Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BMC and BMD of the total body bone and lumbar spine were measured in normal control and patients with metabolic bone diseases by DPA (Dichromatic Bone Densitometer Model 2600, Norland corporation). Also, total body fat mass was measured in patients with obesity. We discussed basic technical problems and showed some data to assess patients with metabolic diseases known to affect the skeleton such as primary and secondary hyperparathyroidism. DPA is useful technique to assess patients with metabolic bone diseases and to monitor the efficacy of treatments.
 ...
PMID:[Dual photon absorptiometry]. 231 20

Evidence suggests that endogenous sugar acids 3,4-dihydroxybutanoic acid (2-deoxytetronic acid, 2-DTA) and 2,4,5-trihydroxypentanoic acid (3-deoxypentonic acid, 3-DPA) may participate in the regulation of feeding. To study the effect of 2-buten-4-olide, a 2-DTA synthetic derivative, on food intake, male Wistar rats were subjected to various applications. Intraperitoneal administration of 2-buten-4-olide in doses of 30 to 100 mg/kg, decreased food intake dose-dependently by reducing meal frequency, meal size and eating rate, and prolonging meal duration, latency to eat the first meal after injection and post-prandial intermeal intervals. Drinking patterns and locomotor activity were not significantly affected. Administration of 2-buten-4-olide intragastrically in doses of 50 to 300 mg/kg, and intra-third cerebroventricularly in doses of 1.2 to 5.0 mumol/rat, dose-dependently reduced food intake. This and previous evidence suggest that: 2-DTA and its derivatives that share its bioactive components suppress food intake in the rat; They might represent a new category of potential therapeutic agents for hyperphagia and obesity.
 ...
PMID:Endogenous sugar acid derivative acting as a feeding suppressant. 378 17

We recently reported the frequent occurrence of polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy, especially when the medication was started before the age of 20 years. In the present study we evaluated the association of obesity and hyperinsulinemia with valproate-related polycystic ovaries and hyperandrogenism in women with epilepsy. Sixty-five women participated in the study. Twenty-two received valproate monotherapy and 43 received carbamazepine monotherapy. In addition to clinical examination, vaginal ultrasonography was performed to determine ovarian size, and the concentrations of serum sex hormones, insulin, insulin-like growth factor 1, and the insulin-like growth factor-binding proteins 1 and 3 (IGFBP-1 and IGFBP-3) were measured. Fifty-nine percent of the women on valproate were obese, and in a retrospective analysis an indisputable weight gain (mean, 21 kg; range, 8-49 kg) was found in 50% of the women taking valproate. Fourteen (64%) of the women on valproate had polycystic ovaries, hyperandrogenism, or both. These women were obese, and in addition to elevated serum androgen levels, they had high concentrations of fasting serum insulin and low levels of serum insulin-like growth factor-binding protein 1. Valproate therapy for epilepsy is associated with weight gain during treatment in approximately 50% of women patients. The weight gain can be progressive, and is associated with hyperinsulinemia and low serum levels of insulin-like growth factor-binding protein 1, which may lead to hyperandrogenism and polycystic ovaries.
 ...
PMID:Obesity and endocrine disorders in women taking valproate for epilepsy. 861 39

Lack of physical activity and low levels of physical fitness are thought to be contributing factors to the high prevalence of obesity in African-American girls. To examine this hypothesis, we compared habitual physical activity and physical fitness in 54 African-American girls with obesity and 96 African-American girls without obesity residing in rural South Carolina. Participation in vigorous (> or = 6 METs) (VPA) or moderate and vigorous physical activity (> or = 4 METs) (MVPA) was assessed on three consecutive days using the Previous Day Physical Activity Recall. Cardiorespiratory fitness was assessed using the PWC 170 cycle ergometer test. Upper body strength was determined at two sites via isometric cable tensiometer tests. Relative to their counterparts without obesity, girls with obesity reported significantly fewer 30-minute blocks of VPA (0.90 +/- 0.14 vs. 1.3 +/- 0.14) and MVPA (1.2 +/- 0.18 vs. 1.7 +/- 0.16) (p < 0.01). Within the entire sample, VPA and MVPA were inversely associated with body mass index (r = -0.17 and r = -0.19) and triceps skinfold thickness (r = -0.19 and r = -0.22) (p < 0.05). In the PWC 170 test and isometric strength tests, girls with obesity demonstrated absolute scores that were similar to, or greater than, those of girls without obesity; however, when scores were expressed relative to bodyweight, girls with obesity demonstrated significantly lower values (p < 0.05). The results support the hypothesis that lack of physical activity and low physical fitness are important contributing factors in the development and/or maintenance of obesity in African-American girls.
 ...
PMID:Physical activity and physical fitness in African-American girls with and without obesity. 944 42

We recently reported the frequent occurrence of polycystic ovaries and hyperandrogenism associated with weight gain and hyperinsulinemia in women taking valproate for epilepsy. The purpose of this study was to evaluate the risks related to valproate-induced hyperinsulinemia and their reversibility after discontinuing the medication. Sixteen women with valproate-related polycystic ovaries or hyperandrogenism participated in the study. Vaginal ultrasonography was performed, and endocrine and lipid parameters were measured. Thereafter, lamotrigine was substituted for valproate and the patients were observed for 12 months. Twenty-four healthy age-matched women served as control subjects. Twelve women completed the 12-month follow-up. While still on valproate they had centripetal obesity with associated hyperinsulinemia and unfavorable serum lipid profiles. The body-mass index and fasting serum insulin and testosterone concentrations decreased during the first year after replacing valproate with lamotrigine whereas the HDL-cholesterol/total cholesterol ratios increased from 0.17 +/- 0.06 to 0.26 +/- 0.05. The total number of polycystic ovaries in these women decreased from 20 during valproate medication to 11 one year after replacing valproate with lamotrigine. Valproate induces a metabolic syndrome with centripetal obesity, hyperinsulinemia, lipid abnormalities, and polycystic ovaries/hyperandrogenism in women with epilepsy. These valproate-related risks can be reduced by substituting lamotrigine for valproate.
 ...
PMID:Valproate, lamotrigine, and insulin-mediated risks in women with epilepsy. 954 24

Long-term treatment with the anticonvulsant valproate (VPA) leads to well-documented weight gain and obesity in humans. In an attempt to develop an animal model of this condition, adult rats were given VPA 20 g/kg (high-dose) or 2 g/kg (low-dose) in their daily feeding or orally 120 mg/kg body weight/day in two divided doses, and food intake and body weight were assessed. Valproate resulted in lower body weights in all protocols. Food intake was lower (p<0.001) for rats receiving high-dose VPA than for controls. Feed efficiency (change in weight divided by cumulative food intake for that period) was lower than that of controls for both high (p<0.0001) and low doses (NS). Metabolic rate and physical activity were not different between control and VPA animals, although decreased food intake would be expected to decrease metabolic rate. Valproate failed to produce obesity in rats in any treatment period. For reasons that are unclear, rats do not appear to be suitable as a model to study this adverse side effect of VPA in humans with epilepsy.
 ...
PMID:Evaluation of a rat model of valproate-induced obesity. 975 18

Valproate is effective for treatment of a variety of seizure types both in adults and in children with epilepsy, but it induces obesity and polycystic ovaries in a considerable proportion of adult women, particularly when the medication is started before the age of 20. In the present study we evaluated reproductive endocrine function in 41 girls, 8 to 18 years old, taking valproate for epilepsy and in 54 healthy control girls. Among the girls taking valproate, 16 were prepubertal, 11 were pubertal, and 14 were postpubertal, and the corresponding numbers were 20, 13, and 21 in the control group. The mean serum testosterone concentrations of prepubertal, pubertal, and postpubertal girls taking valproate were significantly higher than those of the control girls at the same pubertal stage. Hyperandrogenism, defined as serum testosterone levels higher than the mean + 2SD in the control girls at the same pubertal stage, was seen in 38% of prepubertal, 36% of pubertal, and 57% of postpubertal girls taking valproate. In addition, postpubertal girls taking valproate were more obese than the controls and the mean serum insulin-like growth factor binding protein-1 concentration of pubertal and postpubertal hyperandrogenic girls taking valproate was lower than in valproate-treated girls without hyperandrogenism. Valproate may induce hyperandrogenism in girls with epilepsy during the sensitive period of pubertal maturation, and the frequency of hyperandrogenism increases with pubertal development. This emphasizes the importance of careful endocrine observation of girls taking valproate for epilepsy.
 ...
PMID:Valproate-induced hyperandrogenism during pubertal maturation in girls with epilepsy. 1076 74

Valproic acid is effective for treatment of many types of epilepsy, but its use in epileptic patients can be associated with an increase in body weight that could interfere with treatment compliance. The weight gain may result from different mechanisms, but the exact pathogenesis is still unknown. To evaluate insulin sensitivity in adolescents who gained weight during treatment with valproic acid, we studied 20 girls with different types of epilepsy: 15 patients had primary generalized seizures, including absence seizures (3 cases), and 5 patients had partial seizures. After 1 year of valproic acid treatment, the obese patients had serum insulin levels significantly higher than patients who did not gain weight (51.4 +/- 25.3 versus 28.2 +/- 12.9). Moreover, we observed that epileptic patients who gained weight were also insulin resistant in comparison with nonobese epileptic subjects. At the end of treatment, all patients showed normal levels of serum testosterone, androstenedione, dehydroepiandrosterone sulfate, follicle-stimulating hormone (FSH), and luteinizing hormone. We found no significant correlation between insulinemia and serum valproic acid concentrations in obese and nonobese patients treated with valproic acid. Our study demonstrates that basal hyperinsulinemia and insulin resistance can be present in patients who develop obesity during valproic acid treatment. Therefore, these obese patients could be exposed to the risks related to these metabolic abnormalities; if these data are confirmed in longer studies, these side effects may raise some concerns about the safety of valproic acid.
 ...
PMID:Insulin resistance in epileptic girls who gain weight after therapy with valproic acid. 1276 Apr 38

In order to investigate the possible role of valproic acid therapy in the development of obesity, hyperinsulinism and polycystic ovaries (PCOs), we have studied metabolic parameters and ovarian morphology in epileptic women. A total of 105 women, who were treated for at least 2 years with valproate (n = 52) or carbamazepine monotherapy (n = 53), were included in the examination. Menstrual disturbances were reported by 29 (28 %) of the women, 12 (11 %) of the VPA treated women, and 17 (16 %) in the CBZ group. On ultrasound scan polycystic ovaries were found in 28 patients (27 %) of the whole study population, of whom 13 (12 %) received VPA and 15 (14 %) CBZ. The mean body mass index (BMI) was significantly higher in the VPA group (24.4 kg/m(2) +/- 4.1) than in CBZ treated patients (22.9 kg/m(2) +/- 2.4;p < 0.022), and serum triglycerides tended to be increased, while total cholesterol values (178.9 +/- 30.5) and LDL-cholesterol values (92.6 +/- 27.4) were significantly lower in the valproate group, than in the carbamazepine group (207.1 +/- 43.0 vs 115.1 +/- 42.0; p < 0.001). Postprandial insulin, C-peptide and proinsulin levels were significantly higher in VPA treated patients compared with those treated with CBZ, while no differences could be found in the fasting state. In conclusion we could thus demonstrate that the frequency of PCOs in 27 % of epileptic women seems to be similar to that in the general population with a frequency of 20-30 %. The development of PCOs did not reveal a difference with the administration of VPA or CBZ. With respect to the metabolic side-effects of VPA therapy our data indicate that VPA increases glucose stimulated pancreatic insulin secretion, which might be followed by an increase in body weight.
 ...
PMID:Polycystic ovaries, obesity and insulin resistance in women with epilepsy. A comparative study of carbamazepine and valproic acid in 105 women. 1214 Jun 66

Epilepsy is a common neurologic disorder affecting women during the reproductive years. Seizures and some antiepileptic drugs (AEDs) can compromise reproductive health, and some AEDs can adversely affect carbohydrate and bone metabolism. Women with epilepsy have lower birth rates and more frequent anovulatory menstrual cycles. This appears to be related to seizure- and AED-associated reproductive endocrine disturbances. Carbamazepine (CBZ), phenytoin (PHT), and phenobarbital (PB) induce hepatic cytochrome P450 enzymes and lower endogenous estrogens, adrenal and ovarian androgens, and contraceptive steroids. Valproate (VPA) inhibits steroid hormone metabolism, elevates androgens, and predisposes to phenotypic signs of hyperandrogenism-hirsutism, obesity, acne, and frequent anovulatory cycles. VPA is associated with weight gain, probably by altering insulin metabolism. CBZ, PHT, and VPA, but not lamotrigine (LTG), are associated with lower levels of calcium. PHT, but not VPA or LTG, appears to accelerate bone turnover. AED effects on bone mineral metabolism may explain the elevated risk of fracture described in women with epilepsy. Prospective pregnancy registries are beginning to provide information about AED-associated teratogenesis. The North American Antiepileptic Drug Pregnancy Registry reports a 12% rate of major malformations after first trimester exposure to PB and an 8.6% rate after first trimester exposure to VPA. A prospective LTG-specific registry reports a 1.8% chance of major malformations after the first trimester. The registries will continue to release information as data become significant. In the meantime, practitioners can be alert to signs and symptoms of reproductive or metabolic health disturbances and participate in pregnancy registry efforts.
 ...
PMID:Reproductive and metabolic disorders in women with epilepsy. 1282 65


1 2 3 4 Next >>