Oral Glucose Challenge Research Articles

Glycemic management is inversely related to skeletal muscle microvascular endothelial function in patients with type 2 diabetes.

Microvascular endothelial dysfunction precipitates cardiovascular disease mortality in patients with type 2 diabetes mellitus (T2DM). However, the relationship between glycemic management and microvascular endothelial function of these patients remains ill defined. We investigated the association between skeletal muscle microvascular endothelial function with glycemic management (HbA1c) and responses to an oral glucose challenge (OGTT) in 30 patients with T2DM (59 ± 9 years, 31.2 ± 5.1 kg/m2, HbA1c = 7.3 ± 1.3%). On study day 1, microvascular endothelial function was quantified as the increase (Δ from rest) in forearm vascular conductance (FVC, ml/min/100 mmHg) during intra‐arterial acetylcholine infusion at 4.0 and 8.0 μg/dl forearm volume/min (ACh4 and ACh8, respectively). [Glucose] and [insulin] were measured in a fasted state as well as following a 75 g OGTT on a second day with an additional fasting blood sample collected to measure HbA1c. FVC increased (Δ) 221 ± 118 and 251 ± 144 ml/min/100 mm Hg during ACh4 and ACh8 trials, respectively (p < 0.05 between doses). [Glucose] and [insulin] increased at the 1‐h time point, relative to fasting levels, and remained elevated 2 h post‐consumption (p < 0.05 for both variables and time points). [Glucose] nor [insulin], fasting or during the OGTT, were associated with ΔFVC during ACh4 or ACh8, respectively (p = 0.11–0.86), although HbA1c was inversely related (r = −0.47 and −0.46, respectively, p < 0.01 for both). Patients whose HbA1c met the ADA’s therapeutic target of ≤7.0% had greater ΔFVC to ACh4 (272 ± 147 vs. 182 ± 74 ml/100 mm Hg/min) and ACh8 (324 ± 171 vs. 196 ± 90 ml/100 mm Hg/min, p < 0.05 for both trials) compared to those with >7.0%, respectively. Our data show glycemic management is related to acetylcholine‐mediated vasodilation (e.g., microvascular endothelial function) in skeletal muscle of patients with T2DM.

1139 Development of Type II diabetes mellitus in women with gestational diabetes

To identify characteristics that contribute to the development of type II diabetes mellitus (T2DM) in patients with gestational diabetes mellitus (GDM) Case-control study of patients with GDM who delivered at a single site from 2011 to 2019. Cases were defined as patients with recent pregnancy with GDM who developed T2DM within 5 years of delivery. Diagnosis of T2DM was per the American Diabetes Association criteria. Controls included patients with pregnancy complicated by GDM who underwent negative testing for T2DM within five years of delivery. Univariate and multivariable analyses were performed, followed by logistic regression analyses to evaluate for factors that independently contributed to the development of T2DM. Out of 715 patients who met inclusion criteria, 75 (10.5%) were diagnosed with T2DM within five years of delivery. Patients who developed T2DM were more likely to have a higher body mass index (BMI) both early in pregnancy and at the time of delivery, have public insurance, self-identify as non-white, identify as single, have a higher blood glucose on the one hour oral glucose challenge test (OGCT), have a higher fasting blood glucose on the three hour OGTT, be diagnosed earlier in gestation, require pharmacotherapy earlier in gestation, and deliver at an earlier gestational age (Table 1). After controlling for confounders, early pregnancy BMI (aOR 1.32, 95% CI 1.06 – 1.63) and having no insurance (aOR 4.07, 95% CI 1.04-15.93) were persistently independently associated with the development of T2DM within five years of delivery (Table 2) Women with GDM who develop T2DM within five years of delivery were more likely to have a higher early pregnancy BMI and have no insurance. These women may benefit from dietary and exercise lifestyle modifications as well as access to diabetes screening after delivery.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Investigating paediatric hypoglycaemia: Dynamic studies at a tertiary paediatric hospital.

Paediatric hypoglycaemia often requires specific investigations to determine aetiology. Samples from the time of hypoglycaemia may not be available and a diagnostic fasting test may be required. Additionally, fasting studies can determine safe fasting intervals and prolonged oral glucose challenges can assess hypoglycaemia due to abnormal post-prandial glucose handling. This audit reviewed the current utility and yield of fasting studies, prolonged oral glucose challenges and starch loads. Retrospective audit of clinical record to determine purpose and outcome of tests performed at a Tertiary Paediatric Endocrine/Metabolic Testing Unit in Sydney, Australia, from 2013 to 2018 inclusive. One hundred and thirty-eight children (aged 3 weeks-17 years) underwent 170 tests: 122 fasting studies, 20 five-hour OGTTs, 22 uncooked corn starch loads and six modified waxy maize starch (Glycosade) loads. The majority were for diagnostic purposes (n= 113, 66%), with 57 (34%) to guide management in patients with known diagnoses. Following diagnostic studies, 35 (31%) patients received a pathological diagnosis, the most common of which (n= 19, 17%) was accelerated starvation. Hypoglycaemia developed in n= 15/113 (13%) during the diagnostic studies. Management studies helped determine length of safe fast, adjustment of medication or diet and document resolution of pathology. Fasting studies remain a safe and effective method to assist with diagnoses, confirm or exclude pathological causes of childhood hypoglycaemia and to guide management of known diagnoses in the paediatric population.

A Rodent Model of Jejunal-Ileal Loop Bipartition (JILB): a Novel Malabsorptive Operation.

We designed a novel malabsorptive procedure named as jejunal-ileal loop bipartition (JILB), in which a jejunal-ileal loop is created to reduce the effective length of food chyme passage in the small bowel, but without exclusion of any segment of the intestine. This study is to investigate the feasibility and efficacy of JILB on weight loss and glycemic control in obese diabetic mouse model. High-fat diet-induced C57BL/6 mice with typical obese and diabetic phenotypes were randomly divided into two groups according to the surgical procedure performed, including JILB (n = 8) and sham group (n = 8). Age-matched naïve C57BL/6 mice fed with rodent chow diet were adopted as normal controls. Body weight, food intake, fasting plasma glucose (FPG), fasting plasma insulin (FPI), and oral glucose tolerance test (OGTT) were measured in vivo before and 2, 4, and 8weeks after surgery. Plasma glucagon-like peptide 1 (GLP-1) was assayed before and 15min after oral glucose challenge at the 8th week postoperatively. Comparing to the sham animals, JILB group consumed similar amount of food, but had lower body weight after surgery (P < 0.01). It led to significant lower FPG (p < 0.05) and improved glucose tolerance with lower FPI (p < 0.001). And GLP-1 secretion at 15min after oral glucose challenge was higher than shams (P < 0.05). No intestinal obstruction was identified. JILB is potentially a metabolic and bariatric procedure that leads to effective weight loss and diabetes remission in obese diabetic subjects.

Different pre-analytical techniques and the results of 50g oral glucose challenge tests.

We aimed to analyse the pre-analytical process and its effect of 50g of oral glucose challenge test results for screening gestational diabetes mellitus. The 50g oral glucose challenge test was performed to 30 pregnant women, and the blood was collected as two samples for three tubes containing; serum separating jell (SSJ), sodium fluoride-potassium oxalate (NaF - KOx) and sodium citrate-containing tube. The first samples of the three tubes were centrifuged within 30minutes, and second samples were centrifuged after 60minutes and were analysed. One sample in SSJ tube and was analysed in the same day according to hospitals routine practice. The results were compared. Among the 30 samples, the mean decrease in glucose levels was highest in the SSJ tube (0.38mmol/L), followed by 0.16mmol/L in Na citrate tube and 0.14mmol/L in NaF-KOx tube. The hospital routine assessment with SSJ was 6.36±1.90mmol/L. The <30 and >60minutes glucose results were 6.80±1.88mmol/L vs 6.42±1.97mmol/L for SSJ, 5.95±1.60mmol/L vs 5.78±1.51mmol/L for Na Citrate and 6.90±1.86mmol/L vs 6.75±1.90mmol/L for NaF-KOx mg/dL groups, respectively, and both the changes within time and the results between the tubes showed a statistically significant difference (P<.001). In cases with longer assessment time and with different blood sample tubes, the clinician should also keep in mind that, especially with results under but close to the cut-off levels, an underdiagnosed gestational diabetes might be present.

Gestational Diabetes in Mid-trimester Pregnancy in South Asian Women Based on the Oral Glucose Challenge Test and Risk Factor Predictors: A Prospective Observational Study

Introduction: Gestational Diabetes Mellitus (GDM) is a condition potentially occurring during pregnancy. It is associated with adverse foetal and maternal outcomes and is particularly prevalent in South Asian women who comprised this study sample. Aim: To provide a critical analysis of the information on GDM risk that can be identified from screening using the Oral Glucose Challenge Test (OGCT-50 g). Materials and Methods: A prospective cohort study was conducted over eight months. Purposive sampling was used to collect demographic and clinical data {age; Body mass Index (BMI); parity; history of Diabetes Mellitus (DM) in a first degree relative and histories of GDM, polyhydramnious, macrosomia, birth congenital abnormalities and still birth} from 300 South Asian women in mid-trimester pregnancy who consented to undertake an OGCT-50g. Excluded were primigravidas, women with DM or other medical conditions, and women who were unwilling or unable to give informed written consent. Descriptive, comparative and multivariate logistic analyses were used to investigate strengths of correlation between OGCT outcomes and clinical/historical risk factors. Results: The OGCT were 107 (35.7%) positive and 193 (64.3%) negative. The threshold for body mass risk was identified as 27.5 kg/m2. Women with two or more risk factors were OGCT positive on 72.9% occasions whereas women with one or no risk factor were OGCT negative on 81.9% occasions. Approximately, 50% of women had a family history of DM as their only risk factor and 24% of them were OGCT positive. Conclusion: The BMI was the strongest determinant of a positive OGCT result. The logistic regression analysis demonstrated that using the lower BMI threshold of 27.5 compared to 30.0 [as per National Institute for Health and Care Excellence (NICE) guideline] improved agreement between risk factors profile was assessed and OGCT results.

Predictability of Macrosomic Birth based on Maternal Factors and Fetal Aneuploidy Screening Biochemical Markers in Hyperglycemic Mothers.

Background: Macrosomic birth weight has been implicated as a significant risk factor for developing various adult metabolic diseases such as diabetes mellitus and coronary heart diseases; it has also been associated with higher incidences of complicated births. This study aimed to examine the predictability of macrosomic births in hyperglycemic pregnant women using maternal clinical characteristics and serum biomarkers of aneuploidy screening performed in the first half of pregnancy.Methods: A retrospective observational study was performed on a cohort of 1,668 pregnant women who 1) had positive outcomes after undergoing 50-g oral glucose challenge test (OGCT) at two university-based hospitals and 2) underwent any one of the following maternal biomarker screening tests for fetal aneuploidy: triple test, quadruple test, and integrated test. Logistic regression-based models for predicting macrosomic births using maternal characteristics and serum biomarkers were developed and evaluated for prediction power. A nomogram, which is a graphical display of the best predictable model, was then generated.Results: The study cohort included 157 macrosomic birth cases defined as birth weight ≥3,820 g, which was equivalent to the top 10 percentile of the modeling cohort. Three primary models solely based on serum biomarkers achieved area under curves (AUCs) of 0.55-0.62. Expanded models, including maternal demographic and clinical factors, demonstrated an improved performance by 25% (AUCs, 0.69-0.73).Conclusion: Our prediction models will help to identify pregnancies with an elevated risk of macrosomic births in hyperglycemic mothers using maternal clinical factors and serum markers from routine antenatal screening tests. Prediction of macrosomic birth at mid-pregnancy may allow customized antenatal care to reduce the risk of macrosomic births.

Bayesian parameter estimation in the oral minimal model of glucose dynamics from non-fasting conditions using a new function of glucose appearance

Background and objectiveThe oral minimal model (OMM) of glucose dynamics is a prominent method for assessing postprandial glucose metabolism. The model yields estimates of insulin sensitivity and the meal-related appearance of glucose from insulin and glucose data after an oral glucose challenge. Despite its success, the OMM approach has several weaknesses that this paper addresses. MethodsA novel procedure introducing three methodological adaptations to the OMM approach is proposed. These are: (1) the use of a fully Bayesian and efficient method for parameter estimation, (2) the model identification from non-fasting conditions using a generalised model formulation and (3) the introduction of a novel function to represent the meal-related glucose appearance based on two superimposed components utilising a modified structure of the log-normal distribution. The proposed modelling procedure is applied to glucose and insulin data from subjects with normal glucose tolerance consuming three consecutive meals in intervals of four hours. ResultsIt is shown that the glucose effectiveness parameter of the OMM is, contrary to previous results, structurally globally identifiable. In comparison to results from existing studies that use the conventional identification procedure, the proposed approach yields an equivalent level of model fit and a similar precision of insulin sensitivity estimates. Furthermore, the new procedure shows no deterioration of model fit when data from non-fasting conditions are used. In comparison to the conventional, piecewise linear function of glucose appearance, the novel log-normally based function provides an improved model fit in the first 30 min of the response and thus a more realistic estimation of glucose appearance during this period. The identification procedure is implemented in freely accesible MATLAB and Python software packages. ConclusionsWe propose an improved and freely available method for the identification of the OMM which could become the future standardard for the oral minimal modelling method of glucose dynamics.

Caffeine-Containing Energy Shots Cause Acute Impaired Glucoregulation in Adolescents.

Caffeine-containing, nutritionally fortified energy shots are consumed at high rates by adolescents, yet little is known about their metabolic impact. The purpose of this study was to examine the consequences of small format, caffeinated energy shots on glucose metabolism and gastrointestinal hormone secretion in adolescents. Twenty participants aged 13–19 years participated in a double-blind, randomized cross-over study consisting of two trials separated by 1–4 weeks. Participants consumed a volume-matched caffeinated energy shot (CAF, 5 mg/kg) or a decaffeinated energy shot (DECAF) followed by a 2 h oral glucose tolerance test. Blood samples were collected and area under the curve (AUC) calculated for glucose, insulin and gut and metabolic hormones. Consumption of CAF resulted in a 25% increase in glucose and a 26% increase in insulin area under the curve (AUC, p = 0.037; p < 0.0001) compared to DECAF. No impact on gut hormones was observed. To further characterize responses, individuals were classified as either slow or fast caffeine metabolizers based on an allele score. Glucose intolerance was greater in genetically fast vs. slow caffeine metabolizers and differences between groups were supported by distinct serum metabolomics separation. Consumption of caffeine-containing energy shots results in acute impaired glucoregulation in healthy adolescents as characterized by hyperinsulinemia following an oral glucose challenge.

Antecubital vein cannula position impacts on forearm glucose uptake during an oral glucose challenge in healthy volunteers

Rationale: Estimating forearm muscle glucose uptake following an oral glucose challenge has been used to assess the impact of physiological interventions in human volunteer research. This study aimed to understand whether cannula positioning impacted on estimation of forearm glucose uptake, given venous drainage is influenced by muscle, skin and adipose tissue.

The impact of preconditioning exercise on the vascular response to an oral glucose challenge.

Exercise elicits direct benefits to insulin sensitivity but may also indirectly improve glucose uptake by hemodynamic conditioning of the vasculature. The purpose of this study was to examine the modifying effect of 3 different types of exercise on the vascular response to an oral glucose challenge. Twenty healthy adults (9 women, 11 men; aged 23 ± 3 years) completed a standard oral glucose tolerance test (OGTT) at rest, as well as 1.5 hours after moderate continuous cycling exercise (30min; 65% peak oxygen consumption), high-intensity interval cycling exercise (10 × 1 min at 90% peak heart rate), and lower-load higher-repetition resistance exercise (25-35 repetitions/set, 3 sets). Brachial and superficial femoral artery blood flow, conductance, and oscillatory shear index were measured throughout the OGTT. Regardless of rested state or exercise preconditioning, the OGTT induced reductions in brachial artery blood flow and conductance (p< 0.001), and transient increases in brachial and superficial femoral artery oscillatory shear index and retrograde blood flow (p< 0.01). Continuous cycling and resistance exercise were followed with a small degree of protection against prolonged periods of oscillatory flow. Our findings imply transient peripheral vasoconstriction and decreased limb blood flow during a standard OGTT, for which prior exercise was unable to prevent in healthy adults. Novelty: We investigated the impact of continuous, interval, and resistance exercise on the hemodynamic response to an OGTT. Our findings suggest decreased upper-limb blood flow during an OGTT is not prevented by prior exercise in healthy adults.

Antecubital Vein Cannula Position Impacts Assessment of Forearm Glucose Uptake During an Oral Glucose Challenge in Healthy Volunteers.

Skeletal muscle is a major site for whole-body glucose disposal, and determination of skeletal muscle glucose uptake is an important metabolic measurement, particularly in research focussed on interventions that impact muscle insulin sensitivity. Calculating arterial-venous difference in blood glucose can be used as an indirect measure for assessing glucose uptake. However, the possibility of multiple tissues contributing to the composition of venous blood, and the differential in glucose uptake kinetics between tissue types, suggests that sampling from different vein sites could influence the estimation of glucose uptake. This study aimed to determine the impact of venous cannula position on calculated forearm glucose uptake following an oral glucose challenge in resting and post-exercise states. In 9 young, lean, males, the impact of sampling blood from two antecubital vein positions; the perforating vein ('perforating' visit) and, at the bifurcation of superficial and perforating veins ('bifurcation' visit), was assessed. Brachial artery blood flow and arterialised-venous and venous blood glucose concentrations were measured in 3 physiological states; resting-fasted, resting-fed, and fed following intermittent forearm muscle contraction (fed-exercise). Following glucose ingestion, forearm glucose uptake area under the curve was greater for the 'perforating' than for the 'bifurcation' visit in the resting-fed (5.92±1.56 vs. 3.69±1.35 mmol/60 min, P<0.01) and fed-exercise (17.38±7.73 vs. 11.40±7.31 mmol/75 min, P<0.05) states. Antecubital vein cannula position impacts calculated postprandial forearm glucose uptake. These findings have implications for longitudinal intervention studies where serial determination of forearm glucose uptake is required.

Effects of Polyphenols on Insulin Resistance.

Insulin resistance (IR) is apparent when tissues responsible for clearing glucose from the blood, such as adipose and muscle, do not respond properly to appropriate signals. IR is estimated based on fasting blood glucose and insulin, but some measures also incorporate an oral glucose challenge. Certain (poly)phenols, as supplements or in foods, can improve insulin resistance by several mechanisms including lowering postprandial glucose, modulating glucose transport, affecting insulin signalling pathways, and by protecting against damage to insulin-secreting pancreatic β-cells. As shown by intervention studies on volunteers, the most promising candidates for improving insulin resistance are (−)-epicatechin, (−)-epicatechin-containing foods and anthocyanins. It is possible that quercetin and phenolic acids may also be active, but data from intervention studies are mixed. Longer term and especially dose-response studies on mildly insulin resistant participants are required to establish the extent to which (poly)phenols and (poly)phenol-rich foods may improve insulin resistance in compromised groups.

Follistatin-like 1 as a Novel Adipomyokine Related to Insulin Resistance and Physical Activity.

Follistatin-like protein-1 (FSTL-1) is considered to be an adipokine or myokine that could be a potential regulator of metabolism. Our purpose is to investigate the relationship between circulating FSTL-1 levels and insulin resistance (IR) in type 2 diabetes mellitus (T2DM) and to identify the regulatory factors. FSTL-1 expression in C57BL/6J and db/db mice was examined by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blots. Serum FSTL-1 levels were measured by enzyme-linked immunosorbent assay in 298 T2DM patients and 202 healthy controls. Changes in the circulating FSTL-1 level were observed during the oral glucose tolerance test, EHC (euglycemic-hyperinsulinemic clamp), lipid infusion, acute exercise, and cold-exposure test. We found that FSTL-1 protein expression in the adipose tissue of db/db mice was significantly higher than that of wild-type mice. Importantly, circulating FSTL-1 levels in T2DM and overweight/obese participants were higher than those in healthy and lean individuals, and was related to HOMA-IR, adiponectin, and obesity- and metabolism-related parameters. In the intervention study, 45 minutes of physical activity was found to significantly increase the circulating FSTL-1 concentration in young, healthy participants. Further, FSTL-1 protein expression in adipose tissue rose dramatically in response to physical activity in mice. Hyperinsulinemia during EHC and acute elevated FFA induced by lipid infusion resulted in a significant decrease in the circulating FSTL-1 levels. However, no change was found in the circulating FSTL-1 levels in response to the oral glucose challenge or cold-exposure test. FSTL-1 may be an adipomyokine associated with insulin resistance and physical activity, and circulating FSTL-1 levels are increased in patients with T2DM.

75 gr oral glukoz tolerans testi sağlıklı gebelerde maternal ve fetal Doppler parametrelerini etkiler mi? Kesitsel-gözlemsel bir çalışma

Aim: Oral glucose challenge test (OGTT) is widely used around the world screening for gestational diabetes mellitus (GDM). In our study, we aimed to evaluate the effect of 75 g OGTT on maternal and fetal Doppler parameters. Material and Methods: Measurements of umbilical artery PI, RI, S/D, middle cerebral artery (MCA) PSV, PI, RI and mean PI, RI S/D of uterine arteries assessed 1 hour before OGTT and 1 hour following the test in 46 pregnancies between 24-28 weeks of gestation. Mann Whitney-U test was employed to compare variables. Statistical significance was established at p&amp;lt;0.05. Results: The mean age of pregnant women was 24.6±5.4, the mean gravity status was 2.3±0.8, the mean BMI was 25.5±5.5 kg/m, and the mean gestational age was 26.5±1.6 Mean umbilical artery PI: 1.14±0.26, RI: 0.71±0.14, S/D ratio 2.24±0.73 calculated 1 hour before test and mean PI: 1.04±0.43, RI: 0.58±0.21, S/D ratio 2.01±0.44 and there was no significance (p: 0.64, 0,56, 0.71). Mean MCA PSV: 30.4±11.3 cm/sn, PI:1.89±0.36, RI: 0.81±0.19 measured 1 hour before test and 1 hour following test Mean MCA were PSV: 38.4±13.2 cm/sn, PI: 2.11±0.24, RI: 0.68± 0.21 and there was no difference (p: 0.83, 0.66, 0.82). Mean uterine arteries PI:1.13±0.21, RI: 0.69±0.11, S/D ratio 2.03±0.34 measured before the test and mean PI:1.24±0.11, RI: 0.74±0.16, S/D ratio 1.87±0.22 calculated after the test and these results were similar (p: 0.72, 0.79, 0.56). Conclusion: There was no significant effect on maternal and fetal Doppler parameters of 75 g OGTT among healthy pregnancies.

Glycemia and Atherosclerotic Cardiovascular Disease: Exploring the Gap Between Risk Marker and Risk Factor.

There is consistent, unequivocal and reproducible epidemiological evidence derived from diverse populations that various indices of glycemia (fasting plasma glucose, post-prandial or post oral glucose challenge plasma glucose, HbA1c) are associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD), even in the prediabetic state. Furthermore, there is abundant experimental evidence demonstrating that hyperglycemia per se accelerates and aggravates the atherosclerotic process, providing biological plausibility to the concept that hyperglycemia is causally related or a true risk factor for ASCVD. Two studies in particular, DCCT and UKPDS, that enrolled a younger cohort of patients with type 1 diabetes or an older cohort with newly diagnosed type 2 diabetes, respectively, showed trends toward a reduction in ASCVD. The reductions in ASCVD reached statistical significance only after prolonged follow up, and when differences in HbA1c were no longer maintained (referred to by some as a “legacy effect”). More recent studies in those with established type 2 diabetes, in which glycemic control was improved by a variety of strategies, failed to demonstrate reductions in ASCVD. The gap in evidence supporting hyperglycemia as a true causative risk factor for ASCVD or simply a risk marker for some other confounding causative factor is discussed in this review. We conclude that hyperglycemia does appear to be at least partially causative of ASCVD (i.e., an ASCVD risk factor). We discuss how this evidence can be incorporated into an overall therapeutic strategy to prevent ASCVD in those with prediabetes and established diabetes.

1136-P: Glucose Kinetics during Oral Glucose Challenge following Administration of Exenatide and Dapagliflozin Alone and in Combination in Type 2 Diabetes

Aim: To examine the effect of SGLT2i on endogenous glucose production (EGP), tissue glucose disappearance (Rd), and urinary glucose excretion (UGE) following glucose ingestion. Study Design: 28 type 2 diabetes [T2D] patients (Age= 51±2 y; BMI=31.2±0.7; A1C=7.9±0.2%) received 8-hour 3-3H-glucose infusion after an overnight fast. Previously shown, EGP suppression by dapagliflozin (DAPA) compared to placebo (PCB) (Δ=-0.02±0.02 vs. -0.45±0.03, p&amp;lt;0.01 mg/kg.min) was impaired. On a separate day, subjects were randomized to receive 5-hour double-isotope (IV 3-[3H]-glucose and oral [14C]-glucose) OGTT (75-g) preceded by PCB, DAPA 10 mg, EXEN 5 µg, or DAPA+EXEN. Oral [RaO], EGP, Total and Tissue Rd, and UGE were calculated. Results: During 0-300-min, RaO was 65 g in DAPA, 59 g in PCB, 46 g in EXEN, and 48 g in DAPA+EXEN. UGE was 31±4 g in DAPA and 30±4 g in DAPA+EXEN, but only 3±1 g in EXEN and 10±3 g in PCB (p&amp;lt;0.001 vs. DAPA and DAPA+EXEN). Conclusion: The post-OGTT rise in PG was significantly reduced after DAPA+EXEN vs. each drug alone. This resulted from lower oral glucose appearance with greater UGE. During the OGTT, EGP suppression with DAPA (Δ = -0.8±0.1 mg/kg.min) was less than with PCB, EXEN, and DAPA/EXEN (p&amp;lt;0.05-0.01), while EGP suppression with DAPA/EXEN was similar to PCB but required a higher rise in insulin (p&amp;lt;0.05). Tissue glucose clearance was unchanged by any therapy. Disclosure M. Alatrach: None. C. Agyin: None. N. Laichuthai: None. O. Lavrynenko: None. J.M. Adams: None. M. Abdul-Ghani: None. C.L. Triplitt: Speaker’s Bureau; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly Diabetes, Xeris Pharmaceuticals, Inc. R.A. DeFronzo: None. E. Cersosimo: None.

316-OR: Oral vs. Intravenous Glucose Administration Produce Opposing Microvascular Actions in Skeletal Muscle of Healthy People

Skeletal muscle microvascular blood flow (MBF) increases in response to an insulin infusion (hyperinsulinemic-euglycemic clamp) or the consumption of a mixed meal to augment glucose disposal. This microvascular action is impaired during insulin resistance. We recently demonstrated that an oral glucose challenge (50g glucose) acutely impairs skeletal muscle MBF in healthy people, compared to a mixed meal challenge, despite similar levels of hyperinsulinemia. We aimed to determine whether post-prandial hyperglycemia or gut-derived factors are the primary mediators of impaired MBF observed in response to orally ingested glucose. Seven healthy overnight-fasted subjects (sex 2M/5F, age 29±9 yrs, BMI 23.5±3.2 kg/m2, blood glucose 4.5±0.3 mM, HbA1c 5.2±0.3%, total cholesterol 3.9±1.0 mM, triglycerides 0.8±0.3 mM) underwent an oral glucose tolerance test (OGTT, 75g glucose) and an intravenous glucose tolerance test (IVGTT- bypassing the gut) matched for similar blood glucose levels, on successive visits (&amp;lt;4 weeks apart: cross-over design). MBF was assessed in the vastus lateralis by contrast-enhanced ultrasound at baseline, 60 and 120 minutes post-OGTT and -IVGTT. Despite similar area under the glucose time curve (OGTT: 846.8±124.8, IVGTT: 845.9±121.1 mMx2hr, P=0.98), MBF was only stimulated with the IVGTT, at 60 min (Δ MBF: OGTT -0.3± 0.5; IVGTT 0.3± 0.3 Acoustic intensity/sec, P=0.02) and 120 min post- infusion (Δ MBF: OGTT -0.4± 0.3; IVGTT 0.2± 0.3 Acoustic intensity/sec, P&amp;lt;0.01). Therefore, the extent of post-prandial hyperglycemia per se does not acutely impact microvascular responses in skeletal muscle in healthy humans. These data support the role of gut-derived factor(s) in the impairment of MBF following orally ingested glucose. These findings have important physiological implications for the consumption of high glycemic index meals. Disclosure K. Roberts-Thomson: None. L. Parker: None. A.C. Betik: None. M. Keske: None.

Associations of Per- and Polyfluoroalkyl Substances (PFAS) With Glucose Tolerance During Pregnancy in Project Viva.

Per- and polyfluoroalkyl substances (PFAS) exposure may alter glucose homeostasis. Research on PFAS exposure and glucose tolerance during pregnancy is limited. The objective of this work is to estimate associations between first-trimester plasma PFAS concentrations and glucose tolerance assessed in late second pregnancy trimester. Pregnant women (n = 1540) enrolled in Project Viva in 1999 to 2002 provided first-trimester plasma samples analyzed for 8 PFAS. At approximately 28 weeks' gestation, women completed 1-hour nonfasting, 50-g oral glucose challenge tests (GCTs); if abnormal, women completed subsequent 3-hour oral glucose tolerance tests (OGTTs) to screen for gestational diabetes mellitus (GDM). We assessed both continuous GCT glucose levels and 4 categories of glucose tolerance (normal glycemia [reference], isolated hyperglycemia, impaired glucose tolerance, GDM). We used multinomial logistic regression to estimate associations of PFAS with glucose tolerance categories. We used multivariable linear regression and Bayesian kernel machine regression (BKMR) to assess individual and joint effects of PFAS on continuous GCT glucose levels, respectively. We evaluated effect modification by maternal age and race/ethnicity. PFAS were not associated with glucose tolerance categories. In BKMR analyses, we observed a positive association between ln-perfluorooctane sulfonate (PFOS) and glucose levels (Δ25th to 75th percentile: 6.2 mg/dL, 95% CI, 1.1-11.3) and an inverse-U shaped association between 2-(N-perfluorooctane sulfonamide) acetate and glucose levels. Individual linear regression results were similar. We found suggestive evidence that associations varied by age and racial/ethnic group. Certain PFAS may alter glucose homeostasis during pregnancy, but may not be associated with overt GDM.

Does Human Milk Insulin Help Program Infant Pancreatic Function? Variation in Neonatal Human Milk Insulin Is Associated with Later Measures of Infant Glycemic Control

Abstract Objectives Whether variation in human milk (HM) insulin contributes to neonatal blood sugar regulation and pancreatic programming remains unknown. This pilot study investigates whether HM insulin concentrations correlate with infant pancreatic function in exclusively breastfed 5-month old infants. We hypothesize that neonatal exposure to elevated HM insulin will “under stimulate” the infant pancreas, resulting in an exaggerated glycemic response to oral glucose at 5 months. Methods Exclusively breastfed infants of normoglycemic mothers (NG; n = 5) and mothers with minor insulin resistance (IR; n = 5) were administered a 1.75 g/kg oral glucose challenge. Infant capillary glucose was assessed at Fasting (&amp;gt;2 hours), 30 minutes (T30) and 60 minute (T60) after glucose administration. Fasting HM insulin was measured at 2-weeks and 5-months. Repeated Measures ANOVA and linear regression analyses were utilized. Results Using repeated measures analysis, the IR group exhibited a more dramatic glycemic response to the glucose challenge (P = 0.031): exhibiting lower fasting glucose (P = 0.085; n = 10) and higher glucose excursion from fasting to T30 (P = 0.007) compared to the NG group. HM insulin did not differ between the NW and IR groups at 2-weeks or 5-months. However, higher HM insulin concentrations at 2-weeks did correlate with a more dramatic infant glycemic response to oral glucose at 5 months. Fasting HM insulin at 2 weeks was positively associated with infant glucose at T30 (P = 0.033) and with the increase in glucose from fasting to T30 (P = 0.081; n = 8). Furthermore, fasting HM insulin at 2-weeks was negatively associated with infant glucose at T60 (P = 0.031) and the change in glucose from T30-T60 (P = 0.032; n = 7). Conclusions These pilot results suggest that HM insulin may contribute to postnatal programming of infant pancreatic function such that chronic exposure to elevated HM insulin may result in a dampened pancreatic response to an oral glucose challenge. Confirmation in a larger sample size is necessary. Funding Sources NIH/NIDDK; The Gerber Foundation.