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In this pragmatic, randomized trial comparing one-step screening for gestational diabetes mellitus with two-step screening, one-step screening resulted in more diagnoses of gestational diabetes mellitus but did not affect the incidence of adverse perinatal and maternal outcomes.

Microbiome-wide association studies on large population cohorts have highlighted associations between the gut microbiome and complex traits, including type 2 diabetes (T2D) and obesity 1 . However, the causal relationships remain largely unresolved. We leveraged information from 952 normoglycemic individuals for whom genome-wide genotyping, gut metagenomic sequence and fecal short-chain fatty acid (SCFA) levels were available 2 , then combined this information with genome-wide-association summary statistics for 17 metabolic and anthropometric traits. Using bidirectional Mendelian randomization (MR) analyses to assess causality 3 , we found that the host-genetic-driven increase in gut production of the SCFA butyrate was associated with improved insulin response after an oral glucose-tolerance test ( P  = 9.8 × 10 −5 ), whereas abnormalities in the production or absorption of another SCFA, propionate, were causally related to an increased risk of T2D ( P  = 0.004). These data provide evidence of a causal effect of the gut microbiome on metabolic traits and support the use of MR as a means to elucidate causal relationships from microbiome-wide association findings. Mendelian randomization analyses using genotyping data, gut metagenomic sequence and fecal short-chain-fatty-acid levels from 952 individuals combined with GWAS data show evidence of a causal effect of the gut microbiome on metabolic traits.

Abstract Context Gestational diabetes mellitus (GDM) is a common obstetric complication. Although early intervention could prevent the development of GDM, there was no consensus on early identification for women at high risk of GDM. Objective To develop a reliable prediction model of GDM in early pregnancy. Methods In this prospective cohort study, between May 30, 2021, and August 13, 2022, a total of 721 women were included from Women’s Hospital, Zhejiang University School of Medicine. Participants were asked to complete an oral glucose tolerance test (OGTT) during gestational weeks 7 through 14 for early prediction of GDM, and at weeks 24 through 28 for GDM diagnosis. Using OGTT results and baseline characteristics, logistic regression analysis was used to construct the prediction model. Receiver operating characteristic (ROC) curve, Hosmer-Lemeshow test, decision clinical analysis, and a nomogram were used for model performances assessment and visualization. Internal and external validation was performed to testify the stability of this model. Results According to the International Association of Diabetes and Pregnancy Study Groups criteria in early OGTT, the mean (SD) age was 30.5 ± 3.7 years in low-risk participants and 31.0 ± 3.9 years in high-risk participants. The area under ROC curve (AUC) of the existing criteria at weeks 7 through 14 varied from 0.705 to 0.724. Based on maternal age, prepregnancy body mass index, and results of early OGTT, the AUC of our prediction model was 0.8720, which was validated by both internal (AUC 0.8541) and external (AUC 0.8241) confirmation. Conclusions The existing diagnostic criteria were unsatisfactory for early prediction of GDM. By combining early OGTT, we provided an effective prediction model of GDM in the first trimester.

OBJECTIVE:--We sought to determine whether an oral disposition index (DIO) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DIO by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and β-cell function. RESEARCH DESIGN AND METHODS--A total of 613 Japanese-American subjects (322 men and 291 women) underwent a 75-g oral glucose tolerance test (OGTT) at baseline, 5 years, and 10 years. Insulin sensitivity was estimated as 1/fasting insulin or homeostasis model assessment of insulin sensitivity (HOMA-S). Insulin response was estimated as the change in insulin divided by change in glucose from 0 to 30 min (ΔI₀₋₃₀/ΔG₀₋₃₀). RESULTS:--ΔI₀₋₃₀/ΔG₀₋₃₀ demonstrated a curvilinear relationship with 1/fasting insulin and HOMA-S with a left and downward shift as glucose tolerance deteriorated. The confidence limits for the slope of the loge-transformed estimates included -1 for ΔI₀₋₃₀/ΔG₀₋₃₀ versus 1/fasting insulin for all glucose tolerance groups, consistent with a hyperbolic relationship. When HOMA-S was used as the insulin sensitivity measure, the confidence limits for the slope included -1 only for subjects with normal glucose tolerance (NGT) or impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) but not diabetes. On the basis of this hyperbolic relationship, the product of ΔI₀₋₃₀/ΔG₀₋₃₀ and 1/fasting insulin was calculated (DIO) and decreased from NGT to IFG/IGT to diabetes (P < 0.001). Among nondiabetic subjects at baseline, baseline DIO predicted cumulative diabetes at 10 years (P < 0.001) independent of age, sex, BMI, family history of diabetes, and baseline fasting and 2-h glucose concentrations. CONCLUSIONS:--The DIO provides a measure of β-cell function adjusted for insulin sensitivity and is predictive of development of diabetes over 10 years.

Background We piloted a randomised controlled trial (RCT) comparing pregnancy outcomes among women with booking gestational diabetes (GDM) receiving immediate or deferred treatment. Methods Consecutive, consenting women < 20 weeks gestation, with GDM risk factors attending the hospital book-in clinic, completed an oral glucose tolerance test (OGTT). Clinicians were blinded to OGTT results. Women fulfilling World Health Organisation GDM criteria were randomised to either clinic referral /ongoing treatment (Treated Group n  = 11), or no treatment (No Treatment Group n  = 10). Women without ‘Booking GDM’ (‘Decoys’ n  = 58) and those in the No Treatment Group had a repeat OGTT at 24–28 weeks (with GDM treated if diagnosed). Midwives and mothers were asked to complete surveys and attend focus groups before and after the study respectively regarding their experiences and expectations of the study protocol. Results Sufficient women completed each step of the RCT. Gestation at OGTT was late at 18 ± 2 weeks with Treated and No Treatment groups largely similar. At 24–28 weeks gestation, GDM was present in 8/9 (89%) in the No Treatment group and 11/56 (20%) Decoys. NICU admission was highest in the Treated group (36% vs 0% p  = 0.043), largely due to small for gestational age, and Large for Gestational Age babies greatest in the No Treatment group (0% vs 33% p  = 0.030). Conclusion An RCT deferring ‘Booking GDM’ treatment is feasible. Most women with untreated ‘Booking GDM’ in mid 2nd trimester had GDM at 24–28 weeks. Early treatment may have both benefits and harms. A full RCT is needed. Trial registration Australia New Zealand Clinical Trials Registry ACTRN12615000974505. Registered 17th May 2015; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=369100&isReview=true Retrospectively Registered.

Background: An univocal definition for a lack of glucose peak during the oral glucose tolerance test in pregnancy (flat curve) has never been agreed upon. Thus, the aim of this study was to provide a definition for the flat 75 g oral glucose tolerance test (OGTT) and to assess its clinical significance. Methods: A retrospective cohort study, where 8.810 pregnant singleton women were evaluated at the time of a 75 g OGTT between 240 and 286 weeks for the universal screening of gestational diabetes (GDM). The 75 g OGTT was considered flat when the difference between peak and fasting glucose concentrations was ≤30 mg/dL. A total of 953 (10.8%) women were diagnosed as having GDM, while 7.857 (89.2%) had normal glucose tolerance (NGT); 2791 women with normal glucose tolerance (35.5%) had a FLAT curve and 5066 (64.5%) had a concentration difference > 30 mg/dL (NGT). In all groups, we evaluated maternal characteristics and perinatal outcome. Results: Women with a FLAT curve were younger, taller, thinner, and their pre-pregnancy body mass index was lower than the other groups (all p < 0.001). The rate of obesity was also lower (p < 0.01). The vaginal delivery rate was higher than in NGT (80.4% vs. 77.8%; p < 0.01) and women with GDM (73.0%; p < 0.001) and that of primary cesarean lower than in NGT (11.9% vs. 14.8%; p < 0.001) and women with GDM (18.2%; p < 0.001). Between women with a FLAT and NGT OGTT curve, there was no significant difference for birthweight < 10th percentile (6.9% vs. 6.2%; p = 0.2), though the proportion of birthweight > 90th was lower (8% vs. 10%; p < 0.01). Conclusions: A 75 g flat OGTT as defined does not represent an abnormal maternal phenotype nor portend an adverse perinatal outcome.

Background Gestational Diabetes Mellitus (GDM) incidence and adverse outcomes have increased globally. The validity of the oral glucose tolerance test (OGTT) for GDM diagnosis has long been questioned, with no suitable substitute reported yet. Continuous Glucose Monitoring (CGM) is potentially a more acceptable and comprehensive test. The aim of this study was to assess the Freestyle Libre Pro 2 acceptability as a diagnostic test for GDM, then triangulating its results with OGTT results as well as risk factors and sonographic features of GDM. Methods Women wore the CGM device for 7 days at 24–28 weeks, undergoing the OGTT before CGM removal. CGM/OGTT acceptability as well as GDM risk factors evaluation occurred via three online surveys. CGM distribution/variability/time in range parameters, combined in a CGM Score of Variability (CGMSV), were triangulated with OGTT results and a risk-factor-based Total Risk Score (TRS). In a subgroup, GDM ultrasound features (as modified Ultrasound Gestational Diabetes Score – m-UGDS) were also incorporated. Results Of 107 women recruited, 87 (81%) were included: 74 (85%) with negative OGTT (NGT) and 13 (15%) positive (GDM). No significant difference was found between NGT and GDM in terms of demographics (apart from family history of diabetes mellitus), CGM parameters and perinatal outcomes. Women considered CGM significantly more acceptable than OGTT (81% versus 27% rating 5/5, p  < 0.001). Of the 55 NGT with triangulation data, 28 were considered ‘true negative’ (TRS concordant with OGTT and CGMSV): of these 4/5 evaluated at ultrasound had m-UGDS below the cut-off. Five women were considered ‘false negative’ (negative OGTT with both TRS and CGMSV above the respective cut-offs). Triangulation identified also six ‘false positive’ women (positive OGTT but TRS and CGM both below the cut-offs). Only one woman for each of the last two categories had m-UGDS evaluated, with discordant results. Conclusions CGM represents a more acceptable alternative for GDM diagnosis to the OGTT. CGM triangulation analysis suggests OGTT screening may result in both false positives and negatives. Further research including larger cohorts of patients, and additional triangulation elements (such as GDM biomarkers/outcomes and expanded m-UGDS) is needed to explore CGM potential for GDM diagnosis.

Premeal consumption of whey protein improves the postmeal glycemic profile, but little information exists on soy protein. The study aim was to examine the effect of consuming different amounts of a soy protein isolate (SPI) before a 75-g oral glucose tolerance test (OGTT) on subsequent glycemic control. After overnight fasting, eight healthy young subjects consumed a 400-mL liquid meal containing 0 g (SP0), 20 g (SP20) or 40 g (SP40) SPI. Thirty minutes after SPI consumption, an OGTT was performed to evaluate the individual glycemic response. Blood glucose and plasma insulin concentrations were measured immediately before the SPI preload (i.e., 30 min before the start of the OGTT) and before (−10 min) and during the OGTT (15, 30, 45, 60, 90, and 120 min). The incremental area under the curve and peak blood glucose response were significantly less for SP40 than those for SP0 and SP20. Insulin secretion was significantly higher for SP20 and SP40 than that for SP0 before and at 15 min after oral glucose consumption. The incremental area under the curve of plasma insulin was significantly higher for SP20 and SP40 than that for SP0. An SPI preload of 40 g, but not 20 g, improved glycemic control in young healthy subjects. Glycemic control appears to be attributed not only to the exaggerated insulin response to SPI preload, but also to non-insulin dependent mechanism(s), such as delayed gastric emptying. •Soy protein isolate consumption before oral glucose tolerance test (as a simulated carbohydrate-rich main meal) improves postprandial glycemia.•Soy protein isolate preload enhanced the insulinotropic effect in a dose-dependent manner.•This positive effect could be induced by not only stimulating insulin secretion but also by possibly slowing gastric emptying.

OBJECTIVE: The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recently recommended new criteria for diagnosing gestational diabetes mellitus (GDM). This study was undertaken to determine whether adopting the IADPSG criteria would be cost-effective, compared with the current standard of care. RESEARCH DESIGN AND METHODS: We developed a decision analysis model comparing the cost-utility of three strategies to identify GDM: 1) no screening, 2) current screening practice (1-h 50-g glucose challenge test between 24 and 28 weeks followed by 3-h 100-g glucose tolerance test when indicated), or 3) screening practice proposed by the IADPSG. Assumptions included that 1) women diagnosed with GDM received additional prenatal monitoring, mitigating the risks of preeclampsia, shoulder dystocia, and birth injury; and 2) GDM women had opportunity for intensive postdelivery counseling and behavior modification to reduce future diabetes risks. The primary outcome measure was the incremental cost-effectiveness ratio (ICER). RESULTS: Our model demonstrates that the IADPSG recommendations are cost-effective only when postdelivery care reduces diabetes incidence. For every 100,000 women screened, 6,178 quality-adjusted life-years (QALYs) are gained, at a cost of $125,633,826. The ICER for the IADPSG strategy compared with the current standard was $20,336 per QALY gained. When postdelivery care was not accomplished, the IADPSG strategy was no longer cost-effective. These results were robust in sensitivity analyses. CONCLUSIONS: The IADPSG recommendation for glucose screening in pregnancy is cost-effective. The model is most sensitive to the likelihood of preventing future diabetes in patients identified with GDM using postdelivery counseling and intervention.

The gold-standard clamp measurements for insulin sensitivity (cSI), β-cell function (cBCF), and disposition index (cDI = cSI × cBCF) are not practical in large-scale studies. We sought to 1) validate a mathematical model-derived DI from oral glucose tolerance tests (OGTT) with insulin (mDI) and without (mDI-woI) against cDI and oral disposition index (oDI) and 2) evaluate the ability of the novel indices to detect prediabetes and type 2 diabetes (T2D). We carried out a secondary analysis of previously reported cross-sectional observational studies. The Insulin Sensitivity and Secretion mathematical model for glucose-insulin dynamics was applied to 5-point and 3-point OGTTs synchronized with hyperinsulinemic-euglycemic and hyperglycemic clamps from 130 youth with obesity (68 normal glucose tolerance [NGT], 33 impaired glucose tolerance [IGT], 29 T2D). Model-derived DI correlated well with clamp DI (R = 0.76 [logged]). Between NGT and IGT, mDI and mDI-woI decreased more than oDI and cDI, (60% and 59% vs 29% and 27%), and by receiver operating characteristic analysis were superior at detecting IGT compared with oDI and cDI (area under the curve [AUC] 0.88-0.87 vs 0.68-0.65), as was mean glucose (AUC 0.87). mDI-woI is better than oDI or the labor-intensive cDI for detecting dysglycemia in obese youth. Bypassing insulin measurements with mDI-woI from the OGTT provides a cost-effective approach for large-scale epidemiological studies of dysglycemia in youth.