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)

Accelerated glycoxidation takes part in the development of diabetic complications. We determined advanced glycation end-products (AGEs) and advanced oxidation protein products (AOPP) in the sera of 52 patients with diabetes mellitus (DM) - 18 with DM Type 1 and 34 with DM Type 2 and examined their relationship to the compensation of the disease. AGEs were estimated spectrofluorimetrically (350 nm/440 nm) whereas AOPP were determined spectro-photometrically (340 nm). AGEs were elevated only in DM Type 2 (DM2 5.11+/-1.15 x 10(3) AU/g vs controls 4.08+/-0.71 x 10(3) AU/g, p<0.001, vs DM1 4.14+/-0.86 x 10(3) AU/g, p<0.005, DM1 vs controls were not significant). AOPP were elevated significantly in both types of DM with higher levels in DM Type 2 (DM2 157.50+/-75.15 micromol/l vs healthy subjects 79.80+/-23.72 micromol/l, p<0.001, vs DM1 97.50+/-30.91 micromol/l, p<0.005, DM1 vs controls p<0.05). There was a tight correlation between AGEs and AOPP in both types of DM (DM1 r=0.75, DM2 r=0.47 (p<0.05)) and both AGEs and AOPP correlated with triglycerides. In DM Type 1 only, AGEs correlated with HbA1c r=0.47 (p<0.05) and with blood glucose. Slight but not significant differences in AGEs and AOPP levels were observed in patients with or without diabetic complications. Oxidative stress is increased in both types of DM, more in Type 2 where it contributes to the formation of glycoxidation products.
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PMID:Advanced glycation end-products and advanced oxidation protein products in patients with diabetes mellitus. 1251 Nov 84

In skeletal muscle, excitation may cause loss of K+, increased extracellular K+ ([K+]o), intracellular Na+ ([Na+]i), and depolarization. Since these events interfere with excitability, the processes of excitation can be self-limiting. During work, therefore, the impending loss of excitability has to be counterbalanced by prompt restoration of Na+-K+ gradients. Since this is the major function of the Na+-K+ pumps, it is crucial that their activity and capacity are adequate. This is achieved in two ways: 1) by acute activation of the Na+-K+ pumps and 2) by long-term regulation of Na+-K+ pump content or capacity. 1) Depending on frequency of stimulation, excitation may activate up to all of the Na+-K+ pumps available within 10 s, causing up to 22-fold increase in Na+ efflux. Activation of the Na+-K+ pumps by hormones is slower and less pronounced. When muscles are inhibited by high [K+]o or low [Na+]o, acute hormone- or excitation-induced activation of the Na+-K+ pumps can restore excitability and contractile force in 10-20 min. Conversely, inhibition of the Na+-K+ pumps by ouabain leads to progressive loss of contractility and endurance. 2) Na+-K+ pump content is upregulated by training, thyroid hormones, insulin, glucocorticoids, and K+ overload. Downregulation is seen during immobilization, K+ deficiency, hypoxia, heart failure, hypothyroidism, starvation, diabetes, alcoholism, myotonic dystrophy, and McArdle disease. Reduced Na+-K+ pump content leads to loss of contractility and endurance, possibly contributing to the fatigue associated with several of these conditions. Increasing excitation-induced Na+ influx by augmenting the open-time or the content of Na+ channels reduces contractile endurance. Excitability and contractility depend on the ratio between passive Na+-K+ leaks and Na+-K+ pump activity, the passive leaks often playing a dominant role. The Na+-K+ pump is a central target for regulation of Na+-K+ distribution and excitability, essential for second-to-second ongoing maintenance of excitability during work.
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PMID:Na+-K+ pump regulation and skeletal muscle contractility. 1450 6

Morphological characteristics of bone tissues were studied in the feet of patients with diabetes mellitus type 1 and 2 (DM1 and DM2). Osteoblasts and osteoclasts prevalence, the presence of collagen type III in the composition of newly formed bone were characteristic for DM1. Osteocytes prevalence and abundant granulation tissue in newly formed bone was a feature of DM2. The analysis of bone tissue resorption suggests that lacunar osteoclastic resorpsion is the main type in DM1 while periosteocytic osteolysis and smooth resorption are typical for DM2. Thus, osteolysis genesis and synthesis of bone tissue in DM1 and DM2 may be different.
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PMID:[Osteopathy in diabetic foot syndrome]. 1505 2

Insulin-like growth factor-I (IGF-I) has endocrine, autocrine and paracrine properties. Receptors for IGF-I are present on virtually all cell types but are located mainly on cells of mesenchymal origin, such as fibroblasts, chondrocytes and osteoblasts. Growth hormone (GH)-dependent and GH-independent actions of IGF-I have been implicated in normal and abnormal bone growth, diabetes mellitus, malnutrition, cancer, thyroid disease and hematological diseases. The availability of recombinant human IGF-I (rhIGF-I) has led to new treatments for GH-resistant Laron dwarfism and certain diseases associated with severe insulin resistance. IGF-I has recently been investigated as a neurotrophic factor. Phase II efficacy trials with patients with neurological disease such as traumatic brain injury, myotonic dystrophy and amyotrophic lateral sclerosis have shown that rhIGF-I has efficacy on various outcome parameters. Treatment with rhIGF-I may result in reversible side effects of which increased heart rate, papilledema, ophthalmologic and intracranial hypertension, facial and generalized edema, and weight gain are noteworthy.
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PMID:Insulin-like growth factor-I: clinical studies. 1509 66

Few studies have described the genetics of childhood diabetes mellitus (DM) in US minorities. High-risk DQA1 and DQB1 alleles (DQA1*0301, DQB1*0201, and DQB1*0302 in African Americans and Latinos, and DQA1 *0501 in African Americans) were identified from previous studies and tested in 45 African American and 26 Latino patients from the population-based Chicago Childhood Diabetes Registry, and in 50 healthy race-matched controls. Sixteen of the African American patients and three Latinos had youth-onset type 2 DM and were analyzed separately. In African Americans with type 1 DM, both DQA1*0102 and DQB1*0602 were protective (p < 0.0001), and the susceptibility alleles DQA1*0301 and DQB1*0201 were more frequent than in controls (p < 0.01). In Latinos, DQA1*0301 and DQB1*0302 were marginally increased in patients with DM1 compared to controls; no individual DQA1 or DQB1 allele was protective. Patients with DM1 were significantly more likely to carry one or two high-risk DQA1 alleles in both populations; they were also more likely than controls to carry at least one high-risk DQB1 allele. The odds ratio for the ability to form at least two high-risk DQA1-DQB1 heterodimers (cis and/or trans) was 7.9 (95% CI: 1.7-40.0) for African Americans and 5.7 (1.3-25.6) for Latinos with DM1. African American patients with DM2 were not statistically different from controls, and were less likely to carry four high-risk susceptibility alleles than patients with DM1 (p = 0.002). Many of the HLA-DQ associations previously documented in non-Hispanic White populations also are found in African Americans and Latinos with DM1, although some differences exist.
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PMID:HLA-DQA1 and -DQB1 alleles in Latino and African American children with diabetes mellitus. 1511 6

Myotonic dystrophy (DM) is caused by either an untranslated CTG expansion in the 3' untranslated region of the DMPK gene on chromosome 19 (dystrophia myotonica type 1 [DM1]), or an untranslated CCTG tetranucleotide repeat expansion in intron 1 of the ZNF9 gene on chromosome 3 (dystrophia myotonica type 2 [DM2]). RNA-binding proteins adhere to transcripts of the repeat expansions that accumulate in the nucleus, and a trans-dominant dysregulation of pre-mRNA alternative splicing has been demonstrated for several genes. In muscle from patients with DM1, altered insulin-receptor splicing to the nonmuscle isoform corresponds to the insulin insensitivity and diabetes that are part of the DM phenotype; because of insulin-receptor species differences, this effect is not seen in mouse models of the disease. We now demonstrate that comparable splicing abnormalities occur in DM2 muscle prior to the development of muscle histopathology, thus demonstrating an early pathogenic effect of RNA expansions.
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PMID:Insulin receptor splicing alteration in myotonic dystrophy type 2. 1511 29

In obese humans and rodents there is increased expression of the key glucocorticoid (GC) regenerating enzyme, 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), in adipose tissue. This increased expression appears to be of pathogenic importance because transgenic mice overexpressing 11beta-HSD1 selectively in adipose tissue exhibit a full metabolic syndrome with visceral obesity, dyslipidemia, insulin-resistant diabetes, and hypertension. In this model, while systemic plasma GC levels are unaltered, GC delivery to the liver via the portal vein is increased. 11beta-HSD1 is most highly expressed in liver where inhibition or deficiency of its activity improves glucose and lipid homeostasis. To determine the potential contribution of elevated intrahepatic GCs alone toward development of insulin-resistant syndromes we generated transgenic mice expressing increased 11beta-HSD1 activity selectively in the liver under transcriptional control of hepatic regulatory sequences derived from the human apoE gene (apoE-HSD1). Transgenic lines with 2- and 5-fold-elevated 11beta-HSD1 activity exhibited mild insulin resistance without altered fat depot mass. ApoE-HSD1 transgenic mice exhibited fatty liver and dyslipidemia with increased hepatic lipid synthesis/flux associated with elevated hepatic LXRalpha and PPARalpha mRNA levels as well as impaired hepatic lipid clearance. Further, apoE-HSD1 transgenic mice have a marked, transgene-dose-associated hypertension paralleled by incrementally increased liver angiotensinogen expression. These data suggest that elevated hepatic expression of 11beta-HSD1 may relate to the pathogenesis of specific fatty liver, insulin-resistant, and hypertensive syndromes without obesity in humans as may occur in, for example, myotonic dystrophy, and possibly, the metabolically obese, normal-weight individual.
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PMID:Metabolic syndrome without obesity: Hepatic overexpression of 11beta-hydroxysteroid dehydrogenase type 1 in transgenic mice. 1511 95

More than 20 syndromes among the significant and increasing number of degenerative diseases of neuronal tissues are known to be associated with diabetes mellitus, increased insulin resistance and obesity, disturbed insulin sensitivity, and excessive or impaired insulin secretion. This review briefly presents such syndromes, including Alzheimer disease, ataxia-telangiectasia, Down syndrome/trisomy 21, Friedreich ataxia, Huntington disease, several disorders of mitochondria, myotonic dystrophy, Parkinson disease, Prader-Willi syndrome, Werner syndrome, Wolfram syndrome, mitochondrial disorders affecting oxidative phosphorylation, and vitamin B(1) deficiency/inherited thiamine-responsive megaloblastic anemia syndrome as well as their respective relationship to malignancies, cancer, and aging and the nature of their inheritance (including triplet repeat expansions), genetic loci, and corresponding functional biochemistry. Discussed in further detail are disturbances of glucose metabolism including impaired glucose tolerance and both insulin-dependent and non-insulin-dependent diabetes caused by neurodegeneration in humans and mice, sometimes accompanied by degeneration of pancreatic beta-cells. Concordant mouse models obtained by targeted disruption (knock-out), knock-in, or transgenic overexpression of the respective transgene are also described. Preliminary conclusions suggest that many of the diabetogenic neurodegenerative disorders are related to alterations in oxidative phosphorylation (OXPHOS) and mitochondrial nutrient metabolism, which coincide with aberrant protein precipitation in the majority of affected individuals.
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PMID:Neurodegenerative disorders associated with diabetes mellitus. 1517 61

Simultaneous pancreas-kidney transplantation (SPK) recipients have longer survival compared to type 1 diabetes mellitus (DM1) cadaveric kidney recipients. However, DM1 living-related kidney transplant (KTX-LR) recipients have the same mortality as SPK recipients. It is unknown whether cardiovascular (CVD) risk factors pretransplant are similar between the two groups, SPK and DM1 KTX-LR. We analyzed pretransplant characteristics of SPK recipients (n = 39) and DM1 KTX-LR/living unrelated (LUR) recipients (KTX-LR/LUR, n = 20). In individuals who had multiple transplants, only pretransplant data from the first transplant was used. As all characteristics of KTX-LR/LUR recipients were the same, they were grouped for comparison with SPK. Pretransplant blood pressure (BP), body mass index, (BMI), hemoglobin A1c (A1c), total cholesterol (TC), high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides (TG), serum creatinine, type and duration of dialysis, and duration of diabetes were compared between the two groups. Mean age at time of transplantation was 41 +/- 1 years (mean +/- SEM) for SPK versus 39 +/- 2 years for KTX-LR/LUR (P = NS). Pretransplant BP, BMI, duration of diabetes, TC, HDL, LDL, TG, and lipid agent use were not different between the groups. Pretransplant A1c was 7.8 +/- 0.3% for SPK recipients and 8.3 +/- 0.5% for KTX-LR/LUR recipients (P = NS). Pretransplant serum creatinine was higher in KTX-LR/LUR compared to SPK (7.9 +/- 0.6 mg/dL versus 5.4 +/- 0.5 mg/dL; P =.01). Except for serum creatinine, there were no significant differences in traditional CVD risk factors pretransplant. However, factors posttransplant in addition to better glucose control with SPK may still be different between SPK and KTX-LR/LUR groups.
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PMID:There are no differences in pretransplant characteristics of individuals receiving simultaneous pancreas-kidney transplant and individuals with type 1 diabetes mellitus receiving living-related kidney transplant. 1519 77

Patients with type 1 diabetes mellitus (DM1) are at high risk to develop further autoimmune disorders, which are mostly characterized by the presence of organ-specific antibodies in serum and a subclinical disease course. Diabetes-related (glutamic acid decarboxylase, tyrosine phosphatase, IA-2) and thyroid-specific (thyroperoxidase, thyroglobulin) as well as antibodies to 20S proteasome, and anti-nuclear antibodies, were measured at DM1 onset in 147 children and adolescents. Patients were followed prospectively for the development of autoimmune thyroiditis (TSH elevation and/or sonographic thyroid gland enlargement in the presence of thyroid antibodies) up to 12 years, median observation time 4.4 years. Eight of 147 (5.4%) patients developed autoimmune thyroiditis. The cumulative incidence (+/-SE) at 5 years was 0.08+/-0.03. The prevalence of thyroid antibodies was 16.7%, of DM-related 88.4%, 20S proteasome 21.9%, and anti-nuclear antibodies 20.0%. There was a positive correlation between thyroid and anti-nuclear antibodies (p <0.001). Clinical course of DM1 and remission duration were not influenced by the presence of autoantibodies. However, in contrast to patients without antibodies, those with positive antibodies had significantly (p <0.001) elevated cumulative incidence of autoimmune thyroiditis at 5 years: thyroperoxidase 0.40+/-0.13, thyroglobulin 0.38+/-0.15, and anti-nuclear antibodies 0.29+/-0.12, respectively. These data underline that autoimmunity in patients with DM1 is not only restricted to beta-cell antigens at the onset of disease. In particular, patients with positive thyroid and anti-nuclear antibodies are at high risk to develop autoimmune thyroiditis during the first 5 years of DM1.
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PMID:Prevalence of 20S proteasome, anti-nuclear and thyroid antibodies in young patients at onset of type 1 diabetes mellitus and the risk of autoimmune thyroiditis. 1530 Oct 45


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