Elsevier

The Lancet

Volume 378, Issue 9786, 9–15 July 2011, Pages 147-155
The Lancet

Articles
HbA1c 5·7–6·4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study

https://doi.org/10.1016/S0140-6736(11)60472-8Get rights and content

Summary

Background

The clinical relevance of the diagnostic criteria for prediabetes to prediction of progression to diabetes has been little studied. We aimed to compare the prevalence of prediabetes when assessed by the new glycated haemoglobin A1c (HbA1c) 5·7–6·4% criterion or by impaired fasting glucose, and assessed differences in progression rate to diabetes between these two criteria for prediabetes in a Japanese population.

Methods

Our longitudinal cohort study included 4670 men and 1571 women aged 24–82 years without diabetes at baseline (diabetes was defined as fasting plasma glucose ≥7·0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA1c ≥6·5%) who attended Toranomon Hospital (Tokyo, Japan) for a routine health check between 1997 and 2003. Participants with a baseline diagnosis of prediabetes according to impaired fasting glucose (fasting plasma glucose 5·6–6·9 mmol/L) or HbA1c 5·7–6·4%, or both, were divided into four groups on the basis of baseline diagnosis of prediabetes. Rate of progression to diabetes was assessed annually.

Findings

Mean follow-up was 4·7 (SD 0·7) years. 412 (7%) of 6241 participants were diagnosed with prediabetes on the basis of the HbA1c 5·7–6·4% criterion. Screening by HbA1c alone missed 1270 (61%) of the 2092 prediabetic individuals diagnosed by a combination of impaired fasting glucose and HbA1c 5·7–6·4%. Overall cumulative probability of progression to diabetes did not differ significantly between participants with prediabetes discordantly diagnosed by either HbA1c or impaired fasting glucose alone (incidence was 7% for HbA1c alone [n=412 individuals and 30 incident cases] and 9% for impaired fasting glucose alone [n=1270, 108 cases]; log-rank test, p=0·3317). Multivariate-adjusted hazard ratios for incident diabetes were 6·16 (95% CI 4·33–8·77) for those diagnosed with prediabetes by impaired fasting glucose alone and 6·00 (3·76–9·56) for diagnosis by HbA1c alone, and were substantially increased to 31·9 (22·6–45·0) for diagnosis by both impaired fasting glucose and HbA1c compared with normoglycaemic individuals.

Interpretation

Diagnosis of prediabetes by both the new HbA1c criterion and impaired fasting glucose identified individuals with an increased risk of progression to diabetes. Although the new HbA1c criterion identified fewer individuals at high risk than did impaired fasting glucose, the predictive value for progression to diabetes assessed by HbA1c 5·7–6·4% was similar to that assessed by impaired fasting glucose alone. The two tests used together could efficiently target people who are most likely to develop diabetes and allow for early intervention.

Funding

Japan Society for the Promotion of Science; Ministry of Health Labor and Welfare, Japan.

Introduction

In prediabetes, blood glucose concentrations are higher than normal, but are not high enough for diagnosis of diabetes. The disorder is thought to place individuals at high risk of future diabetes, according to the American Diabetes Association (ADA).1 ADA guidelines suggest targeting of individuals identified as having prediabetes for early intervention.1 A new criterion has been proposed for the diagnosis of prediabetes: glycated haemoglobin A1c (HbA1c) 5·7–6·4%. However, the performance of HbA1c as a screening test for identification of prediabetic individuals has been controversial.2, 3, 4, 5, 6 Many individuals who were diagnosed as having prediabetes on the basis of impaired fasting glucose are reclassified as not having the disorder when the new HbA1c 5·7–6·4% criterion is used; thus, screening by HbA1c alone might miss a large number of prediabetic individuals.2, 3, 4, 5 The new criterion's performance in detection of prediabetic individuals differs according to ethnic origin,4, 5 and more evidence of its usefulness in non-western populations is needed.4, 6

Few studies7, 8 have longitudinally compared the difference in progression rate to diabetes after diagnosis of prediabetes with the HbA1c 5·7–6·4% criterion or by impaired fasting glucose, or established which criterion for prediabetes is clinically relevant for prediction of progression. Whether introduction of the new HbA1c criterion in addition to assessment of fasting glucose could efficiently target prediabetic individuals who are most likely to progress to diabetes is unclear. We aimed to evaluate the effect of introduction of the HbA1c 5·7–6·4% criterion into diagnosis of prediabetes by impaired fasting glucose, and to longitudinally assess differences in the progression rate to diabetes between individuals diagnosed with prediabetes on the basis of these two criteria in a large Japanese cohort. We tested whether the two tests used together could target people most likely to progress to diabetes, which would allow early intervention.

Section snippets

Study population

The Toranomon Hospital Health Management Center Study (TOPICS) included a cohort consisting mainly of apparently healthy Japanese government employees who underwent annual examinations for health screening. The details of the study have been described previously.9 The cohort consisted of 32 057 individuals who had a routine health check for the first time between 1997 and 2003 at the Health Management Center, Toranomon Hospital (Tokyo, Japan). Of these 32 057 individuals, our investigation

Results

Prevalence of diabetes in the entire study population was 5% (1684 of 32 057 people). Table 1 shows characteristics of study participants (n=6241). On the basis of the HbA1c 5·7–6·4% criterion, 412 (7%) individuals in the study population had newly diagnosed prediabetes (table 2). Prediabetic individuals diagnosed by impaired fasting glucose but not by HbA1c had significantly different characteristics at the baseline examination compared with those diagnosed by HbA1c but not by fasting glucose.

Discussion

This study showed that diagnosis of prediabetes by both new HbA1c and fasting glucose criteria identified individuals in a Japanese population at a substantially increased risk for progression to diabetes within 5 years. Although the new HbA1c criterion identified fewer participants at high risk than were identified by impaired fasting glucose, the predictive value for progression to diabetes assessed by HbA1c 5·7–6·4% without impaired fasting glucose was similar to that assessed by fasting

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