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

Cystic fibrosis (CF) and type 1 diabetes are two of the most common chronic childhood conditions in the UK; the management of each comprises demanding and perpetual daily regiments. As the life expectancy of patients with CF has improved, there has been a corresponding increase in the number of patients developing CF-related diabetes (CFRD), some of whom are teenagers. For a number of reasons, non-adherence to treatment is a recognized problem in chronically ill teenagers, a problem exacerbated when CF and diabetes co-exist. There is a scarcity of literature concerning CFRD management, particularly in relation to adolescence, with recommendations often being based on anecdotal evidence. In this article, the aetiology, incidence, diagnosis and management of CFRD are outlined. Chronic illness in adolescence and the problem of non-compliance are explored and considered in the context of CFRD. Recommendations for practice for health professionals caring for teenagers with CFRD are offered.
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PMID:Management of cystic fibrosis-related diabetes in adolescence. 1268 87

Transforming growth factor-beta (TGF-beta) plays a central role in fibrosis, contributing to the influx and activation of inflammatory cells, the epithelial to mesenchymal transdifferentiation (EMT) of cells and the influx of fibroblasts and their subsequent elaboration of extracellular matrix. TGF-beta signals through transmembrane receptor serine/threonine kinases to activate novel signalling intermediates called Smad proteins, which modulate the transcription of target genes. The use of mice with a targeted deletion of Smad3, one of the two homologous proteins which signals from TGF-beta/activin, shows that most of the pro-fibrotic activities of TGF-beta are mediated by Smad3. Smad3 null inflammatory cells and fibroblasts do not respond to the chemotactic effects of TGF-beta and do not autoinduce TGF-beta. The loss of Smad3 also interferes with TGF-beta-mediated induction of EMT and genes for collagens, plasminogen activator inhibitor-1 and the tissue inhibitor of metalloprotease-1. Smad3 null mice are resistant to radiation-induced cutaneous fibrosis, bleomycin-induced pulmonary fibrosis, carbon tetrachloride-induced hepatic fibrosis as well as glomerular fibrosis induced by induction of type 1 diabetes with streptozotocin. In fibrotic conditions that are induced by EMT, such as proliferative vitreoretinopathy, ocular capsule injury and glomerulosclerosis resulting from unilateral ureteral obstruction, Smad3 null mice also show an abrogated fibrotic response. Animal models of scleroderma, cystic fibrosis and cirrhosis implicate involvement of Smad3 in the observed fibrosis. Additionally, inhibition of Smad3 by overexpression of the inhibitory Smad7 protein or by treatment with the small molecule, halofuginone, dramatically reduces responses in animal models of kidney, lung, liver and radiation-induced fibrosis. Small moleucule inhibitors of Smad3 may have tremendous clinical potential in the treatment of pathological fibrotic diseases.
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PMID:Smad3 as a mediator of the fibrotic response. 1515 11

We describe identical adolescent twin girls who presented with symptoms consistent with type 1 diabetes. Medical work up for evaluation of gastrointestinal symptoms led to a diagnosis of cystic fibrosis (CF) in both. These cases suggest that diabetes can be a presenting symptom of CF in the absence of pulmonary symptomatology.
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PMID:Cystic fibrosis presenting as new onset diabetes mellitus in adolescent twins. 1518 96

The reasons for the uneven worldwide distribution of Type 1 diabetes mellitus have yet to be fully explained. Epidemiological studies have shown a higher prevalence of Type 1 diabetes in northern Europe, particularly in Scandinavian countries, and Sardinia. Recent animal research has uncovered the importance of the generation of elevated levels of glucose, glycerol and other sugar derivatives as a physiological means for cold adaptation. High concentrations of these substances depress the freezing point of body fluids and prevent the formation of ice crystals in cells through supercooling, thus acting as a cryoprotectant or antifreeze for vital organs as well as in their muscle tissue. In this paper, we hypothesize that factors predisposing to elevated levels of glucose, glycerol and other sugar derivatives may have been selected for, in part, as adaptive measures in exceedingly cold climates. This cryoprotective adaptation would have protected ancestral northern Europeans from the effects of suddenly increasingly colder climates, such as those believed to have arisen around 14,000 years ago and culminating in the Younger Dryas. When life expectancy was short, factors predisposing to Type 1 diabetes provided a survival advantage. However, deleterious consequences of this condition have become significant only in more modern times, as life expectancy has increased, thus outweighing their protective value. Examples of evolutionary adaptations conferring selection advantages against human pathogens that result in deleterious effects have been previously reported as epidemic pathogenic selection (EPS). Such proposed examples include the cystic fibrosis mutations in the CFTR gene bestowing resistance to Salmonella typhi and hemochromatosis mutations conferring protection against iron-seeking intracellular pathogens. This paper is one of the first accounts of a metabolic disorder providing a selection advantage not against a pathogenic stressor alone, but rather against a climatic change. We thus believe that the concept of EPS should now include environmental factors that may be nonorganismal in nature. In so doing we propose that factors resulting in Type 1 diabetes be considered a result of environmental pathogenic selection (EnPS).
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PMID:The sweet thing about Type 1 diabetes: a cryoprotective evolutionary adaptation. 1589 9

Over 90% of cystic fibrosis (CF) patients are treated with bronchodilators, and 6% have diabetes. Some with asthma also have diabetes, and most are treated with bronchodilators. Systemic administration of adrenergic agents can cause increases in blood glucose, but the effect of inhaled agents is unclear. A double-blind study was performed on 10 patients with type 1 diabetes mellitus (DM) without CF (3 male, 7 female, mean age 25.5 years) and 9 patients with insulin-dependent CF-related diabetes (CFRD) (8 male, 1 female, mean age 21.9 years). On 2 separate days before 9 AM fasting and the morning dose of insulin, 2.5 mg of albuterol or nebulized placebo were given. Blood glucose was measured by finger stick with a glucose reflectance meter before and 15, 30, 45, and 60 min after treatment. No significant changes from baseline or differences between placebo and albuterol occurred in either group. The mean maximum increase from baseline in DM was 20 mg/dl on placebo, and 38 mg/dl on albuterol; in the CFRD, the respective changes were 7 and 7 mg/dl. Two DM patients had a > 50 mg/dl increase on albuterol vs. placebo; no CFRD patients had differences of such magnitude. DM patients had greater increases from baseline than CFRD patients on placebo and albuterol. Differences reached statistical significance at 30 and 45 min on placebo, and 45 min on albuterol. Albuterol 2.5 mg by nebulizer causes no clinically significant increases in blood glucose in DM or CFRD patients. Diabetes patients without CF have a significantly greater increase of glucose with time (placebo or albuterol) than CFRD patients.
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PMID:Effect of nebulized albuterol on blood glucose in patients with diabetes mellitus with and without cystic fibrosis. 1596 94

Sleeping Beauty transposons have the potential for use as chromosome-integrating vectors for non-viral gene therapy. Recent preclinical data from mouse models for human genetic disorders have shown efficacy for the Sleeping Beauty transposon system in the treatment of hemophilia, tyrosinemia type I, junctional epidermolysis bullosa and type 1 diabetes. Methods have also been developed to deliver Sleeping Beauty transposons to the lung, liver and tumors for treatments for cystic fibrosis, cardiovascular and metabolic diseases, and cancer. Recent studies characterizing site selection for integration and insertional mutagenesis indicate that the Sleeping Beauty transposon system may be a safer alternative than viral approaches for gene therapy.
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PMID:Awakening gene therapy with Sleeping Beauty transposons. 1608 71

There is movement to expand newborn screening (NBS) to include conditions that challenge the traditional public health screening criteria. Little is known about the attitudes of genetic counselors towards expanding NBS and offering predictive genetic tests to children. For our study genetic counselors completed an internet survey posted on the National Society of Genetic Counselors Listserv regarding five conditions: cystic fibrosis (CF), Duchenne muscular dystrophy (DMD), glucose-6-phosphate dehydrogenase deficiency (G6PD), fragile X (FraX), and type 1 diabetes (T1D). The survey addressed attitudes towards: (1) testing high-risk infants; (2) mandatory NBS; (3) population screening beyond the newborn period; and (4) testing one's own child. Two hundred sixty-seven usable surveys were received. Over two-thirds of respondents supported testing high-risk infants for all conditions except T1D (22%). CF was the only condition for which there was majority support for both mandatory NBS (56%) and later population screening (60%). For all other conditions, later population screening was preferred over NBS (P <or= 0.01). Genetic counselors were most likely to test their own child for CF (46%) and least likely to test their own child for T1D (6%). For each condition, genetic counselors were more likely to support NBS if they chose to screen their own newborn (P < 0.001). Attitudes towards NBS were not influenced by year of graduation or professional experience. We can conclude that genetic counselors are supportive of targeted testing of high-risk infants. They prefer voluntary population screening with consent to mandatory NBS for conditions that challenge Wilson and Jungner criteria. Their support for NBS correlates with their interest in testing their own children and not with professional experience.
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PMID:Attitudes of genetic counselors towards expanding newborn screening and offering predictive genetic testing to children. 1703 12

Cystic fibrosis (CF) is an inherited genetic defect in epithelial chloride transport that results a multisystem disease affecting the sweat glands and the pulmonary and digestive systems. Although pulmonary disease remains the primary cause of morbidity and mortality in these patients, up to 8% may develop focal biliary cirrhosis and portal hypertension. Liver transplantation is an accepted therapy for these patients. About 85% of CF patients develop pancreatic exocrine insufficiency and up to 34% will develop diabetes requiring insulin. We describe a series of 9 patients who underwent liver transplantation (6 transplantation of liver only [LO], and 3 combined en bloc liver-pancreas [LP] transplantation) for CF-related liver disease at our institution,. All 9 patients had pretransplant pancreatic exocrine insufficiency requiring enzyme supplementation. Of the 9, 5 patients (55%) had preoperative insulin dependent diabetes, including all 3 patients who underwent liver pancreas transplantation. Liver-pancreas transplants were performed en bloc. One-year patient survival for both LO and LP patients was 100%. Five-year patient survival was 83% for the LO patients and 100% for the LP patients. All LP patients are off insulin and do not require pancreatic enzyme supplementation. All patients receiving LO continue to need exogenous pancreatic enzyme supplementation. In the 6 patients who received LO, 2 were insulin dependent prior to surgery, and they remain insulin dependent after transplant. Of the 4 patients who received LO who were not insulin dependent pretransplant, 3 have now developed insulin-dependent diabetes. Patients receiving LO were more likely to be diabetic and require exogenous pancreatic enzymes after transplant than those receiving LP (83% vs. 0%, P = 0.04, and 100% vs. 0%, P = 0.01, respectively). In conclusion, patients with CF and end-stage liver disease requiring liver transplantation may benefit from combined liver-pancreas transplantation.
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PMID:Combined en bloc liver pancreas transplantation for children with CF. 1731 57

Circulating levels of adiponectin decrease with increasing visceral obesity and are lower in patients with type 2 diabetes, the metabolic syndrome, and cardiovascular disease compared with controls matched by body mass index. Several reports demonstrated anti-inflammatory effects of adiponectin. Because increased adipose tissue is associated with low-grade chronic inflammation and proinflammatory factors inhibit adiponectin production, the current hypothesis states that chronic inflammation associated with visceral obesity inhibits production of adiponectin, perpetuating inflammation. The negative correlation between adiponectin and markers of inflammation in the aforementioned conditions supports this hypothesis. In contrast with disorders typically associated with excess adiposity and positive energy balance, adiponectin levels are elevated--rather than decreased--in classic chronic inflammatory/autoimmune diseases that are unrelated to increased adipose tissue, such as rheumatoid arthritis, SLE, inflammatory bowel disease, type 1 diabetes, and cystic fibrosis. In these patients, adiponectin levels positively--rather than negatively--correlate with inflammatory markers. Furthermore, proinflammatory effects of adiponectin have been reported in tissues such as joint synovium and colonic epithelium. Thus, adiponectin is regulated in the opposite direction and may exert differential functions in classic versus obesity-associated inflammatory conditions. This article discusses this apparent paradox and presents possible alternative and/or complementary explanations.
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PMID:Adiponectin and inflammation: consensus and controversy. 1877 64

Diabetic ketoacidosis (DKA) is a potentially life-threatening complication of diabetes, most commonly associated with type 1 diabetes. Here, we report the case of a 17-yr-old girl with cystic fibrosis and a prior diagnosis of cystic fibrosis-related diabetes (CFRD) who presented with DKA in the setting of insulin omission and glucocorticoid use. During the course of treatment for DKA, her neurologic status declined and head computerized tomography confirmed cerebral edema. Recognition of DKA and cerebral edema allowed for timely treatment, and the patient recovered without sequelae. This is the first report of DKA complicated by cerebral edema that is attributable to CFRD.
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PMID:A teenage girl with cystic fibrosis-related diabetes, diabetic ketoacidosis, and cerebral edema. 1877 2


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