Screening for pre-diabetes to predict future diabetes using various cut-off points for HbA(1c) and impaired fasting glucose: the Toranomon Hospital Health Management Center Study 4 (TOPICS 4).

To evaluate various screening criteria for pre-diabetes to identify which combination of impaired fasting glucose and elevated HbA(1c) values performs most effectively in predicting future diabetes in a large cohort of Japanese individuals. The study included 4670 men and 1571 women without diabetes (diabetes: fasting plasma glucose ≥ 7.0 mmol/l, HbA(1c) ≥ 48 mmol/mol (≥ 6.5%), or self-reported clinician-diagnosed diabetes). Pre-diabetes was diagnosed by a combination of impaired fasting glucose (fasting plasma glucose 5.6-6.9 mmol/l or 6.1-6.9 mmol/l) and elevated HbA(1c) [39-46 mmol/mol (5.7-6.4%) or 42-46 mmol/mol (6.0-6.4%)]. During a 5-year follow-up, 338 incident cases of diabetes occurred. The combination of HbA(1c) 39-46 mmol/mol (5.7-6.4%) and fasting plasma glucose 5.6-6.9 mmol/l yielded the highest sensitivity (86%) and generated a large population-attributable per cent risk (78%) for predicting development of diabetes. Among individuals classified as having pre-diabetes by any of the four combined criteria, 20.5-32.0% reverted to the normoglycaemic state as having neither elevated HbA(1c) nor impaired fasting glucose at the last follow-up examination. At 5.6 years after the baseline examination, however, pre-diabetic individuals who fulfilled both HbA(1c) 42-46 mmol/mol (6.0-6.4%) and fasting plasma glucose 6.1-6.9 mmol/l had a 100% cumulative risk of developing diabetes. The combination of HbA(1c) 39-46 mmol/mol (5.7-6.4%) and fasting plasma glucose 5.6-6.9 mmol/l would have the best performance in reducing the likelihood of missing future cases of diabetes. Identifying pre-diabetic individuals who strictly fulfil HbA(1c) 42-46 mmol/mol (6.0-6.4%) and fasting plasma glucose 6.1-6.9 mmol/l would predict definite progression to diabetes.

Heianza Y ，Arase Y ，Fujihara K ，Tsuji H ，Saito K ，Hsieh SD ，Kodama S ，Shimano H ，Yamada N ，Hara S ，Sone H ... -  《-》

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.

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 A(1c) (HbA(1c)) 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. 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 HbA(1c) ≥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 HbA(1c) 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. Mean follow-up was 4·7 (SD 0·7) years. 412 (7%) of 6241 participants were diagnosed with prediabetes on the basis of the HbA(1c) 5·7-6·4% criterion. Screening by HbA(1c) alone missed 1270 (61%) of the 2092 prediabetic individuals diagnosed by a combination of impaired fasting glucose and HbA(1c) 5·7-6·4%. Overall cumulative probability of progression to diabetes did not differ significantly between participants with prediabetes discordantly diagnosed by either HbA(1c) or impaired fasting glucose alone (incidence was 7% for HbA(1c) 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 HbA(1c) alone, and were substantially increased to 31·9 (22·6-45·0) for diagnosis by both impaired fasting glucose and HbA(1c) compared with normoglycaemic individuals. Diagnosis of prediabetes by both the new HbA(1c) criterion and impaired fasting glucose identified individuals with an increased risk of progression to diabetes. Although the new HbA(1c) criterion identified fewer individuals at high risk than did impaired fasting glucose, the predictive value for progression to diabetes assessed by HbA(1c) 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. Japan Society for the Promotion of Science; Ministry of Health Labor and Welfare, Japan.

Heianza Y ，Hara S ，Arase Y ，Saito K ，Fujiwara K ，Tsuji H ，Kodama S ，Hsieh SD ，Mori Y ，Shimano H ，Yamada N ，Kosaka K ，Sone H ... -  《-》

Cut-off values of fasting and post-load plasma glucose and HbA1c for predicting Type 2 diabetes in community-dwelling Japanese subjects: the Hisayama Study.

We examined the optimal cut-off values of fasting plasma glucose, 2-h post-load glucose and HbA(1c) for predicting Type 2 diabetes in community-dwelling Japanese subjects. A total of 1982 subjects without diabetes aged 40-79 years who underwent a 75-g oral glucose tolerance test were followed prospectively for 14 years by annual health examination. During the follow-up, 295 subjects developed Type 2 diabetes. Compared with the first decile, the crude hazard ratio for incident Type 2 diabetes was significantly higher in the fifth fasting plasma glucose decile [5.4-5.4 mmol/l (97-98 mg/dl)] or higher, in the seventh 2-h post-load glucose decile [6.9-7.2 mmol/l (124-131 mg/dl)] or higher, and in the fifth HbA(1c) decile [34-36 mmol/mol (5.3-5.4%)] or higher. These associations remained substantially unchanged even after adjustment for confounding factors. The receiver operating characteristic curve analysis showed that the optimal cut-off values for predicting Type 2 diabetes were 5.6 mmol/l (101 mg/dl) for fasting plasma glucose, 6.9 mmol/l (124 mg/dl) for 2-h post-load glucose and 37 mmol/mol (5.5%) for HbA(1c). In a stratified analysis, the cut-off values were approximately 5.6 mmol/l (101 mg/dl) for fasting plasma glucose and 37 mmol/mol (5.5%) for HbA(1c), and these values were unchanged over BMI quartile levels, whereas the 2-h post-load glucose cut-off values declined with decreasing BMI levels. Our findings suggest that the cut-off value for predicting Type 2 diabetes in the Japanese population is 5.6 mmol/l (101 mg/dl) for fasting plasma glucose and 37 mmol/mol (5.5%) for HbA(1c), while the 2-h post-load glucose cut-off value is lower than the diagnostic criterion for impaired glucose tolerance.

Mukai N ，Doi Y ，Ninomiya T ，Hata J ，Hirakawa Y ，Fukuhara M ，Iwase M ，Kiyohara Y ... -  《-》

HbA(1c) as a diagnostic tool for diabetes and pre-diabetes: the Bangladesh experience.

To evaluate HbA(1c) as a tool for the diagnosis of diabetes and pre-diabetes (impaired glucose tolerance and/or impaired fasting glucose) and to identify the optimal cut-off values suitable for a Bangladeshi population. In this cross-sectional survey in a rural community, 2293 randomly selected individuals aged ≥ 20 years without prior history of diabetes were included. HbA(1c) and other clinical covariates necessary for the diagnosis of diabetes were recorded. Diabetes and pre-diabetes were defined according to the World Health Organization 1999 criteria. The receiver operating characteristic curve was used to determine the performance of HbA(1c). The prevalences of diabetes and pre-diabetes were 7.9 and 8.6%, respectively. Based on receiver operating characteristic curve analysis, an HbA(1c) cut-off value of ≥ 42 mmol/mol (≥ 6.0%) gave an optimal sensitivity of 86.2% and specificity of 93.3%, with an area under the curve of 0.949 to predict diabetes using the oral glucose tolerance test as the gold standard; a cut-off value of ≥ 38 mmol/mol (≥ 5.6%) gave an optimal sensitivity of 68.0% and specificity of 66.4%, with an area under the curve of 0.714 to predict pre-diabetes. In subjects at high risk of diabetes, HbA(1c) ≥ 42 mmol/mol (≥ 6.0%) showed higher sensitivity than fasting plasma glucose ≥ 7.0 mmol/l, 2-h plasma glucose ≥ 11.1 mmol/l and HbA(1c) ≥ 48 mmol/mol (≥ 6.5%). An HbA(1c) cut-off value of ≥ 42 mmol/mol (≥ 6.0%) was highly sensitive and specific in diagnosing diabetes mellitus. This optimal cut-off level may be suitable as a diagnostic criterion for diabetes in a Bangladeshi population.

Bhowmik B ，Diep LM ，Munir SB ，Rahman M ，Wright E ，Mahmood S ，Afsana F ，Ahmed T ，Khan AK ，Hussain A ... -  《-》

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).

Heianza Y ，Arase Y ，Hsieh SD ，Saito K ，Tsuji H ，Kodama S ，Tanaka S ，Ohashi Y ，Shimano H ，Yamada N ，Hara S ，Sone H ... -  《-》