2-hour Oral Glucose Tolerance Test Research Articles

Association between polycystic ovarian morphology and insulin resistance in women with polycystic ovary syndrome.

The aim of the present study was to determine whether polycystic ovarian morphology (PCOM) is related to insulin resistance in women with polycystic ovary syndrome (PCOS). A total of 147 Korean women aged 18 to 35 years and diagnosed with PCOS were included in this study. Fasting blood tests and standard 2-hour 75-g oral glucose tolerance tests were performed for all participants. PCOM-related parameters including total antral follicle count (TFC) and total ovarian volume (TOV) were assessed using transvaginal or transrectal ultrasonography. Correlation analysis was conducted to assess the relationships of TFC and TOV with insulin resistance-related clinical and biochemical parameters using Spearman rank correlation coefficients and linear regression analysis, with partial correlations used to control for the effects of confounding covariates. Fasting insulin levels, low-density lipoprotein levels, and insulin sensitivity assessment indices (ISAIs) were significantly correlated with TFC, but neither postprandial blood glucose levels nor insulin levels were significantly associated with TFC. No insulin resistance-related parameter was significantly correlated with TOV. These results did not change after adjustments for other anthropometric covariates. Fasting insulin and some ISAIs differed significantly between groups categorized by the median TFC value (TFC ≤54 and TFC >54). TFC, but not TOV, was found to be related to fasting insulin resistance-related parameters in women with PCOS.

Glucose intolerance is associated with resting heart rate among individuals without diabetes

Elevated resting heart rate is associated with cardiovascular diseases and all-cause mortality. Unmanaged diabetes is associated with high blood pressure and high resting heart rate. Persistent high blood glucose levels in diabetes is known to contribute to the dysfunction of the autonomic nervous system including cardiovascular autonomic nerve fibers leading to higher resting heart rate, heart failure and stroke. In a population without diabetes, however, there is limited knowledge about the relationship between glucose tolerance and indicators of cardiovascular health, therefore, the purpose of the study was to determine how glucose intolerance is associated with resting heart rate and blood pressure in individuals without diabetes. We hypothesized that glucose intolerance will be associated with resting heart rate and blood pressure in a healthy population without diabetes. Eighty five (32 males, 53 females) individuals without diabetes from the border region of El Paso participated in this study (age 26.69±9.45years; BMI 27.85±6.45kg/m2; fasting blood glucose 95.38±10.09mg/dL; resting heart rate 66.15±10.54 bpm; systolic blood pressure 109.2±11.74 mmHg and diastolic blood pressure 71.24±9.03 mmHg). Following an overnight fast of at least 8 hours, resting heart rate systolic blood pressure and diastolic blood pressure were measured with a sphygmomanometer. Fasting blood glucose was measured and a 3-hour oral glucose tolerance test (OGTT) was performed by consuming 75 grams of glucose drink and measuring blood glucose at 15, 30, 90, 120, 150 and 180 minutes after the glucose consumption via a handheld glucometer. Glucose tolerance was assessed by calculating glucose area under the curve (AUC) during OGTT. Spearman’s correlations were performed at 0.05 alpha to determine the associations. Glucose area under the curve, AUC positively correlated with resting heart rate (r=0.39, p=0.0005) whereas fasting blood glucose did not (r=0.02, p=0.9). Blood glucose concentrations at 15 minutes (r=0.10, p=0.4), 30 minutes (r=0.07, p=0.6), and 60 minutes (r=0.2, p=0.1) did not correlate with resting heart rate while blood glucose concentrations at 90 minutes (r=0.3, p=0.02), 120 minutes (r=0.35, p=0.002), 150 minutes (r=0.33, p=0.003), and 180 minutes (r=0.29, p=0.01) during OGTT positively correlated with resting heart rate. Glucose area under the curve was not associated with neither systolic (r=-0.02, p=0.9) nor diastolic (r=0.2, p=0.2) blood pressures. Fasting blood glucose was not associated with neither systolic (r=0.2, p=0.2) nor diastolic (r=0.1, p=0.4) blood pressure. Glucose intolerance rather than fasting blood glucose is reflective of elevated resting heart rate among a healthy population without diabetes. Dodson Grant 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.

Carbohydrate Intake and Oral Glucose Tolerance Test Results in the Postpartum Period.

The American Diabetes Association (ADA) recommends a 3-day preparatory diet prior to a diagnostic oral glucose tolerance test (OGTT), a test often recommended in postpartum individuals with a history of gestational diabetes (GDM). Evaluate the relationship between carbohydrate intake and OGTT glucose in 2 cohorts of postpartum individuals. We performed analyses of postpartum individuals from 2 prospective studies with recent GDM (Balance after Baby Intervention, BABI, n = 177) or risk factors for GDM (Study of Pregnancy Regulation of INsulin and Glucose, SPRING, n = 104) .We measured carbohydrate intake using 24-hour dietary recalls (SPRING) or Food Frequency Questionnaire (BABI) and performed 2-hour 75-g OGTTs. The main outcome measure was 120-minute post-OGTT glucose. There was no relationship between carbohydrate intake and 120-minute post-OGTT glucose level in either study population (SPRING: β = 0.03, [-5.5, 5.5] mg/dL, P = .99; BABI: β = -3.1, [-9.5, 3.4] mg/dL, P = .35). Adding breastfeeding status to the model did not change results (SPRING β = -0.14, [-5.7, 5.5] mg/dL, P = .95; BABI β = -3.9, [-10.4, 2.7] mg/dL, P = .25). There was, however, an inverse relationship between glycemic index and 120-minute post OGTT glucose (BABI: β = -1.1, [-2.2, -0.03] mg/dL, P = .04). Carbohydrate intake is not associated with post-OGTT glucose levels among postpartum individuals. Dietary preparation prior to the OGTT may not be necessary in this population.

Development and validation of a multivariable genotype-informed gestational diabetes prediction algorithm for clinical use in the Mexican population: insights into susceptibility mechanisms

IntroductionGestational diabetes mellitus (GDM) is underdiagnosed in Mexico. Early GDM risk stratification through prediction modeling is expected to improve preventative care. We developed a GDM risk assessment model that integrates...

Associations between pregnancy glucose measurements and risk of preterm birth: a retrospective cohort study of commercially insured women in the United States from 2003 to 2021

To investigate associations between glucose measurements during pregnancy and risk of preterm birth (PTB). Retrospective cohort study of commercially insured women with singleton live births in the United States from 2003 to 2021 using longitudinal medical claims, socioeconomic data, and eight glucose results from different fasting and post-load tests performed between 24 and 28 weeks of gestation for gestational diabetes screening. Risk ratios of PTB (<37 weeks) were estimated via Poisson regression for z-standardized glucose measures. Non-linear relationships for continuous glucose measures were examined via generalized additive models. Elevations in all eight glucose measures were associated with increased risk (adjusted risk ratio point estimates: 1.05-1.19) of PTB for 196,377 women with non-fasting 50-gglucose challenge test (one glucose result), 31,522 women with complete 100-g, 3-hour fasting oral glucose tolerance test (OGTT) results (four glucose results), and 10,978 women with complete 75-g, 2-hour fasting OGTT results (three glucose results). Associations were consistent after adjusting for and stratifying by sociodemographic and clinical factors. Substantial non-linear relationships (U-, J-, and S-shaped) were observed between several glucose measurements and PTB. Elevations in various glucose measures were linearly and non-linearly associated with increased PTB risk, even before diagnostic thresholds for gestational diabetes.

Cost-effectiveness of Strategies for Postpartum Glucose Intolerance Testing

Background Abnormal glucose metabolism after gestational diabetes mellitus can persist postpartum. This study compares the cost and effectiveness of 4 postpartum glucose intolerance screening strategies and their influencing variables. Methods A decision model compared 4 screening strategies: Fasting capillary glucose test (FCG) 24–72 hours postpartum (inpatient FCG) alone (strategy 1); Inpatient FCG plus 2-hour oral glucose tolerance test (OGTT) (strategy 2) or plus home FCG testing (strategy 3) at 4–12 weeks postpartum; No screening (strategy 4). Clinical probabilities and costs were obtained from institutional data, the literature, retail prices, and reimbursement data. The primary outcome was the per-patient cost and effectiveness of detecting diabetes and prediabetes (i.e., disease) and the incremental cost-effectiveness ratio (ICER) between strategies. Effectiveness was the proportion of patients with disease detected. Sensitivity analyses examined parameter uncertainty and variance on primary outcome. Results The base case cost and effectiveness per strategy ranged from $1167 to $1330 and 0%–25%, respectively. Strategy 3 was the most effective and expensive strategy compared to strategy 2 (ICER $837), and remained so when &lt; 36% of patients completed the 2-hour OGTT and when the sensitivity of home FCG testing for detecting diabetes was &gt; 39%. Strategy 2 was more effective and expensive than strategy 1 (ICER $571). Limitations Our model underestimates the cost of a missed case by limiting the horizon to 1 year because of the available data. This is appropriate for our study perspective, but future study is needed to estimate the effect of a longer time horizon on model outcomes. Conclusion Home FCG testing offers a reasonable alternative to the 2-hour OGTT when adherence to the 2-hour OGTT is low. This model serves as a tool to guide postpartum glucose intolerance screening protocols, minimizing missed opportunities for diagnosis and early intervention.

Therapeutic Effect of Tinospora cordifolia (Willd) Extracts on Letrozole-Induced Polycystic Ovarian Syndrome and its Complications in Murine Model.

Tinosopora cordifolia (Willd) (TC) is commonly used in Ayurvedic medicine since long time for number of ailments and its preparations are also considered by food safety and standards authority of India as nutritional supplement. However the scientific evidence on its possible safety and efficacy in polycystic ovarian syndrome and associated complications was not studied in detail. The purpose of this investigation is to examine whether or not TC can have therapeutic effects on letrozole induced PCOS and related complications such as body weight, dyslipidaemia, glucose tolerance, hormonal regulation, insulin resistance and sensitivity, severity of PCOS and histopathological changes in ovary using mice animal model. Present study is a preclinical study involving laboratory animals. After verifying the absence of PCOS, the animals began receiving Letrozole, which lasted for 21 days. Fasting blood glucose (FBG), the oral glucose tolerance test (OGTT), triglycerides, cholesterol, and weight were recorded. The levels of hormones like oestrogen, progesterone, insulin, testosterone, luteinising hormone (LH) and follicle stimulating hormone (FSH), histopathology was carried out. The Institutional Animal Ethics Committee at DITU gave its clearance to the animal experimentation on July 10, 2021 (DITU/IAEC/21-22/07-06). The majority of cornified epithelial cells were seen in groups treated with TC extract during the estrous phase of the cycle. Mice exposed to TC retained normal body weight. FBG, 1- and 2-hour OGTT, triglyceride and cholesterol levels were all significantly improved by extracts. Estradiol, progesterone, testosterone, insulin, LH and FSH concentration were all corrected in TC-treated animals. The HOMA-IR, HOMA-Beta and QUICKI values were also corrected with TC extracts. The morphological and microscopic features of the ovary were also greatly enhanced. Based on these findings, we conclude that treating PCOS mice with TC extracts significantly ameliorates the disease and severity down to nil-to-moderate levels by reducing hyperinsulinemia, hyperandrogenism, dyslipidaemia, enhancing insulin sensitivity, correcting oestrogen, progesterone, LH and FSH levels via enhanced ovarian function. Further molecular and cellular level of study is recommended for further elaboration of mechanism of action. • Tinospora cordifolia satva, oil and hydroalcoholic extract were studied in letrozole-induced PCOS in mice model• Anti PCOS efficacy of 3 preparations studied with respect to their mechanism of action in detail• For the first time proposing method of calculating severity of PCOS in animal model• Tinospora cordifolia oil preparation completely reversed PCOS effect of letrozole and made them normal• Histopathological and morphological studies support the biochemical claims.

Glucose Homeostasis and Assessment of β-Cell Function by 3-hour Oral Glucose Tolerance (OGTT) in Patients with β-Thalassemia Major with Serum Ferritin below 1,000 ng/dL: Results from a Single ICET-A Centre.

The primary aim of this study was to evaluate retrospectively the glucose homeostasis and surrogate indices of insulin sensitivity and resistance, during a 3-hour oral glucose tolerance test (OGTT), in β-thalassemia major patients (β-TM) with serum ferritin (SF) below 1,000 ng/mL. The retrospective cohort study evaluated the medical records of 24 β-TM patients from 2010 to 2022. At the year of study the mean age of patients was 31.0 ± 4.1 (20-37.11) years; 13 (54.1%) were females. The most commonly used iron chelator was deferoxamine (DFO: 75%), followed by deferiprone (DFP:12.5%) and deferasirox (DFX: 12.5%). Insulin sensitivity and resistance indices were derived from OGTT. A liver iron concentration (LIC) < 3 mg/g d.w. and a global heart T2* value > 20 ms were considered as conservative cut-off values for insignificant iron overload (IOL). The mean SF levels in the whole study cohort population at the age of evaluation was 549.6 ± 232.3 ng/mL. Based on the SF levels, two groups were identified: Group A (N = 14) < 500 ng/mL and Group B (N=10) 500-1,000 ng/mL. Normal glucose tolerance (NGT) during OGTT was observed in 4 patients of Group A (28.5 %) and in 5 patients of Group B (50%) (P: 0.29). The remaining 15/24 patients (62.5%) had glucose dysregulation (GD). The mean age at starting iron chelation therapy (ICT) and the mean SF peak in Group A versus Group B were significantly higher in group A. The GD was associated with significantly attenuated IGI (first phase of insulin response) and impaired oral disposition index (oDI). Hypogonadotropic hypogonadism (HH) was the most common associated endocrine complication in both groups of patients. This study showed that efficient iron chelation monotherapy in patients with β-TM and SF < 1,000 ng/ml did not entirely prevent glucose metabolism disorders, abnormalities of insulin secretion and sensitivity, and development of acquired hypogonadism.

Real-world effectiveness of digital and group-based lifestyle interventions as compared with usual care to reduce type 2 diabetes risk - A stop diabetes pragmatic randomised trial.

No real-world randomised controlled trials (RCTs) have explored the effectiveness of lifestyle interventions based on multiple behaviour change theories and using combined digital and group-based face-to-face delivery to improve risk factors for type 2 diabetes (T2D). We conducted a one-year, multi-centre, unblinded, pragmatic RCT in primary healthcare using the habit formation, self-determination, and self-regulation theories among 2907 adults aged 18-74 years at increased T2D risk randomised into a digital lifestyle intervention group (DIGI, n = 967), a combined digital and group-based lifestyle intervention group (DIGI+GROUP, n = 971), and a control group receiving usual care (CONTROL, n = 969). We collected data on primary outcomes (diet quality by Healthy Diet Index [HDI], physical activity, body weight, fasting plasma glucose, 2-hour plasma glucose) and secondary outcomes (sedentary time, waist circumference, fasting plasma insulin) using digital questionnaires, clinical examinations, fasting blood tests, and 2-hour oral glucose tolerance tests. Main statistical analyses were performed using linear mixed-effects models adjusted for age, sex, and province. This RCT was registered with ClinicalTrials.gov, NCT03156478. The 2907 participants assigned were recruited between March 1st, 2017, and February 28th, 2018. Diet quality improved more (3·2 vs. 1·4 HDI points, p<0·001 for difference between groups, p'<0·001 for group*time interaction) and waist circumference tended to decrease more (-1·8 vs. -1·3 cm, p = 0·028, p' = 0·068) in DIGI+GROUP than in CONTROL. Fasting insulin tended to increase in CONTROL but not in DIGI (1·0 vs. 0·0 mU/L, p = 0·033, p' = 0·054) or in DIGI+GROUP (1·0 vs. 0·5 mU/L, p = 0·042, p' = 0·054). Good adherence to DIGI and DIGI+GROUP (≥median of 501 habits/year in DIGI, ≥5 of all 6 sessions in GROUP) was associated with improved diet quality and good adherence to DIGI with increased physical activity and decreased sedentary time. A lifestyle intervention based on multiple behaviour change theories and combined digital and group-based face-to-face delivery improves diet quality and tends to decrease abdominal adiposity and prevent an increase in insulin resistance. Good adherence improves the results of the interventions. Strategic Research Council at Academy of Finland, Academy of Finland, Novo Nordisk Foundation, and Finnish Diabetes Research foundation.

Utilization of a postpartum fasting blood glucose to predict impaired glucose tolerance in gestational diabetics

The Endocrine Society recommends a postpartum fasting blood glucose (FBG) be performed for patients with gestational diabetes mellitus (GDM) prior to hospital discharge to screen for ongoing hyperglycemia. Our objective was to evaluate if FBG correlates with the gold standard 6 week 2-hour oral glucose tolerance test (OGTT), and if so, define cut-offs for clinical use.

Study of the relation between serum omentin-1 levels and insulin resistance in gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is defined as carbohydrate intolerance of variable degree that begins or is first identified during pregnancy. Pregnant women with GDM have an increased risk of adverse metabolic outcomes. It is also associated with a higher likelihood of developing obesity and type 2 diabetes mellitus (T2DM) in a mother and her child. Omentin-1, a novel anti-inflammatory adipokine, is recognized as a main visceral secretory adipokine that may play a role in the context of both glucose homeostasis and insulin resistance (IR). Objective. To evaluate serum omentin-1 levels in GDM and its relationship with glycemic control, IR, and metabolic parameters. Patients and methods. This study included 75 patients who were divided into three groups: group I – 25 pregnant women with GDM diagnosed according to the WHO-2013 criteria, group II – 25 pregnant women with normal glucose tolerance, group III (control) – 25 healthy non-pregnant women. Fasting plasma glucose (FPG) levels, fasting plasma insulin (FPI) levels, fasting lipid profile, omentin-1, and HOMA-IR were measured in all patients, and a 2-hour 75-g oral glucose tolerance test (OGTT) was performed. Results. Between the groups of patients with and without IR, there was a statistically significant difference regarding serum omentin-1 levels, FPG, FPI, HOMA-IR, triglyceride (TG) levels, total cholesterol levels, as well as high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels (p &lt; 0.01). Serum omentin-1 levels had a negative association with FPI and HOMA-IR in all study groups. In addition, there was a strong negative correlation between serum omentin-1 and glycemic control, total cholesterol, TG, and LDL (p &lt; 0.01) and a strong positive correlation between omentin-1 and HDL (p &lt; 0.01) in all study groups. Conclusion. There was a strong negative correlation between omentin-1 and FPI levels, HOMA-IR, glycemic control, total cholesterol, TG, and LDL in all study groups. Moreover, serum omentin-1 levels were positively correlated with HDL. This suggests that omentin-1 has an essential role in IR during pregnancy. Key words: gestational diabetes mellitus, insulin resistance, omentin-1

GLUCOSE INTOLERANCE PREDICTS CARDIORESPIRATORY FITNESS IN A HEALTHY POPULATION

https://youtu.be/oIXKiLYDh6g BACKGROUND Aerobic capacity or maximum oxygen consumption rate (VO2max) is accepted as the single best indicator of cardiorespiratory fitness. VO2max is also an indicator of metabolic health and known as an all-cause mortality predictor. It is well established that glucose intolerance and insulin resistance in patients with diabetes is associated with decline in cardiorespiratory fitness. However, it is not clear if glucose intolerance is associated with poorer cardiorespiratory fitness in a population without diabetes. Therefore, the purpose of this study was to assess if glucose intolerance measured by oral glucose tolerance test (OGTT) is associated with cardiorespiratory fitness in a population without diabetes. METHODS Fifty one (30 males and 21 females) predominantly Mexican-American adults without diabetes (Age 26.1 ± 5.3 years; BMI 26.7 ± 4.2 kg/m2; fasting blood glucose 92.1 ± 10.0 mg/dL) from the border region of El Paso, TX participated in this study. VO2max was assessed using a standardized graded exercise test protocol on a treadmill with Parvomedics metabolic cart. Glucose tolerance was measured by a 3-hour OGTT preformed after a 12-hour overnight fast. Blood glucose measured at fasting and every 30 minutes after the ingestion of 75g of glucose drink during OGTT and glucose area under the curve was determined to access glucose tolerance. Pearson correlation analysis was performed at 0.05 significance level. RESULTS Glucose intolerance measured by glucose area under the curve was negatively correlated with VO2max (r = −0.40, p = 0.006). Additionally, blood glucose level during OGTT test at 120 min (r = −0.43, p = 0.003), 150 min (r = −0.36, p = 0.014), and 180 min (r = −0.32, p = 0.048) were also negatively associated with VO2max. However, fasting blood glucose was not associated with VO2max (r = −0.09, p = 0.56). CONCLUSION Poorer cardiorespiratory fitness is indicated by greater glucose intolerance and a greater surge of glucose level during an OGTT, but not fasting blood glucose in a population without diabetes.

β-Cell Function and Insulin Sensitivity in Youth With Early Type 1 Diabetes From a 2-Hour 7-Sample OGTT.

The oral minimal model is a widely accepted noninvasive tool to quantify both β-cell responsiveness and insulin sensitivity (SI) from glucose, C-peptide, and insulin concentrations during a 3-hour 9-point oral glucose tolerance test (OGTT). Here, we aimed to validate a 2-hour 7-point protocol against the 3-hour OGTT and to test how variation in early sampling frequency impacts estimates of β-cell responsiveness and SI. We conducted a secondary analysis on 15 lean youth with stage 1 type 1 diabetes (T1D; ≥ 2 islet autoantibodies with no dysglycemia) who underwent a 3-hour 9-point OGTT. The oral minimal model was used to quantitate β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI = φtotal × SI). Seven- and 5-point 2-hour OGTT protocols were tested against the 3-hour 9-point gold standard to determine agreement between estimates of φtotal and its dynamic and static components, SI, and DI across different sampling strategies. The 2-hour estimates for the disposition index exhibited a strong correlation with 3-hour measures (r = 0.975; P < .001) with similar results for β-cell responsiveness and SI (r = 0.997 and r = 0.982; P < .001, respectively). The agreement of the 3 estimates between the 7-point 2-hour and 9-point 3-hour protocols fell within the 95% CI on the Bland-Altman grid with a median difference of 16.9% (-35.3 to 32.5), 0.2% (-0.6 to 1.3), and 14.9% (-1.4 to 28.3) for DI, φtotal, and SI. Conversely, the 5-point protocol did not provide reliable estimates of φ dynamic and static components. The 2-hour 7-point OGTT is reliable in individuals with stage 1 T1D for assessment of β-cell responsiveness, SI, and DI. Incorporation of these analyses into current 2-hour diabetes staging and monitoring OGTTs offers the potential to more accurately quantify risk of progression in the early stages of T1D.

CLINICAL TRIAL OF METFORMIN FOR FRAILTY PREVENTION IN COMMUNITY-DWELLING OLDER ADULTS WITH PRE-DIABETES

Abstract Background Metformin may reduce frailty through improving insulin resistance and inflammation, aging mechanisms known to increase frailty risk. We describe a randomized clinical trial of metformin for frailty prevention in community-dwelling older adults with pre-diabetes and provide baseline characteristics of randomized participants. Methods Older adults (65+ years) are studied in this randomized, double-blind, placebo-controlled trial of metformin (max 2,000 mg/day). Pre-diabetes, required for inclusion, is assessed by 2-hour oral glucose tolerance test (OGTT). Individuals with glomerular filtration rate &amp;lt; 45 mL/min and frail individuals (Fried criteria) are excluded. The primary outcome, frailty, is assessed by both Fried criteria and frailty index. Secondary outcomes are physical function (short physical performance battery), lower extremity strength (Biodex), 6-minute walk, inflammation (systemic and skeletal muscle tissue), muscle insulin signaling, insulin sensitivity (insulin clamp), glucose tolerance (OGTT), and body composition (dual-energy x-ray absorptiometry). Subjects are followed for 2 years with safety assessments every 3 months and frailty assessment and OGTT every 6 months. Results 145 participants (49% female, 35% Hispanic) are randomized. Mean age is 71.8 ± 5.4 years (range: 65-88), body mass index is 30.8 ±6 kg/m2, and Hemoglobin A1c is 5.6 ±0.4%. Using Fried criteria, 63.4% have frailty score of 0, 30.3% a score of 1, and 6.2% a score of 2. Conclusion Metformin is being examined as a potential therapeutic agent to prevent frailty in older adults with pre-diabetes. Findings from this trial may have future implications for screening and treatment of pre-diabetes in older adults for the prevention of frailty.

Divergent metabolic phenotypes in two genetic syndromes of low insulin secretion

AimsWe examined the effect of growth hormone (GH) counter-regulation on carbohydrate metabolism in individuals with life-long diminished insulin secretion (DIS). MethodsAdults homozygous for the E180 splice site mutation of GHR [Laron syndrome (LS)], adults with a gain-of-function mutation in CDKN1c [Guevara-Rosenbloom syndrome (GRS)], and controls were evaluated for body composition, leptin, total and high molecular weight (HMW) adiponectin, insulin-like growth factor (IGF) axis molecules, and a 5-hour oral glucose tolerance test (OGTT), with measurements of glucose, insulin, glucagon, ghrelin, pancreatic polypeptide, gastric inhibitory peptide, glucagon-like peptide-1, peptide YY, and islet amyloid polypeptide (IAPP). ResultsBoth syndromic cohorts displayed DIS during OGTT. LS subjects had higher serum concentrations of total and HMW adiponectin, and lower levels of IGF-I, IGF-II, and IGF-Binding Protein-3 than individuals in other study groups. Furthermore, they displayed normal glycemic responses during OGTT with the lowest IAPP secretion. In contrast, individuals with GRS had higher levels of protein glycation, deficient glucose control during OGTT, and increased secretion of IAPP. ConclusionsA distinct metabolic phenotype depending on GH counter-regulatory status, associates with diabetes development and excess glucose-induced IAPP secretion.

Early pregnancy particulate matter exposure, pre-pregnancy adiposity and risk of gestational diabetes mellitus in Finnish primiparous women: An observational cohort study

AimsTo evaluate the association between the exposure of particulate matter with an aerodynamic diameter of ≤ 2.5μm (PM2.5) and with an aerodynamic diameter of ≤ 10μm (PM10) over the first trimester and the risk of gestational diabetes mellitus (GDM), and to assess whether maternal pre-pregnancy body mass index (BMI) modified the GDM risk. MethodsAll Finnish primiparous women without previously diagnosed diabetes who delivered between 2009 and 2015 in the city of Vantaa, Finland, composed the study cohort (N = 6189). Diagnosis of GDM was based on a standard 75 g 2-hour oral glucose tolerance test. The average daily concentration of PM2.5 and PM10 over the first trimester was calculated individually for each woman. The relationship between exposure of PM2.5 and PM10 and GDM was analyzed with logistic models. ResultsNo association was observed between the average daily concentrations of PM2.5 and PM10 over the first trimester and the GDM risk. When simultaneously taking BMI and PM10 into account both mean daily PM10 concentration (p = 0.047) and pre-pregnancy BMI (p = 0.016) increased GDM risk independently and an interaction (p = 0.013) was observed between PM10 concentration and pre-pregnancy BMI. ConclusionsEven globally low PM10 exposure level together with elevated maternal pre-pregnancy BMI seems to increase the GDM risk.

Glycemic Variability in Early Pregnancy May Predict a Subsequent Diagnosis of Gestational Diabetes.

This study examined the prospective association between CGM-derived glycemic variability (GV) and glycemic control (GC) parameters in the first and second trimester, with subsequent diagnosis of GDM in the early third trimester. In a longitudinal observational study, 60 study participants in the first trimester (9-13 weeks' gestation), and 53 participants (18-23 weeks' gestation) in the second trimester of pregnancy had CGM data extracted after a minimum of 8 days' wear time (up to 14 days). At 24-31 weeks' gestation, participants underwent a 75 g, 2-hour oral glucose-tolerance test as per IADPSG criteria to diagnose GDM. GV parameters examined in both first and second trimesters were mean amplitude of glycemic excursion (MAGE), standard deviation (SD), mean glucose, and coefficient of variation (CV). GC parameters measured were J-Index and percentage of time spent in glucose target ranges. The first trimester SD and MAGE were significantly higher in participants subsequently diagnosed with GDM (SD adjusted median 1.31 [interquartile range 1.2-1.3] mmol/L; MAGE 3.26 [3.2-3.3] mmol/L) than those who were not (SD 1.01 [0.9-1.0] mmol/L, MAGE 2.59 [2.4-2.6] mmol/L; p<0.05). Similarly, second trimester SD and MAGE were also significantly higher in participants subsequently diagnosed with GDM (SD 1.35 [1.3-1.4] mmol/L; MAGE 3.32 (3.31-3.41) mmol/L) than those who were not (SD 0.99 [0.98-1.01] mmol/L, MAGE 2.42 [2.42-2.55] mmol/L; p<0.05). Associations between SD and MAGE with GDM outcomes were adjusted for prepregnancy BMI and ethnicity. There were nonsignificant trends of higher J-Index scores in the first and second trimester, higher CV in the first trimester only, and higher mean in the second trimester only in participants diagnosed with GDM. Other study parameters measured were not significantly different between groups (p>0.003). Our study suggests the potential value of CGM-derived SD and MAGE in early pregnancy as potential predictors of subsequent GDM diagnosis.

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

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

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

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

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

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