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)

The heterogeneity within Type II diabetes (NIDDM) and within Maturity-Onset type Diabetes of Young people (MODY), a subset of NIDDM which is inherited in an autosomal dominant fashion, is discussed. Aspects of the definition and phenotypic expression of MODY are reviewed. Within NIDDM there are differences in patterns of inheritance between subgroups. HLA antigen associations are not found in most NIDDM populations but exist in three specific population groups with Type II diabetes. Within NIDDM and within MODY there are differences in the magnitude of insulin responses to glucose, differences in target tissue responsiveness to insulin in vivo, and differences in receptor and post-receptor effects of insulin. Structurally abnormal variant and biologically defective insulin molecules have been found in some Type II diabetic patients and in members of certain MODY families. The presence or absence of obesity may mark heterogeneous groups of Type II diabetic patients, in addition to the importance of obesity in uncovering an insulin secretory defect by causing insulin resistance. There is heterogeneity in susceptibility to vascular disease within NIDDM and MODY. The natural history of carbohydrate metabolism and of insulin secretory responses to glucose in early Type I diabetes and in MODY with low insulin secretory responses are illustrated and similarities and dissimilarities compared and contrasted. Failure to recognize young patients with MODY may contribute to incorrect diagnosis, management, and assignment of prognosis of this form of diabetes in the young by many practicing physicians. The recognition that Type I or insulin-dependent diabetes (IDDM) and Type II or noninsulin-dependent (NIDDM) differ from each other not only phenotypically but also in etiology and pathogenesis led the National Diabetes Data Group (NDDG) to devise the present nomenclature and classification of diabetes mellitus. These were adopted by the World Health Organization. As suggested by the NDDG report, the classification should be reexamined periodically to reflect improved understanding of the disease, to stimulate further research, and to be of help to practicing physicians.
 ...
PMID:Heterogeneity within type II and MODY diabetes. 389 67

Changes in the incidence of the HLA system antigens (A1, A2, A3, A9, A10, A11, A19, A28, A29, B5, B7, B8, B13, B14, B15, B16, B17, B18, B21, B22, B27, B35, B37, B40, B41) was studied in 1134 healthy persons and in 147 patients with diabetes mellitus. In comparison with healthy persons, patients with juvenile diabetes mellitus (62) displayed a significant increase in the incidence of antigens B8, B15, B35, and A10, and patients with adult diabetes mellitus with normal weight (35)--of antigen B8. When adult diabetes mellitus was accompanied by obesity (50) a significant rise in the occurrence of antigen A10 was revealed.
 ...
PMID:[Change in the incidence of HL-A antigens in diabetes mellitus]. 615 26

HLA antigens, complement allotypes, insulin antibodies and thyrogastric autoantibodies were determined in 69 patients with Type 1 (insulin-dependent) diabetes defined by a tendency to ketosis, non-obesity and insulin requirement within 2 years of diagnosis. Analysis of HLA and C4 allotypes suggested that Type 1 diabetes was associated with only certain DR3- and DR4-containing supratypes. Low antibody response to insulin was associated with all HLA-DR3, being present in 89% of those with DR3 compared with 48% of those without. Thyrogastric autoantibodies were associated with a null allele at the C4A locus, usually with HLA-B8-C4AQO-C4B1-BfS-DR3. These results indicate that, unlike Type 1 diabetes, low insulin antibody response was associated with all HLA-DR3. Thyrogastric autoantibodies, on the other hand, were associated with a null allele at the C4A locus. It is probable that while interaction between certain HLA-DR3 and DR4-containing supratypes is important in conferring susceptibility to Type 1 diabetes, other manifestations of autoimmunity are associated with supratypes containing C4AQ0, and in particular the diabetogenic supratype HLA-B8-C4AQ0-C4B1-BfS-DR3.
 ...
PMID:Thyrogastric autoimmunity and MHC associated alleles at the C4 locus in patients with type 1 (insulin-dependent) diabetes. 633 53

By and large, essential diabetes mellitus is thought to be 50% inherited and 50% environmental. In insulin-dependent diabetes mellitus (IDDM) there is a strong link with the HLA system with regard to the inheritance of 'susceptible' diabetic genes, especially the DR3 and DR4 alleles. In IDDM environmental factors act in a predisposed individual to initiate an immune response with resultant beta-cell damage and destruction. Non-insulin-dependent diabetes mellitus (NIDDM) has no clear HLA link, but has been shown in studies of twins to have a stronger genetic basis than IDDM. In NIDDM environmental factors (race, ethnicity, diet, obesity) have an important influence on the clinical expression of the disease and the severity of complications in a genetically predisposed individual. The non-insulin-dependent diabetes of the young (NIDDY) variant and the phenomenon of chlorpropamide-primed alcohol-induced flushing both underline the heterogeneity of NIDDM. Because of the heterogeneous nature and multifactorial inheritance pattern of diabetes mellitus, accurate genetic counselling is not possible as yet. However, data to date suggest that it is unwise to advise prospective parents not to procreate, since the overall risk of the development of clinical diabetes mellitus is extremely low.
 ...
PMID:The genetics of diabetes mellitus, including the South African perspective. 638 8

A possible association between HLA and obesity was investigated in 42 unrelated obese children from Hessen, Germany. A family study was possible in 11 families with a total of 26 children. No significant deviation was observed for one of the HLA ABC antigen frequencies in the sample group compared with controls (n = 220). The linkage analysis in families: a) ruled out a close linkage (less than 10 cM) between HLA and a hypothetical obesity gene (assumption of a dominant mode of inheritance), b) did not exclude recessive inheritance so far, since the importance of penetrance is unknown and a simple gene model is improbable, c) yielded also negative lod scores (which did not reach the elimination level of -2) for an intermediary genetic model.
 ...
PMID:HLA and obesity. 659 67

This study was designed to investigate whether isolated genetic factors, controlled by genes in the HLA chromosomal region, could be indicted as independent contributing influences in the genesis of premature coronary artery disease (CAD). Nineteen patients with fixed obstructive CAD documented by coronary angiography had no coronary risk factors with respect to age; levels of serum cholesterol, fasting triglycerides, and blood glucose; blood pressure; obesity; history of diabetes mellitus or hypertension; and cigarette-smoking history. Sixteen patients had a family history of CAD. HLA typing was restricted to antigens of the A and B loci. Control subjects (n = 1,157) were normal. At the A locus, no antigens demonstrated an observed frequency significantly higher than that expected from the control population. At the B locus, BW 38 had a statistically significant greater frequency (p less than 0.01) in the study group with CAD (21 percent) than in the control population (4 percent). The association between BW 38 and premature CAD lost its statistical significance when conservatively corrected for the number of HLA antigens tested by the Bonferroni adjustment. The relative risk for CAD if a patient had antigen BW 38 was 6.2. Our data suggest a statistically significant trend between the presence of HLA BW 38 and premature CAD. Whether the HLA tissue antigens are involved directly in the pathogenesis of CAD, act as markers for immune response genes, or serve as markers of other yet undefined genetic factors needs further study.
 ...
PMID:Correlation of HLA types in premature coronary artery disease: an attempt to define independent genetic risk factors. 719 67

HLA A and B typing was performed in 86 unrelated obese subjects and in 10 families including at least one parent and one obese sibling. The results in the series of unrelated subjects show no significant difference in antigen frequencies as compared to the control series. However in the 10 families studied, a group of 5 families is characterized by a high penetrance of obesity. In this group, inheritance of obesity seems to be transmitted through a dominant mode, and antigen B 18 appeared 4 times out of 5. The possible existence of a genetic form of obesity is considered in the discussion.
 ...
PMID:Genetic approach of family obesity: study of HLA antigens in 10 families and 86 unrelated obese subjects. 742 78

Genetic heterogeneity, the concept that diabetes can have many different causes, was first suggested by the existence of rare genetic syndromes with diabetes, ethnic differences in clinical features and genetic heterogeneity of animal models. Genetic heterogeneity is now considered to be firmly established by family, twin, metabolic, immunologic and HLA disease association studies that separate idiopathic diabetes into insulin-dependent types (juvenile-onset type) and noninsulin-dependent types (maturity-onset type). Further heterogeneity is being demonstrated within each of these broad groups of disorders--within insulin-dependent diabetes using the HLA antigens and immunologic studies, and within noninsulin-dependent diabetes using such criteria as obesity, insulin response, age of onset and chlorpropamide-primed alcohol-induced flushing. This heterogeneity has major implications for the research and care of our diabetic patients since the precise etiology, risk of complications and genetic counseling are likely to vary among these different disorders that result in diabetes.
 ...
PMID:The genetics of the glucose intolerance disorders. 745 85

Epidemiologic studies are important for both understanding and defining rheumatology practice. Controversy still exists over whether the incidence of rheumatoid arthritis is declining, and genetic studies indicate a diversity of HLA haplotypes in rheumatoid arthritis. Large longitudinal osteoarthritis studies have helped define diagnostic criteria and the role of obesity in disease progression. The negative association between osteoarthritis and osteoporosis at specific sites continues to be explored, and the value of long-term estrogen therapy in preventing bone loss has been examined. Both retrospective and prospective population studies have been used to describe the relationship between silicone gel breast implants and connective tissue disease. These and other studies have helped to define the important role of epidemiologic research in the understanding of rheumatic diseases.
 ...
PMID:Epidemiology of the rheumatic diseases. 776 99

Although simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia and correction of uremia in type I diabetic patients with renal failure, little data are available on long-term outcome and clinical determinants of recovery of peripheral neuropathy. In this prospective study, 219 electrophysiological studies using a standardized protocol were performed before and up to 8 years after SPK in 44 patients. Nine control diabetic recipients with functioning kidney but nonfunctioning pancreas transplants were studied on 35 occasions. Patients were 38.5+/-7.9 years old (mean+/-SD) with pretransplant diabetes present for 25.2+/-7.6 years. Significant polyneuropathy (total nerve conduction scores [NCS] <-1.0) was present in 89% before transplantation, which correlated with body weight (r=0.628, P<0.001). Two distinct patterns of neurological recovery were observed after SPK. Conduction velocity (CV) improved in a biphasic pattern, with a rapid initial recovery followed by subsequent stabilization. In contrast, the recovery of nerve amplitude was monophasic, and continued to improve for up to 8 years. Initial improvement in NCS was primarily due to an increase in CV (P=0.002 vs. baseline), and was best in shorter and younger patients. Recovery of total NCS at 6 months after SPK, assessed by multivariate analysis, was least in obese recipients and when performed in patients who had started dialysis before SPK, and was associated with lower transplant kidney isotopic glomerular filtration rate and HLA mismatch (P<0.05 to 0.001). Subsequent improvement was associated with less severe initial neuropathy, smaller body weight, and longer duration of diabetes (P<0.01 to 0.001). Fasting hyperinsulinemia was associated with impairment of initial recovery and subsequent NCS after SPK, but was worse in the control group. Recovery of nerve action potential amplitudes was predicted by better initial amplitudes and HLA mismatch, lower body weight, and the use of nifedipine (P<0.05 to 0.001). Nifedipine was used for hypertension in 33% of SPK and was associated with better CV and amplitudes, particularly in the upper limbs, where there was less neuropathy. The use of angiotensin-converting enzyme inhibitors also appeared beneficial, but this was confined to the lower limbs. SPK resulted in a gradual, sustained, and late improvement in nerve action potential amplitudes, consistent with axonal regeneration and partial reversal of diabetic neuropathy. These data suggest that early transplantation of uremic diabetic patients before onset of severe neuropathy, minimizing obesity and optimizing renal transplant function, maximizes neurological recovery after SPK. Furthermore, the preliminary data support randomized clinical trials for evaluation of nifedipine and angiotensin-converting enzyme inhibitors in diabetic neuropathy.
 ...
PMID:Diabetic neuropathy after pancreas transplantation: determinants of recovery. 908 22


<< Previous 1 2 3 4 5 6 7 Next >>