Hemoglobin A_Ic in the Glucose-intolerant, Streptozotocin-treated or Pancreatectomized Macaque Monkey

Hemoglobin A_Ic (Hb A_Ic), a glycosylated minor variant of Hb A, is elevated in diabetic patients. In our study, macaque monkey model with acquired glucose intolerance [both streptozotocin (STZ)-treated or pancreatectomized] was evaluated for the presence of Hb A_Ic and for evidence of a possible physiologic effect on oxygen-carrying capacity. Blood from 29 Macaca monkeys (27 rhesus), including 22 with carbohydrate intolerance (17 treated with STZ and five that were pancreatectomized), was analyzed for minor hemoglobins using Amberlite IRC-50 with cyanide-phosphate elution. Unlike in man, no Hb A_Ic peak was identified in any control animals. However, all five pancreatectomized animals and 10 of 17 STZ-treated animals had clearly identified peaks that eluted similarly to human A_Ic and had an increased glucose content after acid hydrolysis relative to the major Hb A peak. Of the more severely carbohydrate-intolerant animals (fasting blood sugar > 200 mg. per deciliter) that were receiving insulin, seven of eight monkeys had Hb A_Ic. peaks compared with seven of 14 animals with less severe carbohydrate intolerance (fasting blood glucose < 200 mg. per deciliter) treated without insulin. During pregnancy, none of the seven STZ-treated animals had a definite peak, although one of these animals demonstrated an Hb A_Ic peak postpartum. In a group of five control and three STZ-treated nonpregnant animals, no differences were observed in whole blood pH, PCO₂, P50, 2,3-diphosphoglycerate, adenosine triphosphate, and adenosine diphosphate, and plasma inorganic phosphate, while plasma glucose was variably elevated. The glucose-intolerant macaque model has potential for studying the long-term effects of acquired hyperglycemia, the biochemistry of the glycohemoglobin, and the possible pathophysioiogic effects of Hb A_Ic in pregnancy.