Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hemoglobin A1c (HbA1c) is a glycosylated derivative of hemoglobin and is one of a family of derivatives whose concentrations are elevated in patients with diabetes mellitus. Published methods for the measurement of HbA1c are relatively tedious and require modest amounts of blood. A high-performance liquid chromatographic (HPLC) method for the determination of HbA1c is presented. The method is rapid (20 minutes), precise (coefficient of variation of 5-10 per cent), uses small amounts of sample (3 microliter.), can be automated. A sample preparation technique using filtration was developed that shortened and simplified preparation of venous blood and allowed use of capillary samples. HbA1c was measured by this method in three age-stratified groups of controls and a group of insulin-requiring juvenile diabetics. There was clear separation of HbA1c values between all normals (5.9 +/- 1.3, 5.6 +/- 0.7, 7.1 +/- 0.9 per cent) and the diabetics (12.1 +/- 2.4 per cent). Use of this method can facilitate large-scale clinical investigations and permit biochemical investigations of the metabolism and formation of hemoglobin A1c where small sample sizes are necessary.
Diabetes 1978 Feb
PMID:A high-performance liquid chromatography method for hemoglobin A1c. 62 38

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.
 ...
PMID:Glycosylated minor components of human adult hemoglobin. Purification, identification, and partial structural analysis. 63 72

Glucose reacts nonenzymatically with the NH2-terminal amino acid of the beta chain of human hemoglobin by way of a ketoamine linkage, resulting in the formation of hemoglobin AIc. Other minor components appear to be adducts of glucose 6-phosphate and fructose 1,6-diphosphate. These hemoglobins are formed slowly and continuously throughout the 120-day life-span of the red cell. There is a two- to threefold increase in hemoglobin AIc in the red cells of patients with diabetes mellitus. By providing an integrated measurement of blood glucose, hemoglobin AIc is useful in assessing the degree of diabetic control. Furthermore, this hemoglobin is a useful model of nonenzymatic glycosylation of other proteins that may be involved in the long-term complications of the disease.
 ...
PMID:The glycosylation of hemoglobin: relevance to diabetes mellitus. 63 69

Isoelectric focusing (IEF) of human erythrocyte hemolystaes on polyacrylamide slab gels over a pH gradient of 6 to 8 provides sufficient resolution of hemoglobin AIc (HbAIc) from other hemoglobin components (AIa, AIb, AII, S, and F) to allow quantification by high-resolution microdensitometry. Twice-chromatographed HbAIc alone and in admixtures with normal and diabetic hemolysates were employed to verify the identification and quantification of the AIc component. Relative concentration was determined as a per cent of the total hemoglobin absorption at 556 nm on acid-fixed, unstained gels. A total of 60 patient samples were examined by IEF, and, for 35 samples, both column chromatography and IEF determination were obtained, revealing excellent correlation between these two methods.
Diabetes 1978 Apr
PMID:A simplified assay of hemoglobin AIc in diabetic patients by use of isoelectric focusing and quantitative microdensitometry. 64 Feb 42

A 6-year-old girl is described who has congenital megaloblastic anemia which completely responded only to pharmacologic doses of thiamine. Relapse was observed twice when the drug was discontinued. The reintroduction of thiamine caused a prompt reticulocytosis and a rise in hemoglobin concentration. Other abnormalities included latent diabetes mellitus, sensorineural deafness, and "situs inversus totalis." Her parents are first cousins, both with partial deafness. Her father has an abnormal oral glucose tolerance test. A single similar case has been reported; the combination of almost the same anomalies seems to represent a newly recognized syndrome. This case reinforces the proposal that thiamine has a role in hematopoesis.
 ...
PMID:Thiamine-responsive megaloblastic anemia, sensorineural deafness, and diabetes mellitus: A new syndrome? 67 Nov 56

Concentrations of glycosylated hemoglobin (GHb) are elevated in diabetes mellitus and are believed to reflect previous metabolic control. To better define possible determinants of GHb in man, we investigated the relationship between GHb and both fasting plasma glucose (FPG) and basal insulin (IRI) in 42 normal subjects and 29 patients with maturity-onset diabetes. Concentrations of GHb in diabetic subjects (12.7 +/- 3.4, x +/- S.D., per cent total hemoglobin) were significantly higher than in normal subjects (8.2 +/- 1.2, p less than 0.001). In normal subjects, FPG (r = 0.52) and GHb (r = 0.58) (both p less than 0.001) correlated with age. GHb did not correlate with IRI in either group. However, GHb was closely associated with FPG in both normal (r = 0.60, p less than 0.001) and diabetic (r = 0.85, p less than 0.001) subjects. Linear regression analysis of the data for the two groups combined was highly significant (r = 0.91, p less than 0.001). However, the slope of the regression line for GHb versus FPG seen in normal subjects was significantly steeper than that of diabetic patients (p less than 0.005). A curve describing a nonenzymatic saturable model was also found to fit the data of the two groups combined (r = 0.85, p less than 0.001), suggesting the possible existence of a saturable system for glycosylation in man.
Diabetes 1978 Aug
PMID:Glycosylated hemoglobin in normal subjects and subjects with maturity-onset diabetes. Evidence for a saturable system in man. 68 Apr 10

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.
 ...
PMID:Simple method for estimating glycosylated hemoglobins, and its application to evaluation of diabetic patients. 69 74

The ultrastructure of rubeosis iridis in sickle cell-hemoglobin C disease is described for the first time. Findings included open interendothelial cell junctions, intraendothelial cytoplasmic attenuations (fenestrations), and pericyte formation. The ultrastructural appearance of rubeosis iridis gives no clue to the underlying etiology and is similar to that reported in rubeosis associated with diabetes mellitus, central retinal vein occlusion, and uveitis. The electron microscopic findings explain the functional incompetence of rubeotic vessels that are manifested by transmural leakage of fluorescein.
 ...
PMID:Rubeosis iridis and glaucoma associated with sickle cell retinopathy: a light and electron microscopic study. 74 Mar 65

Hemoglobin A1c is one of the minor components of normal human hemoglobin. It differs from Hb A by the presence of one molecule of glucose fixed to the N-terminal extremity of every beta chain. It is synthesized from Hb A by a very slow and only slightly reversible mechanism which continuously occurs during the 120 days of the red cell life. Hb A1c represents nearly 5% of total hemoglobin of the normal subject. In patients suffering of diabetes mellitus, its level seems to reflect closely the degree of equilibrium of the disease for 4 to 5 weeks which preceeded the evaluation.
 ...
PMID:[Hemoglobin A1c: a new factor in the supervision of diabetes (author's transl)]. 74 62

Although diet therapy is a concept of the twentieth century, its foundations were laid by such men as Sanctorius in the sixteenth century, Lavoisier in the eighteenth century, and Beaumont in the nineteenth century, whose detailed notes reflected amazingly accurate observations. With the advent of scientific medicine, research provided the knowledge on which diet therapy was built. Data on food composition, which began to be available around the turn of the century, was important to the therapeutic dietitian, and, at mid-century, formed the basis for the development of the first Exchange Lists (only revised this year). Diets early in the century involved rigid routines, in contrast with the trend today to consider the individual. World War I marked the emergence of the trained dietitian and changes in diet therapy, as knowledge of the biologic sciences and the practice of medium expanded. Research on metabolism led to control of hemoglobin and the red cell anemias, while growing knowledge of the role of pancreatic secretions in metabolism made near-normal lives possible for those with diabetes. The dietitian today finds herself in the position of interpreter of scientific findings, developing meal patterns which not only correct poor food habits but are acceptable to patients. More recently, she has been concerned with problems in modification of fat intake in the interest of possible prevention of cardiovascular disease. Obesity and its prevention remain problems. The practice of diet therapy is subject to vogues, as is science, but the challenge to the dietitian remains: that of serving each patient through the best possible use of her education, skill, and sensitivity.
 ...
PMID:Diet therapy in the U.S. in the past 200 years. A Bicentennial study. 78 38


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>