UMLS:C0011854 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0011854 (type 1 diabetes)
20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to study the efficiency and the adverse effects of 2 or 4 IU/m2/day of growth hormone (GH) in the first year and 4 IU/m2/day in the second. Of 29 growth-retarded children with chronic renal failure (CRF) (aged 3.4-15.1 years), 23 completed the first year of therapy, and 16 completed the second year. Height velocity SDS (HVSDS) increased in the first year in the low-dose group with 3.0, and 3.8 in the high-dose group. In the second year, HVSDS increased by 1.3 in the low-dose group and by 2.1 in high-dose group (p < 0.05). The IGF-I/IGFBP-3 ratio rose identically during the first year (p < 0.01). The retarded bone age did not advance inappropriately. The integrated insulin levels (AUC) increased significantly after 1 year of therapy in both groups. HbA1c, levels did not change. The number of adverse events was highest in the low-dose group, in which one patient developed overt insulin dependent diabetes mellitus. In conclusion, glucose metabolism should be monitored in children with CRF during rhGH-treatment. GH therapy in our patients resulted in a significant increase in height velocity with no inappropriate bone age progression and few serious adverse effects, all without relation to the dose of rhGH. The low start dose (2 IU/m2/ day) was of no advantage compared to the high dose.
...
PMID:Recombinant human growth hormone treatment, using two dose regimens in children with chronic renal failure--a report on linear growth and adverse effects. 1201 16

Serum levels of advanced glycation end products (AGEs) are markedly elevated in adults with chronic renal failure (CRF) and diabetes mellitus. Accumulation of AGEs in tissues contributes to the development of long-term complications. Up to now little has been known about the formation of AGEs in childhood. We determined serum levels of the well known AGEs pentosidine and Nvarepsilon-carboxymethyllysine (CML) in children with CRF (n=12), end-stage renal disease (ESRD) (n=9), renal transplantation (n=12), and type 1 diabetes mellitus (n=42) and in healthy children (n=20). Pentosidine was measured by high-performance liquid chromatography (HPLC), CML by a competitive enzyme-linked immunosorbent assay (ELISA) system. Serum levels of pentosidine and CML were significantly higher in the children with CRF and ESRD than in controls (P< 0.001), but nearly within the normal range after transplantation. Both AGEs showed a significant negative correlation with creatinine clearance (P< 0.001). During a single session of low-flux hemodialysis, total pentosidine and CML levels did not change. Free pentosidine, however, was reduced by 78% (P=0.04). Diabetic children showed significantly elevated pentosidine levels (P< 0.001) despite normal renal function. We conclude that, similar to adults, increased formation and accumulation of AGEs also exist in children with CRF and type 1 diabetes mellitus. At present the best prevention of AGE-related complications is an early renal transplantation in children with ESRD, as well as a careful metabolic monitoring of diabetics.
...
PMID:Advanced glycation end products in children with chronic renal failure and type 1 diabetes. 1204 86

Adiponectin, also called GBP-28, apM1, AdipoQ and Acrp30, is a novel adipose tIssue-specific protein that has structural homology to collagen VIII and X and complement factor C1q, and that circulates in human plasma at high levels. It is one of the physiologically active polypeptides secreted by adipose tIssue, whose multiple functions have started to be understood in the last few Years.A reduction in adiponectin expression is associated with insulin resistance in some animal models. Administration of adiponectin has been accompanied by a reduction in plasma glucose and an increase in insulin sensitivity. In addition, thiazolidinediones, drugs that enhance insulin sensitivity through stimulation of the peroxisome proliferator-activated receptor-gamma, increase plasma adiponectin and mRNA levels in mice. On the other hand, this adipocyte protein seems to play a protective role in experimental models of vascular injury. In humans, adiponectin levels are inversely related to the degree of adiposity and positively associated with insulin sensitivity both in healthy subjects and in diabetic patients. Plasma adiponectin levels have been reported to be decreased in some insulin-resistant states, such as obesity and type 2 diabetes mellitus, and also in patients with coronary artery disease. On the contrary, chronic renal failure, type 1 diabetes and anorexia nervosa are associated with increased plasma adiponectin levels. Concentrations of plasma adiponectin have been shown to correlate negatively with glucose, insulin, triglyceride levels and body mass index, and positively with high-density lipoprotein-cholesterol levels and insulin-stimulated glucose disposal. Weight loss and therapy with thiazolidinediones increased endogenous adiponectin production in humans. Adiponectin increases insulin sensitivity by increasing tIssue fat oxidation, resulting in reduced circulating fatty acid levels and reduced intracellular triglyceride contents in liver and muscle. This protein also suppresses the expression of adhesion molecules in vascular endothelial cells and cytokine production from macrophages, thus inhibiting the inflammatory processes that occur during the early phases of atherosclerosis. In view of these data, it is possible that hypoadiponectinemia may play a role in the development of atherosclerotic vascular disease. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, with potential applications in states associated with low plasma adiponectin levels.
...
PMID:The role of the novel adipocyte-derived hormone adiponectin in human disease. 1261 9

Somatomedin-1 binding protein-3 [insulin-like growth factor-1 binding protein-3, SomatoKine] is a recombinant complex of insulin-like growth factor-1 (rhIGF-1) and binding protein-3 (IGFBP-3), which is the major circulating somatomedin (insulin-like growth factor) binding protein; binding protein-3 regulates the delivery of somatomedin-1 to target tissues. Somatomedin-1 binding protein-3 has potential as replacement therapy for somatomedin-1 which may become depleted in indications such as major surgery, organ damage/failure and traumatic injury, resulting in catabolism. It also has potential for the treatment of osteoporosis; diseases associated with protein wasting including chronic renal failure, cachexia and severe trauma; and to attenuate cardiac dysfunction in a variety of disease states, including after severe burn trauma. Combined therapy with somatomedin-1 and somatomedin-1 binding protein-3 would prolong the duration of action of somatomedin-1 and would reduce or eliminate some of the undesirable effects associated with somatomedin-1 monotherapy. Somatomedin-1 is usually linked to binding protein-3 in the normal state of the body, and particular proteases clip them apart in response to stresses and release somatomedin-1 as needed. Therefore, somatomedin-1 binding protein-3 is a self-dosing system and SomatoKine would augment the natural supply of these linked compounds. Somatomedin-1 binding protein-3 was developed by Celtrix using its proprietary recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on June 1 2000. Insmed and Avecia, UK, have signed an agreement for the manufacturing of SomatoKine and its components, IGF-1 and binding protein-3. CGMP clinical production of SomatoKine and its components will be done in Avecia's Advanced Biologics Centre, Billingham, UK, which manufactures recombinant-based medicines and vaccines with a capacity of up to 1000 litres. In 2003, manufacturing of SomatoKine is planned to move to Avecia's larger facility with a capacity of 10 000 litres. Somatomedin-1 binding protein-3 was originally licenced to Welfide for Japan. On October 1 2001, Welfide Corporation merged with Mitsubishi-Tokyo Pharmaceuticals to form Mitsubishi Pharma Corporation. The new company is a subsidiary of Mitsubishi Chemical. In April 2003 Insmed initiated a named patient programme in Europe, that will make available somatomedin-1 binding protein-3 for the treatment of growth hormone insensitivity syndrome (GHIS)--Laron syndrome. The treatment of patients was initiated in Scandinavia, with authorisation pending in several other European countries. Somatomedin-1 binding protein-3 will be made available to those GHIS patients who, in the opinion of their doctor, may benefit from IGF-1 therapy. At precommercial scale quantities, the drug will be available on a limited basis. Safety data generated from the named patient programme will be used to support marketing applications in 2004. A phase II dose-ranging study in children with GHIS was completed at Saint Bartholomew's and the Royal London School of Medicine, London, UK. A single dose of somatomedin-1 binding protein-3 delivered the same amount of IGF-1 as two daily injections of unbound IGF-1. There were no adverse events reported. GHIS is a genetic condition in which patients do not produce adequate quantities of IGF because of a failure to respond to the growth hormone signal. This results in a slower growth rate and short stature. Insmed has acquired an exclusive licence to Pharmacia's regulatory filings concerning yeast-derived IGF-1. These filings were used by Pharmacia to receive marketing approvals in several European countries and also in the investigational New Drug Application with the US FDA. This licence will facilitate the development of SomatoKine for the treatment of children with GHIS. In January 2003, Insmed announced positive results from a double-blind, placebo-controlled, dose-ranging study of SomatoKine in adolescent patients with type 1 diabetes mellitus redolescent patients with type 1 diabetes mellitus receiving insulin therapy. The study was conducted at the University of Cambridge, Cambridge, UK, under the supervision of Professor D. Dunger. It has also been granted orphan drug status for the treatment of GHIS--Laron syndrome in the US and in Europe. Celtrix has been granted 11 US patents for its recombinant protein production technology, which it used for developing somatomedin-1 binding protein-3. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on June 1 2000. Following the acquisition, Insmed announced that it intends to maintain the US rights to Celtrix's products portfolio. These US patents will expire between 2010 through 2017. Insmed is holding a US patent (expires in 2019) for the use of SomatoKine in the treatment of both type 1 and type 2 diabetes mellitus.
...
PMID:Somatomedin-1 binding protein-3: insulin-like growth factor-1 binding protein-3, insulin-like growth factor-1 carrier protein. 1449 68

Transforming growth factor-beta1 (TGF-beta1) is a potent multifunctional polypeptide that is involved in normal renal function and in the development of glomerular sclerosis. It is also an important mediator of the immune and anti-inflammatory responses. The purpose of this study was to examine whether the measurement of urinary TGF-beta1 excretion in patients with different types of renal diseases and in newly diagnosed type 1 diabetes mellitus represents a non-invasive tool to evaluate disease activity and to monitor response to therapy. We studied the urinary excretion of TGF-beta1 in 57 nephropathic patients divided in different groups according to the underlying disease: 15 had mesangial glomerulonephritis (IgAGN), 9 membranous glomerulonephritis (MGN), 7 rapidly progressive glomerulonephritis (RPGN), 8 systemic lupus erythematosus (SLE), 9 interstitial nephritis (IN), 9 chronic renal failure (CRF). TGF-beta1 was also measured in 38 patients with type 1 (insulin-dependent) diabetes mellitus (12 with newly diagnosed diabetes, 26 long-standing diabetes) and 31 healthy controls. Total urinary TGF-beta1 concentration was assayed by enzyme-linked immunoassay (ELISA), and expressed as a ratio to urinary creatinine concentration. The urinary TGF-beta1 levels were compared with the findings of biopsy and clinical parameters. Urinary TGF-beta1 excretion was significantly increased in all groups except MGN, IN and CRF. In non-diabetic patients, urinary TGF-beta1 levels correlated with crescent formation, floccular adhesion and mesangial proliferation, but not with the degree of tubulo-interstitial fibrosis. Urinary TGF-beta1 levels did not correlate with indices of renal function (serum creatinine, glomerular filtration rate (GFR), albumin excretion rate [AER]). Among diabetic patients, HbA(1C) significantly correlated with TGF-beta1 urinary excretion. Urinary TGF-beta1 levels may represent a valid indicator of acute glomerular flogosis associated with mesangial proliferation in glomerulonephrities. In newly diagnosed diabetic patients, hyperglycaemia seems to represent the principal factor leading to TGF-beta1 overproduction. Follow-up studies of urinary TGF-beta1 levels measured during optimal glycaemic control are necessary to clarify the relationship between hyperglycaemia and TGF-beta1 excretion.
...
PMID:Urinary transforming growth factor-beta 1 in various types of nephropathy. 1472 27

Diabetic nephropathy affects 20-35% patients with diabetes mellitus. After 25-30 years of nephropathy, chronic renal failure (CRF) develops in these patients. The aim of the study is to present the influence of simultaneous pancreas and kidney transplantation (SPK) on long-term diabetic complications in patients with CRF in course of insulin dependent diabetes mellitus and the length and quality of life of these patients. SPK has positive influence on nerves function of peripheral and autonomic nerve system, as well as heart ventricle function, but brings only limited benefits as regards progression of diabetic retinopathy and nephropathy. The life time of the patients in which SPK was performed is significantly longer that in dialysed patients treated with insulin and patients, in which only cadaveric kidney transplantation was performed. In patients after SPK an improvement of quality of life is also observed. SPK should be considered at the moment of appearance of renal failure symptoms in patients with long lasting insulin dependent diabetes mellitus. Proceeding like this may significantly improve prognosis in this patients, outstandingly disadvantageous if only intermittent dialysis is applied.
...
PMID:[The influence of simultaneous pancreas and kidney transplantation on long-term diabetic complications in patients with insulin dependent diabetes mellitus]. 1496 43

The prognosis of type 1 diabetes mellitus (T1DM) patients with chronic renal failure (CRF) improves after simultaneous pancreas-kidney (SPK) transplantation. In order to evaluate the changes in cardio-vascular risk (CVR) factors after SKP, we studied nine recipients before and 6 months after SPK. There were five females and four males, with a mean age of 37 +/- 8 years, duration of diabetes of 24 +/- 5 years, three of them before starting dialysis, and six on dialysis (hemodialysis = 5; peritoneal dialysis = 1). Before SPK, all patients received anti-hypertensive therapy (1-4 drugs; mean 2.2 +/- 0.9) and eight received statins. At 6 months after SPK, all patients were under triple immunosuppressive therapy (steroids + tacrolimus + MMF) without statins. They had normal renal function (Plasma Creatinine = 1.2 +/- 0.3 mg/dl) and pancreatic endocrine function (glycemia = 80 +/- 8 mg/dl). HbA1c decreased significantly (8.4 +/- 1.2 vs 4.7 +/- 0.6%; p < 0.007) with a value > 7% in seven patients before SPK and in none 6 months after SKP transplantation (p < 0.001). Although Body Mass Index increased (23 +/- 2 vs 25 +/- 3 kg/m2; p < 0.05), plasma triglycerides decreased (130 +/- 51 vs 88 +/- 33 mg/dl; p < 0.05), and total cholesterol, LDL-cholesterol and HDL-cholesterol were similar. Systolic and diastolic blood pressure (BP) decreased (156 +/- 7 vs 133 +/- 15; p < 0.01 and 96 +/- 7 vs 79 +/- 9; p < 0.007) with only two patients on anti-hypertensive therapy (1 drug). Likewise, before transplantation all patients were hypertensive (six grade 1 and three grade 2) while this was observed in only two at the end of follow-up (both grade 1) (p < 0.001). In conclusion, SPK transplantation with good renal and pancreatic function is associated with a short-term improvement in CVR profile.
...
PMID:[Improved short-term cardiovascular profile after simultaneous pancreas-kidney transplantation]. 1605 13

A 37-year-old man with type I diabetes mellitus and chronic renal failure presented to the emergency department complaining of hallucinations. He was 5 days postoperative for left pars plana vitrectomy and intra-ocular lens implantation and had been taking ophthalmic atropine, tobramycin and prednisolone. He had presented 5 months earlier, on the same ophthalmic medications, with postoperative hallucinations after a right pars plana vitrectomy. Visual hallucinations are a major side effect of anticholinergic poisoning. Ophthalmic instillation of atropine has been documented to cause many central nervous sytstem symptoms, including hallucinations.
...
PMID:Anticholinergic visual hallucinosis from atropine eye drops. 1765 18

External respiratory mechanics was studied in 141 patients with type 1 diabetes mellitus (DM1) and 36 healthy controls using computed analysis of flow-volume loop and total body plethysmography. The DM1 patients were divided into 4 groups: group 1 consisted of patients without clinical signs of microangiopathic complications; groups 2 and 3 consisted of patients with initial and advanced manifestations of late diabetic syndrome (LDS), respectively; group 4 consisted of patients suffering from severe endocrinopathy with end-stage chronic renal failure. The velocity and volume parameters in groups 1 and 2 did not differ significantly from those in the controls. Significant reduction in the vital capacity, forced expiratory volume in one second, and total lung capacity was noted in patients with advanced LDS and uremia. Forced expiratory volume in one second decreased in proportion to reduction in lung vital capacity, which did not cause Tiffno index to leave the reference range. The authors came to the conclusion that DMI causes restrictive ventilatory defect, associated with advanced clinical manifestations of microangiopathic alterations.
...
PMID:[The condition of external respiratory mechanics in patients with type 1 diabetes]. 1803 70

This qualitative study aimed to gain an in-depth understanding of the adaptation of children and families to childhood chronic illness. Considering ecological theories and child empowerment, we departed from the usual practice of relying solely on parental report by also soliciting children's views. Eighteen children aged 7-14 with cancer, chronic renal failure or type 1 diabetes, and 21 of their parents, participated. The inclusion of several conditions enabled the examination of data from a categorical versus non-categorical perspective. Focus groups supplemented by individual interviews explored participants' views about challenges and the processes they considered important in enhancing adaptation to a chronic illness. Children, as well as parents, provided rich material. Thematic analysis revealed 11 main themes. Six concerned the impact of the illness on various aspects of life. The other main themes were the meaning of disease, stress-processing, social support, future concerns and psychosocial interventions. There were many similarities and some differences between parent and child reports. Many issues were common across illness groups, consistent with a non-categorical approach, though there were some illness-specific issues, especially for those with cancer. Positive as well as negative material emerged. Implications for clinical services are discussed.
...
PMID:Parental and child perspectives on adaptation to childhood chronic illness: a qualitative study. 1991 42

<< Previous 1 2 3 4 Next >>