The Potential Impact of Gestational Diabetes Mellitus on Long-Term Kidney Disease: A Narrative Review

Gestational diabetes mellitus (GDM) is a pervasive metabolic disorder associated with a spectrum of long-term adverse outcomes. Recent evidence indicates that women with GDM have a heightened subsequent risk of kidney disease. Persistent factors, both pre-gestational and postpartum, can contribute to these adverse outcomes years after a GDM pregnancy. Metabolic features such as insulin resistance, subclinical inflammation, and endothelial dysfunction can lead to enduring microvascular alterations, ultimately resulting in long-term renal complications. The insulin resistance and beta cell dysfunction that develop during GDM are chronic and progressive, increasing the risk of Type 2 diabetes mellitus, hypertension, and dyslipidaemia, all risk factors for chronic kidney disease (CKD). While few studies have specifically investigated the independent association between GDM and subsequent renal dysfunction, a recent study examining the adverse pregnancy outcomes and long-term risk of CKD identified GDM as one of the independent risk factors. The findings of this review strongly recommend that women who experience adverse pregnancy outcomes like GDM during their reproductive years should be well-informed about their long-term risk of kidney disease. This knowledge is essential for early preventive actions and follow-up care. In future, cardiometabolic surveillance and risk modification strategies in clinical practice are necessary to prevent maternal renal complications among women with a history of GDM.

The impact of gestational diabetes mellitus (GDM) complicated with preeclampsia (PE) on perinatal outcomes in twin pregnancies, particularly across different GDM subtypes, remains unclear. This case-control study included 1,263 twin pregnancies with GDM and categorized participants as follows: (i) GDM without PE and GDM with PE groups, and (ii) GDM subgroups based on oral glucose tolerance test (OGTT) values at different time points, including GDM-IFH, GDM-IPH, and GDM-CH. Initially, the study investigated risk factors for PE occurrence in women with GDM. Subsequently, univariate and multivariate logistic regression analyses were conducted to explore the impact of GDM with PE on perinatal outcomes in twin pregnancies compared to GDM without PE. Stratified analyses and interaction effects were also examined to assess the risk of adverse perinatal outcomes in GDM twin pregnancies with various maternal characteristics combined with PE. Additionally, the study assessed the influence of aspirin on the GDM with PE group. Based on OGTT values, the study further investigated their impact on perinatal outcomes in the GDM with PE group and examined the influence of different GDM subtypes on perinatal outcomes in twin pregnancies with GDM and PE. Baseline characteristics of twin pregnancies with GDM indicated that pre-pregnancy BMI (PBMI) (p < 0.001), weight gain during pregnancy (p < 0.001), nulliparity (p = 0.029), and the use of IVF (p = 0.023) may be risk factors for the occurrence of PE in GDM. Additionally, GDM with PE increased the risk of Intrahepatic Cholestasis of Pregnancy (ICP) (OR 2.00), hypoproteinemia during pregnancy (OR 4.18), anemia during pregnancy (OR 2.34), and MICU admission (OR 5.43) compared to GDM without PE. Regarding neonatal outcomes, the GDM with PE group had significantly higher risks of neonatal hyperbilirubinemia (OR 1.97), preterm labor (OR 1.58), and NICU admission (OR 2.32). In the GDM with PE group, aspirin significantly reduced the risk of preterm labor. Further research indicated that glucose values significantly affected the occurrence of ICP, hypoproteinemia during pregnancy, and anemia during pregnancy in the GDM with PE group. Subgroup analysis based on OGTT glucose values classified GDM subtypes showed that different GDM subtypes are closely related to the risk of hypoproteinemia during pregnancy, neonatal hyperbilirubinemia, and preterm labor in both GDM without PE group and GDM with PE groups. Particularly in GDM-IPH and GDM-CH subtypes, PE combined with GDM significantly increased the risks associated with ICP, hypoproteinemia during pregnancy, and MICU admission. Moreover, GDM-IPH combined with PE significantly increased the risks of anemia during pregnancy, NICU admission, and neonatal hyperbilirubinemia, while GDM-CH combined with PE also significantly increased the risk of preterm birth. Twin pregnancies with GDM complicated by PE are associated with an increased risk of adverse perinatal outcomes, closely related to the subtypes of GDM. However, the use of aspirin has been shown to significantly reduce the risk of preterm birth in twin pregnancies with GDM and PE.

Adverse pregnancy outcomes, such as hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery, are associated with increased risk of maternal cardiovascular disease. Little is known about whether adverse pregnancy outcomes are associated with increased risk of maternal chronic kidney disease (CKD) and end-stage kidney disease (ESKD). To review and synthesize the published literature on adverse pregnancy outcomes (hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery) and subsequent maternal CKD and ESKD. PubMed, Embase, and Web of Science were searched from inception to July 31, 2019, for cohort and case-control studies of adverse pregnancy outcomes and maternal CKD and ESKD. Selected studies included the following: a population of pregnant women, exposure to an adverse pregnancy outcome of interest, and at least 1 primary outcome (CKD or ESKD) or secondary outcome (hospitalization or death due to kidney disease). Adverse pregnancy outcomes included exposure to hypertensive disorders of pregnancy (preeclampsia, gestational hypertension, or chronic hypertension), preterm delivery (<37 weeks), and gestational diabetes. Three reviewers were involved in study selection. Of 5656 studies retrieved, 23 were eligible for inclusion. The Meta-analyses of Observational Studies in Epidemiology (MOOSE) guidelines were followed throughout. Three reviewers extracted data and appraised study quality. Random-effects meta-analyses were used to calculate overall pooled estimates using the generic inverse variance method. Primary outcomes included CKD and ESKD diagnosis, defined using established clinical criteria (estimated glomerular filtration rate or albuminuria values) or hospital records. The protocol for this systematic review was registered on PROSPERO (CRD42018110891). Of 23 studies included (5 769 891 participants), 5 studies reported effect estimates for more than 1 adverse pregnancy outcome. Preeclampsia was associated with significantly increased risk of CKD (pooled adjusted risk ratio [aRR], 2.11; 95% CI, 1.72-2.59), ESKD (aRR, 4.90; 95% CI, 3.56-6.74), and kidney-related hospitalization (aRR, 2.65; 95% CI, 1.03-6.77). Gestational hypertension was associated with increased risk of CKD (aRR, 1.49; 95% CI, 1.11-2.01) and ESKD (aRR, 3.64; 95% CI, 2.34-5.66). Preterm preeclampsia was associated with increased risk of ESKD (aRR, 5.66; 95% CI, 3.06-10.48); this association with ESKD persisted for women who had preterm deliveries without preeclampsia (aRR, 2.09; 95% CI, 1.64-2.66). Gestational diabetes was associated with increased risk of CKD among black women (aRR, 1.78; 95% CI, 1.18-2.70), but not white women (aRR, 0.81; 95% CI, 0.58-1.13). In this meta-analysis, exposure to adverse pregnancy outcomes, including hypertensive disorders of pregnancy, gestational diabetes, and preterm delivery, was associated with higher risk of long-term kidney disease. The risk of ESKD was highest among women who experienced preeclampsia. A systematic approach may be warranted to identify women at increased risk of kidney disease, particularly after hypertensive disorders of pregnancy, and to optimize their long-term follow-up.

Gestational diabetes mellitus (GDM) increases the risk of adverse pregnancy outcomes in any pregnancy and recurrence rates are high in future pregnancies. This study aims to investigate the effect of self-reported history of previous GDM on behaviors in a future pregnancy. This is an interim cross-sectional analysis of the pregnant women who participated in the Mutaba’ah Study between May 2017 and March 2020 in the United Arab Emirates. Participants completed a baseline self-administered questionnaire on sociodemographic and pregnancy-related information about the current pregnancy and previous pregnancies. Regression models assessed the relationships between self-reported history of GDM and pre-pregnancy and pregnancy behaviors in the current pregnancy. Out of 5738 pregnant parous women included in this analysis, nearly 30% (n = 1684) reported a history of GDM in a previous pregnancy. Women with a history of previous GDM were less likely to plan their current pregnancies (adjusted odds ratio (aOR): 0.84, 95% confidence interval (CI) 0.74–0.96) and more likely to be worried about childbirth (aOR: 1.18, 95% CI 1.03–1.36). They had shorter interpregnancy intervals between their previous child and current pregnancy (aOR: 0.88, 95% CI 0.82–0.94, per SD increase). There were no significant differences between women with and without a history of GDM in supplement use, sedentary behavior, or physical activity before and during this current pregnancy. Nearly a third of parous pregnant women in this population had a history of GDM in a previous pregnancy. Pregnant women with a previous history of GDM were similar to their counterparts with no history of GDM in the adopted pre-pregnancy and prenatal health behaviors. More intensive and long-term lifestyle counseling, possibly supported by e-health and social media materials, might be required to empower pregnant women with a history of GDM. This may assist in adopting and maintaining healthy prenatal behaviors early during the pregnancy or the preconception phase to minimize the risk of GDM recurrence and the consequential adverse maternal and infant health outcomes.

Adverse pregnancy outcomes and risk of type 2 diabetes in postmenopausal women

Introduction: Foetuses of mothers with Gestational Diabetes Mellitus (GDM) are at increased risk for cardiac complications even with metabolic control. Conventional Doppler methods often fail to detect early cardiac dysfunction in these cases. The Modified Myocardial Performance Index (Mod-MPI) offers a sensitive and non-invasive tool for early detection of foetal cardiac impairment in GDM pregnancies. Aim: To assess foetal cardiac function using Mod-MPI by doppler in gestational diabetic mothers in early third trimester (28-32 weeks) and to evaluate its utility in prediction of perinatal outcome. Materials and Methods: The present prospective observational study was conducted at VMMC and Safdarjung Hospital, New Delhi, India, from November 2017 to November 2018. A total of 30 singleton pregnant females in the third trimester (28-32 weeks) with a known history of GDM and 30 singleton pregnant females in the third trimester with no history of GDM were included. Patients with multiple pregnancy intrauterine growth retardation, Pre GDM, congenital anomalies, history of cardiac disease or hypertension were excluded from the study. Using doppler ultrasonography, the Mod-MPI was calculated in the foetal left ventricle. Multiple statistical tests and Receiver Operating Characteristic (ROC) analysis was used to determine the optimal Mod-MPI cut-off for predicting adverse foetal outcomes. A p-value &lt;0.05 was considered statistically significant. Results: The pregnant females with GDM had significantly higher mean MPI (0.67±0.14) compared to those females without GDM (0.47±0.08). The mean age in the cases was 26.77±3.45, and in the controls, it was 26.87±3.7 years. Abnormal outcomes were recorded in 9 of 30 foetuses of gestational diabetic mothers, and these foetuses had significantly higher MPI measurements (0.85±0.06), compared to the 21 GDM foetuses who had normal Mod-MPI (0.6±0.09) values without any adverse outcome. The MPI served as an excellent predictor of adverse outcomes in GDM foetuses with a total area under the ROC curve being 0.98. Three abnormal outcomes were recorded in the control group, including Apgar &lt;7, stillbirth, and Intensive Care Unit (ICU) admission. Conclusion: Mod-MPI has the potential to predict adverse pregnancy outcome and improve foetal surveillance in gestational diabetes.

Introduction: Gestational diabetes mellitus (GDM) is one of the most common medical problems occurred during pregnancy. GDM increase the chance for developing type 2 diabetes meletus by seven times. The overall prevalence of GDM in pregnancy is 1-14% according to the American Diabetes Association. Material and Methods: a self-administered questionnaire was used to collect data. The information was collected from pregnant women with gestational DM to assess some maternal risk factors and compare blood glucose level according to different treatment types for GDM. Results: The present study reported that (40.38%) of GDM patients have advanced age (≥35 yrs.). First pregnancy was a risk factors for GDM and it was reported by (9.62%). History of HT and GDM during prior pregnancies were reported by (11.54%) and (% 34.62) respectively. Hypertension or preeclampsia in the current pregnancy was reported by (3.85%). Positive family history of diabetes was associated with (26.92%) GDM patients. All Patients of the present study reported no previous PCOS and smoking history. Also in this study, 44 patients out of 52 GDM patients use medications to control the glucose intolerance, while other patients control it by diet. There were no statistical differences found between treatment groups in term of blood glucose control. Conclusion: Age, history of GDM in the previous pregnancies and family history of diabetes mellitus were identifiable as a risk factors for GDM and their effect were significant in this study while the effect of other risk factors were non-significant. No statistical differences found between treatment groups in term of blood glucose level control and no group achieved the glycemic target.

Summary The aim of the present study was to evaluate the levels of pro-insulin and pro-insulin/ insulin ratio (PIR) in pregnant with normal glucose tolerance (NGT), pregnant with gestational diabetes mellitus (GDM) and women after delivery with GDM history. Normal pregnancy is characterized by progressive insulin resistance, which is physiologically compensated by an increase in insulin secretion. The higher secretion of the insulin precursor pro-insulin has been associated with β-cell dysfunction. A total of 102 pregnant women between 24-28 gestational weeks (53 GDM pregnant, 49 with NGT) and 22 postpartum with GDM history, as assessed by a 2h oral glucose tolerance test, were included in the study. Fasting plasma insulin and pro-insulin (PI) concentrations at the basal state were measured in all women. The ratio pro-insulin/insulin was calculated. BMI was significantly higher in GDM pregnant compared to NGT weight-matched group (30.56 ± 6.9 vs. 30.56 ± 6.9; p &lt; 0, 011) and compared to the levels after delivery (30.56 ± 6.9vs. 27.9 ± 6, 27; p &lt; 0, 001). Significant differences in the levels of PI between NGT and GDM pregnant (3.94 ± 2.78 vs. 7.59 ± 5.27; p = 0.006), between GDM and postpartum women (7.59 ± 5.27 vs. 4.46 ± 1.14; p = 0.022) were established. No signifi cant difference in the level of PIR between two pregnant groups was observed. Separately NGT and GDM showed signifi cant difference compared to young mothers (0.41 ± 0.14 vs. 0.148 ± 0.031, p &lt; 0.02; 0.46 ± 0.16 vs. 0.148 ± 0.031, p = 0.009). Fasting insulin was statistically higher in GDM pregnant compare to NGT and women after delivery (13.84 ± 8.43 vs. 11.35 ± 7.38, p = 0.02; 13.84 ± 8.43 vs. 10.60 ± 7.53, p &lt; 0.01). The correlation between PIR and BMI in the three groups studied were r = 0.416; r = 0,741; r = 0,556 (with statistical significance p = 0.01 between NGT and GDM pregnancy, p = 0.02 between GDM pregnancy and postpartum, p &lt; 0.0001 between NGT pregnancy and young mother with GDM history). In our study, comparison of PI levels between pregnant with NGT and GDM demonstrated that the OR of developing GDM was 1.194 (95% CI, 1.028-1.329, P = 0.001). Increasing the value of PI with 10 pmol/l increases the risk for development of GDM with 19.4%. According to our results, pregnant with GDM have elevated levels of pro-insulin and PIR which could serve as a markers for this condition. These results support our findings about relationship and influence of BMI on β-cell functions, established in this study with normotolerant, gestational diabetes pregnant and women postpartum with GDM history. These results demonstrate that gestational diabetics have abnormalities in pancreatic beta-cell secretion, which are likely to be important both in the etiology of gestational diabetes and non-insulin dependent diabetes.

PurposeTo investigate and identify first-trimester fasting plasma glucose (FPG) is related to gestational diabetes mellitus (GDM) and other adverse pregnancy outcomes in Shenzhen population.MethodsWe used data of 48,444 pregnant women that had been retrospectively collected between 2017 and 2019. Logistic regression analysis was used to evaluated the associations between first-trimester FPG and GDM and adverse pregnancy outcomes, and used to construct a nomogram model for predicting the risk of GDM. The performance of the nomogram was evaluated by using ROC and calibration curves. Decision curve analysis (DCA) was used to determine the clinical usefulness of the first-trimester FPG by quantifying the net benefits at different threshold probabilities.ResultsThe mean first-trimester FPG was 4.62 ± 0.42 mmol/L. A total of 6998 (14.4%) pregnancies developed GDM.489(1.01%) pregnancies developed polyhydramnios, the prevalence rates of gestational hypertensive disorder (GHD), cesarean section, primary cesarean section, preterm delivery before 37 weeks (PD) and dystocia was 1130 (2.33%), 20,426 (42.16%), 7237 (14.94%), 2386 (4.93%), and 1865 (3.85%), respectively. 4233 (8.74%) of the newborns were LGA, and the number of macrosomia was 2272 (4.69%), LBW was 1701 (3.51%) and 5084 (10.49%) newborns had admission to the ICU, which all showed significances between GDM and non-GDM groups (all P < 0.05). The univariate analysis showed that first-trimester FPG was strongly associated with risks of outcomes including GDM, cesarean section, macrosomia, GHD, primary cesarean section, and LGA (all OR > 1, all P < 0.05), furthermore, the risks of GDM, primary cesarean section, and LGA was increasing with first-trimester FPG as early as it was at 4.19–4.63 mmol/L. The multivariable analysis showed that the risks of GDM (ORs for FPG 4.19–4.63, 4.63–5.11 and 5.11–7.0 mmol/L were 1.137, 1.592, and 4.031, respectively, all P < 0.05) increased as early as first-trimester FPG was at 4.19–4.63 mmol/L, and first-trimester FPG which was also associated with the risks of cesarean section, macrosomia and LGA (OR for FPG 5.11–7.0 mmol/L of cesarean section: 1.128; OR for FPG 5.11–7.0 mmol/L of macrosomia: 1.561; OR for FPG 4.63–5.11 and 5.11–7.0 mmol/L of LGA: 1.149 and 1.426, respectively, all P < 0.05) and with its increasing, the risks of LGA increased. Furthermore, the nomogram had a C-indices 0.771(95% CI: 0.763~0.779) and 0.770(95% CI:0.758~0.781) in training and testing validation respectively, which showed an acceptable consistency between the observed, validation and nomogram-predicted probabilities, the DAC curve analysis indicated that the nomogram had important clinical application value for GDM risk prediction.ConclusionsFPG in the first trimester was an independent risk factor for GDM which can be used as a screening test for identifying pregnancies at risk of GDM and adverse pregnancy outcomes.

It has been suggested that the risk of adverse perinatal outcomes in twin pregnancies is exacerbated by concomitant gestational diabetes mellitus (GDM). This study aimed to assess the risk incurred by twin pregnancy and by a diagnosis of GDM, separately, on the development of poor perinatal outcomes. A retrospective cohort study was conducted on all pregnant women at a tertiary center between 2016 and 2017. The impact of GDM and twin pregnancies on perinatal outcomes - birth weight above the 90th centile for gestational age, cesarean delivery, clinical neonatal hypoglycemia, and premature delivery (before 37 weeks' gestation) - was assessed using univariate and multivariate analyses. Overall, 13,527 women were eligible for the study; 11,915 were uncomplicated singleton pregnancies; 1379 of these had GDM; 194 were twin pregnancies, and 39 of these had GDM. Univariate analyses showed that twin pregnancies were associated with a higher risk of all perinatal outcomes except macrosomia. In the multivariate analyses, twin pregnancy was a much higher predictor of cesarean delivery (OR 8.40, 95% CI [6.25, 11.49], p &lt; .0001) and preterm birth (OR 58.82, 95% CI [31.25, 125], p &lt; .0001) compared to GDM but GDM was a higher predictor of neonatal hypoglycemia (OR 4.87, 95% CI [3.74, 6.29], p &lt; .0001). Twin pregnancy is more strongly associated with all adverse perinatal outcomes except macrosomia. GDM does not increase risk of adverse perinatal outcomes except for neonatal hypoglycemia.

To investigate the relationship of different types of gestational diabetes mellitus (GDM) and pregnancy outcomes. A total of 4090 cases, who received prenatal examination and delivered in Peking University First Hospital and performed a 75 g oral glucose tolerance test (75 g OGTT) at 24-28 gestational weeks, from January. 1(st), 2011 to Jul 31(st), 2012 , were divided into 2 groups. Normal blood glucose group:the result of OGTT (fasting plasma glucose, 1 hour glucose and 2 hour glucose ) was normal; Gestational diabetes mellitus group (GDM group): the result of OGTT was abnormal at any time point. GDM group were separated into A, B and C. GDM A means fasting plasma glucose annormal but others were normal, GDM B:fasting plasma glucose, 1 hour and/or 2 hour glucose abnormal, GDM C:fasting plasma glucose normal. To analyse the effect of different number of abnormal result of OGTT on pregnancy outcomes, GDM group were divided into I, II and III.GDMI means one abnormal blood glucose of OGTT result, GDM II: two abnormal blood glucose and GDM III:three abnormal blood glucose. We analyzed the pregnant outcomes of each group. (1) Among the 4090 cases, 858 cases (21.98%) were diagnosed as GDM (GDM group), and 82 cases (9.6%, 82/858) were treated with insulin.other 3232 cases with normal blood glucose (normal blood glucose group). In GDM group, the rate of cesarean section (51.9%, 445/858), premature delivery (8.4%, 72/858) and LGA (5.9%, 51/858) were respectively significantly higher than those of normal blood glucose group [ (43.5%, 1406/3232), (5.8%, 189/3232) and(4.2%, 137/3232)] (P < 0.05). But, there was no statistically significant differences for the rate of macrosomia (P > 0.05) between the GDM group(6.8%, 58/858) and normal blood glucose group (6.2%, 199/3232) . (2) In the GDM group, GDM A was 317 cases (36.9%), GDM B 239 cases (27.8%), GDM C 302 cases (35.2%). The incidence of Macrosomia and LGA in GDM B was significantly higher than that in GDM C and normal blood glucose group (P < 0.05). Comparing with GDM A , there was no statistically significance in GDM B and GDM C (P > 0.05). (3) In GDM group, GDMIwas 521 cases (60.7%), GDM II203 cases (15.6%), GDM III 134 cases (23.7%). Compared with the normal blood glucose group, GDM III had a significantly higher incidence of macrosomia and LGA and cesarean section(P < 0.01);and GDM IIhad only a significantly higher incidence of cesarean section(P < 0.01). (4) Among the 4090 cases, there were 1118 patients (27.3%) whose fasting blood glucose was below 4.4 mmol/L, of which 55 cases were diagnosed as GDM. There were 4 premature infants and 1 macrosomia. The GDM group with more than FBG ≥ 5.1 mmol/L had a higher incidence of adverse pregnancy outcomes, it suggested that we should pay more attention and take actively intervented; the pregnant woman is not recommended for 75g OGTT detection when fasting blood glucose was below 4.4 mmol/L because of the low rate of GDM and adverse pregnancy outcomes among them.

Objective To evaluate clinical features,insulin sensitivity and β-cell function of pregnant women with different glucose tolerance status,so as to identify the possible risk factors for adverse pregnancy outcomes in women with gestational diabetes mellitus (GDM).Methods We retrospectively analyzed the clinical data of 360 pregnant women with positive results of 50 g glucose challenge test who received antenatal care and admitted for delivery in the period from January 2009 to June 2012 in Peking Union Medical College Hospital.According to the result of 100 g oral glucose tolerance test (OGTT),the 360 women were divided into GDM group (n =83),impaired glucose tolerance (IGT) group (n =75),and normal glucose tolerance (NGT) group (n =202).The blood glucose level in all those women was controlled in normal range for gestational period.We compared the general clinical data,biochemical indexes,insulin resistance index,insulin sensitivity index,function index of islet β-cell,first-and second-phase insulin secretion,insulin secretion-sensitivity index as well as the pregnancy outcomes of the 3 groups,analyzing the possible risk factors for adverse pregnancy outcomes in women with GDM.Results Compared with the NGT group,the pregnant women in GDM group were older [(33.1 ± 3.7) years vs.(31.7 ± 3.4) years,P =0.008],had higher systolic blood pressure [(115.8 ± 9.7) mmHg vs.(111.4 ± 13.5) mmHg (1 mmHg =0.133 kPa),P =0.031] and diastolic blood pressure in first trimester [(75.4 ±9.0) mmHg vs.(71.8 ±8.8) mmHg,P =0.010],higher positive rate of family history of diabetes in first-degree relatives (37.3％ vs.22.3％,P =0.012),positive rate of insulin therapy (10.8％ vs.0％,P =0.001),serum triglyceride level [(2.8 ±0.9) mmol/L vs.(2.3 ±0.9) mmol/L,P =0.001],free fatty acid level [(486.7 ± 137.6) μmol/L vs.(438.1 ± 140.7) μmol/L,P =0.033],and C-reactive protein level [(5.7 ± 4.3) mg/L vs.(3.6 ± 3.0) mg/L,P =0.001].The GDM group had a larger pre-pregnancy body mass index [(22.6 ± 2.9) kg/m2] than that in IGT group [(21.3 ± 2.7) kg/m2] (P =0.049) and NGT group [(21.2 ±2.8) kg/m2] (P =0.003).In the order from NGT to IGT to GDM group,the hemoglobin A1c [(5.2 ± 0.3) ％ vs.(5.3 ± 0.3) ％ vs.(5.4 ± 0.3) ％,P =0.001,P =0.007],the areas under curve of glucose [(20.4±2.0) mmol · h/L vs.(22.9 ± 1.5) mmol · h/L vs.(26.9 ±2.1) mmol · h/L,both P=0.001] and the areas under curve of insulin [(1.7 ±0.9) × 103 pmol · h/L vs.(2.1 ± 1.1) × 103 pmol · h/L vs.(2.7±1.3) ×103 pmol · h/L,P=0.001,P=0.007] increased gradually,while insulin sensitivity index (88.1 ± 52.1 vs.80.0 ± 30.6 vs.50.0 ± 24.1,P =0.001,P =0.014) and insulin secretion-sensitivity index (134 507.0 ± 43 291.0 vs.102 542.0 ± 15 291.0 vs.77 582.0 ± 20 764.0,both P =0.001) decreased gradually.The insulin resistance index in the GDM group (3.3 ± 2.2) was significantly higher than that in IGT (2.2 ± 1.0) and NGT groups (3.0 ± 1.1) (both P =0.001).The function of β-cell,first-and second-phase insulin secretion were not significantly different among the 3 groups.Compared with the NGT group,pregnant women with GDM had shorter gestational age [(38.8 ± 1.1) weeks vs.(39.4 ± 1.1) weeks,P=0.004] and higher incidence of adverse pregnancy outcomes (44.6％ vs.21.8％,P =0.001).Seven risk factors predicting adverse pregnancy outcomes in women with GDM were identified,including pre-pregnancy body mass index (P=0.017),0-,1-,and 2-hour blood glucose in 100 g OGTT (P=0.036,P=0.009,P=0.004),3-hour insulin (P =0.014),and hemoglobin A1 c (P =0.002) and C-reactive protein (P =0.005) in second trimester,among which 1-hour blood glucose displayed the highest coefficient (OR =2.767).Conclusions Pregnant women with GDM have elevated blood pressure,dyslipidemia and increased inflammatory cytokine C-reactive protein.Women with GDM and IGT both show insulin resistance and β-cell dysfunction,and these impairments are more severe in women with GDM.Higher pre-pregnancy body mass index and blood glucose levels during pregnancy are associated with adverse pregnancy outcomes in women with GDM. Key words: Gestational diabetes mellitus ; Insulin sensitivity ; Islet β-cell function ; Adverse pregnancy outcomes

BackgroundThe burden of gestational diabetes mellitus (GDM) appears to be increasing in India and may be related to the double burden of malnutrition. The population-based incidence and risk factors of GDM, particularly in lower socio-economic populations, are not known. We conducted analyses on data from a population-based cohort of pregnant women in South Delhi, India, to determine the incidence of GDM, its risk factors and association with adverse pregnancy outcomes (stillbirth, preterm birth, large for gestational age babies) and need for caesarean section.MethodsWe analyzed data from the intervention group of the Women and Infants Integrated Interventions for Growth Study (WINGS), an individually randomized factorial design trial. An oral glucose tolerance test (OGTT) was performed at the time of confirmation of pregnancy, and for those who had a normal test (≤140 mg), it was repeated at 24–28 and at 34–36 weeks. Logistic regression was performed to ascertain risk factors associated with GDM. Risk ratios (RR) were calculated to find association between GDM and adverse pregnancy outcomes and need for caesarean section.Results19.2% (95% CI: 17.6 to 20.9) pregnant women who had at least one OGTT were diagnosed to have GDM. Women who had prediabetes at the time of confirmation of pregnancy had a significantly higher risk of developing GDM (RR 2.08, 95%CI 1.45 to 2.97). Other risk factors independently associated with GDM were woman’s age (adjusted OR (AOR) 1.10, 95% CI 1.06 to 1.15) and BMI (AOR 1.04, 95% CI 1.01 to 1.07). Higher maternal height was found to be protective factor for GDM (AOR 0.98, 95% CI 0.96 to 1.00). Women with GDM, received appropriate treatment did not have an increase in adverse outcomes and no increased need for caesarean sectionConclusionsA substantial proportion of pregnant women from a low to mid socio-economic population in Delhi had GDM, with older age, higher BMI and pre-diabetes as important risk factors. These findings highlight the need for interventions for prevention and provision of appropriate management of GDM in antenatal programmes.Clinical trial registrationClinical Trial Registry – India, #CTRI/2017/06/008908 (http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=19339&EncHid=&userName=society%20for%20applied%20studies).

Pregnancy has long been recognized as a state of relative insulin resistance, and those women who cannot meet the increased demands for insulin during pregnancy have been labeled as having gestational diabetes mellitus (GDM). What threshold should be used in defining GDM (1) and the benefits of (2) and best methods for treating GDM (3, 4) continue to be matters of ongoing investigation and debate. There should be no debate, however, about the relationship between GDM and later diabetes mellitus (DM). Indeed the pioneering work by O’Sullivan and Mahan (5) in the 1960s focused on pregnancy as a stress test for the pancreas that identified women at significant risk for future DM. Results of the Diabetes Prevention Program (DPP) published in this issue of JCEM now argue that identifying GDM offers not just a warning for future DM but also an important opportunity to intervene and prevent incident cases (6). DPP randomized over 3000 individuals with impaired glucose tolerance (IGT), including women identified with IGT as a result of a history of GDM, to treatment with metformin, intensive lifestyle (ILS), or placebo and subsequently evaluated those enrolled semiannually to determine who developed DM. The DPP investigators have previously reported that in the overall cohort, both ILS and metformin reduced the incidence of diabetes by 58 and 31%, respectively, compared with placebo. Their current analysis focuses on women in DPP who reported a history of GDM and compares their outcomes to those of parous women who reported no such history. The results emphasize the risk GDM confers for future DM but, happily given this risk, also argue that women with GDM are more likely to benefit from pharmacological intervention. Among those in the placebo arm, 38% of women with a history of GDM developed DM in the 3 yr after randomization, an alarming rate of progression that echoes many past studies. Moreover, women with a history of GDM were at a 71% increased risk for developing DM compared with other parous subjects, an increase that is remarkable given that all, by definition, had demonstrated IGT and similar glucose levels at entry into DPP. Women with and without a history of GDM benefited similarly from ILS, demonstrating an approximately 50% reduction in risk of progression. Yet, whereas parous women without a history of GDM who were randomized to metformin treatment demonstrated a nonsignificant 14% reduction in progression, the benefits of metformin in the group with a history of GDM matched that of ILS: women with IGT and a history of GDM who were treated with medication were 50% less likely to progress to DM than those with an equivalent history in the placebo group. The investigators estimate that only five to six women with IGT and a history of GDM would need to be treated over 3 yr with either metformin or lifestyle changes to prevent one case of DM. In summary, this report emphasizes what previous DPP results argued: women with IGT after GDM should be encouraged to follow a plan of lifestyle modification or begin metformin treatment. In choosing between these alternatives, some may question whether pharmacological intervention truly prevents DM or simply restores euglycemia in those with preclinical disease. Further follow-up of those treated with metformin may be useful in answering this question, but, in the meantime, normalizing values on glucose testing seems a reasonable and reasonably important surrogate outcome. Because metformin is generally well tolerated, such therapy seems an appropriate alternative to use in treating women with IGT and a history of GDM. Given the time that had elapsed from the identification of GDM until enrollment in DPP, details about the diagnosis and management of GDM were not available. Accordingly, the investigators could not confirm the diagnosis or identify whether further variables—specific results from glucose tolerance testing in pregnancy, need for insulin, fetal macrosomia—could identify those cases at greatest risk. Nor for that matter, were they able to say whether similar variables in the parous controls might be similarly useful. One other important limitation is that because DPP required those enrolled to have identified IGT, the question

Background: Women with a previous history of Gestational Diabetes Mellitus (GDM) have a higher risk of developing adverse metabolic outcomes in comparison to women without GDM. Although after delivery dysglycemia usually subsides, insulin resistance and β-cell defects may not disappear completely postpartum, eventually leading to type-2 diabetes mellitus. So, it is meaningful to investigate the long-term changes in insulin secretion and resistance after delivery. Aim: The aim of this study is to assess the insulin resistance and insulin secretory status of mothers with a history of GDM ≥ 5 years of index pregnancy. Method: In this hospital-based cross-sectional study,107 women with a history of GDM and 101 women without GDM participated. Fasting insulin and C-peptide were measured by the chemiluminescence method. Homeostatic Model Assessment (HOMA) was used to estimate β-cell secretory function (HOMA-B), insulin resistance (HOMA-IR), and insulin sensitivity (HOMA-%S). Data were analyzed by SPSS (version 25). Results: Median time elapsed after index pregnancy was 9 years for the GDM group and 7 years for the NGT group (p=0.004). C-peptide was significantly higher in the GDM group compared to the NGT group [3 (2.34-3.74) vs. 2.52(2.16-3.35); p=0.011]. Fasting insulin and HOMA-IR had similar trends [15.3 (10.6-19.2) vs. 13.3 (10.0-17.25); p=0.044 and 4.06 (2.71-6.25) vs. 3.11 (2.25-4.34); p&lt;0.001, respectively]. On the other hand, HOMA-B was lower among GDM compared to the NGT [117.13 (74.39-185.28) vs. 159.45 (121.91-206.43); p&lt;0.001]. Fasting insulin level (p&lt;0.001), C-peptide (p&lt;0.001), and HOMA-IR (p&lt;0.001) increased progressively with the change of current glycemic status across the NGT, prediabetes (PDM), and diabetes (DM) groups. There was a gradual decline in β-cell function from the NGT to the DM group based on the current glycemic status (p&lt;0.001). Conclusion: Women with GDM also had substantial β-cell dysfunction and insulin resistance after ≥ 5 years of index pregnancy. [J Assoc Clin Endocrinol Diabetol Bangladesh, 2025;4(Suppl 1): S43]