Abnormal Glucose Tolerance Research Articles

A unique compound ameliorating endoplasmic reticulum stress and insulin resistance by binding to β tubulin.

Insulin is secreted by the pancreatic β-cells and regulates glucose uptake. Endoplasmic reticulum (ER) stress is known to induce insulin resistance. Identifying novel compounds, which can ameliorate ER stress and insulin resistance may be beneficial in the treatment of diabetes. Since treatment with compounds sourced from edible plants is relatively safe, this study aimed to identify a plant-derived potential compound attenuating insulin resistance. In the present study, we identified apigenin as an effective compound for ameliorating ER stress and insulin resistance. It attenuated ER stress-induced cell death and hepatic insulin resistance and improved abnormal glucose tolerance in a db/db diabetic model. The molecular mechanism of apigenin involved direct binding to β-tubulin and improving tubulin stability, thereby recovering insulin resistance and developing diabetes. To our knowledge, no known antidiabetic drugs are yet known to target β-tubulin. Edible plants containing apigenins, such as onions, oranges, and parsley, have been consumed since a long time. Therefore, the use of natural edible plants as a source may offer a safe strategy for the prevention of diabetes.

Retrospective cohort study on treatment outcomes of early vs late onset gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) affects roughly 14% of pregnancies, its prevalence is increasing, and it is associated with a significant risk of complications for both mother and offspring. A high proportion of women with GDM can be detected early in pregnancy. In Italy, early GDM screening occurs in a selective way, as it is performed only in the presence of important risk factors. It remains to be elucidated not only how and when to diagnose early GDM but especially whether to treat it. This study aimed to compare the characteristics and complications of early vs late GDM as assessed and treated in a real-world setting, according to the Italian guidelines of the Istituto Superiore di Sanità. We conducted a retrospective cohort study in women with GDM delivering singletons between 2017 and 2021. Women with early GDM had higher BMI and a higher proportion of Middle Eastern or African women. Early GDM was independently associated with the use of insulin (p < 0.001). It required also higher doses of insulin, possibly due to the higher BMI. Early GDM was also independently associated with higher post-prandial (after dinner) glucose levels during the 3° trimester (p = 0.04). Nevertheless, early GDM women achieved glucose targets and put on less weight during gestation. Early GDM was independently associated with preeclampsia (p = 0.05). Otherwise, there were no other differences between early and late GDM in terms of pregnancy complications. After delivery, early GDM was independently associated with abnormal glucose tolerance. Early GDM women exhibited more severe GDM features. However, after achieving recommended glucose and body weight targets, there were no substantial differences between early and late GDM in terms of pregnancy complications apart from preeclampsia. These data support diagnosis and treatment of women with early GDM.

Exogenous insulin does not reduce protein catabolism in pre-diabetic cystic fibrosis patients: A randomized clinical trial

BackgroundCystic Fibrosis (CF) patients historically suffered from undernutrition, infection and inflammation. Insulin insufficiency-related protein catabolism further compromised health. We aimed to determine whether insulin improves protein catabolism in CF youth with abnormal glucose tolerance (AGT). MethodsThis double-masked, placebo-controlled trial in CF youth age 10–25 with AGT who were in their usual state of health used triple-tracer stable-isotope methodology to measure protein turnover during a baseline test meal and after four weeks of insulin/placebo treatment. Healthy controls were assessed once. CF patients were randomized 1:1:1 to once-daily long-acting insulin (0.25 U/kg/d), three-times daily rapid-acting insulin (0.5 U/15gr carbohydrate), or injectable placebo. ResultsThirty CF patients completed the study. There were no differences in any measure of protein turnover between insulin- and placebo-treated subjects, including endogenous protein breakdown (primary study endpoint). In contrast to earlier studies, protein turnover in the 37 CF patients who completed the baseline meal was normal compared to 20 healthy controls. Meal isotope appeared in plasma earlier in CF than controls, suggesting more rapid gut emptying. The study was interrupted by the pandemic; futility analysis led to study discontinuation before the planned remaining 15 CF patients were studied. ConclusionsRecent advances in CF have led to remarkable clinical improvements. In this study, CF youth with AGT had normal protein catabolism at baseline. Pre-meal or daily basal insulin therapy, while safe and well tolerated, did not significantly enhance protein turnover and does not appear to be necessary in clinically stable patients prior to development of CFRD.

Effect of low-dose aspirin on mid-luteal phase uterine Artery blood flow in women with unexplained recurrent pregnancy loss

Objectives: As a possible therapy for recurrent pregnancy loss, this study sought to ascertain if low-dose aspirin was effective in increasing uterine artery blood flow. Study Design: This investigation was structured as a single-arm clinical trial Patients and Methods: All participants were aged 39 years or younger and had no prior or current indications of abnormal glucose tolerance, thyroid dysfunction, hyperprolactinemia, or Antiphospholipid antibody syndrome. Bilateral assessments of the Systolic/Diastolic (S/D) ratio, Resistive Index (RI), and Pulsatility Index (PI) were conducted in the chosen patients in the mid-luteal phase, before to and following a minimum of two weeks of low-dose aspirin administration. Results: The results of this investigation showed significant variation in the S/D and PI prior to and following aspirin administration. There was no discernible shift in RI. The analysis revealed a statistically significant reduction in uterine artery PI after aspirin administration (1.92±0.29) compared to the pre-treatment value (2.22±0.27), with a p-value of 0.0001. Remarkably, the pulsatility indices of the left and right uterine arteries did not significantly differ from one another. Conclusion: For women who have a history of miscarriages, low-dose aspirin can be recommended as an adjuvant therapy as it effectively improves uterine artery blood flow in these patients. However, more well-designed research is required to ascertain whether improved pregnancy outcomes are correlated with improved uterine perfusion. The current study supported the aspirin guideline for women with a history of recurrent miscarriages by showing that aspirin treatment resulted in a reduction in uterine artery PI.

Usefulness of urine dipstick test in the management of adverse events associated with immune checkpoint inhibitors.

The usefulness of urine dipstick tests (UDTs) in patients with diabetes has been reported. The aim of the present study was to investigate the utility of self-performed UDTs and patient diaries in the management of impaired glucose tolerance, one of the adverse events of immune checkpoint inhibitors (ICIs). Patients receiving ICIs underwent self-checks with UDTs twice a week for up to 6months. Pharmacists checked the results at every patient visit, and by phone every 3months. The primary endpoint was to prospectively assess whether symptoms recorded in patient diaries and UDTs could reduce unscheduled hospital admissions due to impaired glucose tolerance. The secondary endpoint was the correlation between the symptoms in the patient diaries and UDT results. A total of 112 patients were enrolled in the study. Out of the 3197 planned self-UDTs, 3128 (97.8%) were performed. Forty-four patients (39.3%) were admitted to the hospital, two (1.8%) of whom were admitted due to abnormal glucose tolerance, with one having a positive UDT. There were 46 unscheduled outpatient visits (41.1%), of which five (4.5%) were due to abnormal glucose tolerance symptoms and four were due to a positive UDT. The correlation between descriptions of fatigue or dry mouth in the patient diaries and positive glucose UDTs was 52.4% in sensitivity and 62.4% in specificity. Self-monitoring of symptoms and self-performing of UDTs could not reduce the emergency hospitalization rate. However, this approach could be effective in the objective monitoring of patient status, especially regarding glucose intolerance occurrences.

6674 Non-Progressive Diabetes Leading to Neurologic Diagnosis

Abstract Disclosure: F.L. Thelmo: None. M. Murugesh: None. B. Simon: None. Introduction: The autoantibody GAD (anti-glutamic acid decarboxylase) is highly associated with Type 1 diabetes (T1DM) and Latent Autoimmune Diabetes in Adulthood (LADA). If GAD is detected before the onset of overt diabetes, typically 80% of patients with abnormal glucose tolerance progress to insulin deficiency and the need for insulin treatment after 5 years.[1] Stiff Person Syndrome (SPS) is also associated with GAD antibodies, but in SPS, the GAD antibodies are believed to be different epitopes that target GABA production in neuromuscular pathways. We present a case of presumed LADA that did not progress for 30 years, with progressive neurologic symptoms leading to a diagnosis of SPS in later adulthood.Case: A 52-year-old female presented for evaluation of T1DM and worsening neuropathies. She had a long history of prediabetes, with mildly elevated glucose values noted on labs since her early twenties. There was no family history of T1DM or autoimmune conditions. Six years ago, she sought endocrine evaluation. HgbA1c values were 6.1 to 6.6%. Intermittent use of continuous glucose monitoring (CGM) revealed post-prandial hyperglycemia up to 180mg/dL, occasionally (but rarely) exceeding 200mg/dL. She recalls being told that she had positive antibodies (unclear which ones tested) and given a diagnosis of T1DM. She declined insulin and maintained glycemic control with carbohydrate restriction and exercise; there were no episodes of diabetic ketoacidosis. She then developed neurologic symptoms: fullness, tightness and bloating in the abdomen (diagnosed with gastroparesis on scanning) and after a COVID 19 booster in 2021, muscle spasms in the legs and back with worsening abdominal tightness. At the time of her current presentation, A1C was 6.4%, glycated albumin was 14.4% (prediabetes range 13.6 - 15.5%) and CGM time in range was 99%. A non-fasting C-peptide was 3.6 ng/mL (1.1- 4.4ng/mL) with glucose of 119 mg/dL. Repeat antibody testing revealed undetectable IA-2 and ZnT8 antibodies, but GAD was grossly elevated at 1,015.3 U/mL. Given the unusually high GAD titer, SPS was suspected, and this diagnosis was confirmed on referral to neurology. The patient was advised to liberalize diet and will be monitored with HgbA1c and serial C-peptide levels to assess progression in the future. Discussion: While high GAD antibody levels are associated with progression to insulin dependence in adults with LADA, in SPS the GAD titers tend to be even higher2. The presence of only one auto-antibody for T1DM (and not multiple), long-standing non-progressive hyperglycemia, and normal C-peptide pointed away from autoimmune diabetes being the etiology for mild glucose intolerance in this patient. If neurologic symptoms are present, high GAD should prompt the evaluation for other syndromes associated with GAD antibody epitopes such as SPS. Presentation: 6/2/2024

5041 Lifecourse Changes in Insulin Demand-adequacy Association and Utility of a Novel Index for Predicting Abnormal Glucose Tolerance

5041 Lifecourse Changes in Insulin Demand-adequacy Association and Utility of a Novel Index for Predicting Abnormal Glucose Tolerance

EXPLORING THE STREPTOZOTOCIN-NICOTINAMIDE MOUSE MODEL IN BALB/C MICE: GAINING INSIGHTS INTO DIABETIC PNEUMOPATHY

Background: Diabetic pneumopathy has been a topic of interest in the present era, and it caught the eye during the COVID-19 pandemic. Extensive research provides compelling data supporting the association between diabetes and lung injury, establishing the lung as a principal organ affected by diabetes. However, the understanding of diabetic lung has always remained under shadow. For this purpose, we aimed to search for diabetic lung conditions by using a type 2 diabetic model in BALB/c mice. Methods: The study spanned from May to June 2023 at Ziauddin University. Nicotinamide, followed by streptozotocin, was injected into the mice. Mice were confirmed diabetic on the 7th day and housed for the onset of diabetic lung complications. After 28 days, mice underwent an oral glucose tolerance test and were then sacrificed, followed by the collection of bronchoalveolar lavage fluid and the extraction of the lungs. Lungs were fixed for histological analysis. Results: The presence of increased glycaemic levels, further verified by abnormal glucose tolerance, confirmed the establishment of the type 2 diabetic model. Additionally, the diabetic group showed lung fibrotic changes. Conclusion: The foundation of a type 2 diabetic model with the target of generating pneumopathy was accomplished successfully. Pak J Physiol 2024;20(3):31?6, DOI: https://doi.org/10.69656/pjp.v20i3.1673

Safety and tolerability of a low glycemic load dietary intervention in adults with cystic fibrosis: a pilot study.

To achieve and maintain adequate weight, people with cystic fibrosis (CF) May often consume energy-dense, nutrient-poor foods high in added sugars and refined carbohydrates; however, little is known about the glycemic and metabolic effects of dietary composition in this patient population. The objective of this pilot study was to investigate the safety and tolerability of a low glycemic load (LGL) diet in adults with CF and abnormal glucose tolerance (AGT). Ten adults with CF and AGT completed this prospective, open-label pilot study. Mean age was 27.0 ± 2.1 years, 64% were female, and all had pancreatic insufficiency. Each participant followed his/her typical diet for 2 weeks, then transitioned to a LGL diet via meal delivery service for 8 weeks. The primary outcome was change in weight from baseline to study completion, with safety established if no significant decline was noted. Other key safety outcomes included change in hypoglycemia measured by patient report and continuous glucose monitoring (CGM). Exploratory outcomes included changes in other CGM measures, body composition by dual energy X-ray absorptiometry (DXA), and patient reported outcomes. There were no significant changes in weight or in subjectively-reported or objectively-measured hypoglycemia. Favorable non-significant changes were noted in CGM measures of hyperglycemia and glycemic variability, DXA measures of fat mass, and gastrointestinal symptom surveys. A LGL dietary intervention was safe and well tolerated in adults with CF and AGT. These results lay the groundwork for future trials investigating the impact of low-glycemic dietary interventions on metabolic outcomes in the CF population.

Arterial Spin Labeling (ASL) MRI in Evaluating Pancreatic Blood Perfusion in Subjects With Different Glucose Tolerances.

The pancreas plays a central role in type 2 diabetes mellitus (T2DM), and its blood flow is usually associated with insulin release demand. To noninvasively assess pancreatic blood flow (PBF) changes and modulation in people with different glucose tolerance following a glucose challenge using ASL MRI. Prospective. Fourteen prediabetes, 22 T2DM, and 40 normal. Pseudo-continuous ASL with a turbo gradient spin echo sequence at 3.0 T. All normal and subjects (diagnosed by oral glucose tolerance test) underwent ASL after fasting for at least 6 hours. The normal and prediabetes groups additionally had ASL scans at 5, 10, 15, 20, and 25 minutes following oral glucose (50 mL, 5%). PBF maps were generated from the ASL data and measured at body and tail. The ability of baseline PBF (BL-PBF) of body, tail (BL-PBFtail), and their average to determine abnormal glucose tolerance and stage was assessed. ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, paired sample t-test, intra-class correlation coefficient, repeated measures ANOVA, correlation analysis, receiver operating characteristic analysis, and logistic regression analysis. A P value <0.05 was considered significant. There were significant differences in BL-PBF among the three groups. The prediabetes group exhibited significantly lower PBF than the normal group at all time points; Both groups showed similar changing trends in PBF (peaking at the 15th minute and subsequently declining). The BL-PBFtail had the highest diagnostic performance when evaluating abnormal glucose tolerance or stage (area under the curves = 0.800, 0.584, respectively) and was an independent risk factor for glucose tolerance status. ASL can noninvasively assess changes in PBF among individuals with varying glucose tolerance and in response to glucose challenge, which could be linked to insulin release demand and might help characterize changes in pancreatic endocrine function. 2 TECHNICAL EFFICACY: Stage 1.

Analysis of Risk Factors Associated with Gestational Diabetes Mellitus: A Retrospective Case-Control Study.

Gestational diabetes mellitus (GDM) is a complication of abnormal glucose tolerance during pregnancy, with incidence is on the rise. There are inconsistent results on the risks of GDM and it has not been reported in our region. The purpose of this study is to explore the risk factors of GDM. A total of 383 pregnant women were analyzed, including 67 (17.5%) pregnant women with GDM and 316 (82.5%) with normal glucose tolerance (NGT). The relationship of personal history, family history and reproductive history of pregnant women, the levels of alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG), inflammatory markers in blood cell analysis at the first prenatal examination, and fetal ultrasound indices and the risk of GDM were analyzed. The fetal biparietal diameter, head circumference, and femur length were negatively correlated with HCG level, but not inflammatory markers. The proportion of pregnant women aged ≥30 years old, body mass index (BMI) in early pregnancy≥24.0 kg/m2, history of polycystic ovary syndrome (PCOS), cesarean section, adverse pregnancy, and oral contraceptive use, and pregnant women who conceived through assisted reproduction in GDM group were higher than those in NGT group. Logistic regression analysis showed that age of pregnant woman ≥30 years old (≥30 vs <30 years old, odds ratio (OR): 2.142, 95% confidence interval (CI): 1.183-3.878, p=0.012), BMI≥24.0 kg/m2 (≥24.0 kg/m2 vs 18.5-23.9 kg/m2, OR: 1.887, 95% CI: 1.041-3.420, p=0.036), history of adverse pregnancy (yes vs no, OR: 1.969, 95% CI: 1.022-3.794, p=0.043), and history of oral contraceptive use (yes vs no, OR: 2.868, 95% CI: 1.046-7.863, p=0.041) were associated with GDM. Age of pregnant woman ≥30 years old, BMI≥24.0 kg/m2, history of adverse pregnancy and oral contraceptive use were independent risk factors for GDM.

Effect of dietary myo-inositol supplementation on the insulin resistance and the prevention of gestational diabetes mellitus: an open-label, randomized controlled trial.

Myo-inositol (MI) is an insulin-sensitizing dietary supplement, enhancing the transfer of glucose into the cell. Gestational diabetes mellitus (GDM) is characterized by abnormal glucose tolerance, which is associated with elevated insulin resistance. The present study aimed to assess the effect of MI supplementation during pregnancy on the incidence of GDM. We performed a single-center, open-label, randomized controlled trial. A cohort of 200 pregnant women at 11-13+6 weeks of gestation were randomly assigned in two groups: MI group (n = 100) and control group (n = 100). The MI group received MI and folic acid (4000 mg MI and 400 mcg folic acid daily), while the control group received folic acid alone (400 mcg folic acid daily) until 26-28 weeks of gestation, when the 75 g Oral Glucose Tolerance Test (OGTT) was performed for the diagnosis of GDM. Clinical and metabolic outcomes were assessed. The incidence of GDM was significantly higher in the MI group (14.9%) compared to the control group (28.5%) (P = 0.024). Women treated with MI had significantly lower OGTT glucose values, than those not treated with MI (P < 0.001). The insulin resistance as assessed by HOMA-IR was significantly lower in the MI group versus control (P = 0.045). Furthermore, MI group had significantly higher insulin sensitivity as measured by the Matsuda Index, compared to the control group (P = 0.037). MI supplementation seems to be an effective option to improve the glycemic control of pregnant women and prevent the onset of GDM. ISRCTN registry: ISRCTN16142533. Registered 09 March 2017.

Abnormal Glucose Tolerance Among Children with Cystic Fibrosis

Abstract Background Cystic fibrosis (CF) is a severe, autosomal recessive disease of high prevalence caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene which is located on the long arm of chromosome 7. Objective to screen for glucose tolerance abnormalities among children with cystic fibrosis. Patients and Methods This was a cross-sectional study conducted on 25 cystic fibrosis patients in the age group from 1 – 15 years in the Pediatric pulmonology clinic, from the first of July 2020 to the end of January 2022. The patients were classified according to their glucose tolerance results into CF patients with normal glucose tolerance and CF patients with abnormal glucose tolerance. Results Our analysis also showed that the most important factor associated with abnormal glucose tolerance test was found to be higher age and glycosylated hemoglobin. The previous findings highlight the need for routine screening of CF patients to exclude CFRD or any abnormality in glucose tolerance in these patients. Conclusion The current study demonstrated that abnormal glucose tolerance is not uncommon among the studied CF patients. Our results concluded that abnormal glucose tolerance was significantly associated with older age and higher glycosylated hemoglobin.

Central Obesity is Associated with Increased Left Ventricular Maximal Wall Thickness and Intrathoracic Adipose Tissue Measured with Cardiac Magnetic Resonance.

Central obesity (CO), characterized by an increased waist circumference increases the risk of cardiovascular disease (CVD) and morbidity, yet the underlying mechanisms are not fully understood. CO is often associated with general obesity, hypertension, and abnormal glucose tolerance, confounding the independent contribution of CO to CVD. We investigated the relationship of CO (without associated disorders) with left ventricular (LV) characteristics and intrathoracic adipose tissue (IAT) by cardiac magnetic resonance. LV characteristics, epicardial (EAT), and mediastinal adipose tissue (MAT) were measured from 29 normoglycemic, normotensive males with CO but without general obesity (waist circumference >100 cm, body mass index (BMI) <30 kg/m2) and 18 non-obese male controls. LV maximal wall thickness (LVMWT) and IAT but not LV mass or volumes were increased in CO subjects compared to controls (LVMWT, 12.3±1.2 vs. 10.7±1.5 mm, p < 0.001; EAT, 5.5±3.0 vs. 2.2±2.0 cm2, p = 0.001; MAT, 31.0±12.8 vs. 15.4±10.7 cm2, p < 0.001). The LVMWT was ≥12 mm in 69% of subjects with CO and 22% of controls (p = 0.002). In CO suspects, EAT correlated inversely with LV end-diastolic volume index (r = -0.403, p = 0.037) and LV stroke volume (SV) (r = -0.425, p = 0.027). MAT correlated inversely with SV (r = -0.427, p=0.026) and positively with LVMWT (r = 0.399, p = 0.035). Among CO subjects, the waist-to-hip ratio (WHR) was an independent predictor of LVMWT (B = 22.4, β = 0.617, p < 0.001). The optimal cut-off with Youden's index for LV hypertrophy was identified at WHR 0.98 (sensitivity 85%, specificity 89%). CO independent of BMI is associated with LV hypertrophy and intrathoracic adipose tissue contributing to cardiovascular burden.

Association of Clinical Factors with the Development of GDM in the Hoosier Mom’s Cohort

Introduction: Gestational diabetes mellitus (GDM) develops during pregnancy, raising the risk of adverse perinatal outcomes. The objective of this study was to investigate potential therapeutic targets for prepregnancy and early pregnancy interventions to decrease the impact of GDM on health during and after pregnancy. Methods: The Hoosier Mom’s Cohort was a prospective pregnancy cohort designed to assess for predictors of GDM. Inclusion criteria were gestational age &lt;20 weeks, a singleton pregnancy, and being at least 18 years old. Individuals with a pregestational diabetes diagnosis, HbA1c at screening of ≥6.5, or abnormal 3-hour oral glucose tolerance test before 20 weeks of gestation were excluded. Study visits with survey completion and biospecimen collection occurred, one at enrollment, and one in the early third trimester. All participants were given a Garmin activity tracker to collect objective physical activity and sleep data. Sociodemographic, medical, behavioral, and psychosocial characteristics were obtained, and obstetric outcomes were abstracted after delivery by certified chart abstractors. The primary outcome was development of GDM. Associations between categorical variables and GDM were made with Chi-square testing, and those between continuous variables and GDM were done with t-test. Results: Of 411 participants recruited into the Hoosier Moms Cohort, complete data was available for 391 (95.1%). Participants had a mean age of 30 years, a BMI of 28, and 17% were of Hispanic ethnicity. Study participants self-identified mostly as White (71%) or Black (16%). 66% of participants were nulliparous. Additionally, 54% reported a family history of diabetes, with 4% of patients also reporting a prior history of GDM. A total of 39 participants (10.0%) developed GDM. Participants who developed GDM had significantly higher BMI at study entry (31.6 ±8.5 vs 27.2 ±6.5, p=0.003), lower probability of being nulliparous (15.38% vs 33.61%, p=0.02), higher baseline HbA1c values (5.24 ±0.3 vs 5.07 ±0.3, p&lt;0.001), higher triglycerides levels (156.85 ±62 vs 134.16 ±54.5, p=0.022), and higher blood glucose values (85.90 ±14.4 vs 79.96 ±17.7, p=0.025) at first study visit. Additionally, 28% of participants who developed GDM had a prior history of GDM, compared to 2% of participants who did not (p&lt;0.0001). Those who developed GDM had higher rates of chronic hypertension (12.82% vs 1.96%, p=0.0034) and higher insomnia scores (9.62 ±5.1 vs 7.80 ±4.7, p=0.028). Conclusion/ Implications: Multiple clinical factors were found to be statistically associated with the development of GDM. These characteristics will be utilized in a comprehensive predictive model using machine learning methodologies to guide clinical decisions early in pregnancy.

Fetal Origin of Abnormal Glucose Tolerance in Adult Offspring Induced by Maternal Bisphenol A Analogs Exposure.

With the widespread use of bisphenol A (BPA) analogs, their health risks have attracted attention. The effects of maternal BPA analogs exposure on glucose homeostasis in adult offspring and the underlying fetal origins require further exploration. Herein, we exposed pregnant mice to two types of BPA analogs─BPB and BPAF; we evaluated glucose homeostasis in adult offspring and maternal-fetal glucose transport by testing intraperitoneal glucose tolerance, determining glucose and glycogen contents, conducting positron emission tomography (PET)/computed tomography (CT), detecting expression of placental nutrient transport factors, and assessing placental barrier status. We observed that adult female offspring maternally exposed to BPB and BPAF exhibited low fasting blood glucose in adulthood, with even abnormal glucose tolerance in the BPAF group. This phenomenon can be traced back to the elevated fetal glucose induced by the increased efficiency of placenta glucose transport in late pregnancy. On the other hand, the expression of genes associated with vascular development and glucose transport was significantly altered in the placenta in the BPAF group, potentially contributing to enhanced fetal glucose. These findings provide preliminary insights into potential mechanisms underlying the disturbance of glucose metabolism in adult female offspring mice induced by maternal exposure to BPA analogs.

Oral Glucose Tolerance Test as a Risk Marker for Developing Post-Transplant Diabetes Mellitus

IntroductionThe incidence of post-transplant diabetes mellitus (PTDM) can reach 30% during the first 6 months after kidney transplantation (KT), increasing the risk of graft failure and mortality. There is no well-established biomarker for predicting PTDM occurrence. This study evaluated the association between the abnormal 2-hour oral glucose tolerance test (OGTT) and the PTDM incidence. MethodsA retrospective single-center study, including adult kidney transplant recipients from deceased donors, was performed between March 2021 and June 2022. Exclusion criteria: age <18 years; pretransplant diabetes mellitus (DM); death with a functioning graft; loss of follow-up and/or graft failure before 6 months post-transplant. The results of pretransplant OGTT, fasting (FPG), and afternoon plasma glucose levels at hospitalization and FPG in the first, second, and third months post-transplant were evaluated. For analysis, patients were grouped according to the PTDM diagnosis: PTDM and non-PTDM. ResultsFrom 164 KT performed in the period, 50 (30%) were included, most male (n = 34, 68%), with a mean age of 48.3 ± 12.5 years. Nine patients (18%) developed PTDM, 44% between 3 and 6 months. General characteristics and immunosuppressive therapy were similar between the groups. The mean FPG in the pretransplant OGTT was significantly higher in the PTDM group compared with the non-PTDM group (85.7 ± 7.9 vs 79.1 ± 8.2, P = .03). The number of patients classified as impaired glucose tolerance (IGT) on the pre-transplant OGTT was significantly higher in the PTDM group. ConclusionIGT in the pretransplant OGTT was associated with PTDM cases in kidney transplant recipients without a previous diagnosis of DM.

Beyond Stages: Predicting Individual Time Dependent Risk for Type 1 Diabetes.

Essentially all individuals with multiple autoantibodies will develop clinical type 1 diabetes. Multiple AABs and normal glucose tolerance define Stage 1 diabetes; abnormal glucose tolerance defines Stage 2. However, the rate of progression within these stages is heterogeneous, necessitating personalized risk calculators to improve clinical implementation. We developed 3 models using TrialNet's Pathway to Prevention data to accommodate the reality that not all risk variables are clinically available. The Small model included AAB status, fasting glucose, HbA1c and age, while the Medium and Large models added predictors of disease progression measured via oral glucose tolerance testing. All models markedly improved granularity regarding personalized risk missing from current categories of stages of T1D. Model derived risk calculations are consistent with the expected reduction of risk with increasing age and increase in risk with higher glucose and lower insulin secretion, illustrating the suitability of the models. Adding glucose and insulin secretion data altered model predicted probabilities within Stages. In those with high 2-hour glucose, a high C-peptide markedly decreased predicted risk; lower C-peptide obviated the age-dependent risk of 2-hour glucose alone, providing a more nuanced estimate of rate of disease progression within Stage 2. While essentially all those with multiple AABs will develop type 1 diabetes, the rate of progression is heterogeneous and not explained by any individual single risk variable. The model-based probabilities developed here provide an adaptable personalized risk calculator to better inform decisions about how and when to monitor disease progression in clinical practice.

Glucose levels measured with continuous glucose monitoring in uncomplicated pregnancies

IntroductionTo characterize glucose levels during uncomplicated pregnancies, defined as pregnancy with a hemoglobin A1c <5.7% (<39 mmol/mol) in early pregnancy, and without a large-for-gestational-age birth, hypertensive disorders of pregnancy, or...

Trajectory of gestational weight gain in patients with gestational diabetes mellitus

Introduction: Weight gain in pregnancy is a significant modifiable factor that impacts immediate and future health of the mother and her fetus Hence, worldwide guidelines are developed about weight gain in pregnancy. In a recent study patients with abnormal glucose tolerance test and diagnosed with gestational diabetes had less deviation from expected gestational weight gain. Purpose: The aim of our study is to look at the trajectory of gestational weight gain for women diagnosed with gestational diabetes followed at the King Faisal Specialist Hospital and Research Centre (KFSH&amp;RC) Methods: Our study population included 215 pregnant women with singleton pregnancy diagnosed with diabetes mellitus who attended the obstetrics outpatient clinic and family health clinics from first antenatal visit until delivery. Results: From among the 215 women in the study cohort, the total number of weight gain was 143. The number of patients who lost weight was 48, and the number of patients who remained stable were 24. Overall, the amount of weight gain for women in this study was comparable to the expected. Conclusion: In our study we found the patients diagnosed with gestational diabetes mellitus have a wide range of changes in their weight gain trajectory from previously expected parameters in the healthy population, which might be explained by other factors like adherence to diet, exercise and medications designed control the metabolism.