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06-01-2018 | Diet | Article

Relative contributions of preprandial and postprandial glucose exposures, glycemic variability, and non-glycemic factors to HbA 1c in individuals with and without diabetes

Journal: Nutrition & Diabetes

Authors: Kristine Færch, Marjan Alssema, David J. Mela, Rikke Borg, Dorte Vistisen

Publisher: Nature Publishing Group UK




There is substantial interest in dietary approaches to reducing postprandial glucose (PPG) responses, but the quantitative contribution of PPG to longer-term glycemic control (reflected in glycated hemoglobin, HbA1c) in the general population is not known. This study quantified the associations of preprandial glucose exposure, PPG exposure, and glycemic variability with HbA1c and estimated the explained variance in HbA1c in individuals with and without type 2 diabetes (T2D).


Participants in the A1c-Derived Average Glucose (ADAG) study without T2D (n = 77) or with non-insulin-treated T2D and HbA1c<6.5% (T2DHbA1c < 6.5%, n = 63) or HbA1c ≥ 6.5% (T2DHbA1c ≥ 6.5%, n = 34) were included in this analysis. Indices of preprandial glucose, PPG, and glycemic variability were calculated from continuous glucose monitoring during four periods over 12 weeks prior to HbA1c measurement. In linear regression models, we estimated the associations of the glycemic exposures with HbA1c and calculated the proportion of variance in HbA1c explained by glycemic and non-glycemic factors (age, sex, body mass index, and ethnicity).


The factors in the analysis explained 35% of the variance in HbA1c in non-diabetic individuals, 49% in T2DHbA1c < 6.5%, and 78% in T2DHbA1c ≥ 6.5%. In non-diabetic individuals PPG exposure was associated with HbA1c in confounder-adjusted analyses (P < 0.05). In the T2DHbA1c < 6.5% group, all glycemic measures were associated with HbA1c (P < 0.05); preprandial glucose and PPG accounted for 14 and 18%, respectively, of the explained variation. In T2DHbA1c ≥ 6.5%, these glycemic exposures accounted for more than 50% of the variation in HbA1c and with equal relative contributions.


Among the glycemic exposures, PPG exposure was most strongly predictive of HbA1c in non-diabetic individuals, suggesting that interventions targeting lowering of the PPG response may be beneficial for long-term glycemic maintenance. In T2D, preprandial glucose and PPG exposure contributed equally to HbA1c.
Gallagher, E. J., Le Roith, D. & Bloomgarden, Z. Review of hemoglobin A(1c) in the management of diabetes. J. Diabetes 1, 9–17 (2009). CrossRefPubMed
Coban, E., Ozdogan, M. & Timuragaoglu, A. Effect of iron deficiency anemia on the levels of hemoglobin A1c in nondiabetic patients. Acta Haematol. 112, 126–128 (2004). CrossRefPubMed
Tancredi, M. et al. Excess mortality among persons with type 2 diabetes. N. Engl. J. Med. 373, 1720–1732 (2015). CrossRefPubMed
Selvin, E. et al. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. N. Engl. J. Med. 362, 800–811 (2010). CrossRefPubMedPubMedCentral
Zhong, G. C., Ye, M. X., Cheng, J. H., Zhao, Y. & Gong, J. P. HbA1c and risks of all-cause and cause-specific death in subjects without known diabetes: a dose–response meta-analysis of prospective cohort studies. Sci. Rep. 6, 24071 (2016). CrossRefPubMedPubMedCentral
Santos-Oliveira, R. et al. Haemoglobin A1c levels and subsequent cardiovascular disease in persons without diabetes: a meta-analysis of prospective cohorts. Diabetologia 54, 1327–1334 (2011). CrossRefPubMed
Borg, R. et al. Real-life glycaemic profiles in non-diabetic individuals with low fasting glucose and normal HbA1c: the A1C-Derived Average Glucose (ADAG) study. Diabetologia 53, 1608–1611 (2010). CrossRefPubMedPubMedCentral
Blaak, E. E. et al. Impact of postprandial glycaemia on health and prevention of disease. Obes. Rev. 13, 923–984 (2012). CrossRefPubMedPubMedCentral
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 26, 881–885 (2003). CrossRefPubMed
Nathan D. M. et al. Translating the A1C assay into estimated average glucose values. Diabetes Care 31, 1473–1478 (2008). CrossRefPubMedPubMedCentral
Service F. J. et al. Mean amplitude of glycemic excursions, a measure of diabetic instability. Diabetes 19, 644–655 (1970). CrossRefPubMed
McDonnell, C. M., Donath, S. M., Vidmar, S. I., Werther, G. A. & Cameron, F. J. A novel approach to continuous glucose analysis utilizing glycemic variation. Diabetes Technol. Ther. 7, 253–263 (2005). CrossRefPubMed
Danne, T. et al. International Consensus on Use of Continuous Glucose Monitoring. Diabetes Care 40, 1631–1640 (2017). CrossRefPubMed
Snieder, H. et al. HbA(1c) levels are genetically determined even in type 1 diabetes: evidence from healthy and diabetic twins. Diabetes 50, 2858–2863 (2001). CrossRefPubMed
Færch, K., Borch-Johnsen, K., Vaag, A., Jørgensen, T. & Witte, D. Sex differences in glucose levels: a consequence of physiology or methodological convenience? The Inter99 study. Diabetologia 53, 858–865 (2010). CrossRefPubMed
Gould, B. J., Davie, S. J. & Yudkin, J. S. Investigation of the mechanism underlying the variability of glycated haemoglobin in non-diabetic subjects not related to glycaemia. Int. J. Clin. Chem. 260, 49–64 (1997).
Alssema, M. et al. Diet and glycaemia: the markers and their meaning. A report of the Unilever Nutrition Workshop. British. J. Nutr. 113, 239–248 (2015). CrossRef
Barclay, A. W. et al. Glycemic index, glycemic load, and chronic disease risk—a meta-analysis of observational studies. Am. J. Clin. Nutr. 87, 627–637 (2008). CrossRefPubMed
Dong, J. Y., Zhang, L., Zhang, Y. H. & Qin, L. Q. Dietary glycaemic index and glycaemic load in relation to the risk of type 2 diabetes: a meta-analysis of prospective cohort studies. Br. J. Nutr. 106, 1649–1654 (2011). CrossRefPubMed
Holman, R. R. et al. Effects of acarbose on cardiovascular and diabetes outcomes in patients with coronary heart disease and impaired glucose tolerance (ACE): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 5, 877–886 (2017). CrossRefPubMed
Hanefeld, M., Sulk, S., Helbig, M., Thomas, A. & Kähler, C. Differences in glycemic variability between normoglycemic and prediabetic subjects. J. Diabetes Sci. Technol. 8, 286–290 (2014). CrossRefPubMedPubMedCentral
Ma, C.-M. et al. Glycemic variability in abdominally obese men with normal glucose tolerance as assessed by continuous glucose monitoring system. Obesity 19, 1616–1622 (2011). CrossRefPubMed
Wang, Y.-m et al. Glycemic variability in normal glucose tolerance women with the previous gestational diabetes mellitus. Diabetol. Metab. Syndr. 7, 1–8 (2015). CrossRef
Lim, L. L. et al. Relationship of glycated hemoglobin, and fasting and postprandial hyperglycemia in type 2 diabetes mellitus patients in Malaysia. J. Diabetes Invest. 8, 453–461 (2017). CrossRef
Wang, J. S. et al. Contribution of postprandial glucose to excess hyperglycaemia in Asian type 2 diabetic patients using continuous glucose monitoring. Diabetes Metab. Res. Rev. 27, 79–84 (2011). CrossRefPubMed
Kang, X. et al. Contributions of basal glucose and postprandial glucose concentrations to hemoglobin A1c in the newly diagnosed patients with type 2 diabetes—the Preliminary Study. Diabetes Technol. Ther. 17, 445–448 (2015). CrossRefPubMedPubMedCentral

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