Insulin secretion in metabolically obese, but normal weight, and in metabolically healthy but obese individuals

Metabolically obese but normal-weight (MONW) individuals present metabolic disturbances typical of obese individuals. Additionally, metabolically healthy but obese (MHO) individuals have been identified who are relatively insulin sensitive and have a favorable cardiovascular risk profile. We compared insulin secretion patterns of MONW and MHO with those of two age-matched groups comprising nonobese individuals or obese insulin-resistant subjects, respectively. To this end, 110 nonobese subjects and 87 obese subjects were stratified into quartile based on their insulin-stimulated glucose disposal (M(FFM)). Insulin secretion was estimated by acute insulin response (AIR) during an intravenous glucose-tolerance test (IVGTT), and the disposition index was calculated as AIR x M(FFM). We found that, as defined, M(FFM) was lower in MONW, who exhibited higher triglycerides, free-fatty acid (FFA), and 2-h postchallenge glucose levels compared to normal nonobese group. Insulin secretion was higher in MONW than in normal nonobese subjects, but disposition index was lower in MONW. Disposition index did not differ between MONW and insulin-resistant obese. M(FFM) was higher in MHO who exhibited lower waist circumference, blood pressure (BP), triglycerides, FFA, insulin levels, and higher high-density lipoprotein (HDL) cholesterol compared to insulin-resistant obese. Insulin secretion did not differ between insulin-resistant obese and MHO, but disposition index was lower in the former group. In conclusion, MONW and insulin-resistant obese showed decreased compensatory insulin secretion compared to normal nonobese and MHO subjects, respectively. Because these subjects also exhibited a worse metabolic risk profile, these findings may account for their increased risk for type 2 diabetes.     

Awakening cortisol response in lean, obese, and reduced obese individuals: effect of gender and fat distribution

Objective: Our goal was to assess the awakening cortisol response (ACR) in obese and reduced obese men and women. Research Methods and Procedures: Fifty‐one men (16 lean, 19 abdominally obese, and 16 reduced obese) and 31 women (12 lean, 10 subcutaneously obese, and 9 reduced obese) were selected to participate to this study. Strict ranges of BMI and waist circumference were used to select the participants. Medical examination, psychological assessment, anthropometric measurements, and blood sampling were undergone at the laboratory. Cortisol response to awakening was determined with saliva cortisol sampling being taken immediately at the time of awakening and 30 minutes thereafter over 3 days within a period of 2 months. Results: Men with visceral obesity exhibited an enhanced ACR, whereas this response tends to return to normal in a reduced obese state. In women, peripheral fat accumulation does not modify ACR, but weight loss increased the response. Discussion: These results highlight gender effects on ACR of obese and reduced obese subjects, which could be accounted for by the different fat distribution profiles that characterize men and women. They also provide further support for the usefulness of ACR in assessing the hypothalamic‐pituitary‐adrenal axis activity status.     

Genes, exercise, growth, and the sedentary, obese child.

It is still not possible to provide an evidence-based answer to the question of whether regular exercise is essential for normal growth. It is also unclear whether very low levels of exercise result in growth deficits. Regular exposure to exercise is characterized by heterogeneity in responsiveness, with most individuals experiencing improvements in fitness traits but a significant proportion showing only very minor gains. Whether a sedentary mode of life during the growing years results in a permanent deficit in cardiorespiratory fitness or a diminished ability to respond favorably to regular exercise later in life remains to be investigated. Although several genes have been associated with fitness levels or response to regular exercise, the quality of the evidence is weak mainly because studies are statistically underpowered. The special case of the obese, sedentary child is discussed, and the importance of the "energy gap" in the excess weight gain during growth is highlighted. Obese, sedentary children have high blood pressure, dyslipidemia, elevated glycemia and type 2 diabetes, hepatic steatosis, respiratory problems, orthopedic complications, and other health disorders more frequently than normal weight, physically active children. The role of genetic differences in the inclination to be sedentary or physically active is reviewed. An understanding of the true role of genetic differences and regular exercise on the growth of children will require more elaborate paradigms incorporating not only DNA sequence variants and exercise exposure but also information on nutrition, programming, and epigenetic events during fetal life and early postnatal years.     

Disability prevalence among healthy weight,overweight, and obese adults

Objective:

Obesity is associated with adverse health outcomes in people with and without disabilities. However, little is known about disability prevalence among people who are obese. The purpose of this study is to determine the prevalence and type of disability among adults who are obese.

Design and Methods:

Pooled data from the 2003‐2009 National Health Interview Survey (NHIS) were analyzed to obtain national prevalence estimates of disability, disability type and obesity. The disability prevalence was stratified by body mass index (BMI): healthy weight (BMI 18.5‐<25.0), overweight (BMI 25.0‐<30.0), and obese (BMI ≥ 30.0).

Results:

In this pooled sample, among the 25.4% of US adults who were obese, 41.7% reported a disability. In contrast, 26.7% of those with a healthy weight and 28.5% of those who were overweight reported a disability. The most common disabilities among respondents with obesity were movement difficulty (32.5%) and work limitation (16.6%).

Conclusions:

This research contributes to the literature on obesity by including disability as a demographic in assessing the burden of obesity. Because of the high prevalence of disability among those who are obese, public health programs should consider the needs of those with disabilities when designing obesity prevention and treatment programs.     

Ketone body kinetics in normal,diabetic, and obese humans

We have developed a model for the kinetics of acetoacetate (A) and β-OH-butyrate (B) in normal subjects. The model contains separate compartments for blood A, B, and acetone, as well as three exchange compartments. By using the model, the synthesis, utilization, and clearance rates of A and B were determined separately. We have compared the model with others that have been proposed for ketone body metabolism and have used the model to analyse studies undertaken in newly diagnosed diabetic patients and obese subjects (before and after a 2 week period of starvation). We found that in diabetic and obese individuals the synthesis of ketone bodies was higher than normal and that the fractional losses of A and B were reduced. The results suggest that ketosis develops as a result of high synthesis rates coupled with decreased fractional loss of ketone bodies. In each group the metabolism of B was altered more than A.     

Postprandial endothelial function, inflammation, and oxidative stress in obese children and adolescents

Most studies in adults suggest that acute glucose consumption induces a transient impairment in endothelial function. We hypothesized that obese youth would demonstrate reduced endothelial function and increased inflammation and oxidative stress following acute glucose ingestion and that transient elevations in plasma glucose would correlate with endothelial dysfunction, inflammation, and oxidative stress. Thirty-four obese (BMI ≥ 95th percentile) children and adolescents (age 12.4 ± 2.6 years; BMI = 37.9 ± 6.7 kg/m2; 50% females) underwent measurement of endothelial function (reactive hyperemic index (RHI)), glucose, insulin, C-reactive protein (CRP), interleukin-6 (IL-6), circulating oxidized low-density lipoprotein (oxLDL), and myeloperoxidase (MPO) in a fasting state and at 1- and 2-h following glucose ingestion. Repeated measures ANOVA with Tukey post-tests and Pearson correlations were performed. Glucose and insulin levels significantly increased at 1- and 2-h (all P values < 0.001). Compared to baseline, there were no statistically significant differences in 1- and 2-h RHI, CRP, IL-6, and oxLDL. However, MPO significantly decreased at the 1- (P < 0.05) and 2-h (P < 0.001) time points. At the 1-h time point, glucose level was significantly inversely correlated with RHI (r = -0.40, P < 0.05) and at the 2-h time point, glucose level was positively correlated with MPO (r = 0.40, P < 0.05). An acute oral glucose load does not reduce endothelial function or increase levels of inflammation or oxidative stress in obese youth. However, associations of postprandial hyperglycemia with endothelial function and oxidative stress may have implications for individuals with impaired glucose tolerance or frank type 2 diabetes.     

Plasma obestatin levels in normal weight, obese and anorectic women

Obestatin is a recently discovered peptide produced in the stomach, which was originally described to suppress food intake and decrease body weight in experimental animals. We investigated fasting plasma obestatin levels in normal weight, obese and anorectic women and associations of plasma obestatin levels with anthropometric and hormonal parameters. Hormonal (obestatin, ghrelin, leptin, insulin) and anthropometric parameters and body composition were examined in 15 normal weight, 21 obese and 15 anorectic women. Fasting obestatin levels were significantly lower in obese than in normal weight and anorectic women, whereas ghrelin to obestatin ratio was increased in anorectic women. Compared to leptin, only minor differences in plasma obestatin levels were observed in women who greatly differed in the amount of fat stores. However, a negative correlation of fasting obestatin level with body fat indexes might suggest a certain role of obestatin in the regulation of energy homeostasis. A significant relationship between plasma obestatin and ghrelin levels, independent of anthropometric parameters, supports simultaneous secretion of both hormones from the common precursor. Lower plasma obestatin levels in obese women compared to normal weight and anorectic women as well as increased ghrelin to obestatin ratio in anorectic women might play a role in body weight regulation in these pathologies.     

Differences in physical activity between non-overweight, overweight and obese children

The purpose of the study was to find out differences in moderate to vigorous physical activity among non-overweight, overweight and obese children, and between boys and girls. The sample included 364 children (179 boys and 185 girls), aged 6.4 years (+/- 0.3 SD). Physical activity was assessed by 7-day questionnaire. Age adapted BMI was used as overweight and obesity indicator. The children were divided into non-overweight, overweight and obese groups. It was found out, that there are significant differences in non-overweight, overweight and obese children (p < 0.05). Boys were significantly (p < 0.05) less moderate to vigorous physical active than girls, especially in indoor activities. There were also significant differences (p < 0.05) in moderate to vigorous physical activity among non-overweight and obese boys and among overweight and obese boys in weekends and total weekly activity. In girls there are significant differences (p < 0.05) in non-overweight, overweight and groups in weekends and total weekly activity. It is possible to conclude, that obese boys and overweight and obese girls, are prone to less physical activity.     

Contributing factors and variability of energy expenditure in non-obese, obese, and post-obese adolescents

Energy expenditure (EE) is a major determinant of energy balance and body composition. The objectives of this paper were to review the contributing factors of the main components of daily EE (DEE) and the inter-individual variability in these components in non-obese (NOb), obese (Ob), and post-obese (POb) adolescents. Body composition especially fat-free mass (FFM), is the major determinant of the basal metabolic rate which contributes 50-70% of DEE, whereas fat mass (FM) is a significant factor only in obese subjects. Physical activity is the second main variation factor of DEE, whereas growth, the thermic effect of food, and thermoregulation are generally of marginal importance. The energy costs and EE associated with various sedentary and physical activities were assessed in NOb, Ob and POb subjects both in standardised and in free-living conditions. The interindividual variability of DEE is high, even after adjustment for body composition, mainly because of great differences in time devoted to the various physical activities. DEE and EE associated with sleep and sedentary activities are significantly higher in Ob than in NOb, but not after adjustment for FFM. On the contrary, EE associated with physical activities is not significantly different between Ob and NOb adolescents, but 61% lower in Ob subjects after adjustment for body composition. Multidisciplinary weight-reduction programmes including moderate energy restriction and physical training result in great FM loss, maintenance of FFM, improvement of physical capacities, but reductions in organ and tissue metabolic rate and in EE associated with the various sedentary and physical activities, which may favour body weight regain in the less active POb subjects.     

Respiratory system mechanics in sedated, paralyzed, morbidly obese patients

Pelosi, P., M. Croci, I. Ravagnan, M. Cerisara, P. Vicardi,A. Lissoni, and L. Gattinoni. Respiratory system mechanics insedated, paralyzed, morbidly obese patients J. Appl.Physiol. 82(3): 811-818, 1997.The effects ofinspiratory flow and inflation volume on the mechanical properties ofthe respiratory system in eight sedated and paralyzed postoperativemorbidly obese patients (aged 37.6 ± 11.8 yr who had never smokedand had normal preoperative seated spirometry) were investigated byusing the technique of rapid airway occlusion during constant-flowinflation. With the patients in the supine position, we measured theinterrupter resistance (Rint,rs), which in humans probably reflectsairway resistance, the "additional" resistance (Rrs) due toviscoelastic pressure dissipation and time-constant inequalities, andstatic respiratory elastance (Est,rs). Intra-abdominalpressure (IAP) was measured by using a bladder catheter, and functionalresidual capacity was measured by the helium-dilution technique. Theresults were compared with a previous study on 16 normal anesthetizedparalyzed humans. Compared with normal persons, we found that in obesesubjects: 1) functional residualcapacity was markedly lower (0.645 ± 0.208 liter) and IAP washigher (24 ± 2.2 cmH₂O);2) alveolar-arterial oxygenationgradient was increased (178 ± 59 mmHg);3) the volume-pressure curve of therespiratory system was curvilinear with an "inflection" point;4) Est,rs, Rint,rs, and Rrs werehigher than normal (29.3 ± 5.04 cmH₂O/l, 5.9 ± 2.4 cmH₂O ^· l^{1 ·} s,and 6.4 ± 1.6 cmH₂O ^· l^{1 ·} s,respectively); 5) Rint,rs increasedwith increasing inspiratory flow, Est,rs did not change, and Rrsdecreased progressively; and 6) withincreasing inflation volume, Rint,rs and Est,rs decreased, whereasRrs rose progressively. Overall, our data suggest that obesesubjects during sedation and paralysis are characterized by hypoxemiaand marked alterations of the mechanical properties of the respiratorysystem, largely explained by a reduction in lung volume due to theexcessive unopposed IAP.

     

Central orexin sensitivity, physical activity, and obesity in diet-induced obese and diet-resistant rats

Nonexercise activity thermogenesis (NEAT), the most variable component of energy expenditure, can account for differential capacities for human weight gain. Also highly variable, spontaneous physical activity (SPA) may similarly affect weight balance in animals. In the following study, we utilized the rat model of obesity, the diet-induced obese (DIO) rat, as well as the diet-resistant (DR) rat strain, to investigate how access to a high-fat diet alters SPA and the associated energy expenditure (i.e., NEAT). DIO and DR rats showed no differences in the amount of SPA before access to the high-fat diet. After 29 days on a high-fat diet, the DIO rats showed significant decreases in SPA, whereas the DR rats did not. Next, we wanted to determine whether the DIO and DR rats showed differential sensitivity to microinjections of orexin into the paraventricular nucleus of the hypothalamus (PVN). Unilateral guide cannulae were implanted, aimed at the PVN. Orexin A (0, 0.125, 0.25, and 1.0 nmol in 500 nl) was microinjected through the guide cannula into the PVN, then SPA and energy expenditure were measured for 2 h. Using the response to vehicle as a baseline, the DR rats showed significantly greater increase in NEAT compared with the DIO rats. These data indicate that diet-induced obesity is associated with decreases in SPA and a lack of increase in NEAT. A putative mechanism for changes in NEAT that accompany obesity is a decreased sensitivity to the NEAT-activating effects of neuropeptides such as orexin.     

Serum phospholipid fatty acids, adipose tissue, and metabolic markers in obese adolescents

Objective: Fatty acid (FA) composition has a role in adipogenesis. The objective was to study serum phospholipid (PL) FAs in adolescents and their relation to abdominal adipose tissue (AT) compartments and metabolic markers. Research Methods and Procedures: Abdominal AT was measured by magnetic resonance imaging and FA pattern was determined in serum PL of 10 obese adolescents (5 females), median age 12.0 years (range, 10.4 to 16.4) and BMI 30.7 (26.8 to 40.4), and 15 lean control subjects (9 females), median age 12.6 years (range, 11.3 to 15.4), and BMI 19.5 (17.1 to 23.4). Results: Obese adolescents had relatively higher levels of saturated FA (SFA) and nervonic acid compared with controls. Serum PL concentration of n‐3 polyunsaturated fatty acids (PUFA) was lower in the obese vs. lean females (p = 0.01), including docosahexaenoic acid (DHA) (p = 0.01). The ratios of arachidonic acid to DHA and total n‐6/n‐3 FA were increased in obese children (p = 0.02 and 0.01, respectively). n‐3 PUFAs were inversely correlated to all subcutaneous AT compartments except visceral AT. The homeostasis model assessment index of β‐cell function related inversely to DHA concentration (p = 0.03). All changes were more marked in the females. Discussion: Serum FA pattern in obese adolescents differed significantly from that in age‐matched lean controls, reflecting a decrease in n‐3 PUFA, especially DHA, and an increase in SFA. The subcutaneous AT, but not visceral AT, correlated to the changes in PUFA and SFA, suggesting an abnormal essential FA metabolism in obese adolescents.     

Glucose dysregulation in obese children: predictive, risk, and potential protective factors

Objective: The aim of our study was to determine the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes (DM2) in obese children and adolescents of Greek origin and compare our data with pertinent literature findings in an attempt to uncover predictive, risk, and preventive factors. Research Methods and Procedures: A total of 117 obese children and adolescents 12.1 ± 2.7 years old underwent a 2‐hour oral glucose tolerance test (OGTT). Insulin resistance (IR) and β‐cell function were estimated using the homeostasis model assessment (HOMA)‐IR and the insulinogenic index, respectively. Results: A total of 17 patients (14.5%) had IGT, and none had DM2. The overall prevalence rates of both IGT and DM2 in our subjects were lower than those reported in a recent multiethnic U.S. study. Nevertheless, the difference between our IGT data and those of the U.S. study was due mostly to the prepubertal subjects (9% vs. 25.4%), whereas no difference was observed in the pubertal population (18% vs. 21%). Fasting glucose, insulin, and HOMA‐IR values were not predictive of IGT. The absolute value of insulin at 2 hours of the OGTT combined with the time‐integrated glycemia (AUCG) can strongly predict IGT, whereas higher area under the curve for insulin (AUCI) values were found to be protective. Discussion: In ethnic groups less prone to diabetes development, IGT or DM2 in obese subjects is more likely to develop at puberty than at the prepubertal stage. It is advisable that physicians caring for obese adolescents perform an OGTT for early detection of IGT because HOMA‐IR values, although higher in IGT subjects and indicative of IR, cannot predict IGT.     

肥胖及2型糖尿病患者内脏脂肪基因差异表达研究

目的：筛查在正常人、单纯性肥胖患者及肥胖伴2型糖尿病患者内脏脂肪组织中差异表达的基因。方法：利用自制的高密度cDNA芯片,比较正常人、单纯性肥胖患者及肥胖伴2型糖尿病患者内脏脂肪组织中差异表达的基因,以寻找脂肪组织特异的与肥胖及糖尿病发生有关的基因。结果：和正常人相比,在肥胖患者及肥胖伴2型糖尿病患者中上调的基因分别有119个和257个,下调的基因分别有46和58个。这些基因中有77个在两组中均上调,其中包括与代谢有关的基因,如丙酮酸脱氢酶激酶4（PDK4）以及窖蛋白、金属硫因蛋白等;8个基因在两组中均下调,其中包括脂肪合成途径中的关键酶,如3-羟基-3-甲基戊二酸单酰辅酶A（MGA）合成酶、脂肪酸合成酶及硬脂酰辅酶A脱氢酶。另外,酪氨酸-3单加氧酶-色氨酸-5单加氧酶活化蛋白θ（YWHAZ）仅在肥胖伴2型糖尿病患者中上调,而在单纯性肥胖患者中不变,该基因所编码的蛋白在胰岛素信号转导途径中起着负调控的作用。结论：脂肪组织中脂肪生成下降、脂肪酸氧化增加可能是肥胖及2型糖尿病中胰岛素抵抗发生的共同原因,其它基因功能的改变也可能参与了肥胖及2型糖尿病的发生,而胰岛素信号转导受阻可能是肥胖向糖尿病转化的促进因素。对这些基因的进一步研究将有助于更好地了解肥胖及糖尿病的发生机制。     

Regional body volumes, BMI, waist circumference, and percentage fat in severely obese adults

Objective: This study presents total body volume (TBV) and regional body volume, and their relationships with widely used body composition indices [BMI, waist circumference (WC), and percentage body fat (% fat)] in severely obese adults (BMI ≥35 kg/m²). Research Methods and Procedures: We measured TBV, trunk volume (TV), arm volume (AV), leg volume (LV), and WC and estimated % fat in 32 severely obese persons with BMI 36 to 62 kg/m² (23 women; age, 19 to 65 years; weight, 91 to 182 kg) and in 58 persons with BMI <35 kg/m² (28 women; age, 18 to 83 years; weight, 48 to 102 kg) using a newly validated 3‐day photonic image scanner (3DPS, Model C9036–02, Hamamatsu Co., Japan) and calculated TV/TBV, AV/TBV, and LV/TBV. Results: Men had significantly larger TBV and higher TV/TBV and AV/TBV, but significantly lower LV/TBV than women, independently of BMI. TV/TBV increased while AV/TBV and LV/TBV decreased with increasing BMI, WC, and % fat, and the rate of increase in TV/TBV per % fat was significantly greater in severely obese individuals than in individuals with BMI <35 kg/m². The relationships for TBV with % fat were much lower than with BMI or WC. Conclusion: Body volume gains were mainly in the trunk region in adults, irrespective of sex or BMI. For a given BMI, WC, or % fat, men had a significantly larger TV than women. The implication is that men could have higher health risks due to having higher trunk body weight as a proportion of total body weight compared with severely obese or less severely obese women.     

Objectively measured sedentary behavior,physical activity,and plasma lipids in overweight and obese children

Objective:

This study examines the associations between objectively measured sedentary behavior, light physical activity (LPA), and moderate‐to‐vigorous physical activity (MVPA), and plasma lipids in overweight and obese children.

Design and Methods:

Cross‐sectional analyses were conducted among 126 children aged 5.5‐9.9 years. Sedentary behavior, LPA, and MVPA were assessed using accelerometry. Fasting blood samples were analyzed for plasma lipids (high‐density lipoprotein cholesterol [HDL‐C], low‐density lipoprotein cholesterol [LDL‐C], total cholesterol [TC], and triglycerides [TG]).

Results:

MVPA was not related to plasma lipids (P > 0.05). Independent of age, sex, energy intake, and waist circumference z‐score, sedentary behavior and LPA were associated with HDL‐C (β = ?0.23, 95% CI ?0.42 to ?0.04, P = 0.020; β = 0.20, 95% CI 0.14 to 0.39, P = 0.036, respectively). The strength of the associations remained after additionally adjusting for MVPA (sedentary behavior: β = ?0.22, 95% CI ?0.44 to 0.006, P = 0.056; LPA: β = 0.19, 95% CI ?0.005 to 0.38, P = 0.056, respectively).

Conclusion:

Substituting at least LPA for sedentary time may contribute to the development of healthy HDL‐C levels among overweight and obese children, independent of their adiposity. Comprehensive prevention and treatment strategies to improve plasma HDL‐C among overweight and obese children should target reductions in total sedentary time and promote the benefits of LPA, in addition to promoting healthy levels of adiposity, healthy dietary behaviors, and MVPA.