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

BACKGROUND: It has become increasingly clear that beta-cell failure plays a critical role in the pathogenesis of type 2 diabetes. Free-radical mediated beta-cell damage has been intensively studied in type 1 diabetes, but not in human type 2 diabetes. Therefore, we studied the protein expression of the DNA repair enzyme Ogg1 in pancreases from type 2 diabetics. Ogg1 was studied because it is the major enzyme involved in repairing 7,8-dihydro-8-oxoguanosine DNA adducts, a lesion previously observed in a rat model of type 2 diabetes. Moreover, in a gene expression screen, Ogg1 was over-expressed in islets from a human type 2 diabetic. METHODS: Immunofluorescent staining of Ogg1 was performed on pancreatic specimens from healthy controls and patients with diabetes for 2-23 years. The intensity and islet area stained for Ogg1 was evaluated by semi-quantitative scoring. RESULTS: Both the intensity and the area of islet Ogg1 staining were significantly increased in islets from the type 2 diabetic subjects compared to the healthy controls. A correlation between increased Ogg1 fluorescent staining intensity and duration of diabetes was also found. Most of the staining observed was cytoplasmic, suggesting that mitochondrial Ogg1 accounts primarily for the increased Ogg1 expression. CONCLUSION: We conclude that oxidative stress related DNA damage may be a novel important factor in the pathogenesis of human type 2 diabetes. An increase of Ogg1 in islet cell mitochondria is consistent with a model in which hyperglycemia and consequent increased beta-cell oxidative metabolism lead to DNA damage and the induction of Ogg1 expression.
BMC Endocr Disord 2002 Apr 25
PMID:Islet expression of the DNA repair enzyme 8-oxoguanosine DNA glycosylase (Ogg1) in human type 2 diabetes. 1200 41

BACKGROUND: Glucagon-like peptide-1 (GLP-1) and its agonists are under assessment in treatment of type 2 diabetes, by virtue of their antidiabetic actions, which include stimulation of insulin secretion, inhibition of glucagon release, and delay of gastric emptying. We examined the potential of GLP-1 to improve glycemic control in type 1 diabetes with no endogenous insulin secretion. METHODS: Dose-finding studies were carried out to establish mid range doses for delay of gastric emptying indicated by postponement of pancreatic polypeptide responses after meals. The selected dose of 0.63 micrograms/kg GLP-1 was administered before breakfast and lunch in 8-hour studies in hospital to establish the efficacy and safety of GLP-1. In outside-hospital studies, GLP-1 or vehicle was self-administered double-blind before meals with usual insulin for five consecutive days by five males and three females with well-controlled C-peptide-negative type 1 diabetes. Capillary blood glucose values were self-monitored before meals, at 30 and 60 min after breakfast and supper, and at bedtime. Breakfast tests with GLP-1 were conducted on the day before and on the day after 5-day studies. Paired t-tests and ANOVA were used for statistical analysis. RESULTS: In 8-hour studies time-averaged incremental (delta) areas under the curves(AUC) for plasma glucose through 8 hours were decreased by GLP-1 compared to vehicle (3.2 PlusMinus; 0.9, mean PlusMinus; se, vs 5.4 PlusMinus; 0.8 mmol/l, p <.05), and for pancreatic polypeptide, an indicator of gastric emptying, through 30 min after meals (4.0 PlusMinus; 3.1 vs 37 PlusMinus; 9.6 pmol/l, p <.05) with no adverse effects. Incremental glucagon levels through 60 min after meals were depressed by GLP-1 compared to vehicle (-3.7 PlusMinus; 2.5 vs 3.1 PlusMinus; 1.9 ng/l, p <.04). In 5-day studies, AUC for capillary blood glucose levels were lower with GLP-1 than with vehicle (-0.64 PlusMinus; 0.33 vs 0.34 PlusMinus; 0.26 mmol/l, p <.05). No assisted episode of hypoglycaemia or change in insulin dosage occurred. Breakfast tests on the days immediately before and after 5-day trials showed no change in the effects of GLP-1. CONCLUSION: We have demonstrated that subcutaneous GLP-1 can improve glucose control in type 1 diabetes without adverse effects when self-administered before meals with usual insulin during established intensive insulin treatment programs.
BMC Endocr Disord 2003 Apr 10
PMID:Glucagon-like peptide 1 improved glycemic control in type 1 diabetes. 1269 69

The purpose of this study was to describe the patterns of antidiabetic medication use and the cost of testing supplies in Canada using information collected by Saskatchewan's Drug Plan (DP) in 2001. The diabetes cohort (n = 41,630) included individuals who met the National Diabetes Surveillance System (NDSS) case definition. An algorithm was then used to identify subjects as having type 1 or type 2 diabetes. Among those identified as having type 2 diabetes (n = 37,625), 38% did not have records for antidiabetic medication in 2001. One-third of patients with type 2 diabetes received monotherapy. Metformin, alone or in combination with other medications, was the most commonly prescribed antidiabetic medication. Just over one-half of the all patients with diabetes had a DP records for diabetes testing supplies. For individuals (n = 4,005) with type 1 diabetes, 79% had a DP record for supplies, with an average annual cost of 472 +/- 560 dollars. For type 2 diabetes, 50% had records for testing supplies, with an average annual cost of 122 +/- 233 dollars. Those individuals with type 2 diabetes who used insulin had higher testing supply costs than those on oral antidiabetic medication alone (359 vs 131 dollars; p < 0.001).
BMC Health Serv Res 2006 Dec 12
PMID:Utilization of diabetes medication and cost of testing supplies in Saskatchewan, 2001. 1716 6

A number of autoimmune and other diseases have well established HLA associations; in many cases there is strong evidence for the direct involvement of the HLA class II peptide-presenting antigens, e.g., HLA DR-DQ for type 1 diabetes (T1D) and HLA-DR for rheumatoid arthritis (RA). The involvement of additional HLA region genes in the disease process is implicated in these diseases. We have developed a model-free approach to detect these additional disease genes using genotype data; the conditional genotype method (CGM) and overall conditional genotype method (OCGM) use all patient and control data and do not require haplotype estimation. Genotypes at marker genes in the HLA region are stratified and their expected values are determined in a way that removes the effects of linkage disequilibrium (LD) with the peptide-presenting HLA genes directly involved in the disease. A statistic has been developed under the null hypothesis of no additional disease genes in the HLA region for the OCGM method and was applied to the Genetic Analysis Workshop 15 simulated data set of Problem 3, which mimics RA (answers were known). In addition to the primary effect of the HLA DR locus, the effects of the other two HLA region simulated genes involved in disease were detected (gene C, 0 cM from DR, increases RA risk only in women; and gene D, 5.12 cM from DR, rare allele increases RA risk five-fold). No false negatives were found. Power calculations were performed.
BMC Proc 2007
PMID:Conditional genotype analysis: detecting secondary disease loci in linkage disequilibrium with a primary disease locus. 1846 9

Children and adolescents with poorly controlled type 1 diabetes mellitus (T1DM) are at risk for decreased bone mass. Growth hormone (GH) and its mediator, IGF-1, promote skeletal growth. Recent observations have suggested that children and adolescents with T1DM are at risk for decreased bone mineral acquisition. We examined the relationships between metabolic control, IGF-1 and its binding proteins (IGFBP-1, -3, -5), and bone mass in T1DM in adolescent girls 12-15 yr of age with T1DM (n = 11) and matched controls (n = 10). Subjects were admitted overnight and given a standardized diet. Periodic blood samples were obtained, and bone measurements were performed. Serum GH, IGFBP-1 and -5, glycosylated hemoglobin (HbA(1c)), glucose, and urine magnesium levels were higher and IGF-1 values were lower in T1DM compared with controls (p < 0.05). Whole body BMC/bone area (BA), femoral neck areal BMD (aBMD) and bone mineral apparent density (BMAD), and tibia cortical BMC were lower in T1DM (p < 0.05). Poor diabetes control predicted lower IGF-1 (r(2) = 0.21) and greater IGFBP-1 (r(2) = 0.39), IGFBP-5 (r(2) = 0.38), and bone-specific alkaline phosphatase (BALP; r(2) = 0.41, p < 0.05). Higher urine magnesium excretion predicted an overall shorter, lighter skeleton, and lower tibia cortical bone size, mineral, and density (r(2) = 0.44-0.75, p < 0.05). In the T1DM cohort, earlier age at diagnosis was predictive of lower IGF-1, higher urine magnesium excretion, and lighter, thinner cortical bone (r(2) >or=0.45, p < 0.01). We conclude that poor metabolic control alters the GH/IGF-1 axis, whereas greater urine magnesium excretion may reflect subtle changes in renal function and/or glucosuria leading to altered bone size and density in adolescent girls with T1DM.
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PMID:IGF-1 and IGF-binding proteins and bone mass, geometry, and strength: relation to metabolic control in adolescent girls with type 1 diabetes. 1884 35

Many autoimmune diseases share similar underlying pathology and have a tendency to cluster within families, giving rise to the concept of shared susceptibility genes among them. In the Genetic Analysis Workshop 16 rheumatoid arthritis (RA) data we sought to replicate the genetic association between single-nucleotide polymorphisms (SNPs) identified in recent genome-wide association studies (GWAS) on RA and five other autoimmune diseases. We identified 164 significantly associated non-HLA SNPs (p < 10-5) from 16 GWAS and 13 candidate gene studies on six different autoimmune diseases, including RA, systemic lupus erythematosus, type 1 diabetes, Crohn disease, multiple sclerosis, and celiac disease. Using both direct and imputation-based association test, we replicated 16 shared susceptibility regions involving RA and at least one of the other autoimmune diseases. We also identified hidden population structure within cases and controls in Genetic Analysis Workshop 16 RA data and assessed the effect of population structure on the shared autoimmunity regions. Because multiple autoimmune diseases share common genetic origin, these could be areas of immense interest for further genetic and clinical association studies.
BMC Proc 2009 Dec 15
PMID:Replication of recently identified associated single-nucleotide polymorphisms from six autoimmune diseases in Genetic Analysis Workshop 16 rheumatoid arthritis data. 2001 22

Type 1 diabetes is one of the most common endocrine problems in childhood and adolescence, and remains a serious chronic disorder with increased morbidity and mortality, and reduced quality of life. Technological innovations positively affect the management of type 1 diabetes. Closed-loop insulin delivery (artificial pancreas) is a recent medical innovation, aiming to reduce the risk of hypoglycemia while achieving tight control of glucose. Characterized by real-time glucose-responsive insulin administration, closed-loop systems combine glucose-sensing and insulin-delivery components. In the most viable and researched configuration, a disposable sensor measures interstitial glucose levels, which are fed into a control algorithm controlling delivery of a rapid-acting insulin analog into the subcutaneous tissue by an insulin pump. Research progress builds on an increasing use of insulin pumps and availability of glucose monitors. We review the current status of insulin delivery, focusing on clinical evaluations of closed-loop systems. Future goals are outlined, and benefits and limitations of closed-loop therapy contrasted. The clinical utility of these systems is constrained by inaccuracies in glucose sensing, inter- and intra-patient variability, and delays due to absorption of insulin from the subcutaneous tissue, all of which are being gradually addressed.
BMC Med 2011 Nov 09
PMID:Closed-loop insulin delivery for treatment of type 1 diabetes. 2207 Dec 83

Due to the easier access to information, the availability of low cost technologies and the involvement of well educated, passionate patients, a group of citizen 'Health Hackers', who are building their own medical systems to help them overcome the unmet needs of their conditions, is emerging. This has recently been the case in the type 1 diabetes community, under the movement #WeAreNotWaiting, with innovative use of current medical devices hacked to access data and Open-Source code producing solutions ranging from remote monitoring of diabetic children to producing an Artificial Pancreas System to automate the management and monitoring of a patient's condition. Timothy Omer is working with the community to utilise the technology already in his pocket to build a mobile- and smartwatch-based Artificial Pancreas System.
BMC Med 2016 08 17
PMID:Empowered citizen 'health hackers' who are not waiting. 2753 Sep 70

Advanced glycation end products (AGE) have been implicated in diabetes associated complications. They have been suggested as potential mediators in the progression of diabetic heart failure and as a potential target for treatment. Brunvand et al. now provided evidence in that the suggested causal relationship between AGE and diastolic myocardial dysfunction cannot be confirmed in children with type 1 diabetes. The early signs of diastolic myocardial impairment were associated with higher BMI, but not with HbA1c levels. Furthermore, higher serum levels of MG-H1 and increased arterial stiffness were not significantly associated with diastolic dysfunction. The lack of association argues against an essential role of AGEs. This sobering finding does not support the potential to treat diastolic dysfunction by reduction approaches AGE in type 1 diabetic patients. Further pathogenic mechanisms involved in diabetic cardiomyopathy, such as alterations of calcium metabolism, or remodeling of the extracellular matrix, and intramyocardial inflammation may be further promising therapeutic targets.
BMC Cardiovasc Disord 2017 Sep 21
PMID:Complexity of pathomechanisms leading to diastolic heart failure in diabetes mellitus - potential field for therapeutic interventions? 2893 28

Gestational Diabetes Mellitus (GDM) is the most common metabolic disorder in pregnancy, and it is associated with increased risk of morbidity in maternal-fetal outcomes. GDM is also associated with a higher risk to develop diabetes in the future. Diabetes-related autoantibodies (AABs) have been detected in a small percentage (usually less than 10%) of women with gestational diabetes. The prevalence in gestational diabetes of these autoimmune markers of type 1 diabetes (T1D) has been assessed in many studies, together with the risk of progression of AABs-positive GDM towards impaired glucose regulation (IFG or IGT) and overt diabetes after pregancy. The question whether it is necessary to test for T1D autoantibodies in all pregnancies with GDM is still debated. Here we examine the epidemiology of T1D autoantibodies in GDM, their clinical relevance in term of future risk of diabetes or impaired glucose regulation and in term of maternal-fetal outcomes, and discuss when it may be the most appropriate time to search for T1D autoantibodies in women with gestational diabetes.
BMC Endocr Disord 2019 May 03
PMID:Testing for type 1 diabetes autoantibodies in gestational diabetes mellitus (GDM): is it clinically useful? 3105 28


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