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)

Diabetes mellitus and osteoporosis are chronic diseases with an elevated and growing incidence in the elderly. Recent epidemiological studies have demonstrated an elevated risk of hip, humerus and foot fractures in elder diabetic subjects. While type 1 diabetes is generally associated with a mild reduction in bone mineral density (BMD), type 2 diabetes, more prevalent in old subjects, is frequently linked to a normal or high BMD. Studies on experimental models of diabetes have suggested an altered bone structure that may help to explain the elevated risk of fractures observed in these animals and may as well help to explain the paradox of an incremented risk of fractures in type 2 diabetic elderly in the presence of normal or elevated BMD. In addition, diabetic elderly have an increased risk of falls, consequent at least in part to a poor vision, peripheral neuropathy, and weaken muscular performance. Diabetes may affect bone tissue by different mechanisms including obesity, hyperinsulinemia, deposit of advanced glycosilation end products in collagen fibre, reduced circulating levels of IGF-1, hypercalciuria, renal function impairment, microangiopathy and chronic inflammation. A better understanding of these mechanisms may help implement the prevention of fractures in the growing population of mature diabetics.
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PMID:[Osteoporosis and diabetes]. 1564 75

In this study, we aimed to compare bone calcium system changes from children with diabetic ketoacidosis or acute metabolic acidosis due to dehydration to find out the relative contribution of metabolic acidosis and diabetes-related factors on expected negative calcium balance. We studied a set of non-invasive parameters of bone remodeling in 16 children with diabetic ketoacidosis due to new onset type 1 diabetes and 25 children with acute metabolic acidosis due to dehydration complicating acute gastroenteritis before and after the correction of acidosis. The two groups of subjects were matched for age, sex, pubertal status, and degree of metabolic acidosis and dehydration. A group of 18 age and sex-matched healthy children served as the control group. Plasma ionized calcium levels were increased in both groups, significantly more so in diabetic ketoacidosis. While osteoblastic markers, osteocalcin and alkaline phosphatase, were depressed to a comparable degree in both groups, urinary calcium/creatinine ratio and hydroxyproline excretion were significantly greater in diabetic ketoacidosis. No significant changes in calcitrophic hormone (intact PTH, calcitonin, 25-hydroxy vitamin D3) levels were observed. All study parameters except for serum phosphate levels behaved in parallel in both clinical conditions, and abnormalities disappeared with the correction of acidosis except for IGF-1, which remained low in diabetic subjects. In conclusion, our results suggest that, in diabetic ketoacidosis, the observed severe negative calcium balance occurred through diminished bone formation mediated by metabolic acidosis per se and increased bone mineral dissolution and bone resorption because of severe insulin deficiency and secondarily via metabolic acidosis. Observed changes appear to be independent of calcitrophic hormones.
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PMID:Bone calcium changes during diabetic ketoacidosis: a comparison with lactic acidosis due to volume depletion. 1586 25

In select cases of type 1 diabetes mellitus (DM1) the pancreas transplantation has been shown to ameliorate the disease, to reduce the need for exogenous insulin and normalize glycosylated hemoglobin (A1c) levels. The efficacy of this therapy in Mauriac Syndrome (SM) is not yet well established. We report a patient with MS treated with intensive insulin therapy, physical activity program, nutritional and psychological assistance, with persistently elevated fast glycemia and A1c levels, inadequate lipid profile and decreased IGF-1 (insulin like growth factor) levels. Due to a poorly metabolic control, pancreas transplantation was indicated. After one year follow up, the patient had no symptoms and showed persistent insulin independence with fast glucose <110 mg/dl, normal lipid profile and IGF-1 levels and significant decrease in A1c (4.6%). The pancreas transplantation improved diabetes control and promoted better quality of life for this patient. Pancreas transplantation proved to be an effective treatment strategy in patients with MS, improving their clinical and biochemical derangements. In this report we present the first case of MS controlled by pancreas transplantation registered in the indexed medical literature, as an alternative therapy in this group of patients.
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PMID:[Pancreas transplantation in Mauriac Syndrome: clinical and biochemical parameters after one year follow up]. 1654 2

Gut peptide YY (PYY) plays an important role in regulating metabolism and is expressed during the ontogeny of the pancreas. However, its biological role during endocrine cell formation is not fully understood, and its role, if any, during pancreatic regeneration in the adult has not yet been explored. The knowledge of factors involved in beta cell renewal in adult animals is clearly relevant for the design of treatment strategies for type 1 diabetes. We therefore sought to determine if observations during fetal pancreas formation also apply to pancreatic growth in adult animals. Indeed, we have found marked expansion of the PYY-expressing population during pancreatic regeneration. In addition, we demonstrate the presence of cells co-expressing PYY and the critical pancreatic transcription factor pancreatic duodenal homeobox1 (PDX-1). Interestingly, these cells also co-expressed specific islet hormones during pancreatic development and re-growth, suggesting a developmental relationship. Furthermore, we have found that PYY can act in concert with IGF-1 to stimulate cellular responsiveness in pancreatic epithelial cells in vitro. Our data suggest that PYY may be a mediator of islet cell development, as well as a cofactor for growth factor responses, not only during fetal pancreas formation but also during regeneration in adult animals.
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PMID:PYY in the expanding pancreatic epithelium. 1718 98

Many surveys have indicated that short stature affects at least 95% of all patients with Turner syndrome (TS). It is also clear that growth hormone (GH) therapy can accelerate the physical development in girls with TS. According to some clinical experience diabetes type 1 may be considered as a contraindication for GH therapy leading to low efficacy and high risk of late complications due to hyperglycaemia and elevated IGF-1 level. We present the results of growth hormone therapy on the metabolic control in a girl with TS and type 1 diabetes treated with continuous subcutaneous insulin infusion. The parameters of metabolic control and insulin doses were compared before and after introducing GH therapy. The correct diurnal glycemia profile was obtained after 4-fold increase of basal insulin and 2-fold increase of the total daily dose. The acceleration of growth was observed during 3.5-year therapy and average linear growth velocity was 7 cm/year. Growth hormone administration in children with Turner syndrome and type 1 diabetes can be efficacious and safe.
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PMID:[Metabolic control and insulin administration in a girl with Turner syndrome and type 1 diabetes during long-term growth hormone therapy]. 1804 18

IGFs (insulin-like growth factors), which in an unbound form induce glucose and amino acid uptake, circulate bound to IGFBPs (IGF-binding proteins), which modulate their bioavailability and activity. The aim of the present study was to examine the effect of a standard meal [2301 kJ (550 kcal)] on the serum levels of IGFBP-1 in obese patients with T2DM (Type 2 diabetes mellitus), non-obese patients with T1DM (Type 1 diabetes mellitus) and healthy controls, using the artificial pancreas (Biostator) to obtain a normal glycaemic response to the meal. IGFBP-1 levels decreased by 50% over 2 h following the meal at a similar clearance in both the healthy controls and patients with T1DM, but no significant decline was seen in the patients with T2DM, despite a several-fold increase in insulin levels. The patients with T2DM were also studied during Sandostatin (somatostatin) infusion to decrease the inappropriate secretion of glucagon during the meal. During the 210 min of somatostatin infusion, the glucagon response was suppressed and IGFBP-1 levels were increased concomitantly with the peak in insulin levels, without any significant decrease after the meal. In conclusion, the impaired IGFBP-1 response to meal-related hyperinsulinaemia in obese patients with T2DM suggests a decreased availability of active IGF-1, leading to a decrease in glucose uptake during and after a meal in these patients. The stimulated meal response to glucagon, which contributes to postprandial hyperglycaemia, could not explain the increase in serum IGFBP-1 in these obese patients with T2DM.
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PMID:Postprandial paradoxical IGFBP-1 response in obese patients with Type 2 diabetes. 1820 2

In terms of development of evolutionary biomedicine using invertebrate animals as models for study of molecular grounds of various human diseases, for the first time the streptozocin (ST) model of insulin-dependent diabetes in the mollusc Anodonta cygnea has been developed. This model is based on the following authors' data: (1) redetection of insulin-related peptides (IRP) in mollusk tissues: (2) discovery of the adenylyl cyclase signal mechanism (ACSM) of action of insulin and other peptides of the insulin superfamily in tissues of mammals, human, and mollusc. A. cygnea; (3) concept of molecular defects in hormonal signal systems as causes of endocrine diseases. Studies on the ST model have revealed in mollusc smooth muscle on the background of hyperglycemia at the 2nd, 4th, and 8th day after the ST administration a decrease of the ACSM response to activating action of insulin, IGF-1, and relaxin. These functional disturbances were the most pronounced at the 2nd day of development and rather less marked at the 4th and 8th day. Analysis of data on effect of hormonal and non-hormonal (NaF, GIDP, and forskolin) ACSM activators has shown that the causes of impair of signal-transducing function of this mechanism are (1) a hyperglycemia-induced increase of the basal AC activity and as a consequence--a decrease of the enzyme catalytic potentials in response to hormone; (2) a decrease of functions of Gs-protein and of its coupling with AC. Besides, administration of ST produced in the mollusc muscles an attenuation of regulation by insulin of carbohydrate metabolism enzyme (glucose-6-phosphate dehydrogenase, glycogensynthase). The pattern of disturbances in the studied parameters in the mollusc is very similar to that revealed by the authors in rat and human muscle tissues in type 1 diabetes.
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PMID:[Streptozocin model of diabetes mellitus in the mollusc Anodonta cygnea: functional state of the adenylyl cyclase mechanisms of action of peptides of the insulin superfamily and their effect on carbohydrate metabolism enzymes]. 1826 56

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

Observations of increased stiffness in the elastic aorta in women with diabetes, but not men, emphasise the need for further analysis regarding early abnormalities in arterial wall properties of women with type 1 diabetes mellitus (DM). Ultrasound was used to study the wall properties of the distal brachial artery (BA) in 37 type 1 diabetic women (aged 22-45 years) without evident complications and in 53 controls (C). Blood samples were drawn for later analysis. Flow-mediated dilatation (FMD) was slightly lower in DM than C, 8.1+/-4.3% vs. 10.3+/-4.9% (p<0.05), and nitrate-mediated dilatation (NMD) was markedly lower, 21.7+/-6.6% vs. 31.4+/-5.7% (p<0.001). Lumen diameter, intima-media thickness and distensibility were similar in DM and C. Insulin-like growth factor (IGF-1) was lower in DM than C, 231+/-65 vs. 349+/-68 ng/ml (p<0.001). Glycosylated haemoglobin (HbA1C) and matrix metalloproteinase (MMP-9) were independent predictors of the reduced NMD in the DM. Brachial artery responsiveness to an exogenous donor of nitric oxide (NO) was markedly reduced in type 1 diabetic women despite only limited reduction in endothelium-dependent dilatation. The negative association between NMD and HbA1C suggests that long-term hyperglycaemia impairs vascular smooth muscle cell function in DM.
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PMID:Long-term hyperglycaemia impairs vascular smooth muscle cell function in women with type 1 diabetes mellitus. 1915 25

Gray and white matter structural deficits may accompany type 1 diabetes. Earlier experimental studies have demonstrated neuronal deficits associated with impaired neurotrophic support, inflammation and oxidative stress. In this study we demonstrate in two patients with histories of poorly controlled type 1 diabetes and fatal brain edema of ketoacidosis neuronal deficits associated with a decreased presence of insulin and IGF-1 receptors and accumulation of nitrotyrosin in neurons of affected areas and the choroid plexus. The findings add support to the suggested genesis of T1DM encephalopathy due to compromised neurotrophic protection, oxidative stress, inflammation and neuronal deficits, as demonstrated in T1DM encephalopathy in the BB/Wor-rat.
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PMID:Insulin and IGF-1 receptors, nitrotyrosin and cerebral neuronal deficits in two young patients with diabetic ketoacidosis and fatal brain edema. 2042 Aug 11


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