75-g OGTT Research Articles

250-LB: Ethnic Disparities in Insulin Secretion and Clearance in Normoglycemic Adults with Parental Type 2 Diabetes

Background: To determine the role of ethnicity vs. heredity in glucoregulation, we assessed insulin secretion in healthy Black and White offspring of parents with T2DM. Methods: Participants were screened with 75-g OGTT, and normoglycemic enrollees underwent assessments, including anthropometry, insulin sensitivity and secretion. Basal insulin secretion (fasting insulin {FI} and HOMA-B) and dynamic secretion (insulinogenic index; corrected insulin response {CIR} from OGTT data; acute insulin response to i.v. glucose {AIR}, insulin-AUC during FSIGT, and disposition index {DI} were quantified. Insulin sensitivity (ISI) was measured with euglycemic clamp. Basal insulin clearance (molar ratio of fasting C-peptide to insulin) and dynamic clearance (molar ratio of plasma C-peptide to insulin levels during FSIGT) were determined. Results: We studied 145 Black and 123 White adults (N=268); 72% women; mean age 44.6±10.1 y. At baseline, fasting glucose (91.0 ± 7.26 vs.93.1 ± 6.31 mg/dl, P=0.012) and ISI (0.062 ± 0.048 vs. 0.077 ± 0.04, P=.014) were lower, and BMI (31.6 ± 7.64 vs. 28.9 ± 6.79, P=.0032) higher, in Black vs. White subjects. Basal insulin secretion was similar, but all measures of dynamic secretion were higher in Black vs. White offspring (Table 1). Conclusions: Insulin clearance is lower but dynamic insulin secretion is greater in Black versus White individuals with parental diabetes. Disclosure P. Asuzu: None. A. Patel: None. J. Y. Wan: None. S. Dagogo-jack: None.

742-P: Diabetes Prevention Effect of Practically Applicable Intervention in Clinical Settings Based on the Korean Diabetes Prevention Study (KDPS)

Background: The Korean Diabetes Prevention Study (KDPS, NCT02981121), a national clinical study to prevent T2DM, started in 2016 and is currently ongoing. This study was to evaluate the preventive effect of KDPS intervention for up to 1 year. Methods: The enrollment criteria are adults aged 30-70 with a BMI ≥ 23 kg/m2 at high risk of T2DM. Three Intervention methods are hospital-based lifestyle modification (hLSM) developed by Korean Diabetes Association, metformin (MET, 250mg~1000mg) and control standard management (STM) including a visit to the doctor every 6 months. LSM consists of 4 times individual diet interventions and lifestyle modification to keep 10 healthy habits with 7 times on-site and 8 times on phone-call contact. We assessed FPG and A1c every 6 months and OGTT every 12 months to check DM progression. Results: A total of 1611 subjects at 15 university hospitals performed screening with 75g OGTT (KDPS 1: 2016.11 ~ 2018.12, KDPS 2: 2020.9 ~ 2022.4). Eight hundred forty-four patients (male 44.2%) were randomized. The mean age was 56.1 years, BMI 26.6 kg/m2, WC 91.2 cm, FPG 103.2 mg/dL, PP2G 154.9 mg/dL, A1c 5.9%, and there was no significant difference between the three groups. KDPS 2 had a short follow-up period, thus DM prevention effect of up to 1 year was analyzed in 485 subjects of KDPS 1. Up to 1 year, the cumulative incidence of DM was 12/100 person-years (PY) in the LSM, 18/100 PY in MET, and 27/100 PY in STM (P=0.1440). Compared to STM, HR for T2DM in LSM was 0.51 (P=0.0508), and the HR in the MET was 0.82 (P=0.5205). Conclusion: The KDPS was intended to evaluate the DM prevention efficacy of the intervention methods practically applicable in clinical settings in Korea. The hLSM tended to have a 49% DM prevention effect compared to the STM. However, in the case of the MET, there was no significant difference from the control group. Further full analysis of KDPS results is needed for long term effect. Disclosure S.Chon: None. S.Yun: None. J.Woo: None. The korean diabetes prevention study investigators: n/a. Funding Korean Disease Control and Prevention Agency (2020-ER6402-00)

1711-P: Assessment of Prediabetes in Patients with Morbid Obesity (MO)

The frequency of prediabetes as well as the optimal method to identify glucose abnormalities in morbid obesity (MO) is subject to debate. We, therefore, evaluated the frequency of prediabetes and the optimal method for its respective diagnosis in a large cohort with MO. We included 1.626 patients with MO (age 34±10 years, BMI 44.6± 7.0 kg/m², 74.3% women). All patients without overt type 2 diabetes (T2D) underwent a 75g OGTT. Prediabetes was diagnosed according to ADA criteria. Demographic, cardiovascular risk-markers, insulin levels and renal parameters were assessed. We excluded 421 (25.9%) patients due to T2D. Regarding prediabetes, 339 patients (28.1%) fulfilled the fasting glucose criterion, 240 the 2-hour postprandial criterion (19.9%), and 594 patients the HbA1c criterion (49.2%). 56 patients (4.6%) fulfilled all three criteria, 810 (67.2%) had at least one criterion. 933 (77.4%) patients fulfilled either the fasting glucose or the HbA1c criterion, and 834 (69.2%) either the 2h postprandial or HbA1c criterion. Patient's characteristics are depicted in table 1. The results of our study suggest that fasting glucose or HbA1c are sufficient to diagnose prediabetes. This is particularly of interest since postoperative changes in gut anatomy following bariatric surgery might render a postoperative OGTT invalid for follow-up, whereas fasting glucose or HbA1c are not affected. Disclosure J.Brix: Advisory Panel; Boehringer Ingelheim Pharma GmbH&Co.KG, Eli Lilly and Company, Novo Nordisk, Speaker's Bureau; AstraZeneca, Eli Lilly and Company, Novo Nordisk. V.Parzer: None. S.L.Huber: None. B.Ludvik: Advisory Panel; Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Pharma GmbH&Co.KG, Amgen Inc., AstraZeneca, Research Support; Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Pharma GmbH&Co.KG, Amgen Inc., AstraZeneca, Speaker's Bureau; Eli Lilly and Company, Novo Nordisk, Boehringer Ingelheim Pharma GmbH&Co.KG, Amgen Inc., AstraZeneca.

1300-P: Glucagon-Like Peptide-1 Levels Mirror Insulin Resistant States in Treatment-Naïve Type 2 Diabetes Mellitus

Introduction: In some Asian populations incretin system has been shown to be preserved in type 2 diabetes mellitus (T2DM). The association between fasting and post-OGTT glucagon-like peptide-1 (GLP-1) levels and insulin resistance in treatment-naïve T2DM population has not been clearly defined. Aim: To assess the insulin resistant states (IRS) by means of insulin resistance index (HOMA-IR) and relate this to the fasting and post-OGTT GLP-1 responses in treatment-naïve T2DM. Methods : Thirty-one treatment-naive T2DM subject underwent a 75-g OGTT. Fasting plasma glucose and insulin levels were obtained for HOMA-IR analyses along with plasma total GLP-1 concentrations measured at 0, 30 and 120 min. Results: Majority of the treatment-naïve T2DM patients were newly-diagnosed (n=28, 96.6%). The GLP-1 levels at 0, 30- and 120-min were 25.59 ± 10.87 pmol/L, 46.86 ± 18.36 pmol/L and 27.02 ± 13.37 pmol/L respectively. Fasting GLP-1, incremental GLP-1 at 30 min (∆GLP-130min) and ∆GLP-1120min were positively correlated with HOMA-IR (r=0.654, p<0.001; r=0.421, p=0.018; r=0.574, p=0.001 respectively). Conclusions: The novel finding of this study is that fasting and post-OGTT GLP-1 levels increased proportionately to IRS. This suggests an adaptive compensatory GLP-1 responses to overcome the worsening insulin resistance in treatment-naïve newly-diagnosed T2DM patients. Disclosure S.Chong: None. N.Sukor: None. S.A.Robert: None. K.Ng: None. N.A.Kamaruddin: Advisory Panel; Zuellig Pharma Holdings Pte. Ltd., Other Relationship; American Association of Clinical Endocrinologists, Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk. Funding National University of Malaysia (GUP-2017-066); Malaysian Endocrine & Metabolic Society (L12-MEMS6)

1299-P: Predictors of Glucagon-Like Peptide-1 Responses following OGTT in Treatment-Naïve Type 2 Diabetes Mellitus among Three Ethnic Groups in Malaysia

Introduction: Predictors of glucagon-like peptide-1 (GLP-1) responses following OGTT in treatment-naïve type 2 diabetes mellitus (T2DM) have not been fully elucidated. In this respect, we aim to investigate the various predictors of GLP-1 responses following OGTT in treatment-naïve T2DM. Aim: To assess the clinical and biochemical predictors of GLP-1 responses following OGTT in treatment-naïve T2DM among three ethnic groups in Malaysia. Methods : Thirty-one treatment-naive T2DM subjects underwent a 75-g OGTT. Total GLP-1 concentrations were measured at 0, 30 and 120 min. By using area under the curve (AUC) for GLP-1 (AUCGLP-1) as an index of GLP-1 secretory response, predictors of GLP-1 responses following OGTT were assessed using multiple linear regression analysis. Results: Majority of the treatment-naïve T2DM patients were newly-diagnosed (n=28, 96.6%). The GLP-1 levels at 0, 30- and 120-min were 25.59 ± 10.87 pmol/L, 46.86 ± 18.36 pmol/L and 27.02 ± 13.37 pmol/L respectively. There was a positive correlation between increasing age and AUCGLP-1 (Β = 8.55, p<0.001). Male had higher GLP-1 response to OGTT than female (Β = -303.04, p<0.001). The Indian ethnicity exhibited higher GLP-1 secretion than the Malays (Β = 244.17, p<0.001). Fasting insulin was positively correlated with AUCGLP-1 (Β = 8.73, p=0.001). AUCGLP-1 was positively correlated with increased systolic blood pressure (Β = 3.65, p=0.03), total cholesterol (Β = 174.32, p=0.004) and LDL-cholesterol (Β = 202.35, p=0.002). Conclusions: Older age, male and Indian ethnicity were independent predictors of GLP-1 responses following OGTT in treatment-naïve T2DM. The positive correlation between risk factors associated with insulin resistance and GLP-1 suggested that these risk factors are responsible for driving GLP-1 secretion. Disclosure S.Chong: None. N.Sukor: None. S.A.Robert: None. K.Ng: None. N.A.Kamaruddin: Advisory Panel; Zuellig Pharma Holdings Pte. Ltd., Other Relationship; American Association of Clinical Endocrinologists, Speaker's Bureau; AstraZeneca, Boehringer-Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk. Funding National University of Malaysia (GUP-2017-066); Malaysian Endocrine & Metabolic Society (L12-MEMS6)

A low-calorie diet raises β-aminoisobutyric acid in relation to glucose regulation and leptin independent of exercise in women with obesity.

Introduction: β-aminoisobutyric acid (BAIBA) is a suggested cytokine secreted from skeletal muscles that regulates insulin sensitivity, pancreatic function, and fat oxidation. However, no studies to date have examined if a low-calorie diet (LCD) or LCD + with interval exercise (LCD + INT) differentially raises BAIBA. The purpose was to examine if LCD or LCD + INT raises circulating BAIBA in relation to cardiometabolic health. Methods: For this, twenty-three women with obesity were randomized to either 2-weeks of LCD (n = 12, 48.4 ± 2.5y, 37.84 ± 1.5kg/m2; ∼1200kcal/day) or LCD + INT (n = 11, 47.6 ± 4.3y, 37.9 ± 2.3kg/m2; ∼60min/d of INT alternating 3min of 90% and 50% HRpeak), with matched energy availability. Fasting BAIBA and adipokines along with glucose, insulin, C-peptide, and FFA after every 30min up to 120min were obtained during a 75g OGTT to estimate total area under the curve (tAUC), insulin sensitivity (SIIS), pancreatic function [disposition index (DI)], and hepatic insulin clearance (HIC). Fuel use (indirect calorimetry) was tested at 0, 60, and 120min of the OGTT along with fitness (VO2peak) and body composition (BodPod). Results: Both treatments lowered body weight (p < 0.001) and leptin (p < 0.001) but raised BAIBA (p = 0.007) and insulin sensitivity (p = 0.02). LCD + INT increased VO2peak (p = 0.02) and REE tAUC120min (p = 0.02) while LCD and LCD + INT decreased carbohydrate oxidation (CHOox) tAUC120min (p < 0.001). Increased BAIBA associated with reduced weight (r = -0.67, p < 0.001), leptin (r = -0.66, p = 0.001), CHOox tAUC120min (r = -0.44, p = 0.03) and DImuscle120min (r = -0.45, p = 0.03), but elevated HIC120min (r = 0.47, p = 0.02). Discussion: Concluding, LCD and LCD + INT increased BAIBA in relation to reduced body weight and pancreatic function in women with obesity. This suggests energy deficit is a key factor regulating circulating BAIBA.

Weight retention and glucose intolerance in early postpartum after gestational diabetes.

To determine risk factors for early postpartum weight retention (PPWR) and glucose intolerance (GI) in women with gestational diabetes (GDM). Prospective, multicenter (n=8) cohort study in 1201 women with a recent history of GDM. Pregnancy and postpartum characteristics, and data from self-administered questionnaires were collected at the 6-16 weeks postpartum 75g OGTT. Of all participants, 38.6% (463) had moderate (>0 and ≤5 kg) and 15.6% (187) had high (>5kg) PPWR. Independent predictors for early PPWR were excessive gestational weight gain (GWG), lack of breastfeeding, higher dietary fat intake, insulin use during pregnancy, multiparity, lower prepregnancy BMI, and lower education degree. Compared to PPWR <5 kg, women with high PPWR had a more impaired postpartum metabolic profile, breastfed less often, had higher depression rates [23.1% (43) vs. 16.0% (74), p=0.035] and anxiety levels, and lower quality of life. Of all participants, 28.0% (336) had GI [26.1% (313) prediabetes and 1.9% (23) diabetes]. Women with high PPWR had more often GI compared to women without PPWR [33.7% (63) vs. 24.9% (137), p=0.020]. Only 12.9% (24) of women with high PPWR perceived themselves at high risk for diabetes but they were more often willing to change their lifestyle than women with moderate PPWR. Modifiable risk factors such as lifestyle, prepregnancy BMI, GWG, and mental health can be used to identify a subgroup of women with GDM at the highest risk of developing early PPWR, allowing for a more personalized follow-up.

Hyperglycaemia in pregnancy: knowledge and correlates amongst antenatal care providers in healthcare facilities in Jos, Nigeria.

Antenatal healthcare providers' (AHPs) knowledge about hyperglycaemia in pregnancy (HIP) and its screening best practices affect the management of affected pregnant women. We assessed the knowledge of HIP and associated factors amongst first line AHPs. This descriptive cross-sectional study involved 188 Doctors, Nurses and Community Health providers directly involved in providing antenatal care at all levels of health care in Jos, Plateau State, Nigeria, selected through total sampling technique. A total of 103 AHPs (54.8%) were females. The mean knowledge score (SD) score was 17.0+/-5.5 (out of 30). Only 93 (49.5%) had a good knowledge of HIP (Knowledge score ≥18). Only 88 (46.8%) could correctly identify 75g OGTT or 100g OGTT as diagnostic tests for GDM. Gender, category of hospital, level of care of the institution and job designation were significantly associated with knowledge of HIP after bivariate analysis (p < 0.05). After multivariate analysis using logistic regression analysis, only the category of institution and job designation were independently associated with knowledge of HIP. The general level of knowledge of HIP among AHPs is average but awareness of testing and management guidelines is very poor hence the need for regular updates for health professionals.

Relation of Aortic Waveforms with Gut Hormones following Continuous and Interval Exercise among Older Adults with Prediabetes.

Prediabetes raises cardiovascular disease risk, in part through elevated aortic waveforms. While insulin is a vasodilatory hormone, the gut hormone relation to aortic waveforms is less clear. We hypothesized that exercise, independent of intensity, would favor aortic waveforms in relation to gut hormones. Older adults (61.3 ± 1.5 yr; 33.2 ± 1.1 kg/m2) with prediabetes (ADA criteria) were randomized to undertake 60 min of work-matched continuous (CONT, n = 14) or interval (INT, n = 14) exercise for 2 wks. During a 180 min 75-g OGTT, a number of aortic waveforms (applanation tonometry) were assessed: the augmentation pressure (AP) and index (AIx75), brachial (bBP) and central blood pressure (cBP), pulse pressure (bPP and cPP), pulse pressure amplification (PPA), and forward (Pf) and backward pressure (Pb) waveforms. Acylated-ghrelin (AG), des-acylated ghrelin (dAG), GIP, and GLP-1active were measured, and correlations were co-varied for insulin. Independent of intensity, exercise increased VO2peak (p = 0.01) and PPA120min (p = 0.01) and reduced weight (p < 0.01), as well as AP120min (p = 0.02) and AIx75120min (p < 0.01). CONT lowered bSBP (p < 0.02) and bDBP (p < 0.02) tAUC180min more than INT. There were decreases dAG0min related to Pb120min (r = 0.47, p = 0.03), cPP120min (r = 0.48, p = 0.02), and AP120min (r = 0.46, p = 0.02). Declines in AG tAUC60min correlated with lower Pb120min (r = 0.47, p = 0.03) and cPP120min (r = 0.49, p = 0.02) were also found. GLP-1active 0min was reduced associated with lowered AP180min (r = 0.49, p = 0.02). Thus, while CONT exercise favored blood pressure, both intensities of exercise improved aortic waveforms in relation to gut hormones after controlling for insulin.

Role of vitamin D on gestational hypertension, diabetes mellitus, timing and mode of delivery.

To determine the efficacy of VD in preventing the development of gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH). The secondary purpose is to investigate the effect of VD on the mode and time of delivery. A vitamin D value of <20 ng/mL during pregnancy is considered a deficiency according to the Endocrine Society, and 400-600 IU/day VD replacement is recommended. Forty patients whose serum VD levels were below 20 ng/mL during routine pregnancy follow-up and who were planned for VD replacement therapy were included in the study. They were divided into two equal groups with 20 patients in each group. Twenty pregnant women with serum VD levels greater than 20 ng/mL were considered as the control group. While 400 IU/day VD replacement was applied to the patients in Group 1, 600 IU/day VD was given to Group 2. Group 3 consisted of control patients who did not undergo VD replacement. VD replacement was continued from the 14th week of pregnancy until delivery. Each group of participants was screened with a 50-g GCT at 24-28 weeks of gestation. Following 50-g GCT if serum glucose level was found >140 mg/dL, patients underwent 100-g OGTT. GDM was diagnosed in the presence of at least two of the following results: fasting serum glucose ≥92 mg/dL and/or 1-hour glycemia ≥180 mg/dL, and/or 2-hour glycemia ≥153 mg/dL. PIH was defined as systolic blood pressure >140 mmHg and diastolic blood pressure >90 mmHg. Patients in each group delivered by cesarean section or normal vaginal route. In addition to the incidence of PIH and GDM, the time and mode of delivery were recorded. PIH was detected in two patients in each of the 400 IU/day and 600 IU/day vitamin D replacement groups (10%). In the control group, PIH developed in 3 patients (15%). Although PIH was detected in an extra case in the control group, no significant difference was found between the replacement group and the control group in terms of PIH (p<0.44). While GDM was not detected in the 400 IU/day vitamin D group, GDM was detected in one patient (5%) in the 600 IU/day vitamin D group. No case of GDM was found in the control group either. There was no significant difference between the VD replacement and the control groups in terms of GDM rates. No significant difference was found between the VD replacement and the control groups in terms of mode of delivery. While the C/S ratio was 65% in the 400 IU/day vitamin D group, this ratio was 75% in the 600 IU/day vitamin D group. There was an insignificant trend of increase in C/S ratios in the group given 600 IU/day of vitamin D. The C/S ratio of the control group, which could not be given VD replacement, was found to be 70%. VD replacement therapy during pregnancy does not prevent the development of PIH and GDM, and does not significantly contribute to the time and mode of delivery.

PMON132 Biochemical and Radiologic Discordance in the Post-operative Surveillance of a Filipino Patient With Acromegaly

Abstract Background Trans-sphenoidal surgery is the recommended initial therapy in patients with acromegaly. Early cure rate is 80-90% for microadenomas and &amp;lt;50% for macroadenomas. The goal is a serum IGF-1 that is normal for age and gender with GH &amp;lt;1mcg/L by immunoradiometric or chemiluminescent assays. Clinical Case A 71-year old male who consulted for diabetes management was eventually worked up for acromegaly He presented with coarsened facial features, hoarse voice, frontal bossing and enlarged hands and feet. Medical history includes hypertension, hepatosplenomegaly, colonic polyposis, obstructive sleep apnea and nasal septal deviation post-repair. Laboratory tests showed elevated IGF-1 (566.15, n: 91-282 ng/ml) and non suppressed GH after 75g OGTT (50.1, n&amp;lt;2.47 ng/mL). Pituitary hormonal profile showed normal prolactin (98.13, n: 86-324 mIU/L), TSH (1.63, n: 0.27-4.2 uIU/ml), FT4 (17.78, n: 12-22 pmol/L), ACTH (35, n: 7.2-63.3 pg/mL), Cortisol (387.4, n: 172-497 nmol/L), LH (4.56, n: 1.7-8.6 mIU/mL) and FSH (15.4, n: 1.5-12.4 mIU/mL). Contrast-enhanced pituitary MRI revealed a 1.5×2.0×1.9 cm pituitary macroadenoma with compression of the optic chiasm. Patient underwent trans-phenoidal surgery and excision of the tumor. Histopathology revealed a homogenous cells in sheets, acidophilic, densely granular and consistent with sommatotrophs, mammotrophs and sommatomammotrophs. Post-procedure GH was normal (2.731 ng/mL). Two months post-operatively, there was a significant decrease in both GH (1.84 ng/mL) and IGF-1 levels (258.59 ng/mL) while other pituitary hormones all within reference range. Contrast-enhanced pituitary MRI at 2 months showed interval surgical removal of the mass, with decompression of the optic chiasm. Clinically, there was softening of facial features and improvement in his voice. His cranial did not show pituitary mass. However, repeat GH after 75g OGTT (0.37 ng/mL, 2.3 ng/mL) and IGF-1 (361 ng/mL, 523,6 ng/mL) at 9 and 12 months post-surgery, respectively, were found above the reference range. Conclusion Discordance between anatomic and biochemical testing must be investigated thoroughly considering pulsatile hormone secretion, comorbidities and possible microscopic residual disease. Testing with the same assay is important to avoid inter-assay variability. Post-operative monitoring should be done at 12 weeks as it may take time for IGF-1 to normalize. If IGF-1 remains elevated, medical, surgical, radiotherapy, or combination may be considered especially in the presence of an identifiable focus. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

LBODP044 Effects Of Dietary Supplementation On Progression To Type 2 Diabetes Single Center Randomized Double-blind Placebo-controlled Trial An Interim Analysis At 24 Weeks

Abstract Objectives To examine the effect of dietary supplements on diabetic risk, blood glucose level and lipid profiles. Methods A randomized, double-blinded, placebo-controlled study was conducted at Rajavithi Hospital. Participants with prediabetes were randomly allocated to three arms of dietary supplements: placebo (PL) or curcumin plus fish oil and vitamin D (CFD), or curcumin plus fish oil (CF) for 24 weeks. Primary outcomes of the trial were progression to overt diabetes and glycemic indices (fasting plasma glucose, 75-g OGTT 2-h plasma glucose or HbA1C). Secondary outcomes were body weight change, BMI and lipid profiles. Results A total of forty-seven participants (PL, n = 16; CFD, n = 15; CF, n = 16) were included in the study. At 24 weeks, the intervention groups significantly lowered the progression of type 2 diabetes among prediabetes individuals, the interventions groups -0.77 ± 1.17, and 0.19 ± 1.28, the placebo group 0.64 ± 1.82, P value = 0. 046 (P&amp;lt;0. 05). However, the results failed to demonstrate the effect of dietary supplements on weight, BMI and blood chemistries. Conclusion The combined dietary supplements which contained curcumin-fish oil-vitamin D, lowered the risk of prediabetes progression to overt diabetes at six months follow up and well-tolerated among the participants. Keywords: dietary supplements, curcumin, fish oil, vitamin d, prediabetes Presentation: No date and time listed

Predictive and Prognostic Value of Plasma Zonulin for Gestational Diabetes Mellitus in Women at 24-28 Weeks of Gestation.

We aimed to examine the predictive and prognostic value of plasma zonulin for gestational diabetes mellitus (GDM) in women at 24-28 weeks of gestation. This retrospective study was carried out with pregnant women with GDM (n=98) and normal glucose tolerance (control group) (n=132). GDM was diagnosed according to American Diabetes Association (ADA) criteria with a one-step 75-g OGTT at 24-28 gestational weeks. Their serum zonulin levels measured during one-step 75-g OGTT and perinatal outcomes were compared, and the cut-off value of plasma zonulin for the prediction of GDM was calculated with receiver operating characteristic curve analysis. Plasma zonulin level was significantly higher in women with GDM compared to controls (28.8±24.9 and 7.3±11.3 ng/mL, respectively). According to logistic regression analysis, plasma zonulin levels and GDM were statistically significant. The plasma zonulin cut-off value was>45.2 ng/mL. The rate of cesarean section, the rate of meconium in the amniotic fluid, and the need for admission to the neonatal intensive care unit significantly differed between women with GDM and controls. In pregnant women with GDM, plasma zonulin increases, and with the cut-off level of>45.2 ng/mL, it can predict GDM with values of sensitivity and specificity levels significantly higher in pregnant women with GDM, suggesting that it can be used as a tool for its screening and early diagnosis.

Prediction of gestational diabetes mellitus in the first trimester: is it possible?

Objective: The aim of this study is to identify the first trimester markers that may be associated with gestational diabetes mellitus (GDM) and to evaluate whether those markers might be used for prediction of gestational diabetes or not. Methods: Pregnant women between 11 and 14 weeks of gestation applying to the university hospital between August 2018 and March 2019 were included in the study. Body mass index calculation and blood tests including complete blood count, TSH, T3, T4, HbA1c, uric acid, CRP, procalcitonin, PAPP-A and b-hCG levels were done during assessment followed by 50 grams of glucose challenge test between the 24 and 28 weeks of gestation for each woman. Patients with positive results were further evaluated with a 3-hour, 100-g OGTT. According to the diagnostic test results, the relationship between biochemical markers during the first trimester, BMI and GDM was statistically analyzed. Results: A hundred and eighty-two pregnant women participated in the study. Fifty-four women had positive glucose challenge test (GCT) results while 128 women had negative results. Pregnant women with positive GCT results underwent 3-hour, 100-g OGTT and, 24 pregnant women were diagnosed with GDM, while 158 pregnant women were considered healthy according to the results. There was no statistically significant difference between GDM and non-GDM groups in terms of age, height, TSH, T3, T4, b-hCG-mom, PAPP-A, PAPP-A-mom, uric acid and procalcitonin (p&gt;0.05). The mean body weight, body mass index and HbA1c levels were higher and b-hCG levels were lower in the GDM group compared to the non-GDM group, and these findings were statistically significant (p&lt;0.001). Conclusion: The use of first trimester markers in GDM prediction seems to have no significance. There is a need for extensive, randomized studies with universal criteria.

Hepatic Steatosis and High-Normal Fasting Glucose as Risk Factors for Incident Prediabetes.

ContextThe role of hepatic steatosis (HS) in the initial stages of developing type 2 diabetes remains unclear.ObjectiveWe aimed to clarify the impact of HS indexed by Fatty Liver Index (FLI) and high-normal fasting plasma glucose (FPG) as risk factors for incident prediabetes in a nonobese cohort.MethodsData from 1125 participants with ADA-defined normal glucose metabolism (median age 52 years; BMI 23.1 kg/m2) were used for retrospective analysis. In the entire population, correlation between normal FPG and FLI was evaluated by multiple regression adjusted for age and sex. Follow-up data from 599 participants in whom 75-g OGTT was repeated 3.7 years later showed that 169 developed prediabetes. This was analyzed by the multivariate Cox proportional hazards model.ResultsIn the entire population, FLI was positively correlated with FPG (P < 0.01): mean FLI increased from 15.8 at FPG 4.2 mmol/L to 31.6 at FPG 5.5 mmol/L. Analysis of the 599 participants (2061 person-years) by Cox model, adjusted for sex, age, family history of diabetes, ISIMATSUDA, and Stumvoll-1, clarified an increased risk of prediabetes with high-normal FPG and FLI. Risk was increased 2.2 times with FLI ≥ 16.5 vs FLI < 16.5, P < 0.001, and increased 2.1 times in participants with FPG ≥ 5.3 mmol/L, P < 0.001. Cutoff values (unadjusted) were obtained by ROC at the point of the largest Youden’s index using the entire range of the variables.ConclusionEven among nonobese individuals, HS indexed by FLI and a high-normal FPG (≥ 5.3 mmol/L) are risk factors for prediabetes, independently from insulin.

Increased fetal epicardial fat thickness: A reflecting finding for GDM and perinatal outcomes.

To study the value of fetal epicardial fat thickness (EFT) in gestational diabetes mellitus in the third trimester of pregnancy and its relationship with clinical parameters and perinatal outcomes. A total of 80 participants, including 40 with diagnosed GDM and 40 healthy pregnant women, were included in the study. Demographic data were obtained from medical records. Sonographic examinations were performed, such as amniotic fluid value, fetal biometric measurements, and Doppler parameters of the umbilical artery. Fetal EFT values were measured at the free wall of the right ventricle using a reference line with echocardiographic methods. Correlation tests were performed to evaluate the relationship between fetal EFT and clinical and perinatal parameters. p<.05 were interpreted as statistically significant. The fetal EFT value was statistically higher in the GDM group than in the control group (p: .000). Spearman and Pearson correlation tests revealed statistically significant but weak positive correlations between fetal EFT value, 1-h 100-g OGTT, birth weight, and BMI (r: .198, p: .047; r: .395, p: .012; r: .360, p: .042, respectively). The optimal fetal EFT threshold for predicting GDM disease was found as 1.55mm, with a specificity of 74.4% and sensitivity of 75.0%. Statistically significant differences between the two groups in umbilical artery Doppler resistance index (RI), pulsatility index (PI), and systolic/diastolic ratio (S/D) were not found (p: .337; p: .503; p: .155;). BMI and amniotic fluid volume were higher in the GDM group compared to the control group (p: .009; p<.01). This study demonstrated that increased fetal EFT may occur as a reflection of changes in glucose metabolism in intrauterine life. Future studies with larger series, including the study of neonatal metabolic parameters, will contribute to the understanding of the importance of fetal EFT in determining the metabolic status of the fetus.

Sequential Screening Strategy in Early, Middle, and Late Pregnancy in Women at High Risk of Hyperglycemia.

BackgroundHyperglycaemia in pregnancy (HIP) is closely associated with short- and long-term adverse fetal and maternal outcomes. However, the screening and diagnostic strategies for pregnant women with risk factors for HIP are not set. This prospective study aimed to explore a screening strategy for women at high risk for HIP.MethodsA total of 610 pregnant women were divided into experimental (n=305) and control (n=305) groups. Pregnant women underwent a 75-g OGTT in early (<20 weeks), middle (24–28 weeks), and late pregnancy (32–34 weeks) in the experimental group and only in middle pregnancy in the control group. The general conditions, HIP diagnosis, and perinatal outcomes of the two groups were compared.ResultsIn the experimental group, HIP was diagnosed in 29.51% (90/305), 13.44% (41/305), and 10.49% (32/305) of patient in early, middle, and late pregnancy, respectively. The total HIP diagnosis rate was significantly higher in the experimental group (53.44% vs. 35.74%, P<0.001). Multivariate logistic regression analysis revealed that previous gestational diabetes mellitus (GDM) (odds ratio, OR=9.676, P<0.001), pre-pregnancy body mass index (BMI) ≥23 kg/m2 (OR=4.273, P<0.001), and maternal age ≥35 years (OR=2.377, P=0.010) were risk factors for HIP diagnosis in early pregnancy. Previous GDM (OR=8.713, P=0.002) was a risk factor for HIP diagnosis in late pregnancy. No significant differences in perinatal clinical data were observed between the experimental and control groups. The gestational age at delivery was significantly earlier in the experimental subgroup with early-HIP than in the experimental and control subgroups with normal blood glucose (NBG). The weight gain during pregnancy was lower in the experimental early-HIP, middle-HIP, and control NBG subgroups.ConclusionsWe recommend sequential screening in early and middle pregnancy for high-risk pregnant women with maternal age ≥35 years or pre-pregnancy BMI ≥23 kg/m2, and in early, middle, and late pregnancy for high-risk pregnant women with a previous history of GDM.Trial RegistrationThis study was registered in the Chinese Clinical Trial Registry (no. ChiCTR2000041278).

933-P: Maternal Choices and Preferences for Screening Strategies of Gestational Diabetes Mellitus: A Discrete Choice Experiment

Aims: This study aimed to investigate maternal preferences for gestational diabetes mellitus (GDM) screening options in China to identify an optimal GDM screening strategy. Methods: Pregnant women at 24−28 gestational weeks were recruited from Shandong province, China. A discrete choice experiment (DCE) was conducted to elicit pregnant women’s preferences for GDM screening strategy defined by five attributes: number of blood draws, out-of-pocket costs, screening waiting-time, number of hospital visits, and positive diagnosis rate. A mixed logit model was employed to quantify maternal preferences, and to estimate the relative importance of included attributes in determining pregnant women’s preferences for two routinely applied screening strategies (“one-step”: 75g oral glucose tolerance test [OGTT] and “two-step”: 50g glucose challenge-test plus 75g OGTT) . Preference heterogeneity was also investigated. Results: N=287 participants completed the DCE survey. All five predefined attributes were associated with pregnant women’s preferences. Diagnostic rate was the most influential attribute (17.5% vs. 8.0%, OR: 2.89; 95%CI: 2.10−3.96) . When changes of the attributes of “two-step” to “one-step” strategies, the changes of women’s uptake probability from full “two-step” to “one-step” was positive with 71.3% (95%CI:52.2%-90.1%) , but no significant difference with the first step of “two-step” (-31.0%,95%CI:-70.2%-8.1%) . Conclusion: Chinese pregnant women preferred the “one-step” screening strategy to the full “two-step” strategy, but were indifferent between “one-step” and the first step of "two-step" strategies. A careful consideration of maternal preferences can assist clinical practitioners and healthcare policymakers in promoting GDM screening acceptability and compliance in rural China to achieve better health outcomes for mothers and babies. Disclosure T.Xu: None.

1441-P: Fidelity of BMI and Waist Circumference as Adiposity Measures in White and Black Adults

Background: Body mass index (BMI) and waist circumference (WC) are routine clinical estimates of obesity. We tested the fidelity of BMI and WC against direct body fat measures in Black (B) vs. White (W) Americans. Subjects and Methods: We analyzed the relationship between BMI vs. total fat, WC vs. trunk fat, and weight vs. lean fat free mass (FFM) in healthy B and W adults. Assessments included clinical exam, biochemistries and a 75-g OGTT. All subjects had normal fasting and 2-hr OGTT glucose levels. Total fat mass, trunk fat mass and FFM were measured using DXA. Results: The participants (n=376; 217 B, 159 W) had an age range of 18-65 years and BMI range of 16.8-66.3 kg/m2 (mean 30.1) . The W vs. B values were: age 46.5 ± 10.5 vs. 42.5 ± 10.3 y, P=0.0003; BMI 28.8 ± 6.78 vs. 31.2 ± 7.40, P=0.0015; total fat mass 29.4 ± 13.21 vs. 31.8 ± 13.76 kg, P=0.11; trunk fat mass 14.77 ± 6.96 vs. 15.34 ± 7.50 kg, P=0.48; FFM 50.12 ± 11.9 vs. 53.± 11.74 kg, P= 0.03. There were tight correlations between adiposity measures: total fat and BMI (r=0.90 in W, 0.92 in B) ; trunk fat and WC (r=0.85 in W, 0.82 in B) ; FFM and weight (r=0.83 in W, 0.87 in B) , with heterogeneity by sex and race. White men and women (vs B) tended to have more body fat per unit BMI or WC and less FFM per unit weight. We assessed 3 integrated ratios (total Fat/BMI, trunk Fat/Waist, FFM/Weight) by sex and race. Total fat/BMI was higher (P&amp;lt;0.0001) in W vs. B (men: 0.946 ± 0.159 vs. 0.833 ± 0.210; women: 1.36 ± 0.189 vs. 1.25 ± 0.164) . Trunk fat/waist was higher in W vs. B men (0.294 + 0.043 in W vs. 0.257 + 0.072, P=0.0046) but similar in women. In contrast, FFM/weight ratio showed no race disparities (men: 0.696 ± 0.055 vs. 0.678 ± 0.200; women: 0.586 ± 0.1vs 0.579 ± 0.076) . The proportion with &amp;gt;3 metabolic syndrome markers was 24.5% in W and 15.7% in B. Conclusion: Among otherwise healthy subjects with a wide BMI range, African Americans had lower body fat than Whites. This finding that argues for ethnic-specific BMI cut-offs for obesity classification. Disclosure Z.Liu: None. A.A.Patel: None. S.Dagogo-jack: Consultant; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Pharmaceuticals, Inc., Medtronic, Merck &amp; Co., Inc., Sanofi. Funding American Diabetes Association (7-07-MN-13) ; NIH, R01 DK067269

106-OR: Fetal Sex Influences Maternal Insulin and Glucose Metabolism in Pregnancy

Aims and Hypothesis: Women carrying a male fetus are suggested to have altered maternal glucose and insulin dynamics and increased rates of GDM, but current literature remains inconclusive. We aimed to determine the relationship between fetal sex and maternal glucose and insulin metabolism and assess whether inclusion of fetal sex improves prediction of IADPSG GDM. Methods: Using blinded data from five Hyperglycaemia and Adverse Pregnancy Outcome study centres, we examined maternal metabolic data at mean gestational week 28 in 6337 untreated women. Stratifying women by either male (n = 3273) or female fetus (n = 3064) we analysed data from the 75g OGTT, estimates of insulin secretion (Stumvoll first phase) and sensitivity (Matsuda index) and their product (oral Disposition index) using multiple linear regression analysis. To assess the relationship and predictive ability of fetal sex and GDM we utilised multiple logistic regression and receiver operating characteristic curve analysis. Results: Women carrying a male fetus were found to have a modest increase in fasting plasma glucose (4.52 vs. 4.44 mmol/L; P=0.008) and 1 h glucose (7.57 vs. 7.46 mmol/L; P=0.015) during OGTT which translated into an overall increase in the OGTT z score (0.vs. 0.02; P=0.005) . The Matsuda (β: -0.06; 95% CI [-0.10, -0.02]; P=0.008) and oral Disposition index (β: -0.07; 95% CI [-0.11, -0.02]; P=0.005) were significantly reduced in women carrying a male fetus after correction for established maternal clinical risk factors. Women carrying a male fetus were not at higher odds of developing GDM in adjusted (aOR: 1.04; 95% CI [0.9, 1.19]; P=0.6) or unadjusted (OR: 1.09; 95% CI [0.96, 1.25]; P=0.16) models. Conclusion/interpretation: The male fetus is associated with increased maternal fasting and postprandial glucose with concomitant decreased insulin sensitivity and β-cell compensation. The alterations in maternal glucose and insulin dynamics associated with having a male fetus does not translate into a clinical diagnosis of GDM. Disclosure T.P.Mullins: None. K.S.Gibbons: None. L.R.Madsen: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. W.H.Tam: None. P.Catalano: None. D.A.Sacks: None. H.L.Barrett: None. D.Mcintyre: None.