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

Familial lipoprotein lipase (LPL) deficiency is a rare genetic disorder accompanied by well-characterized manifestations. The phenotypic expression of heterozygous LPL deficiency has not been so clearly defined. We studied the pedigree of a proband known to be homozygous for a mutation resulting in nonfunctional LPL. Hybridization of DNA from 126 members with allele-specific probes detected 29 carriers of the mutant allele. Adipose tissue LPL activity, measured previously, was reduced by 50% in carriers, but did not reliably distinguish them from noncarriers. Carriers were prone to the expression of a form of familial hypertriglyceridemia characterized by increased plasma triglyceride, VLDL cholesterol and apolipoprotein B, and decreased LDL and HDL cholesterol concentrations. These manifestations were age modulated, with conspicuous differences between carriers and noncarriers observed only after age 40. Several noncarriers exhibited similar lipid abnormalities, but without the inverse relationship between VLDL cholesterol and LDL cholesterol noted among carriers. In addition to age and carrier status, the potentially reversible conditions, obesity, hyperinsulinemia and lipid-raising drug use were contributory. Thus heterozygous lipoprotein lipase deficiency, together with age-related influences, may account for a form of familial hypertriglyceridemia.
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PMID:Phenotypic expression of heterozygous lipoprotein lipase deficiency in the extended pedigree of a proband homozygous for a missense mutation. 239 28

Non-insulin-dependent diabetes mellitus (NIDDM) is a genetic disorder characterized by two major pathogenic processes: reduced insulin action and a relative or absolute decrease in plasma insulin concentrations. We studied 116 nondiabetic siblings from 45 families to determine if in vivo insulin action showed any aggregation among siblings. Subjects were Pima Indians from the Gila River Indian Community in Arizona who, as a group, have the highest reported incidence and prevalence of NIDDM in the world. In vivo insulin action was determined by the euglycemic-clamp technique at two rates of insulin infusion in each subject with resulting mean plasma insulin concentrations of 119 and 1938 microU/ml. After adjustment for age, sex, and degree of obesity, there was significant aggregation among siblings of in vivo insulin action at the high insulin infusion rate (P less than or equal to .0001). Family membership independently accounted for approximately 34% of the variance in this measure of insulin action. Glucose uptake at the lower insulin infusion rate also showed familial aggregation (P less than .01), with family membership independently accounting for approximately 15% of the variance of this measurement. We conclude that in vivo insulin action is a familial characteristic. The familial component of insulin action occurs in addition to the effects of obesity, age, and sex on insulin action. Therefore it is not sufficient to simply know that an individual is lean or obese to predict his/her in vivo insulin resistance, because it must also be known whether he/she is from an insulin-resistant or insulin-sensitive family.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo insulin action is familial characteristic in nondiabetic Pima Indians. 331 55

The Cohen syndrome is a genetic disorder consisting of mental retardation, obesity, hypotonia, and a characteristic craniofacial appearance. Since its original description, 13 patients have been reported. This presentation gives an account of 5 additional cases in 4 families and provides further evidence that this disorder is most probably transmitted as an autosomal recessive trait. This study also demonstrates the range of clinical features observed in this syndrome and suggests that the basic defect may be one of connective tissue.
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PMID:The Cohen syndrome: report of five new cases and a review of the literature. 716 92

The Cohen Syndrome is a rare genetic disorder consisting of obesity, mental retardation, limb abnormalities and characteristic craniofacial appearance. Of the seven previously reported patients, none had any cardio-vascular involvement. This report describes an affected Jewish female, who, in addition to the usual malformations, has a floppy mitral valve.
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PMID:Cardiac involvement in the Cohen syndrome: a case report. 743 89

Diabetes mellitus and obesity are heterogeneous disorders that affect up to 5-8% of the population of Western Europe. The importance of genetic factors in these disorders is well established; however, the genes involved and the defects leading to the manifestation of disease are largely unknown. Family studies are a powerful tool with which to localize chromosomal regions linked to a genetic disorder. A genome-wide search for the genes associated with susceptibility to diabetes mellitus and obesity, combined with a more-specific, candidate-gene approach, should enable the identification of the loci involved in these diseases. Once regions linked to disease are identified, positional-cloning techniques can be used to track down the gene(s) responsible.
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PMID:Human diabetes and obesity: tracking down the genes. 776 95

Prader-Willi syndrome (PWS) is an unusual genetic disorder characterized by short stature, obesity, hypogonadism, hypotonia, cognitive impairment, and dysmorphic facies. There is an interstitial deletion of the proximal long arm of chromosome 15 in about 70 % of patients. Some of these clinical features suggest a central hypothalamic/pituitary dysfunction, and recent investigations have demonstrated a marked impairment in spontaneous growth hormone (GH) secretion. We studied 15 GH-deficient PWS patients by magnetic resonance imaging (MRI) to determine whether there was a diminution in the gross morphological size of the anterior pituitary gland, the site of GH synthesis. We also set out to catalog the pertinent imaging findings in this patient population. Our results indicate that this is the first report documenting pituitary size by MRI in PWS patients. No statistically significant difference was found in the height of the anterior pituitary gland in PWS patients compared with either normal children or children with isolated GH deficiency. An interesting imaging finding is that three of 15 patients (20 %) demonstrated complete absence of the posterior pituitary bright spot (PPBS), and a fourth patient demonstrated a small PPBS. These observations reflect an objective physiologic disturbance in the hypothalamus. The clinical and radiologic implications of these findings are discussed.
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PMID:MR of the pituitary in patients with Prader-Willi syndrome: size determination and imaging findings. 859 94

The Prader-Willi syndrome (PWS) is a genetic disorder which is difficult to diagnose from clinical symptoms in newborns and young children. However, it is known that in PWS a fragment within the q11-13 region of the paternally derived chromosome 15 is deleted. Recently it has been observed that the D15S63 (PW71) locus in chromosome 15q11-13 is methylated on the maternally derived chromosome, but unmethylated on the paternally derived chromosome. Based on this observation a rapid diagnostic test (the PW71 methylation test) using methylation-sensitive restriction enzymes has been developed for patients presumed to have PWS. We have studied 56 patients; 30 patients with classical features of PWS and 26 patients with only psychomotor retardation and obesity, referred to us from different part of Sweden. Twenty-nine of the 30 classical PWS patients were found to have an absence of the unmethylated paternally derived PW71(D15S63) locus in chromosome 15q11-13. None of the patients with only obesity and psychomotor retardation had this "absence" pattern on chromosome 15q11-13. Using the PW71 methylation test on patients with PWS, a concordance of 96% was found. The PW71 methylation test is presently the method of choice for rapid diagnostic testing of patients suspected of having PWS.
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PMID:Diagnosis of the Prader-Willi syndrome by proving the absence of the unmethylated PW71 DNA fragment. 864 49

Although non-insulin-dependent diabetes mellitus (NIDDM) is essentially a genetic disorder, environmental factors after birth including modernization-westernization and its related life style changes play an important role for the development of diabetes. Former prospective studies have indicated high prevalence of diabetes among the subjects with greater impairement of glucose tolerance, family history of diabetes, history of gestational diabetes and obesity. Beside these, more attention has been paid to the elevation of serum fatty acids and food composition as the provocative factors. In some populations, insulin resistance has been suggested to be a major cause of diabetes. In contrast, we have shown that most of the Japanese patients with NIDDM have impaired early insulin response after glucose loading and this should be important as a predictor for NIDDM.
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PMID:[Worsening factors for the progression of impaired glucose tolerance to diabetes mellitus learning from prospective studies]. 891 35

The ob/ob mouse is genetically deficient in leptin and exhibits a phenotype that includes obesity and non-insulin-dependent diabetes mellitus. This phenotype closely resembles the morbid obesity seen in humans. In this study, we demonstrate that a single intramuscular injection of a recombinant adeno-associated virus (AAV) vector encoding mouse leptin (rAAV-leptin) in ob/ob mice leads to prevention of obesity and diabetes. The treated animals show normalization of metabolic abnormalities including hyperglycemia, insulin resistance, impaired glucose tolerance, and lethargy. The effects of a single injection have lasted through the 6-month course of the study. At all time points measured the circulating levels of leptin in the serum were similar to age-matched control C57 mice. These results demonstrate that maintenance of normal levels of leptin (2-5 ng/ml) in the circulation can prevent both the onset of obesity and associated non-insulin-dependent diabetes. Thus a single injection of a rAAV vector expressing a therapeutic gene can lead to complete and long-term correction of a genetic disorder. Our study demonstrates the long-term correction of a disease caused by a genetic defect and proves the feasibility of using rAAV-based vectors for the treatment of chronic disorders like obesity.
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PMID:Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin. 939 Nov 28

We report a patient with Prader-Willi syndrome (PWS) complicated by diabetes mellitus. PWS is a genetic disorder characterized by obesity, mental retardation and hypogonadism. Glucose intolerance in this syndrome is thought to be secondary to insulin resistance associated with morbid obesity. Therapy was directed primarily at decreasing insulin resistance and thereby improving glucose intolerance by the administration of troglitazone, which increases insulin sensitivity. Changes in glucose disposal rate assessed by euglycemic hyperinsulinemic clamp test were measured, as well as glucose and insulin responses to a 75 g-OGTT before and after troglitazone therapy. Glucose disposal rate increased by 36% and plasma glucose responses to 75 g-OGTT decreased by about 50% during 12 weeks of troglitazone therapy despite slight weight gain. Thus, troglitazone has beneficial effects on glycemic control by improving insulin sensitivity in patients with PWS complicated by diabetes mellitus.
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PMID:Troglitazone ameliorates insulin resistance in a diabetic patient with Prader-Willi syndrome. 992 52


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