Reproducibility of Glycemic Measures Among Dysglycemic Youth and Adults in the RISE Study

Abstract

Aims: Previous work found poor reproducibility for measures of glycemia in individuals at risk for dysglycemia. Differences between youth and adults have not been assessed. Using youth and adults in the Restoring Insulin Secretion Study, we tested variability and classification concordance for hemoglobin A1C (HbA1c), fasting and 2-hour glucose from oral glucose tolerance tests (OGTTs).

Methods: HbA1c and glucose on repeated samples obtained ∼6 weeks apart were compared in 66 youth (mean age 14.2 years) and 354 adults (52.7 years). Changes, coefficient of variation (CV), and concordance of diagnostic categories between the 2 visits were compared.

Results: Mean difference between the 2 visits in HbA1c was higher in youth than adults (P < .001), while fasting glucose was similar and 2-hour glucose was lower in youth (P = .051). CV was smallest for HbA1c compared to fasting and 2-hour glucose. For HbA1c, youth had higher CV (P < .001); whereas CV for 2-hour glucose was lower for youth (P = .041). Classification concordance by HbA1c was lower in youth (P = .004). Using OGTT or HbA1c for classification, intervisit variability produced discordant classification in 20% of youth and 28% of adults. Using both fasting glucose and HbA1c, intervisit variability reduced discordant classification to 16% of adults while not improving classification in youth.

Conclusions: Poor reproducibility and lack of classification concordance highlight the limitations of one-time testing, with important implications for assessing eligibility in clinical trials. Consideration should be given to using more than a single parameter for screening and diagnosis, especially when classification category is important.

Trial registration: ClinicalTrials.gov NCT01779362 NCT01779375 NCT01763346.

Keywords: HbA1c; classification criteria; coefficient of variation; diagnosis and classification; oral glucose tolerance test; reproducibility.

Figure 1.

Correlation for HbA1c (A), fasting glucose (B), and 2-hour glucose (C) for youth (blue) and adults (green). On the correlation plots, the line of utility (slope of 1) represents identical values with both tests (dashed line). The Bland-Altman plots show the difference against the mean value for the 2 visits for HbA1c (D), fasting glucose (E), and 2-hour glucose (F) for youth (blue) and adults (green). The solid reference line at 0 represents no difference between the measurements at screening and baseline. The corresponding dashed lines represents the mean differences and the solid lines represent the 95% CI (±1.96*SD) of the mean of the differences. Correlation is stronger in youth than adults for fasting and 2-hour glucose (P = .031 and P = .004, respectively) but not significantly different for HbA1c. Abbreviations: HbA1c, hemoglobin A1C.