Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy and hemolytic anemia can be triggered by many drugs, by the ingestion of fava beans, and by metabolic imbalances. Nonetheless, only sporadic reports of hemolytic anemia due to G6PD deficiency in patients with type 1 diabetes mellitus (DM1) have been reported to date. We describe an 8 year-old Sicilian boy who suffered from hemolytic anemia some days after admission for DM1. On admission, acid-base equilibrium was normal but 4 days later he presented hemolytic anemia with G6PD deficiency, confirmed by personal and family history and laboratory evaluation. We suggest that the hemolytic crisis in this patient was triggered by the relative hypoglycemia that followed insulin administration. The interference of acidosis, infections, drugs, food or other triggering agents was excluded. This report demonstrates that hemolysis may represent a possible complication of DM treatment in patients with G6PD deficiency and we recommend careful clinical surveillance in these patients.
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PMID:Hemolytic crisis in a non-ketotic and euglycemic child with glucose-6-phosphate dehydrogenase deficiency and onset of type 1 diabetes mellitus. 1564 2

In 38 patients with type 1 diabetes (DM 1) and 24 non-diabetics we investigated LDL susceptibility to in vitro oxidation. Fast and post-prandial glycaemia (PPG), glycated hemoglobin (HbA1c) and lipid profile were determined, together with an spectrophotometric analysis of LDL oxidation before and 1, 3, 6 and 24 hours after addition of the oxidant substance - copper sulphate (CuSO4). The LDL oxidation coefficient in the two groups presented similar basal values; however 3 hours after CuSO4, LDL was more oxidized in patients with DM1. There was a negative correlation with PPG (r= -0.2511; p<0.05) and HbA1c (r= -0.2541; p<0.05). We conclude that in our sample of DM patients LDL was oxidized earlier than in the non-diabetics and that the glycemic control is important in this event.
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PMID:[Evaluation of LDL susceptibility of patients with type 1 diabetes to in vitro oxidation and its relation to glycemic control]. 1576 15

We evaluated the influence of body adiposity (BA), which was measured by bioelectrical impedance, body mass index (BMI) and waist circumference (WC), in clinical and laboratorial parameters of 64 patients with type 1 diabetes (DM1), 33 females, matched for diabetes duration. Women had greater BA than men. Fourteen patients were overweight. In the whole group, we found correlations between BA and BMI (r= 0.50; p= 0.001), BA and WC (r= 0.30; p= 0.001) and BA and fasting glucose (r= 0.24; p= 0.048). There were 11 patients with abnormal BA; among them, there were 6 with overweight and abnormal WC. In those patients with abnormal BA, we found higher HbA1c, respectively [(9.8 +/- 2.4) vs. (8.1 +/- 1.5%); p= 0.03], WC [(82.9 +/- 11.4) vs. (72.9 +/- 8.3 cm); p = 0.01] and BMI [(26.1 +/- 2.7) vs. (22.1 +/- 2.5 Kg/m2); p= 0.0001]. We conclude that some DM1 patients can have some characteristics of the metabolic syndrome and the influence of these findings on clinical and laboratory control and on the cardiovascular risk must be analysed in prospectives studies.
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PMID:[Body adiposity and its influence on clinical and metabolic parameters of patients with type 1 diabetes]. 1576 64

Insmed is developing mecasermin rinfabate, a recombinant complex of insulin-like growth factor-I (rhIGF-I) and binding protein-3 (rhIGFBP-3) [insulin-like growth factor-I/insulin-like growth factor binding protein-3, rhIGF-I/rhIGFBP-3, SomatoKine], for a number of metabolic and endocrine indications. In the human body, IGF-I circulates in the blood bound to a binding protein-3 (IGFBP-3), which regulates the delivery of IGF-I to target tissues, and particular proteases clip them apart in response to stresses and release IGF-I as needed. IGF-I, a naturally occurring hormone, is necessary for normal growth and metabolism. For the treatment of IGF-I deficiency, it is desirable to administer IGF-I bound to IGFBP-3 to maintain the normal equilibrium of these proteins in the blood. Mecasermin rinfabate (rhIGF-I/rhIGFBP-3) mimics the effects of the natural protein complex in the bloodstream and would augment the natural supply of these linked compounds. The most advanced indication in development of mecasermin rinfabate is the treatment of severe growth disorders due to growth hormone insensitivity syndrome (GHIS), also called Laron syndrome. 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. Mecasermin rinfabate also has potential as replacement therapy for IGF-I, which may become depleted in indications such as major surgery, organ damage/failure, traumatic injury, cachexia and severe burn trauma. It also has potential for the treatment of osteoporosis. Mecasermin rinfabate was developed by Celtrix using its proprietary recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on 1 June 2000. Insmed and Avecia of the UK have signed an agreement for manufacturing mecasermin rinfabate and its components, rhIGF-1 and rhIGFBP-3. CGMP clinical production of mecasermin rinfabate and its components will be carried out in Avecia's Advanced Biologics Centre, Billingham, UK, which manufactures recombinant-based medicines and vaccines at the capacity of up to 1000L. In April 2004, Insmed announced that it acquired a lease to operate the manufacturing facility formerly operated by Baxter for the commercial production of SomatoKine in Boulder, CO, USA. With the two manufacturing facilities for SomatoKine, Insmed plans to meet the development and commercial demands for the product over the next several years. In its 2003 Form-10K, Insmed announced plans to conduct comparative studies with the previously used drug substance and the new substance produced by Avecia. The comparative data will be included in the regulatory filing for mecasermin rinfabate. Mecasermin rinfabate was originally licensed to Welfide for Japan. On 1 October 2001, Welfide Corporation merged with Mitsubishi-Tokyo Pharmaceuticals to form Mitsubishi Pharma Corporation. The new company is a subsidiary of Mitsubishi Chemical. In October 2004, Insmed announced that Tzamal Pharma has been granted exclusive distribution and marketing rights for mecasermin rinfabate in certain Middle Eastern territories including Israel. Tzamal Pharma also acquired exclusive rights to Insmed's named patient programme for the agent in these territories. Tzamal Pharma intends to begin the appropriate registration activities for mecasermin rinfabate in the treatment of children with growth hormone-insensitivity syndrome. This pivotal, 12-month, multicentre, open-label trial in 30 children with GHIS was initiated in June 2003 and was designed to evaluate the safety and efficacy of the agent in prepubescent children with GHIS. The 6-month endpoint data analysis showed that mecasermin rinfabate given as a once-daily injection was safe and well tolerated. The agent demonstrated a significant increase in height velocity in children with GHIS similar to that observed by Pfizer in their pivotal study with twice-daily injections of rhIGF-I. The full results from the pivotal trial are expected in 2005. In April 2003 Insmed initiated a named patient programme in Europe that will make available mecasermin rinfabate for the treatment of GHIS-Laron syndrome. The treatment of patients was initiated in Scandinavia, with authorisation pending in several other European countries. Mecasermin rinfabate will be made available to those GHIS patients who, in the opinion of their doctor, may benefit from IGF-I therapy. At precommercial scale quantities, the drug will be available on a limited basis.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 mecasermin rinfabate delivered the same amount of IGF-1 as two daily injections of unbound IGF-1. No adverse events were reported. Insmed has acquired an exclusive licence to Pharmacia's regulatory filings concerning yeast-derived insulin-like growth factor 1 (IGF-1). These filings were used by Pharmacia to receive marketing approvals in several European countries and also in the IND application with the US FDA. Insmed believes that this licence will facilitate the development of mecasermin rinfabate for the treatment of children with GHIS. In January 2003, Insmed announced positive results from a double-blind, placebo-controlled, dose-ranging study of mecasermin rinfabate in adolescent patients with type 1 diabetes receiving insulin therapy. The study was conducted at the University of Cambridge, Cambridge, UK, under supervision of Prof. D. Dunger. The researchers from The Robarts Research Institute and the University of Western Ontario, Canada (leading investigator T.L. Delovitch, the Sheldon H. Weinstein scientist in Diabetes at the University of Western Ontario) have found that mecasermin rinfabate complex was significantly more effective than IGF-1 in reducing the severity of insulitis, beta cell destruction and delaying the onset of type 1 diabetes. The study was supported by grants from Canadian Institutes of Health and the Juvenile Diabetes Research Foundation. Insmed plans to initiate large-scale phase II clinical studies in this indication. At the BIO 2004 Annual International Convention (BIO-2004) in June 2004, Insmed announced that it has received a grant from the US National Institutes of Health (NIH)/Muscular Dystrophy Association (MDA) worth USD $6.5 million to investigate the efficacy of mecasermin rinfabate for the treatment of myotonic dystrophy. It has also been granted orphan drug status for the treatment of GHIS-Laron syndrome in the US and Europe. In December 2003, Insmed announced that mecasermin rinfabate was designated orphan drug status by the FDA for the treatment of extreme insulin resistance. This provides Insmed with 7 years of market exclusivity following approval of mecasermin rinfabate for this indication. Insmed has received orphan drug designation for mecasermin rinfabate in the treatment of extreme insulin resistance in Europe (October 2004). In November 2004, Insmed was granted the European patent EP1183042 entitled "Methods for Treating Diabetes". This patent corresponds with the US patent US 6,040,292 also entitled "Methods for Treating Diabetes". Both patents cover type 1 and type 2 diabetes mellitus and insulin resistant diabetes including type A insulin resistance (the least severe form of extreme insulin resistance syndromes). In January 2004, Insmed obtained a non-exclusive licence to the patents for use of IGF-I for the treatment of extreme or severe insulin-resistant diabetes from Fujisawa Pharmaceutical. Insmed will have worldwide rights in territories (excluding Japan) with existing valid patent claims including the US and Europe. Insmed holds 28 US issued or allowed patents for the composition, production, antibodies and methods of use of mecasermin rinfabate. These US patents expire at various times between the years 2010 and 2019. Insmed through their lawyers filed its defense and counterclaim to the alleged patent infringement brought by Tercica against Insmed in the London High Court of Justice. Insmed asserted that it did not infringe any valid patent claims as none of the claims of the patent were patentable because the subject matter was not new. Insmed also stated that the patent did not involve an inventive step, did not have capability of industrial application and had no clear description of the invention so that invention can be performed by the person skilled in the art. Insmed is seeking revocation of the patent on these grounds.
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PMID:Mecasermin rinfabate: insulin-like growth factor-I/insulin-like growth factor binding protein-3, mecaserimin rinfibate, rhIGF-I/rhIGFBP-3. 1577 6

Type 1 diabetes mellitus (DM1) commonly occurs in childhood, although many pediatric centers are now seeing more cases of type 2 diabetes (DM2). Kidney failure caused by either type of diabetes is uncommon during childhood, but these years of hyperglycemia contribute to long-term complications. All children with diabetes warrant screening of glomerular filtration rate, blood pressure, and urine albumin excretion. Screening should begin after 5 years of DM1 or at puberty. A similar screening strategy should start at the time of diagnosis of DM2. Atypical features such as dipstick positive proteinuria or active urine sediment may warrant referral to a nephrologist for evaluation, including biopsy. The first line of treatment in either form of diabetes is achieving the best glycemic control possible. Patients developing microalbuminuria or hypertension should receive antiangiotensin II drugs. Adult studies suggest blood pressure goals should be lower in diabetes than in the general population. Although direct evidence is not yet available in children, achieving blood pressure below the 90th percentile for age, height, and gender seems prudent. Longitudinal studies and new screening tests may allow detection of susceptible children earlier in the course of DM1 or DM2, perhaps allowing prevention of diabetic kidney disease.
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PMID:Pediatric aspects of diabetic kidney disease. 1582 59

This study compared the psychological adjustment between children with short stature and youth with type 1 diabetes mellitus (DM1). The Child Behavior Checklist, Children's Depression Inventory, Social Anxiety Scale for Children--Revised, and Asher Loneliness Scale were administered to 58 children (26 with short stature and 32 with DM1) and a parent during a regularly scheduled clinical appointment for endocrinology care. Results show that the parents of children with short stature rated their children as having more social, thought, and attention problems, and exhibiting greater delinquent behavior, as compared to parental ratings of children with DM1. No diagnostic group differences in child or parent-rated internalizing symptoms were found. Implications of these findings for personnel working with children with short stature are discussed.
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PMID:Psychological adjustment of children with short stature: a comparison of clinic-referred children with short stature and type 1 diabetes mellitus. 1584 74

The most intensively studied autoimmune disorder, type 1 diabetes mellitus (DM1), has attracted perhaps the greatest interest for gene-based therapeutic and prophylactic interventions. The final clinical manifestation of this immunologically and genetically complex disease, the absence of insulin, is the major starting point for almost all the gene therapy modalities attempted to date. Insulin replacement by transplantation of islets of Langerhans or surrogate beta cells is the obvious choice, but the allogeneic nature of the transplants activates potent antidonor immunoreactivity necessitating gene and cell-based immunosuppressive strategies as an alternative to the toxic pharmacologic immunosuppressives indicated for classic solid organ transplants. Accumulating knowledge of the cellular mechanisms involved in onset, however, have yielded promising tolerance induction prophylactic approaches using genes and cells. Despite the early successes in a number of animal models, the true test of efficacy in humans remains to be demonstrated.
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PMID:Gene therapy for type 1 diabetes. 1628 Jun 45

This retrospective study assessed 17 DM1 pediatric patients (15.76 +/- 4.5 years) submitted to 72 h continuous glucose monitoring system (CGMS) (Medtronic, CA). The aim of this study was to evaluate the accuracy of CGMS in children and adolescents with type 1 diabetes mellitus (DM1) and the efficacy of this method to detect unrecognized hypoglycemia in this population. It were analyzed capillary glycemia (CG) and CGMS sensors value; glycemic excursions; postprandial hyperglycemia; unrecognized hypoglycemia; complications and therapeutic management after CGMS. A1c levels were measured at the start and after 3 months of the study. Correlation coefficient during hypo, hyper, and normoglycemia and sensitivity/specificity was determined. The mean CG values were 213.8 +/- 63.4 mg/dl vs. 209.7 +/- 52.5 mg/dl by sensor, with statistical significance by Pearson's correlation (p < 0.001). There was no difference between CGMS and CG value in order to detect glycemic excursions (p = 0.32). The postprandial hyperglycemia and unrecognized hypoglycemia was detected in 66.7% and 56.2% of this patients, respectively. The correlation coefficient during hypoglycemia presented no statistical significance by Pearson's correlation (p = 0.29) vs. during hyperglycemia (p = 0.001). The CGMS sensor presented low sensitivity (63.3%) to detect hypoglycemia. This data showed important decreased level of A1c in this population 3 months after CGMS with statistical significance (p = 0.03). The CGMS showed to be a very safe method, well tolerated, with high accuracy in glycemic values and low complications rate. This results suggest that CGMS is a good method to identify postprandial hyperglycemia, to improve metabolic changes in therapeutics with significant impact in A1c of diabetic pediatric patients. This data confirmed the low sensitivity of CGMS to detect unrecognized hypoglycemia in pediatric DM1 patients.
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PMID:Efficacy of continuous glucose monitoring system to detect unrecognized hypoglycemia in children and adolescents with type 1 diabetes. 1635 87

Despite many improvements in the treatment of type 1 diabetes mellitus (DM1), the non-physiological time-action profiles of conventional insulins remain a significant obstacle. In recent years, recombinant DNA technology has been used to design insulin molecules that overcome the limitations of regular and NPH insulin. The rapid insulin analogs used as prandial and the long-acting insulin analogs used as basal simulate physiological insulin profiles more closely than the older conventional insulins. The efficacy of insulin analogs now available for multiple daily injection (MDI) and continuous subcutaneous insulin infusion (CSII) therapy in DM1 has been established in pediatric patients. Insulin pumps have improved since they were first introduced. CSII therapy may provide an effective alternative for selected pediatric patients with DM1. In most studies at pediatric age, CSII therapy resulted in a improvement in HbA1c, a decreased rate of hypoglycemia without an abnormal increase in BMI, and without adversely affecting psychosocial outcomes in children and adolescents with DM1.
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PMID:Long-acting insulin analogues (insulin glargine or determir) and continuous subcutaneous insulin infusion in the treatment of type 1 diabetes mellitus in the paediatric population. 1639 47

Type 1 diabetes mellitus (DM1), autoimmune thyroid disease (ATD) and autoimmune gastritis often occur together forming the so-called autoimmune polyendocrine syndrome (APS) type 3. Thyroid autoimmunity is evident in up to one third and gastric autoimmunity in up to a quarter of patients with DM1. Also relatives of DM1 patients, particularly mothers, have higher frequencies of these autoimmune conditions. Vice versa, gastric autoimmunity is present in one third of ATD patients and islet autoimmunity in one out ten. The BB-DP rat, the NOD mouse, the OS chicken and the neonatal thymectomy mouse model are animal models of APS type 3. In these models the autoimmune destruction of the various target tissues has been shown to be a multi-step process in which several genetic polymorphisms need to converge to induce both local anomalies in the target gland and anomalies in the immune system. With regard to environmental factors, excess iodine is well known to elicit/aggravate thyroid autoimmunity in these animal models. Screening DM1 patients and their relatives (particularly females) for thyroid autoimmunity is recommended. If positive, excess iodine should be avoided and thyroxin treatment considered. Whether autoimmune thyroiditis and autoimmune gastritis patients should be screened for islet Ab is not clarified.
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PMID:The association between autoimmune thyroiditis, autoimmune gastritis and type 1 diabetes. 1643 10


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