Associations Between Features of Glucose Exposure and A1C: the A1C-Derived Average Glucose (ADAG) Study

Overview

Journal Diabetes

Specialty Endocrinology

Date 2010 Apr 29

PMID 20424232

Citations 33

Authors

Rikke Borg

Judith C Kuenen

Bendix Carstensen

Hui Zheng

David M Nathan

Robert J Heine

Jorn Nerup

Knut Borch-Johnsen

Daniel R Witte

Affiliations

Soon will be listed here.

Abstract

Objective: Various methods are used to quantify postprandial glycemia or glucose variability, but few have been compared and none are standardized. Our objective was to examine the relationship among common indexes of postprandial glycemia, overall hyperglycemia, glucose variability, and A1C using detailed glucose measures obtained during everyday life and to study which blood glucose values of the day provide the strongest prediction of A1C.

Research Design And Methods: In the A1C-Derived Average Glucose (ADAG) study, glucose levels were monitored in 507 participants (268 type 1 diabetic, 159 type 2 diabetic, and 80 nondiabetic subjects) with continuous glucose monitoring (CGM) and frequent self-monitoring of blood glucose (SMBG) during 16 weeks. We calculated several indexes of glycemia and analyzed their intercorrelations. The association between glucose measurements at different times of the day (pre- and postprandial) and A1C was examined using multiple linear regression.

Results: Indexes of glucose variability showed strong intercorrelation. Among postprandial indexes, the area under the glucose curve calculated from CGM 2 h after a meal correlated well with the 90-min SMBG postprandial measurements. Fasting blood glucose (FBG) levels were only moderately correlated with indexes of hyperglycemia and average or postprandial glucose levels. Indexes derived with SMBG strongly correlated with those from CGM. Some SMBG time points had a stronger association with A1C than others. Overall, preprandial glucose values had a stronger association with A1C than postprandial values for both diabetes types, particularly for type 2 diabetes.

Conclusions: Indexes of glucose variability and average and postprandial glycemia intercorrelate strongly within each category. Variability indexes are weakly correlated with the other categories, indicating that these measures convey different information. FBG is not a clear indicator of general glycemia. Preprandial glucose values have a larger impact on A1C levels than postprandial values.

Citing Articles

Efficacy and safety of iGlarLixi versus insulin glargine in type 2 diabetes: a meta-analysis of randomized controlled trials.

Li J, Wang X, Wu J, Geng D, Li F, Liu Y Endocrine. 2025; .

PMID: 40011373 DOI: 10.1007/s12020-025-04207-w.

Glycated Haemoglobin (HbA) in Cardiac Surgery: A Narrative Review.

Luthra S, Viola L, Navaratnarajah M, Thirukumaran D, Velissaris T J Clin Med. 2025; 14(1.

PMID: 39797106 PMC: 11721050. DOI: 10.3390/jcm14010023.

Comparative Effectiveness of Oral Hypoglycemic Agents for Glycemic Control and Glycemic Variability in Patients with Type 2 Diabetes Mellitus: Using Flash Glucose Monitoring.

Venkatachalapathy P, Mohandoss K, Munisamy M, Sellappan M Curr Diabetes Rev. 2024; 21(1):e160124225706.

PMID: 38310479 PMC: 11497140. DOI: 10.2174/0115733998267817231227102553.

Vegetable and Fruit Intake Variety and Cardiovascular Health and Mortality: A Systematic Review and Meta-Analysis of Observational Studies.

Nishi S, Khoury N, Valle Hita C, Zurbau A, Salas-Salvado J, Babio N Nutrients. 2023; 15(23).

PMID: 38068771 PMC: 10707746. DOI: 10.3390/nu15234913.

Population Pharmacokinetic/Pharmacodynamic Analysis of the Glucokinase Activator PB201 in Healthy Volunteers and Patients with Type 2 Diabetes Mellitus: Facilitating the Clinical Development of PB201 in China.

Song L, Cao F, Niu S, Xu M, Liang R, Ding K Clin Pharmacokinet. 2023; 63(1):93-108.

PMID: 37985591 DOI: 10.1007/s40262-023-01321-8.

References

Chiasson J, Josse R, Gomis R, Hanefeld M, Karasik A, Laakso M . Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA. 2003; 290(4):486-94. DOI: 10.1001/jama.290.4.486. View

Heine R, Dekker J . Beyond postprandial hyperglycaemia: metabolic factors associated with cardiovascular disease. Diabetologia. 2002; 45(4):461-75. DOI: 10.1007/s00125-001-0726-0. View

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(12):1822-6. DOI: 10.2337/diacare.20.12.1822. View

Service F, MOLNAR G, ROSEVEAR J, ACKERMAN E, Gatewood L, Taylor W . Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes. 1970; 19(9):644-55. DOI: 10.2337/diab.19.9.644. View

Ceriello A, Colagiuri S, Gerich J, Tuomilehto J . Guideline for management of postmeal glucose. Nutr Metab Cardiovasc Dis. 2008; 18(4):S17-33. DOI: 10.1016/j.numecd.2008.01.012. View

Woerle H, Neumann C, Zschau S, Tenner S, Irsigler A, Schirra J . Impact of fasting and postprandial glycemia on overall glycemic control in type 2 diabetes Importance of postprandial glycemia to achieve target HbA1c levels. Diabetes Res Clin Pract. 2007; 77(2):280-5. DOI: 10.1016/j.diabres.2006.11.011. View

. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. The DECODE study group. European Diabetes Epidemiology Group. Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe. Lancet. 1999; 354(9179):617-21. View

Rohlfing C, Wiedmeyer H, Little R, England J, Tennill A, Goldstein D . 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(2):275-8. DOI: 10.2337/diacare.25.2.275. View

Bonora E, Calcaterra F, Lombardi S, BONFANTE N, Formentini G, Bonadonna R . Plasma glucose levels throughout the day and HbA(1c) interrelationships in type 2 diabetes: implications for treatment and monitoring of metabolic control. Diabetes Care. 2001; 24(12):2023-9. DOI: 10.2337/diacare.24.12.2023. View

10.

Koehler C, Henkel E, LEONHARDT W, Fuecker K, Hanefeld M . Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level. Diabetes Care. 2000; 23(12):1830-4. DOI: 10.2337/diacare.23.12.1830. View

11.

Bloomgarden Z . Glycemic treatment in type 1 and type 2 diabetes. Diabetes Care. 2006; 29(11):2549-55. DOI: 10.2337/dc06-zb11. View

12.

de Veciana M, Major C, Morgan M, Asrat T, Toohey J, Lien J . Postprandial versus preprandial blood glucose monitoring in women with gestational diabetes mellitus requiring insulin therapy. N Engl J Med. 1995; 333(19):1237-41. DOI: 10.1056/NEJM199511093331901. View

13.

Hanefeld M, Fischer S, Julius U, Schulze J, Schwanebeck U, Schmechel H . Risk factors for myocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11-year follow-up. Diabetologia. 1996; 39(12):1577-83. DOI: 10.1007/s001250050617. View

14.

Raz I, Wilson P, Strojek K, Kowalska I, Bozikov V, Gitt A . Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial. Diabetes Care. 2009; 32(3):381-6. PMC: 2646013. DOI: 10.2337/dc08-1671. View

15.

Nathan D, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine R . Translating the A1C assay into estimated average glucose values. Diabetes Care. 2008; 31(8):1473-8. PMC: 2742903. DOI: 10.2337/dc08-0545. View

16.

McDonnell C, Donath S, Vidmar S, Werther G, Cameron F . A novel approach to continuous glucose analysis utilizing glycemic variation. Diabetes Technol Ther. 2005; 7(2):253-63. DOI: 10.1089/dia.2005.7.253. View

17.

Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol J . Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006; 295(14):1681-7. DOI: 10.1001/jama.295.14.1681. View

18.

Monnier L, Lapinski H, Colette C . Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: variations with increasing levels of HbA(1c). Diabetes Care. 2003; 26(3):881-5. DOI: 10.2337/diacare.26.3.881. View

19.

Balkau B, Shipley M, Jarrett R, Pyorala K, Pyorala M, Forhan A . High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men. 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study. Diabetes Care. 1998; 21(3):360-7. DOI: 10.2337/diacare.21.3.360. View

20.

Ceriello A . The post-prandial state and cardiovascular disease: relevance to diabetes mellitus. Diabetes Metab Res Rev. 2000; 16(2):125-32. DOI: 10.1002/(sici)1520-7560(200003/04)16:2<125::aid-dmrr90>3.0.co;2-4. View