75-g Glucose Research Articles

Glucose intake is influencing the concentration of AD‐related plasma biomarkers in healthy adults

AbstractBackgroundBlood biomarker analyses are seen as a great aid to early diagnose and confirm underlying Alzheimer’s disease (AD) pathology. Developing evidence suggests that certain confounders need to be considered which may affect the reliability of biomarker results, e.g., chronic kidney disease. However, little is known with respect to potential confounding effects of energy/nutrient intake on these biomarkers. Thus, we aim to study the short‐term effects of oral glucose intake in healthy, obese adults.Method111 participants (60±7y, BMI 31±4kg/m2, 47 males) ingested 300ml of a glucose syrup (75g glucose, Accu‐Chek, Roche). Neurofilament light, glial fibrillary acidic protein [GFAP], amyloid‐β 42/40 ratio, phosphorylated tau ([p‐tau] 181 and p‐tau 231) were measured in fasting (0 minutes) and postprandial blood samples collected 15, 30, 45, 60, 120 and 180 minutes after ingestion of the glucose syrup using ultra‐sensitive Single molecule array assays. Additionally, a fasting (control) group (n = 26) was followed over the same time period. Statistical analysis was done using polynomial spline of degree 3 to test for differences in parameter progression over time within and between groups.ResultIn both groups, all biomarkers changed significantly over time (glucose group: all p<0.0001, fasting group all p<0.05) compared to baseline (0 minutes). The changes to baseline in GFAP were significantly different after glucose ingestion compared to the fasting state (p<0.0001). The GFAP level decreased in the early postprandial phase (until 60 minutes) and subsequently increased in the late postprandial phase.ConclusionOur results suggest that plasma biomarkers for AD‐related pathologies are influenced by the individual nutritional status (prolonged fasting, postprandial situation). This should be considered when using AD‐related biomarkers for screening and diagnostic purposes.

An oral glucose tolerance test does not affect cerebral blood flow: role of NOS.

Animal data indicate that insulin triggers a robust nitric oxide synthase (NOS)-mediated dilation in cerebral arteries similar to the peripheral tissue vasodilation observed in healthy adults. Insulin's role in regulating cerebral blood flow (CBF) in humans remains unclear but may be important for understanding the links between insulin resistance, diminished CBF, and poor brain health outcomes. We tested the hypothesis that an oral glucose challenge (oral glucose tolerance test, OGTT), which increases systemic insulin and glucose, would acutely increase CBF in healthy adults due to NOS-mediated vasodilation, and that changes in CBF would be greater in anterior regions where NOS expression or activity may be greater. In a randomized, single-blind approach, 18 young healthy adults (24 ± 5 yr) underwent magnetic resonance imaging (MRI) with a placebo before and after an OGTT (75 g glucose), and 11 of these adults also completed an NG-monomethyl-l-arginine (l-NMMA) visit. Four-dimensional (4-D) flow MRI quantified macrovascular CBF and arterial spin labeling (ASL) quantified microvascular perfusion. Subjects completed baseline imaging with a placebo (or l-NMMA), then consumed an OGTT followed by MRI scans and blood sampling every 10-15 min for 90 min. Contrary to our hypothesis, total CBF (P = 0.17) and global perfusion (P > 0.05) did not change at any time point up to 60 min after the OGTT, and no regional changes were detected. l-NMMA did not mediate any effect of OGTT on CBF. These data suggest that insulin-glucose challenge does not acutely alter CBF in healthy adults.

Oral glucose has little or no effect on appetite and satiety sensations despite a significant gastrointestinal response.

The effect of oral glucose-induced release of gastrointestinal hormones on satiety and appetite independently of prevailing plasma glucose excursions is unknown. The objective is to investigate the effect of oral glucose on appetite and satiety sensations as compared to isoglycemic IV glucose infusion (IIGI) in healthy volunteers. A crossover study involving two study days for each participant. Nineteen healthy participants (6 women, mean age 55.1 [SD 14.2] years; mean body mass index 26.7 [SD 2.2] kg/m2). Each participant underwent a 3-h 50-g oral glucose tolerance test (OGTT) and, on a subsequent study day, an IIGI mimicking the glucose excursions from the OGTT. On both study days, appetite and satiety were indicated regularly on visual analog scale (VAS), and blood was drawn regularly for measurement of pancreatic and gut hormones. Difference in appetite and satiety sensations during OGTT and IIGI. Circulating concentrations of glucose-dependent insulinotropic polypeptide (P < .0001), glucagon-like peptide 1 (P < .0001), insulin (P < .0001), C-peptide (P < .0001), and neurotensin (P = .003) increased significantly during the OGTT as compared to the IIGI, whereas glucagon responses were similarly suppressed (P = .991). Visual analog scale-assessed ratings of hunger, satiety, fullness, thirst, well-being, and nausea, respectively, were similar during OGTT and IIGI whether assessed as mean 0-3-h values or area under the curves. For both groups, a similar, slow increase in appetite and decrease in satiation were observed. Area under the curve, for prospective food consumption (P = .049) and overall appetite score (P = .044) were slightly lower during OGTT compared to IIGI, whereas mean 0-3-h values were statistically similar for prospective food consumption (P = .053) and overall appetite score (P = .063). Despite eliciting robust responses of appetite-reducing and/or satiety-promoting gut hormones, we found that oral glucose administration has little or no effect on appetite and satiety as compared to an IIGI, not affecting the release of appetite-modulating hormones. ClinicalTrials.gov: NCT01492283 and NCT06064084.

Gestational diabetes mellitus in pregnancies conceived after infertility treatment: a population-based study in the United States, 2015–2020

To evaluate the risk of gestational diabetes mellitus (GDM) in singleton pregnancies conceived using infertility treatment and examine the influence of race and ethnicity as well as prepregnancy body mass index (BMI). Cross-sectional study using the US vital records data of women that delivered singleton births. United States, 2015-2020. Any infertility treatment was divided into two groups: those that used fertility-enhancing drugs, artificial insemination, or intrauterine insemination, and those that used assisted reproductive technology (ART). Gestational diabetes mellitus, defined as a diagnosis of diabetes mellitus during pregnancy, includes both diet-controlled GDM and medication-controlled GDM in singleton pregnancies conceived with infertility treatment or spontaneously and delivered between 20- and 44-weeks' gestation. We also examined whether the infertility treatment-GDM association was modified by maternal race and ethnicity as well as prepregnancy BMI. Associations were expressed as a rate ratio (RR) and 95% confidence interval (CI), derived from log-linear models after adjustment for potential confounders. A total of 21,943,384 singleton births were included, with 1.5% (n = 318,086) undergoing infertility treatment. Rates of GDM among women undergoing infertility treatment and those who conceived spontaneously were 11.0% (n = 34,946) and 6.5% (n = 1,398,613), respectively (adjusted RR 1.24, 95% CI 1.23, 1.26). The RRs were adjusted for maternal age, parity, education, race and ethnicity, smoking, BMI, chronic hypertension, and year of delivery. The risk of GDM was modestly increased for those using fertility-enhancing drugs (adjusted RR 1.28, 95% CI 1.27, 1.30) compared with ART (adjusted RR 1.18, 95% CI 1.17, 1.20), and this risk was especially apparent for non-Hispanic White women (adjusted RR 1.29, 95% CI 1.26, 1.31) and Hispanic women (adjusted RR 1.35, 95% CI 1.29, 1.41). The number of women who needed to be exposed to infertility treatment to diagnose one case of GDM was 46. Prepregnancy BMI did not modify the infertility treatment-GDM association overall and within strata of race and ethnicity. These general patterns were stronger after potential corrections for misclassification of infertility treatment and unmeasured confounding. Infertility treatment, among those who received fertility-enhancing drugs, is associated with an increased GDM risk. The persistently higher risk of GDM among women who seek infertility treatment, irrespective of prepregnancy weight classification, deserves attention. Infertility specialists must be vigilant with preconception counseling and ensure that all patients, regardless ofrace and ethnicity or BMI, are adequately tested for GDM early in pregnancy using a fasting blood glucose level or a traditional 50-g oral glucose tolerance test. Testing may be completed by the infertility specialist or deferred to the primary prenatal care provider at the first prenatal visit.

A comparison study of maternal and perinatal outcomes with gestational diabetes mellitus, impaired glucose tolerance, and normal glucose tolerance

Gestational diabetes mellitus (GDM) and impaired glucose tolerance (IGT), which are growing health concerns globally, are the most common metabolic and endocrine perinatal issues. It is a contentious entity with competing policies and procedures. Most physicians in the United States employ a two-step procedure, starting with a 50-g non-fasting oral glucose challenge test at 24 to 28 weeks and moving on to a 100-g fasting test for women who receive a positive screening result. Instead, doctors use the Diabetes in Pregnancy Study Group India (DIPSI) technique and conduct just a 75-g, two-hour fasting oral glucose tolerance test. The prospective observational study was approved by the hospital's institutional ethics committee and was conducted from April 2020 to September 2021 at the department of obstetrics and gynecology at Stanley Medical College Hospital in Chennai, Tamil Nadu, India. The patients were chosen in accordance with the inclusion criteria, which called for first-trimester pregnant women without diabetes mellitus. Both oral and written consent were also obtained. DIPSI performed the screening. The WHO standards have been updated to be a one-step process with a single glycemic value. According to the results of this study, GDM is linked to harmful consequences that might affect both the mother and the foetus. The short- and long-term consequences in both the mother and the newborn can be greatly reduced with early detection and timely therapy of this illness. In this study, birth weights ranging from 2.5 to 3.5 kg were the same for GDM and IGT moms. IGT mothers should also be followed up on, and we should be more watchful at birth, even though we monitor GDM mothers.

Differential effect of gastric bypass versus sleeve gastrectomy on insulinotropic action of endogenous incretins.

Prandial hyperinsulinemia after Roux-en-Y gastric bypass surgery (GB), and to lesser degree after sleeve gastrectomy (SG), has been attributed to rapid glucose flux from the gut and increased insulinotropic gut hormones. However, β-cell sensitivity to exogenous incretin is reduced after GB. This study examines the effect of GB versus SG on prandial glycemia and β-cell response to increasing concentrations of endogenous incretins. Glucose kinetics, insulin secretion rate (ISR), and incretin responses to 50-g oral glucose ingestion were compared between ten nondiabetic participants with GB versus nine matched individuals with SG and seven nonoperated normal glucose tolerant control individuals (CN) with and without administration of 200 mg ofsitagliptin. Fasting glucose and hormonal levels were similar among three groups. Increasing plasma concentrations of endogenous incretins by two- to three-fold diminished prandial glycemia and increased β-cell secretion in all three groups (p < 0.05), but insulin secretion per insulin sensitivity (i.e., disposition index) was increased only in GB (p < 0.05 for interaction). However, plot of the slope of ISR (from premeal to peak values) versus plasma glucagon-like peptide-1 concentration was smaller after GB compared with SG and CN. After GB, increasing incretin activity augments prandial β-cell response whereas the β-cell sensitivity to increasing plasma concentrations of endogenous incretin is diminished.

Characteristics of individuals who developed type 2 diabetes from prediabetes despite undergoing interventions, and evaluation of the performance of urinary myo-inositol as a risk factor for developing diabetes.

The aim of this study was to clarify the characteristics of individuals with prediabetes who developed type 2 diabetes despite undergoing interventions, and to evaluate the performance of urinary myo-inositol (UMI) as a noninvasive indicator for the risk of developing diabetes. A total of 51 individuals with prediabetes who underwent a 75-g oral glucose tolerance test, ΔUMI (the difference in the UMI : creatinine ratio between before and 120 min after 75-g glucose loading), fasting plasma glucose, insulin, hemoglobin A1c, noninvasive testing (age, body mass index, blood pressure) and general blood tests were measured at baseline, and underwent dietary/exercise guidance for 8 years were studied. A total of 31 participants developed diabetes in 8 years. At baseline, the group that developed diabetes was characterized by high ΔUMI, hemoglobin A1c, fasting plasma glucose and low high-density lipoprotein cholesterol, and insulinogenic index (I.I.). I.I and ΔUMI showed a higher correlation than fasting plasma glucose and hemoglobin A1c. Regarding diabetes onset within 8 years, Cox regression analysis of diabetes onset showed the baseline ΔUMI is an independent predictor, adjusted for the result of not only noninvasive markers, but also that of noninvasive and general blood markers. The log-rank test showed that all glycemic indicators were significantly associated with diabetes onset. Participants who developed type 2 diabetes from prediabetes despite undergoing interventions were characterized by high glycemic control markers and low I.I. As noninvasive measurement of ΔUMI is associated with I.I. and diabetes onset, it could be a useful indicator for identifying individuals with a high risk of diabetes onset.

The effect of 50 GR oral glucose tolerance test on fetal celiac artery and superior mesenteric artery doppler parameters in healthy pregnancies.

To understand the effect of 50-g oral glucose tolerance test (OGTT) on fetal celiac artery and superior mesenteric artery (SMA) doppler parameters. A total of 43 healthy pregnant women followed inour hospital were included in the study. All doppler parameters of the celiac artery and SMA (PSV:Peak systolicvelocity; PI:Pulsatility index; RI:Resistance index, S/D:Systolic/diastolic ratio; TAMAX:Time average maximum velocity) were obtained by ultrasonography before and 1 h after OGTT. The mean PSV value of the celiac artery decreased statistically significantly after OGTT (37.29±11.96 cm/s; 29.51±10.07 cm/s; p=0.002). While the mean of the PI was 2.09±0.57 before the test, it was found to be 1.84±0.64 afterthe test (p=0.027). Mean PSV (39.82±13.07 cm/s; 35.19±15.27 cm/s; p=0.104) and PI (2.21±0.65; 2.11±0.80; p=0.375) values of SMA were also found to be decreased without statistically significancy. The data obtained from our study reveals that the PSV and PI values of celiac artery and SMA slightly decrease after OGTT.

A Pilot Crossover Study of Berberine and its Short-Term Effects on Blood Glucose Levels in Healthy Volunteers

Introduction: Different berberine preparations were evaluated for their effectiveness on lowering blood glucose in a pilot, open-label, crossover study conducted in healthy adults. Methods: Fourteen healthy volunteers of both sexes were recruited, and seven completed all treatments in the study. Study participants ingested one of three berberine preparations containing 500mg of berberine, respectively. A one week wash out period was included between treatments. A control group was included to measure the participants’ baseline response to a 75g glucose solution without any treatment. The following interventions were administered: berberine powder in hard gelatin capsules, berberine in an oil matrix encapsulated in soft-gelatin capsules, and berberine in LipoMicel® matrix encapsulated in soft-gelatin capsules. Blood glucose concentrations in each participant were monitored from pre-dose baseline, before the capsules were ingested, until up to 3 hours after the capsules were ingested. Results: LipoMicel Berberine treatment led to reduced blood glucose concentrations Area Under Curve (AUC, mean difference: 1.57; 95% CI: 0.021 – 3.12; P = 0.046; Cohen’s d = 1.53) and reduced maximum glucose concentration (Gmax, mean difference: 1.07; 95% CI 0.004 – 2.14; P = 0.049; Cohen’s d = 1.52) compared to the control group when no-treatment was given. No adverse events related to berberine treatments were reported by participants throughout the study period. Conclusions: LipoMicel Berberine was effective in lowering blood glucose levels by 12% after two 500mg doses. Berberine in other formulations may require a longer dosing regimen before blood glucose lowering effects can be demonstrated.

The evolution and future of diagnostic criteria for diabetes mellitus

Background: The diagnostic criteria for diabetes mellitus have evolved over time, taking into account new evidence. Here, the author would like to review the evolution of diagnostic criteria for diabetes mellitus, the current diagnostic criteria, and future perspectives.Current Concepts: For the first time, in 1965, the World Health Organization (WHO) recommended that a 2-hour plasma glucose concentration of 130 mg/dL or more after taking a 50-g or 100-g oral glucose bolus may be used to make the diagnosis in people younger than 45 years and that other clinical data might be used to make the diagnosis in people older than 45 years. The 2003 American Diabetes Association Diagnostic Criteria set the threshold for normal fasting glucose at 100 mg/dL. The International Expert Committee (IEC) in 2009, the American Diabetes Association in 2010, and the WHO in 2011 proposed new diagnostic criteria for diabetes: glycated hemoglobin (HbA1c) of 6.5% or higher. More recently, diabetes has been diagnosed via a fasting blood glucose of 126 mg/dL or higher after fasting for at least 8 hours, a 2-hour postprandial blood glucose of 200 mg/dL or higher, glycated hemoglobin of 6.5% or higher, or a random blood glucose of 200 mg/dL or higher with symptoms of hyperglycemia.Discussion and Conclusion: Further research is needed on the accuracy of other markers, such as HbA1c, fructosamine, and 1,5-anhydroglusitol, in the diagnosis of diabetes, and sufficient evidence is required to determine whether it is appropriate to use the same diagnostic criteria for diabetes in aged people and different ethnic groups.

Plasma insulin is required for the increase in plasma angiopoietin-like protein 8 in response to nutrient ingestion.

Plasma levels of angiopoietin-like protein 8 (ANGPTL8) are regulated by feeding and they increase following glucose ingestion. Because both plasma glucose and insulin increase following food ingestion, we aimed to determine whether the increase in plasma insulin and glucose or both are responsible for the increase in ANGPTL8 levels. ANGPTL8 levels were measured in 30 subjects, 14 with impaired fasting glucose (IFG), and 16 with normal fasting glucose (NFG); the subjectsreceived 75g glucose oral Glucose tolerance test (OGTT), multistep euglycaemic hyperinsulinemic clamp and hyperglycaemic clamp with pancreatic clamp. Subjects with IFG had significantly higher ANGPTL8 than NGT subjects during the fasting state (p<0.05). During the OGTT, plasma ANGPTL8 concentration increased by 62% above the fasting level (p<0.0001), and the increase above fasting in ANGPTL8 levels was similar in NFG and IFG individuals. During the multistep insulin clamp, there was a dose-dependent increase in plasma ANGPTL8 concentration. During the 2-step hyperglycaemic clamp, the rise in plasma glucose concentration failed to cause any change in the plasma ANGPTL8 concentration from baseline. In response to nutrient ingestion, ANGPTL8 level increased due to increased plasma insulin concentration, not to the rise in plasma glucose. The incremental increase above baseline in plasma ANGLPTL8 during OGTT was comparable between people with normal glucose tolerance and IFG.

1847-PUB: Neutrophil Count Predicts Cardiovascular and Metabolic Health Risk Factors in a Population without Diabetes

Subclinical inflammation is implicated in cardio-metabolic conditions such as impaired glucose metabolism, diabetes, and hypertension. Neutrophils are first line of immune defense call and play a role in systemic inflammation. We therefore hypothesized that neutrophil quantity will be positively associated with cardio-metabolic risk factors among individuals without diabetes. Purpose: This study sought to determine the relevance of neutrophil count as a biomarker for cardio-metabolic health. Methods: Forty participants without diabetes (11 males, 29 females; age 28.4±10.7 years; BMI 28.2±6.0 kg/m2, fasting blood glucose 97.28±11.09 mg/dL) participated in the study. Following overnight fasting, participants’ blood pressure and resting heart rate were measured, and venous blood draw was performed. All participants completed a 3-hour oral glucose tolerance test with 75g glucose drink. Hematological and serum chemistry analyses were performed. Body composition was measured by dual X-ray absorptiometry. Homeostatic model assessment for insulin resistance (HOMA-IR) was computed from standard equations. Spearman’s correlation was performed to determine relationship between neutrophil count and markers of cardio-metabolic health. Results: Neutrophil count is positively correlated with resting heart (r=0.5, p=0.004), triglycerides (r=0.5, p=0.002), triglycerides-HDL ratio (r=0.5, p=0.002), VLDL (r=0.5, p=0.001), Globulin (r=0.3, p=0.03), BUN/creatinine ratio (r=0.5, p=0.0004), fasting insulin (r=0.7, p=0.004), fasting blood glucose (r=0.5, p=0.0008), 2-hour OGTT glucose (r=0.5, p=0.003), glucose area under the curve (r=0.5, p=0.0001), percent body fat (r=0.6, p=0.0003), HOMA-IR (r=0.6, p=0.008) and negatively correlated with albumin/globulin ratio (r=-0.4, p=0.01), HDL (r=-0.3, p=0.04). Conclusion: Neutrophil count is a biomarker for cardio-metabolic health risk factors in a population without diabetes. Disclosure J.Labadah: None. J.Apaflo: None. G.Narvaez: None. V.M.Rocha: None. A.Mossayebi: None. S.Bajpeyi: None. Funding The University of Texas at El Paso

1283-P: Pilot Study Reveals Excellent Agreement between the Newly Developed Pastry Sugar Tolerance Test and the OGTT in the Diagnosis of Diabetes

Achieving early diagnosis of type 2 diabetes (T2D) in Africans is challenging. The Glucola used in the OGTT is expensive and unavailable in most African countries. Alternatives to the OGTT are fasting plasma glucose (FPG) and A1C, but they have a low diagnostic sensitivity in Africans. As an alternative to the Glucola (75g glucose) used in the OGTT, we developed the Pastry Sugar Tolerance Test (PSTT) with pastry sugar (75g glucose powder) dissolved in hot water. Pastry sugar is inexpensive and widely available in Africa. Hence, our aim was to determine the diagnostic agreement between (1) OGTT and PSTT; (2) OGTT and A1C; (3) OGTT and FPG in the detection of T2D in 48 African-born Blacks living in America (male: 67%; age: 41±10y (mean±SD)). At Visit 1, an OGTT, A1C and FPG were performed. At Visit 2, which occurred 8±3 days later, a PSTT was performed (Fig). ADA criteria were used for the OGTT, A1C≥6.5% and FPG≥126 mg/dL. Agreement between tests was determined by κ-statistic. T2D, prediabetes and normal glucose tolerance occurred in 8% (4/48), 31% (15/48) and 61% (29/48), resp. All individuals with T2D were detected by both the OGTT and PSTT (κ=0.99). Yet, A1C only detected 50% (2/4) (κ=0.65), and FPG only detected 25% (1/4) (κ=0.38) of Africans with T2D. This pilot study suggests that in the detection of T2D, agreement between the PSTT and the OGTT may be both excellent and superior to A1C and FPG. Disclosure B.R.Schenk: None. A.E.Sumner: None. J.Hurston: None. J.Gatete: None. C.Dubose: None. L.Mabundo: None. S.Yang: None. C.Worthy: None. A.B.Courville: None. R.Jagannathan: None.

1191-P: GDM in Twin Pregnancies—Maternal Characteristics and Pregnancy Outcomes

The incidence of both gestational diabetes mellitus (GDM) and twin pregnancies have increased over the past two decades. While the same GDM diagnostic criteria and treatment targets are used for singleton and twin pregnancies, data on outcomes for twin pregnancies with GDM are limited. The aim of this retrospective cohort study is to present comprehensive data on maternal characteristics and pregnancy outcomes for individuals with a twin pregnancy who were diagnosed with GDM and attended our center for prenatal care from 2002-22. In total 185 individuals were identified with a mean age of 32 (± 5) years and a mean prepregnancy body mass index of 31.3 (± 7) kg/m2. The majority were dichorionic diamniotic (n=146, 79%), 32 (17%) had a prior diagnosis of GDM and 63 (34%) had prepregnancy fertility treatment. Women underwent universal screening with a 50g glucose challenge test (normal &amp;lt;140mg/dL) and Carpenter and Coustan Criteria were used to diagnose GDM. Pharmacological therapy was required to treat GDM in 68 (37%) cases. Hypertensive disorders of pregnancy were common (n=55, 30%), as was Cesarean delivery (n= 133, 72%). Assessment of pregnancy outcomes (n=370) revealed 360 (97%) livebirths, 8 (2%) stillbirths and 2 (0.6%) neonatal deaths. Among livebirths and neonatal deaths, premature delivery &amp;lt; 37 weeks was recorded in 225 (62.2%) and &amp;lt;34 weeks in 57 (15.7%). Neonatal macrosomia (birthweight &amp;gt;4.0kg) was rare (n=4, 1%), but low birthweight (&amp;lt;2.5kg) occurred in 168 (46%). Neonatal hypoglycemia was documented in 89 (25%) infants. Maternal attendance at the postpartum glucose tolerance test was low (n=47, 25.5%) individuals, and 38 had a subsequent pregnancy with GDM diagnosed in 18 (47%). In summary, the standard GDM diagnostic criteria applied to twin pregnancies identify a maternal cohort at high risk of pregnancy complications and future GDM. Future work should address the optimal nutritional and glycemic goals for this population, particularly considering the high risk of low birthweight and premature neonates. Disclosure D.M.Das: None. A.Vella: Advisory Panel; Rezolute, Inc., Consultant; Crinetics Pharmaceuticals, Inc., Hanmi Pharm. Co., Ltd., Zealand Pharma A/S, Other Relationship; Novo Nordisk. A.M.Egan: None. Funding National Institutes of Health (DK092721, HD065987)

1645-P: Diabetes-Associated Variation in TCF7L2 Is Associated with a Longitudinal Decline in Glucose Tolerance Accompanied by Impaired Suppression of Postprandial Glucagon Secretion

Diabetes-associated alleles in TCF7L2 increase the rate of conversion from prediabetes to type 2 diabetes (T2DM). Multiple studies have shown an association of the T allele at rs7903146 with impaired β-cell function and more recently with defective suppression of α-cell secretion by glucose. However, the temporal relationship of these abnormalities is uncertain. To study the longitudinal changes in islet function, we recruited 140 individuals half of whom were homozygous for the diabetes-associated allele (TT) at rs7903146. The remainder were homozygous for the protective allele (CC). Subjects were studied on 2 occasions, 3 years apart using an oral 75g glucose challenge. This was labelled with 13C-glucose, in concert with intravenously infused tracers to enable measurement of endogenous glucose production, meal appearance and glucose disposal. Indices for insulin secretion and action were estimated using the oral minimal model. Fasting, peak and integrated (443 ± 27 vs. 428 ± 50 mmol/l per 6hr, p = 0.54) post-prandial glucose concentrations did not differ over time in people with the CC genotype. In contrast, post-prandial integrated glucose concentrations increased (441 ± 29 vs. 544 ± 37 mmol/l per 6hr, p &amp;lt; 0.01) in people with the TT genotype. This was accompanied by an increase in integrated postprandial glucagon concentrations (526 ± 39 vs. 618 ± 61 pmol/l per 2hr, p = 0.04) that was not observed in the CC genotype (537 ± 50 vs. 525 ± 65 pmol/l per 2hr, p = 0.07). There were no baseline differences in β-cell function between genotype groups. Disposition Index in both TT (950 ± 130 vs. 868 ± 92 10-4 dl/kg/min per μU/ml, baseline vs. follow-up study respectively, p=0.42) and CC (896 ± 177 vs. 1062 ± 289 10-4 dl/kg/min per μU/ml, p=0.65) groups did not change. This data would suggest that α-cell dysfunction associated with the TT genotype (rs7903146) precedes β-cell dysfunction in people prior to the development of T2DM. Disclosure M.Zeini: None. K.Muthusamy: None. A.M.Egan: None. M.C.Laurenti: None. C.Cobelli: None. C.Dalla man: Research Support; Sanofi-Aventis Deutschland GmbH, Becton, Dickinson and Company. A.Vella: Advisory Panel; Rezolute, Inc., Consultant; Crinetics Pharmaceuticals, Inc., Hanmi Pharm. Co., Ltd., Zealand Pharma A/S, Other Relationship; Novo Nordisk. Funding National Institutes of Health (DK116723)

600-P: Higher Hydration Status Is Indicative of Better Glucose Tolerance

Introduction: Water intake is an important dietary behavior to replace high-caloric beverages and to enhance metabolic health. Type 2 diabetes is a metabolic disorder that has been shown to be more prevalent in Hispanics, a population shown to consume relatively less water compared to non-Hispanic Whites. The underlying cause of type 2 diabetes is insulin resistance, characterized by hyperglycemia and impaired glycemic control. However, whether a relationship exists between dehydration and the development of diabetes remains to be elucidated. Purpose: To evaluate if hydration status indicates glucose tolerance among a dominant Mexican American population. Methods: Sixty-one participants without diabetes (Age: 26.5 ± 9.1 years; BMI: 27.5 ± 6.0 kg/m2) participated in the study. Fasting blood glucose level was determined, and a 2-hour glucose tolerance test was performed following the ingestion of a 75g glucose drink. Blood glucose concentration levels were determined at 15−, 30−, 60−, 90−, and 120-minute time intervals post ingestion and glucose area under the curve was analyzed as well. Blood works were performed to determine blood urea nitrogen (BUN) and creatinine concentrations. Hydration status was estimated using the ratio of BUN to creatinine values. Results: Hydration status measured by BUN/Creatinine was positively associated with glucose intolerance measured at 15−, 30−, 60−, and 90-minute post glucose load and by glucose area under the curve (r=0.33; r=0.43; r=0.37; r=0.27; and r=0.41 respectively; p&amp;lt;0.05). Conclusion: Adequate fluid consumption should be encouraged for glycemic control, especially among people with high diabetes risks. Disclosure J.Apaflo: None. J.Labadah: None. G.Narvaez: None. V.M.Rocha: None. A.Mossayebi: None. S.Bajpeyi: None.

Hemoglobin A1c as a Substitute for Oral Glucose Testing in Early Pregnancy Screening.

Current recommendations for individuals with risk factors for gestational diabetes mellitus (GDM) call for screening in early pregnancy. However, there is currently no clear consensus on a specific screening modality. This study evaluates whether a hemoglobin A1c (HbA1c) screening in individuals with risk factors for gestational diabetes (GDM) could be used instead of an early 1-hour glucose challenge test (GCT). We hypothesized that the HbA1c could replace 1-hour GCT in early pregnancy evaluation STUDY DESIGN: This is a prospective observational trial at a single tertiary referral center of women with at least one risk factor for GDM who were screened at <16 weeks of gestation with both 1-hour GCT or HbA1c. Exclusion criteria include: previous diagnosis of diabetes mellitus, multiple gestation, miscarriage, or missing delivery information. The diagnosis of GDM was made by a 3-hour 100-g glucose tolerance test, using the Carpenter-Coustan criteria (at least two results >94, 179, 154, and 139 mg/dL for fasting, 1-, 2-, and 3-hour values, respectively), 1-hour GCT > 200 mg/dL, or HbA1c > 6.5%. A total of 758 patients met inclusion criteria. A total of 566 completed a 1-hour GCT and 729 had an HbA1c collected. The median gestational age at testing was 91/7 weeks (range: 40/7-156/7 weeks]. Twenty-one participants were diagnosed with GDM at <16 weeks' GA. The receiver operating characteristic (ROC) curves identified the optimal valves for a positive screen for an HbA1c > 5.6%. The HbA1c had a sensitivity of 84.2%, a specificity of 83.3%, and a false positive rate of 16.7% (p < 0.001). The area under the ROC curve for the HbA1c was 0.898. Gestational age of delivery was slightly earlier with individuals with an elevated HbA1c but no other changes in delivery or neonatal outcomes. Contingent screening improved specificity (97.7%) and decreased false positive rate to 4.4%. HbA1c may be a good assessment in early pregnancy for gestational diabetes. · HbA1c is a rational assessment in early pregnancy.. · An HbA1c > 5.6% is associated with gestational diabetes.. · Contingent screening limits the need for additional testing..

Likelihood of Subsequent Type 2 Diabetes Diagnosis Among Patients Diagnosed With Gestational Diabetes and a 50-Gram 1-Hour Glucose Test Value of 200 mg/dL or Greater [ID: 1379006

INTRODUCTION: Patients with gestational diabetes mellitus (GDM) are at increased risk for lifelong type 2 diabetes mellitus (T2DM). We sought to identify whether a 1-hour 50-g glucose result of 200 mg/dL or greater increased likelihood of T2DM among individuals with GDM. METHODS: This was a retrospective cohort study at a single tertiary care site from 2011 to 2019. Participants were included if diagnosed and treated for GDM during pregnancy, at least 18 years of age, and had singleton pregnancy. Exclusion criteria were significant fetal anomalies or incomplete records. Participants with values of 200 mg/dL or greater were then grouped and compared to participants with a value less than 200 mg/dL. Primary outcome was diagnosis of T2DM within 5 or less years of pregnancy. T tests, χ2, Fisher’s exact, and logistic regression were utilized for statistical analyses. RESULTS: Seven hundred eight participants met inclusion criteria. Among these, 100 (14.1%) had a value of 200 mg/dL or greater on the 1-hour 50-g glucose test. Groups were similar, with the exception that those with a very elevated 1-hour glucose result were more likely to be publicly insured (32.0% versus 17.1%, P=.009), identify as non-Hispanic Black (19% versus 14.6%, P=.036), and likely to be married (28.0% versus 25.8%, P=.039). Of the 708 participants, 31 (31.0%) were found to have T2DM among those with 1 hour of 200 mg/dL or greater versus 93 (15.3%) of those with lower 1-hour glucose results (P&lt;.001). After controlling for confounders, T2DM remained independently associated with 1-hour glucose of 200 mg/dL or greater (adjusted odds ratio 2.14, 95% CI 1.22–3.74). CONCLUSION: Elevated screening results (≥200 mg/dL) on the 1-hour 50-g glucose test predicts an increased likelihood for T2DM.

Does increasing insulin resistance in adolescence actively decrease cerebral perfusion to oral glucose tolerance test?

Background: Approximately 20% of American adolescents are obese, and nearly half demonstrate some form of insulin resistance (IR). Insulin acts as a metabolic hormone, a neurotrophic growth factor, and a vasodilator. Notably, adults with neurologic disease often exhibit IR and reduced cerebral blood flow (CBF). Adolescent brains are actively growing such that IR may negatively impact brain health in part due to lower brain perfusion. Specifically, given the role of insulin as a potential vasodilator, we hypothesized CBF would increase in response to a physiologic glucose-insulin surge, but this effect would lessen as IR level increased. Methods: Adolescents (n=11, 3 females, age=14.8±2 yr, BMI=24.7±7) taking no medications were studied. IR was estimated by calculating HOMA-IR using fasting glucose and insulin, spanning a spectrum of IR (excluding diabetes). Subjects completed a magnetic resonance imaging (MRI) study visit to assess cerebral perfusion using arterial spin labeling (ASL). Heart rate (HR), mean arterial pressure (MAP) and end tidal CO 2 (ETCO 2 ) were assessed at baseline and during oral glucose tolerance test (OGTT); ingesting 75g glucose in 296mL water (Trutol). Venous blood was sampled at baseline and 5, 10, 20, 30, 45, and 60 minutes post OGTT. Perfusion at peak plasma insulin was compared to baseline. Significance was determined using linear regression of change in perfusion (peak- baseline) versus HOMA-IR and set at p≤0.05. Results: Results are mean±SD. HR (p=0.9), MAP (p=0.22) and ETCO 2 (p=0.75) were similar across HOMA-IR. MAP (p=0.44) and ETCO 2 (p=0.15) did not change during OGTT at insulin peak. Peak insulin occurred at 44±13 min post OGTT (baseline: 8±4 vs. peak: 65±38 μU/mL, p=0.001). Glucose changed from 79±6 to 142±30 mg/dL at peak insulin (p=0.0005). There were no significant associations between HOMA-IR and changes in perfusion in gray matter (R 2 =0.06, p=0.43) and white matter (R 2 =0.07, p=0.13). There were no significant associations for the following regions: hippocampus, amygdala, thalamus, anterior and posterior insula, and precuneus (R 2 all &lt;0.2, p all &gt;0.14). There was a trend toward negative regression in anterior cingulate gyrus (R 2 =0.25, p=0.11). Conclusions: These data suggest an OGTT does not acutely change brain perfusion at a global or regional level in adolescents, except possibly the anterior cingulate gyrus that is negatively impacted by increasing IR. The majority of present findings do not support our hypothesis that OGTT-mediated changes in cerebral perfusion are associated with IR in adolescents. NIH R21HD097510 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Outcomes of Diabetic Intervention With One Abnormal Value on the 3-Hour 100-Gram Glucose Tolerance Test [ID: 1381570

INTRODUCTION: Recent studies identified an increased risk of adverse perinatal outcomes in women who have one abnormal value on the 3-hour 100-g glucose tolerance test (GTT) compared to women without gestational diabetes (GDM). Limited data are available on the benefit of diabetic intervention with these patients. We examined outcomes of pregnancies diagnosed and managed with GDM based on one abnormal value compared to those receiving routine care. METHODS: We performed a retrospective cohort study of all women with one abnormal value, comparing outcomes for those patients who received routine prenatal care (January 2016 to February 2018) versus those treated for gestational diabetes (March 2018 to July 2021). The primary outcome was birth weight greater than 4,000 g. Secondary outcomes included large for gestational age and cesarean delivery secondary to labor dystocia. Nonparametric tests were used to compare outcomes between groups. Study was IRB exempt. RESULTS: One hundred twenty-six women had one abnormal value on the 3-hour GTT. 76 (55.88%) were diagnosed with GDM and managed accordingly, while 50 (36.76%) were followed with routine care. Of the women diagnosed with GDM, 27 (35.52%) required pharmacologic treatment. Diagnosis of GDM and intervention were associated with a significant reduction in birth weight greater than 4,000 g (5.26% versus 20%, odds ratio 0.22, 95% CI 0.07–0.75). There were no significant differences for secondary outcomes. CONCLUSION: Pregnancies with one abnormal value on 3-hour GTT who received diabetic intervention were less likely to have birth weights greater than 4,000 g. Although further studies with larger cohorts are needed, this supports the use of one abnormal value for the diagnosis of GDM.