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)

The syndrome of insulin resistance comprises the following H-phenomena: 1. Hyperinsulinism compensating the inborn postreceptor insulin resistance, 2. Hyperglycaemia-non-insulin-dependent diabetes mellitus, 3. Hyperlipoproteinaemia with android obesity, 4. Hypertension, 5. Hirsutism with the syndrome of polycystic ovaries as a manifestation of a hyperandrogenic situation in the female organism. Molecular syndromes of this syndrome of insulin resistance are obscure. They are the subject of intensive studies because H-phenomena are an aggregation of the main risk factors of atherogenesis. Recently attention is focused also on amylin--a 37 amino acid peptide with a 50% homologous amino acid sequence with a calcitonin-gene--related peptide (CGRP), which is the product of a gene made up of three introns on the 12th chromosome. Amylin acts in the beta-cells of the pancreas as a co-secretion of insulin. If in excess, it is deposited in the form of an amyloid in the beta-cells. In the early stage of NIDDM it alters the physiological response of the beta-cell to glycaemic stimuli and food, in later stages of the disease, after accumulation, it causes apoptosis of the beta-cell and reduces thus the secretory capacity of the Langerhans islets. It is excreted in the urine and thus, if the glomerular filtration is reduced, it cumulates in the blood stream and thus enhances insulin resistance already in the early stages of chronic renal insufficiency, or in diabetic nephropathy. In type II diabetes similarly as insulin levels also amylin levels are elevated, while in type I diabetes with early autoimmune destruction of the beta-cells the insulin and amylin levels are reduced or even zero. Amylin reduces in the muscle, probably by inhibition of glycogen synthase, the insulin stimulated non-oxidative utilization of glucose into muscle glycogen and conversely by stimulation of phosphorylase it stimulates glycogenolysis and thus also lactate production and gluconeogenesis in the liver which all are anti-insulin effects which intensify the insulin resistance of the main target tissues. Amylin, similarly as CGRP or calcitonin, reduces Ca blood levels and has a vasodilatating effect; it reduces the BP but in different minimal and maximal doses and by a different mechanism and via special receptors because the link of amylin to calcitonin receptors is 100 times lower and does not produce a rise of cAMP in the target cell. The effect on the enhancement of insulin resistance in muscle was proved also by direct measurements using an hyperinsulinaemic euglycaemic clamp. After prolongation of the clamp to more than two hours the effect on insulin resistance disappeared, although the hypocalcinaemic effect persisted. Amylin is able by its biological action to modify the secretion as well as the effectiveness of insulin to pathological values. These two characteristics are typical for impaired glucose tolerance in type II diabetes. Studies are under way to find out whether the effect of amylin is involved directly also in the pathogenesis of the other H-phenomena or only via accentuation of hyperinsulinism. In any case amylin is a new link the role of which in the pathogenesis of NIDDM and the syndrome of insulin resistance awaits evaluation. Due to its effect on gastric evacuation it participates also in the postprandial glycaemic control in particular in type I diabetes where it it begins to be used in therapy. Perhaps it will be possible to administer it in these patients along with insulin to improve diabetes compensation.
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PMID:[Amylin as an additional possible pathogenic factor in NIDDM and the insulin resistance syndrome]. 896 27

Various studies have convincingly shown that recombinant human growth hormone (rhGH) therapy accelerates growth significantly in children with growth retardation secondary to chronic renal insufficiency (CRI) and after renal transplantation (RTx). rhGH therapy appeared remarkably safe intermediate-term, but paediatricians are concerned about the potential adverse effects on glucose homeostasis and insulin action. Particularly in children with CRI and after RTx, pre-existing insulin resistance may be aggravated by exogenous rhGH therapy. Patients after RTx had significantly higher pretreatment insulin levels than controls (p < 0.001). Various studies in both patient groups showed that one year of rhGH therapy at 4 i.u./m2/day did not impair glucose tolerance but significantly increased plasma insulin levels (p < 0.001). No patients developed impaired glucose tolerance or permanent diabetes mellitus (DM), but from these studies, it was concluded that euglycemia was maintained at the expense of increased insulin levels. The long-term consequences of the compensatory hyperinsulinaemia are not yet known. Although permanent DM has not been reported in any of the rhGH trials in renal patients, it cannot be excluded that some patients with CRI or after RTx may develop impaired glucose tolerance and/or permanent DM during long-term rhGH therapy, particularly those with risk factors such as familial type II DM and obesity. Long-term studies, including careful monitoring of carbohydrate metabolism, are required.
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PMID:Can glucose intolerance and/or diabetes be predicted in patients treated with rhGH? 899 34

Dyslipidemia increases the risk of cardiovascular events among individuals with renal disease, and there is a growing body of evidence that it hastens the progression of renal disease itself. Children with nephrotic syndrome or renal transplants have easily recognized hyperlipidemia. Among those with chronic renal insufficiency or end-stage renal disease, detection of dyslipidemia requires more careful analysis and knowledge of normal pediatric ranges. Disordered lipoprotein metabolism results from complex interactions among many factors, including the primary disease process, use of medications such as corticosteroids, the presence of malnutrition or obesity, and diet. The systematic treatment of dyslipidemia in children with chronic renal disease is controversial because conclusive data regarding the risks and benefits are lacking. Hepatic 3-methylglutaryl coenzyme A reductase inhibitors (statins), fibrates, plant stanols, bile acid-binding resins, and dietary manipulation are options for individualized treatment. Prospective investigations are required to guide clinical management.
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PMID:Dyslipidemia in pediatric renal disease: epidemiology, pathophysiology, and management. 1198 Dec 90

In recent years several multicentric prospective studies have demonstrated the efficacy of some therapeutic measures to slow the progression of renal diseases. Inhibition of renin-angiotensin system (RAS) both by ACE inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) is probably the strongest therapeutic alternative: The antiproteinuric effect of these drugs is an excellent surrogate marker and a predictor of the beneficial influences on the progression of renal failure. The type of renal disease, an inadequate control of blood pressure, and the presence of obesity may counteract the beneficial influences of RAS inhibition, whereas early treatment of all patients with significant proteinuria before the appearance of renal insufficiency and combined therapy with an ACEI and an ARA may augment it. Dietary protein restriction is a classic treatment of chronic renal insufficiency whose effectiveness has been validated by multicentric studies. However, a poor compliance of the patient and the risk of malnutrition with very strict protein restriction could limit the benefits of this treatment. Treatment of hyperlipidemia, prevention of obesity, avoidance of smoking, and regular physical exercise are interventions whose therapeutic potential is progressively recognized, particularly in type 2 diabetic nephropathy. Early correction of anemia may contribute to the slowing of renal disease progression. Although further studies are required, the accumulated evidence and the likelihood of additive beneficial effect of these therapeutic measures advise their combined implementation in patients with chronic renal diseases.
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PMID:Slowing the progression of renal failure. 1198 7

This study investigates the changing referral patterns of young patients to a tertiary pediatric nephrology center with a well-defined catchment area over two consecutive 8.5-year periods. We paid special attention to the known increase of obesity and diabetes mellitus in childhood. Demographic data (site of residence, height, weight, gender and renal diagnosis) were collected on 6,154 children aged 0-19 years, referred as in- and outpatients to the Children's Hospital of Eastern Ontario for nephrological work-up. Body mass index (BMI) Z-scores were calculated on the basis of data from the National (USA) Center for Health Statistics (2000). In 6,124 (99.5%) patients a final renal diagnosis could be made, allowing calculation of the incidence of a variety of renal diseases in pediatric patients, data that are not readily available. BMI increased significantly over the years, with a Z-score that rose from a median of +0.20 to +0.32 in the two 8.5-year study periods (p<0.0001). The increase in obesity coincided with a significant increase in the incidence of chronic renal insufficiency (CRI). The combined incidence of CRI and end stage renal disease rose from 0.994 to 2.334 per 100,000 children per year (p=0.0014). This study provides new information on the (changing) pattern of pediatric renal disease over almost two decades. Pediatric renal patients became progressively overweight and showed an increase in the incidence of CRI. This is the first time that this phenomenon, well known in adults, has been observed in the pediatric age group.
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PMID:Changing trends in the referral patterns of pediatric nephrology patients. 1577 41

Obesity represents one of serious risk factors in chronic renal failure patients (CRF). In three years prospective double-blind randomised multicentre study we monitored 66 patients with advanced chronic renal insufficiency, GFR 24.4-37.3 ml/min (0.41 to 0.62 ml/s) and BMI > or = 30 kg/m2 on long term low-protein diet (0.6 P/kg BW/day) and ACEI + ARB. Thirty four randomly selected patients (group I) were treated with keto amino acids, 32 patients in control group (group II) with placebo. During the study period significant decrease of BMI, proteinuria and slowing in progression of renal failure (C(in)) were found. Significant changes were also noted in parameters of albumin and transferrin (p < 0.02), leucin and WQ (p < 0.01 - p < 0.02), glycaemia and HbA1c (p < 0.02), triglycerides (p < 0.01), leptin and ObRe (p < 0.01) and selected parameters of endothelial dysfunction (ET1, p < 0.02, TGFbeta1, p < 0.02). Significantly also decreased PTH value (p < 0.01). Successful treatment of obesity can significantly improve long term prognosis in CRF patients.
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PMID:[Obesity and progression of chronic renal insufficiency: a Czech long term prospective double-blind randomised multicentre study]. 1687 60

Incidence and prevalence of Type 2 Diabetes, together with its long term complications is explosively rising. The trans-border project "INTERREG III" tries to explore the epidemiology in the 3 concerned countries and to tie a network between the health providers. Estimation of prevalence is around 3% of the adult population but rising for example in the Grand Duchy by 4.5% per year, meaning the number of affected patients will double in 16 years, mainly due to the increase in obesity. Chronic renal insufficiency will rise and the number of patients will double in 8 years. Cardiovascular diseases and peripheral necrosis explain the high rate of hospitalisations and the loss of Life-expectancy that seems to be reduced by 5 to 10 years. A cost analysis in this article reveals the necessity of primary and secondary prevention programs of "diabesity" in this region, together with better multidisciplinary approaches of treatment and follow-up. This article emphasizes the need of a collaboration of all actors in the field, medical and para-medical.
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PMID:[Epidemiology of diabetes in the INTERREG III Province of Luxembourg, the Grand Duchy of Luxembourg, Lorraine]. 1795 79

Cystic renal lymphangiectasia (CRL) is a rare malformation of lymphatics that can present in childhood and adulthood. Symptoms and radiologic features are relatively well defined, but clinical evolution and prognosis remain unclear. We treated a boy with CRL who developed chronic renal insufficiency. The first manifestation was abdominal swelling associated with an umbilical hernia noted incidentally at 1.6 years. Computed tomography with intravenous contrast administration demonstrated perirenal cysts with fluid collection, suggesting CRL. Intractable ascites resisted pharmacologic treatments such as diuretics. After approximately 7 years, the ascites resolved spontaneously, but the perirenal cysts persisted. At 11 years, proteinuria was noted. A renal biopsy specimen showed interstitial abnormalities consistent with CRL, glomeruli showed a focal segmental mesangial increase. Proteinuria persisted despite administration of an angiotensin-converting enzyme inhibitor, increasing as obesity and hypertension worsened. Renal function gradually declined in the ensuing years. Polycythemia coexisted with a normal serum erythropoietin concentration. A follow-up renal biopsy specimen disclosed glomerular enlargement together with focal segmental mesangial expansion, suggesting obesity-related glomerulopathy. Our observation suggest that under some specific circumstances like our patient CRL may exacerbate. Management of complicating obesity and hypertension are likely to be important for maintaining normal renal function, especially in the diffuse bilateral type of CRL present in our patient.
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PMID:Chronic renal insufficiency in a boy with cystic renal lymphangiectasia: morphological findings and long-term follow-up. 1818 26

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.
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PMID:Recognizing calcific uremic arteriolopathy in autoimmune disease: an emerging mimicker of vasculitis. 1877 19

Intracranial hypertension (IH) is a rare condition in children. However, a relationship between recombinant human growth hormone (rhGH) therapy and IH has been well documented. Risk factors were assessed for 70 rhGH-naive patients enrolled in the National Cooperative Growth Study with reports of IH after treatment initiation. Patients with severe growth hormone deficiency, Turner syndrome, chronic renal insufficiency (CRI), and obesity (particularly in the CRI group) were at highest risk of developing IH during the first year of therapy, suggesting initiation of careful early monitoring. In some patients, factors such as corticosteroid use or other chromosomal abnormalities appear to confer a delayed risk of IH, and these patients should be monitored long-term for signs and symptoms of IH.
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PMID:Intracranial hypertension in pediatric patients treated with recombinant human growth hormone: data from 25 years of the Genentech National Cooperative Growth Study. 2214 47


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