Glucose Challenge Research Articles

Mitotic CDK1 and 4E-BP1 II: A single phosphomimetic mutation in 4E-BP1 induces glucose intolerance in mice.

Cyclin-dependent kinase 1 (CDK1)/cyclin B1 phosphorylates many of the same substrates as mTORC1 (a key regulator of glucose metabolism), including the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). Only mitotic CDK1 phosphorylates 4E-BP1 at residue S82 in mice (S83 in humans), in addition to the common 4E-BP1 phospho-acceptor sites phosphorylated by both CDK1 and mTORC1. We examined glucose metabolism in mice having a single aspartate phosphomimetic amino acid knock in substitution at the 4E-BP1 serine 82 (4E-BP1S82D) mimicking constitutive CDK1 phosphorylation. Knock-in homozygous 4E-BP1S82D and 4E-BP1S82A C57Bl/6N mice were assessed for glucose tolerance testing (GTT) and metabolic cage analysis on regular and on high-fat chow diets. Gastrocnemius tissues from 4E-BP1S82D and WT mice were subject to Reverse Phase Protein Array analysis. Since the bone marrow is one of the few tissues typically having cycling cells that transit mitosis, reciprocal bone-marrow transplants were performed between male 4E-BP1S82D and WT mice, followed by metabolic assessment, to determine the role of actively cycling cells on glucose homeostasis. Homozygous knock-in 4E-BP1S82D mice showed glucose intolerance that was markedly accentuated with a diabetogenic high-fat diet (p = 0.004). In contrast, homozygous mice with the unphosphorylatable alanine substitution (4E-BP1S82A) had normal glucose tolerance. Protein profiling of lean muscle tissues, largely arrested in G0, did not show protein expression or signaling changes that could account for these results. Reciprocal bone-marrow transplantation between 4E-BP1S82D and wild-type littermates revealed a trend for wild-type mice with 4E-BP1S82D marrow engraftment on high-fat diets to become hyperglycemic after glucose challenge. 4E-BP1S82D is a single amino acid substitution that induces glucose intolerance in mice. These findings indicate that glucose metabolism may be regulated by CDK1 4E-BP1 phosphorylation independent from mTOR and point towards an unexpected role for cycling cells that transit mitosis in diabetic glucose control.

High Glucose Promotes Inflammation and Weakens Placental Defenses against E. coli and S. agalactiae Infection: Protective Role of Insulin and Metformin.

Placentas from gestational diabetes mellitus (GDM) patients undergo significant metabolic and immunologic adaptations due to hyperglycemia, which results in an exacerbated synthesis of proinflammatory cytokines and an increased risk for infections. Insulin or metformin are clinically indicated for the treatment of GDM; however, there is limited information about the immunomodulatory activity of these drugs in the human placenta, especially in the context of maternal infections. Our objective was to study the role of insulin and metformin in the placental inflammatory response and innate defense against common etiopathological agents of pregnancy bacterial infections, such as E. coli and S. agalactiae, in a hyperglycemic environment. Term placental explants were cultivated with glucose (10 and 50 mM), insulin (50-500 nM) or metformin (125-500 µM) for 48 h, and then they were challenged with live bacteria (1 × 105 CFU/mL). We evaluated the inflammatory cytokine secretion, beta defensins production, bacterial count and bacterial tissue invasiveness after 4-8 h of infection. Our results showed that a GDM-associated hyperglycemic environment induced an inflammatory response and a decreased beta defensins synthesis unable to restrain bacterial infection. Notably, both insulin and metformin exerted anti-inflammatory effects under hyperglycemic infectious and non-infectious scenarios. Moreover, both drugs fortified placental barrier defenses, resulting in reduced E. coli counts, as well as decreased S. agalactiae and E. coli invasiveness of placental villous trees. Remarkably, the double challenge of high glucose and infection provoked a pathogen-specific attenuated placental inflammatory response in the hyperglycemic condition, mainly denoted by reduced TNF-α and IL-6 secretion after S. agalactiae infection and by IL-1β after E. coli infection. Altogether, these results suggest that metabolically uncontrolled GDM mothers develop diverse immune placental alterations, which may help to explain their increased vulnerability to bacterial pathogens.

Islet function changes of post-glucose-challenge relate closely to 15 years mortality of elderly men with a history of hyperglycemia

AimsWe aimed to investigate the relationship between islet function changes during a glucose challenge and 15-year mortality in elderly men. MethodsElderly men who did the oral glucose tolerance test in 2005 owing to an abnormal glucose history without diabetes were included. Changes in insulin resistance and secretion were evaluated using the homeostasis model assessment (HOMA) of fast, post-load, and ratios. Comparisons between the dead and the survival groups were analyzed using the Student's t-test (continuous variables) or χ2 test (Categorical variables). Single-factor logistic regression was used to identify the possible affecting factors. Multifactorial logistic regression was used to identify the independent risk factors in total population and in the subgroups. ROC curve was used to assess the predictive ability of risk factor and to determine the cut-off value. ResultsOf the 220 elderly men, 67 died according to 15-year retrospection. Age (OR = 1.243, P = 0.000), diastolic pressure (OR = 0.958, P = 0.027), and HOMA-IR (2 h/0 h) (OR = 1.040, P = 0.010) were independent risk factors for 15-year mortality. Subgroup analysis showed that HOMA-IR (2 h/0 h) was an obvious risk factor, especially for normal glucose tolerance (OR = 1.060, P = 0.030), age 60–70 years (OR = 1.068, P = 0.005), and hypertension (OR = 1.048, P = 0.013); HOMA-β (2 h/0 h) showed some protective effects in the impaired glucose regulation subgroup (OR = 0.779, P = 0.057). HOMA-IR (2 h/0 h) cut-off value was 15. ConclusionsHOMA-IR (2 h/0 h) higher than 15 was an independent risk factor for 15-year mortality in elderly men with hyperglycemia history.

Association between Gestational Diabetes Mellitus and Postpartum Depression among Women in Eastern India: A Cohort Study.

The study was planned to evaluate the association between Gestational Diabetes Mellitus (GDM) and Postpartum Depression (PPD) in a rural population of Odisha, Eastern India. Pregnant women in the first trimester were recruited and followed up till six weeks of postpartum. Gestational Diabetes Mellitus was assessed with 75 grams glucose challenge test and PPD was assessed at six weeks after delivery with Edinburgh Postnatal Depression Scale. Statistical difference between variables was assessed using Chi-square test, Fischer's exact test, and unpaired T-test. Covariates were adjusted using bivariate and multivariate logistic regression to estimate the association between GDM and PPD. Out of 436 pregnant women recruited, 347 (89.6%) remained in the study. Prevalence of GDM was 13.9% (95% CI: 10.7-17.3) and PPD was 9.8% (95% CI: 6.6-12.9). Incidence of PPD in the GDM group was 14.58% (95% CI: 4.2-24.9) and in women without GDM was 9.06% (95% CI: 5.76-12.3). However, the association was not significant on multivariate logistic regression (Risk Ratio (RR) = 1.56, 95% C.I: 0.61-6.16; P-value = 0.35). This study demonstrated that women with GDM were at higher risk of developing PPD suggesting that an "at risk" approach should be implemented for screening.

Continuous Glucose Monitoring in Prediabetic and Type II Diabetic Mellitus Patients: A Rapid Review

Background: COVID changed healthcare modalities and we found out that needed services were not met for diabetic patients. Continuous glucose monitoring (CGM) has been a technology used for Type 1 diabetic patients for years. With the rising numbers of both Type 2 diabetic (T2DM) and prediabetic patients, expanding the use of this technology could be beneficial in this population. Methodology: A review of nursing and medical literature was completed using search engines from the Simmons library, CINAHL, Medline databases, and Google Scholar. The key terms that were used in combinations were Diabetes Mellitus Type 2, T2DM, Prediabetes, Continuous Glucose Monitor, CGM, benefits/advantages, prevention, nursing, and challenges. This is a rapid review of the literature. Findings: After reviewing the literature, three themes emerged including findings that indicated that the use of CGM is an important tool for prediabetic and T2DM patients; as lifestyles changed, HbA1C results lowered, and these patients had less hypoglycemic episodes.

Abstract P246: Association Between Life’s Essential 8 Cardiovascular Health Scores During Pregnancy and Vascular Integrity in the Placenta

Background: Adverse pregnancy outcomes (APOs) identify pregnant people at increased risk of later cardiovascular disease. Poor antenatal cardiovascular health (CVH) quantified using components of the Life’s Simple 7 ideal CVH framework has been associated with higher APO incidence, indicating modifiable aspects of CVH during pregnancy may be related to pregnancy health. Placental pathology is also common in APOs, but it is unclear if antenatal CVH is directly related to placental health. Further, clinically-used dichotomous measures of placental pathology limit investigation of associations. Thus, the aim of this study was to examine the relationship between antenatal CVH and a novel, continuous marker of placental vascularization. Hypothesis: We hypothesized higher (healthier) antenatal CVH scores would be associated with higher (healthier) vascularization in the placenta. Methods: Participants enrolled in the Magee Obstetric Maternal & Infant Biobank and one of two prospective observational cohort studies examining activity patterns in pregnancy (MoM Health or Pregnancy 24/7). Antenatal CVH was quantified with a pregnancy-adapted Life’s Essential 8 framework assessed during each trimester and averaged across gestation. Components included sleep, diet, smoking, objective physical activity, pre-pregnancy BMI, blood pressure, 50g glucose challenge test results, and gestational weight gain. Component scores were averaged for a composite score (possible range, 0-100; higher indicated better CVH). Immunohistochemistry of placenta tissue was performed. Sections were stained with CD34 antibody to highlight vascular endothelial cells and counterstained with hematoxylin. Whole-slide images were digitized. Software computed the number of pixels positive for CD34 (numerator) and the total pixels (denominator); the ratio was the outcome of fetal vascular percentage (FV%), or the proportion of villous tissue occupied by fetal vessels. Linear regression associated CVH scores with FV%. Results: Placenta tissue was obtained from 64 participants (mean±SD age = 32±4.9 years). CVH score averaged across gestation was 72.6±10.7 points and decreased significantly from the first to third trimester (72.8±12.7 vs. 65.1±11.9, p<0.01). FV% was 26.3±5.13 percentage points. Associations between CVH scores and FV% approached but did not reach significance (p<0.2) in each trimester and across gestation. A 10-point increase in CVH averaged across gestation was non-significantly associated with a 0.82 percentage point increase in FV% (p=0.18). Post-hoc power analysis of this novel metric identified sufficient power to detect a 1.5 percentage point change in FV% per 10-point change in CVH score. Conclusion: Antenatal CVH was not significantly associated with placental vasculature, though a small sample size limits conclusions. Replication in a fully-powered sample is warranted.

Indicators of Cardiometabolic Function in Pregnancy and Long-Term Risk of COVID-19: Population-Based Cohort Study.

Pregnancy increases a woman's susceptibility to severe COVID-19, especially those with metabolic dysfunction. It isunknown if markers of metabolic dysfunction commonly assessed around pregnancy are associated with COVID-19 illness after pregnancy. The aim of this study is to evaluatethe indicators of metabolic dysfunction collected in pregnancy and the future risk ofsevere COVID-19 after pregnancy. This population-based cohort study was completed in all of Ontario, comprising 417,713 women aged 15-49 years with a hospital birth between April 2007 and March 2018. The main exposure was each 1-kg/m2higher body mass index (BMI), 1-mmol/L higher glucose concentration at the 50-g glucose challenge test, and one-week earlier gestational week at delivery. The main outcome was severe COVID-19 illness or death, from the start of the pandemic period on March 1, 2020, till December 31, 2021. The adjusted hazard ratio (aHR) of COVID-19 illness increased per 1-kg/m2higher BMI (1.05, 95% CI 1.04-1.06), per 1-mmol/L higher serum glucose concentration (1.16, 95% CI 1.10-1.22), and for each one-week earlier gestational week at delivery (1.12, 95% CI 1.03-1.23). Relative to women with no dichotomized risk factors, the aHR for severe COVID-19 was 1.60 (95% CI 1.28-2.01) with one factor, 3.34 (95% CI 2.51-4.44) with two factors, and 4.52 (95% CI 2.11-9.67) with three factors. The number, and degree, of standard metabolic indicators measured around pregnancy predict the future risk of severe COVID-19 remotely after that pregnancy.

E-DES-PROT: A novel computational model to describe the effects of amino acids and protein on postprandial glucose and insulin dynamics in humans

Current computational models of whole-body glucose homeostasis describe physiological processes by which insulin regulates circulating glucose concentrations. While these models perform well in response to oral glucose challenges, interaction with other nutrients that impact postprandial glucose metabolism, such as amino acids (AAs), is not considered. Here, we developed a computational model of the human glucose-insulin system, which incorporates the effects of AAs on insulin secretion and hepatic glucose production. This model was applied to postprandial glucose and insulin time-series data following different AA challenges (with and without co-ingestion of glucose), dried milk protein ingredients, and dairy products. Our findings demonstrate that this model allows accurate description of postprandial glucose and insulin dynamics and provides insight into the physiological processes underlying meal responses. This model may facilitate the development of computational models that describe glucose homeostasis following the intake of multiple macronutrients, while capturing relevant features of an individual's metabolic health.

Rate of Spontaneous Preterm Delivery Between Pregnant Women With and Without Gestational Diabetes.

Objective The aim of this study is to compare the rate of spontaneous preterm delivery between gestational diabetes mellitus (GDM) and normal pregnancy. Pregnancy outcomes and associated risk factors for spontaneous preterm delivery were evaluated. Methods A retrospective cohort study was conducted on 120 GDM and 480 normal pregnant women. All women received GDM screening with 50-g glucose challenge test and 100-g oral glucose tolerance test at the first visit and repeated at 24-28 weeks. Data were retrieved from medical records and included baseline and obstetric characteristics, preterm risks, GDM risks, and pregnancy outcomes. Spontaneous preterm birth was defined as delivery before 37 completed weeks of gestation that had been preceded by spontaneous labor. Results GDM women were more likely to be ≥30 years (p=0.032) and have previous GDM (p=0.013). Incidence of overall preterm delivery was significantly higher in GDM women (17.5% vs. 8.5%, p=0.004), as well as the incidence of spontaneous preterm delivery (15.8% vs. 7.1%, p=0.004). GDM women had less gestational weight gain (p<0.001) and were less likely to have excessive weight gain (p=0.002). GDM women were more likely to deliver large for gestational age (LGA) (p=0.02) and macrosomic infants (p=0.027). Neonatal hypoglycemia was significantly more common among GDM women (p=0.013). Multivariate analysis showed that previous preterm birth and GDM independently increased the risk of spontaneous preterm delivery (adjusted OR: 2.56, 95% CI: 1.13-5.79, p=0.024, and adjusted OR: 2.15, 95% CI: 1.2-3.84, p = 0.010, respectively). Conclusion GDM and previous preterm birth significantly increased the risk of spontaneous preterm delivery. GDM also increased the risk of LGA, macrosomia, and neonatal hypoglycemia.

One-step versus two-step screening for diagnosis of gestational diabetes mellitus in Iranian population: A randomized community trial.

There is considerable worldwide controversy regarding optimal screening and diagnostic approaches for GDM. This study aimed to compare the prevalence, maternal and neonatal outcomes of a One-step with a Two-step approach for the screening and diagnosis of GDM in a large community sample of pregnant women. We conducted a secondary analysis of a randomized community non-inferiority trial of GDM screening in Iran. For the current study, all pregnant women who met the inclusion criteria were randomized into two groups for GDM screening. The first group of women (n = 14611) was screened by a One-step screening approach [75-g 2-h oral glucose tolerance test (OGTT)] and the second group (n = 14160) by a Two-step method (the 50-g glucose challenge test followed by the 100-g OGTT). All study participants were followed up until delivery, and the adverse maternal and neonatal outcomes were recorded in detail. GDM was diagnosed in 9.3% of the pregnant women who were assigned to the One-step and in 5.4% of those assigned to the Two-step approach with a statistically significant difference between them (p < 0.001). Intention-to-treat analyses showed no significant differences between the One-step and the Two-step group in the unadjusted risks of the adverse pregnancy outcomes of macrosomia, primary cesarean-section, preterm birth, hypoglycemia, hypocalcemia, hyperbilirubinemia, preeclampsia, neonatal intensive care unit admission, birth trauma, low birth weight, and intrauterine fetal death. Results remained unchanged after adjustment for potential confounder variables including gestational age at enrollment and delivery, maternal body mass index, gestational weight gain, type of delivery, treatment modality, and GDM diagnosis in the first trimester. We found that although the rates of GDM more than doubled with the One-step strategy, the One-step approach was similar to the Two-step approach in terms of maternal and neonatal outcomes. These findings may warn that more caution should be exercised in adopting the One-step method worldwide. Future research is needed to assess the long-term harm and benefits of those approaches to GDM screening for both mothers and their offspring. https://www.irct.ir/trial/518, identifier (IRCT138707081281N1).

Regional quantification of cardiac metabolism with hyperpolarized [1-13C]-pyruvate CMR evaluated in an oral glucose challenge

BackgroundThe heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP) 13C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP 13C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy. MethodsWe developed and applied methods for whole-heart imaging of 13C-pyruvate, 13C-lactate and 13C-bicarbonate, following intravenous administration of [1-13C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated 13C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load). ResultsWe demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6 × 6 × 21 mm3 (13C-pyruvate) and 12 × 12 × 21 mm3 (13C-lactate, 13C-bicarbonate). 13C-pyruvate and 13C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial 13C-pyruvate-SNR, 13C-lactate-SNR, 13C-bicarbonate-SNR, 13C-lactate/pyruvate ratio, 13C-pyruvate-to-lactate conversion rate, kPL, and 13C-pyruvate-to-bicarbonate conversion rate, kPB, all had statistically significant increases following oral glucose challenge. kPB, reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant. ConclusionsWe demonstrate first-in-human regional quantifications of cardiac metabolism by HP 13C-pyruvate MRI that aims to reflect LDH and PDH activity.

The Belgian Diabetes in Pregnancy Follow-Up Study (BEDIP-FUS): A Multi-Centric Prospective Cohort Study on the Long-Term Metabolic Risk across Different Degrees of Gestational Glucose Intolerance: Methodology and Design.

The Belgian Diabetes in Pregnancy follow-up study (BEDIP-FUS) aims to investigate the impact of body mass index (BMI), adiposity and different degrees of glucose intolerance on the metabolic profile and future risk for type 2 diabetes (T2D) in women and offspring five years after delivery in the BEDIP study. The BEDIP study was a prospective cohort study to evaluate different screening strategies for gestational diabetes (GDM) based on the 2013 WHO criteria. The aim of the BEDIP-FUS is to recruit 375 women-offspring pairs, stratified according to three different subgroups based on the antenatal result of the glucose challenge test (GCT) and oral glucose tolerance test (OGTT) during the BEDIP pregnancy. The follow-up visit consists of a 75 g OGTT, anthropometric measurements and questionnaires for the mothers, and a fasting blood sample with anthropometric measurements for the child. Primary outcome for the mother is glucose intolerance defined by the American Diabetes Association criteria and for the offspring the BMI z-score. Recruitment began in January 2021. The BEDIP-FUS study will help to better individualize follow-up in women with different degrees of hyperglycemia in pregnancy and their offspring.

The National Clinical Care Commission Report to Congress: Leveraging Federal Policies and Programs to Prevent Diabetes in People With Prediabetes.

Individuals with an elevated fasting glucose level, elevated glucose level after glucose challenge, or elevated hemoglobin A1c level below the diagnostic threshold for diabetes (collectively termed prediabetes) are at increased risk for type 2 diabetes. More than one-third of U.S. adults have prediabetes but fewer than one in five are aware of the diagnosis. Rigorous scientific research has demonstrated the efficacy of both intensive lifestyle interventions and metformin in delaying or preventing progression from prediabetes to type 2 diabetes. The National Clinical Care Commission (NCCC) was a federal advisory committee charged with evaluating and making recommendations to improve federal programs related to the prevention of diabetes and its complications. In this article, we describe the recommendations of an NCCC subcommittee that focused primarily on prevention of type 2 diabetes in people with prediabetes. These recommendations aim to improve current federal diabetes prevention activities by 1) increasing awareness of and diagnosis of prediabetes on a population basis; 2) increasing the availability of, referral to, and insurance coverage for the National Diabetes Prevention Program and the Medicare Diabetes Prevention Program; 3) facilitating Food and Drug Administration review and approval of metformin for diabetes prevention; and 4) supporting research to enhance the effectiveness of diabetes prevention. Cognizant of the burden of type 1 diabetes, the recommendations also highlight the importance of research to advance our understanding of the etiology of and opportunities for prevention of type 1 diabetes.

The genetic polymorphisms and levels of adipokines and adipocytokines that influence the risk of developing gestational diabetes mellitus in Thai pregnant women

IntroductionAberrant immune and inflammatory response is thought to be involved in the pathogenesis of gestational diabetes mellitus (GDM). ObjectiveTo investigate the genetic polymorphisms and levels of adipokines/adipocytokines that influence the risk of developing GDM in Thai women. Research design & methodsThis case-control recruited 400 pregnant Thai women. A total of 12 gene polymorphisms at ADIPOQ, adipsin, lipocalin-2, PAI-1, resistin, IL-1β, IL-4, IL-17A, TGF-β, IL-10, IL-6, and TNF-α were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and RNase H2 enzyme-based amplification (rhAmp) SNP assay. Serum levels of adipokines/adipocytokines were evaluated using Luminex assays. ResultsMean age, weight before and during pregnancy, body mass index before and during pregnancy, blood pressure, gestational age at blood collection, and median 50 g glucose challenge test were significantly higher in GDM women than control. Significantly lower adiponectin and higher IL-4 levels were found in GDM compared to controls (p = 0.001 and p = 0.03, respectively). The genotype frequencies of IL-17A (rs3819025) were significantly different between GDM and controls (p = 0.01). Using additive models, IL-17A (rs3819025) and.TNF-α (rs1800629) were found to be independently associated with increased risk of GDM (odds ratio [OR]: 2.867; 95 % confidence interval [CI]: 1.171–7.017; p = 0.021; and OR: 12.163; 95 %CI: 1.368–108.153; p = 0.025, respectively). In GDM with IL-17A (rs3819025), there was a significant negative correlation with lipocalin-2 and PAI-1 levels (p = 0.038 and p = 0.004, respectively). ConclusionThe results of this study highlight the need for genetic testing to predict/prevent GDM, and the importance of evaluating adipokine/adipocytokine levels in Thai GDM women.

A low chromium diet increases body fat, energy intake and circulating triglycerides and insulin in male and female rats fed a moderately high-fat, high-sucrose diet from peripuberty to young adult age.

Trivalent chromium (Cr) may function to potentiate the action of insulin, but the effects of chromium intakes on metabolic parameters are unclear. Cr is listed as a potentially beneficial element for rodents based on studies that show feeding low quantities affect glucose metabolism. Cr is recommended at 1 mg per kg in rodent diets. This study examined the effects of different levels of dietary Cr on body weight, body composition, energy intake, food efficiency and metabolic parameters of lipid and glucose metabolism in male and female rats when fed from peripuberty to young adult age in the background of a moderately high-fat, high-sucrose diet. Sprague-Dawley CD rats (n = 10 males and 10 females/group) at 35 days of age were assigned by weight to the low (LCr, 0.33 ± 0.06 mg/kg), normal (NCr, 1.20 ± 0.11 mg/kg) or high (HCr, 9.15 ± 0.65 mg/kg) Cr diets. Diets were fed ad libitum for 12 weeks (83 days). At baseline, body weights and composition were similar (p≥0.05) among diet groups. Compared to the NCr group, the LCr group weighed more (p<0.01) and consumed more energy (food) from Day 56 onwards, but food efficiency was unaffected. Following an oral glucose challenge (Day 77), dietary chromium levels did not affect plasma glucose, but fasting plasma insulin and insulin at 30 and 60 min after dosing were higher in the LCr group compared to the NCr group. At the end of the study, whole-body fat, accrued body fat from baseline and fasting serum triglycerides were higher in the LCr group compared to the NCr group. Effects were similar in both sexes and not observed in the HCr group. These data show that low dietary Cr affects metabolic parameters common in chronic diseases underscoring the need for clinical trials to define the nutritional and/or pharmacological effects of Cr.

Oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of sodium-glucose co-transporter 1 in enterocytes

Metformin (MET) is the most prescribed antidiabetic drug, but its mechanisms of action remain elusive. Recent data point to the gut as MET's primary target. Here, we explored the effect of MET on the gut glucose transport machinery. Using human enterocytes (Caco-2/TC7 cells) invitro, we showed that MET transiently reduced the apical density of sodium-glucose transporter 1 (SGLT1) and decreased the absorption of glucose, without changes in the mRNA levels of the transporter. Administered 1h before a glucose challenge in rats (Wistar, GK), C57BL6 mice and mice pigs, oral MET reduced the post-prandial glucose response (PGR). This effectwas abrogated in SGLT1-KO mice. MET also reduced the luminal clearance of 2-(18F)-fluoro-2-deoxy-D-glucose after oral administration in rats. In conclusion, oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of SGLT1 in enterocytes, which may contribute to the clinical effects of the drug.

Intergenerational arsenic exposure on the mouse epigenome and metabolic physiology.

Inorganic arsenic (iAs) is one of the largest toxic exposures to impact humanity worldwide. Exposure to iAs during pregnancy may disrupt the proper remodeling of the epigenome of F1 developing offspring and potentially their F2 grand-offspring via disruption of fetal primordial germ cells (PGCs). There is a limited understanding between the correlation of disease phenotype and methylation profile within offspring of both generations and whether it persists to adulthood. Our study aims to understand the intergenerational effects of in utero iAs exposure on the epigenetic profile and onset of disease phenotypes within F1 and F2 adult offspring, despite the lifelong absence of direct arsenic exposure within these generations. We exposed F0 female mice (C57BL6/J) to the following doses of iAs in drinking water 2 weeks before pregnancy until the birth of the F1 offspring: 1, 10, 245, and 2300 ppb. We found sex- and dose-specific changes in weight and body composition that persist from early time to adulthood within both generations. Fasting blood glucose challenge suggests iAs exposure causes dysregulation of glucose metabolism, revealing generational, exposure, and sex-specific differences. Toward understanding the mechanism, genome-wide DNA methylation data highlights exposure-specific patterns in liver, finding dysregulation within genes associated with cancer, T2D, and obesity. We also identified regions containing persistently differentially methylated CpG sites between F1 and F2 generations. Our results indicate the F1 developing embryos and their PGCs, which will result in F2 progeny, retain epigenetic damage established during the prenatal period and are associated with adult metabolic dysfunction.

Circulating HHIP Levels in Women with Insulin Resistance and PCOS: Effects of Physical Activity, Cold Stimulation and Anti-Diabetic Drug Therapy.

Serum human hedgehog-interacting protein (HHIP) concentration is associated with diabetes. However, the relationship between HHIP and polycystic ovary syndrome (PCOS) or abnormal sex hormones remains unknown. This study was an observational cross-sectional study, with additional short-term intervention studies and follow-up studies. Bioinformatics analysis was performed to explore the association of PCOS with metabolic-related genes and signaling pathways. OGTT and EHC were performed on all participants. Lipid infusion, cold exposure, and 45-min treadmill test were performed on all healthy women. A total of 137 women with PCOS were treated with metformin, GLP-1RA, or TZDs for 24 weeks. Serum HHIP levels were higher in insulin resistance (IR) and PCOS women. Circulating HHIP levels were significantly correlated with adiponectin (Adipoq) levels, obesity, IR, and metabolic indicators. A correlation presented between HHIP and DHEA-S, FAI, SHBG, and FSH. Serum HHIP levels were significantly elevated by oral glucose challenge in healthy women, but not affected by EHC. Lipid infusion decreased serum HHIP levels, while cold exposure increased HHIP levels in healthy women. GLP-1RA and TZD treatment reduced serum HHIP levels in PCOS women, while metformin treatment did not affect HHIP levels. HHIP may be a useful biomarker and novel drug target for PCOS and IR individuals.

The Impact of Acute Nutritional Interventions on the Plasma Proteome.

Humans respond profoundly to changes in diet, while nutrition and environment have a great impact on population health. It is therefore important to deeply characterize the human nutritional responses. Endocrine parameters and the metabolome of human plasma are rapidly responding to acute nutritional interventions such as caloric restriction or a glucose challenge. It is less well understood whether the plasma proteome would be equally dynamic, and whether it could be a source of corresponding biomarkers. We used high-throughput mass spectrometry to determine changes in the plasma proteome of i) 10 healthy, young, male individuals in response to 2 days of acute caloric restriction followed by refeeding; ii) 200 individuals of the Ely epidemiological study before and after a glucose tolerance test at 4 time points (0, 30, 60, 120 minutes); and iii) 200 random individuals from the Generation Scotland study. We compared the proteomic changes detected with metabolome data and endocrine parameters. Both caloric restriction and the glucose challenge substantially impacted the plasma proteome. Proteins responded across individuals or in an individual-specific manner. We identified nutrient-responsive plasma proteins that correlate with changes in the metabolome, as well as with endocrine parameters. In particular, our study highlights the role of apolipoprotein C1 (APOC1), a small, understudied apolipoprotein that was affected by caloric restriction and dominated the response to glucose consumption and differed in abundance between individuals with and without type 2 diabetes. Our study identifies APOC1 as a dominant nutritional responder in humans and highlights the interdependency of acute nutritional response proteins and the endocrine system.

An Electronic Medical Record Intervention to Increase Early Screening Rates for Gestational Diabetes.

Our objective was to implement an electronic medical record reminder to perform the early gestational diabetes mellitus (GDM) screening test and to evaluate if this intervention increased screening rates. We performed a retrospective chart review of all deliveries at Mount Sinai West in January 2020 to determine the number of patients that met criteria for and actually underwent early GDM screening. A total of 314 patients had complete charts with pregnancy data. The following American College of Obstetricians and Gynecologists (ACOG)-defined risk factors were collected: body mass index greater than 25 (Asians greater than 23), history of GDM, history of macrosomia, hypertension (systolic >140 or diastolic >90), polycystic ovarian syndrome, hemoglobin A1c above 5.7, cardiovascular disease, and family history of diabetes. We used this data to advocate for and design an electronic medical record-based intervention to remind obstetric providers to complete the early glucose challenge test screening for eligible patients at the first prenatal visit. Our investigation confirms there is a low adherence rate of 12% at our facility to ACOG's updated early GDM screening guidelines (12 out of 97 patients). Furthermore, nearly one-fifth (16 out of 85) of eligible patients who did not receive screening were eventually diagnosed with GDM by screening at 24 to 28 weeks. After implementing an electronic medical record reminder at the initial prenatal visit, screening rates more than doubled to 28% (33 out of 115 eligible patients). The most common diabetic risk factors were high-risk ethnic background, current hypertension, family history of diabetes, history of polycystic ovarian syndrome, and body mass index of 40 or greater. Our data suggests that obstetricians could be missing an opportunity to improve maternal and neonatal outcomes by diagnosing GDM earlier in pregnancy, as recommended by ACOG. The adoption of an electronic medical record reminder seems to improve the rate of indicated early GDM screening. · There is a low adherence rate of 16% to ACOG's updated early GDM screening guidelines.. · After implementing an electronic medical record alert at the initial prenatal visit, screening rates nearly doubled.. · Screening rates were higher at prenatal practices with resident physician involvement in patient care..