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)

There is evidence that infants of insulin-dependent diabetics have increased intrauterine bone resorption and reduced bone mineral content at birth. The aim of this study was to determine if type I diabetes is associated with abnormal maternal bone metabolism. We measured the circulating levels of carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in the third trimester of pregnancy in samples obtained from 19 pregnant women with type I diabetes and 19 pregnant controls, to monitor the rate of bone formation and degradation, respectively. Diabetic control was considered to be good as the mean hemoglobin A(1) level was less than 8.5%. The circulating levels of PICP were significantly higher in pregnant women with insulin-dependent diabetes than in controls with uncomplicated pregnancy (median IDDM 147 microgram/liter, control 115 microgram/liter, P = 0.0014), but there was no significant difference in the circulating levels of ICTP between the two groups (median IDDM 4.6 microgram/liter, control 4.6 microgram/liter, P = 0.907). Therefore, our findings suggest that there is an increase in bone formation in pregnant women with type I diabetes which may be related to the increased amount of insulin administered and the improvement in diabetic control associated with pregnancy.
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PMID:Increased maternal bone formation in type I diabetic pregnancies. 1044 52

We recently demonstrated that children with type 1 diabetes mellitus (DM) have decreased lumbar spine bone mineral density (BMD) as early as four years after clinical diagnosis of the disease. In order to determine whether osteopenia is already present in patients very early on after diagnosis of clinical DM, we evaluated the bone mineral status of a group of newly diagnosed children (5.8 +/- 1.5 mo after diagnosis). We studied 23 prepubertal children (7 M, 16 F) with a mean chronological age of 9.5 +/- 2.2 yr and a mean glycosylated hemoglobin of 8.9 +/- 2.4%. Lumbar spine and femoral neck BMD were measured by dual X-ray absorptiometry, while bone turnover was assessed by the determination of the serum concentration of the carboxy-terminal propeptide of type I collagen (PICP) and the carboxy-terminal cross-linked telopeptide of type I collagen (N-telopeptide). Results were compared to those of age, height, and pubertal status matched controls. Lumbar spine BMD Z-scores were decreased in patients compared to controls (Z-scores of -0.89 +/- 1.2, with 10 of 22 patients showing values >1 SD below the mean). When lumbar spine Z-scores were analyzed in those patients with <3 months or > or =3 months since diagnosis of DM a significant difference was noticed between groups (-0.648 +/- 1.12 vs -1.267 +/- 1.17; p <0.02). No significant differences were noted in femoral neck BMD and total BMD between groups. Serum PICP levels were decreased when compared to controls (233.6 +/- 39.3 vs 375.9 +/- 50.7 microg/l; p <0.002), while serum N-telopeptide concentrations, although increased, were not significantly different (9.3 +/- 1.3 vs 5.7 +/- 1.5 microg/l). In summary, early on after the diagnosis of type 1 DM, children present with decreased lumbar spine BMD and decreased bone formation markers.
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PMID:Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus. 1139 73

The effects of insulin dependent diabetes mellitus (IDDM) on bone metabolism are still not well defined. We evaluated total bone mineral content (TBMC) and bone mineral density (BMD) at the lumbar spine and femoral neck using dual X-ray absorptiometry in 26 IDDM children (15 M, 11 F) with a mean chronological age of 12.1+/-3.1 yr (range 7.1-14.2 yr). Duration of diabetes was 4.3+/-2.9 yr, with a mean glycosylated hemoglobin of 9.2+/-0.4%. BMD and TBMC standard deviation scores (Z-scores) were determined by comparing our results to controls matched for age, sex and pubertal status. BMD and bone formation and resorption markers were determined at the beginning of the study and after one year of follow up. Mean lumbar spine Z-score was -1.06+/-0.2, with negative values in 24 of 26 children (92.6%); 14/26 patients (53.8%) had a lumbar spine Z-score >1.0 SD below the mean. Mean lumbar spine Z-score remained unchanged after one year of follow up (-1.02+/-0.3). No significant differences were obtained in femoral neck BMD or TBMC between groups. No correlation was observed between lumbar spine BMD Z-scores and duration of IDDM or degree of diabetes control, as assessed by the mean glycosylated hemoglobin. Daily urinary calcium excretion was elevated in our patients initially and after one year of follow up; however, no correlation was obtained between lumbar spine BMD and 24 h urinary calcium excretion. Carboxy-terminal propeptide of type 1 collagen values and levels of urinary cross-linked N-telopeptides of type 1 collagen in the diabetic children were significantly lower than those of the matched controls. Osteoblastic activity as assessed by serum osteocalcin and by the carboxy-terminal propeptide of type I collagen and bone resorption as measured by cross-linked N-telopeptides of type 1 collagen did not correlate with the lumbar spine Z-scores. When IDDM patients were subdivided into males and females and into children with more than or less than 2 yr duration of diabetes since diagnosis, no differences between groups were found. These results suggest that insulin dependent diabetes in children is associated with low bone turnover resulting in a deficit in bone mass which may be manifested as osteopenia in the growing bone. This defect is already present in trabecular bone early on in the disease and seems not to be related to glycemic control.
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PMID:Decreased lumbar spine bone mass and low bone turnover in children and adolescents with insulin dependent diabetes mellitus followed longitudinally. 1151 57

In this report, we have shown that the standard laboratory diet administered to Psammomys obesus (sand rat) from Beni Abbes in Algeria, induced a non-insulin dependent diabetes, characterised by increase of body weight (p<0.001) as well as hyperinsulinemia, hyperglycemia and hypercholesterolemia. In cultured aortic smooth muscle cells (SMC) of sand rats, type I and type III collagen biosynthesis and insulin effects, at low dose, on these parameters were investigated. In all experimental conditions of cultured SMC study, The alpha chains of type I collagen were analysed by immunoblotting in media and cells. Metabolic radiolabelling and Immunochemical procedures revealed that, in diabetic state, synthetic SMC (SMCs) actively produce type I and III collagen which are synthesised in the cells and secreted in the medium; type I collagen was predominant as compared with type III collagen. Diabetes enhanced the collagen synthesis. Low dose of Insulin added to the medium, during 48 h of incubation, induced a marked reduction in the synthesis of collagen types, especially type I collagen.
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PMID:Non insulin dependent diabetes in sand rat (Psammomys obesus) and production of collagen in cultured aortic smooth muscle cells. influence of insulin. 1236 25

Limited joint mobility (LJM), a long-term complication of diabetes, has been shown to be associated with microvascular complications of diabetes. Connective tissue alterations may contribute to the development of LJM and other diabetic complications. We tested whether biochemical markers of types I and III collagen metabolism are associated with LJM in type 1 diabetes. We studied 28 male patients of mean age 43.4 years (SD=9.5) and with a duration of diabetes of 25.2 years (SD=9.7) years. LJM assessment included goniometric measurements of the joints and classification by Rosenbloom's method. We measured serum concentrations of aminoterminal propeptide of type III procollagen (PIIINP), carboxyterminal propeptide of type I procollagen (PICP) and carboxyterminal crosslinked telopeptide of type I collagen (ICTP); urinary excretion of crosslinked N-telopeptides of type I collagen (NTX) and deoxypyridinoline crosslinks (DPyr) was also measured. Although average serum PIIINP tended to be higher in subjects with moderate-severe LJM (3.1 +/- 1.3 microg/l) than in subjects with mild LJM (2.5 +/- 0.7 microg/l) or without LJM (2.6 +/- 0.4 microg/l), no significant association was found (p<0.27). Concentrations of the other collagen markers were not different in subjects with or without LJM. We conclude that synthesis and degradation of types I and III collagen in diabetic subjects with LJM did not differ from those without LJM to reflect changes in the biochemical markers of these proteins.
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PMID:Biochemical markers of types I and III collagen and limited joint mobility in type 1 diabetic patients. 1474 Feb 73

The effects of type 1 diabetes on de novo bone formation during tibial distraction osteogenesis (DO) and on intact trabecular and cortical bone were studied using nonobese diabetic (NOD) mice and comparably aged nondiabetic NOD mice. Diabetic mice received treatment with insulin, vehicle, or no treatment during a 14-day DO procedure. Distracted tibiae were analyzed radiographically, histologically, and by microcomputed tomography (microCT). Contralateral tibiae were analyzed using microCT. Serum levels of insulin, osteocalcin, and cross-linked C-telopeptide of type I collagen were measured. Total new bone in the DO gap was reduced histologically (P < or = 0.001) and radiographically (P < or = 0.05) in diabetic mice compared with nondiabetic mice but preserved by insulin treatment. Serum osteocalcin concentrations were also reduced in diabetic mice (P < or = 0.001) and normalized with insulin treatment. Evaluation of the contralateral tibiae by microCT and mechanical testing demonstrated reductions in trabecular bone volume and thickness, cortical thickness, cortical strength, and an increase in endosteal perimeter in diabetic animals, which were prevented by insulin treatment. These studies demonstrate that bone formation during DO is impaired in a model of type 1 diabetes and preserved by systemic insulin administration.
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PMID:Bone formation is impaired in a model of type 1 diabetes. 1618 88

Decorin, a proteoglycan that inhibits active transforming growth factor-beta, is increased in diabetic nephropathy; however, its functional significance is unclear. In this study, we used low-dose streptozotocin to induce type 1 diabetes in wild-type (C57BL/6J Dcn(+/+)), Dcn(-/-), and Dcn(+/-) mice and studied the mice for up to 1 year of diabetes. Decorin gene dose had no effect on severity of diabetes; however, the Dcn(-/-) diabetic mice died significantly earlier than nondiabetic controls (57 versus 7.3% mortality). In contrast to wild-type diabetic mice, which failed to develop significant nephropathy, the Dcn(-/-) diabetic mice developed a significant increase in albuminuria and plasma creatinine and a concurrent decrease in circulating adiponectin levels. Interestingly, adiponectin levels at 6 months of diabetes were predictive of mortality in diabetic mice. Dcn(-/-) diabetic mice exhibited advanced glomerular lesions, including diffuse mesangial matrix accumulation and fibrin cap formation. By immunohistochemistry, Dcn(-/-) diabetic mice exhibited significant increases in glomerular transforming growth factor-beta, type I collagen, macrophage infiltration, and Nox4. We conclude that decorin is a natural protective factor against diabetic nephropathy and that the Dcn(-/-) diabetic mouse is a useful new model of progressive diabetic nephropathy.
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PMID:Decorin deficiency enhances progressive nephropathy in diabetic mice. 1788 68

The aims of this study were to evaluate bone mineral density (BMD) and bone turnover markers in patients with type 1 diabetes and screening-identified evidence of celiac disease, i.e., celiac autoimmunity. We screened 50 consecutive type 1 diabetic patients for IgA antitissue transglutaminase to identify those with celiac autoimmunity. Eight seropositive patients were identified on this screening, and 12 patients matched for gender and age range were selected as a control group from among the type 1 diabetic patients without celiac autoimmunity. Patients and controls underwent dual-energy X-ray absorptiometry (DEXA) for measurement of bone mineral status and had their blood levels of osteocalcin, carboxy-terminal telopeptide of type I collagen (CTX), calcium, and phosphorus determined. BMD was further adjusted for height, weight, and pubertal stage. Radiographic and blood markers of bone mineralization were compared between patients and controls. BMD (Z-score) at the lumbar spine was -1.44 +/- 0.5 SD for patients and 0.04 +/- 0.2 SD for controls (P = 0.02). Bone mineral content was 37.9 +/- 4.5 g for patients and 49.4 +/- 2.6 g for controls (P = 0.049). Adjusted BMD was -0.62 +/- 0.5 SD for patients and 0.81 +/- 0.09 SD for controls (P = 0.04). After adjustment, four patients and none of the controls presented BMD < -1 SD (P = 0.01). Osteocalcin, CTX, calcium, and phosphorus blood levels were not significantly different between patients and controls. Celiac autoimmunity is associated with reduced bone mineralization in type 1 diabetic patients. The pathophysiological mechanisms and clinical relevance of this finding remain to be further investigated.
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PMID:Bone mineralization in young patients with type 1 diabetes mellitus and screening-identified evidence of celiac disease. 1793 41

Diabetic patients have an increased risk of prosthesis failure requiring revision surgery. Furthermore, skeletal defects are observed in conjunction with type 1 diabetes. Using a titanium particle-induced calvarial osteolysis model in diabetic mice, we investigated the effect of diabetes on the osteolytic process and the role of naringin in its prevention. Three groups each of nondiabetic or diabetic mice were treated with vehicle only, with particles only, or with particles then naringin for 10 days. Alteration of bone indices near the midline suture were then analyzed by microcomputed tomography scanning and histology. Serum levels of osteocalcin (OCN) and cross-linked N-telopeptide of type I collagen (NTx) were measured by enzyme-linked immunosorbent assay. The decreases in new bone formation (p < 0.05), calvaria thickness (p < 0.05), bone volume (p < 0.05), midline suture area (p < 0.05), and OCN concentration (p < 0.05) found in diabetic mice were normalized with naringin treatment. Diabetic state promoted particle-induced osteolysis. Naringin, an osteoanabolic agent, improved bone indices apparently by stimulating bone formation. Therefore, naringin may be beneficial in preventing and treating debris-mediated periprosthetic osteolysis after total joint replacement, especially in diabetics.
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PMID:Promotion of bone formation by naringin in a titanium particle-induced diabetic murine calvarial osteolysis model. 1982 55

Several studies have established an association between diabetes and alterations in bone metabolism; however, the underlying mechanism is not well established. Although zinc is recognized as a potential preventive agent against diabetes-induced bone loss, there is no evidence demonstrating its effect in chronic diabetic conditions. This study evaluated the effects of zinc supplementation in a chronic (90 days) type 1 diabetes-induced bone-loss model. Male Wistar rats were distributed in three groups: control, type 1 diabetes mellitus (T1DM), and T1DM plus zinc supplementation (T1DMS). Serum biochemical analysis; tibia histomorphometric, biomechanical, and collagen-content analyses; and femur mRNA expression were evaluated. Relative to T1DM, the zinc-supplemented group showed increased histomorphometric parameters such as TbWi and BAr and decreased TbSp, increased biomechanical parameters (maximum load, stiffness, ultimate strain, and Young's modulus), and increased type I collagen content. Interestingly, similar values for these parameters were observed between the T1DMS and control groups. These results demonstrate the protective effect of zinc on the maintenance of bone strength and flexibility. In addition, downregulation of OPG, COL1A, and MMP-9 genes was observed in T1DMS, and the anabolic effects of zinc were evidenced by increased OC expression and serum ALP activity, both related to osteoblastogenesis, demonstrating a positive effect on bone formation. In contrast, T1DM showed excessive bone loss, observed through reduced histomorphometric and biomechanical parameters, characterizing diabetes-associated bone loss. The bone loss was also observed through upregulation of OPG, COL1A, and MMP-9 genes. In conclusion, zinc showed a positive effect on the maintenance of bone architecture and biomechanical parameters. Indeed, OC upregulation and control of expression of OPG, COL1A, and MMP-9 mRNAs, even in chronic hyperglycemia, support an anabolic and protective effect of zinc under chronic diabetic conditions. Furthermore, these results indicate that zinc supplementation could act as a complementary therapy in chronic T1DM.
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PMID:Protection against T1DM-Induced Bone Loss by Zinc Supplementation: Biomechanical, Histomorphometric, and Molecular Analyses in STZ-Induced Diabetic Rats. 2593 89


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