Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to determine maternal and fetal lipoprotein profiles in type 1 diabetic pregnancies differing in glycemic control. Serum lipid, apolipoprotein, and lipoprotein lipid concentrations were investigated in mothers with poorly controlled or well-controlled type 1 diabetes as reflected by hemoglobin A1c(HbA1c) concentrations performed by isolab column chromatography and in their macrosomic (body wt = 4650 +/- 90 g) or appropriate-for-gestational-age newborns (body wt = 3616 +/- 68 g), and these levels were compared with those in healthy mothers and in their control newborns (body wt = 3290 +/- 45 g). In mothers with well-controlled diabetes and in their infants, serum lipid, apolipoprotein, and lipoprotein lipid concentrations were comparable to those in control mothers and in their control newborns. Mothers with poorly controlled diabetes presented higher serum triglyceride and apoprotein B-100 (apo B-100) levels but lower apo A-I and HDL3 cholesterol and phospholipid levels as compared with control values. In their macrosomic newborns, all serum lipid, apolipoprotein, and lipoprotein lipid levels were higher than those in control newborns. Maternal HbA1c and triglyceride levels in late gestation were significant predictors of fetal lipids and lipoproteins in the poorly controlled diabetes group. In conclusion, when under good metabolic control, type 1 diabetes did not affect maternal and fetal lipid levels. However, when under poor metabolic control, type 1 diabetes is associated with maternal and fetal lipoprotein abnormalities.
 ...
PMID:Maternal and fetal serum lipid and lipoprotein concentrations and compositions in type 1 diabetic pregnancy: relationship with maternal glycemic control. 1112 45

The epsilon4 allele of the apolipoprotein-E (APOE) gene is associated with poor outcome following various cerebral insults. The relationship between APOE genotype and cognitive function in patients with type 1 diabetes is unknown. In a cross-sectional study of 96 people with type 1 diabetes, subjects were APOE genotyped, previous exposure to severe hypoglycemia was estimated by questionnaire, and cognition was assessed by neuropsychological testing. Cognitive abilities were compared using multivariate general linear modeling (multiple analysis of covariance, MANCOVA) in those with (n = 21) and without (n = 75) the APOE epsilon4 allele. APOE epsilon4 selectively influenced cognitive ability in a sex-specific manner (F = 2.3, P = 0.044, Eta(2) = 0.15); women with APOE epsilon4 performed less well on tests of current, nonverbal intellectual ability (Wechsler Adult Intelligence Scale-Revised performance test score, P = 0.001, Eta(2) 0.26) and frontal lobe and executive function (Borkowski verbal fluency, P = 0.016, Eta(2) = 0.15). Previous exposure to severe hypoglycemia did not interact with APOE epsilon4 to produce cognitive disadvantage. The APOE epsilon4 genotype is associated with specific cognitive disadvantage in young women with type 1 diabetes. APOE epsilon4 is unlikely to mediate susceptibility to hypoglycemia-induced cognitive disadvantage.
 ...
PMID:Apolipoprotein-e influences aspects of intellectual ability in type 1 diabetes. 1250 5

The aim of the study was to test the hypothesis that in diabetic patients without overt nephropathy there may be a correlation between the activity of natural anticoagulant proteins and glomerular dysfunction. Assays for functional activity of proteins S and C, measurements of urinary albumin excretion, lipid parameters and haemoglobin A1c were performed in 91 patients with type 1 diabetes mellitus and 85 patients with type 2. Patients with type 1 diabetes and microalbuminuria had significantly higher mean age (44.1 +/- 10.9 vs. 37.9 +/- 12.7 years; p<0.05), fibrinogen level (3.75 +/- 1.0 vs. 3.21 +/- 0.8 g/l; p<0.01), protein S activity (92.3 +/- 17.6 vs. 84.5 +/- 15.5%; p<0.05) and higher prevalence of retinopathy (p<0.01) and macrovascular disease (p<0.01) than those with normoalbuminuria. Albumin excretion was significantly correlated to age (r=0.25, p<0.05), fibrinogen level (r=0.39, p<0.01), protein S activity (r=0.27; p<0.05), total cholesterol (r=0.23; p<0.05), apoprotein B (r=0.22; p<0.05), retinopathy (r=0.33; p<0.01) and macrovascular disease (r=0.33; p<0.01). Patients with type 2 diabetes mellitus and microalbuminuria had significantly higher apoprotein B levels (1.17 +/- 0.3 vs. 1.06 +/- 1.2 mg/dl; p<0.05) than those with normoalbuminuria, and apoprotein B was significantly correlated to albumin excretion (r=0.22; p<0.05). In a multivariate model of type 1 diabetes mellitus with fibrinogen, protein S and C activity, cholesterol, triglycerides, haemoglobin A1c, retinopathy, and macrovascular disease as independent parameters (r=0.53; p<0.003), there was significant independent correlation of fibrinogen (beta=0.28; p<0.01), protein S activity (beta=0.27; p<0.05) and retinopathy (beta=0.21; p<0.01) with albumin excretion. We conclude that in type 1 diabetes, relative elevation of fibrinogen level and protein S activity appear in the early stages of development of diabetic nephropathy, and may be related to the pathogenesis of diabetic kidney disease.
 ...
PMID:Urinary albumin excretion is correlated to fibrinogen levels and protein S activity in patients with type 1 diabetes mellitus without overt diabetic nephropathy. 1514 63

The influence of diabetes mellitus on brain pathology is increasingly recognized. Previous contributions of our laboratory demonstrated in models of type 1 diabetes (nonobese diabetic and streptozotocin (STZ)-treated mice), a marked astrogliosis and neurogenesis deficit in hippocampus and increased expression of hypothalamic neuropeptides. In the present investigation, we further analyzed alterations of astroglia and neurons in the hippocampus of mice 1 month after STZ-induced diabetes. Results showed that these STZ-diabetic mice presented: (a) increased number of astrocytes positive for apolipoprotein-E (Apo-E), a marker of ongoing neuronal dysfunction; (b) abnormal expression of early gene products associated with neuronal activation, including a high number of Jun + neurons in CA1 and CA3 layers and dentate gyrus, and of Fos-expressing neurons in CA3 layer; (c) augmented activity of NADPH-diaphorase, linked to oxidative stress, in CA3 region. These data support the concept that uncontrolled diabetes leads to hippocampal pathology, which adjoin to changes in other brain structures such as hypothalamus and cerebral cortex.
 ...
PMID:Neuronal and astroglial alterations in the hippocampus of a mouse model for type 1 diabetes. 1574 69

Diabetes mellitus (DM) is a highly prevalent complex genetic disorder. There has been a worldwide effort in the identification of susceptibility genes for DM and its complications, and the 5-10-methylenetetrahydrofolate reductase (MTHFR) and apolipoprotein-E (APOE) genes have been considered good candidate susceptibility genes to this condition. The objectives of the present study were to determine if the 677T MTHFR and epsilon2/epsilon3/epsilon4 APOE alleles are risk factors for DM and for severity of diabetic retinopathy (DR). A total of 248 individuals were studied: 107 healthy individuals and 141 diabetic patients (46 with type 1 diabetes and 95 with type 2 diabetes), who also had DR (81 with non-proliferative DR and 60 with proliferative DR). The polymorphisms were analyzed by PCR followed by digestion with restriction enzyme or the single-nucleotide primer extension method. No evidence of association between the 677TT genotype of MTHFR gene and DM [cases: TT = 10/95 (10.6%); controls: TT = 14/107 (13%)] or with severity of DR was observed [cases: TT = 5/60 (8.5%); controls: TT = 9/81 (11.1%); P > 0.05]. We also did not find evidence of an association between APOE alleles and proliferative DR (epsilon2, epsilon3 and epsilon4 in cases: 9, 76, and 15%, and in controls: 5, 88, and 12%, respectively) but the carriers of epsilon2 allele were more frequent among patients with type 2 DM and DR than in controls [cases: 15/95 (15.8%); controls: 7/107 (6.5%); P < 0.05]. Therefore, our results suggest that the epsilon2 allele/APOE might be a risk factor for diabetes in the Brazilian population.
 ...
PMID:Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients. 1686 78

In well-controlled patients with type 1 diabetes mellitus, serum lipid and lipoprotein concentrations are similar to those in nondiabetic people. However, in poor glycaemic control, i.e., insulin deficiency, disordered lipid and lipoprotein metabolism is common, characterized with increased concentrations of triglycerides and triglyceride-rich lipoproteins (chilomicrons and VLDL). Insulin deficiency is associated with the increased hepatic production of apoprotein B-containing lipoproteins and ineffective lipoprotein clearance due to decreased activity of the insulin-dependent lipoprotein lipase. Severely insulin-deficient patients with ketosis may develop severe lipaemia with chylomicronaemia. All these abnormalities are rapidly corrected with an adequate insulin therapy, through the decreased hepatic lipoprotein production and the increased lipoprotein lipase activity (increased lipoprotein clearance). In addition to the quantitative changes, some qualitative abnormalities (compositional changes) in lipoproteins can be also present in diabetics, leading to the disturbed lipid and lipoprotein metabolism. An adequate insulin treatment will enable a good diabetes control and the dual prevention: of the lipid and lipoprotein disorders and at the same time prevention of the diabetic complications.
 ...
PMID:[Changes of lipoproteins during insulin therapy in diabetes mellitus type 1]. 1970 19

Patients with diabetes mellitus have increased mortality and morbidity of cardiovascular diseases compared with nondiabetic patients. Although clinical studies have shown that effective glycemic control with insulin treatment in patients with type 1 diabetes is associated with reduced cardiovascular events, the underlying mechanisms have not been well understood. In this study, we treated diabetic apolipoprotein E-deficient (apoE-/-) mice with insulin for 20 weeks and studied the effect of insulin treatment on intimal lesion size and matrix metalloproteinase (MMP) 9 expression known to be involved in plaque destabilization. Results showed that insulin treatment, which effectively reduced plasma glucose level in diabetic mice, attenuated diabetes-increased intimal lesion size and significantly inhibited diabetes-increased MMP9 expression, but had no effect on tissue inhibitor of metalloproteinase 1 in atherosclerotic plaques. Furthermore, we observed that insulin treatment did not reduce diabetes-increased macrophage content but inhibited interleukin 6 expression, a stimulator for MMP expression. Taken together, this study has shown for the first time that insulin treatment in diabetic apoE-/- mice changes atherosclerotic lesions and gene expression to a state that favors plaque stability.
 ...
PMID:Insulin treatment attenuates diabetes-increased atherosclerotic intimal lesions and matrix metalloproteinase 9 expression in apolipoprotein E-deficient mice. 2155 44

Neuregulin-1 (NRG-1) is an endothelium-derived growth factor with cardioprotective and antiatherosclerotic properties and is currently being tested in clinical trials as a treatment for systolic heart failure. In clinical practice, heart failure often coexists with renal failure, sharing an overlapping pathophysiological background. In this study, we hypothesized that NRG-1 might protect against cardiomyopathy, atherosclerosis, and nephropathy within one disease process. We tested this hypothesis in a hypercholesterolemic apolipoprotein E-deficient (apoE(-/-)) type 1 diabetes mouse model prone to the development of cardiomyopathy, atherosclerosis, and nephropathy and compared the effects of NRG-1 with insulin. Upon onset of hyperglycemia induced by streptozotocin, apoE(-/-)mice were treated with vehicle, insulin, or recombinant human (rh)NRG-1 for 14 wk and were compared with nondiabetic apoE(-/-)littermates. Vehicle-treated diabetic apoE(-/-)mice developed left ventricular (LV) dilatation and dysfunction, dense atherosclerotic plaques, and signs of nephropathy. Nephropathy was characterized by abnormalities including hyperfiltration, albuminuria, increased urinary neutrophil gelatinase-associated lipocalin (NGAL), upregulation of renal fibrotic markers, and glomerulosclerosis. rhNRG-1 treatment induced systemic activation of ErbB2 and ErbB4 receptors in both heart and kidneys and prevented LV dilatation, improved LV contractile function, and reduced atherosclerotic plaque size. rhNRG-1 also significantly reduced albuminuria, NGALuria, glomerular fibrosis, and expression of fibrotic markers. Regarding the renal effects of rhNRG-1, further analysis showed that rhNRG-1 inhibited collagen synthesis of glomerular mesangial cells in vitro but did not affect AngII-induced vasoconstriction of glomerular arterioles. In conclusion, systemic administration of rhNRG-1 in hypercholesterolemic type 1 diabetic mice simultaneously protects against complications in the heart, arteries and kidneys.
...
PMID:Neuregulin-1 attenuates development of nephropathy in a type 1 diabetes mouse model with high cardiovascular risk. 2678 78


<< Previous 1 2