Summary
This study was designed to examine the appearance and disappearance kinetics of glycosylated haemoglobin during abrupt changes of blood glucose in the rat. The concentration of the fast haemoglobin component, which has similar chromatographic and electrophoretic profiles to human haemoglobin A1, was measured after the induction of diabetes by streptozotocin and its cure by syngeneic intraportal islet transplantation. Fast haemoglobin was increased in 12 diabetic rats compared with 22 controls(15.8±0.8 versus 8.2±0.3%, mean ± SEM). In a group with mild diabetes (n= 8, blood glucose < 22 mmol/l), fast haemoglobin rose to 13.7±1.0% by week 8. In a group with severe diabetes (n=4, blood glucose > 22 mmol/l), fast haemoglobin rose more quickly (in 3 weeks) to a higher level (18.2±3.3%) and changed little thereafter. This suggests a saturable system in which the rate of increase and final value depend upon the degree of hyperglycaemia. After islet transplantation, fast haemoglobin returned to normal in 4 weeks (n=5, 17.6±1.4 to 9.4±0.9%). This delay is shorter than expected from the red cell lifespan (around 60 days), suggesting that haemoglobin glycosylation may be partly reversible. These results suggest that in unstable diabetes the interpretation of haemoglobin A1 levels is not as simple as was supposed previously.
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Beccaria L, Chiumello G, Gianazza E, Lippis B, Righetti PG (1978) Haemoglobin A1c repartition by isoelectric focussing. Am J Hematol 4: 367–374
Bunn HF, Haney DN, Kamin S, Gabbay KH, Gallop PH (1976) The biosynthesis of human haemoglobin A1c: slow glycosylation of haemoglobin in vitro. J Clin Invest 57: 1652–1659
Ditzel J, Kjaergaard JJ (1978) Haemoglobin A1c concentrations after initial insulin treatment for newly discovered diabetes. Br Med J 1: 741–742
Dunn PJ, Firoozabadi H, Cole RA, Younger D, Graham CA, Gleason RE, Soeldner JS (1978) Relative influence of remote and proximal glycaemic events on glycosylated haemoglobin %. Diabetes 27: 434 (Abstract)
Fizgibbons JF, Koler RD, Jones RT (1976) Red cell age-related changes of haemoglobin A1a+b and A1c in normal and diabetic subjects. J Clin Invest 58: 820–824
Fluckiger R, Winterhalter KH (1976) In vitro synthesis of haemoglobin A1c. FEBS Lett 71: 356–360
Gabbay KH, Hasty K, Breslow JL, Ellison RC, Bunn HF, Gallop PM (1977) Glycosylated haemoglobins and longterm blood glucose control in diabetes mellitus. J Clin Endocrinol Metab 44: 859–864
Ganzoni AM (1970) Kinetik und Regulation der Erythrocyten-Produktion. Springer, Berlin Heidelberg New-York
Gonen B, Rubenstein AH (1978) Haemoglobin A1 and diabetes mellitus. Diabetologia 15: 1–8
Graf RJ, Halter JB, Porte D (1978) Glycosylated haemoglobin in normal subjects and subjects with maturity onset-diabetes. Evidence for saturable system in man. Diabetes 27: 834–839
Junod A, Lambert AE, Stauffacher W, Renold AE (1969) Diabetogenic action of streptozotocin: relationship of dose to metabolic response. J Clin Invest 48: 2129–2139
Katsilambros N, Rahman YA, Hinz M (1970) Action of streptozotocin on insulin and glucagon responses of rat islet. Horm Metab Res 2: 268–270
Kemp CB, Knight MJ, Scharp DW, Lacy PE, Ballinger WF (1973) Transplantation of isolated pancreatic islets into the portal vein of diabetic rats. Nature 244: 447–448
Koenig RJ, Cerami A (1975) Synthesis of minor haemoglobin in normal and diabetic mice: A potential model of basement membrane thickening. Proc Natl Acad Sci USA 72: 3 687–3 691
Koenig RJ, Araujo DC, Cerami A (1976) Increased haemoglobin A1c in diabetic mice Diabetes 25: 1–5
Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A (1976) Correlation of glucose regulation and haemoglobin A1c in diabetes mellitus. N Engl J Med 295: 417–420
Lacy PE, Kostianowsky M (1967) Method for the isolation of intact islets of Langerhans from rat pancreas. Diabetes 16: 35–39
Mauer SM, Sutherland DER, Steffes MW, Leonard RJ, Najarian JS, Michael AF, Brown DM (1974) Pancreatic transplantation. Effects on the glomerular lesions of experimental diabetes in the rat. Diabetes 23: 748–753
Paulsen EP, Koury M (1977) Haemoglobin A1c level in insulindependent and independent diabetes mellitus. Diabetes 26: 890–896
Pipeleers-Marichal MA, Pipeleers DC, Cutler J, Lacy PE, Kipnis DM (1976) Metabolic and morphologic studies in intraportal-islet-transplantedrats. Diabetes 25: 1041–1051
Rahbar S, Blumenfeld O, Ranney HM (1969) Studies of an unusual haemoglobin in patients with diabetes mellitus. Biochem Biophys Res Commun 36: 838–843
Schalm OW (1965) Veterinary hematology. Lea Lebiger, Philadelphia
Schnatz JD, Formaniak JM, Chlouverakis C (1972) The origin of hypertriglyceridaemia in streptozotocin diabetics rats. Diabetologia 8: 125–130
Spicer KM, Allen RC, Hallet D, Buse MG (1979) Synthesis of haemoglobin A1c and related minor haemoglobin by erythrocytes: in vitro study of regulation. J Clin Invest 64: 40–48
Steffes MW, Sutherland DER, Mauer SM, Leonard RJ, Najarian JS, Brown DM (1975) Plasma insulin and glucose levels in diabetic rats prior to and following islet transplantation. J Lab Clin Med 85: 75–81
Svendsen PAA, Christiansen JS, Søegaard U, Welinder BS, Nerup J (1980) Rapid changes in chromatographically determined haemoglobin A1c induced by short-term changes in glucose concentration. Diabetologia 19: 130–136
Trivelli LA, Ranney HM, Lai HT (1971) Haemoglobin components in patients with diabetes mellitus. N Engl J Med 284: 353–357
Vague PH, Vovan L, Vialettes B, Boustiere C, Serin N (1979) Concentration sanguine en hémoglobine glycosylée (A1c), indice du contrôle du diabète dans le mois précédent. Nouv Presse Med 8: 491–494
Vialettes B, Sutherland DER, Matas AJ, Payne WD, Najarian JS (1979) Amelioration of streptozotocin induced diabetes in rats. Effect of islet isografts on plasma lipids and other metabolic abnormalities. Metabolism 28: 489–494
Ziegler MN, Reckard CR, Barker CF (1974) Long term metabolic and immunological consideration in transplantation of pancreatic islets. J Surg Res 16: 575–581
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Vialettes, B., Vovan, L., Simon, M.C. et al. Kinetics of fast haemoglobin in diabetic rats. Diabetologia 22, 264–268 (1982). https://doi.org/10.1007/BF00281303
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DOI: https://doi.org/10.1007/BF00281303