Glycation of hemoglobin (Hb) measured by A1C depends on red blood cell (RBC) lifespan, thus may misrepresent intracellular glucose exposure in other tissues, and may explain observed dissociations between A1C and microvascular complications. A kinetic model that accounts for rates of RBC turnover and intracellular glucose transport was evaluated for A1C individualization using continuous glucose monitoring data (CGM) and laboratory A1C from 58 individuals with diabetes (type 1/type 2 = 5/53, mean age 58 years (range 27 to 77, M/F=38/20). A1C was performed at 0, 3, and 6 months with concurrent CGM for 6 months, having a minimum of 80% coverage and no gaps >36 hours. The adjustment required to calculate individualized A1C is expressed as follows: A1C/(A1C+(1-A1C)*KTR/KT), where KT is the Hb and RBC turnover rate, and KTR is the reference Hb and RBC turnover rate. The mean (±SD) rate of Hb and RBC turnover was 1.18±0.20%/day as depicted in the Figure, showing the individualized A1C calculation. These data suggest that laboratory A1C does not only underestimate cellular glucose exposure in some patients but can also overestimate average glucose levels making the individual prone to hypoglycemia through unnecessary escalation of antidiabetic therapies. Quantitative individualization of A1C derived from A1C and CGM readings has the potential to more accurately assess intracellular glycemic exposure.


R.M. Bergenstal: Research Support; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Dexcom, Inc., Glooko, Inc., Hygieia, JDRF, Johnson & Johnson Medical Devices Companies, Lilly Diabetes, Medtronic MiniMed, Inc., Merck & Co., Inc., National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk Inc., Roche Diabetes Care, Sanofi. Other Relationship; Self; Abbott, Helmsley Charitable Trust, Hygieia, Lilly Diabetes, Novo Nordisk Inc., Onduo LLC, Sanofi, UnitedHealth Group Inc. T. Dunn: Employee; Self; Abbott Laboratories. Y. Xu: Employee; Self; Abbott Laboratories. R. Ajjan: Consultant; Self; Abbott. Research Support; Self; Abbott, LifeScan, Inc.


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