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)

Five glycoproteins have been measured in the blood of 145 diabetic patients with and without clinical evidence of complications. Patients with diabetic complications have higher glycoproteins levels particularly when expressed as a ratio to serum albumin levels. In 32 pairs of patients matched for age, sex, body weight, duration and treatment of diabetes, significantly higher haptoglobin, fibrinogen and caeruloplasmin levels were associated with the presence of diabetic complications, but blood glucose levels were not significantly different. Beta-lipoprotein levels were positively correlated with age and alpha2-macroglobulin levels with the duration of clinical disease, but the type of antidiabetic therapy administered did not significantly alter glycoprotein levels. It is suggested that rising levels of certain glycoproteins in the blood of diabetic patients may indicate the development of diabetic vascular complications, but a prospective study is required before it can be decided whether this change predates the clinical appearance of the complications.
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PMID:Blood glycoprotein levels in diabetes mellitus. 6 Feb 65

The isolated rat liver perfused for 12 hours at pH 7.10 with a suspension of bovine erythrocytes in Krebs-Ringer bicarbonate buffer containing 3 per cent bovine serum albumin has been used as a test system to study effects of glucagon and of dexamethasone in the presence and absence of insulin on net biosynthesis of rat serum albumin, fibrinogen, alpah1-acid glycoprotein, alpha2-(acute phase) globulin, and haptoglobin. Quantitative measurement of perfusate glucose, amino acid nitrogen, and urea affords a basis for determining net glucose and nitrogen balance in the perfusion system. Although the dose of dexamethasone (total 1.0 mug.) used was insufficient to induce synthesis of alpha2-acute phase globulin, net syntheses of albumin, fibrogen, alpha1-acid glycoprotein, and haptoglobin were increased. Glucagon given with dexamethasone depressed albumin and haptoglobin synthesis markedly, but not that of fibrinogen and alpha1-acid glycoprotein. Glucagon with dexamethasone markedly enhanced ureogenesis and glycogenolysis and elicited an exaggerated negative nitrogen balance. The unfavorable effects of glucagon on albumin and haptoglobin synthesis and on nitrogen balance were reversed by giving insulin simultaneously. It is emphasized that insulin is essential for positive nitrogen balance.
Diabetes 1976
PMID:Direct effects of glucagon on protein and amino acid metabolism in the isolated perfused rat liver. Interactions with insulin and dexamethasone in net synthesis of albumin and acute-phase proteins. 6 Nov 40

Intravascular coagulation necrosis of the skin is rare and appears as hemorrhagic infiltrates that may develop ulcerating necrosis, mainly on the acral areas. The face, arms, and legs were severely involved in our patient. In this patient intravascular coagulation necrosis was associated with cryofibrinogenemia, diabetes mellitus, and IgM cardiolipin autoantibodies. In addition, rheumatoid factor, elevated polyclonal IgA, and haptoglobin were present as risk factors for the vasculopathy. Skin biopsy specimens showed plugging of dermal venules by thrombi formed of fibrin and erythrocytes. Immunohistologic staining revealed a strong positive reaction for fibrinogen, with some positivity for C3, C4, IgG, IgA, and IgM. Erythrocyte extravasation occurred in late lesions without being accompanied by perivascular leukocytic infiltrates. Detailed clinical examination failed to identify an underlying malignancy. Treatment with heparin and prednisolone produced only a brief remission. However, the combination of chlorambucil (7 mg/day orally) with low-dose oral prednisolone (10 mg/day) for several weeks controlled the disease and greatly reduced the cryofibrinogen. No relapse occurred after discontinuation of treatment.
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PMID:Intravascular coagulation necrosis of the skin associated with cryofibrinogenemia, diabetes mellitus, and cardiolipin autoantibodies. 143 Mar 78

An analysis of haptoglobin (HP) phenotypes in 81 cases of diabetes mellitus (DM) without retinopathy and 122 cases with diabetic retinopathy (DR) were studied in relation to 180 normal and healthy controls matched for age and sex. A significant decrease in HP 2-1 frequency was found, suggesting protection for heterozygotes in both DM and DR (with a relative risk of about 0.31). As an acute-phase reactant HP may be functionally involved in the etiology of DM and DR, which are associated with immunologic and inflammatory processes, respectively. No significant differences were found with respect to sex, age at onset, duration of DR, types of DM and DR, and family history.
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PMID:Haptoglobin phenotypes in diabetes mellitus and diabetic retinopathy. 177 11

Epidemiologic data suggest that having a parent with Type 2 (non-insulin-dependent) diabetes mellitus increases the risk for Type 1 (insulin-dependent) diabetes in siblings of a Type 1 diabetes proband. This increase in risk is consistent with a shared genetic susceptibility between Type 1 diabetes and Type 2 diabetes. We contrast genetic risk factors in three sets of families, consisting of (1) a single Type 1 diabetic child (proband) and non-diabetic parents, (2) multiple Type 1 diabetic siblings and non-diabetic parents, and (3) at least one Type 1 diabetic child and at least one Type 2 diabetic parent. Previous studies have demonstrated that HLA region genes, which elevate the risk in Type 1 diabetes, have no significant effect with respect to the risk for developing Type 2 diabetes. An earlier report cited a contribution by the haptoglobin locus to genetic susceptibility for Type 2 diabetes. We provide evidence that a high risk HLA antigen (HLA-DR3) is decreased to a greater extent in Type 1 patients with a Type 2 parent than in Type 1 patients in which the parents are not diabetic. The role of HLA-DR4 is maintained in these families, with an unexpectedly significant increased rate of transmission of the HLA-DR4 allele from Type 2 parent to Type 1 offspring. The role of haptoglobin in these families does not appear to be important, either with respect to association with diabetes or with respect to linkage with a secondary susceptibility locus. These results indicate that families with a Type 2 parent and Type 1 child, heavily determined by HLA-DR4 linked factors, may represent a homogeneous subset of diabetes susceptibility.
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PMID:Shared genetic susceptibility of type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus: contributions of HLA and haptoglobin. 186 90

In this study we demonstrate that haptoglobin, a serum glycoprotein secreted by the liver, has altered structure in the BB/Wor diabetic rat. SDS-PAGE of haptoglobin (a tetramer composed of two glycosylated beta-chains each containing two sites for Asn-linked oligosaccharides connected by disulfide bonds with two nonglycosylated alpha-chains) clearly shows that the beta-chain of haptoglobin from diabetic rats is smaller than normal, with a molecular mass of 39 instead of 40 kDa. Both acute and chronic diabetic rats exhibit the defect. Defective haptoglobin appears in the serum within 4 days of onset of the disease, but insulin therapy prevents the defect. Removal of Asn-linked oligosaccharides with peptide: N-glycosidase F from Flavobacterium meningosepticum abolished the size difference between the beta-chains from normal and diabetic haptoglobin, with the molecular mass in both cases shifting to 30 kDa. Haptoglobin from both normal and diabetic rats was resistant to digestion by endoglycosidase H from Streptomyces griseus, which cleaves high mannose-type chains. Removal of sialic acid with neuraminidase treatment resulted in a reduction in the molecular mass in both cases, but without eliminating the size difference between the two. These results demonstrate that haptoglobin from diabetic BB/Wor rats contains a structural abnormality which correlates with onset of the disease. The defect is most likely due to an alteration in Asn-linked oligosaccharides, probably involving a change in the neutral sugars of complex-type oligosaccharide chains. This finding represents the first example of an altered Asn-linked oligosaccharides in diabetes.
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PMID:Diabetic BB/Wor rat haptoglobin exhibits a probable structural abnormality in Asn-linked oligosaccharides. 202 25

Adult male Sprague-Dawley rats with streptozotocin-induced diabetes (6 to 8 wk duration), treated or untreated with insulin, were studied with two aims: (a) to ascertain whether protracted diabetes in the rat is associated with changes in circulating plasma protein levels analogous to those reported in human diabetic patients with clinical evidence of complications; (b) to evaluate the effects of experimental diabetes on the net cumulative biosynthesis of 10 specific plasma proteins by the isolated liver, perfused for 24 hr. Samples of liver donor plasma and samples of perfusate were analyzed by single radial immunodiffusion or by rocket immunoelectrophoresis for albumin, alpha 1-macroglobulin and the acute phase glycoproteins: fibrinogen, alpha 1-acid glycoprotein (Darcy), alpha 1-acid glycoprotein (Kawasaki), haptoglobin, alpha 2-(acute phase) globulin, hemopexin, C3-complement and ceruloplasmin. Diabetes (6 to 8 wk), untreated with insulin, resulted in significantly increased liver donor plasma levels of alpha 1-acid glycoprotein (Darcy) and alpha 1-acid glycoprotein (Kawasaki); plasma levels of hemopexin and of C3 decreased to 75% and 30% of normal, respectively. Insulin treatment of diabetic liver donors for 6 to 8 wk prevented the increase in alpha 1-acid glycoprotein (Darcy) and alpha 1-acid glycoprotein (Kawasaki) and minimized the decrease in C3 to 75% of normal. Perfused livers from untreated diabetic rats (6 to 8 wk) showed slightly decreased cumulative synthesis and secretion of alpha 1-acid glycoprotein (Darcy); however, synthesis of albumin was reduced to 35% of normal and that of eight glycoproteins ranged from 25% of normal (fibrinogen) to 12% of normal (C3). The striking in vitro induction of increased synthesis of acute-phase proteins by cortisol plus insulin in the isolated perfused normal liver was in contrast to the severely attenuated induction in perfused livers of untreated diabetic rats, which ranges from 50% of normal for alpha 1-acid glycoprotein (Darcy) to 5% of normal (C3). Severely negative perfusate nitrogen balance and impaired glucose utilization by perfused untreated diabetic livers contrasted with positive nitrogen balance and good glucose utilization of normal livers in response to insulin plus cortisol. The plasma protein synthetic capacity and the in vitro response to insulin plus cortisol of perfused livers from insulin-treated diabetic rats were normal for seven of the proteins but moderately decreased for albumin, haptoglobin and C3.
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PMID:Effects of streptozotocin diabetes in the rat on blood levels of ten specific plasma proteins and on their net biosynthesis by the isolated perfused liver. 213 29

Human arterial hypertension is likely a multifactorial trait resulting from multiple measurable monogenes, blended polygenes, shared family environment, and individual environment. Familial aggregation of hypertension and familial correlation of blood pressure appears to be more due to genes than to shared family environment. Total genetic heritability of 80% with some recessive major gene effects have been found for several traits associated with hypertension including urinary kallikrein excretion, intraerythrocytic sodium, and sodium-lithium countertransport. Other interesting factors regarding hypertension genetics include: non-modulation of the renin angiotensin system, intralymphocytic sodium, ionized calcium, and several genetic markers such as haptoglobin, HLA, and MNS blood type. Probably the most clinically useful information regarding the genetics of hypertension is evolving in several studies reporting a strong association of hypertension with dyslipidemia, diabetes, and obesity.
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PMID:Genetics of hypertension: what we know and don't know. 220 56

In the plasma of patients with type II diabetes a statistically significant increase was found of the concentration of glycosylated proteins, haptoglobin and sialic acid, in relation to controls. The concentration of glycosylated proteins was determined by the fructosamine method and by a method based on reaction with thiobarbituric acid. The "r" correlation coefficient between both methods in the diabetics was 0.58. No significant correlation was found between fructosamine concentration and the determined acute phase factors. The statistical analysis of the obtained results related to the coexistence of macroangiopathy or microangiopathy, diabetes duration or treatment method showed only a significantly higher fructosamine concentration expressed as mM of fructose in relation to one gram of albumin when the group of diabetics with vascular complications was compared with that without these complications.
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PMID:[Glycosylated proteins and various acute phase factors in patients with type II diabetes]. 236 3

Serum levels of six acute phase proteins (APP)--C-reactive protein (CRP), serum amyloid A (SAA), alpha 1-antitrypsin, haptoglobin and complement fractions C3 and C4--were serially studied in 24 patients with poorly controlled diabetes mellitus, ten of whom had unequivocal evidence of an underlying infection. In diabetic patients without infection, no change in APP levels was noted suggesting that hyperglycaemia per se does not quantitatively influence the acute phase response. No correlation between the presence of infection, and fever, leukocytosis, a raised erythrocyte sedimentation rate, or serum levels of alpha 1-antitrypsin, haptoglobin or complement was apparent in these patients. However, serum CRP and SAA were initially increased 10-100 times above normal in diabetic patients with an underlying infection (P less than 0.01); during the following week circulating levels of CRP and SAA decreased steadily in response to the infection being brought under control. We conclude that serial measurement of CRP and/or SAA is a sensitive, albeit non-specific, parameter to detect and monitor the activity of infection in patients with diabetes.
Diabetes Res Clin Pract 1988 Jul 13
PMID:Circulating acute phase reactive proteins as indicators of infection in poorly controlled diabetes mellitus. 245 16


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