The association between HbA1c, fasting glucose, 1-hour glucose and 2-hour glucose during an oral glucose tolerance test and cardiovascular disease in individuals with elevated risk for diabetes.

Marcus Lind,Olle Nerman,Pirjo Ilanne-Parikka,Sirkka Keinänen-Kiukaanniemi,Jaakko Tuomilehto,Aldina Pivodic,Matti Uusitupa,Markku Peltonen,Johan Eriksson,Jaana Lindström

doi:10.1371/journal.pone.0109506

Abstract

ObjectiveTo determine the association between HbA1c, fasting plasma glucose (FPG), 1-hour (1 hPG) and 2-hour (2 hPG) glucose after an oral glucose tolerance test (OGTT) and cardiovascular disease in individuals with elevated risk for diabetes.DesignWe studied the relationship between baseline, updated mean and updated (last) value of HbA1c, FPG, 1 hPG and 2 hPG after an oral 75 g glucose tolerance test (OGTT) and acute CVD events in 504 individuals with impaired glucose tolerance (IGT) at baseline enrolled in the Finnish Diabetes Prevention Study.SettingFollow-up of clinical trial.Participants504 individuals with IGT were followed with yearly evaluations with OGTT, FPG and HbA1c.Main Outcome MeasureRelative risk of CVD.ResultsOver a median follow-up of 9.0 years 34 (6.7%) participants had a CVD event, which increased to 52 (10.3%) over a median follow-up of 13.0 years when including events that occurred among participants following a diagnosis of diabetes. Updated mean HbA1c, 1 hPG and 2 hPG, HR per 1 unit SD of 1.57 (95% CI 1.16 to 2.11), p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not FPG (p = 0.11), were related to CVD. In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), p<0.0001, respectively but only 2 hPG remained significant in pairwise comparisons. Including the follow-up period after diabetes onset updated 2 hPG (p = 0.003) but not updated mean HbA1c (p = 0.08) was related to CVD.Conclusions and RelevanceCurrent 2 hPG level in people with IGT is associated with increased risk of CVD. This supports its use in screening for prediabetes and monitoring glycaemic levels of people with prediabetes.

Highlights

The global prevalence of diabetes is increasing rapidly, and in 2030 over 500 million individuals are expected to suffer from diabetes, mostly type 2 (T2D) [1]
Updated mean HbA1c, 1 hPG and 2-hour post-challenge plasma glucose (2 hPG), Hazard ratios (HR) per 1 unit standard deviation (SD) of 1.57, p = 0.0032, 1.51 (1.03 to 2.23), p = 0.036 and 1.60 (1.10 to 2.34), p = 0.014, respectively, but not fasting plasma glucose (FPG) (p = 0.11), were related to CVD
In analyses of the last value prior to the CVD event the same three glycaemic measurements were associated with the CVD events, with HRs per 1 unit SD of 1.45 (1.06 to 1.98), p = 0.020, 1.55 (1.04 to 2.29), p = 0.030 and 2.19 (1.51 to 3.18), p,0.0001, respectively but only 2 hPG remained significant in pairwise comparisons

Summary

Introduction

The global prevalence of diabetes is increasing rapidly, and in 2030 over 500 million individuals are expected to suffer from diabetes, mostly type 2 (T2D) [1]. The landmark Finnish Diabetes Prevention Study (DPS) showed that intensive lifestyle intervention among individuals with impaired glucose tolerance (IGT) effectively prevented progression from IGT to diabetes [3]. This benefit has been subsequently confirmed by others [4,5]. In a recent systematic review, the relationships between 2-h plasma glucose (2 hPG) and fasting plasma glucose (FPG) and risk of future CVD and mortality were shown to be relatively weak [2] These studies only examined baseline FPG and 2 hPG measurements, thereby information on glycaemic control during follow-up (i.e., when the events occurred), may have weakened the associations. It is unclear whether prediabetes per se and/or the development of diabetes during a later point in time is relevant to the association between IFG, IGT and CVD events, as well as relevant confounders including physical activity, which were generally missing in previous studies [2]

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Conclusion