Prognostic value of haemoglobin A1c and fasting plasma glucose for incident diabetes and implications for screening

Abstract

The aim of this analysis is to compare screening strategies with haemoglobin A(1c) (HbA(1c)), fasting plasma glucose (FPG) or combined measures in the identification of individuals at high risk for diabetes. Applying American Diabetes Association thresholds for FPG and HbA(1c) screening, 6,803 subjects free of diabetes were classified as non-diabetic, pre-diabetic and possibly diabetic by FPG (<100, 100-125 and >125 mg/dl) and HbA(1c) (<5.7, 5.7-6.4 and >6.4%). Hazard ratios, sensitivity and specificity were estimated for individuals with pre-diabetes with respect to incident diabetes in the following 5 years. Areas under the receiver operating characteristic curves (AUC) were estimated for levels of FPG ≤ 125 mg/dl and HbA(1c) ≤ 6.4% in diabetes prediction. Although FPG and HbA(1c) screenings poorly agreed in classifying individuals as pre-diabetic, hazard ratios [95% confidence interval] for incident diabetes were similarly increased in univariate models in the two pre-diabetic groups: FPG 100-125 mg/dl, 4.72 [3.69; 6.05]; HbA(1c) 5.7-6.4%, 3.97 [3.05; 5.23]. HbA(1c) and FPG had comparable AUCs (FPG, 0.732; HbA(1c), 0.725) and consequently similar 5-year sensitivities and specificities for their pre-diabetes definitions (when the lower cut-off for HbA(1c)-defined pre-diabetes was increased to a level between 5.8 and 5.9%). Combining HbA(1c) and FPG increased the AUC to 0.778, and a further increase to 0.817 was seen with additional inclusion of conventional risk factors. FPG and HbA(1c) have comparable (yet insufficient) abilities in identifying individuals at high risk for diabetes. Effectiveness of a diabetes screening program could be improved by a risk score including FPG and HbA(1c).

Fasting plasma glucose and HbA1c in cardiovascular risk prediction: a sex-specific comparison in individuals without diabetes mellitus

“…In agreement with other studies [10,11,25], we showed in a previous analysis of the ESTHER data that the new HbA 1c -based prediabetes definition and IFG have a low proportion of overlap [12]. Nevertheless, individuals with IFG and those with HbA 1c -defined prediabetes showed a similarly increased burden of cardiovascular risk factors.…”

“…Individuals with IFG, IGT and HbA 1c levels below 48 mmol/mol (6.5%) have been shown to be at increased risk for adverse cardiovascular outcomes [2,6,7], but estimates were mostly non-significant and studies comparing the cardiovascular risk of individuals with IFG or IGT with the new HbA 1c -defined prediabetes definition are sparse [8]. There is a need for detailed comparisons in large-scale cohorts because the overlap of prediabetes definitions is low [9][10][11][12]. The comparison of IFGand HbA 1c -defined prediabetes has the greatest relevance for clinical practice because the OGTT is unlikely to be used in primary prevention programmes because of its poor reproducibility, time requirement and costs [13,14].…”

Development of a new scoring system for predicting the 5 year incidence of type 2 diabetes in Japan: the Toranomon Hospital Health Management Center Study 6 (TOPICS 6)

“…Results of the EPIC-Potsdam Study also suggested that risk reclassification was improved by adding FPG (IDI 0.0553) or HbA 1c (IDI 0.0974) values using the prediction model by the German Diabetes Risk Score as a reference [14]. Recent prospective studies have examined the utility of introducing HbA 1c testing for predicting diabetes [15,16,[23][24][25][26][27], and some reports have described the development of models to predict future diabetes using blood variables including FPG and HbA 1c [15,25,29]. More recently and concomitantly with the preparation of this manuscript, a risk score that concurrently included measurements of FPG, HbA 1c and other biochemical markers was reported in a Korean population [40].…”

“…Introducing HbA 1c into a prediction model has been suggested to be effective in screening for future diabetes [14][15][16][22][23][24][25][26][27][28], and a few models to predict the development of diabetes have recently been developed that concurrently include measurements of FPG, HbA 1c and other blood markers [15,25,29]. After revising the diagnostic criteria for type 2 diabetes by introducing HbA 1c in 2010 [30], the ADA published guidelines and recommendations for diagnosing diabetes based on published data or derived from expert consensus [31].…”

The potential of novel biomarkers to improve risk prediction of type 2 diabetes

“…In the multiethnic Atherosclerosis Risk in Communities (ARIC) [22]. Figure 1 and ESM Table 2 show that the separate addition of fasting glucose, HbA 1c or 2 h glucose to basic models with non-invasive variables leads to a strong increase in model accuracy [18,24,[36][37][38]. In several studies, HbA 1c improved the predictive power to a similar extent to fasting glucose.…”