UMLS:C0011849 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus (DM) is associated with oxidative stress, elevation of inflammatory markers and other mechanisms, which may contribute to accelerated atherosclerosis. The aim of the study was to determine prominent factors of these pathogenic processes in patients with DM, to examine their relationship in serum, and to find out the differences between DM1 and DM2. Advanced oxidation protein products (AOPP), C-reactive protein (CRP), pregnancy-associated plasma protein-A (PAPP-A), anticardiolipin antibodies (ACA) and anti-beta2-glycoprotein-1 antibodies (anti-beta2-GPI) were determined in 27 patients with DM1, 27 patients with DM2 and 23 healthy subjects. AOPP, CRP and anti-beta2-GPI were significantly elevated in DM2 in comparison with healthy subjects (p<0.01, p<0.0001, p<0.0001, respectively). In DM1, anti-beta2-GPI were elevated (p<0.0001) as well, but there was no increase of either AOPP or CRP. There was no difference in PAPP-A levels in DM1 or DM2 and healthy subjects. In DM 1, AOPP correlate significantly with anti-beta2-GPI (r = 0.68, p<0.05). In DM2, there is a significant correlation between anti-beta2-GPI and PAPP-A (r=0.45, p<0.05). Oxidative stress and inflammation are more expressed in DM2 and they are partly related. In DM1, oxidative stress seems to be in closer link to autoimmune reaction than to inflammation.
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PMID:Oxidative stress, inflammation and autoimmune reaction in type 1 and type 2 diabetes mellitus. 1535 43

This study was designed to determine the prevalence of microalbuminuria and the associated risk factors in patients with childhood-onset diabetes mellitus (DM). One hundred and sixty-three patients (141 with type 1 DM [DM1] and 22 with type 2 DM [DM21), aged 8 to 28 years, were evaluated for albumin excretion rate and HbA(1c). The mean duration of DM was 8.1 +/- 3.4 and 5.5 +/- 3.9 years in DM1 and DM2, respectively. Persistent microalbuminuria and macroalbuminuria were observed in 11.3% and 2.8% of patients with DM1, and 18.2% and 4.5% in patients with DM2, respectively. In DM1, the duration of DM, age of onset, and HbA(1c) levels were significant predictors of microalbuminuria. Our observations suggest that screening for microalbuminuria should be started from early adolescence in patients with DM1 and DM2.
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PMID:Prevalence of microalbuminuria in young patients with type 1 and type 2 diabetes mellitus. 1552 21

The authors evaluated a screening program for lower extremity arterial disease (LEAD) in diabetic patients and focused on the value of toe blood pressure assessment. They recruited 437 subjects, ages 30-70 years (134 healthy controls, 166 type 1 and 137 type 2 diabetic patients; control [Ctr], DM1, and DM2) with no previous history of LEAD. They were enrolled in a longitudinal study with a planned follow-up of 10 years. Patients were consecutively enrolled from outpatient diabetes units of 2 university hospitals. Subjects were screened with respect to peripheral circulation by use of established noninvasive techniques. These included arm, ankle (AP), and toe (TP) blood pressure measurements; evaluation of peripheral neuropathy; and a standardized physical examination. Results from the baseline examination are presented in this report. The number of patients who presented peripheral pressures or indices below normal (< mean -2 SD for controls) was higher among diabetic patients; 24% of DM1 and 31% of DM2, as compared to 6% of Ctr, had at least 1 lower limb with a low TP, AP, toe/arm index (TI), or ankle/arm index (AI), and these subjects were mainly identified by using the toe/arm index. TI was independently and negatively associated with fasting blood glucose in both patient groups, and with smoking, age, and diabetes duration in DM1. The mean AP was higher in the DM1 and DM2 groups compared to Ctr, whereas overall TP, TI, and AI were similar in the groups. It was also shown that abnormally low TI was significantly more common than low AI among diabetics (p<0.001), and this was true for TP vs AP as well (p<0.05). It is beneficial to include assessment of toe blood pressure and toe/arm blood pressure index to detect early LEAD in diabetic patients. Ankle blood pressure and indices alone are less efficient, owing probably to medial sclerosis in diabetic patients. Up to 30% of diabetic patients with no ischemic symptoms may have signs of impaired arterial circulation.
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PMID:Assessment of toe blood pressure is an effective screening method to identify diabetes patients with lower extremity arterial disease. 1554 50

A case of myotonic dystrophy with 47 XYY presented with tall stature and mental retardation. The patient was a 37-year-old male. In addition to grip myotonia and percussion myotonia, severe weakness and atrophy were noted in the face and the neck muscles and in the distal muscles of the four limbs. He also had diabetes mellitus, cataracts and sexual behavior abnormalities. He was found to be 47 XYY from chromosomal examinations. The combination of 47 XYY syndrome and myotonic dystrophy has not been reported previously.
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PMID:Myotonic dystrophy associated with 47 XYY syndrome. 1555 88

Diabetes is associated with a hypercoagulable state. Eighty percent of patients with diabetes mellitus die due to various thrombotic vascular complications. Disorder of coagulation and fibrynolysis is associated with diabetic retinopathy and nephropathy. Angiogenesis requires degradation of vascular basement membrane prior to migration and proliferation of endothelial cells. Various serine proteases play important role in this process. The homeostatic system is also the source of endogenous inhibitors of angiogenesis. Human serum contains various factors able to induce or suppress formation of new blood vessels. The aim of the present study was to evaluate the activity of some angiogenesis inhibitors, anti-proteases, anti-thrombin III, a1 anti-trypsin and a2 anti-plasmin in sera of patients with diabetes mellitus type 1 and 2 and non-proliferative retinopathy, and to correlate this activity to total angiogenic potential of these sera, measured by mice cutaneous test. Sera of 22 persons with DM1, aged 33-70 years, 35 persons with DM2, aged 37-79 years, and 51 healthy people, aged 22-80 years (as control group) were studied. Direct serum-induced cutaneous angiogenesis test in mice (SIA) was applied. Berichrom (ade Behring) tests and immunoturbidimetric method were used for evaluation of anti-proteases activity. Angiogenic activity of DM1 patients sera was statistically lower than this parameter in DM2 patients and in control group. Levels of anti-proteases were similar in DM1, DM2 and control group, with one exception: anti-thrombin level was lower in DM2 patients' sera than this in the control group. Analysis of correlation revealed important difference in behaviour of DM1 sera, as compared to other groups. Significant negative correlation was observed between angiogenic activity and anti-thrombin, as well as anti-trypsin level of DM1 patients' sera. On the other hand, correlation analysis performed for the sera of control group revealed significant positive correlation between their angiogenic activity and anti-thrombin level. No other correlations were found.
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PMID:[Proteinases inhibitors in sera of diabetic patients with non-proliferative retinopathy]. 1563 23

Psychological aspects and patients' acceptance of type 1 diabetes (DM1) may exercise some influence in their glycemic control. In this project the influence of psychological aspects were evaluated on glycemic control of DM1 patients. A retrospective study of participants from Diabetes Weekend (DW), an educational project in DM1 was carried out in Minas Gerais. In a sample of 150 subjects (66M/84F, 21.6+/-13.5 years and duration of DM of 8.5+/-7.9 years) we analyzed: type of insulin, insulin delivery, insulin dose per day and insulin dose per day in DW, psychological profile, capillary glycemia and previous history of convulsion crisis, severe hypoglycemia or diabetic ketoacidosis (CAD). Glucose was monitored 4 times a day by a digital glucose monitor. 20.9% of the patients with DM1 felt very well (G1); 39.5% well (G2), 25.6% with difficult glycemic control (G3), 9.3% trying to accept (G4) and 4.7% reported to be very bad about their DM1. The average capillary glycemia (ACG, in mg/dl) was significantly lower in G1 than in the others (169.8; G2: 182.3; G3: 199.3; G4: 200.7). There were no significant association of this psychological aspects and previous history of CAD, hypoglycemia or convulsion crisis. DM1 duration over 5 years was associated to lower acceptance of the disease (p= 0.017) and age of patients (p= 0.000). 13.9% of patients reported to be ashamed of their disease; the ACG was significantly higher in this group as compared to others (246.2 vs. 178.1; p= 0.007). In 91 patients (60.4%) who mention to have apprehension of feeling sick in public the ACG was significantly higher (200.4 vs. 184.5; p= 0.014). The systematic glucose monitoring showed positive association between psychological aspects and worse glycemic control. The psychological and multidisciplinary approach of DM1 patients is very important to try to improve the metabolic control, to prevent future complications, which results in better quality of life for these patients.
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PMID:[Psychological aspects and blood glucose control of a type 1 diabetes mellitus group from Minas Gerais]. 1564 Aug 81

The majority of the type 1 Diabetes (DM1) patients are seen in Public Health Services. The management of these children, by several reasons, did not meet most of the standards for good diabetes control. In the present study we compare 2 different insulin treatment strategies in 53 uncontrolled DM1 adolescents despite a twice-a-day insulin regimen. A regimen: NPH + R before breakfast, R insulin before dinner and bedtime NPH. B regimen: NPH + R before breakfast and lunch and bedtime NPH. This was a 12-month open-label, randomized, clinical trial conducted in a Public Hospital. BMI (A: 23.4+/-3.5 Kg/m2 x B: 23.5+/-0.8 Kg/m2), average daily insulin dose (A: 1.04+/-0.28 U/Kg/d x B: 1.08+/-0.22 U/Kg/d) as well as the overall frequency of severe hypoglycemia (A: 9.4% x B: 7.5%) were similar in both groups during the study. However, HbA1c values at the end of the study were significantly lower in the B (9%) as compared to the A regimen (7,5%; p = 0.05). In conclusion, we have shown that breakfast and lunchtime NPH + R insulin plus bedtime NPH insulin is superior to pre-dinner R insulin plus breakfast and bedtime NPH insulin for overall glycemic control with similar weight status and comparable frequency of hypoglycemia. Thus, three times a day NPH insulin application is a feasible option for public service patients.
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PMID:[Comparison of pre-dinner regular versus pre-lunch NPH of a third insulin application in adolescents with type 1 diabetes from a Public Health Service]. 1576 56

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

We explored the relationship between frequency and perceived burden of different self-management activities and HbA1c%, symptoms of diabetes, fatigue, depression, and quality of life in 292 employees between 30 and 60 years of age with insulin-treated diabetes. Participants completed questionnaires that assess self-management and health-related variables. t-Tests were performed for type 1 (DM1) and type 2 diabetes (DM2) separately to compare the mean health scores of individuals who frequently or infrequently perform self-management activities and who do or do not perceive this as a burden. Participants frequently perform their self-management activities, particularly injection of insulin (96.1%), following dietary guidelines (70.8%) and eating regularly (65.6%). Dietary self-management is most often seen as a burden (70.4%), while injecting insulin is seen as least burdensome (12.8%). The perceived burden of self-management is more strongly related to health than the frequency of self-management. Frequency of self-management especially relates to HbA1c% in DM1. People with DM2 who frequently follow the dietary guidelines have more positive health outcomes. Participants who perceive dietary self-management and injecting insulin as a burden have more negative health outcomes. Because different relationships were found between frequency and perceived burden of self-management and health indicators, both aspects should be assessed and considered separately when evaluating self-management and examining patient's health.
Diabetes Res Clin Pract 2005 Apr
PMID:Frequency and perceived burden of diabetes self-management activities in employees with insulin-treated diabetes: relationships with health outcomes. 1581 66

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