Summary
Estimations of HbA1 levels have been used to assess long-term glycaemic control in spontaneously diabetic BB/E rats. The degree of metabolic control achieved by once daily insulin injections and continuous insulin infusion by osmotic minipump was compared. Citrate gel electrophoresis of lysed erythrocytes, previously washed and incubated in 0.9% NaCl, gave accurate HbA1 values without interference from either abnormal Hb variants or labile glycosylation products. Over a 12 week period there was no significant difference in the mean random weekly plasma glucose concentrations between diabetic rats maintained on insulin injections or continuous infusion therapy. The HbA1 values in the injection-treated animals remained unchanged throughout the study period (mean±SEM = 5.1±0.1%). Diabetic rats treated by osmotic minipump showed a steady decline in values over the same period (4.1±0.1%; p<0.001 vs injected rats) but levels remained higher than those recorded in non-diabetic control rats (2.9±0.01%; p<0.001 vs pump-treated rats). These differences in HbA1 were reflected in the plasma glucose values obtained during a 30 h glucose profile performed after six weeks of insulin therapy. Diabetic rats on injection therapy showed considerable diurnal variation in plasma glucose concentration (5.5–11.2 mmol/l; mean 8.9±0.5) but continuous insulin infusion eliminated the fluctuations giving a significantly lower mean glucose level over the 30 h period (7.3±0.1 mmol/l; p<0.005). HbA1 levels show a poor correlation with random plasma glucose estimations (r=0.43) but provide a simple and accurate assessment of long-term glycaemic control without the need for multiple 24 h glucose profiles.
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References
Marliss EB, Nakhooda AF, Poussier P, Sima AAF (1982) The diabetic syndrome of the BB Wistar rat: possible relevance to Type 1 (insulin-dependent) diabetes in man. Diabetologia 22: 225–232
Nakhooda AF, Like AA, Chappel CJ, Murray FT, Marliss EB (1977) The spontaneously diabetic Wistar rat. Metabolic and morphologic studies. Diabetes 26: 100–112
Burrin JM, Baird JD, Brown D, Smith W, Bone AJ (1986) Metabolic profiles throughout the life of the spontaneously diabetic insulin-dependent BB/E rat. Diab Med 3: 252 (Abstract)
Sima AAF (1983) The development and structural characterisation of the neuropathies in the spontaneously diabetic BB Wistar rat. Metabolism 32 [Suppl 1]: 106–111
Sima AAF, Garcia-Salinas R, Basu PK (1983) The BB Wistar rat: an experimental model for the study of diabetic retinopathy. Metabolism 32 [Suppl 1]: 136–140
Brown DM, Steffes MW, Thibert P, Ajar S, Maver SM (1983) Glomerular manifestations of diabetes in the BB rat. Metabolism 32 [Suppl 1]: 131–135
Gabbay KH, Haney DN, Hasty K, Gallop PM, Bunn HF (1976) Glycosylation of haemoglobin in vivo: a monitor of diabetic control. Diabetes 25: 336 (Abstract)
Brooks AP, Nairn IM, Baird JD (1980) Changes in glycosylated haemoglobin after poor control in insulin-dependent diabetics. Br Med J 281: 707–710
Gruenholz A, Wood R, Rogers P, Mangiardi V (1979) Rapid quantitative determination of haemoglobin A1 using ion-exchange chromatography. Clin Chem 25: 1598–1602
Cole RA, Soeldner JS, Dunn PJ (1978) A rapid method for the determination of glycosylated haemoglobins using high pressure liquid chromatography. Metabolism 27: 289–302
Dunn PJ, Cole RA, Soeldner JS (1979) Further developments and the automation of a high pressure liquid chromatography method for the determination of glycosylated haemoglobins. Metabolism 28: 777–779
Higgins PJ, Garlick RL, Bunn HF (1982) Glycosylated haemoglobin in human and animal red cells: role of glucose permeability. Diabetes 31: 743–748
Bouriotis V, Scott J, Galloway A, Bellingham AJ, Dean PDG (1981) Measurement of glycosylated haemoglobins using affinity chromatography. Diabetologia 21: 579–580 (Letter)
Powell HC, Ivor LP, Costello ML, Wolf PL (1982) Elevated haemoglobin A1 in streptozotocin diabetic rats and in rats on sucrose and galactose-enriched diets. Clin Biochem 15: 133–137
Gould BJ, Flatt PR, Kotehca S, Collett S, Swanston-Flatt SK (1986) Measurement of glycosylated haemoglobins and glycosylated plasma proteins in animal models with diabetes or inappropriate hypoglycaemia. Horm Metabol Res 18: 793–799
Service FJ, Molnar GD, Rosevear JW, Ackermann E, Gatewood LC, Taylor WF (1970) Mean amplitude of glycaemic excursions, a measure of diabetic instability. Diabetes 19: 644–655
Koenig RJ, Cerami A (1975) Synthesis of minor haemoglobins in normal and diabetic mice: a potential model of basement membrane thickening. Proc Natl Acad Sci 73: 3687–3691
Vialettes B, Vovan L, Simon MC, Lassmann V, Altomare E, Vague Ph (1982) Kinetics of fast haemoglobin in diabetic rats. Diabetologia 22: 264–268
Blanc MH, Rhie FH, Dunn PJ, Soeldner JS (1981) The determination of glycosylated haemoglobins in rats using high pressure liquid chromatography. Metabolism 30: 317–322
Nathan DM (1981) Labile glycosylated haemoglobin contributes to haemoglobin A1 as measured by liquid chromatography or electrophoresis. Clin Chem 27: 1261–1263
Gonen B, Rubenstein AH, Rochman H, Tanega SP, Horwitz DL (1977) Haemoglobin A1: an indicator of the metabolic control of diabetic patients. Lancet II: 734–736
Puukka R, Leppilampi M (1982) Electrophoretically determined haemoglobin A1 concentrations during short-term changes in glucose concentration. Ann Clin Biochem 19: 350–353
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Tames, F.J., Baird, J.D. & Bone, A.J. HbA1 in assessment of metabolic control in diabetic BB/E rats. Diabetologia 33, 257–261 (1990). https://doi.org/10.1007/BF00403317
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DOI: https://doi.org/10.1007/BF00403317