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)

Human hemolysate contains several minor components designated Hb A1a, Hb A1b, Hb A1c, which are post-translational modifications of the major hemoglobin component A0. Individuals with diabetes mellitus have elevated levels of Hb A1c, a hemoglobin modified with a glucose moiety at the NH2 terminus of each beta chain. A new chromatographic technique using Bio-Rex 70 is described which not only allows complete separation of Hb A1a from Hb A1b but also resolution of Hb A1a into two components, designated Hb A1a1 and Hb A1a2. Carbohydrate determinations with the thiobarbituric acid procedure revealed that Hb A1a1, Hb A1a2, and Hb A1b as well as Hb A1c were glycosylated. Total phosphate analysis revealed 2.06 and 1.01 mol of phosphorus/alphabeta dimer for Hb A1a1 and Hb A1a2 respectively; Hb A1b and Hb A1c contained no detectable phosphate. Hemoglobin incubated with D-[14C]glucose-6-P co-chromatographs precisely with Hb A1a2, strongly suggesting that Hb A1a2 is glucose-6-P hemoglobin. Levels of Hb A1a1 and Hb A1a2 are normal in individuals with diabetes mellitus. Furthermore, diabetic red cells contain normal levels of glucose-6-P. Therefore, glucose-6-P hemoglobin does not serve as a significant precursor to Hb A1c. Instead Hb A1c is formed by the direct reaction of hemoglobin with glucose. This suggests that hemoglobin can serve as a model system for nonenzymatic glycosylation of protein.
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PMID:Glycosylated minor components of human adult hemoglobin. Purification, identification, and partial structural analysis. 63 72

Recent reports have suggested that determination of glycosylated hemoglobin may serve as a clinical aid for long-term blood glucose control in diabetes mellitus. We describe a simple procedure for measuring it by ion-exchange chromatography. Hemolysates were subjected to Bio-Rex 70 chromatographic separation on small columns. Percentages in the normal group ranged from 4.7 to 8.8% of total hemoglobin; the mean +/- standard error was 6.61 +/- 0.31%. Values in the diabetic group ranged from 6.9 to 17.4%; the mean was 10.83 +/- 0.34. Plasma glucose concentrations after fasting, plotted vs. the percent of glycosylated hemoglobin, revealed a linear relationship at normal or moderately high glucose concentrations. However, the values for glycosylated hemolgobin approached a plateau with grossly higher plasma glucose concentrations after fasting. Our results support the view that, due to its long half-life, the estimation of glycoylated hemoglobin reflects the integrated glucose concentrations to which the erythrocytes have been previously exposed.
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PMID:Simple method for estimating glycosylated hemoglobins, and its application to evaluation of diabetic patients. 69 74

The present paper analyses the results obtained in 82 patients with diabetes mellitus of the 2nd type: 59 women and 23 men, between 41 and 74 years old (average +/- DS, 58 +/- 9 years), of which 58 had an index of the body weight higher than 26. The diabetes duration ranged between newly discovered and 11 years. Each patient was given, 3 times a day, a 150 ml cup containing an infusion of the following mixture of plants previously cut into small pieces: Phaseolus vulgaris (pod), Morus alba (leaf), and Vaccinum myrtillus (leaves). The approximate dose used was of about 15 g/day. The treatment lasted for two months. Before and after treatment, the following parameters were determined: Hb Al (Bio-Rex method) in 31 cases; the average of 3 consequent glycemias; the value of glycemia and insulinemia recorded after a standard lunch, consisting of about 40 g glucides, 14 g proteins and 6 g lipids (50 g bread, a boiled egg and a boiled apple of 100 g). Analysis of the results obtained enabled the following temporary conclusions (1). In 74 out of the 82 cases studied, the average values of glycemia, after the treatment with plants, were lower than those recorded before the treatment (the average values of the whole lot: 219 +/- 82 mg/dl before treatment and 166 +/- 76 mg/dl after treatment (2). The overall decrease recorded, of 53 mg/dl, represents 24.3% of the initial value (3).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of a plant mixture on the metabolic equilibrium in patients with type-2 diabetes mellitus]. 257 33

A beta-variant hemoglobin, first misjudged as a marked elevation of Hb A1, was found in a 68-year-old Japanese female with diabetes mellitus. This hemoglobin was isolated by Bio-Rex 70 chromatography combined with chromatofocusing, and was found to be Hb Hope, beta 136(H14)Gly----Asp, by classical and high performance liquid chromatographic peptide mapping techniques. Intrinsic oxygen affinity of this hemoglobin was approximately one-third as compared with that of Hb A0. This property was still observed in the constituent beta subunits isolated. Effects of such allosteric effectors as H+ (at a fixed concentration of Cl-), anion (Cl-), 2,3-diphosphoglycerate and carbon dioxide were more or less depressed. Among others, a marked reduction in the carbamate effect should be noted in a structural interpretation of the functional modifications. Subunit cooperativity, on the contrary, was not different from that in Hb A0 (n = 2.8-2.9). Explanation of these altered functions were attempted on the basis of the altered structure. The reduced stability of Hb Hope is also described.
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PMID:Hb Hope, beta 136(H14)Gly----Asp, in a diabetic Japanese female and its functional characterization. 270 63

Hemoglobin South Florida is a recently identified hemoglobin variant that is not associated with any clinical disorder. The standard electrophoretic procedures routinely utilized to identify hemoglobin variants did not recognize hemoglobin South Florida. The acetylated form of this hemoglobin co-eluted with hemoglobin A1c on a Bio-Rex 70 column. The quantity of this hemoglobin component was consistent with the amount of hemoglobin A1c associated with uncontrolled diabetes mellitus. The affected individuals did not have diabetes. This observation led to the characterization of a hemoglobin variant that otherwise would have gone unrecognized. This is an example of a variant peptide that was unrecognized for two generations in one family. It is likely that this type of unrecognized peptide variation is common in mammals. These silent structural alterations may be responsible for the variable physical responses occurring in humans exposed to the same environmental agents.
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PMID:Hemoglobin South Florida: a genetic variant with laboratory recognition of only 20% of its product. 313 Aug 58

In patients with diabetes mellitus nonenzymatic glycosylation of hemo-globin is a result of increased blood glucose concentrations. In analogy glycosylated hemo-globin fractions were determined in 23 patients with hereditary fructose intolerance (HFI) and 8 patients with galactosemia (G) by means of hemoglobin chromatography on a column packed with Bio-Rex 70 resin. The concentrations were compared to those of 14 control patients and 43 patients with type 1 diabetes mellitus. Compared to controls, in HFI- and G-patients HbAlab was significantly increased. In contrast diabetic patients presented with a marked and significant increase of the HbAlc fraction. When purified hemoglobin was incubated with different monosaccharides respectively monosaccharide phosphates, an increase of HbAlab resulted mainly after galactose and fructose-1-phosphate. The determination of HbAlab in patients with HFI and G is considered a possible means of metabolic control.
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PMID:Increased concentrations of HbAlab in hereditary fructose intolerance and galactosemia. 358 91

An 8.75-yr-old Caucasian boy was discovered to have a markedly elevated (14.8%) hemoglobin A1c (HbA1c) as estimated by ion-exchange chromatography (Bio Rex 70). Glycohemoglobin (GHb) measured by a colorimetric method with thiobarbituric acid (TBA) was normal (equivalent to a 6.4% HbA1c). Nondiabetic quantities of GHb were found with affinity chromatography, and the glucose tolerance test was normal. Intensive efforts to identify an abnormal variant hemoglobin by several electrophoretic methods were unsuccessful. A family survey identified a similar abnormality in 11 other individuals, revealing an autosomal-dominant pattern. None of the affected individuals had any other hematologic abnormality. Structural analysis in one family member revealed a new hemoglobin variant (approximately 45% of the total hemoglobin) with the substitution of methionine for valine at the beta-NH2-terminal. In addition, the initiator methionine residue was preserved. Approximately 20% of the variant hemoglobin was modified by acetylation of the NH2-terminal methionine. The modified variant coeluted with HbA1c. We suggest that patients who do not have an explanation for their elevated HbA1c should have GHb measured by the TBA method or affinity chromatography because hemoglobin electrophoresis does not identify this confounding artifact.
Diabetes 1986 Oct
PMID:Hemoglobin South Florida. New variant with normal electrophoretic pattern mistaken for glycosylated hemoglobin. 375 92

To determine red cell age-related changes in the formation of glycosylated (glyco) hemoglobins (Hbs), red cells were fractionated by dextran 40 density gradient centrifugation and glyco Hbs determined by both Bio-Rex 70 cation exchange and phenylboronate-agarose affinity chromatographic methods. Blood samples from a normal adult, adults with White's class A diabetes and insulin dependent diabetes mellitus (IDDM), and newborns of normal and diabetic women were used for this study. Red cell fractions from the newborns and the adults showed a steady increase in the levels of glyco Hb determined by the affinity method with increasing red cell density. In the newborns, the absolute levels and the increase of glyco Hb were smaller than in the adults, probably because of decreased red cell survival in fetuses compared to adults. The glyco Hb value for each cell fraction was significantly higher in the adult with IDDM and in the newborns of diabetic women. In the adults, the levels of Hb Ala + b and Hb Alc determined by Bio-Rex 70 chromatography also showed an increase with increasing red cell age. In the newborns, Hb Flc, which contains predominantly acetylated and some glycosylated Hb F, showed only a small increase with increasing red cell age over and above that due to a concomitant increase in Hb F. On the contrary, Hb Fla + b, which contains mostly glyco Hb F, showed a larger increase. The results confirm that glycosylation, but not acetylation, of Hb F takes place over the entire lifespan of red cells.
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PMID:Changes in glycosylated hemoglobins with red cell aging in normal and diabetic subjects and in newborn infants of normal and diabetic mothers. 619 35

Glycosylated hemoglobin in red blood cell hemolysates of five patients homozygous for CC, 18 patients with SC condition, and 13 patients heterozygous for Hb C with or without insulin-dependent diabetes mellitus were separated by Bio-Rex 70 chromatography. The various glycosylated components were identified by analysis of the hemoglobin components for ketoamine and phosphate, in vitro glycosylation studies, and by the quantitative differences in the minor components between the participants with and without diabetes. The percentages of Hb A1a + b, Hb A1c, and Hb C1c were significantly increased in the Hb C heterozygote with diabetes. Similarly, the percentages of Hb S1a + b and Hb S1c were elevated in the SC patient with diabetes. It was noteworthy that the levels of these components became normal after adequate control of diabetes. Moreover, the levels of Hb C1c in the CC participants and Hb S1c (Hb S1c/total Hb S) in the SC patients were significantly higher than the Hb S1c levels previously reported in patients with sickle cell anemia. These findings might reflect the fact that CC and SC patients have less severe hemolytic anemia. Moreover, the relative proportions of Hb A1c and Hb C1c were nearly the same in Hb C heterozygotes, which indicated that Hb A and Hb C were glycosylated in vivo to approximately the same extent.
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PMID:Glycosylated hemoglobins in heterozygotes and homozygotes for hemoglobin C with or without diabetes. 648 Dec 20

Several studies have revealed a correlation between blood levels of glucose and hemoglobin A1c (HbA1c), a minor form of hemoglobin (Hb) present at elevated concentrations in patients with diabetes mellitus. To facilitate a clinical study of the level of circulating HbA1c we have developed an automatic chromatographic system. An efficient separation of HbA1c from HbA0 and other rapid hemoglobins (HbA1a, HbA1b) was achieved on Bio-Rex-70 columns using three buffers. This system allows the daily analysis of 40 samples. The mean level of HbA1c in normal subjects was 5.4 +/- 0.4%. The method also detects the presence of elevated levels of HbF and the most frequent forms of abnormal hemoglobin (HbS, HbC).
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PMID:An automatic method for determination of glycosylated hemoglobins using low-pressure liquid chromatography. 687 71


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