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)

Despite the enormous cardiovascular disease epidemic and poor survival among individuals with chronic kidney disease (CKD), traditional risk factors such as hypercholesterolemia, hypertension, and obesity appear not as relevant as was previously thought, nor would their management improve survival in patients with CKD who are undergoing dialysis. On the contrary, kidney disease wasting (KDW) (also known as the malnutrition-inflammation complex), renal anemia, and kidney bone disease (KBD) appear to be the 3 most important nontraditional risk factors associated with cardiovascular disease in CKD. KBD-associated hyperparathyroidism may contribute to worsening refractory anemia and KDW/inflammation. The main cause of secondary hyperparathyroidism is active vitamin D deficiency. Hence, treatment of patients with KBD with vitamin D analogs, especially those with lesser effects on calcium and phosphorus such as paricalcitol, may be the most promising option for improving CKD outcomes. By conducting survival analyses in a 2-year (7/2001 to 6/2003) cohort of 58,058 patients on hemodialysis, we recently found that associations between high serum parathyroid hormone and increased death risk were masked by the demographic and clinical characteristics of patients, and that alkaline phosphatase had an incremental association with mortality. Administration of paricalcitol was associated with improved survival in time-varying models. We now present additional subgroup analyses that show that administration of any dose of paricalcitol, when compared with no paricalcitol, is associated with better likelihood of survival in virtually all subgroups of patients on hemodialysis. Because these associations may be secondary to bias by indication, randomized clinical trials are necessary to verify the findings of this and similar observational studies.
 ...
PMID:Impact of kidney bone disease and its management on survival of patients on dialysis. 1719 30

Insulin resistance is commonly observed in uremic patients. Glucose-based peritoneal dialysis solutions have long-term metabolic complications like hyperinsulinemia, hyperlipidemia, and obesity. The purpose of this study was to examine the insulin resistance in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with standard glucose and icodextrin containing solutions. The entire non diabetic CAPD patients of our center were studied: forty-four patients in all who were on CAPD treatment for 36.2 +/- 23.7 months. Twenty-seven of them (11 male and 16 female) with a mean age of 46 +/- 16 years were treated with standard glucose solutions (glucose group). The other 17 patients (10 male and 7 female) with a mean age of 49 +/- 16 years were treated with standard glucose solutions during the day and icodextrin dwell during the night, for a median of 12 +/- 6.3 months (icodextrin group). Morning fasting serum insulin levels were 20.59 +/- 17.86 in the glucose group and 10.15 +/- 6.87 in the icodextrin group (p = 0.0001). Homeostasis Model Assessment Method scores of the glucose group were significantly higher (4.8+/-4.1 vs 2.3+/- 1.7; p = 0.025) than the icodextrin group. A significant positive correlation of HOMA score with insulin, fasting plasma glucose, and triglyceride levels were found in HOMA (IR+) patients. Twenty patients of the icodextrin group (74%) and 15 patients of the glucose group (88%) were hypertensive, but there was no statistically significant difference between the two groups (p = 0.13). The groups showed no significant differences for body mass index and serum levels of glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, triglyceride, intact parathyroid hormone (iPTH), and fibrinogen. In conclusion, the use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.
 ...
PMID:Icodextrine and insulin resistance in continuous ambulatory peritoneal dialysis patients. 1749 42

Low 25-hydroxyvitamin D (25[OH] D) results in hyperparathyroidism and is among the endocrine derangements of adult obesity. There are differing recommendations on defining low 25(OH) D: hypovitaminosis D (serum 25[OH] D concentration <75 nmol/L) and vitamin D deficiency (serum 25[OH] D concentration <50 nmol/L). We sought to evaluate the prevalence of low levels of 25(OH) D by examining hypovitaminosis D (<75 nmol/L), vitamin D sufficiency (> or =75 nmol/L), vitamin D insufficiency (50-74.9 nmol/L), and vitamin D deficiency (<50 nmol/L) in pediatric obesity and the relationship to other calciotropic hormones and adiposity. Serum 25(OH) D, intact parathyroid hormone (iPTH), ionized calcium, glucose, and insulin levels along with hemoglobin A(1c) (HbA(1c)) and quantitative insulin sensitivity check index (QUICKI) were determined in 127 subjects aged 13.0 +/- 3.0 years (49 Caucasian [C], 39 Hispanic [H], and 39 African American [AA]; 61.2% female; body mass index 36.4 +/- 8.1 kg/m(2)) during fall/winter (F/W) and spring/summer (S/S). Body composition was determined by bioelectrical impedance. Hypovitaminosis D was present in 74% of the cohort, but was more prevalent in the H (76.9%, P < .05) and AA (87.2%, P < .05) groups than in the C group (59.1%). Hypovitaminosis D corresponded to decreased vitamin D intake (P < .005) and was more prevalent in F/W than S/S (98.4% vs 49.2, P < .01). Vitamin D deficiency was identified in 32.3% of the entire cohort and was more prevalent in the H (43.6%, P < .0001) and AA (48.7%, P < .0001) groups than in the C group (10.2%) associated with decreased vitamin D intake (P < .0001). Vitamin D insufficiency was present in 41.7% of the cohort, with similar prevalence among C (48.9%), H (33.3%), and AA (38.5%). Vitamin D insufficiency corresponded to decreased vitamin D intake (P < .005), with similar prevalence in F/W and S/S (45.3% vs 38.1%), whereas vitamin D deficiency was not only accompanied by decreased vitamin D intake (P < .0001) but was more prevalent in F/W than S/S (53.1% vs 11.1%, P < .0001). Serum 25(OH) D and iPTH (r = -0.41, P < .0001) levels were negatively correlated without seasonal and ethnic/racial influences. Hypovitaminosis D and vitamin D-deficient groups had higher body mass index, fat mass (FM), and iPTH, but had lower QUICKI than vitamin D-sufficient group (P < .01). Whereas FM was negatively correlated with 25(OH) D (r = -0.40, P < .0001), it was positively correlated with iPTH (r = 0.46, P < .0001) without seasonal and racial/ethnic influences. Serum 25(OH) D was also positively correlated with QUICKI (r = 0.24, P < .01), but was inversely correlated with HbA(1c) (r = -0.23, P < .01). Hypovitaminosis D was identified in 74% of obese subjects, whereas vitamin D deficiency was observed in 32.3% of our cohort. Vitamin D status was influenced by vitamin D intake, season, ethnicity/race, and adiposity. Interrelationships between 25(OH) D, iPTH, and FM were not influenced by season and race/ethnicity. Furthermore, serum 25(OH) D was positively correlated with insulin sensitivity, which was FM mediated, but negatively correlated with HbA(1c), implying that obese children and adolescents with low vitamin D status may be at increased risk of developing impaired glucose metabolism independent of body adiposity. Additional studies are needed to evaluate the underlying mechanisms.
 ...
PMID:Hypovitaminosis D in obese children and adolescents: relationship with adiposity, insulin sensitivity, ethnicity, and season. 1819 Oct 47

Pseudohypoparathyroidism type Ia (PHP-Ia), one of 4 types of PHP, is a genetic disease characterized by clinical hypoparathyroidism caused by parathyroid hormone (PTH) resistance. In addition, patients with PHP-Ia show resistance to other hormones as well as Albright's hereditary osteodystrophy (AHO), a constellation of features including short stature, obesity, brachydactyly, ectopic ossifications, and/or mental retardation. Hypocalcemia is one of the hallmarks of PHP-Ia, but several PHP-Ia patients have been described to have normocalcemia. We encountered a 10-year-old girl with typical Albright's hereditary osteodystrophy with round face, short stature, brachydactyly, and obesity. Biochemical examination showed normocalcemia and increased PTH levels. Ellsworth-Howard test did not show any responses of urinary cAMP and phosphate. Based on these findings, she was diagnosed as having PHP-Ia with normocalcemia. Sequencing analysis of the GNAS gene identified a heterozygous missense mutation in exon 13 (R385H), which was previously reported in a PHP-Ia patient. The exact reason for her normocalcemia is not determined, but we must recognize heterogeneous biochemical findings even in PHP-Ia.
 ...
PMID:A pseudohypoparathyroidism type Ia patient with normocalcemia. 1825 May 41

For 5 months a year the UK has insufficient sunlight for cutaneous synthesis of vitamin D and winter requirements are met from stores made the previous summer. Although there are few natural dietary sources, dietary intake may help maintain vitamin D status. We investigated the relationship between 25-hydroxyvitamin D (25(OH)D), bone health, overweight, sunlight exposure and dietary vitamin D in 3113 women (age 54.8 [SD 2.3] years) living at latitude 57 degrees N between 1998-2000. Serum 25(OH)D was measured by high performance liquid chromatography (HPLC), dietary intakes (food frequency questionnaire, n=2598), sunlight exposure (questionnaire, n=2402) and bone markers were assessed. Bone mineral density (BMD) was measured by dual x-ray absorptiometry in all women at the sampling visit and 6 years before. Seasonal variation in 25(OH)D was not substantial with a peak in the autumn (23.7 [9.9] ng/ml) and a nadir in spring (19.7 [7.6] ng/ml). Daily intake of vitamin D was 4.2 [2.5] mug from food only and 5.8 [4.0] mug including vitamin D from cod liver oil and multivitamins. The latter was associated with 25(OH)D at each season whereas vitamin D simply from food was associated with 25(OH)D in winter and spring only. Sunlight exposure was associated with 25(OH)D in summer and autumn. 25(OH)D was negatively associated with increased bone resorption and bone loss (P<0.05) remaining significant after adjustment for confounders (age, weight, height, menopausal status/HRT use, physical activity and socio-economic status). Using an insufficiency cut-off of <28 ng/ml 25(OH)D, showed lower concentrations of bone resorption markers in the upper category (fDPD/Cr 5.1 [1.7] nmol/mmol compared to 5.3 [2.1] nmol/mmol, P=0.03) and no difference in BMD or bone loss. 25(OH)D was lower (P<0.01) and parathyroid hormone higher (P<0.01) in the top quintile of body mass index. In conclusion, low vitamin D status is associated with greater bone turnover, bone loss and obesity. Diet appears to attenuate the seasonal variation of vitamin D status in early postmenopausal women at northerly latitude where quality of sunlight for production of vitamin D is diminished.
 ...
PMID:Vitamin D status in postmenopausal women living at higher latitudes in the UK in relation to bone health, overweight, sunlight exposure and dietary vitamin D. 1832 55

Genetic variation in G protein-coupled receptors (GPCRs) results in the disruption of GPCR function in a wide variety of human genetic diseases. In vitro strategies have been used to elucidate the molecular pathologies that underlie naturally occurring GPCR mutations. Various degrees of inactive, overactive, or constitutively active receptors have been identified. These mutations often alter ligand binding, G protein coupling, receptor desensitization, and receptor recycling. The role of inactivating and activating calcium-sensing receptor (CASR) mutations is discussed with respect to familial hypocalciuric hypercalemia (FHH) and autosomal dominant hypocalemia (ADH). Among ADH mutations, those associated with tonic-clonic seizures are discussed. Other receptors discussed include rhodopsin, thyrotropin, parathyroid hormone, melanocortin, follicle-stimulating hormone, luteinizing hormone, gonadotropin-releasing hormone (GnRHR), adrenocorticotropic hormone, vasopressin, endothelin-beta, purinergic, and the G protein associated with asthma (GPRA). Diseases caused by mutations that disrupt GPCR function are significant because they might be selectively targeted by drugs that rescue altered receptors. Examples of drug development based on targeting GPCRs mutated in disease include the calcimimetics used to compensate for some CASR mutations, obesity therapeutics targeting melanocortin receptors, interventions that alter GnRHR loss from the cell surface in idiopathic hypogonadotropic hypogonadism and novel drugs that might rescue the P2RY12 receptor in a rare bleeding disorder. The discovery of GPRA suggests that drug screens against variant GPCRs may identify novel drugs. This review of the variety of GPCRs that are disrupted in monogenic disease provides the basis for examining the significance of common pharmacogenetic variants.
 ...
PMID:G protein-coupled receptors disrupted in human genetic disease. 1837 Feb 33

African Americans have lower serum 25-hydroxyvitamin D concentrations and a lower risk of fragility fractures than do other populations. I review the evidence on factors other than vitamin D that might explain this paradox and the calcium economy in different life stages. Researchers are actively trying to explain this genetically programmed advantage. Factors that could protect African Americans against fracture include their higher peak bone mass, increased obesity rates, greater muscle mass, lower bone turnover rates, and advantageous femur geometry. In addition, bone histomorphometry in young adults shows longer periods of bone formation. Although African Americans fall as frequently as do whites, the direction of their falls and their manner of breaking falls could protect them from fractures. African American girls accrue more calcium than do white girls during adolescence as the result of increased calcium absorption and superior renal calcium conservation. In adulthood, higher parathyroid hormone concentrations do not result in increased bone loss in African Americans because of their skeletal resistance to parathyroid hormone, and their superior renal conservation of calcium persists. These advantages diminish in the elderly, in whom further increases in parathyroid hormone result in increased bone turnover and bone loss. Ultimately, I explain the paradox by multiple factors associated with fracture risk and calcium economy in African Americans. Despite African Americans' reduced risk of osteoporotic fractures, such fractures remain an important public health problem for this population that vitamin D intervention studies have not addressed.
 ...
PMID:African Americans, 25-hydroxyvitamin D, and osteoporosis: a paradox. 1868 99

Based on cell culture and studies in mice, increased dietary calcium appears to stimulate lipolysis and could possibly reduce body adiposity through hormonal influences on adipocyte calcium uptake. In this study, we investigated the effects of 1,500 mg supplemental calcium daily for 3 months on hormones regulating calcium and energy metabolism and rates of lipid oxidation and lipolysis in overweight women. Fifteen overweight (BMI > 25 kg/m(2)) premenopausal women were supplemented with 1,500 mg of calcium, as CaCO(3), per day for 3 months while maintaining their usual diets and activity levels. Baseline and endpoint measurements were obtained after the subjects consumed a standardized 25% fat diet for 4 days. Lipid oxidation was measured by indirect calorimetry, lipolysis by infusion of deuterated glycerol, and body fat by dual-energy X-ray absorptiometry. Urinary calcium, circulating levels of hormones involved in energy and lipid metabolism (insulin, leptin, and adiponectin) or calcium metabolism (25(OH)D, 1,25(OH)(2)D), and parathyroid hormone (PTH)) were also measured. Urinary levels of calcium (P = 0.005) increased and 1,25(OH)(2)D declined (P = 0.03). However other parameters, including body weight, body fat, PTH, insulin, leptin, adiponectin, 25(OH)D, as well as rates of lipid oxidation and lipolysis were not altered by calcium supplementation. Calcium supplementation for 3 months increased urinary calcium excretion, decreased circulating levels of 1,25(OH)(2)-D, but had no effect on rates of lipid oxidation or lipolysis, in these overweight women.
Obesity (Silver Spring) 2008 Nov
PMID:Calcium supplementation does not alter lipid oxidation or lipolysis in overweight/obese women. 1871 72

Calcinosis has long been associated with autoimmune disease and has a distinctive profile in scleroderma, dermatomyositis, systemic lupus erythematosus, and overlap syndromes. However, there have also been a number of case studies of calcific uremic arteriolopathy, or calciphylaxis, described within vessels, including patients with chronic renal insufficiency and several forms of vasculitis. Interestingly, the calciphylaxis associated with vasculitis appears to be unique, although relatively uncommon and is likely secondary to a disruption in the calcium-phosphate-parathyroid hormone axis. However, there appears to be an additional trigger, given that calciphylaxis is seen both in the absence of chronic kidney disease, and in the absence of a deranged calcium-phosphate-parathyroid hormone axis. These additional triggers include a high female predominance, obesity, diabetes and, possibly, warfarin use. In this review, we describe the clinical features of calciphylaxis, particularly in the context of autoimmune disease.
 ...
PMID:Recognizing calcific uremic arteriolopathy in autoimmune disease: an emerging mimicker of vasculitis. 1877 19

Pseudohypoparathyroidism Ia (Albright hereditary osteodystrophy or Albright syndrome) is a rare disease, caused by the resistance to the action of the parathyroid hormone in target tissues, such as the bone, kidney, and intestine, with consequent hypocalcemia and hyperphosphatemia and increased levels of parathyroid hormone. The phenotype of Albright syndrome includes 5 common features: brachydactyly, obesity, short stature, a round face, and mental retardation. We report on a child with a classic form of pseudohypoparathyroidism and associated Albright syndrome who developed Evans syndrome (ie, the cooccurrence of severe autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura). To our knowledge, no cases of Evans syndrome have been observed associated with pseudohypoparathyroidism 1a.
 ...
PMID:Pseudohypoparathyroidism Ia with Evans syndrome. 1879 44


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>