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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several adrenoceptor subtypes are expressed in adipocytes, which together exert their influence on adipocyte metabolism. Therefore, we specifically examined the interactive effect of Trp64Arg (beta3) and Glu12/Glu9 (alpha2b) adrenoceptor (AR) polymorphisms on energy metabolism and body composition in healthy women with a wide range of body habitus. We genotyped 909 unrelated women (age 55 +/- 12 [mean +/- SD] years, range 19-87; body weight 88 +/- 22 kg, range 40-167; and BMI 33 +/- 8 kg/m2, range 16-64) for Trp64Arg beta3AR and Glu12/Glu9 alpha2bAR variants. We examined the independent effect of the Glu12/Glu9 alpha2bAR variant on body composition and energy balance, in a large cohort of Caucasian women (n = 909). A second goal was to examine the interaction effect of Glu12/Glu9 alpha2bAR and Trp64Arg beta3AR on the same phenotypes. The obesity-related phenotypes studied were as follows: body weight, BMI, fat mass, visceral fat, fat-free mass, resting metabolic rate (RMR), VO2max, leisure time physical activity, and daily energy intake. Body composition and body fat distribution were measured by dual-energy X-ray absorptiometry and radiographic imagery, VO2max by a treadmill test to exhaustion, and RMR by indirect calorimetry. An analysis of covariance indicated that in the entire cohort, there was no significant difference between Glu12/Glu9 alpha2bAR carriers and control subjects for any of the obesity-related phenotypes that were examined. However, we observed a significant interaction effect of the Trp64Arg and Glu12/Glu9 variants on fat mass (P = 0.009) and percent fat (P = 0.016). Age, height, body weight, BMI, fat-free mass, visceral fat, energy expenditure, respiratory quotient, physical fitness, and energy intake were not different among groups. Collectively, these findings support an interaction effect of the two adrenoceptor variants on body fatness in Caucasian women, although the physiological mechanism by which they exert this effect remains to be determined.
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PMID:Identification of an interactive effect of beta3- and alpha2b-adrenoceptor gene polymorphisms on fat mass in Caucasian women. 1114

Obesity is often associated with a reduced ventilatory response and a decreased maximal exercise capacity. GABA is a major inhibitory neurotransmitter in the mammalian central nervous system. Altered GABAergic mechanisms have been detected in obese Zucker rats and implicated in their hyperphagic response. Whether altered GABAergic mechanisms also contribute to regulate ventilation and influence exercise capacity in obese Zucker rats is unknown and formed the basis of the present study. Eight lean [317 +/- 18 (SD) g] and eight obese (450 +/- 27 g) Zucker rats were studied at 12 wk of age. Ventilation at rest and ventilation during hypoxic (10% O(2)) and hypercapnic (4% CO(2)) challenges were measured by the barometric method. Peak O(2) consumption (VO(2 peak)) in response to a progressive treadmill test to exhaustion was measured in a metabolic treadmill. Ventilation and VO(2 peak) were assessed after administration of equal volumes of DMSO (vehicle) and the GABA(A) receptor antagonist bicuculline (1 mg/kg). In lean animals, bicuculline administration had no effect on ventilation and VO(2 peak). In obese rats, bicuculline administration significantly (P < 0.05) increased resting ventilation (465 +/- 53 and 542 +/- 72 ml. kg(-1). min(-1) for control and bicuculline, respectively), ventilation during exposure to hypoxia (899 +/- 148 and 1,038 +/- 83 ml. kg(-1). min(-1) for control and bicuculline, respectively), and VO(2 peak) (62 +/- 3.7 and 67 +/- 3.5 ml. kg(-0.75). min(-1) for control and bicuculline, respectively). However, in obese Zucker rats, ventilation in response to hypercapnia did not change after bicuculline administration (608 +/- 96 vs. 580 +/- 69 ml. kg(-1). min(-1)). Our findings indicate that endogenous GABA depresses ventilation and limits exercise performance in obese Zucker rats.
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PMID:GABAergic modulation of ventilation and peak oxygen consumption in obese Zucker rats. 1129 59

Insulin is released from the pancreas in a biphasic manner in response to a square-wave increase in arterial glucose concentration. The first phase consists of a brief spike lasting approximately 10 min followed by the second phase, which reaches a plateau at 2-3 h. It is widely thought that diminution of first-phase insulin release is the earliest detectable defect of beta-cell function in individuals destined to develop type 2 diabetes and that this defect largely represents beta-cell exhaustion after years of compensation for antecedent insulin resistance. In this article, the origins of these concepts are reviewed and recent evidence is presented suggesting that reductions in both phases of insulin release are equally early, that they precede insulin resistance other than that simply due to obesity, and that they therefore may represent the primary genetic risk factor predisposing individuals to type 2 diabetes.
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PMID:Is reduced first-phase insulin release the earliest detectable abnormality in individuals destined to develop type 2 diabetes? 1181 69

Overload of pancreatic beta cells in conditions such as hyperglycemia, obesity, and long-term treatment with sulfonylureas leads to beta cell exhaustion and type 2 diabetes. Because beta cell mass declines under these conditions, apparently as a result of apoptosis, we speculated that overload kills beta cells as a result of endoplasmic reticulum (ER) stress. The Akita mouse, which carries a conformation-altering missense mutation (Cys96Tyr) in Insulin 2, likewise exhibits hyperglycemia and a reduced beta cell mass. In the development of diabetes in Akita mice, mRNAs for the ER chaperone Bip and the ER stress-associated apoptosis factor Chop were induced in the pancreas. Overexpression of the mutant insulin in mouse MIN6 beta cells induced Chop expression and led to apoptosis. Targeted disruption of the Chop gene delayed the onset of diabetes in heterozygous Akita mice by 8-10 weeks. We conclude that ER overload in beta cells causes ER stress and leads to apoptosis via Chop induction. Our findings suggest a new therapeutic approach for preventing the onset of diabetes by inhibiting Chop induction or by increasing chaperone capacity in the ER.
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PMID:Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetes. 1185 14

To investigate the effects of obesity on the regulation of end-expiratory lung volume (EELV) during exercise we studied nine obese (41 +/- 6% body fat and 35 +/- 7 yr, mean +/- SD) and eight lean (18 +/- 3% body fat and 34 +/- 4 yr) women. We hypothesized that the simple mass loading of obesity would constrain the decrease in EELV in the supine position and during exercise. All subjects underwent respiratory mechanics measurements in the supine and seated positions, and during graded cycle ergometry to exhaustion. Data were analyzed between groups by independent t-test in the supine and seated postures, and during exercise at ventilatory threshold and peak. Total lung capacity (TLC) was reduced in the obese women (P < 0.05). EELV was significantly lower in the obese subjects in the supine (37 +/- 6 vs. 45 +/- 5% TLC) and seated (45 +/- 6 vs. 53 +/- 5% TLC) positions and at ventilatory threshold (41 +/- 4 vs. 49 +/- 5% TLC) (P < 0.01). In conclusion, despite reduced resting lung volumes and alterations in respiratory mechanics during exercise, mild obesity in women does not appear to constrain EELV during cycling nor does it limit exercise capacity. Also, these data suggest that other nonmechanical factors also regulate the level of EELV during exercise.
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PMID:Mild obesity does not limit change in end-expiratory lung volume during cycling in young women. 1201 63

Gestational diabetes (GD) develops because pregnancy increases requirements for insulin secretion while increasing insulin resistance. Women with GD often have impaired pancreatic beta-cell compensation for insulin resistance. The nature of GD is currently contentious, with debate about its existence, diagnosis and ramifications for both mother and offspring from pregnancy into later life. Also contentious are the outcomes of intervention with diet, insulin, glyburide (Glynase trade mark, Pharmacia Upjohn) and metformin (Glucophage trade mark, Bristol-Myers Squibb). There is consensus that women with unequivocal GD have a significant risk of adverse perinatal outcomes and increased risk of later type 2 diabetes mellitus. Foetuses from pregnancies with GD have a higher risk of macrosomia (associated with higher rate of birth injuries), asphyxia, and neonatal hypoglycaemia and hyperinsulinaemia. Uncontrolled GD predisposes foetuses to accelerated, excessive fat accumulation, insulin resistance, pancreatic exhaustion secondary to prenatal hyperglycaemia and possible higher risk of child and adult obesity and type 2 diabetes mellitus later in adult life. However, there is no consensus as to whether glucose intolerance of a severity below unequivocal GD is related to adverse maternal, fetal or perinatal outcomes, and whether this relationship is a continuous one. If dietary intervention is not sufficient in the treatment of GD, then, historically, insulin has been added. Recent studies suggest that glyburide may be efficaciously substituted for insulin. Preliminary studies suggest that metformin may have the unique potential to prevent the development of GD.
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PMID:The contentious nature of gestational diabetes: diet, insulin, glyburide and metformin. 1243 90

We examined the effects of weight loss induced by diet-orlistat (DO) and diet-orlistat combined with exercise (DOE) on maximal work rate production (Wmax) capacity in obese patients. Total of 24 obese patients were involved in this study. Twelve of them were subjected to DO therapy only and the remaining 12 patients participated in a regular aerobic exercise-training program in addition to DO therapy (DOE). Each patient performed two incremental ramp exercise tests up to exhaustion using an electromagnetically-braked cycle ergometer: one at the onset and one at the end of the 4th week. DOE therapy caused a significant decrease in total body weight: 101.5+/-17.4 kg (basal) vs 96.3+/-17.3 kg (4 wk) associated with a significant decrease in body fat mass: 45.0+/-10.5 kg (basal) vs 40.9+/-9.8 kg (4 wk). DO therapy also resulted in a significant decrease of total body weight 94.9+/-14.9 kg (basal) vs 91.6+/-13.5 kg (4 wk) associated with small but significant decreases in body fat mass: 37.7+/-5.6 kg (basal) to 36.0+/-6.2 kg (4 wk). Weight reduction achieved during DO therapy was not associated with increased Wmax capacity: 106+/-32 W (basal) vs 106+/-33 W (4 wk), while DOE therapy resulted in a markedly increased Wmax capacity: 109+/-39 W (basal) vs 138+/-30 W (4 wk). DO therapy combined with aerobic exercise training resulted in a significant reduction of fat mass tissue and markedly improved the aerobic fitness and Wmax capacities of obese patients. Considering this improvement within such a short period, physicians should consider applying an aerobic exercise-training program to sedentary obese patients for improving their physical fitness and thereby reduce the negative outcomes of obesity.
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PMID:Effects of short-period exercise training and orlistat therapy on body composition and maximal power production capacity in obese patients. 1498 14

The purpose of the study was to examine the stability of variables associated with the metabolic syndrome from adolescence to adulthood. The sample included 48 subjects from the Aerobics Center Longitudinal Study who had one clinical visit during adolescence (mean age = 15.8 years) and a follow-up visit during adulthood (mean age = 26.6 years). The following variables were considered: treadmill time to exhaustion (TM), body mass index (BMI), waist circumference (WC), percent body fat (%BF), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC:HDL-C, triglycerides (TG), glucose (GLU), and systolic (SBP), diastolic (DBP), and mean (MAP) blood pressure. A composite risk factor score using variables consistent with the WHO and ATP III definition of the metabolic syndrome (WC, HDL-C, TG, MAP, and GLU) was calculated. Tracking coefficients were computed as partial correlations, controlling for length of follow-up (mean = 11 years). Tracking coefficients (r values) were moderate for all variables (TM, 0.53; BMI, 0.64; WC; 0.79;%BF, 0.44; TC, 0.62; HDL-C, 0.60; TG, 0.54; TC:HDL-C, 0.78; SBP, 0.45; and MAP, 0.41), except GLU (0.26) and DBP (0.21). The composite risk factor score also tracked moderately well (0.56) from adolescence into adulthood. The results support previous findings that variables associated with the metabolic syndrome track moderately well from adolescence to adulthood. The findings support the prevention and treatment of obesity, atherosclerosis, type 2 diabetes, and the metabolic syndrome during childhood and adolescence.
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PMID:Stability of variables associated with the metabolic syndrome from adolescence to adulthood: the Aerobics Center Longitudinal Study. 1549 27

A comparative assessment was made of the short-term effects of orlistat therapy and exercise training on body composition and aerobic fitness in obese females. A total of 24 obese patients were enrolled in to the study; 12 received orlistat therapy (DO) and 12 participated in a regular aerobic exercise-training programme (DE). All patients were on hypocaloric diets. Each patient performed three incremental ramp exercise tests (one at Week 0, one at the end of Week 4 and one at the end of Week 8) to exhaustion using an electromagnetically braked cycle ergometer to determine their anaerobic threshold and maximal exercise (Wmax) capacity. Patients in the DE group performed continuous exercise at a work rate that corresponded to the anaerobic threshold. Weight loss and loss of fat mass after 8 weeks were -6.4% (P=0.002) and -13.4% (DE) vs -5.8% (P=0.002) and -6.4% (P=0.008) (DO), respectively. Wmax capacity was 90.8+/-5 W (basal) vs 92.9+/-5 W (Week 4, P=0.1) and 100.4+/-6 W (Week 8, 10.5%, P=0.04) in the DO group, and 96.2+/-6 W (basal) vs 129.1+/-4 W (Week 4, 34.1%, P=0.002) and 137.5+/-5 W(Week 8, 42.9%, P=0.002) in the DE group. Despite similar decreases in body weight in both groups, patients in the DE group achieved a markedly higher level of Wmax, reflecting a better improvement in cardiopulmonary fitness, compared with patients in the DO group. Considering the improvement of aerobic fitness in the short term, an aerobic exercise-training programme should be considered for sedentary obese patients to improve their aerobic fitness and thereby reduce the negative outcomes of obesity.
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PMID:Effects of eight weeks of exercise training and orlistat therapy on body composition and maximal exercise capacity in obese females. 1619 82

Type 2 diabetes mellitus (DM) is a progressive disease characterized by insulin resistance and impaired insulin secretion. To compensate for these metabolic dysfunctions, pancreatic beta-cells begin to overproduce insulin; however, it is this compensatory mechanism that eventually results in beta-cell exhaustion, impaired insulin secretion, and relative insulin deficiency. The metabolic abnormalities associated with diabetes also contribute to vascular dysfunction and an increased risk of coronary heart disease. Among patients with type 2 DM, cardiovascular disease, particularly macrovascular disease, is the primary cause of mortality, accounting for 55% of deaths. Management of the disease, therefore, must address all of the contributing factors, including a sedentary lifestyle and diet that contribute to overweight/obesity, and comorbidities such as hypertension and dyslipidemia. In this paper, we present a case study based on actual clinical experience to illustrate an evidence-based rationale for early and aggressive intervention for patients with type 2 DM, including lifestyle modification, oral antidiabetic agents, and insulin.
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PMID:Early intervention to achieve optimal outcomes in type 2 diabetes: a case presentation. 1693 76


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