Glycated hemoglobin. Reaction and biokinetic studies. Clinical application of hemoglobin A1c in the assessment of metabolic control in children with diabetes mellitus.

The introduction briefly describes the necessity of maintaining a good metabolic control in children with diabetes mellitus. Thereupon, the object of the study is defined, viz. the wish to elucidate glycation of hemoglobin by means of reaction and biokinetic studies and to evaluate the applicability of the glycated hemoglobin fraction HbA1c in the clinical control of children with diabetes mellitus. In the subsequent historical section the most important studies on glycated hemoglobin are reviewed, with a particular view to the formation of this hemoglobin fraction and its clinical applicability. A brief description follows of the pathway in which hemoglobin A, via condensation with glucose, first forms a labile intermediate adduct, designated HbA1d, which is thereafter rearranged to the more stable HbA1c form. The methods used for determining glycated hemoglobin are described and their specificity assessed. In addition, an account is given of the reasons for choosing isoelectric focusing for a further elucidation of the glycation of hemoglobin. Among the results of the present studies it may be mentioned that by using the method of isoelectric focusing for separation of hemoglobin it is possible to: separate HbA1d and HbA1c and to determine the rate and equilibrium constants for the formation and dissociation of these glycated hemoglobin fractions; calculate, by the use of a biokinetic model, that HbA1c reflects the mean blood glucose concentration of the preceding 4 weeks; ascertain that HbA1c is preferable to HbA1 as a parameter for assessing the glycemic control; demonstrate that in children with newly diagnosed diabetes mellitus HbA1c is a useful index for defining the start and cessation of the remission period and for predicting the length of this period; demonstrate that HbA1c in children with diabetes mellitus is positively correlated to the clinical control and negatively correlated to linear growth; demonstrate a seasonal variation in the HbA1c substance fraction which shows the lowest level in the months of June and July; demonstrate that the transport of glucose across the erythrocyte membrane in children with diabetes mellitus is not notably affected by the glycemic control. The final section deals with the possibility whether glycation of hemoglobin and of other proteins can be a contributory cause of long-term diabetic complications.