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      Estimation of the Glycation Gap in Diabetic Patients With Stable Glycemic Control

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          Abstract

          OBJECTIVE

          The glycation gap (the difference between measured A1C and the value predicted by regression on fructosamine) is stable and is associated with microvascular complications of diabetes but has not hitherto been estimated within a clinically useful time frame. We investigated whether two determinations 30 days apart suffice for a reasonably reliable estimate if both A1C and fructosamine exhibit stability.

          RESEARCH DESIGN AND METHODS

          We studied 311 patients with type 1 or type 2 diabetes for whom simultaneous measurements of A1C and serum fructosamine had been made on at least two occasions separated by 1 month ( t 0 and t 1). Glycemia was deemed stable if A1C( t 1) – A1C( t 0) and fructosamine( t 1) − fructosamine( t 0) were both less than their reference change values (RCVs). Instantaneous glycation gaps [ gg( t 0) and gg( t 1)] and their mean ( GG), were calculated using the data from all stable patients for the required regression.

          RESULTS

          Stable glycemia was shown by 144 patients. In 90% of unstable case subjects, a change in medication was identified as the cause of instability. Among 129 stable patients with an average of eight gg determinations prior to t 0, GG correlated closely with the mean of these prior determinations ( r 2 = 0.902, slope 1.025, intercept −0.038).

          CONCLUSIONS

          The glycation gap can be calculated reliably from pairs of A1C and fructosamine measurements taken 1 month apart if these measurements satisfy the RCV criteria for glycemic control.

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          Most cited references18

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          Defining the relationship between plasma glucose and HbA(1c): analysis of glucose profiles and HbA(1c) in the Diabetes Control and Complications Trial.

          To define the relationship between HbA(1c) and plasma glucose (PG) levels in patients with type 1 diabetes using data from the Diabetes Control and Complications Trial (DCCT). The DCCT was a multicenter, randomized clinical trial designed to compare intensive and conventional therapies and their relative effects on the development and progression of diabetic complications in patients with type 1 diabetes. Quarterly HbA(1c) and corresponding seven-point capillary blood glucose profiles (premeal, postmeal, and bedtime) obtained in the DCCT were analyzed to define the relationship between HbA(1c) and PG. Only data from complete profiles with corresponding HbA(1c) were used (n = 26,056). Of the 1,441 subjects who participated in the study, 2 were excluded due to missing data. Mean plasma glucose (MPG) was estimated by multiplying capillary blood glucose by 1.11. Linear regression analysis weighted by the number of observations per subject was used to correlate MPG and HbA(1c). Linear regression analysis, using MPG and HbA(1c) summarized by patient (n = 1,439), produced a relationship of MPG (mmol/l) = (1.98 . HbA(1c)) - 4.29 or MPG (mg/dl) = (35.6 . HbA(1c)) - 77.3, r = 0.82). Among individual time points, afternoon and evening PG (postlunch, predinner, postdinner, and bedtime) showed higher correlations with HbA(1c) than the morning time points (prebreakfast, postbreakfast, and prelunch). We have defined the relationship between HbA(1c) and PG as assessed in the DCCT. Knowing this relationship can help patients with diabetes and their healthcare providers set day-to-day targets for PG to achieve specific HbA(1c) goals.
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            Tests of glycemia in diabetes.

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              Red cell life span heterogeneity in hematologically normal people is sufficient to alter HbA1c.

              Although red blood cell (RBC) life span is a known determinant of percentage hemoglobin A1c (HbA1c), its variation has been considered insufficient to affect clinical decisions in hematologically normal persons. However, an unexplained discordance between HbA1c and other measures of glycemic control can be observed that could be, in part, the result of differences in RBC life span. To explore the hypothesis that variation in RBC life span could alter measured HbA1c sufficiently to explain some of this discordance, we determined RBC life span using a biotin label in 6 people with diabetes and 6 nondiabetic controls. Mean RBC age was calculated from the RBC survival curve for all circulating RBCs and for labeled RBCs at multiple time points as they aged. In addition, HbA1c in magnetically isolated labeled RBCs and in isolated transferrin receptor-positivereticulocytes was used to determine the in vivo synthetic rate of HbA1c. The mean age of circulating RBCs ranged from 39 to 56 days in diabetic subjects and 38 to 60 days in nondiabetic controls. HbA1c synthesis was linear and correlated with mean whole blood HbA1c (R(2) = 0.91). The observed variation in RBC survival was large enough to cause clinically important differences in HbA1c for a given mean blood glucose.
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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                December 2012
                14 November 2012
                : 35
                : 12
                : 2447-2450
                Affiliations
                [1] 1Department of Biochemistry and Molecular Biology, University of Santiago de Compostela, Santiago de Compostela, A Coruña, Spain
                [2] 2Department of Biochemistry, University Hospital Clinical Biochemistry Laboratory, University of Santiago de Compostela, Santiago de Compostela, A Coruña, Spain
                [3] 3Division of Endocrinology, Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, A Coruña, Spain
                [4] 4Physiopathology of Obesity and Nutrition Biomedical Research Network Consortium, Santiago de Compostela, A Coruña, Spain
                Author notes
                Corresponding author: Santiago Rodríguez-Segade, ssegade@ 123456telefonica.net .
                Article
                2450
                10.2337/dc11-2450
                3507558
                22961579
                2a727cb9-95e1-4684-8758-60c235f15b2b
                © 2012 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                : 16 December 2011
                : 2 June 2012
                Categories
                Original Research
                Clinical Care/Education/Nutrition/Psychosocial Research

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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