Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Estimation of blood glucose control in diabetes mellitus

David K McCulloch, MD
Section Editors
David M Nathan, MD
Joseph I Wolfsdorf, MB, BCh
Deputy Editor
Jean E Mulder, MD


The demonstration that the development of microvascular complications in patients with type 1 diabetes can be slowed by treating hyperglycemia has led to increased use of intensive insulin regimens to attain strict glycemic control (figure 1 and figure 2) [1-3]. The efficacy of these regimens requires an accurate method to estimate the degree to which this is achieved. It is helpful to first review some basic concepts before discussing the utility of measurements of glycated hemoglobin (A1C) and serum fructosamine to assess glycemic control.

There are three useful measurements for defining glycemic control:

The mean blood glucose concentration has often been measured in clinical trials as the mean of values obtained before breakfast, mid-morning, before lunch, mid-afternoon, before dinner, and before sleep each day. Clinically, this can be replaced with or supplemented by the more simple measurement of A1C. In some cases, however, there is a disparity between the A1C values and mean blood glucose values. (See 'Recommendations in type 1 diabetes' below.)

The degree to which blood glucose concentrations fluctuate within the same day can be formally measured as the mean amplitude of glycemic excursions [4].

The degree to which blood glucose concentrations fluctuate from day to day can be formally measured as the mean of daily differences [5].


Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Sep 2016. | This topic last updated: Sep 15, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
  1. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 1993; 329:977.
  2. Wang PH, Lau J, Chalmers TC. Meta-analysis of effects of intensive blood-glucose control on late complications of type I diabetes. Lancet 1993; 341:1306.
  3. Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med 1993; 329:304.
  4. Service FJ, Molnar GD, Rosevear JW, et al. Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 1970; 19:644.
  5. Molnar GD, Taylor WF, Ho MM. Day-to-day variation of continuously monitored glycaemia: a further measure of diabetic instability. Diabetologia 1972; 8:342.
  6. Bunn HF, Haney DN, Gabbay KH, Gallop PM. Further identification of the nature and linkage of the carbohydrate in hemoglobin A1c. Biochem Biophys Res Commun 1975; 67:103.
  7. Nathan DM, Singer DE, Hurxthal K, Goodson JD. The clinical information value of the glycosylated hemoglobin assay. N Engl J Med 1984; 310:341.
  8. Goldstein DE. Is glycosylated hemoglobin clinically useful? N Engl J Med 1984; 310:384.
  9. Rohlfing CL, Wiedmeyer HM, Little RR, et al. Defining the relationship between plasma glucose and HbA(1c): analysis of glucose profiles and HbA(1c) in the Diabetes Control and Complications Trial. Diabetes Care 2002; 25:275.
  10. Svendsen PA, Lauritzen T, Søegaard U, Nerup J. Glycosylated haemoglobin and steady-state mean blood glucose concentration in Type 1 (insulin-dependent) diabetes. Diabetologia 1982; 23:403.
  11. Nathan DM, Turgeon H, Regan S. Relationship between glycated haemoglobin levels and mean glucose levels over time. Diabetologia 2007; 50:2239.
  12. Nathan DM, Kuenen J, Borg R, et al. Translating the A1C assay into estimated average glucose values. Diabetes Care 2008; 31:1473.
  13. Little RR, Wiedmeyer HM, England JD, et al. Interlaboratory comparison of glycohemoglobin results: College of American Pathologists Survey data. Clin Chem 1991; 37:1725.
  14. Steffes MW, Sacks DB. Measurement of circulating glucose concentrations: the time is now for consistency among methods and types of samples. Clin Chem 2005; 51:1569.
  15. Hanas R, John G, International HBA1c Consensus Committee. 2010 consensus statement on the worldwide standardization of the hemoglobin A1C measurement. Diabetes Care 2010; 33:1903.
  16. National Glycohemoglobin Standardization Program (NGSP) website, which contains up to date information about substances that interfere with glycohemoglobin (HbA1c) test results. http://www.ngsp.org (Accessed on November 04, 2011).
  17. Panzer S, Kronik G, Lechner K, et al. Glycosylated hemoglobins (GHb): an index of red cell survival. Blood 1982; 59:1348.
  18. Polgreen PM, Putz D, Stapleton JT. Inaccurate glycosylated hemoglobin A1C measurements in human immunodeficiency virus-positive patients with diabetes mellitus. Clin Infect Dis 2003; 37:e53.
  19. Brown JN, Kemp DW, Brice KR. Class effect of erythropoietin therapy on hemoglobin A(1c) in a patient with diabetes mellitus and chronic kidney disease not undergoing hemodialysis. Pharmacotherapy 2009; 29:468.
  20. Ng JM, Cooke M, Bhandari S, et al. The effect of iron and erythropoietin treatment on the A1C of patients with diabetes and chronic kidney disease. Diabetes Care 2010; 33:2310.
  21. Roberts WL, Safar-Pour S, De BK, et al. Effects of hemoglobin C and S traits on glycohemoglobin measurements by eleven methods. Clin Chem 2005; 51:776.
  22. Saaddine JB, Fagot-Campagna A, Rolka D, et al. Distribution of HbA(1c) levels for children and young adults in the U.S.: Third National Health and Nutrition Examination Survey. Diabetes Care 2002; 25:1326.
  23. Herman WH, Ma Y, Uwaifo G, et al. Differences in A1C by race and ethnicity among patients with impaired glucose tolerance in the Diabetes Prevention Program. Diabetes Care 2007; 30:2453.
  24. Herman WH, Dungan KM, Wolffenbuttel BH, et al. Racial and ethnic differences in mean plasma glucose, hemoglobin A1c, and 1,5-anhydroglucitol in over 2000 patients with type 2 diabetes. J Clin Endocrinol Metab 2009; 94:1689.
  25. Selvin E, Steffes MW, Ballantyne CM, et al. Racial differences in glycemic markers: a cross-sectional analysis of community-based data. Ann Intern Med 2011; 154:303.
  26. Herman WH, Cohen RM. Racial and ethnic differences in the relationship between HbA1c and blood glucose: implications for the diagnosis of diabetes. J Clin Endocrinol Metab 2012; 97:1067.
  27. Ziemer DC, Kolm P, Weintraub WS, et al. Glucose-independent, black-white differences in hemoglobin A1c levels: a cross-sectional analysis of 2 studies. Ann Intern Med 2010; 152:770.
  28. Selvin E, Steffes MW, Zhu H, et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N Engl J Med 2010; 362:800.
  29. Tsugawa Y, Mukamal KJ, Davis RB, et al. Should the hemoglobin A1c diagnostic cutoff differ between blacks and whites? A cross-sectional study. Ann Intern Med 2012; 157:153.
  30. Selvin E, Ning Y, Steffes MW, et al. Glycated hemoglobin and the risk of kidney disease and retinopathy in adults with and without diabetes. Diabetes 2011; 60:298.
  31. Bower JK, Brancati FL, Selvin E. No ethnic differences in the association of glycated hemoglobin with retinopathy: the national health and nutrition examination survey 2005-2008. Diabetes Care 2013; 36:569.
  32. Cohen RM, Holmes YR, Chenier TC, Joiner CH. Discordance between HbA1c and fructosamine: evidence for a glycosylation gap and its relation to diabetic nephropathy. Diabetes Care 2003; 26:163.
  33. Cohen RM, Franco RS, Khera PK, et al. Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c. Blood 2008; 112:4284.
  34. Armbruster DA. Fructosamine: structure, analysis, and clinical usefulness. Clin Chem 1987; 33:2153.
  35. Vlassara H. Protein glycation in the kidney: role in diabetes and aging. Kidney Int 1996; 49:1795.
  36. Baker JR, Metcalf PA, Holdaway IM, Johnson RN. Serum fructosamine concentration as measure of blood glucose control in type I (insulin dependent) diabetes mellitus. Br Med J (Clin Res Ed) 1985; 290:352.
  37. Pandya HC, Livingstone S, Colgan ME, et al. Serum fructosamine as an index of glycaemia: Comparison with glycated haemoglobin in diabetic and non-diabetic individuals. Pract Diabetes 1987; 4:126.
  38. Narbonne H, Renacco E, Pradel V, et al. Can fructosamine be a surrogate for HbA(1c) in evaluating the achievement of therapeutic goals in diabetes? Diabetes Metab 2001; 27:598.
  39. Howey JE, Bennet WM, Browning MC, et al. Clinical utility of assays of glycosylated haemoglobin and serum fructosamine compared: use of data on biological variation. Diabet Med 1989; 6:793.
  40. Howey JE, Browning MC, Fraser CG. Assay of serum fructosamine that minimizes standardization and matrix problems: use to assess components of biological variation. Clin Chem 1987; 33:269.
  41. Ashby JP, Frier BM. Is serum fructosamine a clinically useful test? Diabet Med 1988; 5:118.
  42. Kilpatrick ES, Rigby AS, Atkin SL. The effect of glucose variability on the risk of microvascular complications in type 1 diabetes. Diabetes Care 2006; 29:1486.
  43. Kishimoto M, Yamasaki Y, Kubota M, et al. 1,5-Anhydro-D-glucitol evaluates daily glycemic excursions in well-controlled NIDDM. Diabetes Care 1995; 18:1156.
  44. McGill JB, Cole TG, Nowatzke W, et al. Circulating 1,5-anhydroglucitol levels in adult patients with diabetes reflect longitudinal changes of glycemia: a U.S. trial of the GlycoMark assay. Diabetes Care 2004; 27:1859.
  45. Dungan KM, Buse JB, Largay J, et al. 1,5-anhydroglucitol and postprandial hyperglycemia as measured by continuous glucose monitoring system in moderately controlled patients with diabetes. Diabetes Care 2006; 29:1214.
  46. Buse JB, Freeman JL, Edelman SV, et al. Serum 1,5-anhydroglucitol (GlycoMark ): a short-term glycemic marker. Diabetes Technol Ther 2003; 5:355.
  47. Dungan KM. 1,5-anhydroglucitol (GlycoMark) as a marker of short-term glycemic control and glycemic excursions. Expert Rev Mol Diagn 2008; 8:9.
  48. Stettler C, Stahl M, Allemann S, et al. Association of 1,5-anhydroglucitol and 2-h postprandial blood glucose in type 2 diabetic patients. Diabetes Care 2008; 31:1534.
  49. Howey DC, Bowsher RR, Brunelle RL, Woodworth JR. [Lys(B28), Pro(B29)]-human insulin. A rapidly absorbed analogue of human insulin. Diabetes 1994; 43:396.
  50. Howe-Davies S, Simpson RW, Turner RC. Control of maturity-onset diabetes by monitoring fasting blood glucose and body weight. Diabetes Care 1980; 3:607.
  51. Avignon A, Radauceanu A, Monnier L. Nonfasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. Diabetes Care 1997; 20:1822.
  52. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998; 352:837.
  53. Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359:1577.
  54. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008; 358:2545.
  55. ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008; 358:2560.
  56. ACCORD Study Group, ACCORD Eye Study Group, Chew EY, et al. Effects of medical therapies on retinopathy progression in type 2 diabetes. N Engl J Med 2010; 363:233.
  57. Ismail-Beigi F, Craven T, Banerji MA, et al. Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 2010; 376:419.
  58. Beulens JW, Patel A, Vingerling JR, et al. Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial. Diabetologia 2009; 52:2027.
  59. Cagliero E, Levina EV, Nathan DM. Immediate feedback of HbA1c levels improves glycemic control in type 1 and insulin-treated type 2 diabetic patients. Diabetes Care 1999; 22:1785.
  60. Thaler LM, Ziemer DC, Gallina DL, et al. Diabetes in urban African-Americans. XVII. Availability of rapid HbA1c measurements enhances clinical decision-making. Diabetes Care 1999; 22:1415.
  61. Agus MS, Alexander JL, Wolfsdorf JI. Utility of immediate hemoglobin A1c in children with type I diabetes mellitus. Pediatr Diabetes 2010; 11:450.