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Article history: Aims: We investigated the specificity of the 75 g oral glucose tolerance test (OGTT) and the
Received 31 March 2017 clinical usefulness of the 2 h post loading glucose (2 h PLG) value in the clinical care of
Received in revised form diabetes patients.
31 May 2017 Methods: The 75 g OGTT data of 1755 subjects were analyzed. The relationships and degrees of
Accepted 3 June 2017 consistency among 2 h PLG, fasting plasma glucose (FPG), and HbA1c values were assessed.
We also investigated the degree of contribution of 2 h PLG in the prescription of glucose-
lowering agents and in the pitfall group for use of 75 g OGTT.
Keywords: Results: Among 595 subjects with normal FPG, only 329 (55.3%) showed normal 2 h PLG level,
Diabetes and 66 (11.1%) patients could be considered as having diabetes. Among 454 diabetes patients
Oral glucose tolerance test (based on FPG and HbA1c), 409(90.1%) showed 2 h PLG values in the range of diabetes, 45
2 h post loading glucose (PLG) (9.9%) subjects did not exhibit diabetes. Pitfall group who used 75 g OGTT for diagnosis
diabetes (lower 2 h PLG value compared to fasting and upper 2 h PLG value compared to
fasting) showed differences in body weight and height.
Conclusions: Based on OGTT results, around 10% patients cannot be diagnosed with diabetes
based solely on the 2 h PLG value. Further studies on differences in glucose loading according
to body weight, individual life pattern, and calorie requirement are needed for improvement
of the specificity of the OGTT in the clinical management of diabetes.
© 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
∗
Corresponding author at: Division of Endocrinology and Metabolism, Department of Internal Medicine, Chonbuk National University
Medical School, Gungiro 20 (634-18, Keum-Am Dong), Deok Jin Gu, Jeonju 561-712, South Korea. Fax: +82 63 254 1609.
E-mail address: mdjinhy@jbnu.ac.kr (H.Y. Jin).
http://dx.doi.org/10.1016/j.pcd.2017.06.003
1751-9918/© 2017 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
556 p r i m a r y c a r e d i a b e t e s 1 1 ( 2 0 1 7 ) 555–560
or pre-diabetes range in self-monitoring blood glucose (SMBG) 05-030-001). 270 patients were excluded due to malignancy,
records in routine daily life. Such patients do not need anti- anemia, chronic kidney disease or other disease. Therefore,
diabetes medication, and life style modification is the initial OGTT results of total 1755 patients were analyzed in this study.
management strategy of choice. However, the possibility that We performed a retrospective analysis of 75 g OGTT data in
these patients might be over-diagnosed with diabetes due to 1755 patients. We evaluated history of disease, family his-
the relatively high glucose dose of 75 g in the OGTT should tory, and medications using medical records. We also assessed
not be overlooked. This situation might be common in clini- body weight, height, BMI, and all laboratory findings, including
cal practice. The 75 g OGTT is well known to be helpful for the HbA1c, 75 g OGTT glucose level, fasting insulin, and c-peptide
diagnosis of diabetes, especially when patients show an IFG level.
state; however, it is not clear why a 75 g dose of glucose is used Diagnoses of diabetes, pre-diabetes, and normal glu-
and whether this amount is adequate for every IFG patient. In cose state were defined based on the ADA guidelines
addition, inter-or intra-individual variability and low repro- follows [4] normal, FPG <5.6 mmol/L; impaired fasting
ducibility can be pitfalls in the 75 g OGTT. The amount of glucose, 5.6 mmol/L ≤ FPG <7.0 mmol/L; and diabetes, FPG
glucose loading might need to be individualized according to ≥7.0 mmol/L. 2 h post loading glucose (PLG) after 75 g OGTT
body weight, height, daily caloric intake, and race, if neces- <7.8 mmol/L indicated a normal state, 7.8 mmol/L ≤ 2 h PLG
sary, although 75 g is well accepted as a standard glucose dose <11.1 mmol/L indicated impaired glucose tolerance, and 2 h
in the OGTT. PLG ≥11.1 mmol/L indicated the presence of diabetes. Among
Therefore, we need to reconsider whether 75 g glucose 1755 patients, 595 patients (33.9%) showed normal FPG (below
load is appropriate irrespective of patient clinical charac- 5.6 mmol/L), however, they had high risk factors of diabetes
teristics. The relationship between glucose value and 75 g such as 40 years old, family history of diabetes, overweight,
OGTT and its clinical significance should also be considered hypertension, dyslipidemia, or cardiovascular disease [4] or
in the clinical care of high-risk patients with diabetes with showed 7.8–11.1 mmol/L range of random glucose value. FPG
regard to medication initiation and avoidance of unnecessary of 706 patients (40.2%) were between 5.6 and 7.0 mmol/L,
medication. Micro-vascular complications such as diabetic hence OGTT was performed to diagnosis prediabetes or dia-
autonomic neuropathies can also impact the glucose level, betes exactly. 454 patients (25.9%) already showed FPG over
resulting in a lack of response despite the loaded glucose 7.0 mmol/L, however, OGTT also was performed to assess the
amount [3]. However, the glucose response from a 75 g glu- degree of glucose tolerance. The 75 g OGTT data of 1755 sub-
cose load is expected to differ according to variable patient jects were analyzed to compare the 2 h PLG value after 75 g
factors such as beta cell function, enteric hormones, and neu- glucose loading with HbA1c and FPG in the coincidence of dia-
ral responses to nutrient ingestion. For example, the results betes diagnosis to reaffirm the accuracy of the 2 h PLG value
might differ between a 50 kg patient and a 100 kg patient, in the diagnosis of diabetes. We also reviewed the role of the
even if they have similar pancreatic beta cell function or 2 h glucose value in the decision to initiate glucose-lowering
insulin resistance. Therefore, low-body weight patients might agents in diabetes patients who were diagnosed by 75 g OGTT.
be diagnosed with diabetes, even though routine daily glu- Furthermore, we evaluated the clinical characteristics of the
cose values do not exceed the diabetes threshold. On the pitfall group in the use of 2 h glucose value after 75 g OGTT for
contrary, high-body weight patients might not show glucose the diagnosis of diabetes.
values indicating diabetes, even though routine daily glucose All statistical analyses were performed using the Statis-
values are in the diabetic range, because 75 g is too small of a tical Package for the Social Sciences 18 (SPSS Inc., Chicago,
dose to increase the glucose level to 11.1 mmol/L compared to IL). Data are expressed as mean ± standard deviation (SD)
the routine daily caloric intake needed to maintain their body or median (interquartile range [IQR]), and categorical vari-
mass index (BMI). ables are presented as percentage. For comparisons between
In this study, we investigated the rate of diagnosis of dia- groups, Student’s t test was used for normally distributed vari-
betes based on the 75 g OGTT compared to that based on the ables and the Mann–Whitney U test for variables with skewed
FPG and HbA1c. Furthermore, we analyzed the usefulness of distribution. The Spearman correlation method was used for
75 g OGTT results in the decision to prescribe anti-diabetes evaluation of significant correlation between variables. We
medication in clinical practice. We also assessed the charac- assessed the sensitivity and specificity of each glucose value
teristics of the pitfall group in the use 75 g OGTT, which could determined in the 75 g OGTT for diabetes diagnosis and ana-
be under-diagnosed or over-diagnosed with diabetes using a lyzed receiver operating characteristic curves for the diagnosis
75 g glucose load compared to FBS, HbA1c, and SMBG results of diabetes according to 75 g OGTT fasting, 1 h, and 2 h glucose
based on routine daily caloric intake. levels, and HbA1c. P values <0.05 were considered statistically
significant for all calculations.
2. Methods
3. Results
Total 2810 patients had 75 g OGTT in Chonbuk National Univer-
sity Hospital, Korea from 1995 to 2013. And there was already 3.1. Subject characteristics
an informed consent of permission for using patient’s OGTT
data in the future for study at that time. Based on these Baseline subject characteristics are presented in Table 1. The
consents, we received the approval of Institutional Review mean age of 1755 subjects was 52.2 ± 12.9 years. Among 1755
Board of Choubuk national university hospital (Reg. No. 2016- patients, the number of subjects less than 30 years old was
p r i m a r y c a r e d i a b e t e s 1 1 ( 2 0 1 7 ) 555–560 557
cose value according to glucose tolerant state (Table 2). Among FPG: fasting plasma glucose, IFG: impaired fasting glucose, IGT:
595 patients with normal FPG, only 329 (55.3%) were in a nor- impaired glucose tolerance, PLG: post loading glucose.
mal glucose tolerance state according to 2 h PLG (<7.8 mmol/L)
and HbA1c ( < 5.7%). Two hundred patients (33.6%) with a
normal FPG level showed an IGT state, 66 patients (11.1%) PLG of 75 g OGTT based on daily caloric intake. Among 454
showed 2 h PLG greater than 11.1 mmol/L, and 16 patients patients with diabetes based on FPG, 409 (90.1%) also showed
showed HbA1c higher than 6.5%, compatible with a diagno- 2 h PLG higher than 11.1 mmol/L, and 347 (76.4%) showed
sis of diabetes according to the ADA criteria. Among these HbA1c higher than 6.5%. However, 45 patients (9.9%) showed
66 patients with diabetes, only 28 (42.0%) had been treated 2 h PLG below 11.1 mmol/L. The accordance rate of 2 h PLG
with glucose-lowering agents; the others underwent glucose level with FPG was 55.1% in the normal group and 90.1% in
monitoring due to a random glucose value lower than 2 h the diabetes group to confirm a normal state and diabetic
558 p r i m a r y c a r e d i a b e t e s 1 1 ( 2 0 1 7 ) 555–560
Table 3 – Clinical characteristics of patients with diabetes medication (n = 592) by glucose tolerance test results (2 h PLG).
2h 2h 7.8 mmol/L ≤ 2 h P value
PLG < 7.8 mmol/L PLG ≥ 11.1 mmol/L PLG < 11.1 mmol/L
(n = 23) (n = 450) (n = 119)
Age (year) 43.5 ± 17.5 51.5 ± 12.4 51.2 ± 14.4 <0.01
Sex (female/male) 15/8 201/249 58/61
HbA1c (%) 5.3 ± 0.5 7.8 ± 1.7 6.3 ± 0.7 <0.01
OGTT fasting (mmol/L) 5.2 ± 0.3 8.4 ± 2.5 6.0 ± 0.8 <0.01
OGTT 1 h (mmol/L) 8.8 ± 2.1 16.9 ± 3.8 11.8 ± 2.5 <0.01
OGTT 2 h (mmol/L) 6.8 ± 0.4 17.0 ± 4.6 8.8 ± 1.6 <0.01
Insulin (pmol/L) 0.05 [0.04–0.07] 0.07 [0.07–0.08] 0.07 [0.06–0.08] 0.70
C-peptide (nmol/L) 1.7 [0.8–2.6] 0.9 [0.8–0.9] 0.8 [0.7–0.9] 0.47
Height (cm) 163.3 ± 4.6 162.6 ± 8.5 162.0 ± 9.8 0.83
Body weight (kg) 68.2 ± 7.3 67.3 ± 12.0 66.7 ± 10.8 0.53
BMI (kg/m2 ) 25.7 ± 3.4 25.5 ± 3.9 25.4 ± 3.4 0.68
BMI: body mass index, OGTT: oral glucose tolerance test
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Acknowledgements Intra-individual variation of glucose, specific insulin and
proinsulin concentrations measured by two oral glucose
We would like to thank the Research Institute of Clinical tolerance tests in a general Caucasian population: the Hoorn
Medicine of Chonbuk National University and the Biomedical Study, Diabetologia 39 (3) (1996) 298–305.
Research Institute of Chonbuk National University Hospital for
partly supporting our research with a grant.
references