Diabetologia

, Volume 33, Issue 4, pp 208–215

Unexplained variability of glycated haemoglobin in non-diabetic subjects not related to glycaemia

  • J. S. Yudkin
  • R. D. Forrest
  • C. A. Jackson
  • A. J. Ryle
  • S. Davie
  • B. J. Gould
Originals

Summary

We have studied levels of glycated haemoglobin in a sample of 223 people aged over 40 years without known diabetes mellitus screened in a community study. Each had a glucose tolerance test and glycated haemoglobin measured by four methods — agar gel electrophoresis with and without removal of Schiff base, affinity chromatography and isoelectric focusing. The correlation coefficients between 2 h blood glucose and levels of glycated haemoglobin were between 0.43 and 0.64. This poor correlation was not explained on the basis of assay or biological variability of either 2 h blood glucose or glycated haemoglobin. Multiple regression analysis showed that other assays of glycated haemoglobin contributed to the variance of any single glycated haemoglobin value by 0.1%–52.9% (median 12.8%) compared to the variance of 18.6%–41.4% (median 30.8%) explained by 2 h blood glucose alone, suggesting that in a non-diabetic population, the degree of glucose intolerance may explain only one third of the variance of glycated haemoglobin levels, but other factors operate to produce consistent changes in levels of glycated haemoglobin. Investigation of 42 subjects with consistently high (20 subjects) or low (22 subjects) levels of glycated haemoglobin relative to their 2 h blood glucose level showed no difference in age, gender, body mass index, haemoglobin levels or smoking, although 50% of low glycators had impaired glucose tolerance. Neither ambient bloodglucose levels, as estimated on two five-point blood-glucose profiles, nor dietary intake of carbohydrate, starch, sugars, fibre or alcohol, explained the difference between high and low glycators. The determinants of the consistent interindividual differences in levels of glycated haemoglobin in nondiabetic subjects remain to be determined.

Key words

Glycated haemoglobin glucose intolerance ambient blood-glucose levels dietary carbohydrate dietary fibre 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Kennedy L, Baynes JW (1984) Nonenzymatic glycosylation and the chronic complications of diabetes: an overview. Diabetologia 26: 93–98Google Scholar
  2. 2.
    Brownlee M, Vlassara H, Cerami A (1984) Nonenzymatic glycosylation and the pathogenesis of diabetic complications. Ann Int Med 101: 527–537Google Scholar
  3. 3.
    Editorial (1986) Browning and diabetic complications. Lancet I: 1192–1193Google Scholar
  4. 4.
    Koenig RJ, Peterson CM, Jones RL, Saudek C, Lehrman M, Cerami A (1976) Correlation of glucose regulation and hemoglobin A1c in diabetes mellitus. N Engl J Med 295: 417–420Google Scholar
  5. 5.
    Svendsen PA, Lauritzen T, Soegaard U, Nerup J (1982) Glycosylated haemoglobin and steady-state mean blood glucose concentration in Type 1 (insulin-dependent) diabetes. Diabetologia 23: 403–405Google Scholar
  6. 6.
    Boucher BJ, Welch SG, Beer MS (1981) Glycosylated haemoglobins in the diagnosis of diabetes mellitus and for the assessment of chronic hyperglycaemia. Diabetologia 21: 34–36Google Scholar
  7. 7.
    John WG, Richardson RW (1986) Glycosylated haemoglobin levels in patients referred for oral glucose tolerance tests. Diab Med 3: 46–48Google Scholar
  8. 8.
    Lev-Ran A, VanderLaan WP (1979) Glycohemoglobins and glucose tolerance. JAMA 241: 912–914Google Scholar
  9. 9.
    Simon D, Coignet MC, Thibult N, Senan C, Eschwege E (1985) Comparison of glycosylated hemoglobin and fasting plasma glucose with two-hour post-load plasma glucose in the detection of diabetes mellitus. Am J Epidemiol 122: 589–593Google Scholar
  10. 10.
    Forrest RD, Jackson CA, Yudkin JS (1986) Glucose intolerance and hypertension in North London. The Islington Diabetes Survey. Diab Med 3: 338–342Google Scholar
  11. 11.
    Forrest RD, Jackson CA, Yudkin JS (1987) The glycohaemoglobin assay as a screening test for diabetes mellitus. The Islington Diabetes Survey. Diab Med 4: 254–259Google Scholar
  12. 12.
    Forrest RD (1987) Screening for diabetes mellitus. Evaluation of glycohaemoglobin assays as screening tests. The Islington Diabetes Survey. MD Thesis, University of London, pp 254Google Scholar
  13. 13.
    Forrest RD, Jackson CA, Casburn-Budd M, Taylor JE, Gould BJ, Yudkin JS (1987) Short term effect of 75 g oral glucose on glycohaemoglobin levels. Ann Clin Biochem 24: 53–57Google Scholar
  14. 14.
    Forrest RD, Jackson CA, Gould BJ, Casburn-Budd M, Taylor JE, Yudkin JS (1988) Four assays of glycated hemoglobin compared as screening tests for diabetes mellitus: the Islington Diabetes Survey. Clin Chem 34: 145–148Google Scholar
  15. 15.
    Holdsworth MD, Davies L, Wilson A (1984) Simultaneous use of four methods of estimating food consumption. Hum Nutr: Appl Nutr 38A: 132–137Google Scholar
  16. 16.
    Paul AA, Southgate DAT (1978) McCance and Widdowson's The composition of foods, 4th edn. HMSO, London, pp 418Google Scholar
  17. 17.
    Southgate DAT, Paul AA, Dean AC, Christie AA (1978) Free sugars in foods. J Hum Nutr 32: 335–347Google Scholar
  18. 18.
    Englyst HN, Cummings JH (1984) Simplified method for the measurement of total non-starch polysaccharides by gas-liquid chromatography of constituent sugars as alditol acetates. Analyst 109: 937–942Google Scholar
  19. 19.
    Englyst HN, Bingham SA, Runswick SA, Collinson E, Cummings JH (1988) Dietary fibre (non-starch polysaccharides) in fruit, vegetables and nuts. J Human Nutr Dietetics 1: 247–286Google Scholar
  20. 20.
    Holman RR, Turner RC (1980) The basal plasma glucose: a simple relevant index of maturity-onset diabetes. Clin Endocrinol 14: 279–286Google Scholar
  21. 21.
    Paisey RB, Bradshaw P, Hartog M (1980) Home blood glucose concentrations in maturity-onset diabetes. Br Med J 280: 596–598Google Scholar
  22. 22.
    Pecoraro RE, Koepsell TD, Chen MS, Lipsky BA, Belcher DW, Inui TS (1986) Comparative clinical reliability of fasting plasma glucose and glycosylated hemoglobin in non-insulin-dependent diabetes mellitus. Diabetes Care 9: 365–369Google Scholar
  23. 23.
    Burrin JM, Price CP (1984) Performance of three enzymic methods for filter paper glucose determination. Ann Clin Biochem 21: 411–416Google Scholar
  24. 24.
    Menard L, Dempsey ME, Blankstein LA, Aleyassine H, Wacks M, Soeldner JS (1980) Quantitative determination of glycosylated hemoglobin A1 by agar gel electrophoresis. Clin Chem 26: 1598–1602Google Scholar
  25. 25.
    Nathan DM, Dunn BS, Francis TB (1984) Two commercial methods evaluated for eliminating the labile fraction from the assay for glycated hemoglobin (glycohemoglobin). Clin Chem 30: 109–110Google Scholar
  26. 26.
    Gould BJ, Hall PM, Cook JGH (1982) Measurement of glycosylated haemoglobins using an affinity chromatography method. Clin Chim Acta 25: 41–48Google Scholar
  27. 27.
    Mortensen HB (1980) Quantitative determination of hemoglobin A1c by thin layer iso-electric focusing. J Chromatog 182: 325–333Google Scholar
  28. 28.
    Little RR, England JD, Weidmeyer H-M, Goldstein DE (1983) Effects of whole blood storage on results for glycosylated hemoglobin as measured by ion-exchange chromatography, affinity chromatography and colorimetry. Clin Chem 29: 1113–1115Google Scholar
  29. 29.
    Forrest RD, Jackson CA, Yudkin JS (1987) The epidemiology of the haemoglobin level — a study of 1057 subjects in general practice. Postgrad Med J 63: 625–628Google Scholar
  30. 30.
    World Health Organisation Study Group on Diabetes Mellitus (1985) A Report of a WHO Study Group. Technical Report Series, No 727, WHO, GenevaGoogle Scholar
  31. 31.
    Forrest RD, Jackson CA, Yudkin JS (1988) The abbreviated glucose tolerance test in screening for diabetes: the Islington Diabetes Survey. Diab Med 5: 557–561Google Scholar
  32. 32.
    McDonald GW, Fisher GF, Burnham C (1965) Reproducibility of the oral glucose tolerance test. Diabetes 14: 473–480Google Scholar
  33. 33.
    Riccardi G, Vaccaro O, Rivellese A, Pignalosa S, Tutino L, Mancini M (1985) Reproducibility of the new diagnostic criteria for impaired glucose tolerance. Am J Epidemiol 121: 422–429Google Scholar
  34. 34.
    Forrest RD, Jackson CA, Yudkin JS (1987) Glucose tolerance and glycohaemoglobin; a population study of male-to-female ratios. Diab Med 4: 322–324Google Scholar
  35. 35.
    Stickland MH, Paton RC, Wales JK (1984) Haemoglobin A1cconcentrations in men and women with diabetes. Br Med J 289: 733Google Scholar
  36. 36.
    Jones RB, Johnston DI, Allison SP, Peacock I, Hosking DJ, Tattersall RB (1984) Haemoglobin A1c concentrations in men and women with diabetes (Letter). Br Med J 289: 1381Google Scholar
  37. 37.
    Dix D, Cohen P, Kingsley S, Senkbeil J, Sexton K (1979) Glycohemoglobin and glucose tolerance tests compared as indicators of borderline diabetes. Clin Chem 25: 877–879Google Scholar
  38. 38.
    Dods RF, Bolmey C (1979) Glycosylated hemoglobin assay and oral glucose tolerance test compared for detection of diabetes mellitus. Clin Chem 25: 764–768Google Scholar
  39. 39.
    Modan M, Meytes D, Rozeman P, Yosef SB, Sehayek E, Yosef NB, Lusky A, Halkin H (1988) Significance of high HbA1 level in normal glucose tolerance. Diabetes Care 11: 422–428Google Scholar
  40. 40.
    Gould BJ, Hall PM (1987) m-Aminophenylboronate affinity ligands distinguish between nonenzymically glycosylated proteins and glycoproteins. Clin Chim Acta 163: 225–230Google Scholar
  41. 41.
    Flückiger R, Harman W, Meier W, Loo S, Gabbay KH (1981) Hemoglobin carbamylation in uremia. N Engl J Med 304: 823–827Google Scholar
  42. 42.
    Bridges KR, Schmidt GJ, Jensen M, Cerami A, Bunn HF (1975) The acetylation of hemoglobin by aspirin in vitro and in vivo. J Clin Invest 56: 201–207Google Scholar
  43. 43.
    Eberentz-Lhomme C, Ducrocq R, Intrator S, Elion J, Nunez E, Assan R (1984) Haemoglobinopathies: a pitfall in the assessment of glycosylated haemoglobin by ion-exchange chromatography. Diabetologia 27: 596–598Google Scholar
  44. 44.
    Madsen H, Ditzel J, Hansen P, Hahnemann N, Andersen OP, Kjaergaard J-J (1981) Hemoglobin A1c determinations in diabetic pregnancy. Diabetes Care 4: 541–546Google Scholar
  45. 45.
    Starkman HS, Soeldner JS, Gleason RE (1987) Oral glucose tolerance: relationship with haemoglobin A1c. Diab Res Clin Pract 3: 343–349Google Scholar
  46. 46.
    Albutt EC, Nattrass M, Northam BE (1985) Glucose tolerance test and glycosylated haemoglobin measurement for diagnosis of diabetes mellitus — an assessment of the criteria of the WHO Expert Committee on Diabetes Mellitus. Ann Clin Biochem 22: 67–73Google Scholar
  47. 47.
    Wilkerson HLC, Hyman H, Kaufman M, McCuistion AC, Francis JO'S (1960) Diagnostic evaluation of oral glucose tolerance tests in nondiabetic subjects after various levels of carbohydrate intake. N Engl J Med 262: 1047–1053Google Scholar
  48. 48.
    Ktorza P, Baigts F, Fumeron F, Rizkalla S, Kinebanyan FM (1985) Effects of slight plasma glucose decrease on glycosylated hemoglobin in healthy subjects during caloric restriction (letter). N Engl J Med 313: 958–959Google Scholar
  49. 49.
    Brunzell JD, Lerner RI, Hazzard WR, Porte D, Bierman EL (1971) Improved glucose tolerance with high carbohydrate feeding in mild diabetes. N Engl J Med 284: 521–524Google Scholar
  50. 50.
    Simpson RW, Mann JI, Eaton J, Moore RA, Carter R, Hockaday TDR (1979) Improved glucose control in maturity-onset diabetes treated with high-carbohydrate-modified fat diet. Br Med J 1: 1753–1756Google Scholar
  51. 51.
    Shepard DC, Hitz JB, Dain JA (1985) Pyridoxal 5′-phosphate inhibits nonenzymatic glycosylation of proteins. Biochem Arch 1: 143–151Google Scholar
  52. 52.
    Štolba P, Hátle K, Krnáková A, Strěda M, Stárka L (1987) Effects of ascorbic acid on nonenzymatic glycation of serum proteins in vitro and in vivo. Diabetologia 30: 585 (Abstract)Google Scholar
  53. 53.
    Burke BS (1947) The dietary history as a tool in research. J Am Diet Assn 23: 1041–1046Google Scholar
  54. 54.
    James WPT, Bingham SA, Cole TJ (1980) Epidemiological assessment of dietary intake. Nutr Cancer 2: 203–212Google Scholar
  55. 55.
    Elliott P, Forrest RD, Jackson CA, Yudkin JS (1988) Sodium and blood pressure: positive associations in a North London population with consideration of the methodological problems of within-population surveys. J Hum Hypertens 2: 89–95Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • J. S. Yudkin
    • 1
  • R. D. Forrest
    • 4
  • C. A. Jackson
    • 1
  • A. J. Ryle
    • 2
  • S. Davie
    • 3
  • B. J. Gould
    • 3
  1. 1.Academic Unit of Diabetes and Endocrinology, Department of MedicineUniversity College and Middlesex School of Medicine, Whittington HospitalLondon
  2. 2.Department of Nutrition and DieteticsWhittington HospitalLondon
  3. 3.Department of BiochemistryUniversity of SurreyGuildfordUK
  4. 4.Department of Clinical ChemistryBodenSweden

Personalised recommendations