Glucose Tolerance Test Values Research Articles

Maternal and Neonatal Outcomes with One Abnormal Value on 100g Three Hour Glucose Tolerance Test in Pregnancy

Purpose: The primary objective of this study was to compare pregnancy outcomes for patients with no elevated glucose values, one elevated glucose value, and 2 or more elevated glucose values on the 3-hour glucose tolerance test (GTT). Methods: This was a retrospective chart review of obstetric patients seen by residents and attending physicians at a single institution from 2015 to 2020 who were required to complete a 3-hour glucose tolerance test (GTT). Data extracted from the maternal chart included demographic information, BMI, route of delivery, presence of preeclampsia, chorioamnionitis, shoulder dystocia and preterm labor. Data extracted from the neonatal chart included blood glucose level after birth, birth weight, Apgar scores, and if NICU admission was required. Continuous data were analyzed using one-way ANOVA to compare the 3 groups, followed by post-hoc Tukey HSD to compare the 1 abnormal value group to the control group. Dichotomous data were analyzed using Chi square tests. Logistic regression was performed using shoulder dystocia as the outcome. Results: Patients with two or more elevated GTT values had higher age and BMI and were more likely to be prescribed diabetic medications compared to those with normal or one elevated value. They were also more likely to deliver at an earlier gestational age. Patients with one elevated GTT value experienced a statistically significant higher chance of shoulder dystocia compared to patients with all normal GTT results (OR 2.34; 95% CI 1.05, 5.20). Patients with two or more elevated values were more likely to have preeclampsia and a neonate requiring NICU admission. There were no differences in cesarean delivery rate, hemorrhage or chorioamnionitis between the groups. Conclusions: Patients with one elevated GTT value are a special subset of patients who do not meet criteria for gestational diabetes, yet do not have normal glucose testing results. We hypothesize that this group is at higher risk of shoulder dystocia because these patients may have hyperglycemia but often do not receive the same type of monitoring, dietary education, medication initiation and induction timing as patients who meet criteria for gestational diabetes.

Perinatal Outcomes of Diet Therapy in Gestational Diabetes Mellitus Diagnosed before 24 Gestational Weeks.

To evaluate perinatal outcomes and risk factors for large for gestational age (LGA; birth weight over 90 percentile) in gestational diabetes diagnosed before 24 gestational weeks and treated with diet therapy alone until delivery (Diet Early gestational diabetes mellitus (Diet Early GDM)), we assessed the maternal characteristics and perinatal outcomes of patients with early GDM (n = 309) and normal glucose tolerance (NGT; n = 309) at Keio University Hospital. The gestational weight gain (GWG) expected at 40 weeks was significantly lower in the Diet Early GDM group than in the NGT group. The Diet Early GDM group exhibited a significantly lower incidence of low birth weight (<2500 g) and higher Apgar score at 5 min than the NGT group. Multiple logistic regression analysis revealed that the pre-pregnancy body mass index and GWG expected at 40 weeks were significantly associated with LGA for Diet Early GDM. No differences were observed in random plasma glucose levels in the first trimester, 75 g oral glucose tolerance test values, and initial increase or subsequent decrease between the two groups. Dietary early GDM did not exhibit a worse prognosis than NGT. To prevent LGA, it might be important to control maternal body weight not only during pregnancy but also before conception.

Dietary Intake and Oral Glucose Tolerance Test Results in Women with Gestational Diabetes

Background/Objective: Diet is a risk factor for gestational diabetes mellitus (GDM). There are few studies on women’s diet and glucose tolerance test (GTT) results during pregnancy. The objective of this study was to evaluate the relationship between one’s previous diet and the number of abnormal values on the diagnostic GTT in women with GDM. We hypothesized that there would be an inverse relation between antioxidant micronutrient consumption and the number of abnormal GTT values. Methods: This cross-sectional study included 60 women diagnosed with GDM (2-h, 75 g-GTT), divided in two groups as follows: 1 abnormal glucose value and 2–3 abnormal values. Shortly after the diagnosis, participants answered a validated food frequency questionnaire to assess their food consumption in the last 6 months. The Mann–Whitney test was used to compare the dietary intake of the participants in the two groups. Results: The participant characteristics were similar. The median intake of total calories, carbohydrates, lipids, and proteins did not differ significantly between groups. Participants with 1 abnormal GTT value had significantly higher intakes of fiber (11.9 vs. 11.0 g/day p = 0.049), vitamin D (40.6 vs. 40.4 mcg/day p = 0.049), and vitamin C (180.0 vs. 151.0 mg/day p = 0.008) than those with 2–3 abnormal values. Conclusions: Our results suggest a possible association between the consumption of fiber and antioxidant micronutrients and the number of abnormal GTT values.

Gestational Diabetes Mellitus Subtypes Classified by Oral Glucose Tolerance Test and Maternal and Perinatal Outcomes: Results of a Mexican Multicenter Prospective Cohort Study "Cuido Mi Embarazo".

This study explores the impact of gestational diabetes mellitus (GDM) subtypes classified by oral glucose tolerance test (OGTT) values on maternal and perinatal outcomes. This multicenter prospective cohort study (May 2019-December 2022) included participants from the Mexican multicenter cohort study Cuido mi Embarazo (CME). Women were classified into four groups per 75-g 2-h OGTT: 1) normal glucose tolerance (normal OGTT), 2) GDM-Sensitivity (isolated abnormal fasting or abnormal fasting in combination with 1-h or 2-h abnormal results), 3) GDM-Secretion (isolated abnormal values at 1-h or 2-h or their combination), and 4) GDM-Mixed (three abnormal values). Cesarean delivery, neonates large for gestational age (LGA), and pre-term birth rates were among the outcomes compared. Between-group comparisons were analyzed using either the t-test, chi-square test, or Fisher's exact test. Of 2,056 Mexican pregnant women in the CME cohort, 294 (14.3%) had GDM; 53.7%, 34.4%, and 11.9% were classified as GDM-Sensitivity, GDM-Secretion, and GDM-Mixed subtypes, respectively. Women with GDM were older (p = 0.0001) and more often multiparous (p = 0.119) vs without GDM. Cesarean delivery (63.3%; p = 0.02) and neonate LGA (10.7%; p = 0.078) were higher in the GDM-Mixed group than the overall GDM group (55.6% and 8.4%, respectively). Pre-term birth was more common in the GDM-Sensitivity group than in the overall GDM group (10.2% vs 8.5%, respectively; p=0.022). At 6 months postpartum, prediabetes was more frequent in the GDM-Sensitivity group than in the overall GDM group (31.6% vs 25.5%). Type 2 diabetes was more common in the GDM-Mixed group than in the overall GDM group (10.0% vs 3.3%). GDM subtypes effectively stratified maternal and perinatal risks. GDM-Mixed subtype increased the risk of cesarean delivery, LGA, and type 2 diabetes postpartum. GDM subtypes may help personalize clinical interventions and optimize maternal and perinatal outcomes.

Are maternal serum subfatin levels altered in women with one abnormal glucose tolerance test value?

Subfatin, a newly discovered adipokine, plays a pivotal role in the regulation of glucose metabolism. The relationship between gestational diabetes mellitus and maternal dyslipidemia is well-documented. This study aims to assess serum subfatin levels and the triglyceride/high-density lipoprotein cholesterol ratio in women with one abnormal glucose tolerance test value and those with gestational diabetes mellitus. In this case-control study, 105 pregnant women were categorized into three groups: women with normal 3-h oral glucose tolerance test results (n=35), women with one abnormal 3-h oral glucose tolerance test result (n=35), and women diagnosed with gestational diabetes mellitus (n=35). Serum subfatin levels were measured using human enzyme-linked immunosorbent assay kits. Serum subfatin levels were significantly lower in the gestational diabetes mellitus group (0.94±0.15 ng/mL) compared to the normal oral glucose tolerance test group (1.48±0.55 ng/mL) and the group with one abnormal oral glucose tolerance test result (1.50±0.59 ng/mL). The triglyceride/high-density lipoprotein cholesterol ratio was also lower in the healthy control group than in the gestational diabetes mellitus and one abnormal oral glucose tolerance test result groups. Serum subfatin levels in women with one abnormal abnormal glucose tolerance test value are compared to those in the control group, while the triglyceride/high-density lipoprotein cholesterol ratio is significantly altered in women with one abnormal abnormal glucose tolerance test value when compared to the control group.

Bariatric surgery induces pancreatic cell transdifferentiation as indicated by single-cell transcriptomics in Zucker diabetic rats.

Bariatric surgery results in rapid recovery of glucose control in subjects with type 2 diabetes mellitus. However, the underlying mechanisms are still largely unknown. The present study aims to clarify how bariatric surgery modifies pancreatic cell subgroup differentiation and transformation in the single-cell RNA level. Male, 8-week-old Zucker diabetic fatty (ZDF) rats with obesity and diabetes phenotypes were randomized into sleeve gastrectomy (Sleeve, n = 9), Roux-en-Y gastric bypass (RYGB, n = 9), and Sham (n = 7) groups. Two weeks after surgery, the pancreas specimen was further analyzed using single-cell RNA-sequencing technique. Two weeks after surgery, compared to the Sham group, the metabolic parameters including fasting plasma glucose, plasma insulin, and oral glucose tolerance test values were dramatically improved after RYGB and Sleeve procedures (p < .05) as predicted. In addition, RYGB and Sleeve groups increased the proportion of pancreatic β cells and reduced the ratio of α cells. Two multiple hormone-expressing cells were identified, the Gcg+/Ppy + and Ins+/Gcg+/Ppy + cells. The pancreatic Ins+/Gcg+/Ppy + cells were defined for the first time, and further investigation indicates similarities with α and β cells, with unique gene expression patterns, which implies that pancreatic cell transdifferentiation occurs following bariatric surgery. For the first time, using the single-cell transcriptome map of ZDF rats, we reported a comprehensive characterization of the heterogeneity and differentiation of pancreatic endocrinal cells after bariatric surgery, which may contribute to the underlying mechanisms. Further studies will be needed to elucidate these results.

Future diabetes risk can be predicted by the number of abnormal oral glucose tolerance test values during pregnancy.

To quantify the future risk of type 2 diabetes (T2D) in women with gestational diabetes (GD) based on baseline metabolic characteristics and the number of abnormal values during a 3-hour 100-g oral glucose tolerance test (OGTT). We conducted a population-based retrospective cohort study of 10 023 pregnant women who underwent testing for GD in a large health maintenance organization in Israel using a 100-g OGTT. Glucose values were obtained at four time points, 0, 60, 120 and 180 minutes. We identified 9939 women who met the study criteria. Median follow-up was 3.25 (interquartile range 1.5-5.1; maximum 10.1) years. Using women without GD as reference, women with GD were at an increased risk of future T2D (hazard ratio [HR] 5.33 [95% confidence interval {CI} 3.86-7.34]). This risk increased with a greater number of abnormal OGTT values, with the highest risk seen in women with four abnormal values (HR 16.67 [95% CI 7.94-35.01]). In a multivariate model, a higher number of abnormal values, Arab ethnicity, higher body mass index, triglycerides and prepregnancy glucose were significantly associated with increased risk. Future T2D risk was also affected by the type of OGTT abnormality; an abnormal fasting value had the greatest risk, whereas an abnormal 3-hour value had the lowest risk (HR 3.61 [95% CI 2.42-5.38] vs. 1.50 [95% CI 0.93-2.43], respectively). GD isa heterogenous disease, with varying degrees of glucose intolerance and subsequent T2D risk. Targeting interventions to womenat the highest risk may help to improve postpartum adherence and effective long-term follow-up strategies.

Cardiometabolic profile of women with a history of overt diabetes compared to gestational diabetes and normoglycemia in index pregnancy: Results from CHIP-F study.

We aimed to evaluate the prevalence of postpartum diabetes among women with a history of overt diabetes in pregnancy (ODiP) and compare with women having a history of gestational diabetes mellitus (GDM) and normoglycemia in pregnancy. We have an established longitudinal cohort of postpartum women with a history of hyperglycemia (preexisting diabetes [PED] [n = 101], ODiP [n = 92], GDM [n = 643]), and normoglycemia (n = 183) in pregnancy. For this study, we excluded women with PED and invited other eligible women in a fasting state for clinical and biochemical evaluation. We evaluated 918 women with a mean (SD) age of 33.6 (5.0) years and at a median (interquartile range) postpartum interval of 31 (20-45) months. Diabetes was diagnosed in 65 (70.7%) women in ODiP compared to 99 (15.4%) in GDM (p < .001) and 4 (2.2%) in normoglycemia group (p < .001). In the ODiP group, the prevalence of diabetes was 47.4% among women tested in the first year postpartum, increasing to 86.8% among women tested at >3 years postpartum. Diabetes was more common when ODiP was diagnosed in the first (27/29, 93.1%) compared to the second trimester of pregnancy (35/57, 61.4%). The adjusted odds ratio for diabetes in ODiP was 14.82 (95% confidence interval, 8.49-25.87; p < .001; reference category: GDM). The prevalence of postpartum diabetes was significantly higher in women with ODiP compared to GDM. Nearly 50% of women with ODiP did not develop diabetes in the first year of follow-up, especially when ODiP was diagnosed after the first trimester of pregnancy and on the basis of a 2-h oral glucose tolerance test value. Such women are amenable to prevention strategies.

1465-P: Identification of GCK Gene Variants and Clinical Characterization in Japanese Pediatric MODY2 Cases

Maturity-onset diabetes of the young (MODY) is traditionally characterized by early onset and a heterogeneous autosomal dominant form of inheritance. MODY2 may be common in the Japanese, but the difference in clinical characteristics compared to Europeans and Americans remains unclear. Here, we examined the characteristics in Japanese pediatric patients diagnosed with MODY2. We retrospectively reviewed the diagnostic data of Japanese MODY2 patients diagnosed at our hospital between 2009 and 2022. Genetic screening for MODY2 was performed by direct sequencing followed by multiplex ligation amplification assays. We identified 20 missense mutations in 25 patients and 2 nonsense mutations in 2 patients. We detected 5 deletions in 6 patients. The mean age at diagnosis was 10 years (range 2-14 years), the mean BMI percentile was 46.2%, with none being obese. Mean HbA1c was 6.54%. A glucose tolerance test was performed on 29 patients, 15 of whom were diabetic (7 were diabetic at fasting, 5 were diabetic at 120 min, 3 were diabetic at both) and 14 of borderline diabetes (IFG + IGT: 11, IFG: 2, and IGT: 1). The average glucose tolerance test values were 121.6 mg/dL at 0 min and 182.2 mg/dL at 120 min. No correlation was found between age at onset and plasma glucose value at 0 and 120 min. Reportedly, MODY2 causes a slight increase in post-load blood glucose levels, however the difference between 120 min and 0 min was 56.0 mg/dL (−32 to 140). A negative correlation was observed between 0 min and 120 min blood glucose levels. HOMAIR average was 1.85, 27% of which patients were 2.5 or higher; HOMA-β average was 37.0%, 39% of which showed &amp;lt;30%; and insulinogenic index averaged 0.63, 25% of which showed &amp;lt;0.4, indicating decreased initial insulin secretion. In this study, it is suggested that in Japanese MODY2 cases, glucose sensor dysfunction due to GCK gene mutation causes decreased initial insulin secretion. Disclosure R.Katashima: None. S.Yoshida: None. Y.Watanabe: None. M.Moritani: None. I.Yokota: None.

Can We Predict Isolated Fasting Hyperglycemia in Patients With GDM? [ID: 1368593

INTRODUCTION: One-third of patients with gestational diabetes mellitus (GDM) require hypoglycemic agents. There is a subset of patients who control their postprandial values with diet, yet they have persistent fasting hyperglycemia requiring bedtime hypoglycemic agents (GDMHS). As fasting hyperglycemia is an independent risk factor for adverse pregnancy outcomes, we aimed to identify risk factors to predict (and subsequently counsel) GDM patients with a risk of isolated fasting hyperglycemia requiring treatment with bedtime hypoglycemic agents. METHODS: This was an IRB-approved retrospective cohort study of patients diagnosed with GDM after 24 weeks from 2016 to 2020. Patients monitored glucose four times daily (fasting and 2 hours postprandial); fasting hyperglycemia was defined as more than 50% fasting values greater than 90 mg/dL. Patients completely controlled with diet (GDMA1) were compared to those with GDMHS. A multivariate analysis assessed whether age, body mass index (BMI), fasting glucose tolerance test (GTT) value, HbA1c at diagnosis, history of polycystic ovarian syndrome or previous GDM, Asian race, or family history of diabetes predicted isolated fasting hyperglycemia. RESULTS: Four hundred five patients had GDM. 57% had GDMA1, and 28% had GDMHS. Compared to GDMA1, patients with GDMHS were older, had higher BMI, higher fasting GTT value, higher HbA1c, and higher incidence of previous GDM or family history of diabetes. After adjusting for confounders, higher HbA1c at GDM diagnosis (odds ratio [OR] 3.55), older age (OR 1.08), and higher fasting GTT value (OR 1.06) were significantly associated with an increased probability of persistent fasting hyperglycemia. Asian race was associated with decreased probability of fasting hyperglycemia but was confounded by lower fasting GTT and lower BMI. CONCLUSION: Our data suggest that elevated HbA1c, higher fasting GTT value, and older age may predict persistent isolated fasting hyperglycemia in GDM patients who are otherwise controlled with diet. These data can be used to educate and counsel patients to alleviate frustration encountered with persistent fasting hyperglycemia despite postprandial diet control.

Gut microbiome-mediated glucose and lipid metabolism mechanism of star apple leaf polyphenol-enriched fraction on metabolic syndrome in diabetic mice

BackgroundDiabetes is a kind of metabolic syndrome (MetS) that seriously threatens human health globally. The leaf of star apple (Chrysophyllum cainito L.) is an incompletely explored folk medicine on diabetes. And, the effects and mechanisms on diabetes complicated glycolipid metabolism disorders are unknown till now. PurposeThis study aimed to investigate the constituents of star apple leaf polyphenol enriched-fraction (SAP), and elucidate their treatment effects and mechanism on diabetes and accompanied other MetS. MethodsThe components of SAP were tentatively identified by HPLC-Q-TOF-MS/MS. The antioxidant activity was determined by the scavenging of free radicals and hypoglycemic activities by inhibition of α-glucosidase in vitro. HepG2 cells were used for evaluating the alleviation effects of SAP on lipid accumulation. Streptozotocin and high-fat diet induced diabetic mice were grouped to evaluate the effects of different dosages of SAP. 16S rRNA was conducted to analysis gut microbiome-mediated glucose and lipid metabolism mechanism. ResultsIt showed that myricitrin was one of the main active constituents of SAP. SAP not only showed low IC50 on -glucosidase (24.427± 0.626 μg/mL), OH·(3.680± 0.054 μg/mL) and ABTS· (9.155±0.234 μg/mL), but significantly induced the lipid accumulation in HepG2 cells (p < 0.05). SAP at 200 mg/kg·day significantly decreased the blood glucose, insulin and oral glucose tolerance test value (p < 0.05). The insulin resistance indexes and oxidative stress were alleviated after administration. SAP not only attenuated hepatic lipid deposition, but also reversed the hepatic glycogen storage. 16S rRNA sequencing results revealed that the interaction between SAP and gut microbiota led to the positive regulation of beneficial bacteria including Akkermansia, Unspecified S24_7, Alistipes and Unspecified_Ruminococcaceae, which might be one of the mechanisms of SAP on MetS. ConclusionFor the first time, this study explored the regulation effect of star apple leaf polyphenols on the hepatic glycolipid metabolism and studied the underlying mechanism from the view of gut microbiota. These findings indicated that SAP possesses great potential to serve as a complementary medicine for diabetes and associated MetS. It provided scientific evidence for folk complementary medicine on the treatment of diabetes-complicated multiple metabolic disorders.

Beta cell regeneration upon magainin and growth hormone treatment as a possible alternative to insulin therapy.

Insulin therapy, pancreas transplantation and β cell regeneration are among the suggested treatment strategies for type 1 diabetes. It has been shown that some antimicrobial peptides have the potential to increase insulin release and to improve glucose tolerance, although the mechanism by which they promote the regeneration of damaged pancreatic cells to functional β-like cells remains unknown. To answer this question, we evaluated the in vivo effects of magainin-AM2 and growth hormone (GH) on the regeneration of streptozotocin (STZ)-damaged mouse pancreas. Treatment with magainin-AM2 and GH ameliorated the effects of STZ on fasting blood glucose and glucose tolerance test values, and also resulted in a significant increase in total cell counts (α and β) and the number of insulin+ and glucagon+ cells per islet and a decrease in the number of T and B cells. In addition, we observed a 1.43- and 2.21-fold increase in expression of paired box 4, one of the main factors for α to β-like cell conversion, in normal- and diabetes-treated mice, respectively. Similarly, expression of P-S6 and extracellular signal-regulated kinases 1 and 2, required for cell proliferation/differentiation, increased by 3.27- and 2.19-fold among the diabetes-treated and control diabetic mice, respectively. Furthermore, in all experiments, amelioration of the effects of STZ were greatest upon Mag treatment followed by GH administration. The present in vivo data provide evidence in support of the possibility of pharmaceutical induction of α cell production and their trans-differentiation to functional β-like cells.

A Comparative Study on Improving Streptozotocin-Induced Type 2 Diabetes in Rats by Hydrosol, Extract and Nanoemulsion Prepared from Cinnamon Leaves.

Cinnamomoum osmophloeum Kanehira (C. osmophloeum) contains various biologically active antioxidant compounds such as flavonoids, phenolic acids and cinnamaldehyde. Type 2 diabetes mellitus is a chronic disease of metabolic abnormality caused by insulin deficiency or resistance. The objectives of this study were to analyze various bioactive compounds in C. osmophloeum leaves by ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and compare the effects of hydrosol, extract and nanoemulsion prepared from C. osmophloeum leaves on improving type 2 diabetes in rats. Our results show that a total of 15 bioactive compounds in C. osmophloeum leaves, including quercetin, quercetin-3-O-galactoside, quercetin-3-O-glucoside, rutin, caffeic acid, benzoic acid, 5-O-caffeoylquinic acid, kaempferol 3-β-D-glucopyranoside, trans-cinnamic acid, coumarin, cinnamyl alcohol, p-coumaric acid, eugenol, kaempferol and cinnamaldehyde, were separated within 14 min for subsequent identification and quantitation by UPLC-MS/MS. The nanoemulsion was successfully prepared by mixing C. osmophloeum leaf extract, soybean oil, lecithin, Tween 80 and deionized water in an appropriate proportion with a mean particle size, polydispersity index, zeta potential and encapsulation efficiency of 36.58 nm, 0.222, -42.6 mV and 91.22%, respectively, while a high storage and heating stability was obtained. The animal experiment results reveal that the high-dose nanoemulsion was the most effective in reducing both fasting blood glucose and oral glucose tolerance test value, followed by low-dose nanoemulsion, high-dose extract, low-dose extract and leaf powder in hydrosol. A similar trend was shown in reducing serum insulin and the homeostatic model assessment of insulin resistance index. In addition, the contents of serum biochemical parameters, including total cholesterol, triglyceride, aspartate aminotransferase, alanine aminotransferase, uric acid, urea nitrogen and creatinine, were reduced, with the high-dose nanoemulsion showing the most pronounced effect. Collectively, the high-dose nanoemulsion may possess great potential to be developed into a hypoglycemic health food or botanic drug.

Assessment of the Validity of Administrative Data for Gestational Diabetes Ascertainment

Administrative data, including International Classification of Diseases codes and birth certificate records, are often used for retrospective gestational diabetes research investigations to describe associations of gestational diabetes with perinatal complications and long-term outcomes, and to determine gestational diabetes prevalence. Research investigating the validity of using International Classification of Diseases codes and birth certificates for gestational diabetes ascertainment shows varying degrees of reliability. This study aimed to evaluate the accuracy of both International Classification of Diseases codes and birth certificate diagnosis for gestational diabetes ascertainment in a large hospital-based cohort of pregnant individuals, using laboratory criteria for gestational diabetes mellitus as the reference. We studied individuals who received prenatal care at an academic hospital and affiliated community health centers between 1998 and 2016. In the setting of universal 2-step screening for gestational diabetes, pregnant individuals were classified as having gestational diabetes if ≥2 oral glucose tolerance test values met or exceeded National Diabetes Data Group thresholds. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value for International Classification of Diseases code and birth certificate ascertainment of gestational diabetes, and their exact binomial 95% confidence intervals. In a cohort of 51,059 pregnancies with complete glucose screening, 1303 (2.6%) met National Diabetes Data Group laboratory criteria for gestational diabetes. Gestational diabetes International Classification of Diseases codes had moderate sensitivity of 70.5% (95% confidence interval, 67.9-72.9), high specificity of 99.3% (95% confidence interval, 99.3-99.4), a positive predictive value of 73.3% (95% confidence interval, 70.8-75.8), and a negative predictive value of 99.2% (95% confidence interval, 99.1-99.3). In the 46,512 pregnancies linked to birth certificate data, birth certificate diagnosis had moderate sensitivity (66.3% [95% confidence interval, 63.6-69.0]), high specificity (98.9% [95% confidence interval, 98.8-99.0]), moderate positive predictive value (62.1% [95% confidence interval, 59.8-64.4]), and high negative predictive value (99.1% [95% confidence interval, 99.0-99.2]). Ascertainment of gestational diabetes using administrative data, including International Classification of Diseases codes or birth certificates, has moderate sensitivity, moderate positive predictive value, high specificity, and high negative predictive value. Our findings provide context for interpreting the validity of studies that depend on administrative data for ascertainment of gestational diabetes and comparing them with prospective studies that use laboratory-based gestational diabetes criteria.

Placental DNA methylation changes in gestational diabetes mellitus

ABSTRACT In this study, we investigated the association between altered methylation in the maternal placenta and hyperglycaemia and explored the epigenetic mechanisms underlying gestational diabetes mellitus (GDM). Reduced representation bisulphite sequencing (RRBS) and RNA sequencing (RNA-seq) were performed on placental tissues obtained from women with GDM and healthy controls. Further, pyrosequencing, correlation analyses, and linear regression analyses were performed to valuate relationships between aberrantly methylated-differentially expressed genes and clinical parameters. The EMBOSS and JASPAR databases were used for a computational analysis of CpG islands and transcription factor-binding sites in the TRIM67 promoter region. A CpG island with a length of 264 bp in the placental TRIM67 promoter region in the GDM group exhibited significant hypermethylation at four CpG sites. The hypermethylation of the TRIM67 promoter region in the maternal placenta showed a significant, positive correlation with the 1 h and 2 h oral glucose tolerance test (OGTT) values and a negative correlation with lipoprotein(a). Placental DNA methylation levels in the TRIM67 promoter region were markedly elevated in GDM and were associated with blood glucose and lipid levels during healthy pregnancy.

Do pregnancy outcomes of women with false-positive early gestational diabetes mellitus differ from those of women with normal glucose tolerance?

BackgroundTo investigate whether false-positive early gestational diabetes mellitus (GDM) women can be managed similarly as normal glucose tolerance (NGT) women.MethodsThis retrospective study was conducted at a tertiary care center in Japan. Pregnancy and neonatal outcomes of 67 singleton pregnancies with false-positive early GDM and 1774 singleton pregnancies with NGT who delivered after 22 weeks of gestation were compared. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria (patients having one or more of the following: fasting plasma glucose ≥ 92 mg/dL and a 75 g oral glucose tolerance test (OGTT) value ≥ 180 mg/dL at 1 h, or ≥ 153 mg/dL at 2 h). Pregnant women diagnosed with GDM in early pregnancy who did not meet the diagnostic criteria on the second OGTT were defined as having false-positive early GDM. Women with false-positive early GDM did not receive any therapeutic intervention during gestation.ResultsMaternal age, pre-pregnancy body mass index, and gestational weight gain were significantly higher in the false-positive GDM group than in the NGT group. No significant differences were found in pregnancy outcomes, including gestational age, birth weight, large for gestational age rate, and cesarean delivery rate. Except for a higher neonatal hypoglycemia rate in the false-positive early GDM group, no significant differences were found in neonatal outcomes.ConclusionsThere were no clinically significant differences between early GDM false-positive women exhibiting GDM patterns only during early pregnancy and NGT women. False-positive early GDM women can be managed similarly as NGT women, suggesting that World Health Organization diagnostic guidelines, applying the IADPSG criteria during early pregnancy, need revision.

111-LB: CHM-273S Peptide Decreases Blood Glucose Level, Improves Insulin Sensitivity, and Induces Insulin Signaling Pathways in the Liver of Rats with Diet-Induced Metabolic Disorder

CHM-273S is a novel peptide derived from proprietary milk hydrolysate. It demonstrated the ability to induce IRS2 expression in primary murine fibroblasts. IRS2 is one of the main components of insulin receptor signaling pathway, and its expression activation is associated with the changes in the functioning of insulin- and glucose-dependent intracellular mechanisms in general. Such effect is typical for the main antidiabetic drugs including metformin and GLP-1R agonists and potentially indicates that CHM-273S can regulate cellular response to glucose and insulin. In the present work, we studied the ability of CHM-273S to alleviate symptoms of metabolic disorder caused by a high-sucrose diet (HSD) . Sprague-Dawley male rats (N=50) were given free access to 30% sucrose solution for 5 weeks. Animals with symptoms of a metabolic disorder - a stable significant increase in blood glucose concentration - were tested in the glucose tolerance test (GTT) . Single 1 mg/kg and 10 mg/kg CHM-273S i.p. administration 12, 2 and 0 hours prior to oral glucose injection in GTT significantly reduced blood glucose level. Additionally, CHM-273S administration 2 and 12 hours before blood sampling led to a decrease in fasting blood insulin concentration measured by ELISA and insulin resistance index HOMA-IR elevated as a result of HSD. These data indicates the peptide’s ability to alleviate the HSD-caused insulin resistance in experimental animals. Finally, the rats received CHM-273S and after 12 hours were injected with insulin 3 minutes before liver samples collection. CHM-273S restored pAKT (Thr308) and induced p-AKT (Ser473) levels in the liver, which indicates the ability of the peptide to normalize insulin signaling. The effect of CHM-273S on insulin signaling pathways in liver cells highly correlates with the observed decrease in blood glucose level in GTT and HOMA-IR values and could underly the mechanism of these effects. Disclosure V. Pavshintsev: None. N. Mitkin: None. I. Doronin: None. E. Emelianova: None. M. Lovat: None. G. Babkin: None. A. Malyshev: None.

Sex-dependent influence of maternal predictors on fetal anthropometry in pregnancies with gestational diabetes mellitus

BackgroundThird trimester fetal anthropometric parameters are known to predict neonatal complications. A better understanding of predictors of adverse fetal parameters might help to personalize the use and frequency of fetal ultrasound. The objectives of this study were:(a) to evaluate the utility of maternal sociodemographic, anthropometric and metabolic predictors to predict 3rd trimester fetal anthropometric parameters in women with gestational diabetes mellitus (GDM),(b) to assess whether the impact of these maternal predictors is fetal sex-dependent, and(c) to provide a risk stratification for markers of fetal overgrowth (fetal weight centile (FWC) and fetal abdominal circumference centile (FACC) depending on prepregnancy BMI and gestational weight gain (GWG) until the 1st GDM visit.MethodsThis prospective study included 189 women with GDM. Maternal predictors were age, ethnicity, prepregnancy BMI, GWG and excessive weight gain until the 1st GDM visit, fasting, 1-hour and 2-hour blood glucose oral glucose tolerance test values, HbA1c at the 1st visit and medical treatment requirement. Fetal outcomes included FWC, FWC >90% and <10%, FACC, FACC >90% and <10%, at 29 0/7 to 35 6/7 weeks of gestational age. We performed univariate and multivariate regression analyses and probability analyses.ResultsIn multivariate analyses, prepregnancy BMI was associated with FWC, FWC > 90% and FACC. GWG until the 1st GDM visit was associated with FWC, FACC and FACC > 90% (all p ≤ 0.045). Other maternal parameters were not significantly associated with fetal anthropometry in multivariate analyses (all p ≥ 0.054). In female fetuses, only GWG was associated with FACC (p= 0.044). However, in male fetuses, prepregnancy BMI was associated with FWC, FWC > 90% and FACC and GWG with FWC in multivariate analyses (all p ≤ 0.030). In women with a prepregnancy BMI of ≥ 25 kg/m2 and a GWG until the 1st GDM visit ≥ 10.3 kg (mean GWG), the risk for FWC > 90% and FACC > 90% was 5.3 and 4 times higher than in their counterparts.ConclusionsA personalized fetal ultrasound surveillance guided by fetal sex, prepregnancy BMI and GWG may be beneficial in reducing adverse fetal and neonatal outcomes.

Maternal exposure to traffic-related ambient particles and risk of gestational diabetes mellitus with isolated fasting hyperglycaemia: A retrospective cohort study in Beijing, China.

Ambient particles have been associated with gestational diabetes mellitus (GDM), however, no study has evaluated the effects of traffic-related ambient particles on the risks of GDM subgroups classified by oral glucose tolerance test (OGTT) values. A retrospective analysis was conducted among 24,001 pregnant women who underwent regular prenatal care and received OGTT at Haidian Maternal and Child Health Hospital in Beijing, China, 2014-2017. A total of 3,168 (13.2%) pregnant women were diagnosed with GDM, including 1,206 with isolated fasting hyperglycaemia (GDM-IFH). At a fixed-location monitoring station, routinely monitored ambient particles included fine particulate matter (PM2.5), black carbon (BC) and particles in size ranges of 5-560nm (PNC5-560). Contributions of PNC5-560 sources were apportioned by positive matrix factorization model. Logistic regression model was applied to estimate odds ratio (OR) of ambient particles on GDM risk. Among the 24,001 pregnancy women recruited in this study, 3,168 (13.2%) were diagnosed with GDM, including 1,206 with isolated fasting hyperglycaemia (GDM-IFH) and 1,295 with isolated post-load hyperglycaemia (GDM-IPH). We observed increased GDM-IFH risk with per interquartile range increase in first-trimester exposures to PM2.5 (OR=1.94; 95% Confidence Intervals: 1.23-3.07), BC (OR=2.14; 1.73-2.66) and PNC5-560 (OR=2.46; 1.90-3.19). PNC5-560 originated from diesel and gasoline vehicle emissions were found in associations with increases in GDM-IFH risk, but not in GDM-IPH risk. Our findings suggest that exposure to traffic-related ambient particles may increase GDM risk by exerting adverse effects on fasting glucose levels during pregnancy, and support continuing efforts to reduce traffic emissions for protecting vulnerable population who are at greater risk of glucose metabolism disorder.

Characteristics of pregnancy with gestational diabetes mellitus and the consecutive pregnancy as predictors for future diabetes mellitus type 2

AimTo explore possible obstetrical history-related, modifiable risk factors of future type 2 diabetes mellitus (T2DM), with focus on characteristics of the index gestational diabetes mellitus (GDM) pregnancy and the consecutive pregnancy. MethodsThis retrospective, population-based, cohort study included 788 women with GDM, who had consecutive deliveries at Emek Medical Center during 1991–2012. Women with pre-existing diabetes were excluded. Factors associated with T2DM development were examined using stepwise multiple Cox regression model. ResultsOverall 178 women developed T2DM (23%). Multivariable analysis demonstrated that the most significant independent risk factors for T2DM development were birth weight ≥ 4000 g (HRadj1.7 95% CI [1.001–2.8]), fasting oral glucose tolerance test value (OGTT, HRadj1.03 95% CI [1.01–1.04], 1-hour post-OGTT glucose value (HRadj1.01 95% CI [1.006–1.02]), earlier gestational week in which GDM was diagnosed (HRadj 0.96 95% CI [0.93–0.99]), higher parity (HRadj 1.15 95% CI [1.06–1.25] and GDM recurrence in the consecutive delivery (HRadj2.4 95% CI [1.6–3.7]). Kaplan Meier survival curve of the time from the consecutive pregnancy until T2DM development showed a statistically significant effect of GDM recurrence and the risk for T2DM. Body mass index (BMI) gain between pregnancies and inter-pregnancy interval were not independent risk factors for T2DM. ConclusionsObstetric characteristics of women with GDM and particularly GDM recurrence are associated with increased risk for T2DM. Strategies to prevent those factors and especially GDM recurrence might reduce the risk of future T2DM.