ABSTRACT
Aims/Introduction
This study evaluated the risk factors for insulin therapy before 24 gestational weeks (early insulin therapy) in pregnant women with gestational diabetes diagnosed before 24 gestational weeks (E‐GDM).
Materials and Methods
This study included 530 singleton mothers with E‐GDM who underwent a 75 g oral glucose tolerance test (OGTT) in the first trimester at Keio University Hospital between January 2013 and December 2021. E‐GDM can be classified according to its management into only diet therapy until delivery (Diet E‐GDM), insulin therapy started before 24 gestational weeks (EarlyIns E‐GDM), and insulin therapy started after 24 gestational weeks (LateIns E‐GDM). We analyzed the risk factors for EarlyIns E‐GDM.
Results
Patients with EarlyIns E‐GDM had a significantly higher maternal age at delivery, pre‐pregnancy BMI, first trimester hemoglobin A1c, 1 h plasma glucose levels (1 h‐PG), and 2 h‐PG, as well as a more pronounced initial increase and subsequent decrease, compared with those in the Diet E‐GDM group. However, the Apgar scores at both 1 and 5 min were significantly lower in patients with EarlyIns E‐GDM than in those with Diet E‐GDM. The number of abnormal values in the OGTT showed the largest area under the receiver operating characteristic curve (AUC) for predicting EarlyIns E‐GDM (0.83, 95% confidence interval [CI]: 0.79–0.86), followed by the 1 h‐PG value (AUC: 0.81, 95% CI: 0.77–0.85). The initial increase showed the third largest AUC (0.78, 95% CI: 0.74–0.82).
Conclusions
Although further research is needed, our data suggest the importance of early insulin therapy in cases of E‐GDM with multiple abnormal OGTT values, especially with high 1 h‐PG levels and initial increase.
Keywords: Gestational diabetes mellitus, Insulin, Oral glucose tolerance test
Although further research using a larger sample size and randomized control study are needed, our data suggest the necessity of early insulin therapy for cases of E‐GDM with multiple abnormal OGTT values, especially with high 1 h‐PG levels and initial increase.
INTRODUCTION
Gestational diabetes mellitus (GDM) is a common perinatal complication. Overt diabetes mellitus (DM) or GDM is usually diagnosed during early gestation, and GDM is diagnosed at 24–28 gestational weeks based on several criteria 1 , 2 . In Japan, pregnant women with risk factors for GDM undergo the 75 g oral glucose tolerance test (OGTT) during early gestation and are diagnosed with GDM using the cut‐off values of the International Association of the Diabetes and Pregnancy Study Groups 3 . GDM diagnosed by the second trimester (E‐GDM) has adverse perinatal outcomes (e.g., hypertensive disorders of pregnancy [HDP], cesarean section, large gestational age [birthweight ≥90th percentile], macrosomia [birthweight ≥4,000 g], neonatal hypoglycemia, and neonatal jaundice) 4 , 5 , 6 . According to the Treatment of Booking Gestational Diabetes Mellitus trial published in 2023, adverse neonatal outcomes in the immediate treatment group were lower than those in the non‐immediate treatment group for GDM diagnosed before 20 gestational weeks 7 . However, the diagnostic criteria for E‐GDM remain unclear. When women with E‐GDM underwent another 75 g OGTT after 24 gestational weeks, the positive rate was approximately 50% 7 , similar to that reported in a Japanese population 8 . Therefore, among individuals with E‐GDM, identifying those who need to be treated from early gestation is crucial.
E‐GDM can be classified into three groups according to its management: only diet therapy until delivery (Diet E‐GDM), insulin therapy started before 24 gestational weeks (EarlyIns E‐GDM), and insulin therapy started after 24 gestational weeks (LateIns E‐GDM; Figure S1). The risk factors for insulin therapy in E‐GDM were a pre‐pregnancy body mass index (BMI) of ≥25 kg/m2, family history of diabetes, higher fasting plasma glucose level (FPG), 1 h plasma glucose level during a 75 g OGTT (1 h‐PG), and 2 h plasma glucose level during a 75 g OGTT (2 h‐PG) 9 . Recently, glucose variability (GV) has been used to evaluate risk factors for several complications of type 2 diabetes mellitus 10 , 11 . However, the differences in perinatal outcomes between patients with EarlyIns E‐GDM and LateIns E‐GDM and the risk factors, including glucose variability, for early insulin therapy in E‐GDM have not been evaluated.
This study evaluated the perinatal outcomes of the E‐GDM treatment categories. We analyzed the differences in maternal and perinatal outcomes between EarlyIns E‐GDM and LateIns E‐GDM to investigate the risk factors for EarlyIns E‐GDM.
MATERIALS AND METHODS
In this study, E‐GDM was diagnosed as diabetes mellitus before 24 gestational weeks using a 75 g OGTT, as recommended by the Japan Society of Obstetrics and Gynecology 3 , 9 . The present study included 530 high‐risk singleton expectant mothers with E‐GDM who underwent a 75 g OGTT in the first trimester and were cared for at Keio University Hospital between January 2013 and December 2021. High‐risk expectant mothers with GDM are defined in our previous report 9 . Women diagnosed with pre‐existing diabetes (type 1 or 2) were excluded. This study was reviewed and approved by the Keio University Hospital Ethics Committee (approval nos. 20150103 and 20150168), and it conforms to the provisions of the Declaration of Helsinki. Because this was a retrospective study, we received a waiver to obtain informed consent from the patients. The management of E‐GDM has been described in our previous study 9 . In Japan, the management of GDM typically involves only diet and/or insulin therapy; medicines that decrease plasma glucose levels (PG), such as metformin, are not allowed. Insulin was administered when dietary treatment alone did not achieve the glycemic goal (FPG <100 mg/dL or 2 h‐PG after meal <120 mg/dL). The expected gestational weight gain at gestational week 40 was calculated 12 . We evaluated GV using initial increase and subsequent decrease. The initial increase was calculated as 1 h‐PG − FPG (mg/dL), and the subsequent decrease was calculated as 1 h‐PG − 2 h‐PG (mg/dL) 13 .
To investigate the perinatal outcomes of EarlyIns E‐GDM and LateIns E‐GDM, we analyzed continuous data of maternal characteristics and perinatal outcomes using analysis of variance (anova), followed by a Tukey's post‐hoc test for those variables presenting a statistically significant difference (P < 0.05). Data are presented as the average ± SD or number of cases (percentage). Categorical variables were analyzed using the chi‐square or Fisher's exact test. The trend for the number of abnormal values in OGTT was analyzed using Cochran–Armitage trend analysis. Correlation coefficients of the 75 g OGTT values were evaluated using Pearson's test. The nonlinear association between each 75 g OGTT value and EarlyIns E‐GDM was analyzed using generalized additive models, adjusting for maternal age at delivery, pre‐pregnancy BMI, and parity. The predictive values of the maternal characteristics and parameters from the diagnostic 75 g OGTT for the EarlyIns E‐GDM were obtained using multiple logistic regression and receiver operating characteristic (ROC) analyses. Statistical analyses were performed using JMP software (ver. 17; SAS Institute, Cary, NC, USA) and R version 4.3.2 (https://cran.r‐project.org/), and P values <0.05 were considered significant.
RESULTS
Of the 530 patients with E‐GDM, 313 received Diet E‐GDM, 150 EarlyIns E‐GDM, and 67 LateIns E‐GDM. The comparisons of the maternal characteristics and the perinatal outcomes among the EarlyIns E‐GDM, LateIns E‐GDM, and Diet E‐GDM groups are presented in Table 1. Patients with EarlyIns E‐GDM had a higher maternal age at delivery, pre‐pregnancy BMI, first trimester hemoglobin A1c, 1 h‐PG, 2 h‐PG, as well as a more pronounced initial increase and subsequent decrease, compared with those with Diet E‐GDM (P < 0.05). However, the Apgar scores at both 1 and 5 min were significantly lower in patients with EarlyIns E‐GDM than in those with Diet E‐GDM (P < 0.05). Regarding perinatal outcomes, the birthweight was significantly lower in patients with EarlyIns E‐GDM than in those with Diet E‐GDM (P < 0.05). Furthermore, the 2 h‐PG levels were significantly higher in patients with LateIns E‐GDM compared with those with Diet E‐GDM (P < 0.05), while the Apgar score at 5 min was lower. However, no significant differences were observed between the two groups regarding other characteristics and perinatal outcomes. Patients with E‐GDM with two or three abnormal values in the OGTT were at a higher risk of EarlyIns E‐GDM (P < 0.001) but not LateIns E‐GDM (P = 0.42).
Table 1.
Comparison of maternal characteristics and perinatal outcomes in the three groups
| Early insulin | Late insulin | Diet therapy | P value | |
|---|---|---|---|---|
| (n = 150) | (n = 67) | (n = 313) | ||
| Maternal age at delivery (years) | 38.3 ± 5.9† | 36.9 ± 4.7 | 37.0 ± 4.8† | 0.03 |
| Nulliparity | 86 (57%) | 33 (49%) | 183 (58%) | 0.38 |
| Pre‐pregnancy BMI (kg/m2) | 22.9 ± 0.3† | 22.1 ± 0.5 | 22.0 ± 0.2† | 0.046 |
| Maternal pre‐pregnancy BMI category | ||||
| Underweight (BMI < 18.5) | 21 (14%) | 7 (10%) | 38 (12%) | 0.60 |
| Normal weight (18.5 ≤ BMI < 25.0) | 95 (63%) | 48 (72%) | 213 (68%) | |
| Overweight (25.0 ≤ BMI < 30.0) | 23 (15%) | 9 (13%) | 51 (16%) | |
| Obese (30 ≤ BMI) | 11 (7%) | 3 (4%) | 11 (4%) | |
| Gestational weight gain (kg/40 weeks) | 8.4 ± 0.4 | 9.0 ± 0.6 |
8.6 ± 0.3 |
0.64 |
| Family history of diabetes | 43 (29%) | 22 (33%) | 65 (21%) | 0.04 |
| Gestational weeks diagnosed GDM (weeks) | 13.8 ± 0.2*† | 15.2 ± 0.4* | 14.6 ± 0.2† | <0.01 |
| HbA1c at the first trimester (%) | 5.4 ± 0.03† | 5.3 ± 0.04 | 5.3 ± 0.02† | <0.01 |
| Random plasma glucose level at the first trimester (mg/dL) | 106.9 ± 1.4 | 101.9 ± 2.1 | 103.4 ± 1.0 | 0.07 |
| 75 g OGTT at diagnosed gestational weeks | ||||
| Fasting glucose level (mg/dL) | 92.4 ± 7.8 | 90.7 ± 6.8 | 90.8 ± 6.9 | 0.05 |
| 1 h glucose level (mg/dL) | 188.9 ± 27.2*† | 159.6 ± 37.4* | 151.1 ± 32.1† | <0.0001 |
| 2 h glucose level (mg/dL) | 160.7 ± 28.0*† | 146.8 ± 27.9*# | 135.5 ± 27.1†# | <0.0001 |
| Initial increase (mg/dL) | 96.5 ± 2.8*† | 69.0 ± 4.1* | 60.3 ± 1.9† | <0.0001 |
| Subsequent decrease (mg/dL) | 28.1 ± 26.3*† | 12.8 ± 30.0* | 15.6 ± 27.4† | <0.0001 |
| Abnormal values of diagnostic OGTT | ||||
| Fasting glucose level (≥92 mg/dL) | 89 (59%) | 34 (51%) | 194 (62%) | 0.23 |
| 1 h glucose level (≥180 mg/dL) | 111 (74%) | 17 (25%) | 74 (24%) | <0.0001 |
| 2 h glucose level (≥153 mg/dL) | 100 (67%) | 28 (42%) | 88 (28%) | <0.0001 |
| Number of abnormal values in diagnostic OGTT | ||||
| 1 point | 36 (24%) | 55 (82%) | 275 (88%) | <0.0001 |
| 2 points | 78 (52%) | 12 (18%) | 33 (11%) | |
| 3 points | 36 (24%) | 0 (0%) | 5 (2%) | |
| Gestational weeks at delivery (weeks) | 37.4 ± 2.5 | 37.4 ± 2.9 | 38.0 ± 2.2 | 0.03 |
| Preterm delivery | 29 (19%) | 16 (24%) | 39 (12%) | 0.03 |
| Cesarean section delivery | 87 (58%) | 36 (54%) | 151 (48%) | 0.14 |
| Birthweight (g) | 2,733 ± 31† | 2,910 ± 66 | 2,893 ± 31† | <0.01 |
| Macrosomia | 0 (0%) | 0 (0%) | 0 (0%) | NA |
| Low birthweight | 39 (26%) | 14 (21%) | 38 (12%) | <0.01 |
| Large for gestational age | 0 (0%) | 0 (0%) | 2 (1%) | NA |
| Small for gestational age | 1 (1%) | 1 (1%) | 1 (0%) | NA |
| Apgar score 1 min | 7.7 ± 1.5† | 7.6 ± 1.7 | 8.0 ± 1.2† | 0.01 |
| Apgar score 5 min | 8.6 ± 0.9† | 8.6 ± 1.1# | 8.9 ± 0.8†# | <0.01 |
Dimensions compared with anova. Data are average ± SD or n (%). *†# Values with same symbol significantly different on Tukey's post‐hoc test. BMI, body mass index; GDM, gestational diabetes mellitus; OGTT, oral glucose tolerance test.
The association between the diagnostic 75 g OGTT and EarlyIns E‐GDM is shown in Figure 1a. Although the strongest correlation was observed between the 1 h‐PG and the initial increase (r = 0.98), the correlation between the 1 h‐PG and the subsequent decrease was moderate (r = 0.59). Furthermore, the initial increase was moderately correlated with the 2 h‐PG (r = 0.67) and the subsequent decrease (r = 0.54). Correlations between FPG and other values calculated using the 75 g OGTT were weak. According to the generalized additive model using maternal age at delivery, pre‐pregnancy BMI, and parity, 1 h‐PG, 2 h‐PG, initial increase, and subsequent decrease were linearly and positively associated with EarlyIns E‐GDM (Figure 1b). The area under the curve (AUC) for predicting EarlyIns E‐GDM is shown in Table 2. The pre‐pregnancy BMI, FPG, 1 h‐PG, 2 h‐PG, initial increase, and the subsequent decrease were significantly associated with EarlyIns E‐GDM. The number of abnormal values in the OGTT showed the largest area under the ROC curve (AUC 0.83, 95% CI: 0.79–0.86). The 1 h‐PG value showed the second largest area under the ROC curve (AUC 0.81, 95% CI: 0.77–0.85), with a cut‐off value of 171 mg/dL. The initial increase showed the third largest area under the ROC curve (AUC 0.78, 95% CI: 0.74–0.82), with a cut‐off value of 85 mg/dL.
Figure 1.
Association between values of the diagnostic 75 g oral glucose tolerance test (OGTT) and insulin therapy started before 24 gestational weeks among women with early gestational diabetes. (a) The correlogram was evaluated using the Pearson correlation analysis. The strongest correlation was observed between the 1 h plasma glucose level and the initial increase. (b) The adjusted values and 95% confidence interval of early insulin therapy for each 75 g OGTT parameter were calculated using a generalized additive model, using maternal age at delivery, pre‐pregnancy body mass index, and parity as covariables.
Table 2.
Predictive values of clinical features for the risk of gestational diabetes treated insulin therapy before 24 gestational weeks
| AUC | 95% CI | Cut‐off | Sensitivity (%) | Specificity (%) | PPV (%) | NPV (%) | |
|---|---|---|---|---|---|---|---|
| Pre‐pregnancy BMI | 0.56 | 0.50–0.61 | 21.4 | 52.9 | 62.0 | 77.9 | 34.3 |
| FPG | 0.54 | 0.48–0.59 | 101 | 97.4 | 12.7 | 73.9 | 65.5 |
| 1 h‐PG | 0.81 | 0.77–0.85 | 171 | 70.0 | 83.3 | 91.4 | 52.3 |
| 2 h‐PG | 0.73 | 0.68–0.78 | 147 | 66.1 | 75.3 | 87.2 | 46.7 |
| Number of abnormal values in the OGTT | 0.83 | 0.79–0.86 | 2 | 76.0 | 86.8 | 74.0 | 90.2 |
| Initial increase | 0.78 | 0.74–0.82 | 85 | 74.7 | 72.1 | 51.4 | 87.8 |
| Subsequent decrease | 0.65 | 0.59–0.70 | 19 | 68.7 | 57.6 | 39.0 | 82.3 |
1 h‐PG, plasma glucose at 1 h in the oral glucose tolerance test; 2 h‐PG, plasma glucose at 2 h in the oral glucose tolerance test; AUC, area under the receiver operating characteristics curve; BMI, body mass index; CI, confidence interval; FPG, fasting glucose; NPV, negative predictive value; OGTT, oral glucose tolerance test; PPV, positive predictive value.
DISCUSSION
Among the patients with E‐GDM, the rate of EarlyIns E‐GDM was 28%. The characteristics and perinatal outcomes of patients with EarlyIns E‐GDM were worse than those of patients with LateIns E‐GDM and Diet E‐GDM. The risk factors for early insulin therapy in women with E‐GDM were multiple abnormal OGTT values, an especially high 1 h‐PG and initial increase.
E‐GDM was recently shown to improve perinatal outcomes. Our previous epigenetic analysis emphasized the importance of treating E‐GDM during early gestation because there was no difference in cord blood DNA methylation between patients with E‐GDM and those with normal glucose tolerance (NGT) 14 . Furthermore, Nakanishi et al. 15 reported that patients with false‐positive E‐GDM who had abnormal 75 g OGTT values before 20 gestational weeks but not at 24–28 gestational weeks without any therapy for GDM from early gestation, had a higher risk of hypertensive disorders of pregnancy compared with those with a normal glucose tolerance. However, the suitable treatment of E‐GDM during early gestation remains controversial. E‐GDM is classified into EarlyIns E‐GDM and LateIns E‐GDM based on the timing of the initiation of insulin therapy. As patients with EarlyIns E‐GDM might require treatment, we considered the risk factors for its occurrence. Furthermore, there is a paucity of data on the use of glucose variability in E‐GDM. GV has been used to predict complications in patients with impaired glucose tolerance 10 , 11 , 16 , 17 . In the perinatal period, GV during early gestation can predict the development of HDP in the Japanese population 13 . The association between GV and 75 g OGTT values from our data was similar to that in a previous report 13 . Therefore, GV is a good predictor of adverse treatment outcomes in women with GDM.
Individuals with E‐GDM with two or three abnormal OGTT values were at a higher risk of EarlyIns E‐GDM, and the 1 h‐PG had the second highest predictive value for EarlyIns E‐GDM. In a previous report, GDM with multiple positive points during the OGTT in the first pregnancy was associated with a higher risk of recurrent GDM onset 18 . The incidence of multiple positive points during the OGTT in E‐GDM was significantly higher than that in GDM diagnosed after 24 gestational weeks 9 . Multiple positive points on the OGTT may suggest impaired glucose tolerance.
This study had some limitations. First, it was a retrospective cohort study with a small sample size. However, to our knowledge, there is a lack of data on the risk factors for EarlyIns E‐GDM. We believe that our data will be useful for managing E‐GDM. Second, we selected patients who underwent a 75 g OGTT during the first trimester. However, in the Japanese GDM diagnostic criteria, patients with GDM diagnosed after 24 gestational weeks who did not undergo a 75 g OGTT in the first trimester but underwent a 50 g glucose challenge test and a 75 g OGTT at 24–28 gestational weeks were included. To evaluate the values during the 75 g OGTT in the first trimester, we excluded pregnant women who did not undergo the test.
In conclusion, multiple abnormal values in the OGTT, especially a high 1 h‐PG and initial increase, were good predictors of EarlyIns E‐GDM and may be associated with a higher risk of adverse perinatal outcomes. Although further research using a larger sample size and a randomized control study are needed, our data suggest that patients with E‐GDM and multiple abnormal values in the OGTT, especially high 1 h‐PG and initial increase, should receive early gestational treatment.
DISCLOSURE
The authors declare no conflicts of interest.
Approval of the research protocol: The protocol for this research project has been approved by the Keio University Hospital Ethics Committee (approval nos. 20150103 [June 23, 2015] and 20150168 [July 31, 2015]), and it conforms to the provisions of the Declaration of Helsinki.
Informed consent: Because this was a retrospective study, we received a waiver to obtain informed consent from the patients.
Approval date of registry and the registration no. of the study/trial: N/A.
Animal studies: N/A.
Supporting information
Figure S1. Classification of the treatment of gestational diabetes before 24 gestational weeks.
ACKNOWLEDGMENT
We thank the medical staff for caring for expectant mothers at Keio University Hospital. We also want to thank Editage (www.editage.jp) for English language editing. The research was financially supported by the Seiichi Imai Memorial Foundation Research Grant.
REFERENCES
- 1. ElSayed NA, Aleppo G, Aroda VR, et al. 2. Classification and diagnosis of diabetes: Standards of care in diabetes‐2023. Diabetes Care 2023; 46: S19–S40. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. Diabetes in pregnancy: Management from Preconception to the Postnatal Period. London: National Institute for Health and Care Excellence (NICE), 2020. [PubMed] [Google Scholar]
- 3. Itakura A, Shoji S, Shigeru A, et al. Guidelines for obstetrical practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2020 edition. J Obstet Gynaecol Res 2023; 49: 5–53. [DOI] [PubMed] [Google Scholar]
- 4. Usami T, Yokoyama M, Ueno M, et al. Comparison of pregnancy outcomes between women with early‐onset and late‐onset gestational diabetes in a retrospective multi‐institutional study in Japan. J Diabetes Investig 2020; 11: 216–222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Feghali MN, Abebe KZ, Comer DM, et al. Pregnancy outcomes in women with an early diagnosis of gestational diabetes mellitus. Diabetes Res Clin Pract 2018; 138: 177–186. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Sweeting AN, Ross GP, Hyett J, et al. Gestational diabetes mellitus in early pregnancy: Evidence for poor pregnancy outcomes despite treatment. Diabetes Care 2016; 39: 75–81. [DOI] [PubMed] [Google Scholar]
- 7. Simmons D, Immanuel J, Hague WM, et al. Treatment of gestational diabetes mellitus diagnosed early in pregnancy. N Engl J Med 2023; 388: 2132–2144. [DOI] [PubMed] [Google Scholar]
- 8. Nakanishi S, Aoki S, Kasai J, et al. Non‐efficacy of early intervention strategy for non‐obese patients with early‐onset gestational diabetes mellitus: Solely based on the short‐term outcomes. BMJ Open Diabetes Res Care 2023; 11: e003230. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. Tamagawa M, Kasuga Y, Saisho Y, et al. Predictors of later insulin therapy for gestational diabetes diagnosed in early pregnancy. Endocr J 2021; 68: 1321–1328. [DOI] [PubMed] [Google Scholar]
- 10. Di Flaviani A, Picconi F, Di Stefano P, et al. Impact of glycemic and blood pressure variability on surrogate measures of cardiovascular outcomes in type 2 diabetic patients. Diabetes Care 2011; 34: 1605–1609. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. Habte‐Asres HH, Murrells T, Nitsch D, et al. Glycaemic variability and progression of chronic kidney disease in people with diabetes and comorbid kidney disease: Retrospective cohort study. Diabetes Res Clin Pract 2022; 193: 110117. [DOI] [PubMed] [Google Scholar]
- 12. Morisaki N, Nagata C, Jwa SC, et al. Pre‐pregnancy BMI‐specific optimal gestational weight gain for women in Japan. J Epidemiol 2017; 27: 492–498. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13. Tano S, Kotani T, Ushida T, et al. Evaluating glucose variability through OGTT in early pregnancy and its association with hypertensive disorders of pregnancy in non‐diabetic pregnancies: A large‐scale multi‐center retrospective study. Diabetol Metab Syndr 2023; 15: 123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14. Kasuga Y, Kawai T, Miyakoshi K, et al. DNA methylation analysis of cord blood samples in neonates born to gestational diabetes mothers diagnosed before 24 gestational weeks. BMJ Open Diabetes Res Care 2022; 10: e002539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. Nakanishi S, Aoki S, Shindo R, et al. Do pregnancy outcomes of women with false‐positive early gestational diabetes mellitus differ from those of women with normal glucose tolerance? BMC Endocr Disord 2022; 22: 203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16. Ceriello A, Esposito K, Piconi L, et al. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes 2008; 57: 1349–1354. [DOI] [PubMed] [Google Scholar]
- 17. Papachristoforou E, Lambadiari V, Maratou E, et al. Association of glycemic indices (hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress and diabetic complications. J Diabetes Res 2020; 2020: 7489795. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. Morikawa M, Yamada T, Saito Y, et al. Predictors of recurrent gestational diabetes mellitus: A Japanese multicenter cohort study and literature review. J Obstet Gynaecol Res 2021; 47: 1292–1304. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Figure S1. Classification of the treatment of gestational diabetes before 24 gestational weeks.