Hb AIc Research Articles

Determination of the glycosylated hemoglobins (HB AI) with a new microcolumn procedure. Suitability of the technique for assessing the clinical management of diabetes mellitus.

Fifty-seven children who attended a diabetes camp were divided into five groups on the basis of retrospective evaluation of the management of their diabetes mellitus over the previous three or more months. Shortly after their arrival at camp, fasting blood samples were obtained for the measurement of glucose and the quantitation of Hb AI and for hemoglobin typing. Samples were obtained from 12 normal (nondiabetic) camp personnel at the same time. The Hb AI components were measured by the “macrocolumn” procedure of Trivelli et al., by the colorimetric procedure of Flukinger and Winterhalter, and by a new microcolumn procedure employing columns and reagents provided by Isolab, Inc. As might be expected from a number of previous reports by other investigators, there was no significant correlation of the percentage of Hb AI with single fasting blood sugar values. Hb AI tended to decrease as the management of diabetes became more adequate according to clinical ratings. Comparison of the Hb AI (Hb AIa+b+c) determinations showed an acceptable correlation of percentages obtained by the relatively laborious macrocolumn procedure and the more facile microcolumn procedure, indicating that the latter would be clinically useful. Values of Hb AIc obtained by the colorimetric procedure, which has been proposed as a procedure suitable for the clinical laboratory, did not correlate well with Hb AIc values determined by the macrocolumn technique, nor did these show as good an inverse relationship to the ratings of the management of diabetes.

223 GLYCOHEMOGLOBIN (Hb AIc): CORRELATION WITH MATERIAL BLOOD GLUCOSE CONTROL IN PREGNANCY

Hemoglobin AIc (Hb AIc), the glycosylated form (β-chain) of Hb A, normally comprises <6% of total hemoglobin, but has been found by us previously in third trimester diabetic pregnancy to be elevated (7-10%) and to correlate with infant birth weight. In contrast, non-pregnant uncontrolled diabetics have glycohemoglobin levels which may be 8-15% and may represent the integrated mean blood glucose level over the previous weeks and months. Since fetal size in infants of diabetic mothers has been related to maternal third trimester blood glucose control, we examined the relationship between third trimester maternal Hb AIc and maternal blood glucose control. Twelve diabetic women without evidence of vascular disease and with singleton births had Hb AIc levels determined in their third trimester using Amberlite cation exchange chromatography. Mean random blood glucose values (n=5-32) for each subject were determined for the twelve week period prior to Hb AIc measurement. Hb AIc correlated significantly with mean random blood glucose (r=0.84, p <0.01) as well as birth weight corrected for gestational age (r=0.78, p <0.01). In eight of these same women who required insulin, Hb AIc was determined serially 5-8 months postpartum. Seven of eight had higher Hb AIc levels postpartum (6.0±0.5 vs 8.4±0.6, M±SEM) at a time when glucose management was not accomplished. We speculate that lower levels of Hb AIc later in diabetic pregnancy are due to better blood glucose control during this period.

Haemoglobin AIc concentrations after initial insulin treatment for newly discovered diabetes.

Glycosylated haemoglobins AIa+Ib and AIc were measured serially in 10 consecutive cases of newly discovered non-acidotic diabetes before and after diet and insulin treatment. The average concentration of Hb AIc was 11.4% in untreated diabetics as compared with 4.3% in healthy controls. With prolonged optimal regulation of blood glucose Hb AIc slowly decreased to a mean concentration of 5.5%. The concentration of Hb AIc was significantly correlated with the fasting blood sugar value. The findings suggest that determining Hb AIc may give valuable information on the regulation of carbohydrate metabolism in the preceding one to two months and thus become an important aid to management.

Correlation of serum triglyceride levels and hemoglobin AIc concentrations in diabetes mellitus.

Studies in 10 nonketotic diabetic subjects (five juvenile- and five adult-onset) before and after control of carbohydrate metabolism showed a high degree of correlation between hemoglobin AIc (HbAIc) concentrations and serum triglyceride levels. Serum triglyceride levels were found to correlate more closely with Hb AIc (r = 0.91, p less than 0.001) than did serum cholesterol (r = 0.47, p greater than 0.05), thus indicating a more direct relationship to carbohydrate metabolism.

EFFECTS OF PREGNANCY ON HEMOGLOBIN AIc IN NORMAL GESTATIONAL DIABETIC AND DIABETIC WOMEN

Hemoglobin AIc, a normal minor hemoglobin, has glucose linked by a Schiff base to the N-terminal end of the beta chain. The glucose interferes with the binding of 2,3 diphosphoglycerate, probably resulting in an increased affinity of that hemoglobin for oxygen. Hb AIc is increased to twice normal levels in juvenile-onset (insulin-dependent) diabetes. In the present studies, the Hb AIc, when expressed as per cent of total hemoglobin, was found to be elevated slightly in pregnany normal (m = 6.97 per cent), pregnant nondiabetic obese (m = 6.89 per cent), and gestationally diabetic subjects (m = 8.77 per cent) above that of normal females (m = 5.68 per cent). A remarkable difference was observed between the nonpregnant diabetics (m = 12.77 per cent) and the pregnant diabetics (m = 8.46 per cent). This decrease in the level of Hb AIc in diabetics who are pregnant more than 30 weeks may reflect either a better state of diabetic control and/or a compensatory mechanism to protect the fetus by facilitating oxygen exchange from mother to fetus.

Effects of Pregnancy on Hemoglobin AIc in Normal, Gestational Diabetic, and Diabetic Women

Hemoglobin AIc, a normal minor hemoglobin, has glucose linked by a Schiff base to the N-terminal end of the beta chain. The glucose interferes with the binding of 2,3 diphosphoglycerate, probably resulting in an increased affinity of that hemoglobin for oxygen. Hb AIc is increased to twice normal levels in juvenile-onset (insulin-dependent) diabetes. In the present studies, the Hb AIc, when expressed as per cent of total hemoglobin, was found to be elevated slightly in pregnany normal (m = 6.97 per cent), pregnant nondiabetic obese (m = 6.89 per cent), and gestationally diabetic subjects (m = 8.77 per cent) above that of normal females (m = 5.68 per cent). A remarkable difference was observed between the nonpregnant diabetics (m = 12.77 per cent) and the pregnant diabetics (m = 8.46 per cent). This decrease in the level of Hb AIc in diabetics who are pregnant more than 30 weeks may reflect either a better state of diabetic control and/or a compensatory mechanism to protect the fetus by facilitating oxygen exchange from mother to fetus.

Red cell age-related changes of hemoglobins AIa+b and AIc in normal and diabetic subjects.

The minor hemoglobin components, hemoglobin AIa+b and hemoglobin AIc, were measured in the 10% youngest and 10% oldest erythrocytes of 15 normal and 14 diabetic subjects. Erythrocyte fractions were obtained by centrifugation in isopyknic concentrations of dextran: 28.5% of 40,000-mol wt dextran yeilded the 10% lightest of young cells, and 30.5% dextran provided the 10% heaviest or old erythrocytes. Both normal and diabetic erythrocytes contain increased amounts of Hb AIa+b and Hb AIc in old as compared to young cells. In normal subjects, young cells contained 1.2+/-0.2%, and old cells contained 1.8+/-0.4% Hb AIa+b. Corresponding values for diabetic cells were 1.7+/-0.6 and 2.6+/-0.9%. Hb AIc increased from 3.1+/-0.8 to 6.0+/-1.1% in normals and from 5.1+/-2.1 to 10.1+/-3.7% in diabetics. The results indicate that both cell age and diabetes are significant determinants of the amounts of Hb AIa+b and Hb AIc.

Synthesis of hemoglobin AIc in normal and diabetic mice: potential model of basement membrane thickening.

Adult diabetic mice (C57Bl/KsJ--db/db) have increased amounts of a minor hemoglobin in their peripheral blood compared to wild-type (+/+) mice. This increase is analogous to the 2-fold increase of a glycohemoglobin with similar chromatographic mobility (Hb AIc) seen in the blood of patients with diabetes mellitus. Although the exact chemical nature of human or mouse Hb AIc is unknown, both contain a sodium-borohydride-reducible linkage on the beta chain which is a presumed Schiff base between a sugar moiety and the protein. The db/db animals, which have normal amounts of mouse Hb AIc at weaning, show the increase approximately 4 weeks after the onset of the signs of diabetes. This rise is brought about by an increase in a circulating factor that determines directly or indirectly the synthesis of mouse Hb AIc as a post-synthetic modification of Hb A. Evidence for this was obtained by showing that the rate of synthesis of the modified Hb is linear for at least the first 50 days of the life of the red cell and that the rate of synthesis is dependent on the environment in which the cells circulate. Thus the rate of mouse Hb AIc synthesis in +/+ cells is greater when those cells circulate in a db/db host than when they circulate in a +/+ host. The nature of the humoral factor is unknown. If glycosylations of basement membrane proteins and hemoglobin proceed via a common mechanism, then the monitoring of Hb AIc could provide a useful model for studying the early events of basement membrane thickening.