Yonago Acta medica 2009;52:105–114

Screening Criteria of Diabetes Mellitus andImpaired Glucose Tolerance of the Japanese Population
in a Rural Area of Japan: The Tottori-Kofu Study
Tsuyoshi Ohkura, Shin-ichi Taniguchi, Kazuoki Inoue, Naoya Yamamoto, KazuhikoMatsuzawa, Youhei Fujioka, Keisuke Sumi, Shoichiro Izawa, Mikio Takechi*, Yoneatsu
Osaki† and Chiaki Shigemasa
Division of Molecular Medicine and Therapeutics, Department of Multidisciplinary Internal Medicine,
School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8504, *Ebi Clinic, Kofu 6894401, †Division of Environmental and Preventive Medicine, Department of Social Medicine, School of
Medicine, Tottori University Faculty of Medicine, Yonago 683-8503 Japan

We performed the Tottori-Kofu Study to develop an early detection method of the Japanese with diabetes mellitus (DM) and impaired glucose tolerance (IGT), using simple predictors such as fasting plasma glucose (FPG) and other risk information obtainable frombasic medical check-ups. In 2005, 734 residents of Kofu Town received a basic medical
check-up including blood examination. Some of them meeting the following criteria further underwent the oral glucose tolerance test (OGTT): 5.5 mmol/L (100 mg/dL) ≤ FPG <7.0 mmol/L (126 mg/dL); or FPG < 5.5 mmol/L, HbA1c ≥ 5.5%, BMI ≥ 25 kg/m2, triglyceride ≥ 1.69 mmol/L (150 mg/dL), hypertension treatment and family history of DM. Amongthe 734, only 4 persons with FPG ≥ 7.0 mmol/L were newly diagnosed as having DM, and17 persons with FPG ≥ 6.1 mmol/L (110 mg/dL) were diagnosed with impaired fasting glucose. Among 220 persons who received the OGTT, 115 had normal glucose tolerance, 85
had IGT and 20 had DM. When the above-mentioned criteria were added to FPG levels,
additional 67 persons with abnormal glucose tolerance were found. The optimal level todetect IGT and DM was 5.2 mmol/L (93 mg/dL) for FPG and 5.3% for HbA1c. Of persons
only with the single risk factor of hypertension treatment, 39.3% had IGT. In conclusion,
the results indicate that FPG of 5.2 mmol/L (93 mg/dL), HbA1c of 5.3% and hypertension
treatment are useful in detecting early stages of IGT and DM.
Key words: diabetes; hypertension; Japanese; risk factor

Atherosclerotic diseases such as heart disease andcerebral stroke are increasing in Japan with theaging of population in Japan and with changes oflifestyle. It is necessary to elucidate risk factors
and to establish a useful and cost-benefit method
to prevent the onset of diabetes mellitus (DM) and

impaired glucose tolerance (IGT). The American
Diabetes Association proposed new criteria forthe diagnosis of diabetes (1997). The Association recommended the diagnosis of diabetes withthe fasting plasma glucose (FPG) levels and notwith the oral glucose tolerance test (OGTT) in a

Abbreviations: BMI, body mass index; BP, blood pressure; DECODA, Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Asia; DECODE, Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe; DM, diabetes
mellitus; FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test; ROC, receiver operating characteristic; WHO, World Health Organization

105

T. Ohkura et al.

clinical setting, from the viewpoint of cost andconvenience (Expert Committee on the Diagnosis and Classification of Diabetes Mellitus, 1997).
The use of OGTT is still emphasized for clinicaldiagnosis of IGT and DM in Japan. In 1999, theJapan Diabetes Society published new diagnostic
criteria of diabetes, and had left the OGTT as amethod of diagnosis (Kuzuya et al., 2002). The useof OGTT stems from the fact that the pathology ofdiabetes in Asians including the Japanese does notarise mainly from obesity and insulin resistance,
as in Europeans and Americans. In Japan, half ofdiabetics have a genetic background, and in leanpersons, insulin secretion is impaired. Therefore, it
is difficult to detect diabetes in its early stages with
the FPG level alone (Kadowaki et al., 1984, 1994).
The DECODA Study showed that 45% of diabetics
were missed when the OGTT was not performed(Qiao et al., 2000). Therefore, the World HealthOrganization (WHO) also has recommended the
OGTT as a screening for diabetes (Alberti et al.,1998). We think it important to develop a screening protocol for persons at high risk of diabetes byusing a combination of FPG and HbA1c because of
its simplicity.
The criteria for glucose intolerance in the basic health examination of residents are establishedin the Law of Health and Medical Service for the
Aged in Japan. The criteria recommend that medical treatment is necessary in persons with FPG ≥ 7.0
mmol/L (126 mg/dL), casual plasma glucose ≥ 11.1
mmol/L (200 mg/dL) and HbA1c ≥ 6.1%. However, if the test results are the following, the patient
will need lifestyle guidance and will not require
the intensive examination at a medical institution: 6.1 mmol/L (110 mg/dL) ≤ FPG < 7.0 mmol/
L (126 mg/dL), 7.8 mmol/L (140 mg/dL) ≤ casualplasma glucose < 11.1 mmol/L (200 mg/dL), 5.5%
≤ HbA1c < 6.1%. The persons with the following
results will be considered to have no abnormality:
FPG < 6.1 mmol/L (110 mg/dL), casual plasma glucose < 7.8 mmol/L (140 mg/dL) and HbA1c < 5.5%.
There have been reports that the following criteria
have high sensitivity to detect diabetes in Japanese:
FPG ≥7.0 mmol/L (126 mg/dL) and HbA1c ≥ 6.1%
(Takahashi et al., 2000; Ito et al., 2000). However,it has been reported that a plasma glucose level of
11.1 mmol/L (200 mg/dL) at 2 h after glucose load (2h-LPG) was equivalent to FPG level of 5.8 mmol/
L (104 mg/dL) in Asians (Nakagami et al., 2002).
Moreover, in 2003, the American Diabetes Association indicated that the cutoff level for IFG should
be reduced from 110 to 100 mg/dL, and that IFG
should be redefined as an FPG of 100 to 125 mg/
dL (5.6–6.9 mmol/L) (The Expert Committee on
the Diagnosis and Classification of Diabetes Mellitus, 2003). Although the criteria described above
appear to be sensitive enough to detect apparent
diabetes, persons with early stage diabetes or IGT
may be missed.
Kofu Town is located near the Tottori University Faculty of Medicine. The residents of Kofu
Town have suffered from a 3-fold higher incidenceof cerebral stroke than the national average in Japan.
In order to prevent cerebral stroke events, a newprogram called the Tottori-Kofu Study was started
in 2005. The program intends to detect high-risk
persons for cerebral stroke and recruit them into
early intervention protocols such as lifestyle guidance. Within the program, we tried to develop an
effective screening method for IGT or DM, since
IGT or DM are recognized as high-risk factors forstroke. The aim of this study is to develop an effective and low-cost strategy for early detection of DM
and IGT. This strategy utilized simple predictors
including FPG, HbA1c and body mass index (BMI)
from the basic examination results.

Subjects and Methods
Research design and subjects
This is a cross-sectional study. The subjects were
734 residents aged 35 years or older who had undergone a basic medical check-up in 2005 in Kofu
Town, Tottori Prefecture, Japan (Fig. 1).
Confirmation of risk factors
At the basic medical check-up for the 734 residents, height, weight and blood pressure (BP) were106

Tottori-Kofu Study

FPG dose equivalence:

734 persons, FPG measured

5.5 mmol/L to 100 mg/dL
6.1 mmol/L to 110 mg/dL
7.0 mmol/L to 126 mg/dL

32 persons, DM treatment
4 persons, DM (FPG ≥ 7.0 mmol/L)
698 persons, not diagnosed as having DM
348 persons with FPG < 5.5 mmol/L, HbA1c < 5.5% and no other risk factors*
350 persons with FPG ≥ 5.5 mmol/L, HbA1c ≥ 5.5% and other risk factors*,requested to take OGTT
130 persons did not accept OGTT

*Other risk factors:
BMI ≥ 25 kg/m2
Triglyceride ≥ 150 mg/dL
Hypertension treatment
Familial history of DM

220 persons received OGTT
53 persons: 5.5 mmol/L ≤ FGP < 7.0 mmol/L		
167 persons: FPG < 5.5 mmol/L with other risk factors

27 IGT and 11 DM persons
58 IGT and 9 DM persons

Fig. 1. Cross-sectional study design for the Tottori-Kofu Study. BMI, body mass index; DM, diabetes mellitus; FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; OGTT, oral glucose tolerance test.

measured. Blood was also collected and plasma
glucose, HbA1c and serum triglyceride levels were
measured. Plasma glucose was measured with theglucose oxidase method, and HbA1c by high-performance liquid chromatography. The BMI [bodyweight (kg)/height2 (m2)] and serum triglyceride
levels were used to determine whether or not thepersons were overweight (BMI ≥ 25 kg/m2: highBMI) or hypertriglyceridemic [triglyceride ≥ 1.69
mmol/L (150 mg/dL): high-triglyceride]. In addition, the following history was confirmed: historyof hypertension treatment and family history of
diabetes in relatives within 3 degrees of kinship.
To establish the risk criteria for this study, we
referred to past reports in the literature. One of thereports examined plasma glucose and HbA1c of another Asians, Chinese subjects. It stated that FPG≥ 5.6 mmol/L (104 mg/dL) and HbA1c ≥ 5.5% werethe most sensitive and specific (Ko et al., 1998). In
Japanese persons, the risk of DM for those under
60 years of age and with BMI ≥ 25 kg/m2 is 50%
higher than for those who do not meet these conditions (Ito et al., 1994). When factors related to 2
h-LPG were examined, the profiles of age, BMI,
triglyceride and hypertension were considered to
be predictors for 2 h-LPG (Bando et al., 2001). According to the DECODE (DECODE Study Group,2003), DECODA (Nakagami and DECODA
Study Group, 2004), Hisayama (Fujishima et al.,107

1996) and Funagata (Tominaga et al., 1999) Studies, the risk of a cardiovascular event in IGT wasapproximately 2 times higher than in the normal
type. The Third National Health and Nutrition
Examination Survey in the United States indicatedthat the IGT risk is high in those with risks suchas FPG ≥ 5.5 mmol/L (100 mg/dL), age of 64 to
74 years, triglyceride ≥ 1.69 mmol/L (150 mg/dL),
BMI ≥ 30 kg/m2 and hypertension (Nelson et al.,2003). Moreover, another Japanese study reported
that the familial history for hypertension, diabetes
and dyslipidemia is an important aid towards aprevention strategy and public health practice formetabolic disorders (Wada et al., 2006). Based on
the previous reports, we applied the OGTT for our
subjects who had a risk of 5.5 mmol/L (100 mg/dL) ≤ FPG < 7.0 mmol/L (126 mg/dL); or who had
FPG < 5.5 mmol/L but had HbA1c ≥ 5.5%, BMI≥ 25 kg/m2, triglyceride ≥ 1.69 mmol/L (150 mg/dL), hypertension treatment or family history of
DM. The number of high-risk residents of the latter group was 350. However, diabetics with FPG< 5.5 mmol/L and HbA1c < 5.5% are rare, as reported in Chinese and Japanese population studies
as only 2% of these participants was DM (Ko et al.,
1998; Takahashi et al., 2001). When the BMI wasless than 25, 24.9% of the sample population was
diabetic (Ito, 1983). When the triglyceride level wasless than 150 mg/dL, 4% of the sample population

T. Ohkura et al.

h-LPG ≥ 10.0 mmol/L (180 mg/dL), the risk ofdeveloping diabetes is higher than those having 1
h-LPG < 10.0 mmol/L. The persons with 1 h-LPG≥ 10.0 mmol/L should be handled as with IGT accordingly (Kuzuya et al., 2002). In a recent report,
the cutoff value for impaired glucose regulation
was 10.1 mmol/L (182 mg/dL) for blood glucose
at 60 min (Zhou et al., 2006a, 2006b). One study
from the United States indicates that a high levelof plasma glucose at 30 to 90 min is associatedwith increased cardiovascular risk factors, even ingroups with normal FPG and 2 h-LPG (Modan etal., 1989). Therefore, persons with 1 h-LPG ≥ 10.0
mmol/L (180 mg/dL) were determined to have IGT.
Persons not classified into either group were determined to have normal glucose tolerance: their FPG
was < 6.1 mmol/L (110 mg/dL), 1 h-LPG < 10.0
mmol/L (180 mg/dL) and 2 h-LPG < 7.8 mmol/L(140 mg/dL).

was diabetic (Kametani et al., 2002). According
to these studies, in participants with FPG < 5.5mmol/L, HbA1c < 5.5%, BMI < 25 kg/m2 and triglyceride < 1.69 mmol/L, the percentage of DM wascalculated as 2% by 25% by 4%, resulting as 0.02%.
So, we did not apply the OGTT to the 348 residents
with FPG < 5.5 mmol/L, HbA1c < 5.5%, BMI <25kg/m2, triglyceride < 1.69 mmol/L, with no family history of DM or with no hypertension treatment. Finally, the OGTT was performed on 220
residents of the 350, the remaining 130 refusing thetest. However, there was no significant difference
between the 220 performed and 130 nonperformed
residents according to age, BMI, FPG, HbA1c, triglyceride level, SBP and DPB (unpaired t-test, data
not shown).
Measurement of waist circumference is notincluded in a routine medical check-up under the
Health and Medical Service Law for the Aged. But
in this study, we decided to measure waist circumference to estimate the clinical relevance of waist
abnormality. The diagnostic criteria of metabolic
syndrome in Japan were applied to determine theabnormal waist circumference sizes as ≥ 85 cm formales and ≥ 90 cm for females (Examination Committee of Criteria for ‘Obesity Disease’ in Japan,
2002).

Statistical analysis
Data were expressed as mean ± SEM. Significanceof differences in mean values was determined byusing unpaired t-tests. In the logistic regression
analysis, the persons determined to have IGT and
DM were combined as persons with abnormal glucose tolerance (IGT + DM). The dependent variable was abnormal glucose tolerance (IGT + DM),and the explanatory variables were male, HbA1c≥ 5.5%, high-BMI, high-triglyceride, hypertension
treatment, family history of diabetes, family history of hypertension, waist abnormality and age. Binomial logistic regression was performed, and thefactors with significant odds ratios were obtained.
Odds ratios were determined if the explanatory
variables were redundant. A P value, 0.05 or less,was considered to be statistically significant.
To evaluate the DM + IGT, we determinedthe cutoff values from the receiver operating characteristic (ROC) analysis of the optimal FPG and
HbA1c. The sensitivity of FPG and HbA1c cutoff
points on the results of the basic medical checkup was defined as its ability to correctly identify
persons who had abnormal glucose tolerance (IGTor DM) in the OGTT. The specificity was defined

Determination of abnormal glucose tolerance
As a secondary screening test, the 75-g OGTT
was used for persons who accepted to take the test.
The determination of diabetes was based on the1998 diagnostic criteria of the WHO and with thelevels of FPG and 2 h-LPG (Alberti et al., 1998).
The subjects were determined to have DM if they
had FPG ≥ 7.0 mmol/L (126 mg/dL) or 2 h-LPG ≥11.1 mmol/L (200 mg/dL). The subjects were determined to have IGT if they had FPG < 7.0 mmol/
L (126 mg/dL) and 7.8 mmol/L (140 mg/dL) ≤ 2
h-LPG < 11.1 mmol/L (200 mg/dL). The subjects
were determined to have impaired fasting glucose(IFG) if they had 6.1 mmol/L (110 mg/dL) ≤ FPG <7.0 mmol/L (126 mg/dL) and 2 h-LPG < 7.8 mmol/
L (140 mg/dL). Even if the subjects were normal
based on the WHO criteria, if a Japanese has 1
108

Tottori-Kofu Study(91.4 mg/d L), mean HbA1c 5.19%, mean systolic
BP 127.8 mmHg, mean diastolic BP 76.0 mmHg
and mean fasting triglyceride 1.16 mmol/L (103.5
mg/dL) (Table 1). From the 734, 32 persons who
had already been treated for diabetes were excluded. Of the 702 not treated for diabetes, only 4
persons with FPG ≥ 7.0 mmol/L (126 mg/dL) were
newly diagnosed as having diabetes and only 17
persons with 6.1 mmol/L (110 mg/dL) ≤ FPG < 7.0mmol/L, as having IFG (Table 2). As described in
the Subjects and Methods, a total of 220 persons
accepted the OGTT as the secondary examination.
In the results of the OGTT for the 220 persons, mean BMI was 23.9 kg/m2, mean FPG, 5.17mmol/L (93.0 mg/dL) and mean HbA1c, 5.20%(Table 1). Mean levels in BMI, systolic BP, diastolic BP and triglyceride were significantly higher in
the OGTT-received persons than the basic medical
checked-up, but those in FPG and HbA1c were not.
Among the OGTT-received persons, 115 (52.3%)
had normal glucose tolerance, 85 (38.6%) had IGT
and 20 (9.1%) had DM (Table 2). No person had
IFG. Among 14 persons with 6.1 mmol/L (110 mg/dL) ≤ FPG < 7.0 mmol/L (126 mg/dL), 5 persons(35.7%) had IGT and 7 persons (50%) had DM.
Two persons showed normal glucose tolerance

as its ability to correctly identify persons who had
NGT in the OGTT. To compare the ability of FPG
and HbA1c measurements to detect the presenceor absence of abnormal glucose tolerance (IGTor DM), we plotted ROC curves. The diagnostic
properties of specific cutoff levels of FPG and
HbA1c were defined by maximizing the sensitivity
and specificity to identify IGT or DM. An ROC
curve is a graph of sensitivity versus (1 – specificity) for various cutoff definitions of a positive
diagnostic test result. The optimal cutoff points
were obtained from the Youden index [maximum(sensitivity + specificity – 1)], and the point on the
ROC curve closest to (0,1) was calculated as theminimum value of the square root of [(1 – sensitivity)2 + (1 – specificity)2] (Youden, 1950; Perkins etal., 2006). Greater accuracy is reflected by a larger
Youden index and a smaller distance to (0, 1). SPSS
15.0 (SPSS, Chicago, IL) was used for analysis.

Results
The present 734 subjects consisted of 272 males
and 462 females. Their mean age was 66.4 years,
mean BMI 22.7 kg/m2, mean FPG 5.07 mmol/L

Table 1. Clinical characteristics of persons who received the basic medical check-up and the secondary OGTT
Persons who received
The basic medical check-up
The OGTT
Number of persons
Male/female ratio
Age
HeightWeightBody mass index
FPG
HbA1c
Systolic BP
Diastolic BP
Total cholesterol
Triglyceride
HDL-cholesterol(year)(cm)(kg)(kg/m2)(mmol/L)(%)(mmHg)(mmHg)(mmol/L)(mmol/L)(mmol/L)

734
272/46266.4 ± 13.0
155.6 ± 8.5
55.1 ± 10.3
22.7 ± 3.5
5.07 ± 0.67
5.19 ± 0.4
127.8 ± 17.8
76.0 ± 10.6
5.27 ± 0.84
1.16 ± 0.67
1.49 ± 0.35

22082/13866.5 ± 11.4
154.8 ± 8.2
57.4 ± 10.0
23.9 ± 3.2
5.17 ± 0.53
5.20 ± 0.3
133.8 ± 16.8
79.0 ± 9.2
5.37 ± 0.83
1.42 ± 0.82
1.40 ± 0.33

P valueNSNS< 0.005< 0.005
NSNS< 0.005< 0.005NS< 0.005< 0.005

Data represent mean ± SD.
P values represent results of comparison between groups of persons receiving the basic check-up and the secondary OGTT.
Unpaired t-test was used for statistical analysis.
BP, blood pressure; FPG, fasting plasma glucose; HDL, high-density lipoprotein; NS, not significant; OGTT, oral glucose tolerance test.

109

T. Ohkura et al.

Table 2. Results of OGTT classified by FPG levels and other factors
FPG levelin the basic medical
check-up

Persons who received			Results of the OGTTThe basic medical
The
Normal		Abnormalcheck-up
OGTT
(NGT)
IGT
DM

DM treatment (+)
7.0 mmol/L ≤ FPG
6.1 mmol/L ≤ FPG < 7.0 mmol/L
5.5 mmol/L ≤ FPG < 6.1 mmol/L
FPG < 5.5 mmol/L with other risk factors
FPG < 5.5 mmol/L and HbA1c < 5.5%
with no other risk factors
Total

IGT + DM

32
4
17
60
238

14
39
167

2 (14.3)
13 (33.3)
100 (59.8)

5 (35.7)
22 (56.4)
58 (34.7)

7 (50.0)
4 (10.3)
9 ( 5.3)

12 (85.7)
26 (66.7)
67 (40.1)

348
734

220

115 (52.3)

85 (38.6)

20 ( 9.1)

105 (47.7)

FPG dose equivalence: 5.5 mmol/L equivalent to 100 mg/dL; 6.1 mmol/L, to 110 mg/dL; 7.0 mmol/L, to 126 mg/dL.
Data represent number of persons: ( ), %.
No one with impaired fasting glucose.
DM, diabetes mellitus; FPG, fasting plasma glucose; IGT, impaired glucose tolerance; NGT, normal glucose tolerance;
OGGT, oral glucose tolerance test.

Table 3. Results of the OGTT in persons with FPG < 5.5 mmol/L and other risk factors
Risk factor
HbA1c BMI Triglyceride Hyper≥ 5.5≥ 25≥ 1.69tensionkg/m2 mmol/L treatment
+
–
–
–
–
–
–
–
–

+ or –
+
–
–
+
+
–
+
–

+ or –
–
+
–
+
–
+
+
–

+ or –
–
–
+
–
+
+
+
–

Results of the OGTT
Normal		Abnormal
(NGT)
IGT
DM

IGT + DM

22
33
16
61
14
4
5
5
7

4 ( 18.2)
24 ( 72.7)
14 ( 87.5)
37 ( 60.7)
7 ( 50.0)
2 ( 50.0)
2 ( 40.0)
5 (100 )
5 ( 71.4)

12 (54.6)
9 (27.3)
1 ( 6.3)
24 (39.3)
6 (42.8)
2 (50.0)
2 (40.0)0( 0 )
2 (28.6)

6 (27.3)0( 0 )
1 ( 6.3)0( 0 )
1 ( 7.1)0( 0 )
1 (20.0)0( 0 )0( 0 )

18 (81.8)
9 (27.3)
2 (12.6)
24 (39.3)
7 (50.0)
2 (50.0)
3 (60.0)0 ( 0)
2 (28.6)

167

100 ( 59.8)

58 (34.7)

9 ( 5.3)

67 (40.1)

Familial
historyof DM

Numberofpersons+ or –+ or –+ or –+ or –+ or –+ or –+ or –+ or –+

Subtotal in FPG < 5.5 mmol/L with other risk factors

FPG dose equivalence: 5.5 mmol/L equivalent to 100 mg/dL.
Data represent number of persons: ( ), %.
BMI, body mass index; DM, diabetes mellitus; FPG, fasting plasma glucose; IGT, impaired glucose tolerance; NGT, normal
glucose tolerance; OGGT, oral glucose tolerance test.

with FPG < 6.1 mmol/L (110 mg/dL) in the OGTTin spite of their FPG ≥ 6.1 mmol/L in the basic
medical check-up. Among the 39 persons with 5.5mmol/L (100 mg/dL) ≤ FPG < 6.1 mmol/L (110mg/dL), 22 persons (56.4%) had IGT and 4 persons(10.3%) had DM. Among 167 persons with FPG <5.5 mmol/L (100 mg/dL) with other risk factors, 58
persons (34.7%) had IGT and 9 persons (5.3%) had
DM.
In analyzing persons with FPG < 5.5 mmol/
L (100 mg/dL) and with another single risk factor (Table 3), persons with a single risk factor of

HbA1c ≥ 5.5% were accounted for 22, who included 12 IGT persons (54.6%) and 6 DM persons (27%).
Persons with a single risk factor of high-BMI were
accounted for 33, who included 9 IGT persons(27.3%). Those with a single risk factor of hightriglyceride were 16, including 1 IGT person (6.3%)
and 1 DM person (6.3%). Those with a single risk
factor of hypertension treatment were 61, including
24 IGT persons (39.3%). Those with a single risk
factor of family history of DM were 7, including 2
IGT persons (28%). Therefore, of all 220 persons
who received the OGTT, a total number of persons
110Tottori-Kofu Study

Table 4. Odds ratio for IGT + DM by multiple regression analysis

with glucose intolerance was 105 (47.7%). Whenthe above-mentioned criteria were added to FPG
for the 220, additional 67 abnormal persons weredetected (Table 3).
Logistic analysis was applied to statisticallyexamine the risk factors for abnormal glucose tolerance (DM + IGT). For abnormal glucose tolerance (DM + IGT), the odds ratio of hypertension
treatment was 2.43 (P = 0.077; 95% confidence
interval, 0.91–6.49) and that of familial history of
DM was 2.64 (P = 0.094; 95% confidence interval,
0.85–8.23), indicating a weak tendency, respectively (Table 4). We also examined the criteria of
the abnormal waist size as ≥ 85 cm for males and ≥90 cm for females, but the abnormal waist size was
not a significant risk factor. Next, we determined
FPG with the highest sensitivity and specificity using the ROC curve for abnormal glucose tolerance(DM + IGT). The optimal FPG was 5.2 mmol/L (93mg/dL) (sensitivity, 0.62 and specificity, 0.65) (Fig.
2a), and the optimal HbA1c, 5.3% (sensitivity, 0.57
and specificity, 0.74) (Fig. 2b).

Risk factor

Abnormal glucose tolerance(IGT + DM)
Odds
P
95%
ratio value Confidence			interval
Age
0.99
Gender (male)
1.10
BMI ≥ 25.0 kg/m2
1.70
Triglyceride ≥ 1.69 mmol/L
0.95
Hypertension treatment
2.43
HbA1c ≥ 5.5%
16.3
Familial history of DM
2.64
Familial history of hypertension 1.29
Waist abnormality
1.32

0.618
0.803
0.294
0.899
0.077
0.001
0.094
0.532
0.558

0.96–1.02
0.50–2.45
0.63–4.55
0.40–2.23
0.91–6.49
4.09–65.8
0.85–8.23
0.58–2.84
0.52–3.39

Data are the dependent variable (abnormal glucose tolerance) versus the explanatory variable (NGT): abnormal
glucose tolerance, DM in 20 and IGT in 85 persons; NGT in
115 persons.
Adjusted for all explanatory variables.
BMI, body mass index; DM, diabetes mellitus; IGT, impaired glucose tolerance; NGT, normal glucose tolerance.

a

FPG

1.0

b

Sensitivity

In this study, the Government-driven criteria were
specific to detect relevant IGT and DM; however,it was not sufficient for early detection of mild
DM and IGT. When a condition such as hightriglyceride or hypertension treatment was added
to Government-driven FPG and HbA1c criteria, we
could detect many people with abnormal glucose
tolerance.
The optimal HbA1c to detect the IGT + DM
pattern in the ROC analysis was 5.3%: this result
was compatible with other studies in Asians (Nakagami et al., 2002). However, the optimal FPG
we observed to detect IGT + DM was 5.2 mmol/
L (93 mg/dL). Our sample population was muchsmaller than that of the DECODA Study. Recently,
the High-risk and Population Strategy for Occupational Health Promotion Study reported that therisk of diabetes abruptly rose in persons with blood
glucose levels higher than 5.2 mmol/L (94 mg/dL)(Hayashino et al., 2007). We consider that FPG 5.2

0.6
0.4

FPG 5.2 mmol/L(93 mg/dL)

0.2
0.0
0.0

0.2

0.4

0.6

0.8

1.0

1 – Specificity

HbA1c

1.0
0.8

Sensitivity

Discussion

Abnormal glucose tolerance (DM + IGT)

0.8

0.6
0.4

HbA1c 5.3%
0.2
0.0

0.0

0.2

0.4

0.6

0.8

1.0

1 – Specificity

Fig. 2. Receiver operating characteristic curves for FPG
and HbA1c in predicting DM + IGT in the OGTT. Sensitivity is plotted as a function of (1 – specificity). Points
on the curve representing optimal FPG and HbA1c aremarked with circles. DM, diabetes mellitus; FPG, fasting
plasma glucose; IGT, impaired glucose tolerance; OGTT,
oral glucose tolerance test.

111

T. Ohkura et al.

mmol/L and HbA1c 5.3% were effective to detect
IGT and DM.
Of persons with only a single risk factor ofhypertension treatment, 39.3% showed the IGT pattern. These results indicated that FPG and HbA1c
are effective enough to find DM, but FPG and
HbA1c alone are insufficient to find IGT. It is important to examine risk factors additional to hypertension treatment. In general, hypertension alone
is not considered as a high-risk factor for abnormal
glucose tolerance. However, there are several reports that hypertension is associated with the angiotensin II and aldosterone system, which affects
insulin resistance (Folli et al., 1997; Sowers, 2004;
Catena et al., 2006; Colussi et al., 2007). Basedon the present study, hypertension was a majorrisk factor for IGT. These results are very interesting from the view of novel IGT criteria. Recently,
the United States Preventive Services Task Forcereported that evidence is lacking on the health benefits of detecting type 2 diabetes by either targeted
or mass screening, but persons with hypertension
probably benefit from screening (Norris et al.,2008). According to the 2004 survey of hypertension treatment of Kofu Town, 289 patients had received hypertension treatment: 216 patients (74.7%)
used a calcium antagonist, 33 patients (11.4%) used
an angiotensin-converting enzyme inhibitor, 163
patients (56.4%) used an angiotension II receptor
blocker, 113 patients (39.1%) used an alpha-blocker,
17 patients (5.8%) used a beta-blocker and 63 patients (21.8%) used a diuretic (data not shown). In
the present study, we did not examine the prevalence of glucose intolerance according to the hypertension drugs. However, risk analysis by eachdrug would be a topic of future study.
There are few reports describing criteria forscreening IGT and DM in Japanese and Asian
populations. The criteria we presented here are anovel method to target early stages of IGT and DM
in Japanese and Asian populations. The Japanese
Government plans to drop the FPG criteria from 6.1
to 5.5 mmol/L (110 to 100 mg/dL), in order to findthe early stage of diabetes and prevent the following cardiovascular event. Although the interpretation of this study is limited because of the small

number of participants and no cohort study, thisstudy supports such a new guideline for the Japanese population and any other Asians. Residentsof Kofu Town have shown a high incidence of
cerebral stroke. According to NIPPON DATA80,
which is an observation cohort study on strokein the Japanese population, the stroke mortality
tended to be almost 2 times higher in rural areas
than in urban areas in Japan (Nishi et al., 2007).
The mortality rate of stroke in rural areas is nearly
equal to that of Kofu Town. The reason for thisgeographical variation is likely to be related to theprevalence of hypertension. This type of environment is similar to Kofu Town, so our criteria would
be applicable to other rural areas in Japan.
In conclusion, we were able to detect earlystages of abnormal glucose tolerance using combinations of FPG, HbA1c, BMI, triglyceride, hypertension treatment and family history of DM.
The results indicate that only FPG ≥ 6.1 mmol/L(110 mg/dL) is not sufficient to detect early stagesof DM and IGT. The most useful criteria for early
detection of IGT and DM were FPG ≥ 5.2 mmol/
L (93 mg/dL) and HbA1c ≥ 5.3%. In addition, even
if FPG was less than 5.5 mmol/L (100 mg/dL), hypertension treatment might be taken into accountfor the IGT risk, since 39.3% of persons with asingle risk factor of hypertension treatment showed
the IGT pattern. The interpretation of this study
was limited, since it was not a cohort study and thegroup of 220 OGTT-received residents was biased.
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Received June 22, 2009; accepted July 16, 2009
Corresponding author: Shin-ichi Taniguchi, MD, PhD

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