diabetes research and clinical practice 107 (2015) 400–406

Contents available at ScienceDirect

Diabetes Research
and Clinical Practice
jou rnal hom ep ag e: w ww.e l s e v i er . c om/ loca te / d i ab r es

Efficacy of nutrition therapy for glucose intolerance

in Japanese women diagnosed with gestational
diabetes based on IADPSG criteria during early
gestation

Ichiro Horie a,*, Eiji Kawasaki b, Ai Sakanaka b,c, Miwa Takashima b,c,
Miwa Maeyama b,c, Takao Ando a, Hirokazu Hanada b,c,
Atsushi Kawakami a
a
Department of Endocrinology and Metabolism, Nagasaki University Hospital, Nagasaki, Japan
b
Department of Metabolism, Diabetes and Clinical Nutrition, Nagasaki University Hospital, Nagasaki, Japan
c
Division of Dietary Service, Nagasaki University Hospital, Nagasaki, Japan

article info abstract

Article history: Aims: Among women with gestational diabetes mellitus (GDM), the aggravation of glucose
Received 8 May 2014 intolerance during gestation differs substantially. We retrospectively investigated whether
Received in revised form the glucose intolerance of women diagnosed with GDM during early gestation (i.e., early-
12 September 2014 onset GDM) improved in the mid-gestation under appropriate nutrition therapy.
Accepted 25 December 2014 Methods: We conducted a longitudinal analysis of glucose tolerance derived from 75-g oral
Available online 21 January 2015 glucose tolerance test (OGTT) in 41 Japanese women with early-onset GDM defined by
International Association of Diabetes and Pregnancy Study Group criteria during early
Keywords: gestation (<20 weeks). Glucose tolerance was also evaluated in mid-gestation (24–32 weeks)
Gestational diabetes and postpartum. Insulin sensitivity, insulin secretion, and b-cell function were assessed at
Nutrition each period.
IADPSG Results: The glucose tolerance in 18 of the 41 early-onset GDM patients normalized during
OGTT mid-gestation with appropriate nutrition therapy, defined as GDM ! NGT. These women
Early gestation did not require insulin therapy during their pregnancies, whereas 39.1% of women who
retained GDM in mid-gestation (defined as GDM ! GDM) required insulin therapy. The
frequency of the postpartum development of type 2 diabetes or impaired glucose tolerance
was significantly lower (5.6% vs. 39.1% in GDM ! NGT vs. GDM ! GDM, p = 0.03). Primiparity
was determined as a predictive factor whether or not glucose intolerance was improved by
nutrition therapy, but results of plasma glucose levels from OGTT at early gestation were
not, in a multivariate logistic regression analysis.

* Corresponding author at: Department of Endocrinology and Metabolism, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-
8501, Japan. Tel.: +81 95 819 7262; fax: +81 95 849 7270.
E-mail address: holy197741@me.com (I. Horie).
Abbreviations: BMI, body mass index; GDM, gestational diabetes mellitus; HAPO, hyperglycemia and adverse pregnancy outcome;
HOMA-IR, homeostasis model assessment of insulin resistance; IADPSG, International Association of Diabetes and Pregnancy Study
Group; ISSI-2, insulin secretion-sensitivity index-2; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; IRI, immunoreactive
insulin; PG, plasma glucose; ANOVA, analyses of variance.
http://dx.doi.org/10.1016/j.diabres.2014.12.011
0168-8227/# 2015 Elsevier Ireland Ltd. All rights reserved.
 diabetes research and clinical practice 107 (2015) 400–406
Conclusions: Appropriate nutrition therapy for women with early-onset GDM seemed effec-
tive to improve glucose tolerance during pregnancy. OGTT retesting during their mid-
gestation seemed effective for predicting the appropriate treatment after the second trimester.
1. Introduction
Gestational diabetes mellitus (GDM) is a common medical
complication of pregnancy. GDM is defined as a less severe
form of glucose intolerance than overt diabetes, with onset or
first recognition during pregnancy [1]. Pregnancy is diabeto-
genic because of insulin resistance caused by anti-insulin
hormones secreted by the placenta [2]. Insulin resistance is
known to increase as pregnancy advances, exacerbating
during the second trimester of pregnancy and reaching a
plateau in the third trimester [3]. Pregnant women are believed
to develop GDM when insulin secretion fails to compensate for
the elevated insulin resistance as gestation advances.
The importance of universal screening for GDM in all
pregnant women between 24 and 28 weeks of gestation has
been emphasized [1,4–7] because the Hyperglycemia and
Adverse Pregnancy Outcome (HAPO) Research Group indicat-
ed in 2008 that adverse perinatal outcomes are associated with
plasma glucose levels which were lower than those that had
been considered pathogenic [8].
However, it has not been determined whether universal
screening for glucose intolerance before 24 weeks of gestation
to detect GDM is of clinical value or cost-effective [6]. Several
small studies have shown that early screening and therapeutic
intervention prevented heavy-for-gestational-age newborns
and diabetes-related complications in women with GDM
diagnosed during early gestation [9–12]. It has been shown
that more women required insulin therapy who developed
glucose intolerance in early gestation when compared to those
with GDM diagnosed during late gestation [10,13]. However,
the exacerbation of glucose intolerance during gestation may
differ substantially between individuals.
Here we retrospectively examined the glucose intolerance
of women diagnosed with GDM prior to 20 weeks of gestation
(defined as early-onset GDM) longitudinally by repeating an
oral glucose tolerance test (OGTT) at middle gestation and
postpartum. We also characterized pregnant women whose
glucose intolerance in early gestation was normalized under
an appropriate nutrition therapy.
2. Materials and methods
2.1. Patients
We retrospectively identified 116 pregnant Japanese women
who had undergone a 75-g OGTT in early gestation (before 20
weeks of gestation), by examining their medical charts. These
women underwent the OGTT because of abnormal screening
results (random plasma glucose 100 mg/dL or 135 mg/dL at
1 h by 50-g oral glucose challenge test) or/and high risk factors
401
# 2015 Elsevier Ireland Ltd. All rights reserved.
of GDM (i.e., obesity, family history of type 2 diabetes, history
of GDM, history of delivering heavy babies, and higher
gestational age) at Nagasaki University Hospital from 1990
to 2010. Among the 116 patients, we found 68 patients who
were diagnosed with GDM as defined by the International
Association of Diabetes and Pregnancy Study Group (IADPSG)
criteria [1]. The patients with GDM were instructed with
appropriate nutrition therapy. Of the 68 GDM patients defined
by IADPSG criteria, 41 patients had undergone second 75-g
OGTT at least 4 weeks after nutrition therapy between 24 and
32 weeks of gestation and third 75-g OGTT 4–8 weeks after
delivery.
The patients who showed any glucose intolerance before
conception or were diagnosed with overt diabetes in pregnan-
cy (fasting glucose  126 mg/dL, 2-h glucose  200 mg/dL
or HbA1c  6.5% [48 mmol/mol]) were excluded from this
study.
We also studied the maternal characteristics and perinatal
outcomes of the patients retrospectively by medical records
(Table 1). The body weight of each monthly visit was found in
31 out of 41 patients diagnosed with GDM during early
gestation and these data were used to study the weight gain in
each pregnant trimester.
2.2. Management of GDM patients
Nutrition therapy was instructed by dieticians as follows: a
30 kcal/kg/day diet of pre-gestational ideal body weight to
obese women (BMI  25 kg/m2) and a 35 kcal/kg/day diet to
non-obese women (BMI < 25 kg/m2) comprised of carbohy-
drates at 50–60% of total calories. All patients were instructed
to take ‘‘six-times-divided meals’’ in which the carbohydrate
content was divided into three small-sized main meals and
three snacks. The nutritional counseling was performed in a
personal interview at the first diagnosis of GDM, and was
repeated one to three additional times during the gestational
period depending on the adherence to the nutritional therapy
of the patient. The patients were also instructed to monitor
their blood glucose at home. When a patient’s fasting and
preprandial blood glucose level >100 mg/dL or the postpran-
dial 2-h blood glucose level >120 mg/dL continued for more
than 2 weeks after the initiation of nutrition therapy, the
patient was treated with insulin.
2.3. Assessment of insulin sensitivity, insulin secretion,
and b-cell function
Insulin sensitivity was estimated by the homeostasis model
assessment of insulin resistance (HOMA-IR) [14], and the
Matsuda index [15,16]. Insulin secretion was assessed by the 1-
h DIRI/DPG calculated as [(IRI60min  IRI0min)/(PG60min – PG0min)]
and the ratio of the total area under the IRI curve to the total
402 diabetes research and clinical practice 107 (2015) 400–406

Table 1 – Maternal characteristics and perinatal outcomes of women diagnosed with GDM during early pregnancy.
GDM ! GDM (n = 23) GDM ! NGT (n = 18) p-Value
Maternal age (years) 32.4  4.1 29.6  4.0 0.03
Primipara (%) 21.7 72.2 0.002
Parity (n) 1.26  1.01 0.44  0.86 0.009
Chronic hypertension (%) 8.7 0.0 0.50
Family history of diabetes (%) 60.9 33.3 0.17
Parental history of diabetes (%) 34.8 16.7 0.29
Pregravid body weight (kg) 59.1  8.8 57.3  11.9 0.57
Pregravid BMI (kg/m2) 25.2  4.5 23.1  5.4 0.19
Obese (BMI  25) (%) 47.8 22.2 0.11
Total weight gain (kg) 4.5  5.5 8.3  5.1 0.06
Insulin therapy (%) 39.1 0.0 0.002
Pregnancy induced hypertension (%) 4.3 0.0 0.90
Preeclampsia (%) 0.0 0.0 –
Cesarean delivery (%) 26.1 22.2 0.94
Gestational weeks at delivery 38.9  1.5 39.5  2.0 0.25
Preterm delivery (%) 8.7 0.0 0.50
Neonatal weight (g) 3018  328 3077  417 0.62
Small for gestational age (%) 8.7 5.6 0.83
Heavy for gestational age (%) 17.4 5.6 0.36
1-min Apgar score < 6 (%) 8.7 5.6 0.83
5-min Apgar score < 7 (%) 0.0 0.0 –
Neonatal hypoglycemia (%) 0.0 0.0 –
Neonatal hyperbilirubinemia (%) 4.3 5.6 0.85
NICU admission (%) 4.3 5.6 0.85
GDM, gestational diabetes mellitus; NGT, normal glucose tolerance; BMI, body mass index; NICU, neonatal intensive care unit.

area under the PG curve (AUCIRI/PG) derived from the 75-g
OGTT. b-Cell function was also assessed by the Insulin
Secretion-Sensitivity Index-2 (ISSI-2), reported by Retnakaran
and colleagues [17], expressed as AUCIRI/PG multiplied by the
Matsuda index.
2.4. Statistical analysis
glucose tolerance to normal glucose tolerance (NGT) at the
second OGTT and are referred to hereafter as the GDM ! NGT
group. The remaining 23 patients who continued to show GDM
were categorized as the GDM ! GDM group (Fig. 1).
3.2. Maternal characteristics and perinatal outcomes of
patients with early-onset GDM

The results are given as a mean  SD, unless otherwise The mean maternal age of the GDM ! NGT patients (29.6  4.0
indicated. Fisher’s exact tests and analyses of variance years) was significantly younger than those of the GDM ! GDM
(ANOVA) were performed to study the difference in the results patients (32.4  4.1 years, p = 0.03). The GDM ! NGT patients
of 75-g OGTT between GDM ! GDM group and GDM ! NGT were significantly more frequently low-parity; approx. three-
group. Multivariate logistic regression analyses were per- quarters of the patients were primipara. There were no
formed to study the factors influencing the outcome of
pregnant women; those who responded to nutrition therapy
OGTT before 20 wks of gestation (n=116)
and those who needed insulin therapy until delivery. The
statistical analyses were performed by using StatFlex version 6
(Artech Co., Osaka, Japan). p-Values less than 0.05 were
NGT GDM Overt DM
considered significant.
(n=13) (n=68) (n=35)

3. Results Nutrition therapy

3.1. Glucose intolerance in the early gestation improved OGTT at 24–32 wks of gestation (n=41)
and/or normalized in mid-gestation with appropriate
nutrition therapy
NGT GDM
Among the 68 patients diagnosed with GDM defined by the (n=18) (n=23)
IADPSG criteria [1], 41 were tested with three glucose tolerance
tests; prior to 20 weeks of gestation, between 24 and 32 weeks Fig. 1 – Flowchart of the study groups. OGTT, 75-g oral
of gestation, and at 4–8 weeks of the postpartum period. These glucose tolerance test; NGT, normal glucose tolerance;
patients were instructed with nutrition therapy after the first GDM, gestational diabetes mellitus; Overt DM, overt
glucose tolerance test. Of these 41 patients, 18 improved their diabetes mellitus.
 diabetes research and clinical practice 107 (2015) 400–406 403

Table 2 – Multivariate logistic regression analyses of predictors that characterized women with GDM ! NGT and the need
of insulin therapy until delivery.
GDM ! NGT Insulin therapy

OR (95% CI) p-Value OR (95% CI) p-Value

Maternal age (years) 0.97 (0.77–1.21) 0.76 1.02 (0.78–1.35) 0.87
Primipara 12.2 (1.84–81.5) 0.009 0.10 (0.01–1.12) 0.06
Family history of diabetes 0.27 (0.04–1.84) 0.18 1.21 (0.18–8.19) 0.85
Pregravid obese (BMI  25) 0.31 (0.04–2.60) 0.28 3.82 (0.53–27.4) 0.18
Fasting PG  92 mg/dL 0.13 (0.01–1.63) 0.11 1.87 (0.21–16.4) 0.57
PG at 1 h  180 mg/dL 1.25 (0.14–10.9) 0.84 5.56 (0.39–80.1) 0.21
PG at 2 h  153 mg/dL 2.01 (0.14–29.4) 0.61 0.87 (0.10–7.62) 0.90
AIC = 49.72, AUC = 0.89 AIC = 46.00, AUC = 0.83
Fasting PG, PG at 1 h, and PG at 2 h means each results of 75-g OGTT at early gestation.

significant differences in family history of type 2 diabetes, studied patients developed impaired glucose tolerance (IGT)
pregravid BMI, or frequency of pregravid obesity between the and type 2 diabetes after delivery. There was significant
two groups (Table 1). difference between the GDM ! NGT group (5.6%) and the
The glucose levels of the 41 women with early-onset GDM GDM ! GDM group (39.1%) ( p = 0.03). There were significant
were well-controlled with diet or/and insulin therapy until differences in the time-by-group interaction for the OGTT
delivery. It was notable that 39.1% of the GDM ! GDM patients results between GDM ! GDM group and GDM ! NGT group by
required insulin therapy whereas none of the GDM ! NGT using repeated-measures ANOVA (Fig. 2).
patients did. There was no significant difference between the
two groups in the frequency of each perinatal adverse event
studied. We found that the mean total weight gain during
pregnancy tended to be larger in the GDM ! NGT patients
than in the GDM ! NGT group (Table 1). We were also able to
study the weight gain in each pregnancy trimester in some
pregnant women. We found that the weight gain in the first
trimester tended to be larger in the GDM ! NGT group (n = 13,
3.2  3.4 kg) than in the GDM ! GDM group (n = 18,
0.6  2.8 kg) ( p = 0.09). The weight gain was comparable in
the second trimester (2.3  2.7 kg in GDM ! NGT; vs.
2.9  2.9 kg in GDM ! GDM, p = 0.65).
We next performed multivariate logistic regression anal-
yses to characterize women with GDM ! NGT or women who
need insulin therapy until delivery (Table 2). The primiparity
was found as a predictive factor that the pregnant women
with GDM ! NGT.

3.3. Longitudinal observation of glucose tolerance during

gestation and the postpartum period in patients with early-
onset GDM

The results of the 75-g OGTTs during early gestation (prior to

20 weeks), mid-gestation (24–32 weeks), and the postpartum
period are shown in Fig. 2. In the OGTTs during early gestation,
we found that patients with higher levels of fasting plasma
glucose (92 mg/dL) was significantly less in the GDM ! NGT
group than in the GDM ! GDM group (5.6% vs. 47.8%,
p = 0.003). The plasma glucose levels at fasting, 1 h, and 2 h
were not significantly different between the two groups.
Although the plasma glucose levels, especially at 1 h and 2 h in
OGTT, improved significantly in the GDM ! NGT group at
mid-gestation, the glucose intolerance of the GDM ! GDM
patients did not improve in the OGTTs conducted at mid-
gestation.
We found that plasma glucose levels were significantly
lower in the GDM ! NGT group than in the GDM ! GDM group
at the three time points studied in OGTTs postpartum. We
Fig. 2 – Results of 75-g OGTT during gestation and
postpartum. The means of plasma glucose levels at fasting
(A), at 1 h (B) and at 2 h (C) after the ingestion of 75-g oral
glucose were showed. The fine bars indicate + 1 SD. * and **
indicate p < 0.05 and p < 0.001 between GDM ! GDM group
and GDM ! NGT group which was calculated using
repeated-measures ANOVA. # indicates p < 0.01 vs. the
GDM ! GDM group during the same term which was
calculated by one-way ANOVA.
404 diabetes research and clinical practice 107 (2015) 400–406

Fig. 3 – Indexes of insulin sensitivity, insulin secretion and b-cell function during gestation and the postpartum period.
Insulin sensitivity (A and B), insulin secretion (C and D) and b-cell function (E) of the subsets of the GDM ! GDM group
(n = 14) and GDM!NGT group (n = 8). These indexes are defined in the Research Design and Methods section. The fine bars
indicate + 1 SD. * and ** indicate p < 0.05 and p < 0.01 between GDM ! GDM group and GDM ! NGT group which was
calculated using repeated-measures ANOVA. # indicates p < 0.05 vs. the GDM ! GDM group during the same term which
was calculated by one-way ANOVA.

3.4. Changes in insulin sensitivity, insulin secretion and
b-cell function during gestation and the postpartum period in
patients with early-onset GDM
We studied insulin sensitivity, insulin secretion and b-cell
function in the patients with plasma IRI values available at all
three points of OGTT (Fig. 3): 14 patients in the GDM ! GDM
group and 8 patients in the GDM ! NGT group. These patients’
insulin sensitivity evaluated using the HOMA-IR or Matsuda
index were very similar between two groups throughout the
gestation and postpartum. Their insulin sensitivity did not
change over the two OGTTs during pregnancy, but it improved
after delivery in both groups (Fig. 3A and B). This contrasts
with insulin secretion expressed as 1 h-DIRI/DPG or AUCIRI/PG
which increased as pregnancy advances in the GDM ! NGT
group but did not increase in the GDM ! GDM group. The
differences were statistically significant (Fig. 3C and D).
We assessed the patients’ b-cell function by the ISSI-2 [17],
which has been demonstrated to show a modest correlation
with the disposition index calculated by a frequently sampled
intravenous glucose tolerance test [18,19]. The ISSI-2 values
were significantly higher in the GDM ! NGT subset than in the
GDM ! GDM subset in the postpartum period (2.80  0.35 vs.
1.70  0.64; p < 0.001) (Fig. 3E).
4. Discussion
In this study, we found that glucose intolerance in patients
with early-onset GDM was normalized during mid-gestation
 diabetes research and clinical practice 107 (2015) 400–406
by appropriate nutrition therapy. These women, defined as the
GDM ! NGT group, showed good prognoses since their
plasma glucose levels could be well controlled throughout
their pregnancies. These patients also showed better glucose
tolerance at the postpartum period compare to the women
who continued to show GDM at mid-gestation (i.e., the
GDM ! GDM group).
It is difficult to predict whether a woman with early-onset
GDM will need insulin therapy or maintain her glucose levels
well by nutrition therapy at the time of GDM diagnosis. We
found here that only primipara was associated with women in
GDM ! NGT group in the multivariate logistic analysis. The
plasma glucose data in 75-g OGTT at early gestation failed to
predict whether or not glucose intolerance was improved by
nutrition therapy. The GDM ! NGT group have additional
clinical characteristics of younger maternal age compared to
the GDM ! GDM group in this study. This is atypical for
patients with GDM [20,21].
We found the weight gain in the first trimester was larger in
the GDM ! NGT group (3.2  3.4 kg) as compared to the
GDM ! GDM group (0.6  2.8 kg) or Japanese standard healthy
pregnant women (1.2  1.9 kg) as previously reported [22]. The
rapid weight gain in the first trimester might have caused GDM
in early gestation in the GDM ! NGT group, and thus glucose
intolerance may be corrected with nutrition therapy alone.
Taken together, our GDM ! NGT group may have developed
glucose intolerance with backgrounds different from those of
the GDM ! GDM group. We showed that 75-g OGTT was useful
to identify GDM ! NGT patients in the mid-gestation as a
result of nutrition therapy. Our findings suggest that an OGTT
may be re-evaluated in patients susceptible to nutrition
therapy such as primipara patients with large weight gain
in the first trimester showing glucose profiles in mid-gestation
after nutrition therapy.
We found that better b-cell function evaluated by a 75-g
OGTT, especially the insulin secretary capacity, seemed to be
one of the important factors to improve glucose intolerance
during mid-gestation by appropriate nutrition therapy. This
was because insulin sensitivity did not change significantly
before and after nutrition therapy in both the GDM ! NGT and
GDM ! GDM groups. Our data showed that lower insulin
secretary capacity assessed by 1 h-DIRI/DPG or AUCIRI/PG and
lower b-cell function assessed by the ISSI-2 in the women with
GDM were also associated with postpartum conversion to type
2 diabetes. This is consistent with a previous report from
Korea [23].
The present study has certain limitations. The number of
patients was small. The patients were instructed with
nutrition therapy by a nutritionist from one to four times
during their pregnancies; the numbers of instruction sessions
were not uniform. We also could not determine how precisely
each patient adhered to the diet therapy. We do not know
whether the results of our study can be applied to all women
with GDM, because the characteristics of GDM women such as
the rate of obesity and the insulin secretary capacities differ
between Asians and Caucasians [24].
In conclusion, we demonstrated that the glucose intoler-
ance of pregnant Japanese women diagnosed with GDM based
on the IADPSG criteria during early gestation did not
necessarily exacerbate as their gestation advanced. Glucose
405
intolerance could be normalized during mid-gestation by diet
therapy without requiring insulin therapy until delivery and
the frequency of postpartum development with type 2
diabetes or IGT was lower in such individuals. OGTTs should
be performed again during mid-gestation for women with
early-onset GDM to determine the appropriate treatment and
predict the pregnancy outcome after the second trimester.
Conflict of interest
The authors declared no conflict of interest.
Acknowledgments
We thank Dr. Misa Imaizumi and Dr. Shuntaro Sato for their
helpful suggestions in the statistical analyses.
references
[1] Metzger BE, Gabbe SG, Persson B, Buchanan TA, Catalano
PA, Damm P, et al. International association of diabetes and
pregnancy study groups recommendations on the
diagnosis and classification of hyperglycemia in pregnancy.
Diabetes Care 2010;33:676–82.
[2] Cousins L. Insulin sensitivity in pregnancy. Diabetes
1991;40(Suppl. 2):39–43.
[3] Catalano PM, Tyzbir ED, Roman NM, Amini SB, Sims EA.
Longitudinal changes in insulin release and insulin
resistance in nonobese pregnant women. Am J Obstet
Gynecol 1991;165:1667–72.
[4] Jiwani A, Marseille E, Lohse N, Damm P, Hod M, Kahn JG.
Gestational diabetes mellitus: results from a survey of
country prevalence and practices. J Matern Fetal Neonatal
Med 2012;25:600–10.
[5] Donovan L, Hartling L, Muise M, Guthrie A, Vandermeer B,
Dryden DM. Screening tests for gestational diabetes: a
systematic review for the U.S. Preventive Services Task
Force. Ann Intern Med 2013;159:115–22.
[6] Blumer I, Hadar E, Hadden DR, Jovanovic L, Mestman JH,
Murad MH, et al. Diabetes and pregnancy: an endocrine
society clinical practice guideline. J Clin Endocrinol Metab
2013;98:4227–49.
[7] Standards of medical care in diabetes – 2014. Diabetes Care
2014;37(Suppl. 1):S14–20.
[8] Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U,
Coustan DR, et al. Hyperglycemia and adverse pregnancy
outcomes. N Engl J Med 2008;358:1991–2002.
[9] Super DM, Edelberg SC, Philipson EH, Hertz RH, Kalhan SC.
Diagnosis of gestational diabetes in early pregnancy.
Diabetes Care 1991;14:288–94.
[10] Meyer WJ, Carbone J, Gauthier DW, Gottmann DA. Early
gestational glucose screening and gestational diabetes. J
Reprod Med 1996;41:675–9.
[11] Bartha JL, Martinez-Del-Fresno P, Comino-Delgado R. Early
diagnosis of gestational diabetes mellitus and prevention of
diabetes-related complications. Eur J Obstet Gynecol
Reprod Biol 2003;109:41–4.
[12] Seshiah V, Cynthia A, Balaji V, Balaji MS, Ashalata S, Sheela
R, et al. Detection and care of women with gestational
diabetes mellitus from early weeks of pregnancy results in
birth weight of newborn babies appropriate for gestational
age. Diabetes Res Clin Pract 2008;80:199–202.
406 diabetes research and clinical practice 107 (2015) 400–406
[13] Bartha JL, Martinez-Del-Fresno P, Comino-Delgado R.
Gestational diabetes mellitus diagnosed during
early pregnancy. Am J Obstet Gynecol 2000;182:
346–50.
[14] Bonora E, Targher G, Alberiche M, Bonadonna RC, Saggiani
F, Zenere MB, et al. Homeostasis model assessment closely
mirrors the glucose clamp technique in the assessment of
insulin sensitivity: studies in subjects with various degrees
of glucose tolerance and insulin sensitivity. Diabetes Care
2000;23:57–63.
[15] Matsuda M, DeFronzo RA. Insulin sensitivity indices
obtained from oral glucose tolerance testing: comparison
with the euglycemic insulin clamp. Diabetes Care
1999;22:1462–70.
[16] DeFronzo RA, Matsuda M. Reduced time points to calculate
the composite index. Diabetes Care 2010;33:e93.
[17] Retnakaran R, Qi Y, Goran MI, Hamilton JK. Evaluation
of proposed oral disposition index measures in relation
to the actual disposition index. Diabet Med 2009;26:
1198–203.
[18] Bergman RN, Phillips LS, Cobelli C. Physiologic evaluation
of factors controlling glucose tolerance in man:
measurement of insulin sensitivity and beta-cell glucose
sensitivity from the response to intravenous glucose. J Clin
Invest 1981;68:1456–67.
[19] Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN,
Schwartz MW, et al. Quantification of the relationship
between insulin sensitivity and beta-cell function in
human subjects. Evidence for a hyperbolic function.
Diabetes 1993;42:1663–72.
[20] Ikenoue S, Miyakoshi K, Saisho Y, Sakai K, Kasuga Y,
Fukutake M, et al. Clinical impact of women with
gestational diabetes mellitus by the new consensus criteria:
two year experience in a single institution in Japan. Endocr
J 2014;61:353–8.
[21] Sugiyama T, Nagao K, Metoki H, Nishigori H, Saito M,
Tokunaga H, et al. Pregnancy outcomes of gestational
diabetes mellitus according to pre-gestational BMI in a
retrospective multi-institutional study in Japan. Endocr J
2014;61:373–80.
[22] Nishijima M, Yoshihara H, Saitoh K, Nakashima T. The
weight gain during pregnancy and the control of body
weight. Sanfujinka Chiryo 2000;80:291–7 (in Japanese).
[23] Kwak SH, Choi SH, Jung HS, Cho YM, Lim S, Cho NH, et al.
Clinical and genetic risk factors for type 2 diabetes at early
or late post partum after gestational diabetes mellitus. J
Clin Endocrinol Metab 2013;98:E744–52.
[24] Yoon KH, Lee JH, Kim JW, Cho JH, Choi YH, Ko SH, et al.
Epidemic obesity and type 2 diabetes in Asia. Lancet
2006;368:1681–8.