2-hour Oral Glucose Tolerance Test Research Articles

Association of maternal triglyceride responses to thyroid function in early pregnancy with gestational diabetes mellitus.

The prevalence of Gestational Diabetes Mellitus (GDM) is increasing globally, and high levels of triglyceride (TG) and low levels of free thyroxine (FT4) in early pregnancy are associated with an increased risk of GDM; however, the interaction and mediation effects remain unknown. The aim of the present study is to examine the impact of FT4 and TG combined effects on the prevalence of GDM and the corresponding casual paths among women in early pregnancy. This study comprised 40,156 pregnant women for whom early pregnancy thyroid hormones, fasting blood glucose as well as triglyceride were available. GDM was diagnosed using a 2-hour 75-g oral glucose tolerance test (OGTT) according to the American Diabetes Association guidelines, and the pregnant women were grouped and compared according to the results. An L-shaped association between FT4 and GDM was observed. The prevalence of GDM increased with increasing TG levels. After accounting for multiple covariables, the highest risk for GDM was found among pregnant women of lower FT4 with the highest TG concentrations (odds ratio, 2.44, 95% CI, 2.14 to 2.80; P<0.001) compared with mothers of higher FT4 with the TG levels in the lowest quartile (Q1). There was a significant interaction effect of maternal FT4 and TG levels on the risk for GDM (P for interaction = 0.036). The estimated proportion of the mediating effect of maternal TG levels was 21.3% (95% CI, 15.6% to 36.0%; P < 0.001). In the sensitivity analysis, the mediating effect of TG levels was stable across subgroups. This study demonstrated an L-shaped association between maternal FT4 levels and GDM and the benefit of low TG levels, in which maternal TG levels act as an important mediator in this association. Our findings suggested that pregnant women who treat hypothyroidism should also reduce triglycerides levels in early pregnancy to prevent GDM development.

RF02 | PMON308 Hyperglycemia Is the Main Determinant of Cardiac Autonomic Dysfunction in Youth With Obesity Across the Spectrum of Glycemic Regulation.

Abstract Heart Rate Variability (HRV) results from the autonomic nervous system activity, it is a non-invasive marker of cardiac autonomic function. Loss of parasympathetic function (PNS) and sympathetic (SNS) override, reflected in decreased HRV, is one of the earliest subclinical manifestations of cardiac autonomic dysfunction. Lower HRV is associated with increased risk of cardiac events in adults. We aimed to characterize HRV in normal weight and overweight children with and without dysglycemia and to investigate the determinants of HRV in these youth, including body composition, glycemia measures, beta-cell function and inflammatory markers. We evaluated 94 adolescents (50 males/44 females), age 15 ± 2.1 years; 21 normal weight with normal glucose tolerance (NW-NGT), 23 overweight with NGT (OW-NGT) and 50 overweight with impaired glucose regulation (OW-IGR) including prediabetes (n= 27) and type 2 diabetes (n= 23). They underwent assessment of anthropometrics, body composition (DXA scan), inflammatory markers (hs-CRP and TNF-α), fasting labs and 2-hour oral glucose tolerance test (OGTT) with determination of glucose and insulin concentration. EndoPat was used to measure HRV: frequency-domain indices [high-frequency (HF) reflecting PNS, low-frequency (LF) reflecting both PNS and SNS, and LF/HF (higher is worse) estimating the ratio between SNS and PNS] and time-domain indices [the inter-beat interval of normal sinus beats (NN) and the standard deviation of NN (SDNN) measuring overall HRV, the square root of the mean squared difference of successive NN (RMSSD) and the NN intervals differing by more than 50 milliseconds (NN50) measuring PNS activity]. LF/HF was higher in the OW-IGR group compared with NW and OW-NGT (p=0.005). After controlling for sex, race and Tanner stage, fasting glucose (FBG) negatively correlated with NN (r=-0.22,p=0.04), SDNN (r=-0.21,p=0.05), RMSSD (r=-0.3,p=0.004), NN50 (r=-0.27,p=0.01) and HF (r=-0.26,p=0.02). LF/HF was positively related to FBG (r=0.39,p&amp;lt;0.001), 2hr-glucose (r=0.31,p=0.004) and HbA1c (r=0.22,p=0.04), and negatively with the insulinogenic index (r=-0.27,p=0.02), but not fasting insulin or HOMA-IR; LF/HF also correlated with percent body fat (r=0.22,p=0.04), hs-CRP (r=0.33,p=0.002) and TNF-α (r=0.38,p=0.006). In a linear regression model with LnLF/HF as the dependent variable and percent body fat, hs-CRP, FBG and HOMA-IR as the independent variables, FBG (beta=0.39,p=0.003) and hs-CRP (beta=0.21,p=0.09) were the significant determinants of LnLF/HF independent of age, sex, race and Tanner stage as covariates (R2= 0.23,p=0.013). Youth with impaired glucose metabolism have evidence of early subclinical cardiac autonomic dysfunction with decreased HRV, loss of parasympathetic function and sympathetic overdrive as reflected by lower time-domain indices, lower HF and higher LF/HF, related to glycemia and systemic inflammation. Presentation: Saturday, June 11, 2022 1:00 p.m. - 2:00 p.m., Saturday, June 11, 2022 1:12 p.m. - 1:17 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Assessment of the risk factors associated with type 2 diabetes and prediabetes mellitus: A national survey in Vietnam.

This study aims to estimating the prevalence of type 2 diabetes and prediabetes among adult from 30 to 69 years old and assess the association of risk factor with the conditions. A total of 5244 aged 30 to 69 years old were participated in this cross-sectional study, using nationally representative sampling frame. All participants were taking blood sample to measure fasting blood glucose level and 2-hour postload oral glucose tolerance test by National Hospital of Endocrinology, Vietnam. Multinomial logistic regressions with baseline-category logit models were conducted to identify factors associated with diabetes and prediabetes among respondents. The prediabetes prevalence was in 17.9% and diabetes in 7.3%. Patients who were male (reference group vs female OR = 0.79; 95% CI: 0.64, 0.97), in the 50 to 59 years old group (OR = 1.60; 95% CI: 1.28, 2.00), have hypertension and WHR risk have higher prevalence to have prediabetes (OR = 1.31; 95% CI: 1.12, 1.53; OR = 1.37; 95% CI: 1.11, 1.70, respectively). Male patients (reference group vs female OR = 0.62; 95% CI: 0.45, 0.84), patients who were in 40 to 49; 50 to 59; 60 to 69 years old, those who were housewife (OR = 2.17; 95% CI: 1.43, 3.28; OR = 2.85; 95% CI: 1.91, 4.27; OR = 3.12; 95% CI: 2.08, 4.69; OR = 1.71; 95% CI: 1.22, 2.40, respectively). Diabetes have significant associated with participants have hypertension (OR = 1.19; 95% CI: 1.72, 2.70). The common factor directly related to prediabetes and diabetes in both genders is age. Other factors directly associated with prediabetes and diabetes include BMI, WHR, hypertension, educational level, and job.

Ameliorating prediabetic subject status via fermented tea supplementation: A randomized, double-blind, parallel-group comparison study

Fermented tea consumption has been reported to alleviate diabetes and dyslipidemia, inducing an antiobesity effect. Here, we investigated the effects of microbial fermented tea and microbial fermented twig tea, which are made from Camellia sinensis by fermentation with Aspergillus sp., on glucose tolerance and metabolic syndrome in prediabetic subjects in a randomized, double-blind study. They were asked to consume the tea three times a day for 12 weeks. Fasting blood glucose, HbA1c, and 2-h oral glucose tolerance test (OGTT) were measured as primary endpoints. After 12 weeks, fasting blood glucose level was significantly reduced in the microbial fermented twig tea group (n = 19) as compared with that in the microbial fermented tea group (n = 16, p = 0.017). There was no significant difference in the 2-hour OGTT and HbA1c values between the two groups. Triglyceride levels were significantly lower in the microbial fermented tea group than in the microbial fermented twig tea group at 12 weeks (p = 0.049).

Atherosclerosis Risk Factors in Patients with Reactive Hypoglycemia.

PurposeGlucose metabolism disorders are an established risk factor for atherosclerosis. Although reactive hypoglycemia (RH) can be classified as one of these disorders, its role as a potential atherosclerosis risk factor remains unclear. The aim of the study was to assess whether patients with RH have a higher risk of atherosclerosis.Patients and MethodsWe recruited 178 patients (N=178) with suspected RH who were hospitalized after 2014 and underwent a prolonged 5-hour oral glucose tolerance test. The study cohort was divided into 2 groups depending on the results of the oral glucose tolerance test: Group 1 – subjects without RH (n=44), Group 2 –subjects with RH (n=134).ResultsThe analyzed groups differed significantly in terms of the following risk factors for atherosclerosis: high-density lipoprotein (HDL) cholesterol levels (54.3±18.8 mg/dL vs 63±18.5 mg/dL, p=0.003) and atherogenic indices (Castelli I: 3.7±1.2 vs 3.1±1.3, p=0.004; Castelli II: 2.1±0.9 vs 1.7±0.9, p=0.007; the atherogenic index of plasma: 0.34±0.33 vs 0.18±0.3, p=0.006; and the atherogenic coefficient: 2.7±1.2 vs 2.1±1.3, p=0.004). Univariate logistic regression showed that RH should not be considered to be a predictor of an increased atherogenic index of plasma (odds ratio [OR]=0.3 [95% confidence interval [CI] [0.16–0.7], p=0.002). Multivariate logistic regression revealed triglyceride levels (OR 1.14 [1.07–1.2], p=0.001) and body weight (OR 1.07 [1.03–1.12], p=0.002) to be independent risk factors for atherosclerosis.ConclusionAtherosclerosis risk factors are no more prevalent in patients with RH. RH does not increase the risk of an abnormal atherogenic index of plasma.

Ovarian volume as an independent marker for metabolic dysfunction in women with suspected androgen excess

To determine whether ovarian volume (OV) alone is an independent marker for metabolic dysfunction in women with suspected androgen excess. Retrospective cohort study. Tertiary academic reproductive endocrinology clinic. Women aged ≥21 years recruited/referred for symptoms related to androgen excess. Transvaginal ovarian ultrasound, physical and medical evaluation, 2-hour 75-g oral glucose tolerance test (oGTT), and blood sampling. Prevalence of hyperandrogenism and metabolic dysfunction. This study included 666 women, of whom 412 (61.9%) and 254 had OVs of >10 and ≤10 mL, respectively. An OV of >10 mL was associated with a higher prevalence of hirsutism (65.1% vs. 51.5%) than an OV of ≤10 mL. Polycystic ovary syndrome by the National Institutes of Health 1990 criteria was found in 67.3% and 51.4% of women with OVs of >10 and ≤10 mL, respectively. Metabolic parameters, including body mass index, waist circumference, and 1-hour insulin levels during the oGTT (odds ratio, 1.98; 95% confidence interval, 1.18-3.31), were significantly higher in women with an OV of >10 mL than in those with an OV of ≤10 mL. An OV of ≤10 mL had a 76.3% negative predictive value for hyperinsulinemia at 1 hour. In women with suspected androgen excess, an OV of >10 mL in at least 1 ovary is not associated with metabolic syndrome but is associated with younger age; an increased body mass index and waist circumference; a higher prevalence of hirsutism, oligoovulation, and polycystic ovary syndrome; and a higher 60-minute insulin level during the oGTT. Overall, an increased OV appears to be a good marker for hyperinsulinemia and hyperandrogenism in women suspected of having an androgen excess disorder.

Frequent Cannabis Smoking and Association with Prediabetes and Diabetes in Early Adulthood

Background: Cannabis use in young adulthood has been linked with increased risk of prediabetes later in life. However, many previous studies have only used fasting blood samples to determine risk for type 2 diabetes (T2D), which may not detect early changes in glucose homeostasis. The objective of this study was to determine the association between cannabis use and risk for prediabetes and T2D in young adults using several measures of glucose homeostasis, including an oral glucose tolerance test (OGTT). Methods: The Meta-CHEM study is a subset (N=84) of overweight and obese young adults aged 22–25 years from the Children&amp;#x27;s Health Study (CHS). Participants underwent a single clinical visit which included a 2-hour OGTT and questionnaire about cannabis smoking habits in the past year. Participants were classified as non-smokers, light cannabis smokers (smoke &amp;#x3c;once a week), and heavy cannabis smokers (smoke &amp;#x3e;once a week). Those smoking more than one cigarette in the past week were excluded from the study. Participants were classified as having prediabetes or T2D if they had a HbA1c &amp;#x3e;5.6%, fasting glucose &amp;#x3e;99 mg/dL, and/or 2-hour OGTT glucose &amp;#x3e;139 mg/dL. Logistic regression was used to assess the associations between cannabis smoking habits and metabolic outcomes after adjusting for age, sex, education, body mass index, Hispanic ethnicity, physical activity, and alcohol consumption. Results: 52 (62%) participants were non-diabetic, 28 (33%) had pre-diabetes, and 4 (0.05%) had T2D. 25 (30%) participants were nonsmokers, 47 (56%) were light cannabis smokers, and 12 (14%) were heavy cannabis smokers. The odds of having prediabetes or T2D was 7.3 times higher among heavy smokers (95% CI: 0.94, 7.7), and 1.5 times higher among light smokers (CI: 0.43, 6.0) than nonsmokers (P-value for trend = 0.03). Conclusion: Cannabis use in overweight and obese young adults was significantly associated with risk of having prediabetes or T2D.

Difference on Glucose Profile From Continuous Glucose Monitoring in People With Prediabetes vs. Normoglycemic Individuals: A Matched-Pair Analysis.

Comprehensive characteristics of the glycemic profile for prediabetes derived by continuous glucose monitoring (CGM) are unknown. We evaluate the difference of CGM profiles between individuals with prediabetes and normoglycemic individuals, including the response to oral glucose tolerance test (OGTT). Individuals with prediabetes matched for age, sex, and BMI with normoglycemic individuals were instructed to use professional CGM for 1 week. OGTT was performed on the second day. The primary outcomes were percentages of glucose readings time below range (TBR): <54 or <70 mg/dL, time in range (TIR): 70 to 180 mg/dL, and time above range (TAR): >180 or >250 mg/dL. Area under the curve (AUC) was calculated following the OGTT. Glucose variability was depicted by coefficient of variation (CV), SD, and mean amplitude of glucose excursion (MAGE). Wilcoxon sign-ranked test, McNemar mid P-test and linear regression models were employed. In all, 36 participants (median age 51 years; median body mass index [BMI] = 26.4 kg/m2) formed 18 matched pairs. Statistically significant differences were observed for 24-hour time in range (TIR; median 98.5% vs. 99.9%, P = .013), time above range (TAR) >180 mg/dl (0.4% vs. 0%, P = .0062), and 24-hour mean interstitial glucose (113.8 vs. 108.8 mg/dL, P = .0038) between people with prediabetes compared to normoglycemic participants. Statistically significant differences favoring the normoglycemic group were found for glycemic variability indexes (median CV 15.2% vs. 11.9%, P = .0156; median MAGE 44.3 vs. 33.3 mg/dL, P = 0.0043). Following OGTT, the AUC was significantly lower in normoglycemic compared to the prediabetes group (median 18615.3 vs. 16370.0, P = .0347 for total and 4666.5 vs. 2792.7, P = .0429 for incremental 2-hour post OGTT). Individuals with prediabetes have different glucose profiles compared to normoglycemic individuals. CGM might be helpful in individuals with borderline glucose values for a more accurate reclassification.

Thirty-Minute Post-load Glucose Could Be a Useful Screening Measure for Abnormal Oral Glucose Tolerance Test Response in Adolescents with Obesity

BackgroundWith the growing obesity epidemic, subjecting every child with obesity to a 2-hour oral glucose tolerance test (OGTT) is impractical. Instead, 30-minute plasma glucose (PG), which reflects the acute phase of insulin secretion, might be a useful measure in the initial assessment of such individuals. Our study aimed to evaluate the optimal cutoff of 30-minute PG in predicting abnormal OGTT response and to compare the predictive value of this cutoff with that of the previously reported values from a combination of non-fasting parameters.MethodsFor this study, 332 overweight or obese pediatric individuals who had undergone the OGTT under the Department of Pediatrics and Adolescent Medicine, Queen Mary Hospital, Hong Kong, from 2012 to 2018 were included. The optimal cutoff of 30-minute PG for prediction of abnormal OGTT response was determined using a receiver operating characteristics curve, and the positive predictive value (PPV) was evaluated.ResultsThere were 180 males (54.2%) and the mean age of the included individuals was 15.4±2.3 years. A 30-minute PG ≥9.2 mmol/L predicts abnormal OGTT response with the best combination of sensitivity and specificity. The PPV for abnormal OGTT response at this cutoff was 45%. Addition of this 30-minute PG cutoff to non-fasting parameters, including glycated hemoglobin, abnormal alanine transaminase, and family history of diabetes, resulted in an improved PPV of 70% for abnormal OGTT response.ConclusionAddition of 30-minute PG to non-fasting parameters improved the clinical utility in identifying high-risk individuals for abnormal OGTT response.

Lipid-induced glucose intolerance is driven by impaired glucose kinetics and insulin metabolism in healthy individuals

AimsHypertriglyceridemia is associated with an increased risk of type 2 diabetes. We aimed to comprehensively examine the effects of hypertriglyceridemia on major glucose homeostatic mechanisms involved in diabetes progression. MethodsIn this randomized, cross-over, single-blinded study, two dual-labeled, 3-hour oral glucose tolerance tests were performed during 5-hour intravenous infusions of either 20 % Intralipid or saline in 12 healthy subjects (age 27.9 ± 2.6 years, 11 men, BMI 22.6 ± 1.4 kg/m2) to evaluate lipid-induced changes in insulin metabolism and glucose kinetics. Insulin sensitivity, β cell secretory function, and insulin clearance were assessed by modeling glucose, insulin and C-peptide data. Intestinal glucose absorption, endogenous glucose production, and glucose clearance were assessed from glucose tracers. The effect of triglycerides on β-cell secretory function was examined in perifusion experiments in murine pseudoislets and human pancreatic islets. ResultsMild acute hypertriglyceridemia impaired oral glucose tolerance (mean glucose: +0.9 [0.3, 1.5] mmol/L, p = 0.008) and whole-body insulin sensitivity (Matsuda index: −1.67 [−0.50, −2.84], p = 0.009). Post-glucose hyperinsulinemia (mean insulin: +99 [17, 182] pmol/L, p = 0.009) resulted from reduced insulin clearance (−0.16 [−0.32, −0.01] L min−1 m−2, p = 0.04) and enhanced hyperglycemia-induced total insulin secretion (+11.9 [1.1, 22.8] nmol/m2, p = 0.02), which occurred despite a decline in model-derived β cell glucose sensitivity (−41[−74, −7] pmol min−1 m−2 mmol−1 L, p = 0.04). The analysis of tracer-derived glucose metabolic fluxes during lipid infusion revealed lower glucose clearance (−96 [−152, −41] mL/kgFFM, p = 0.005), increased 2-hour oral glucose absorption (+380 [42, 718] μmol/kgFFM, p = 0.04) and suppressed endogenous glucose production (−448 [−573, −123] μmol/kgFFM, p = 0.005). High-physiologic triglyceride levels increased acute basal insulin secretion in murine pseudoislets (+11 [3, 19] pg/aliquot, p = 0.02) and human pancreatic islets (+286 [59, 512] pg/islet, p = 0.02). ConclusionOur findings support a critical role for hypertriglyceridemia in the pathogenesis of type 2 diabetes in otherwise healthy individuals and dissect the glucose homeostatic mechanisms involved, encompassing insulin sensitivity, β cell function and oral glucose absorption.

Prolactin and Maternal Metabolism in Women With a Recent GDM Pregnancy and Links to Future T2D: The SWIFT Study.

Prolactin is a multifaceted hormone known to regulate lactation. In women with gestational diabetes mellitus (GDM) history, intensive lactation has been associated with lower relative risk of future type 2 diabetes (T2D). However, the role of prolactin in T2D development and maternal metabolism in women with a recent GDM pregnancy has not been ascertained. We examined the relationships among prolactin, future T2D risk, and key clinical and metabolic parameters. We utilized a prospective GDM research cohort (the SWIFT study) and followed T2D onset by performing 2-hour 75-g research oral glucose tolerance test (OGTT) at study baseline (6-9 weeks postpartum) and again annually for 2 years, and also by retrieving clinical diagnoses of T2D from 2 years through 10 years of follow up from electronic medical records. Targeted metabolomics and lipidomics were applied on fasting plasma samples collected at study baseline from 2-hour 75-g research OGTTs in a nested case-control study (100 future incident T2D cases vs 100 no T2D controls). Decreasing prolactin quartiles were associated with increased future T2D risk (adjusted odds ratio 2.48; 95% CI, 0.81-7.58; P = 0.05). In women who maintained normoglycemia during the 10-year follow-up period, higher prolactin at baseline was associated with higher insulin sensitivity (P = 0.038) and HDL-cholesterol (P = 0.01), but lower BMI (P = 0.001) and leptin (P = 0.002). Remarkably, among women who developed future T2D, prolactin was not correlated with a favorable metabolic status (all P > 0.05). Metabolomics and lipidomics showed that lower circulating prolactin strongly correlated with a T2D-high risk lipid profile, with elevated circulating neutral lipids and lower concentrations of specific phospholipids/sphingolipids. In women with recent GDM pregnancy, low circulating prolactin is associated with specific clinical and metabolic parameters and lipid metabolites linked to a high risk of developing T2D.

The rs10830963 Polymorphism of the MTNR1B Gene: Association With Abnormal Glucose, Insulin and C-peptide Kinetics.

BackgroundThe MTNR1B gene encodes a receptor for melatonin, a hormone regulating biorhythms. Disruptions in biorhythms contribute to the development of type 2 diabetes mellitus (T2DM). Genetic studies suggest that variability in the MTNR1B gene affects T2DM development. Our aim was to compare the distribution of the genetic variant rs10830963 between persons differing in glucose tolerance in a sample of the Czech population (N=1206). We also evaluated possible associations of the polymorphism with insulin sensitivity, beta cell function, with the shape of glucose, insulin and C-peptide trajectories measured 7 times during a 3-hour oral glucose tolerance test (OGTT) and with glucagon response. In a subgroup of 268 volunteers we also evaluated sleep patterns and biorhythm.Results13 persons were diagnosed with T2DM, 119 had impaired fasting blood glucose (IFG) and/or impaired glucose tolerance (IGT). 1074 participants showed normal results and formed a control group. A higher frequency of minor allele G was found in the IFG/IGT group in comparison with controls. The GG constellation was present in 23% of diabetics, in 17% of IFG/IGT probands and in 11% of controls. Compared to CC and CG genotypes, GG homozygotes showed higher stimulated glycemia levels during the OGTT. Homozygous as well as heterozygous carriers of the G allele showed lower very early phase of insulin and C-peptide secretion with unchanged insulin sensitivity. These differences remained significant after excluding diabetics and the IFG/IGT group from the analysis. No associations of the genotype with the shape of OGTT-based trajectories, with glucagon or with chronobiological patterns were observed. However, the shape of the trajectories differed significantly between men and women.ConclusionIn a representative sample of the Czech population, the G allele of the rs10830963 polymorphism is associated with impaired early phase of beta cell function, and this is evident even in healthy individuals.

Uptake of guideline-recommended postpartum diabetes screening among diverse women with gestational diabetes: associations with patient factors in an integrated health system in USA

IntroductionClinical guidelines urge timely postpartum screening for diabetes among women with gestational diabetes mellitus (GDM), yet patient factors associated with screening uptake remain unclear. We aimed to identify patient factors...

63-OR: A Model-Based Clinical Trial Simulation Tool to Optimize Clinical Trial Designs for Type 1 Diabetes Prevention Studies

Trials seeking to delay or prevent type 1 diabetes (T1D) continue to face multiple challenges, including both clinical endpoint (s) and cohort selection. While it is clear that individuals who possess islet cell autoantibodies (AAbs) are at elevated risk for developing T1D, it remains unclear as to what additional factors, including metabolic activities and anthropometric data, may contribute to this increased risk. The aim of this project was to inform T1D prevention trial designs by developing a quantitative joint model based-clinical trial simulation (CTS) tool. Individual-level data obtained from the NIH TEDDY and TrialNet TNnatural history studies were used in this tool’s development. To describe T1D disease progression quantitatively, both longitudinal and time-to-event variables were simultaneously quantified as a joint model, with results from a 2-hour oral glucose tolerance test (OGTT) assessed at each visit included as a time-varying longitudinal covariate affecting the T1D diagnosis event. Our study focused on individuals at risk of developing T1D with two or more AAbs. Among the investigated individuals, those with a high BMI and the presence of GADA AAb at baseline had less risk, while those with an elevated HbA1c value, high fasting OGTT value, increased fasting OGTT to 2-hour OGTT ratio, and the presence of the IA2A AAb at baseline had higher risk. The developed model based-CTS tool, where users can specify the trial design, participants’ characteristics and hypothetical drug effect, provides a framework to perform T1D prevention clinical trial simulations with the intention to assist in future trial design decision-making processes. Disclosure J.F. Morales: None. R. Muse: None. J. Podichetty: None. S. David: None. M.A. Atkinson: None. M.J. Haller: Advisory Panel; SAB Biotherapeutics. Consultant; MannKind Corporation, Sanofi. M. Campbell-Thompson: Consultant; TRex Bio. K. Romero: None. I. O'Doherty: None. S. Schmidt: None. S. Kim: None. Funding JDRF (grant #: 2-SRA-2020-903-A-N) ; NIDDK Central Repositories

1042-P: Large-for-Gestational-Age Birthweight in Gestational Glucose Intolerance

Background: Treatment of gestational diabetes (GDM) reduces the risk of large for gestational age (LGA) birthweight and associated complications in infants. Pregnant people with gestational glucose intolerance (GGI, abnormal glucose loading test (GLT) without GDM) usually remain untreated. We examined the risk of LGA among women with GGI in a large cohort. Methods: In a retrospective cohort study of 44,628 singleton pregnancies delivered at an academic center at &amp;gt;28 weeks' gestation, pregnancies with a GLT &amp;gt;140 mg/dl and either a normal 3-hour 100-gram oral glucose tolerance test (OGTT) or one abnormal OGTT value were classified as GGI, and those with 2 abnormal OGTT values as GDM. We used generalized estimating equations for logistic regression to examine the risk of LGA (birthweight &amp;gt;90th percentile for gestational age) in GGI versus normal glucose tolerance (NGT, GLT &amp;lt;140 mg/dl) pregnancies after adjustment for age, gender, 1st trimester BMI, parity, insurance, race/ethnicity, and marital status. A second model adjusted for gestational weight gain (GWG) . Results: LGA was present in 7.7% of 36,964 pregnancies with NGT, 9.6% of 4357 with GGI and normal OGTT, 14.3% of 15with GGI and one abnormal OGTT value, and 14.5% of 1800 with GDM. The odds of LGA were higher in GGI than NGT pregnancies (adjusted OR 1.4 [1.3-1.5], p&amp;lt;0.001) . When compared separately with NGT, both types of GGI had elevated odds of LGA: normal OGTT adjusted OR 1.2 [1.1-1.4], p&amp;lt;0.001, one abnormal OGTT value adjusted OR 1.8 [1.5-2.1], p&amp;lt;0.001. The latter was similar to that in GDM compared to NGT: adjusted OR 1.8 [1.5-2.0], p&amp;lt;0.001. Increased odds of LGA were also present for GGI/GDM groups after GWG adjustment: normal OGTT OR 1.3 [1.2-1.5] p&amp;lt;0.001, 1 abnormal OGTT value OR 1.8 [1.5-2.1] p&amp;lt;0.0GDM OR 2.2 [1.9-2.5] p&amp;lt;0.001. Conclusion: Infants of untreated people with GGI have increased risk of LGA birthweight. The risk of LGA in GGI pregnancies with one abnormal OGTT value was similar to that in GDM in a clinical setting where only GDM was treated. Disclosure J.Maya: None. D.J.Selen: None. T.Thaweethai: None. S.Hsu: None. C.Yu: None. K.James: None. A.Kaimal: None. M.Hivert: Advisory Panel; American Heart Association, Research Support; American Diabetes Association. C.E.Powe: None. Funding MGH (Physician Scientist Development Award and Claflin Distinguished Scholar's Award)

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.

61-OR: Machine Learning Framework Predicts Metabolic Subphenotypes Using Glucose Dynamics during Oral Glucose Tolerance Test

Type 2 diabetes (T2D) is classically defined by measures of glycemia which do not take into account its physiologic basis, which differs between individuals. Defining the relative contribution of fundamental physiologic processes to glucose dysregulation would facilitate targeted treatment approaches for diabetes prevention and treatment. We propose that muscle insulin resistance, beta cell dysfunction, incretin defect, and hepatic insulin resistance are present to varying degrees in individuals predisposed to T2D, who can be thus classified according to their metabolic subphenotype. While this transformative approach to T2D is appealing, traditional metabolic tests are invasive and unavailable outside research units. We tested the ability of the shape of the glucose response curve during an oral glucose tolerance test (OGTT) to identify metabolic subphenotypes. 32 participants underwent gold-standard metabolic tests including frequently-sampled 3-hour OGTT, isoglycemic intravenous glucose infusion for quantification of incretin effect, steady-state plasma glucose measurement of insulin resistance, and calculated hepatic insulin resistance. We developed a machine learning framework to predict metabolic subphenotypes of an individual using dynamic features of the glucose time series during the OGTT. Metabolic testing revealed extensive inter-individual heterogeneity and the existence of four major metabolic subphenotypes. The features of the glucose time series identified insulin resistance, beta cell deficiency, and incretin deficiency with auROCs of 94%, 76%, and 75%, respectively. These were superior to standard clinical and laboratory measures of metabolic phenotypes. We suggest that identification of distinct metabolic subphenotypes using features of the glucose time series during OGTT may both enhance early identification of at-risk individuals as well as inform targeted therapeutic approaches to prevent and treat T2D. Disclosure A.A.Metwally: None. D.Perelman: None. H.Park: None. A.L.Gloyn: Other Relationship; Genentech, Inc., Roche Pharmaceuticals. T.Mclaughlin: Board Member; January, Inc., Research Support; Merck &amp; Co., Inc., Novo Nordisk, Stock/Shareholder; Eiger BioPharmaceuticals. M.Snyder: Stock/Shareholder; January, Inc. Funding National Institutes of Health (R01DK110186-01) National Institute of Diabetes and Digestive and Kidney Diseases (U01-DK105535; U01-DK085545, UM1DK126185)

Comparison of Continuous Glucose Monitoring in Cystic Fibrosis Patients With or Without Pancreatic Exocrine Insufficiency.

This study aimed to compare continuous glucose monitoring (CGM) in cystic fibrosis (CF) according to pancreatic exocrine status.CGM and oral glucose tolerance testing (OGTT) were realized annually over five years in people with CF (pwCF) aged≥10 years without cystic fibrosis-related diabetes (CFRD). CGM parameters in patients with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and newly diagnosed CFRD were compared according to presence of pancreatic sufficiency (PS) or insufficiency (PI).Overall, 547 OGTTs and 501 CGMs were performed in 147 CF patients, comprising 122 PI and 25 PS. In PS patients, 84% displayed NGT, 12% IGT, and 4% CFRD vs. 58%, 32%, and 10% (p=0.05) in PI. Among participants displaying normal OGTT, time in glucose range (70-140 mg/dl) was significantly increased, 97% (93, 99) vs. 92% (85, 96), p<0.001, and time above glucose range > 140 mg/dl significantly decreased, 1% (0, 2) % vs. 6% (2, 13), in patients with PS compared to those with PI. No significant differences were highlighted in patients with IGT.CGM revealed significant different glucose tolerance abnormalities in PI versus PS, which were undetected by standard 2-hour OGTT glucose.

Validation of a novel mobile phone application for type 2 diabetes screening following gestational diabetes mellitus.

We sought to determine if using fasting blood glucose (FBG) through text-based care is an effective screening tool for type 2 diabetes in the postpartum period compared to in-person, 2-hour oral glucose tolerance testing (2hr OGTT). This was a single-center interventional study that included individuals diagnosed with gestational diabetes. Patients were enrolled in standard, office-based 2hr OGTT in combination with text-based remote diabetes screening. Study participants were instructed to record FBG for 3 consecutive days using a mobile application. We assessed agreement with 2hr OGTT using sensitivity, specificity, positive and negative predictive value with exact binomial 95% confidence intervals. A total of 446 individuals diagnosed with gestational diabetes met inclusion criteria, 239 of which were enrolled in standard office-based screening and 207 were enrolled in dual screening using standard 2hr OGTT testing combined with text-based remote FBG screening. A FBG value less than 100 mg/dL had 100% sensitivity (86-100%), 86% specificity (77-93%) with a 100% (94-100%) negative predictive value and 71% (54-85%) positive predictive value. Follow-up was significantly higher among individuals enrolled in remote text-based screening compared to standard in-office screening (48% vs. 25%, respectively; P<0.001). Text-based screening may be a feasible alternative to in-office screening. A mobile-based system using FBG successfully screened all patients with type 2 diabetes in the postpartum period with 100% sensitivity and negative predictive value. Remote telehealth screening significantly increased follow-up with type 2 diabetes screening.

Characterization of glucose metabolism in youth with vs. without cystic fibrosis liver disease: A pilot study

BackgroundDiabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease. MethodsIn this two-center cross-sectional study, 20 youth with CF with and without liver disease underwent a 3-hour oral glucose tolerance test. Subjects were categorized by liver disease (LD) status [no LD, mild LD, severe LD] and diabetes status. Measures of glucose excursion, islet cell secretory responses, insulin sensitivity and clearance were obtained. ResultsParticipants with severe LD had the highest fasting, peak, and glucose area under the curve over 3 h (AUC3h) among individuals with CFRD (interaction p < 0.05). In parallel with glycemic changes, prandial β-cell secretory response (AUC C-peptide 3h) was lower in those with severe LD compared to mild or no LD (p < 0.01). There was a trend of higher HOMA-IR in those with severe LD (p = 0.1) as well as lower fasting insulin clearance in those with mild and severe LD compared to no LD (p = 0.06) and lower prandial insulin clearance in severe LD among those with CFRD (interaction p = 0.1). ConclusionIn this small cohort, subjects with severe LD tended to have more impaired glycemia, insulin secretion, insulin sensitivity and clearance. Larger studies are imperative to define the pathogenesis to inform clinical care guidelines in terms of CFRD screening, diagnosis, and treatment options.