IR (obese: 3.38 +/- 2.2; non-obese: 1.20 +/- 0.7; p < 0.001). Obesity was not a confounding factor in linear regression analyses among HOMA-IR, HDL-C, TG, Lp(a), Apo A-I and the methods used to measure body fat distribution. Waist circumference was the method that best explained HOMA-IR (R(2) = 34.9%, p < 0.001) and TG concentration (R(2) = 10.9%, p = 0.002). HDL-C presented a positive association with subcutaneous fat evaluated by ultrasonography (R(2) = 12.5%, p < 0.001). Obesity was a confounding factor in multiple regression analyses between TC and LDL-C, when related to abdominal fat evaluated by ultrasonography, and resulted in a positive association among the obese and a negative association among the non-obese women. The sensibility of this method was related to the quantity of fat in the visceral region. CONCLUSIONS: Waist circumference showed the highest association with insulin resistance. Fat distribution evaluated by dual-energy X-ray absorptiometry and ultrasound was also associated with insulin resistance, but with lower intensity. The relationship of visceral fat distribution evaluated by ultrasound to TC cholesterol and LDL-C showed opposed results between obese and non-obese menopausal women.

Absorptiometry, Photon↗
PubMed2001

Cross-national comparison of childhood obesity: the epidemic and the relationship between obesity and socioeconomic status.

BACKGROUND: Obesity has become a worldwide epidemic. Recently WHO acknowledged an urgent need to examine child obesity across countries using a standardized international standard. Studies in adults find obesity and socioeconomic factors (SES) factors are correlated, but results are inconsistent for children. Using an international standard, we examined the prevalence of obesity and compared the associations between SES factors and obesity across countries. METHODS: Data for children aged 6-18 from nationwide surveys in the US (NHANES III, 1988-1994), China (1993), and Russia (1992) were used. We used the recently updated US NCHS body mass index (BMI = wt/ht(2)) reference to define obesity (BMI > or =95th percentile) and overweight (85th< or =BMI<95th percentile). The WHO recommends an early version of the NCHS reference for international use. We conducted logistic analyses to examine the relationship between SES and obesity. RESULTS: The prevalence of obesity and overweight was 11.1% and 14.3%, respectively, in the US, 6.0% and 10.0% in Russia, and 3.6% and 3.4% in China. The relationship between obesity and SES varied across countries. Higher SES subjects were more likely to be obese in China and Russia, but in the US low-SES groups were at a higher risk. Obesity was more prevalent in urban areas in China but in rural areas in Russia. CONCLUSIONS: Child obesity is becoming a public health problem worldwide, but the prevalence of obesity varies remarkably across countries with different socioeconomic development levels. Different SES groups are at different risks, and the relationship between obesity and SES varies across countries.

Adolescent↗
PubMed1986

Brown adipose tissue: contributions of nature and nurture to the obesity of an obese mutant mouse (ob/ob).

The aim of this investigation was to compare the contributions of the genotype of the brown adipose tissue (BAT) and of its environment to the obesity of the mutant mouse C57 BL/6J ob/ob. Pieces of interscapular BAT from lean or obese mice were transplanted to a site underneath the kidney capsule of recipient lean or obese mice. The grafts were left in place for 6 to 12 weeks and then examined by histological methods by electron microscopy to examine the ultrastructure of the mitochondria and by fluorescence histochemistry to examine the catecholaminergic innervation of the grafts. When lean BAT was grafted into obese mice, or when obese BAT was grafted into lean mice, kept at ambient temperatures, the characteristics of the donor BAT (i.e. lipid droplet size, mitochondrial ultrastructure and catecholaminergic innervation) transformed partially, but not completely, towards those of BAT in the host mouse. However, if lean mice containing obese BAT grafts were cold-acclimated at 4 degrees C or obese mice containing lean BAT grafts were warm-acclimated at 33 degrees C, the characteristics of the donor BAT transformed completely towards those of the BAT in the host mouse. This complete transformation occurred even if the host mice were returned to 23 degrees C after the period of temperature acclimation. Fluorescent histochemical observations indicated that the sympathetic innervation of BAT grafts was only indistinguishable from that of the lean or obese host BAT when the mice received a period of temperature acclimation (cold for lean mice; warm for obese mice). We conclude that BAT grafts from lean mice can assume the typical characteristics of BAT in obese hosts and that BAT grafts from obese mice can assume the typical characteristics of BAT in lean hosts provided that both the sympathetic innervation and the vascularization of the grafts is the same as in the host. Intrinsic properties of BAT in genetically obese mice are therefore unlikely to be of paramount importance in determining the obesity of the ob/ob mouse. Our results support the conclusions of other workers in implicating the low activity of the sympathetic innervation of BAT as being crucially important in causing the reduction of thermogenic activity.

Acclimatization↗
PubMed2002

Determinants of resting energy expenditure in obese and non-obese children and adolescents.

Resting energy expenditure (REE) is the largest component of total daily energy expenditure. Objectives of this study were to examine whether differences in REE exist after obesity develops in a group of children and adolescents, and to determine the effects of body composition, gender, age, pubertal development and parental obesity on REE. In 116 Caucasian children and adolescents (57 obese and 59 non-obese), aged 7.8 to 16.6 years, REE was assessed by open-circuit indirect calorimetry and different anthropometric variables and bioelectrical impedance were obtained (weight, height, skinfold thicknesses, waist and hip circumferences). Anthropometric indices and body compartments were calculated: the body mass index, surface area (SA), fat-free mass (FFM), fat-mass (FM) and percentage of FM. Differences between obese and non-obese subjects were tested and stepwise multiple regression analysis was performed with REE as dependent variable. Results show that REE was significantly higher in obese than in non-obese children and adolescents but REE/FFM ratio was not significantly different between these groups. In the non-obese group, FFM explained 73.1% of the variability in REE and gender, age and SA added 3.8%, 2.6%, and 2.6% to it, respectively. In the obese group, FFM was also the most powerful predictor of REE with 72.3%, followed by waist circumference and age with 2.5% and 2.1%, respectively. These results show that REE differences between obese and lean children do not seem to justify the maintenance of obesity. The main determinant of REE is FFM in both groups. No significant contribution of FM, pubertal development or parental obesity in REE was found in children and adolescents.

Adipose Tissue↗
PubMed1993

Lack of insulin feedback inhibition in non-obese and obese men.

The existence of insulin feedback inhibition is a controversial issue. The present study adopted a novel approach to determine whether insulin feedback inhibition exists in vivo during physiologic hyperinsulinemia and if it could contribute to enhanced insulin secretion in obesity. Serial plasma insulin and C-peptide levels were determined during a basal state and a hyperinsulinemic clamp (287 pmol/min/m2) and following discontinuation of the insulin infusion under euglycemic conditions. Insulin secretion rates were derived from plasma C-peptide levels and individual C-peptide kinetics using a two-compartment model. Eight non-obese and nine obese men were recruited for the studies, which were performed in random order. Men with significant variations in glucose levels during hyperinsulinemia were excluded from the analysis. Plasma glucose levels were similar between the non-obese and obese groups during all phases of the study, and similar plasma insulin levels were achieved in both groups during euglycemic hyperinsulinemia. In obese men, C-peptide levels were significantly greater compared with non-obese men during euglycemic hyperinsulinemia (P < .05). However, neither the non-obese nor the obese group demonstrated significant suppression of insulin secretion rates during euglycemic hyperinsulinemia. Expressing the data in absolute terms or as a percent of basal did not alter the results. Moreover, there was no significant change between the non-obese and the obese group during the rapid onset and cessation of hyperinsulinemia. Under euglycemic conditions, physiologic hyperinsulinemia does not induce suppression of endogenous insulin secretion in non-obese or obese men.

Adult↗
PubMedDate not supplied

Sympathetic activity and response to ACE inhibitor (enalapril) in normotensive obese and non-obese subjects.

BACKGROUND: Angiotensinogen has been proposed as a possible link between obesity and hypertension because the adipocyte produces angiotensinogen and contains the enzymes required for its conversion. Moreover, sympathetic overactivity has been reported in obese subjects. The aim of this study was to compare heart sympathetic activation and serum angiotensinogen levels in obese and non-obese normotensive subjects, their relationship, and the effect of a drug that modifies the renin-angiotensin system. METHODS: Serum angiotensinogen, leptin, lipids, glucose, and insulin levels were measured and 24-h electrocardiograph monitoring was carried out in 41 (20 non-obese and 21 obese) volunteers before and after administration of 5 mg enalapril twice/day for 7 days. RESULTS: Obese subjects had higher values than non-obese subjects for % body fat (35.1+/-4.6 vs. 30.5+/-5.2; p=0.005), triglycerides (1.93+/-0.9 vs. 1.25+/-0.7 g/L, p=0.002), insulin (114.8+/-82.5 vs. 45.9+/-22.2 pmol/L), leptin (31.4+/-20.4 vs. 14.1+/-11.2 ng/mL, p=0.002), and LF/HFn index (4.3+/-2.9 vs. 2.2+/-1.3, p<0.005). Enalapril increased angiotensinogen levels only in the non-obese group (4.2+/-3.9 vs. 9.7+/-5.4 ng/mL, p=0.001) and diminished the LF/HFn index (4.3+/-2.9 vs. 3.0+/-1.4, p=0.007) in the group of obese subjects. There was no association between angiotensinogen levels and sympathetic activity. CONCLUSIONS: Higher level of sympathetic activity was found in normotensive obese as compared with non-obese subjects. Enalapril treatment reduced heart sympathetic activity in obese subjects but did not change angiotensinogen levels.

Adult↗
PubMed2000

Plasma leptin levels in obese and non-obese postmenopausal women before and after hormone replacement therapy.

OBJECTIVE: the aim of this study was to investigate the effect of hormone replacement therapy (HRT) on plasma leptin levels in postmenopausal women, and the relationship between the plasma leptin levels and obesity. METHODS: premenopausal women with normal cycles (n=30; mean ages, 35.4+/-8.3 years) and postmenopausal women (n=45; mean ages, 49.5+/-4.7 years) were randomly selected. Women were classified as obese (BMI>27 kg/m(2)) and as non-obese (BMI<27 kg/m(2)). Blood samples were obtained from the premenopausal women at the beginning of cycle, and from the postmenopausal women before and 6 months after HRT. Plasma leptin levels were measured by radioimmunassay. RESULTS: plasma leptin levels were significantly higher in premenopausal women than in postmenopausal women (18. 60+/-5.0; 3.67+/-2.44 ng/ml, respectively, P<0.001). Obese premenopausal women (n=15) had significantly higher plasma leptin levels (24. 60+/-7.81 ng/ml) in comparison with the levels of the non-obese premenopausal women (n=15; 12.50+/-4. 63 ng/ml) (P<0.001). Although there was no significant difference in the plasma leptin levels between obese (n=25) and non-obese (n=20) postmenopausal women before HRT, plasma leptin levels were significantly elevated in both obese and non-obese postmenopausal women after HRT (P<0.001), and the obese women had significantly higher plasma leptin levels than the non-obese (29.05+/-10.53; 14.78+/-6.76 ng/ml, respectively, P<0.001). CONCLUSION: HRT is effective in the elevation of the plasma leptin levels in postmenopausal women, and in obese women the increase of the plasma leptin levels are more marked than the non-obese women after HRT.

Adult↗
PubMed1998

DNA polymorphism in the uncoupling protein 1 (UCP1) gene has no effect on obesity related phenotypes in the Swedish Obese Subjects cohorts.

OBJECTIVE: To investigate the relationships between the A-G point mutation at position -3826 bp in the 5' flanking domain of the uncoupling protein 1 (UCP1 A-3826G) and some obesity phenotypes in the Swedish Obese Subjects (SOS) cohorts of obese and non-obese men and women. Previous studies have supported the hypothesis of an association between the UCP1 A-3826G polymorphism and body weight regulation in humans. DESIGN: Case-control study comparing obese subjects from the SOS registry and a sample of the Swedish general population (body mass index (BMI) <27 kg/m2) with respect to genotype and allele frequencies of the UCP1 A-3826G polymorphism. SUBJECTS: A total of 985 Swedish subjects including 674 obese (310 Male; 364 Female) and 311 non-obese subjects (54 Male; 257 Female) from the SOS cohorts. MEASUREMENTS: DNA was extracted from total blood and genotyped by PCR-RFLP. Obesity-related phenotypes include weight history for SOS obese cohort and current weight, BMI, waist circumference and waist to hip ratio (WHR) for obese and normal weight subjects. RESULTS: No significant difference in the allelic frequencies between obese and non-obese subjects (0.25 vs 0.24; P = 0.67). In both genders, current weight, BMI, waist circumference, WHR and weight gain over time (either measures of maximal weight ever achieved minus weight at 20 y or current weight minus weight at 20 y) were similar in carriers and non-carriers of the UCP1 A-3826G mutation (P>0.05). Similar results were obtained when the three genotypes were compared. CONCLUSIONS: In contrast to what was found in other populations, the UCP1 A-3826G sequence variation is not associated with obesity-related phenotypes and weight gain over time in subjects from the SOS cohorts.

Adult↗
PubMed1999

How should the obese patient be managed? Possible approaches to a national obesity management network.

There is clearly a need for novel approaches to obesity and its management. This has been addressed by the Czech Society for the Study of Obesity, which established a multi-level obesity management network in response to the increasing prevalence of obesity in the Czech Republic. This network includes obesity management centres attached to major teaching hospitals, combined with input from obesity specialists, other specialists, primary healthcare physicians and weight reduction groups. Such an obesity management system aims to provide appropriate diagnostic and treatment facilities for various degrees of obesity throughout the country. The proposed density of the obesity management network takes into account the limited resources in the healthcare system. The network is designed to overcome the current poor level of understanding of obesity and the lack of time and financial resources which have been the most significant barriers to more involvement of primary care physicians in obesity management. In order to implement this system, a comprehensive education programme on obesity was initiated with postgraduate courses for obesity specialists and with training for counsellors of weight reduction groups.

Czech Republic↗
PubMed2001

Self-efficacy in relation to eating behaviour among obese and non-obese women.

OBJECTIVE: To assess the effect of a 3 month behaviour modification weight management programme on self-efficacy and anthropometric variables among obese women seeking treatment at an obesity management clinic and to compare self-efficacy among these obese women to non-obese women. DESIGN: Cross sectional. SUBJECTS: A total of 161 non-obese (BMI 22.6+/-2.9 kg/m(2)) and 138 obese (BMI 37.7+/-5.8 kg/m(2)) women of similar age. MEASUREMENTS: Self-efficacy in relation to eating was assessed by the Weight Efficacy Lifestyle (WEL) questionnaire. Demographic information was obtained by interview and questionnaire in the obese and by questionnaire in the non-obese. Anthropometric measurements were obtained by direct measure in the obese and BMI was calculated from self-reported weight and height in the non-obese. RESULTS: At entry to the programme obese women scored significantly less (P<0.0001) than non-obese women on the WEL (99.4+/-34.1 vs 139.0+/-24.9). Women who completed the programme (n=65) demonstrated a decrease in waist circumference of 3.9+/-5.3 cm, a 10.0+/-11.5% loss of excess weight and a significant improvement in total WEL score from 106.0+/-30.3 to 126.5+/-28.4. CONCLUSION: Improvements in some dimensions of self-efficacy among obese women were of sufficient magnitude to attain scores similar to women of a normal weight. The WEL questionnaire may provide an additional measure of success as well as provide positive feedback and encouragement to the client.

Adolescent↗
PubMed2005

Leptin is favourably associated with vascular function in obese Caucasians, but not in obese Africans.

The comparison of the associations between chronically elevated leptin levels and cardiovascular function in obese Africans and Caucasians has not yet been determined. Therefore, the aim of this study was to compare leptin's associations with cardiovascular function in obese African and obese Caucasian women to determine whether leptin's associations differ between these two groups. This study consisted of two case-case control studies. The first study included a sample of 102 apparently healthy African women and the second, 115 apparently healthy Caucasian women. All lean and obese subjects were selected from each study. The Finometer apparatus was used to obtain a more elaborate cardiovascular profile. Serum leptin levels, insulin levels and the lipid profile were determined. Stroke volume (SV) and cardiac output (CO) were significantly (P< or =0.01) elevated in both obese African and Caucasian groups compared to their lean controls. Total peripheral resistance (TPR) was significantly decreased and arterial compliance (C(W)) significantly increased in both obese African and Caucasian groups. In the obese Caucasian group, diastolic blood pressure (DBP) was significantly (P< or =0.01) lower, SV and C(W) significantly higher (P< or =0.01) and TPR significantly lower compared to the age, body mass index (BMI), and leptin-matched obese African group. After adjusting for age and BMI, leptin correlated negatively with DBP (P< or =0.05; r=-0.33) and TPR (P< or =0.05; r=-0.36) in the obese Caucasian group, but not in the obese African group. Even though leptin levels were similar in obese African and Caucasian women, leptin is favourably associated with vascular function in obese Caucasians, but not in obese Africans.

Adult↗
PubMed1985

Bile lipid secretion in obese and non-obese individuals with and without gallstones.

Biliary lipid secretion rates were measured in non-obese and obese individuals with and without cholesterol gallstones, using a steady-state, amino acid duodenal perfusion method. In addition, biliary lipid secretion rates were measured in five obese gallstone patients receiving high-dose chenodeoxycholic acid therapy (16-22 mg day-1 kg-1). Bile acid secretion rates in the non-obese patients with cholesterol gallstones (563 +/- SEM 70 mumol/h, n = 6) were significantly lower than in the non-obese controls (1078 +/- 210 mumol/h, n = 10, P less than 0.05), whereas cholesterol secretion rates were similar in the non-obese individuals with and without gallstones (51 +/- 7 and 42 +/- 4 mumol/h respectively). In the obese, both with and without gallstones, the major abnormality was hypersecretion of cholesterol (107 +/- 7 mumol/h, n = 7, and 81 +/- 15 mumol/h, n = 7, respectively). Both these values were significantly greater than those in the non-obese controls (P less than 0.01-0.02). Biliary cholesterol secretion rates correlated significantly with bile acid secretion rates but, for every mole of bile acid secreted, the obese secreted more cholesterol than the non-obese. Chenodeoxycholic acid treatment lowered biliary cholesterol saturation in obese gallstone patients by reducing biliary cholesterol secretion. These results suggest that there are two major types of defect in biliary lipid secretion in gallstone patients: reduced biliary bile acid secretion in non-obese gallstone patients and excessive biliary cholesterol secretion in the obese.

Adult↗
PubMed1993

Polycystic ovaries in non-obese and obese patients: possible pathophysiological mechanism based on new interpretation of facts and findings.

This study was designed to investigate the basic concentrations of different hormones in obese and non-obese patients with polycystic ovarian disease (PCOD). Eight women with PCOD, of whom four were obese with body mass index (BMI, kg/m2) of > 25 and four were non-obese with BMI < 25, volunteered to participate in this study. Serum samples were taken every 20 min over an 8 h period, starting at 2300 h, on day 5 of a spontaneous or gestagen-induced cycle. Basic insulin concentration was found to be significantly higher in the obese women compared with their non-obese counterparts (P < 0.0001). Serum concentrations of insulin-like growth factor binding protein (IGFBP-I) and sex hormone binding globulin (SHBG) were found to be significantly lower (P < 0.001 for both hormones) in the obese compared with the non-obese women. Serum concentrations of insulin-like growth factor I (IGF-I) did not differ between the two groups. The non-obese women had significantly higher serum concentrations of luteinizing hormone (LH) (P < 0.001) and of growth hormone (GH) (P < 0.002) than their obese counterparts. Based on these results, two models of the development of PCOD were suggested. In obese women, hyperinsulinaemia causes an excessive production of androgens through the enhancement of IGF-I receptors which, in synergism with LH, causes increased activity of cytochrome P-450c 17a. In non-obese patients, relative increase of GH concentration stimulates excessive ovarian IGF-I production. At this point synergism with LH results in excessive production of androgens by the same mechanism as in obese patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2005

Individual igf-I responsiveness to a fixed regimen of low-dose growth hormone replacement is increased with less variability in obese compared to non-obese adults with severe growth hormone deficiency.

BACKGROUND/AIMS: Decreased GH and IGF-I levels and increased GH responsiveness are frequently reported in obesity. As GH-deficient adults are commonly obese, the role of obesity in affecting hepatic responsiveness of IGF-I generation to GH stimulation is unclear in severe GH-deficient states. To address this question, we challenged a cohort of severely GH-deficient non-obese and obese adults with a fixed low GH dose (0.2 mg/day), and examined the relationship of body mass index (BMI) with IGF-I response. METHODS: 12 non-obese (6 males, median BMI 24.7 kg/m2) and 14 obese (7 males, median BMI 45.2 kg/m2) adults with severe GH deficiency were studied for 8 weeks. Blood samples were collected at baseline, and weeks 4 and 8. RESULTS: There was a larger increment and reduced variability of IGF-I levels in obese compared to non-obese GH-deficient adults at week 8, but not at week 4. A similar but smaller increment and less variability was observed with IGFBP-3. Increment IGF-I positively correlated with baseline BMI at weeks 4 (r=0.49, p<0.02) and 8 (r=0.47, p<0.02). No gender differences were observed with the IGF-I and IGFBP-3 response. CONCLUSIONS: This study demonstrates that there is a larger increment and deceased individual variability of IGF-I to the low GH replacement dose in obese compared to non-obese adults with severe GH deficiency, regardless of gender. The positive association of IGF-I increment with BMI implies a greater impact of obesity rather than GH deficiency in enhancing hepatic sensitivity to GH. These findings, thus, question the reliability of interpreting single serum IGF-I levels in non-obese adults with severe GH deficiency treated with low GH replacement doses.

3-Hydroxybutyric Acid↗
PubMed1989

Defects in insulin-receptor internalization and processing in monocytes of obese subjects and obese NIDDM patients.

We investigated intracellular processing of the insulin-receptor complex in monocytes from 12 healthy control subjects, 11 obese nondiabetic subjects, and 13 obese patients with non-insulin-dependent diabetes mellitus (NIDDM) by measuring receptor internalization, recovery of cell-surface insulin binding after receptor internalization, and the release of intracellular intact insulin (insulin retroendocytosis). When monocytes from the three groups of subjects were exposed to 100 nM unlabeled insulin for 30 min at 37 degrees C, the subsequent cell-surface 125I-labeled insulin binding was reduced, but the total number of insulin receptors, measured by radioimmunoassay, was not changed. These findings indicate a redistribution of insulin receptors from the surface to the cell interior. Insulin-receptor internalization was significantly lower in monocytes of obese NIDDM patients (mean +/- SE 17.8 +/- 4.7%) than in obese subjects and healthy control subjects (33.5 +/- 4.5%, P less than .05, and 34.4 +/- 3.7%, P less than .02, respectively). Moreover, in downregulated cells, a complete recovery of the initial insulin binding was observed in control subjects but not in obese NIDDM patients or obese nondiabetic subjects. The release of internalized insulin was also reduced in obese NIDDM patients and obese subjects (t 1/2 = 49.0 +/- 2.4 min, P less than .02; 47.4 +/- 5.7 min, P less than .05; and 32.9 +/- 3.8 in NIDDM patients, obese subjects, and control subjects, respectively). In the radioactivity released from monocytes of obese subjects and obese NIDDM patients, the percentage of intact insulin was higher (P less than .05) than in control subjects, suggesting reduced intracellular insulin degradation in obese subjects and obese NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Diabetes Mellitus↗
PubMed1996

Effect of exercise intensity on glucose and insulin metabolism in obese individuals and obese NIDDM patients.

OBJECTIVE: The primary purpose of this study was to evaluate the acute effect of exercise of differing intensity on plasma glucose and insulin responses to an oral glucose challenge. RESEARCH DESIGN AND METHODS: Six obese men and six obese men with NIDDM of similar age, weight, percentage body fat, and VO2peak participated in the study. Each subject underwent two 7-day exercise programs in a counterbalanced order at 2-week intervals. During each 7-day exercise period, the subjects cycled every day at a power output corresponding to 50% VO2peak for 70 min or 70% VO2peak for 50 min. Muscle glycogen utilization was estimated during exercise on day 7 using a [3H]glucose infusion technique in conjunction with indirect calorimetry. During the day before and after each 7-day exercise period, a 3-h oral glucose tolerance test (OGTT) was administered after a 12-h overnight fast. RESULTS: The average caloric expenditure did not differ between exercise at 50 and 70% VO2peak in both obese and obese NIDDM subjects. However, the carbohydrate oxidation was higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (77 +/- 5 vs. 68 +/- 6 g) and obese NIDDM subjects (70 +/- 4 vs. 58 +/- 6 g). Muscle glycogen utilization was also higher (P < 0.05) during exercise at 70 than 50% VO2peak in obese subjects (59 +/- 9 vs. 30 +/- 7 g) and in obese NIDDM subjects (48 +/- 5 vs. 24 +/- 5 g). In obese subjects, plasma glucose response area during the OGTT did not change after 7 days of exercise at either 50 or 70% VO2peak. Plasma insulin response area during the OGTT also did not change after 7 days of exercise at 50% VO2peak. However, plasma insulin response area was reduced (P < 0.05) after 7 days of exercise at 70% VO2peak (9,644 +/- 1,783 vs 7,538 +/- 1,522 microU.ml-1.180 min-1). In obese NIDDM subjects, both plasma glucose and insulin response areas during the OGTT did not decrease after 7 days of exercise at either 50 or 70% VO2peak. CONCLUSIONS: It is concluded that the exercise-induced improvement in insulin sensitivity is influenced by exercise intensity in obese individuals. The improved insulin sensitivity after 7 days of exercise at 70% VO2peak in obese individuals may be related to greater muscle glycogen utilization during exercise. The lack of improvement in glucose tolerance and insulin sensitivity after 7 days of exercise at either 50 or 70% VO2peak in obese NIDDM patients may be due to the fact that the NIDDM patients selected in the present study were relatively hypoinsulinemic.

Adipose Tissue↗