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Gestational diabetes mellitus in Korea: prevalence and prediction of glucose intolerance at early postpartum
Diabetes Research and Clinical Practice 61 (2003) 117 /124 www.elsevier.com/locate/diabres
Gestational diabetes mellitus in Korea: prevalence and prediction of glucose intolerance at early postpartum Hak C. Jang a,*, Chang-Hoon Yim b, Ki O. Han b, Hyun-Koo Yoon b, In-Kwon Han b, Moon-Young Kim c, Jae-Hyug Yang c, Nam H. Cho d a
Department of Internal Medicine, Seoul National University Bundang Hospital, 300 Gumi-Dong, Bundang-Ku, Sungnam City, KyongkiDo 463-707, South Korea b Department of Medicine, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea c Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea d Department of Preventive Medicine, Ajou University Medical School, Suwon, South Korea Received 27 January 2003; received in revised form 11 March 2003; accepted 14 April 2003
Abstract To determine the prevalence of glucose intolerance in Korean women with gestational diabetes mellitus (GDM) between 6 and 8 weeks postpartum and identify which antepartum variables were predictive of postpartum diabetes and impaired glucose tolerance (IGT), we prospectively performed 75 g oral glucose tolerance test (OGTT) between 6 and 8 weeks postpartum in women with GDM. WHO criteria were used for classification of glucose tolerance postpartum. Of 392 women with GDM were detected during the study period, 311 women participated in this study. Of the 311 participants, 119 (38.3%) women were found to have persistent glucose intolerance; 47 (15.1%) had diabetes and 72 (23.2%) had IGT. The prevalence of postpartum IGT and diabetes increased in parallel with the metabolic severity during pregnancy. Multiple logistic regression analysis revealed that pre-pregnancy weight, gestational age at diagnosis of GDM, 2-h glucose and 3-h insulin concentrations of diagnostic OGTT were independently associated with postpartum diabetes. Pre-pregnancy weight, 2-h glucose and 1-h insulin concentrations were independently associated with postpartum IGT. Our results support the importance of postpartum testing in Korean women with GDM, and demonstrated that impaired b-cell function and pre-pregnancy obesity were associated with glucose intolerance at early postpartum. # 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Gestational diabetes mellitus; Postpartum glucose intolerance; Prevalence; Risk factors
1. Introduction
Presented in part at the Tenth Japan /Korea Symposium on Diabetes Mellitus, Kumamoto, Japan, 8 /9 October 1999. * Corresponding author. Tel.: /82-31-787-7005; fax: /8231-787-4051. E-mail address: [email protected] (H.C. Jang).
Gestational diabetes mellitus (GDM) is defined as glucose intolerance of variable severity with onset or first recognition during pregnancy [1]. Although most women with GDM have a normal
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glucose tolerance (NGT) when tested several weeks postpartum, impaired insulin secretion and/or increased insulin resistance has been reported in these women [2,3], and a substantial proportion of the women with previous GDM will eventually develop type 2 diabetes [4 /6]. Thus the Fourth International Workshop-Conference on GDM and American Diabetes Association (ADA) recommend postpartum oral glucose tolerance test (OGTT) in women with GDM for reclassification of glucose tolerance status and prevention of type 2 diabetes [7,8]. Several studies from North America have reported postpartum diabetes rates from 3 to 38% within 1 year after delivery [9 /12]. However, there have been few studies of postpartum glucose intolerance in Asian women with previous GDM. We found two studies performed in Asian women with GDM. One study from Hong Kong reported 20% prevalence of glucose intolerance early postpartum in Chinese women with GDM [13]. The other study from South Korea described 18.5% prevalence of glucose intolerance at 6 weeks postpartum [14]. The purpose of our study was to determine the prevalence of glucose intolerance in Korean women with GDM between 6 and 8 weeks postpartum and identify which antepartum clinical and metabolic variables were predictive of postpartum diabetes and impaired glucose tolerance (IGT).
2. Materials and methods 2.1. Subjects Since 1991, all pregnant women have been screened for GDM at 24 /28 weeks’ gestation as recommended by the Third International Workshop-Conference on GDM [15] at the Samsung Cheil Hospital in Seoul, Korea. Our standard approaches for screening, diagnosis, and management of GDM have been described in the previous publications in detail [16,17]. Briefly, screening test was performed at any time of day without regard to time or size of the last meal. Women with one or more risk factors for GDM were screened earlier than 24 weeks’ gestation. Women with a positive
screen (plasma glucose concentration ]/7.2 mmol/ l, 1 h after 50 g glucose load) were recalled for a 3h, 100 g OGTT within 2 weeks. Patients were considered to have GDM if at least two values reach or exceed the following: 5.8 mmol/l at fasting, 10.6 mmol/l at 1 h, 9.2 mmol/l at 2 h, 8.1 mmol/l at 3 h. Women with GDM were managed with medical nutritional therapy and exercise, and insulin therapy was added if their fasting plasma glucose levels of diagnostic OGTT were ]/5.8 mmol/l and when two fasting blood glucose level were ]/5.5 mmol/l or 2-h postprandial blood glucose level ]/6.7 mmol/l. From January 1993 to June 1997, 16 654 pregnant women were screened for GDM. We identified a total of 392 women with GDM. The cases of subsequent pregnancy in women with GDM were excluded from the study. Of those with GDM, 311 women consented to follow-up evaluation of glucose intolerance between 6 and 8 weeks postpartum. This study was approved by the Research and Ethics Committee of Samsung Cheil Hospital. 2.2. Antepartum characteristics and postpartum test At the time of the screening test, following information was recorded prospectively for each patient; age, height, pre-pregnancy weight from patient’s recall, present weight, obstetric history including gestational age and parity, and family history of diabetes in the first relatives. Maternal weight and pregnancy outcome were also recorded at the time of delivery. Women with GDM were scheduled for 75 g OGTT between 6 and 8 weeks after delivery and instructed to consume ]/150 g carbohydrate per day for 3 days and fast for ]/10 h before the OGTT. After overnight fasting, a venous blood sample was obtained and then at 30, 60, 90, and 120 min after the ingestion of 75 g glucose solution. Postpartum OGTT results were interpreted according to the WHO criteria [18], because some women had postpartum OGTT results that fit neither the normal nor the IGT in the National Diabetes Data Group (NDDG) classification. We also reanalysed the results of postpartum OGTT using the new ADA criteria for diabetes [8].
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Plasma glucose concentration was measured by a glucose oxidase method using YSI 2300 STAT (Yellow Springs Instrument Co., USA). The concentration of insulin was measured in duplicate, using human specific RIA kit (Linco Research, USA). The intra-assay and inter-assay coefficients of variation for insulin measurements were 4.5 and 8.8%. 2.3. Statistical analysis Data are presented as mean9/S.D. and percentage unless otherwise stated. The differences of normally distributed variables between and among groups were analysed by Student t -test, ANOVA and post-Hoc (Duncan’s multiple range) test. The insulin concentration was log-transformed to correct for non-normal distributions. Kruskal /Wallis test, Chi-square (x2)-test and Fisher’s exact test were also used to analyse non-normally distributed and dichotomous variables (e.g. percent obesity, family history of diabetes, parity and GDM class). Multiple logistic regression analysis was used to determine which variables were independently predictive of persistent glucose intolerance. Two separate analyses were performed: one to identify antepartum predictors of postpartum diabetes and one to identify predictors of postpartum IGT. In the latter analysis, women with postpartum diabetes were excluded. All analyses were performed with SPSS for Windows (Chicago, IL).
3. Results Of the 392 women with previous GDM, 311 participated in the follow-up examination between 6 and 8 weeks postpartum. The antepartum characteristics and metabolic severity of the women who did not participate in the follow-up examination were not different from those who participated, but pre-pregnancy BMI was higher in the non-participants (Table 1). Of the 311 participants, 119 (38.3%) women were found to have persistent glucose intolerance; 47 (15.1%) had diabetes and 72 (23.2%) had IGT. We compared the antepartum clinical characteristics of women with NGT, IGT and diabetes by
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the results of postpartum OGTT (Table 2). There was a significant difference in age, height, prepregnancy weight, postpartum weight and percent of obesity in women with postpartum diabetes as compared with NGT. Total weight gain during pregnancy and gestational age at diagnosis of GDM were lower in the postpartum diabetes as compared with NGT. When women with IGT and NGT were compared, pre-pregnancy weight and BMI, percent of family history of diabetes were significantly different. The plasma glucose value of screening test and fasting, 2- and 3-h glucose concentrations of diagnostic test were the highest in women with postpartum diabetes and the lowest in NGT (Table 3). The 1-h glucose concentration was not different between IGT and NGT groups, but that of women with postpartum diabetes was higher than NGT. However, the 1-, 2- and 3-h insulin concentrations of diagnostic test showed reverse trends. Women with postpartum NGT had the highest insulin concentrations and women with postpartum diabetes had the lowest insulin concentrations. However, fasting insulin concentration was not different among women with NGT, IGT and diabetes. We stratified the women with GDM by their metabolic severity during pregnancy, using fasting plasma glucose of diagnostic test [10]. Three groups were defined; class A1: 224 women with fasting plasma glucose values B/5.8 mmol/l, class A2: 63 women with fasting glucose ]/5.8 and B/ 7.2 mmol/l and class B1: 24 women with fasting glucose ]/7.2 mmol/l (Table 4). The prevalence of postpartum IGT and diabetes increased in parallel with the metabolic severity during pregnancy. Of the 224 women in the class A1, 49 (22%) had postpartum IGT and 16 (7%) had postpartum diabetes. Postpartum IGT and diabetes were more common in the class A2 than class A1 (P B/0.05). Nineteen women (30%) had IGT and 15 (24%) had diabetes. The prevalence of postpartum IGT and diabetes in the class B1 was 17 and 67%, respectively, and especially the prevalence of postpartum diabetes in the class B1 was greater than in either the class A1 or the class A2. Thus, severe fasting hyperglycemia during pregnancy was associated with an increased risk of postpartum diabetes.
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Table 1 Antepartum and metabolic characteristics of women with gestational diabetes
N Age (years) Height (cm) Pre-pregnancy Weight (kg) BMI (kg/m2) Parity Family history of DM (%) Glucose challenge test (mmol/l) Gestational age at diagnosis of GDM (weeks) GDM classa A1 (%) A2 (%) B1 (%)
With follow-up test
Without follow-up test
P
311 30.99/4.1 158.19/4.8
81 31.29/3.9 157.69/4.9
0.51 0.50
56.89/9.2 22.79/3.5 0.59/0.7 40.5% 9.99/2.3 28.39/3.9
58.99/10.4 23.79/4.0 0.59/0.6 35.8% 9.59/1.5 28.89/3.8
72.0 20.3 7.7
80.2 17.3 2.5
0.08 0.04 0.81 0.26 0.11 0.31 0.17
Data are means9/S.D. unless otherwise indicated. a Subclassification of GDM is based on the level of antepartum fasting plasma glucose (FPG) wherein class A1 denotes values for FPG of B/5.8 mmol/l; class A2, 5.8 /7.1 mmol/l; and class B1, ]/7.2 mmol/l.
When we reclassified the results of postpartum OGTT according to the new ADA criteria, 183 women with previous GDM had NGT, 76 women had postpartum impaired fasting glucose (IFG) or IGT, and 52 women had postpartum diabetes. The prevalence of postpartum IFG or IGT and diabetes as classified by the new ADA criteria was slightly increased overall and in each of the three
GDM classes; however, that did not reach statistical significance. Multiple logistic regression analysis was performed to identify antepartum variables significantly and independently associated with postpartum IGT and diabetes (Table 5). We included the variables those were statistically significant by the univariate analysis; age, height,
Table 2 Clinical characteristics of women with gestational diabetes according to glucose tolerance status postpartum Glucose tolerance status at postpartum
P
NGT
IGT
Diabetes
N Age (years) Height (cm)
192 (61.7%) 30.49/3.9a 157.79/4.9a
72 (23.2%) 31.59/4.3 158.09/4.4
47 (15.1%) 31.79/4.1a 159.69/5.1a
0.04 0.04
Pre-pregnancy Weight (kg) BMI (kg/m2) Obesity (]/25 kg/m2 (%) Total weight gain (kg) Weight at postpartum test (kg) Parity Family history of diabetes (%) Gestational age at diagnosis of GDM (weeks)
55.69/8.6a,b 22.49/3.3a 19.2a 11.39/4.5a 57.59/8.5a 0.59/0.7 34.7a 28.99/2.8a
58.49/9.4a 23.39/3.6a 26.8 11.49/4.0b 59.49/8.0 0.59/0.7 50.7a 28.49/4.7b
59.59/10.2b 23.39/3.6 34.0a 9.69/5.3a,b 60.99/8.6a 0.59/0.7 48.9 25.99/5.5a,b
0.01 0.07 0.07 0.06 0.03 0.89 0.03 0.001
ab
P B/0.05; values in each line that share the same symbol are significantly different.
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Table 3 Metabolic characteristics of women with gestational diabetes according to glucose tolerance status postpartum Antepartum
Glucose tolerance status at postpartum NGT
IGT
Diabetes
P
192 9.29/1.4a,b
72 10.39/1.8a,c
47 12.69/3.5b,c
0.001
Glucose (mmol/l ) Fasting 1-h 2-h 3-h
5.09/0.9a,b 11.09/1.3a 10.19/1.4a,b 8.29/1.7a,b
5.69/1.3a,c 11.49/1.8b 11.09/2.2a,c 9.29/2.2a,c
6.89/1.8b,c 13.29/3.1a,b 13.69/3.6b,c 11.69/3.5b,c
0.001 0.001 0.001 0.001
Insulin (pmol/l ) Fasting 1-h 2-h 3-h
659/28 3649/230a,b 5349/387a,b 4039/250a
689/32 2909/199a,c 4249/460a,c 3459/265b
619/24 1909/107b,c 2669/176b,c 2449/149a,b
0.40 0.0001 0.0001 0.001
N Screening test (mmol/l) Diagnostic test
abc
P B/0.05; values each line that share the same symbol are significantly different.
pre-pregnancy weight (pre-pregnancy BMI), weight at postpartum test, family history of diabetes, gestational age at diagnosis, and glucose and insulin concentrations of diagnostic test. Prepregnancy weight, gestational age at diagnosis of GDM, 2-h glucose and 3-h insulin concentrations of diagnostic test were the independent predictors of postpartum diabetes in these women. In case of the postpartum IGT, pre-pregnancy weight, 2-h glucose and 1-h insulin concentrations were the best predictors of postpartum IGT.
4. Discussion The results of this study demonstrate that 38% of Korean women with GDM have persistent glucose intolerance. Of 392 women with GDM detected during study period, 311 women (79%) participated in this study. No differences in the proportion of GDM class and antepartum clinical characteristics (except pre-pregnancy BMI) between participants and non-participants suggested that the possibility of self-selection that the
Table 4 Prevalence of IGT and diabetes in women with GDM according to WHO and new ADA criteria GDM classa
A1 (%) A2 (%) B1 (%) Total a
n
224 63 24 311
WHO criteria
New ADA criteria
NGT
IGT
Diabetes
NGT
IFG or IGT
Diabetes
159 (71%) 29 (46%) 4 (17%) 192 (62%)
49 (22%) 19 (30%) 4 (17%) 72 (23%)
16 15 16 47
154 (69%) 25 (40%) 4 (17%) 183 (59%)
53 (24%) 21 (33%) 2 (8%) 76 (24%)
17 17 18 52
(7%) (24%)b (67%)b,c (15%)
(8%) (27%) (75%) (17%)
Subclassification of GDM is based on the level of antepartum FPG wherein class A1 denotes values for FPG of B/5.8 mmol/l; class A2, 5.8 /7.1 mmol/l; and class B1, ]/7.2 mmol/l. b P B/0.05 vs. class A1. c P B/0.05 vs. class A2.
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Table 5 Multiple logistic regression modela for IGT and diabetes at early postpartum Variable
Coefficient S.E.
Significance
Diabetes Pre-pregnancy weight Gestational age at diagnosis 2-h glucose 3-h insulin
0.3639 /0.0928 0.0156 /0.0241
0.1027 0.0539 0.0075 0.0094
0.001 0.008 0.004 0.010
IGT Pre-pregnancy weight 2-h glucose 1-h insulin
1.5843 0.0111 /0.0163
0.7828 0.043 0.0055 0.044 0.0062 0.008
a Included variables: age, height, pre-pregnancy weight, prepregnancy BMI, family history of diabetes, weight at postpartum test, gestational age at diagnosis and glucose and insulin concentrations of diagnostic test.
participants of this study attended for higher risk of postpartum glucose intolerance or type 2 diabetes could be excluded. Of the 311 women with GDM who underwent 75 g OGTT between 6 and 8 weeks postpartum, 15% had diabetes and 23% had IGT by the WHO diagnostic criteria for diabetes. Thus, glucose intolerance at early postpartum is clearly more prevalent in this population. As there was considerable variation in the reported prevalence of GDM among different ethnic groups, the prevalence of glucose intolerance at least 1 year postpartum in women with previous GDM was reported as 7/57% [9 /14]. The differences in diagnostic tests and criteria applied for diabetes and the time of postpartum testing in concert with known differences in the prevalence of type 2 diabetes might be the major determinants of this variation. The prevalence of postpartum glucose intolerance in Korean women with GDM was somewhat lower than that was described by Metzger et al. [10]. The applied diagnostic criteria for IGT and diabetes by Metzger et al. were similar to those of our study but the glucose load for diagnostic test and the proportion of GDM class A2 and B1 in the study population were greater than in our study. However, the prevalence of glucose intolerance in our study was higher than other previous reports. Kjos et al. found that 19% of predomi-
nantly Hispanic women with GDM had glucose intolerance (9% diabetes, 10% IGT) at early postpartum by using NDDG criteria [11]. Catalano et al. reported 22% of glucose intolerance (3% diabetes, 4% IGT, 15% non-diagnostic) in their study population of predominantly white women [9]. Dacus et al. also reported 15% of glucose intolerance (10% diabetes, 5% IGT) and 26% of non-diagnostic OGTT in the predominantly black women with GDM by using same diagnostic criteria [12]. The women with GDM, studied by Catalano et al., were diagnosed by the Carpenter / Coustan criteria during pregnancy. Thus, the metabolic severity of study subjects might be less than that of our population. However, one of the major contributors for this difference might be the applied diagnostic test. Conway and Langer found that the prevalence of postpartum glucose intolerance in women with GDM was increased from 11 to 28% when the new ADA criteria were used [19]. The prevalence of postpartum diabetes was increased from 5.6 to 7.8%, and the prevalence of postpartum IGT or IFG was increased from 5.0 to 20.1% because most women with non-diagnostic OGTT by the NDDG criteria had glucose intolerance by the new ADA criteria. Recently, Kjos and her colleagues also reported 14% prevalence of diabetes and 22% of IFG or IGT at early postpartum in their study population using the new ADA criteria [20]. Thus, their results seemed to be compatible with our results (17% diabetes, 24% IGT or IFG) when the new ADA criteria were applied. Kim et al. reported 9.5% prevalence of diabetes and 9% of IGT early postpartum in Korean women with GDM [14] and the prevalence of postpartum glucose intolerance in GDM class A1 was 8%. These results were lower than our findings. However, the proportion of GDM class A2 and B1 in their study population was 20% and that was lower than our study. Previously, we reported that the prevalence of GDM in Korean women was 2.0%, which was very similar to that in white women but lower than black and Hispanic women in North America. Although the demographic characteristics of the Korean women were considerably different from those in North America, the risk factors for GDM
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were similar to those were found in women of North America [21]. We found several independent factors that were associated with glucose intolerance early postpartum. Four antepartum variables were predictive of diabetes: pre-pregnancy weight, gestational age at diagnosis, 2-h glucose and 3-h insulin concentrations of diagnostic OGTT. Three antepartum variables were also associated with postpartum IGT: pre-pregnancy weight, 2-h glucose and 1-h insulin concentration. The association between postpartum diabetes and an early gestational age at diagnosis of GDM has been also reported by several groups [9,11,20]. The possible explanation for this association is that women with risk factors for GDM, which is very similar to risk factors of type 2 diabetes in nonpregnant individuals, are recommended to screen earlier than 24 weeks’ gestation. The fact that the gestational age at diagnosis of GDM in women with postpartum diabetes was earlier than in postpartum NGT or postpartum IGT and that the women with postpartum diabetes had more risk factors for GDM support this association. The lack of association between postpartum IGT and an early gestational age at diagnosis probably was related to the fact that the gestational age at diagnosis of GDM in women with postpartum IGT was not different from women with postpartum NGT. The association between postpartum diabetes or IGT and the metabolic severity during pregnancy (as represented by the 2-h glucose concentration) and impaired -cell function (3- or 1-h insulin concentration) has been also found by several groups [4,9 /11,20,22]. Especially our finding of 2-h glucose concentration as an independent predictor is in agreement with the findings of Metzger al. [4,10]. The pre-pregnancy weight was also founded as an independent risk factor for postpartum glucose intolerance in our study population even though the pre-pregnancy weight and BMI in Korean women with GDM was considerably different from in other studies, especially from North America as described by our previous reports. Metzger et al. reported that prepregnancy obesity was associated with later onset of diabetes in women with previous GDM [4]. Thus, the risk factors for postpartum glucose intolerance in Korean women with GDM were
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also similar to those found in women of North America. In conclusion, we found that 38% of Korean women with GDM had persistent glucose intolerance early postpartum, and pre-pregnancy obesity, severity of antepartum hyperglycemia, early gestational age at diagnosis of GDM, and lower insulin response to glucose were independent predictors for postpartum glucose intolerance. These results support the importance of postpartum testing in women with GDM, and the diabetes educations for the primary and/or secondary prevention of type 2 diabetes should begin during pregnancy.
Acknowledgements We thank Dr E.S. Kim, Dr H.M. Ryu in Obstetrics for their contributions. We also thank Dr Metzger for comments and advise.
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[8] The expert committee on the diagnosis and classification of diabetes mellitus, Report of the expert committee on the diagnosis and classification of diabetes mellitus, Diabetes Care 20 (1997) 1183 /1197. [9] P.M. Catalano, K.M. Vargo, I.M. Bernstein, S.B. Amini, Incidence and risk associated with abnormal glucose tolerance in women with gestational diabetes, Am. J. Obstet. Gynecol. 165 (1991) 914 /919. [10] B.E. Metzger, D.E. Bybee, N. Freinkel, R.L. Phelps, R.M. Radvany, N. Vaisrub, Gestational diabetes mellitus: correlation between the phenotypic and genotypic characteristics of mother and abnormal glucose tolerance during the first year postpartum, Diabetes 43 (Suppl. 2) (1985) 111 / 115. [11] S.L. Kjos, T.A. Buchanan, J.S. Greenspoon, M. Montoro, G.S. Bernstein, J.H. Mestman, Gestational diabetes mellitus: the prevalence of glucose intolerance and diabetes mellitus in the first two months postpartum, Am. J. Obstet. Gynecol. 163 (1990) 93 /98. [12] J.V. Dacus, N.L. Meyer, D. Muram, R. Stilson, P. Phipps, B.M. Sibai, Gestational diabetes: postpartum glucose tolerance testing, Am. J. Obstet. Gyncecol. 171 (1994) 927 /931. [13] K.S.L. Lam, D.F. Li, I.J. Lauder, C.P. Lee, A.W.C. Kung, J.T.C. Ma, Prediction of persistent carbohydrate intolerance in patients with gestational diabetes, Diabetes Res. Clin. Pract. 12 (1991) 181 /186. [14] Y.L. Kim, Y.W. Cho, S.W. Park, et al., Antepartum characteristics predicting persistent postpartum glucose intolerance in the patients with gestational diabetes, J. Korean Diabetes Assoc. 24 (2000) 46 /59.
[15] B.E. Metzger, Summary and recommendations of the Third International Workshop-Conference on Gestational Diabetes, Diabetes 40 (Suppl.) (1991) 197 /201. [16] H.C. Jang, N.H. Cho, K.B. Jung, K.S. Oh, S.L. Dooley, B.E. Metzger, Screening for gestational diabetes mellitus in Korea, Int. J. Gynecol. Obstet. 51 (1995) 115 /122. [17] H.C. Jang, N.H. Cho, Y.K. Min, I.K. Han, K.B. Jung, B.E. Metzger, Increased macrosomia and perinatal morbidity independent of maternal obesity or advanced maternal age in Korean women with GDM, Diabetes Care 20 (1997) 1582 /1588. [18] World Health Organization, Diabetes Mellitus, Report of a Study Group, WHO Technical Report Series, no. 727, Geneva, Switzerland, 1985. [19] D.L. Conway, O. Langer, Effects of new criteria for type 2 diabetes on the rate of postpartum glucose intolerance in women with gestational diabetes, Am. J. Obstet. Gynecol. 181 (1999) 610 /614. [20] U.M. Schaefer-Graf, T.A. Buchanan, A.H. Xiang, R.K. Peters, S.L. Kjos, Clinical predictors for a high risk for the development of diabetes mellitus in the early puerperium in women with recent gestational diabetes mellitus, Am. J. Obstet. Gynecol. 186 (2002) 751 /756. [21] H.C. Jang, H.K. Min, H.K. Lee, N.H. Cho, B.E. Metzger, Short stature in Korean women: a contribution to the multifactorial predisposition to gestational diabetes mellitus, Diabetologia 41 (1998) 778 /783. [22] T.A. Buchanan, A. Xiang, S.L. Kjos, et al., Gestational diabetes: antepartum characteristics that predict postpartum glucose intolerance and type 2 diabetes in Latino women, Diabetes 47 (1998) 1302 /1310.
Gestational diabetes mellitus in Korea: prevalence and prediction of glucose intolerance at early postpartum Hak C. Jang a,*, Chang-Hoon Yim b, Ki O. Han b, Hyun-Koo Yoon b, In-Kwon Han b, Moon-Young Kim c, Jae-Hyug Yang c, Nam H. Cho d a
Department of Internal Medicine, Seoul National University Bundang Hospital, 300 Gumi-Dong, Bundang-Ku, Sungnam City, KyongkiDo 463-707, South Korea b Department of Medicine, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea c Department of Obstetrics and Gynecology, Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea d Department of Preventive Medicine, Ajou University Medical School, Suwon, South Korea Received 27 January 2003; received in revised form 11 March 2003; accepted 14 April 2003
Abstract To determine the prevalence of glucose intolerance in Korean women with gestational diabetes mellitus (GDM) between 6 and 8 weeks postpartum and identify which antepartum variables were predictive of postpartum diabetes and impaired glucose tolerance (IGT), we prospectively performed 75 g oral glucose tolerance test (OGTT) between 6 and 8 weeks postpartum in women with GDM. WHO criteria were used for classification of glucose tolerance postpartum. Of 392 women with GDM were detected during the study period, 311 women participated in this study. Of the 311 participants, 119 (38.3%) women were found to have persistent glucose intolerance; 47 (15.1%) had diabetes and 72 (23.2%) had IGT. The prevalence of postpartum IGT and diabetes increased in parallel with the metabolic severity during pregnancy. Multiple logistic regression analysis revealed that pre-pregnancy weight, gestational age at diagnosis of GDM, 2-h glucose and 3-h insulin concentrations of diagnostic OGTT were independently associated with postpartum diabetes. Pre-pregnancy weight, 2-h glucose and 1-h insulin concentrations were independently associated with postpartum IGT. Our results support the importance of postpartum testing in Korean women with GDM, and demonstrated that impaired b-cell function and pre-pregnancy obesity were associated with glucose intolerance at early postpartum. # 2003 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Gestational diabetes mellitus; Postpartum glucose intolerance; Prevalence; Risk factors
1. Introduction
Presented in part at the Tenth Japan /Korea Symposium on Diabetes Mellitus, Kumamoto, Japan, 8 /9 October 1999. * Corresponding author. Tel.: /82-31-787-7005; fax: /8231-787-4051. E-mail address: [email protected] (H.C. Jang).
Gestational diabetes mellitus (GDM) is defined as glucose intolerance of variable severity with onset or first recognition during pregnancy [1]. Although most women with GDM have a normal
0168-8227/03/$ - see front matter # 2003 Elsevier Science Ireland Ltd. All rights reserved. doi:10.1016/S0168-8227(03)00110-4
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glucose tolerance (NGT) when tested several weeks postpartum, impaired insulin secretion and/or increased insulin resistance has been reported in these women [2,3], and a substantial proportion of the women with previous GDM will eventually develop type 2 diabetes [4 /6]. Thus the Fourth International Workshop-Conference on GDM and American Diabetes Association (ADA) recommend postpartum oral glucose tolerance test (OGTT) in women with GDM for reclassification of glucose tolerance status and prevention of type 2 diabetes [7,8]. Several studies from North America have reported postpartum diabetes rates from 3 to 38% within 1 year after delivery [9 /12]. However, there have been few studies of postpartum glucose intolerance in Asian women with previous GDM. We found two studies performed in Asian women with GDM. One study from Hong Kong reported 20% prevalence of glucose intolerance early postpartum in Chinese women with GDM [13]. The other study from South Korea described 18.5% prevalence of glucose intolerance at 6 weeks postpartum [14]. The purpose of our study was to determine the prevalence of glucose intolerance in Korean women with GDM between 6 and 8 weeks postpartum and identify which antepartum clinical and metabolic variables were predictive of postpartum diabetes and impaired glucose tolerance (IGT).
2. Materials and methods 2.1. Subjects Since 1991, all pregnant women have been screened for GDM at 24 /28 weeks’ gestation as recommended by the Third International Workshop-Conference on GDM [15] at the Samsung Cheil Hospital in Seoul, Korea. Our standard approaches for screening, diagnosis, and management of GDM have been described in the previous publications in detail [16,17]. Briefly, screening test was performed at any time of day without regard to time or size of the last meal. Women with one or more risk factors for GDM were screened earlier than 24 weeks’ gestation. Women with a positive
screen (plasma glucose concentration ]/7.2 mmol/ l, 1 h after 50 g glucose load) were recalled for a 3h, 100 g OGTT within 2 weeks. Patients were considered to have GDM if at least two values reach or exceed the following: 5.8 mmol/l at fasting, 10.6 mmol/l at 1 h, 9.2 mmol/l at 2 h, 8.1 mmol/l at 3 h. Women with GDM were managed with medical nutritional therapy and exercise, and insulin therapy was added if their fasting plasma glucose levels of diagnostic OGTT were ]/5.8 mmol/l and when two fasting blood glucose level were ]/5.5 mmol/l or 2-h postprandial blood glucose level ]/6.7 mmol/l. From January 1993 to June 1997, 16 654 pregnant women were screened for GDM. We identified a total of 392 women with GDM. The cases of subsequent pregnancy in women with GDM were excluded from the study. Of those with GDM, 311 women consented to follow-up evaluation of glucose intolerance between 6 and 8 weeks postpartum. This study was approved by the Research and Ethics Committee of Samsung Cheil Hospital. 2.2. Antepartum characteristics and postpartum test At the time of the screening test, following information was recorded prospectively for each patient; age, height, pre-pregnancy weight from patient’s recall, present weight, obstetric history including gestational age and parity, and family history of diabetes in the first relatives. Maternal weight and pregnancy outcome were also recorded at the time of delivery. Women with GDM were scheduled for 75 g OGTT between 6 and 8 weeks after delivery and instructed to consume ]/150 g carbohydrate per day for 3 days and fast for ]/10 h before the OGTT. After overnight fasting, a venous blood sample was obtained and then at 30, 60, 90, and 120 min after the ingestion of 75 g glucose solution. Postpartum OGTT results were interpreted according to the WHO criteria [18], because some women had postpartum OGTT results that fit neither the normal nor the IGT in the National Diabetes Data Group (NDDG) classification. We also reanalysed the results of postpartum OGTT using the new ADA criteria for diabetes [8].
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Plasma glucose concentration was measured by a glucose oxidase method using YSI 2300 STAT (Yellow Springs Instrument Co., USA). The concentration of insulin was measured in duplicate, using human specific RIA kit (Linco Research, USA). The intra-assay and inter-assay coefficients of variation for insulin measurements were 4.5 and 8.8%. 2.3. Statistical analysis Data are presented as mean9/S.D. and percentage unless otherwise stated. The differences of normally distributed variables between and among groups were analysed by Student t -test, ANOVA and post-Hoc (Duncan’s multiple range) test. The insulin concentration was log-transformed to correct for non-normal distributions. Kruskal /Wallis test, Chi-square (x2)-test and Fisher’s exact test were also used to analyse non-normally distributed and dichotomous variables (e.g. percent obesity, family history of diabetes, parity and GDM class). Multiple logistic regression analysis was used to determine which variables were independently predictive of persistent glucose intolerance. Two separate analyses were performed: one to identify antepartum predictors of postpartum diabetes and one to identify predictors of postpartum IGT. In the latter analysis, women with postpartum diabetes were excluded. All analyses were performed with SPSS for Windows (Chicago, IL).
3. Results Of the 392 women with previous GDM, 311 participated in the follow-up examination between 6 and 8 weeks postpartum. The antepartum characteristics and metabolic severity of the women who did not participate in the follow-up examination were not different from those who participated, but pre-pregnancy BMI was higher in the non-participants (Table 1). Of the 311 participants, 119 (38.3%) women were found to have persistent glucose intolerance; 47 (15.1%) had diabetes and 72 (23.2%) had IGT. We compared the antepartum clinical characteristics of women with NGT, IGT and diabetes by
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the results of postpartum OGTT (Table 2). There was a significant difference in age, height, prepregnancy weight, postpartum weight and percent of obesity in women with postpartum diabetes as compared with NGT. Total weight gain during pregnancy and gestational age at diagnosis of GDM were lower in the postpartum diabetes as compared with NGT. When women with IGT and NGT were compared, pre-pregnancy weight and BMI, percent of family history of diabetes were significantly different. The plasma glucose value of screening test and fasting, 2- and 3-h glucose concentrations of diagnostic test were the highest in women with postpartum diabetes and the lowest in NGT (Table 3). The 1-h glucose concentration was not different between IGT and NGT groups, but that of women with postpartum diabetes was higher than NGT. However, the 1-, 2- and 3-h insulin concentrations of diagnostic test showed reverse trends. Women with postpartum NGT had the highest insulin concentrations and women with postpartum diabetes had the lowest insulin concentrations. However, fasting insulin concentration was not different among women with NGT, IGT and diabetes. We stratified the women with GDM by their metabolic severity during pregnancy, using fasting plasma glucose of diagnostic test [10]. Three groups were defined; class A1: 224 women with fasting plasma glucose values B/5.8 mmol/l, class A2: 63 women with fasting glucose ]/5.8 and B/ 7.2 mmol/l and class B1: 24 women with fasting glucose ]/7.2 mmol/l (Table 4). The prevalence of postpartum IGT and diabetes increased in parallel with the metabolic severity during pregnancy. Of the 224 women in the class A1, 49 (22%) had postpartum IGT and 16 (7%) had postpartum diabetes. Postpartum IGT and diabetes were more common in the class A2 than class A1 (P B/0.05). Nineteen women (30%) had IGT and 15 (24%) had diabetes. The prevalence of postpartum IGT and diabetes in the class B1 was 17 and 67%, respectively, and especially the prevalence of postpartum diabetes in the class B1 was greater than in either the class A1 or the class A2. Thus, severe fasting hyperglycemia during pregnancy was associated with an increased risk of postpartum diabetes.
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Table 1 Antepartum and metabolic characteristics of women with gestational diabetes
N Age (years) Height (cm) Pre-pregnancy Weight (kg) BMI (kg/m2) Parity Family history of DM (%) Glucose challenge test (mmol/l) Gestational age at diagnosis of GDM (weeks) GDM classa A1 (%) A2 (%) B1 (%)
With follow-up test
Without follow-up test
P
311 30.99/4.1 158.19/4.8
81 31.29/3.9 157.69/4.9
0.51 0.50
56.89/9.2 22.79/3.5 0.59/0.7 40.5% 9.99/2.3 28.39/3.9
58.99/10.4 23.79/4.0 0.59/0.6 35.8% 9.59/1.5 28.89/3.8
72.0 20.3 7.7
80.2 17.3 2.5
0.08 0.04 0.81 0.26 0.11 0.31 0.17
Data are means9/S.D. unless otherwise indicated. a Subclassification of GDM is based on the level of antepartum fasting plasma glucose (FPG) wherein class A1 denotes values for FPG of B/5.8 mmol/l; class A2, 5.8 /7.1 mmol/l; and class B1, ]/7.2 mmol/l.
When we reclassified the results of postpartum OGTT according to the new ADA criteria, 183 women with previous GDM had NGT, 76 women had postpartum impaired fasting glucose (IFG) or IGT, and 52 women had postpartum diabetes. The prevalence of postpartum IFG or IGT and diabetes as classified by the new ADA criteria was slightly increased overall and in each of the three
GDM classes; however, that did not reach statistical significance. Multiple logistic regression analysis was performed to identify antepartum variables significantly and independently associated with postpartum IGT and diabetes (Table 5). We included the variables those were statistically significant by the univariate analysis; age, height,
Table 2 Clinical characteristics of women with gestational diabetes according to glucose tolerance status postpartum Glucose tolerance status at postpartum
P
NGT
IGT
Diabetes
N Age (years) Height (cm)
192 (61.7%) 30.49/3.9a 157.79/4.9a
72 (23.2%) 31.59/4.3 158.09/4.4
47 (15.1%) 31.79/4.1a 159.69/5.1a
0.04 0.04
Pre-pregnancy Weight (kg) BMI (kg/m2) Obesity (]/25 kg/m2 (%) Total weight gain (kg) Weight at postpartum test (kg) Parity Family history of diabetes (%) Gestational age at diagnosis of GDM (weeks)
55.69/8.6a,b 22.49/3.3a 19.2a 11.39/4.5a 57.59/8.5a 0.59/0.7 34.7a 28.99/2.8a
58.49/9.4a 23.39/3.6a 26.8 11.49/4.0b 59.49/8.0 0.59/0.7 50.7a 28.49/4.7b
59.59/10.2b 23.39/3.6 34.0a 9.69/5.3a,b 60.99/8.6a 0.59/0.7 48.9 25.99/5.5a,b
0.01 0.07 0.07 0.06 0.03 0.89 0.03 0.001
ab
P B/0.05; values in each line that share the same symbol are significantly different.
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Table 3 Metabolic characteristics of women with gestational diabetes according to glucose tolerance status postpartum Antepartum
Glucose tolerance status at postpartum NGT
IGT
Diabetes
P
192 9.29/1.4a,b
72 10.39/1.8a,c
47 12.69/3.5b,c
0.001
Glucose (mmol/l ) Fasting 1-h 2-h 3-h
5.09/0.9a,b 11.09/1.3a 10.19/1.4a,b 8.29/1.7a,b
5.69/1.3a,c 11.49/1.8b 11.09/2.2a,c 9.29/2.2a,c
6.89/1.8b,c 13.29/3.1a,b 13.69/3.6b,c 11.69/3.5b,c
0.001 0.001 0.001 0.001
Insulin (pmol/l ) Fasting 1-h 2-h 3-h
659/28 3649/230a,b 5349/387a,b 4039/250a
689/32 2909/199a,c 4249/460a,c 3459/265b
619/24 1909/107b,c 2669/176b,c 2449/149a,b
0.40 0.0001 0.0001 0.001
N Screening test (mmol/l) Diagnostic test
abc
P B/0.05; values each line that share the same symbol are significantly different.
pre-pregnancy weight (pre-pregnancy BMI), weight at postpartum test, family history of diabetes, gestational age at diagnosis, and glucose and insulin concentrations of diagnostic test. Prepregnancy weight, gestational age at diagnosis of GDM, 2-h glucose and 3-h insulin concentrations of diagnostic test were the independent predictors of postpartum diabetes in these women. In case of the postpartum IGT, pre-pregnancy weight, 2-h glucose and 1-h insulin concentrations were the best predictors of postpartum IGT.
4. Discussion The results of this study demonstrate that 38% of Korean women with GDM have persistent glucose intolerance. Of 392 women with GDM detected during study period, 311 women (79%) participated in this study. No differences in the proportion of GDM class and antepartum clinical characteristics (except pre-pregnancy BMI) between participants and non-participants suggested that the possibility of self-selection that the
Table 4 Prevalence of IGT and diabetes in women with GDM according to WHO and new ADA criteria GDM classa
A1 (%) A2 (%) B1 (%) Total a
n
224 63 24 311
WHO criteria
New ADA criteria
NGT
IGT
Diabetes
NGT
IFG or IGT
Diabetes
159 (71%) 29 (46%) 4 (17%) 192 (62%)
49 (22%) 19 (30%) 4 (17%) 72 (23%)
16 15 16 47
154 (69%) 25 (40%) 4 (17%) 183 (59%)
53 (24%) 21 (33%) 2 (8%) 76 (24%)
17 17 18 52
(7%) (24%)b (67%)b,c (15%)
(8%) (27%) (75%) (17%)
Subclassification of GDM is based on the level of antepartum FPG wherein class A1 denotes values for FPG of B/5.8 mmol/l; class A2, 5.8 /7.1 mmol/l; and class B1, ]/7.2 mmol/l. b P B/0.05 vs. class A1. c P B/0.05 vs. class A2.
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Table 5 Multiple logistic regression modela for IGT and diabetes at early postpartum Variable
Coefficient S.E.
Significance
Diabetes Pre-pregnancy weight Gestational age at diagnosis 2-h glucose 3-h insulin
0.3639 /0.0928 0.0156 /0.0241
0.1027 0.0539 0.0075 0.0094
0.001 0.008 0.004 0.010
IGT Pre-pregnancy weight 2-h glucose 1-h insulin
1.5843 0.0111 /0.0163
0.7828 0.043 0.0055 0.044 0.0062 0.008
a Included variables: age, height, pre-pregnancy weight, prepregnancy BMI, family history of diabetes, weight at postpartum test, gestational age at diagnosis and glucose and insulin concentrations of diagnostic test.
participants of this study attended for higher risk of postpartum glucose intolerance or type 2 diabetes could be excluded. Of the 311 women with GDM who underwent 75 g OGTT between 6 and 8 weeks postpartum, 15% had diabetes and 23% had IGT by the WHO diagnostic criteria for diabetes. Thus, glucose intolerance at early postpartum is clearly more prevalent in this population. As there was considerable variation in the reported prevalence of GDM among different ethnic groups, the prevalence of glucose intolerance at least 1 year postpartum in women with previous GDM was reported as 7/57% [9 /14]. The differences in diagnostic tests and criteria applied for diabetes and the time of postpartum testing in concert with known differences in the prevalence of type 2 diabetes might be the major determinants of this variation. The prevalence of postpartum glucose intolerance in Korean women with GDM was somewhat lower than that was described by Metzger et al. [10]. The applied diagnostic criteria for IGT and diabetes by Metzger et al. were similar to those of our study but the glucose load for diagnostic test and the proportion of GDM class A2 and B1 in the study population were greater than in our study. However, the prevalence of glucose intolerance in our study was higher than other previous reports. Kjos et al. found that 19% of predomi-
nantly Hispanic women with GDM had glucose intolerance (9% diabetes, 10% IGT) at early postpartum by using NDDG criteria [11]. Catalano et al. reported 22% of glucose intolerance (3% diabetes, 4% IGT, 15% non-diagnostic) in their study population of predominantly white women [9]. Dacus et al. also reported 15% of glucose intolerance (10% diabetes, 5% IGT) and 26% of non-diagnostic OGTT in the predominantly black women with GDM by using same diagnostic criteria [12]. The women with GDM, studied by Catalano et al., were diagnosed by the Carpenter / Coustan criteria during pregnancy. Thus, the metabolic severity of study subjects might be less than that of our population. However, one of the major contributors for this difference might be the applied diagnostic test. Conway and Langer found that the prevalence of postpartum glucose intolerance in women with GDM was increased from 11 to 28% when the new ADA criteria were used [19]. The prevalence of postpartum diabetes was increased from 5.6 to 7.8%, and the prevalence of postpartum IGT or IFG was increased from 5.0 to 20.1% because most women with non-diagnostic OGTT by the NDDG criteria had glucose intolerance by the new ADA criteria. Recently, Kjos and her colleagues also reported 14% prevalence of diabetes and 22% of IFG or IGT at early postpartum in their study population using the new ADA criteria [20]. Thus, their results seemed to be compatible with our results (17% diabetes, 24% IGT or IFG) when the new ADA criteria were applied. Kim et al. reported 9.5% prevalence of diabetes and 9% of IGT early postpartum in Korean women with GDM [14] and the prevalence of postpartum glucose intolerance in GDM class A1 was 8%. These results were lower than our findings. However, the proportion of GDM class A2 and B1 in their study population was 20% and that was lower than our study. Previously, we reported that the prevalence of GDM in Korean women was 2.0%, which was very similar to that in white women but lower than black and Hispanic women in North America. Although the demographic characteristics of the Korean women were considerably different from those in North America, the risk factors for GDM
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were similar to those were found in women of North America [21]. We found several independent factors that were associated with glucose intolerance early postpartum. Four antepartum variables were predictive of diabetes: pre-pregnancy weight, gestational age at diagnosis, 2-h glucose and 3-h insulin concentrations of diagnostic OGTT. Three antepartum variables were also associated with postpartum IGT: pre-pregnancy weight, 2-h glucose and 1-h insulin concentration. The association between postpartum diabetes and an early gestational age at diagnosis of GDM has been also reported by several groups [9,11,20]. The possible explanation for this association is that women with risk factors for GDM, which is very similar to risk factors of type 2 diabetes in nonpregnant individuals, are recommended to screen earlier than 24 weeks’ gestation. The fact that the gestational age at diagnosis of GDM in women with postpartum diabetes was earlier than in postpartum NGT or postpartum IGT and that the women with postpartum diabetes had more risk factors for GDM support this association. The lack of association between postpartum IGT and an early gestational age at diagnosis probably was related to the fact that the gestational age at diagnosis of GDM in women with postpartum IGT was not different from women with postpartum NGT. The association between postpartum diabetes or IGT and the metabolic severity during pregnancy (as represented by the 2-h glucose concentration) and impaired -cell function (3- or 1-h insulin concentration) has been also found by several groups [4,9 /11,20,22]. Especially our finding of 2-h glucose concentration as an independent predictor is in agreement with the findings of Metzger al. [4,10]. The pre-pregnancy weight was also founded as an independent risk factor for postpartum glucose intolerance in our study population even though the pre-pregnancy weight and BMI in Korean women with GDM was considerably different from in other studies, especially from North America as described by our previous reports. Metzger et al. reported that prepregnancy obesity was associated with later onset of diabetes in women with previous GDM [4]. Thus, the risk factors for postpartum glucose intolerance in Korean women with GDM were
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also similar to those found in women of North America. In conclusion, we found that 38% of Korean women with GDM had persistent glucose intolerance early postpartum, and pre-pregnancy obesity, severity of antepartum hyperglycemia, early gestational age at diagnosis of GDM, and lower insulin response to glucose were independent predictors for postpartum glucose intolerance. These results support the importance of postpartum testing in women with GDM, and the diabetes educations for the primary and/or secondary prevention of type 2 diabetes should begin during pregnancy.
Acknowledgements We thank Dr E.S. Kim, Dr H.M. Ryu in Obstetrics for their contributions. We also thank Dr Metzger for comments and advise.
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