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Variability in the Relationship between Mean Plasma Glucose and HbA_1c: Implications for the Assessment of Glycemic Control

¹ Department of Clinical Biochemistry, Hull Royal Infirmary, Hull, United Kingdom.
² Academic Department of Cardiology, University of Hull, Hull, United Kingdom.
³ Department of Diabetes, Hull York Medical School, Hull, United Kingdom.

^aAddress correspondence to this author at: Department of Clinical Biochemistry, Hull Royal Infirmary, Anlaby Rd., Hull HU3 2JZ, United Kingdom. Fax 441482-607752; e-mail Eric.Kilpatrick{at}hey.nhs.uk.

Background: Previous studies have shown a single linear relationship between mean plasma glucose (MPG) and hemoglobin A_1c (HbA_1c). We examined the relationship in different treatment groups of patients with type 1 diabetes participating in the Diabetes Control and Complications Trial (DCCT).

Methods: Seven-point glucose profiles (premeal, postmeal, and bedtime) and HbA_1c were measured quarterly during the DCCT. We studied measurements from (a) intensively treated patients at study commencement, (b) intensively treated patients after stabilization of their glycemia (from 6 months onward), and (c) conventionally treated patients from 6 months onward. Only complete glucose profile and HbA_1c pairings were considered (n = 589, 11 483, and 11 855, respectively).

Results: From 6 months into the trial, conventionally treated patients had consistently higher MPG concentrations than intensively treated patients at any given HbA_1c value (mean difference, 1.6 mmol/L at 7% HbA_1c, increasing to 2.8 mmol/L at 11% HbA_1c). Similarly, at the same HbA_1c, the MPG of intensively treated patients at baseline was higher than in the same individuals after 6 months of intensive treatment (1.2 mmol/L difference at 7% HbA_1c, increasing to 4.6 mmol/L at 11% HbA_1c).

Conclusions: The relationship between MPG and HbA_1c is not constant but differs depending on the glycemic control of the population being studied. Having lower mean glucose at the same HbA_1c may help explain why intensive DCCT treatment appeared intrinsically linked to both increased hypoglycemia and decreased microvascular complications compared with conventional treatment. These findings may also have implications for expressing HbA_1c as mean blood glucose equivalent.

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