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)

Clinical symptoms of type 1 diabetes are preceded by a long period of prediabetes stage characterised by anti-islet antibodies occurrence as well as insulin and C-peptide secretion disturbances. The aim of this study was to define the prognostic value of type 1 diabetes antiislet humoral markers (ICA, anti-GAD, anti-IA2 and IAA) and to find out thresholds for insulin and C-peptide levels at which clinically overt type 1 diabetes develops. Antiislet antibodies, serum C-peptide and insulin were determined in 86 children who, considering their antiislet autoantibodies levels, were classified as prediabetics (mean value of the observation period: 50 months). 8 (9.3%) children, who after a mean time of 35 months of prediabetes stage developed clinically overt type 1 diabetes, were selected from this group. ICA were determined by indirect immunofluorescence; anti-GAD and IAA by radioimmunoprecipitation. C-peptide and insulin levels were evaluated by radioimmunologic assays (CIS Bio International, France). Kaplan-Meier life table analysis revealed pEFS=0.89 after 92 months' observation. The risk of developing diabetes within 80 months was established. For children with positive ICA the risk rate was 0.21, for ICA and anti-GAD positive individuals - 0.39, and for ICA and IA2 positive - 0.74. A significant difference in insulin and C-peptide levels was found between children who developed clinically overt type 1 diabetes and those in prediabetes stage (9.90 vs. 21.45 micro U/ml, p<0.008; 0.34 vs. 0.67 pM/ml, p<0.001 respectively). For both hormones thresholds for high risk of developing clinically overt diabetes were pointed out. Using ROC method the threshold for insulin was determined at 12.9 micro U/ml, for C-peptide at 0.45 pM/ml. Not only the presence and levels of autoantibodies but also the plasma concentrations of C-peptide and insulin are important prognostics of clinical onset of type 1 diabetes mellitus.
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PMID:[Prognostic value of humoral and metabolic markers as an evaluation of risk for developing type 1 diabetes]. 1283 33

The Melbourne Prediabetes Family Study, a prospective study of first-degree relatives of people with type 1 diabetes (T1D), provided an opportunity to examine late-onset autoimmune diabetes within the context of a family history of T1D. We compared genetic, immunologic, and clinical features in relatives of people with T1D, who developed early- versus late-onset diabetes.
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PMID:Late-onset autoimmune diabetes in relatives of people with type 1 diabetes. 1467 94

Numerous authors suggested postprandial blood glucose elevation as a significant contributor in development of macroangiopathy. Epidemiological studies and animal experiments delivered supportive data about causal relationship between postprandial hyperglycaemia and macroangiopathy in type 2 diabetes. Interestingly there is no chronological correlation between presence of hyperglycaemia and development of macroangiopathy neither in type 2, nor in type 1 diabetics. Strict metabolic control does not result in slowing progression of macroangiopathy (glucose paradox). Premature macroangiopathy documented in the prediabetes phase of type 2 diabetes is strongly related to presence of insulin resistance, hyperinsulinaemia, high blood pressure, and dyslipidaemia; development of atherosclerosis in advanced stage of type 1 diabetes is also rather associated with presence of high blood pressure and dyslipidaemia but not that of hyperglycaemia. With regard to role of postprandial hyperglycaemia it should be emphasized, that not the postprandial blood glucose elevation per se, but rather the postprandial complex metabolic cluster (hyperinsulinaemia, hypertrygliceriadaemia, etc) is supposed to be related with development of macroangiopathy in patients with metabolic syndrome and type 2 diabetes.
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PMID:[Clinical significance of blood glucose levels in the pathogenesis of (atherosclerotic) macroangiopathy]. 1515 91

Predicting type 1 diabetes mellitus (T1DM) is a prerequisite for disease prevention. Prediction is currently performed on three levels, which include the genetic susceptibility for disease, the identification of preclinical T1DM by way of circulating islet autoantibodies, and the use of metabolic tests to stage preclinical disease into late or early prediabetes. Combinations of genetic markers such as HLA genotype, INS genotype, and if and how much family history of T1DM is present can stratify disease risk more than 1000-fold, and can be used for selection of first-degree relatives of patients with T1DM for primary intervention trials. Measurement of autoantibodies in genetically at-risk subjects identifies future cases of T1DM. Further stratification of diabetes risk in autoantibody-positive subjects can be made on the basis of autoantibody characteristics that correspond to the magnitude of the autoantibody response.
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PMID:Predicting type 1 diabetes. 1579 11

In the aorta of prediabetic non-obese diabetic mice, a model of human type 1 diabetes, we investigated gene expression of the endothelin receptors and contractility to big endothelin-1 and endothelin-1 at the ages of 10 and 16 weeks. A subgroup of 10- week-old animals was treated with the endothelin ETA receptor antagonist LU461314 (30 mg/kg per day for 6 weeks). Blood glucose levels were normal in all animals. Real-time polymerase chain reaction analysis revealed that vascular ETB receptor expression was higher in 10-week-old non-obese diabetic (NOD) mice compared with controls. In 16-week-old NOD mice, but not in control mice, ETB receptor mRNA was twofold lower (P < 0.05 vs 10-week-old NOD mice). In all groups ETA receptor expression was unaffected by age or treatment. Contractions to big endothelin-1 and endothelin-1 were lower in 10-week-old NOD mice compared with controls. Treatment with LU461314 increased ETB receptor expression in 16-week-old NOD mice, but had no effect on vascular contractility. These data indicate that dysregulation of ETB receptor expression and a decreased contractile response to big endothelin-1 and endothelin-1 are present in the prediabetic state of a model of human type 1 diabetes. These alterations occur independent of glucose levels. Furthermore, ETA receptor blockade is effective in increasing ETB receptor gene expression, suggesting a potential role for endothelin ETA antagonists in the treatment of type 1 diabetes.
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PMID:Upregulation of vascular ET(B) receptor gene expression after chronic ET(A) receptor blockade in prediabetic NOD mice. 1583 54

IL-15 is a 14-15 kD cytokine produced by monocytes/macrophages and shares some biological actions with IL-2. The serum concentration of IL-15 in type 1 diabetic patients has not been reported seriously. Our studies were performed on 51 patients (28 women and 23 men) with type 1 diabetes mellitus. Healthy control subjects (n=22, 12 women and 10 men, mean age 29 years, range 24-32 years) were recruited from medical staff. IL-15 serum levels were detected by ELISA (R & D systems, USA). Short-term and long-term metabolic control parameters, lipid profile and C-reactive protein levels were also estimated. There was a statistically significant increase of serum IL-15 in type 1 diabetic patients in comparison to the control subjects (4.4 (1.5-11.8) versus 2.9 (1.5-6.0) pg/ml, p<0.05). Diabetic patients with higher IL-15 serum levels had higher HbA1c values. A correlation was found between IL-15 serum concentration and HbA1c (N(s)=0.31, p=0.029). There was no relation between acute hyperglycaemic episodes and IL-15 serum level. The potential associations between IL-15 serum level and long-term diabetic control lead us to speculate that IL-15 may serve as a target for future treatment in patients with prediabetes and/or for prevention of late diabetic complications.
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PMID:IL-15 is elevated in serum patients with type 1 diabetes mellitus. 1609 19

DiaPep277, a 24-amino acid peptide based on residues 437 to 460 of heat shock protein 60, is undergoing phase II clinical trials by DeveloGen for the potential treatment and prevention of established and newly diagnosed type 1 diabetes symptoms of the prediabetic state and of latent autoimmune diabetes of the adult.
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PMID:DiaPep277 (DeveloGen). 1625 26

The dramatic rise in the incidence and prevalence of type 2 diabetes mellitus in the pediatric and adolescent populations has been associated with the ongoing epidemic of overweight, obesity, insulin resistance, and metabolic syndrome seen in these age groups. Although the majority of pediatric patients diagnosed with diabetes are still classified as having type 1 diabetes, almost 50% of patients with diabetes in the pediatric age range (under 18 years) may have type 2 diabetes. Screening of high-risk patients for diabetes and prediabetes is important. Prompt diagnosis and accurate diabetes classification facilitate appropriate and timely treatment and may reduce the risk for complications. This is especially important in children because lifestyle interventions may be successful and the lifelong risk for complications is greatest. Treatment usually begins with dietary modification, weight loss, and a structured program of physical exercise. Oral antidiabetic agents are added when lifestyle intervention alone fails to maintain glycemic control. Given the natural history of type 2 diabetes, most if not all patients will eventually require insulin therapy. In those requiring insulin, improved glycemic control and reduced frequency of hypoglycemia can be achieved with insulin analogs. It is common to add insulin therapy to existing oral therapy only when oral agents no longer provide adequate glycemic control.
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PMID:Diabetes screening, diagnosis, and therapy in pediatric patients with type 2 diabetes. 1892 36

Type 2 diabetes mellitus (T2DM) in children and adolescents is an important Public Health problem against the backdrop of the epidemic of childhood obesity. The clinical presentation of T2DM in youth is heterogeneous from minimal symptomatology to diabetic ketoacidosis. The increasing rates of youth T2DM have paralleled the escalating rates of obesity, which is the major risk factor impacting insulin sensitivity. Additional risk factors include minority race, family history of diabetes mellitus, maternal diabetes during pregnancy, pubertal age group and conditions associated with insulin resistance (IR) - such as polycystic ovary syndrome (PCOS). The pathophysiology of T2DM has been studied extensively in adults, and it is widely accepted that IR together with beta-cell failure are necessary for the development of clinical diabetes mellitus in adulthood. However, pathophysiologic studies in youth are limited and in some cases conflicting. Similar to adults, IR is a prerequisite, but beta-cell failure is necessary for progression from normal glucose tolerance to prediabetes and frank diabetes in youth. Even though rates of T2DM in youth are increasing, the overall prevalence remains low if compared with type 1 diabetes mellitus (T1DM). However, as youth with T1DM are becoming obese, the clinical distinction between T2DM and obese T1DM has become difficult, because of the overlapping clinical picture with evidence of islet cell autoimmunity in a significant proportion of clinically diagnosed youth with T2DM. The latter are most likely obese children with autoimmune T1DM who carry a misdiagnosis of T2DM. Further research is needed to probe the pathophysiological, immunological, and metabolic differences between these two groups in the hopes of assigning appropriate therapeutic regimens. These challenges combined with the evolving picture of youth T2DM and its future complications provide unending opportunities for acquisition of new knowledge in the field of childhood diabetes.
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PMID:Pathophysiology of type 2 diabetes mellitus in youth: the evolving chameleon. 1946 9

The relative efficiencies of allogeneic and syngeneic bone marrow transplantation and the threshold levels of donor chimerism required to control autoimmune insulitis were evaluated in prediabetic NOD mice. Male and female NOD mice were conditioned by radiation and grafted with bone marrow cells from allogeneic and syngeneic sex-mismatched donors. Establishment of full allogeneic chimerism in peripheral blood reversed insulitis and restored glucose tolerance despite persistence of residual host immune cells. By contrast, sublethal total body irradiation (with or without syngeneic transplant) reduced the incidence and delayed the onset of diabetes. The latter pattern was also seen in mice that rejected the bone marrow allografts. Low levels of stable allogeneic hematopoietic chimerism (>1%) were sufficient to prevent the evolution of diabetes following allogeneic transplantation. The data indicate that immunomodulation attained at low levels of allogeneic, but not syngeneic, hematopoietic chimerism is effective in resolution of islet inflammation at even relatively late stages in the evolution of the prediabetic state in a preclinical model. However, our data question the efficacy and rationale behind syngeneic (autologous-like) immuno-hematopoietic reconstitution in type 1 diabetes.
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PMID:Low levels of allogeneic but not syngeneic hematopoietic chimerism reverse autoimmune insulitis in prediabetic NOD mice. 1963 89


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