Risk Of Hyperglycemia Research Articles

Adequate sleep duration accentuates the effect of glucagon-like peptide-1 receptor variant on HbA1c: A gene-environment interaction study

BackgroundBoth glucagon-like peptide-1 receptor (GLP1R) agonists and lifestyle modifications are widely adopted in managing glycemia. However, the joint effects of GLP1R agonists with lifestyle on glycemic traits have not been evaluated. MethodsThis gene-environment study tested the interaction between GLP1R-rs10305492 variant, consistent with the effect of GLP1R agonist therapies, and four lifestyle factors (diet, physical activity, sleep duration, and chronotype) for glucose and glycated hemoglobin (HbA1c) levels among 263,846 UK Biobank participants. Linear regression models were conducted to evaluate the effects of the rs10305492 and lifestyle factors on glucose and HbA1c levels. ResultsGLP1R-rs10305492-AA/AG genotype combined a healthy diet, regular physical activity, adequate sleep duration, or morning chronotype were associated with lower glucose and HbA1c levels (all P for trend < 0.001). A synergistic effect was found between rs10305492 and sleep duration on HbA1c, suggesting a recommended adequate sleep duration (7–8 h/day) may amplify the HbA1c lowering effect of GLP1R agonists. Joint effects of the rs10305492 and adequate sleep were associated with a 26 % reduced risk of hyperglycemia (>7.8 mmol/L) risk and a 22 % lower of high HbA1c (>39 mmol/mol or 5.7 %). ConclusionsCombining GLP1R agonists with adequate sleep may provide additional benefits for glycemic control in clinical practice.

A phase II study of ME2136 (Asenapine Maleate) plus standard antiemetic therapy for patients, including diabetic patients, receiving cisplatin-based chemotherapy.

Olanzapine combined with the neurokinin-1 receptor antagonist, palonosetron and dexamethasone is the standard treatment for chemotherapy-induced nausea and vomiting (CINV) due to highly emetogenic chemotherapy (HEC). However, the use of olanzapine poses challenges in patients with diabetes mellitus (DM) due to the potential risk of hyperglycemia. ME2136, antipsychotic similar to olanzapine, is associated with a lower risk of hyperglycemia. This study investigated the antiemetic efficacy and safety of ME2136 for HEC. This single-arm phase 2 study examined the safety and efficacy of ME2136 5mg for 4days in combination with triplet-combination antiemetic therapy. Two cohorts were established for the safety assessment: DM and non-DM. Eligible patients had malignant tumors and were receiving cisplatin-based chemotherapy for the first time. The primary endpoint was the complete response (CR) rate, defined as the percentage of patients without vomiting and not requiring rescue medications in the delayed phase (24-120h). Between December 2020 and January 2022, 40 patients were enrolled, with 20 in each cohort. All patients were included in the safety analysis and 35 in the efficacy analysis. The CR rate in the delayed phase was 71.4% [60% CI 63.1-78.6%] for all patients, 66.7% in the DM cohort, and 76.5% in the non-DM cohort. No treatment-related adverse events ≥ grade 3, including hyperglycemia, were reported. ME2136, when combined with standard triplet-combination antiemetic therapy, is expected to exert similar antiemetic effects to the standard treatment for CINV due to HEC. Currently, ME2136-02 trial is underway to examine the safety and efficacy of triplet-combination antiemetic therapy and a 5-day treatment with ME2136. This study was registered with the Japan Registry of Clinical Trials (jRCT2041200071) on 10 December 2020. Clinical trial registration: This study was registered with the Japan Registry of Clinical Trials (jRCT2041200071) on 10 December 2020.

Association of triglyceride-glucose index with diabetes or prediabetes in Chinese hypertensive patients: A retrospective cohort study.

Insulin resistance is a key factor in diabetes development. This study aimed to investigate the association between baseline triglyceride-glucose (TyG) index, a surrogate marker of insulin resistance, and the onset of hyperglycemia in Chinese individuals with hypertension. Using the Rich Healthcare Group database, this retrospective cohort study included 28,687 hypertensive individuals without preexisting diabetes. A wide range of demographic information and baseline biochemical indicators was collected and rigorously analyzed. This study utilized the Cox proportional hazards model and smooth curve fitting to explore the link between TyG index and the risk of developing hyperglycemia. The robustness of the findings was validated by sensitivity and subgroup analyses. During longitudinal monitoring of hypertensive patients in our retrospective cohort study, we observed that 5.31% (1524/28,687) progressed to diabetes, while 21.66% (4620/21,326) developed prediabetes. After adjusting for confounding variables, a statistically significant positive association was observed between the TyG index and the risk of hyperglycemia. Subgroup and sensitivity analyses further supported these findings, demonstrating consistent outcomes and reinforcing the robustness of our conclusions. The TyG index, which is significantly linked to hyperglycemia in hypertensives, can aid early risk identification and intervention.

Explainable Machine-Learning Models to Predict Weekly Risk of Hyperglycemia, Hypoglycemia, and Glycemic Variability in Patients With Type 1 Diabetes Based on Continuous Glucose Monitoring.

The aim of this study was to develop and validate explainable prediction models based on continuous glucose monitoring (CGM) and baseline data to identify a week-to-week risk of CGM key metrics (hyperglycemia, hypoglycemia, glycemic variability). By having a weekly prediction of CGM key metrics, it is possible for the patient or health care personnel to take immediate preemptive action. We analyzed, trained, and internally tested three prediction models (Logistic regression, XGBoost, and TabNet) using CGM data from 187 type 1 diabetes patients with long-term CGM monitoring. A binary classification approach combined with feature engineering deployed on the CGM signals was used to predict hyperglycemia, hypoglycemia, and glycemic variability based on consensus targets (time above range ≥5%, time below range ≥4%, coefficient of variation ≥36%). The models were validated in two independent cohorts with a total of 223 additional patients of varying ages. A total of 46 593 weeks of CGM data were included in the analysis. For the best model (XGBoost), the area under the receiver operating characteristic curve (ROC-AUC) was 0.9 [95% confidence interval (CI) = 0.89-0.91], 0.89 [95% CI = 0.88-0.9], and 0.8 [95% CI = 0.79-0.81] for predicting hyperglycemia, hypoglycemia, and glycemic variability in the interval validation, respectively. The validation test showed good generalizability of the models with ROC-AUC of 0.88 to 0.95, 0.84 to 0.89, and 0.80 to 0.82 for predicting the glycemic outcomes. Prediction models based on real-world CGM data can be used to predict the risk of unstable glycemic control in the forthcoming week. The models showed good performance in both internal and external validation cohorts.

8035 Severe Hyperglycemia Induced By Enfortumab Vedotin (EV) Treatment For Urothelial Carcinoma

Abstract Disclosure: N. Semreen: None. M.D. Goldberg: None. Introduction: Immunotherapy has revolutionized cancer treatment, but it has a wide range of adverse events including endocrinopathies. Here we present a case of severe hyperglycemia induced by enfortumab vedotin (EV) treatment for advanced urothelial carcinoma. Clinical Case: A 56-year-old male was admitted to our hospital with a painful rash in sun-exposed areas. He had metastatic urothelial carcinoma, with progression of disease after platinum-based chemotherapy, radiation therapy, and pembrolizumab, and had begun treatment with EV six weeks prior to presentation. He also had type 2 diabetes mellitus, with a recent A1c of 6.1% on metformin monotherapy, and obesity (BMI, 31 kg/m2). His blood glucose on admission was 600 mg/dL, and insulin therapy was initiated. There was no evidence for DKA or HHS. Over the course of his 9-day admission he required approximately 200 units of insulin per day to control his glucose. A fasting C-peptide level was 6.89 ng/mL (0.81-3.89 ng/mL) concurrent with a glucose of 181 mg/dL. Skin biopsy revealed erythema multiforme, which represented a grade 4 toxicity of EV treatment, and the EV was discontinued. Symptoms improved with oral glucocorticoids. The patient was discharged on multiple daily injections of insulin in addition to metformin. His insulin requirements fell rapidly, and one month later he was able to discontinue insulin completely. He was started on sacituzumab for his cancer treatment. Discussion: EV is a first-in-class antibody-drug conjugate directed against Nectin-4, which was approved in 2019 for previously treated locally advanced or metastatic urothelial carcinoma. Hyperglycemia was reported in 6.4% of patients receiving EV in the initial phase III study; BMI ≥ 30 kg/m2 and pretreatment A1c ≥ 6.5% were identified as risk factors. In a 24-month follow-up analysis, the incidence of grade ≥ 3 hyperglycemia was 4.4%, and the median time to onset of hyperglycemia was 19 days. There have been postmarketing reports of EV-induced DKA, as well as cases of refractory hyperglycemia requiring more than 1,000 units of insulin daily. The mechanism explaining the hyperglycemia is not yet defined, but in the prior case reports, as well as the current case, C-peptide levels have been elevated. It is assumed, therefore, that the mechanism involves insulin resistance as opposed to insulin deficiency. The marked hyperglycemia appears to be reversible once EV therapy is discontinued. In 2023, EV was approved in combination with pembrolizumab for first-line therapy of locally advanced or metastatic urothelial cancer, as an alternative to platinum-based chemotherapy. With this expanded indication, providers should be aware of the risk of hyperglycemia, which in some cases may be severe. Presentation: 6/3/2024

Profile of Oral Corticosteroid Use in Patients in Madison City Pharmacies

Hyperglycemia induced by corticosteroid use depends on the dose, indication and setting of use. The type of corticosteroid that causes a greater degree of hyperglycemia is the use of Deksametasonor metilprednisolonrednisolone compared to prednisolone or hydrocortisone. High risk of hyperglycemia due to the use of oral corticosteroids, especially Deksametasonor metilprednisolonrednisolone. The aim of this study was to determine the profile of oral corticosteroid use in Madiun City pharmacies. This research is an observational study using retrospective data. Where data was obtained from profile data on the use of oral corticosteroids in one of the pharmacies in Madiun City. Then the data is analyzed, percentages are calculated and presented in the form of tables, graphs and diagrams. The results obtained were that the number of oral corticosteroids used in Madiun City pharmacies in 2022 was 44,270 tablets and increased in 2023, namely 50,680 tablets. Meanwhile, the type of oral corticosteroid that is widely used is metilprednisolonrednisone 4 mg, namely 13,090 tablets (29.57%) in 2022 and 14,950 tablets (29.50%) in 2023. The increase in the use of metilprednisolonrednisolone 4mg from 2022-2023 is 1,860 tablets . The conclusion of this research is that the use of oral corticosteroids in Madiun City pharmacies in 2022 and 2023 will increase and the most common type of corticosteroid is metilprednisolonrednisolone 4 mg.

Caring for patients with diabetes in the outpatient surgical setting: current recommendations and controversies.

Perioperative outpatient (ambulatory) care of the adult patient with diabetes requires unique considerations that vary from the inpatient setting. This review highlights specific pre, intra, and postoperative care steps for patients with diabetes undergoing ambulatory surgery, summarizing recent clinical trials, expert reviews, and emerging evidence. There is a paucity of evidence examining optimal diabetes management in the outpatient setting. Currently, there are limited studies regarding preoperative management of oral hypoglycemic agents, home insulin, and carbohydrate-containing beverages. Future research needs to specifically examine chronic blood glucose control, day of surgery targets, effective home medication management and the risk of perioperative hyperglycemia in ambulatory surgery. Education, protocols and resources to support the care of perioperative patients in the outpatient setting will aid providers on the day of surgery and provide optimal diabetes care leading up to surgery.

Elevated risk of pre-diabetes and diabetes in people with past history of COVID-19 in northeastern Nigeria

BackgroundAn increased risk of diabetes mellitus (DM) after COVID-19 has been reported in the United States, Europe, and Asia. The burden of COVID-related DM has yet to be described in Africa, where the overall risk of DM has been increasing rapidly. Our objective was to compare the prevalence of pre-DM and DM in Nigerian individuals with a history of COVID-19 to individuals without known COVID-19 infection.MethodsWe undertook a retrospective cohort study with 256 individuals with a past medical history of COVID-19 with no history of pre-DM or DM and 256 individuals without a history of COVID-19 or pre-DM/DM. Participants were categorized as pre-DM (fasting capillary glucose 100–125 mg/dL) or DM (fasting capillary glucose ≥ 126 mg/dL). We employed univariate and multivariable logistic regression to identify key predictors and adjust for confounders related to hyperglycaemia risk factors. Additionally, we used multinomial logistic regression to analyze the relationship between COVID-19 history and diabetes status, distinguishing between normal, pre-diabetic, and diabetic glucose levels. All models were adjusted for age, gender, hypertension, physical activity, central adiposity, and family history of DM.ResultsCompared to the control group, those with a history of COVID-19 had a similar median age (38 vs. 40 years, p = 0.84), had a higher proportion of men (63% vs. 49%), and had a lower prevalence of central adiposity (waist: hip ratio ≥ 0.90 for males and WHR ≥ 0.85 for females) (48% vs. 56.3%, p = 0.06). Of the 256 with a history of COVID-19, 44 (17%) required in-patient care. The median (interquartile range) time interval between COVID-19 diagnosis and the glycaemic assessment was 19 (IQR: 14, 24) months. Pre-DM prevalence was 27% in the post-COVID-19 group and 4% in the control group, whereas the prevalence of DM was 7% in the post-COVID-19 group and 2% in the control group. After multivariable adjustment, the odds of pre-DM were 8.12 (95% confidence interval (CI): 3.98, 16.58; p < 0.001) higher, and the odds of DM were 3.97 (95% CI: 1.16, 13.63) higher in those with a history of COVID-19 compared to controls. In the adjusted multinomial logistic regression analysis, individuals with a history of COVID-19 exhibited significantly elevated risks for pre-diabetes (RRR = 7.55, 95% CI: 3.76–15.17) and diabetes (RRR = 3.44, 95% CI: 1.01–11.71) compared to those without COVID-19.ConclusionPrevious COVID-19 was found to be a risk factor for prevalent pre-diabetes and diabetes mellitus in Nigeria. More intensive screening for DM in those with a history of COVID-19 should be considered.

Comparative Analysis of Epidural Dexamethasone and Epidural Morphine (EM) for Postoperative Pain Control After Total Abdominal Hysterectomy: A Randomized Clinical Trial

Background: Epidural anesthesia is commonly utilized for pain management following lower abdominal surgeries; however, the search for an optimal analgesic additive continues. Objectives: This study aimed to compare the efficacy of epidural dexamethasone versus epidural morphine (EM) in managing postoperative pain after total abdominal hysterectomy. Methods: This randomized controlled trial enrolled patients undergoing total abdominal hysterectomy (TBAH) and assigned them to two groups: Group D (Dexamethasone), which received epidural dexamethasone (8 mg) with bupivacaine, and Group M (Morphine), which received epidural morphine (10 mg) with bupivacaine. Marcaine (bupivacaine) 0.25% was used in both groups. Baseline characteristics, surgical outcomes, physiological parameters, pain management, adverse effects, and blood sugar levels were analyzed and compared between the groups. Results: The groups exhibited similar initial characteristics and surgical outcomes. Vital signs, including heart rate (HR), mean arterial pressure, respiratory rate, and oxygen saturation, remained consistent before and after surgery. The Dexamethasone group (Group D) demonstrated superior pain control compared to the Morphine group (Group M). Patients in Group D required pain medication for a significantly shorter duration (24 hours vs. 36 hours, P &lt; 0.05), representing a 50% reduction in medication duration. Additionally, Group D patients required fewer rescue analgesics (1.2 doses vs. 2.1 doses, P &lt; 0.05), indicating a 43% decrease in the need for additional medication. The time to a visual analog scale (VAS) score exceeding 4 was significantly longer in Group D, indicating less intense pain for an extended period. Although no significant differences were observed in common postoperative side effects, Group D exhibited a lower incidence of these effects, albeit not statistically significant. Furthermore, Group D showed a significantly lower incidence of hyperglycemia at the 8th hour post-surgery compared to Group M (P &lt; 0.05), suggesting a potential benefit of epidural dexamethasone in mitigating hyperglycemia risk. Conclusions: Epidural dexamethasone appears to offer superior analgesic efficacy compared to epidural morphine in postoperative pain management after total abdominal hysterectomy. The findings suggest that Group D (Dexamethasone) experienced improved pain management, reduced medication requirements, and a lower incidence of hyperglycemia. Further research with larger cohorts and extended follow-up is warranted to validate these findings and guide clinical practice.

The Association between Diet Quality and Metabolic Syndrome among Older African American Women.

Diet is a modifiable lifestyle factor that could impact the development of Metabolic Syndrome (MetS) and its components. MetS prevalence is high and diet quality is suboptimal among older African American women. MetS has been associated with many individual food groups, however, emerging research suggests that analyzing overall diet quality provides insight into the synergistic effects of food groups on health outcomes. In the current cross-sectional study, we examined the relationship between diet quality and MetS, and investigated associations between diet quality and MetS components among older African American women. This study was based on 357 African American women between 45 and 65 years from the NHANES 2011-2018 datasets. This analysis utilized the NCEP ATP III (2001) criteria for women to diagnose MetS. MetS was dichotomized in addition to a MetS z-score being calculated for each participant using a sex- and race-specific equation. Participants' diet quality was measured using the HEI-2015. Linear and logistic regressions were performed to assess the association between HEI-2015 diet quality and metabolic syndrome and its components. 65% of African American women aged 45-65 in the NHANES 2011-2018 had MetS. Study participants had an average HEI-2015 score of 55.4 out of 100. As HEI-2015 quartiles increased, the mean MetS z-score decreased (p-value: 0.0011). Age-adjusted models demonstrated statistically significant inverse relationships between HEI-2015 and waist circumference (β: -0.217; 95% CI: -0.372, -0.063), systolic blood pressure (β: -0.215; 95% CI: -0.359, -0.072), blood glucose (β: -0.344; 95% CI: -0.681, -0.0066), and triglycerides (β: -0.652; 95% CI: -1.05, -0.251). Significant associations could not be established between MetS and diet quality, assessed with the HEI-2015, among African American women aged 45-65 enrolled in NHANES 2011-2018. However, statistically significant relationships were observed between increased HEI-2015 scores and lowered risks of abdominal obesity, hyperglycemia, hypertriglyceridemia, and systolic hypertension. The findings of this study affirm the necessity of public health strategies to improve diet quality among African-American women which could help to reduce their risks of chronic diseases.

Systemic steroids and bronchopulmonary dysplasia: a systematic review and meta-analysis.

It is unclear if systemic steroids decrease the risk of Bronchopulmonary Dysplasia (BPD) while increasing the risk of neurodevelopmental impairment (NDI). Conduct a systematic review of randomized controlled trials of systemic steroids to evaluate the risk of BPD, mortality, and NDI in premature infants ≤30 weeks. MEDLINE, EBSCOhost, Web of Science, Cochrane Library, Embase, and CINAHL. Randomized clinical trials of Dexamethasone (DEX) or Hydrocortisone (HC) to prevent BPD in premature infants ≤ 30 weeks. Data were extracted using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Random-effects meta-analyses and multivariable meta-regression were conducted. Primary outcomes were BPD, mortality, and NDI. Secondary outcomes were hypertension, hyperglycemia, sepsis, intestinal perforation, necrotizing enterocolitis (NEC), and retinopathy of prematurity (ROP). The a priori hypothesis was that steroids would reduce the risk of BPD without increasing NDI. There were 6377 preterm infants in the 44 (32 DEX, 13 HC) selected studies. DEX significantly reduced the risk of BPD, RR = 0.66, (95% CI, 0.56-0.78). The most effective DEX regimen was medium cumulative dose (2 to 3 mg/kg), RR = 0.43 (95% CI, 0.29-0.65); day of initiation <8 days: RR = 0.68, (95% CI, 0.59-0.79); and treatment for ≥14 days: RR = 0.67 (95% CI, 0.55-0.80). HC did not significantly decrease the risk of BPD, RR = 0.98, (95% CI, 0.87-1.10). Neither DEX, (RR = 0.92, 95% CI, 0.78-1.09) nor HC (RR = 0.83, 95% CI, 0.68-1.01) decrease the risk of mortality. The risk of CP was not increased by either DEX (RR = 1.09, 95% CI, 0.55-2.17) or HC (RR = 1.18, 95% CI, 0.75-1.87). There were no significant differences between steroids and placebo for MDI/PDI scores. Multivariable meta-regression models showed that DEX significantly reduced the risk of BPD without increased risk of CP. DEX increased the risk of hypertension and hyperglycemia. Studies showed high heterogeneity, differing treatment regimen, missing data and different rates of follow-up. DEX, but not HC, significantly decreased the risk of BPD. Neither steroid showed an increased risk of NDI or mortality.

Abstract P407: Sex and age differences in cardiovascular health in youth referred for hypertension disorders at baseline: A SUPERHERO Registry analysis

Background: The prevalence of hypertension (HTN) and other cardiovascular (CV) disease risk factors (e.g., target organ injury (TOI), obesity, dyslipidemia, hyperglycemia) are increasing steadily in youth. In adults, sex and age differences are established, but remain unknown in children (1–12 years) and adolescents (≥13 years). Objective: Determine sex and age differences in blood pressure (BP) severity, TOI, and CV health in youth referred for HTN disorders. Design/Methods: Cross-sectional analysis of baseline data from the Study of the Epidemiology of Pediatric Hypertension (SUPERHERO), a multisite retrospective Registry of youth referred to subspecialty care for HTN disorders using EHR data. Inclusion criteria were an initial subspecialty clinic visit for HTN disorders identified by ICD-10 codes from 1/1/2016–12/31/2023 and age &lt;19 years. Exclusion criteria were kidney failure on dialysis, kidney transplantation, or pregnancy by ICD-10 codes. The exposures were sex and age at the index visit. Outcomes were BP severity at the index visit based on age, sex, and height-based U.S. guidelines, obesity by BMI or weight-for-length percentiles, and dyslipidemia, hyperglycemia, and TOI (heart and kidney-specific) by ICD-10 codes. We estimated the associations with unadjusted generalized linear models; our directed acyclic graphs did not identify any open, biasing paths necessitating adjustment for confounding factors . Results: Of the 9,356 participants, mean age ± SD was 12.8 ±4.5 years, 36% (n=3,372) were female, 56% (n=5,261) were adolescents, 23% (n=2,162) had stage 2 HTN, 5% (n=451) had TOI (2% heart, 3% kidney), 60% (n=5,655) had obesity, 9% (n=834) had dyslipidemia, and 10% (n=944) had hyperglycemia. Despite less BP severity, females had a higher risk of kidney TOI (RR 1.49, CI: 1.19 to 1.86), hyperglycemia (RR 1.48, CI: 1.3 to 1.68), and number of CV health risk factors (RR 1.1, CI:1.01 to 1.19). Compared to children, adolescents were more likely to have worse BP severity (RR 1.7, CI: 1.6 to 1.8) and HTN (RR 1.1, CI:1.1 to 1.2), and less risk for dyslipidemia (RR: 0.8, 0.7 to 0.9) Conclusions: In a large multisite cohort of youth referred for HTN disorders, females had a 49% higher risk of TOI and 48% greater risk for hyperglycemia despite lower BP severity. Adolescents had more severe BP and HTN compared to children. Next steps in this study include investigating age and sex differences in ambulatory BP and laboratory and echocardiogram data.

Nutritional support in hospitalised patients with diabetes and risk for malnutrition: a secondary analysis of an investigator-initiated, Swiss, randomised controlled multicentre trial

ObjectivesThe main objective of this study was to investigate the effects of nutritional support on mortality in hospitalised patients with diabetes and nutritional risk participating in the Effect of early...

Biochemical study of the effect of lead exposure in nonobese gasoline station workers and risk of hyperglycemia: A retrospective case-control study.

Evaluate the relationship between blood lead (Pb) levels and other biomedical markers and the risk of diabetes in gasoline station workers. The participants were separated into 2 groups: group A consisted of 26 workers from gasoline filling stations, while group B comprised 26 healthy individuals. Serum levels of malondialdehyde, IL-1β, visfatin, insulin, fasting blood sugar, and vitamin D were assessed. Mean Pb level was significantly higher in group A compared to group B (almost 2.9 times higher levels) (14.43 ± 1.01 vs 5.01 ± 1.41, µg/dL). The levels of visfatin (23.19 ± 0.96 vs 3.88 ± 0.58, ng/mL), insulin (22.14 ± 1.31 vs 11.26 ± 0.75, mU/L), fasting blood sugar (118.4 ± 26.1 vs 82.7 ± 9.2, gm/dL), malondialdehyde (6.40 ± 0.27 vs 1.62 ± 0.21, nmol/mL), and IL-1β (330.25 ± 10.34 vs 12.35 ± 1.43, pg/mL) were significantly higher in group A, meanwhile; vitamin D (11.99 ± 1.55 vs 35.41 ± 3.16, ng/mL) were significantly lower in group A. A positive association exists between blood Pb levels and increased inflammatory markers. Lead exposure increases serum insulin and fasting blood sugar, which suggests that it is diabetogenic and that increased inflammation is a possible cause.

Functional genetics reveals the contribution of delta opioid receptor to type 2 diabetes and beta-cell function

Functional genetics has identified drug targets for metabolic disorders. Opioid use impacts metabolic homeostasis, although mechanisms remain elusive. Here, we explore the OPRD1 gene (encoding delta opioid receptor, DOP) to understand its impact on type 2 diabetes. Large-scale sequencing of OPRD1 and in vitro analysis reveal that loss-of-function variants are associated with higher adiposity and lower hyperglycemia risk, whereas gain-of-function variants are associated with lower adiposity and higher type 2 diabetes risk. These findings align with studies of opium addicts. OPRD1 is expressed in human islets and beta cells, with decreased expression under type 2 diabetes conditions. DOP inhibition by an antagonist enhances insulin secretion from human beta cells and islets. RNA-sequencing identifies pathways regulated by DOP antagonism, including nerve growth factor, circadian clock, and nuclear receptor pathways. Our study highlights DOP as a key player between opioids and metabolic homeostasis, suggesting its potential as a therapeutic target for type 2 diabetes.

Relationship Between Early-Pregnancy Glycemia and Adverse Outcomes: Findings From the TOBOGM Study.

We evaluated associations between early-pregnancy oral glucose tolerance test (OGTT) glucose and complications in the Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) cohort to inform prognostic OGTT thresholds. Individuals with risk factors for hyperglycemia were recruited for an international, multicenter, randomized controlled gestational diabetes mellitus (GDM) (World Health Organization 2013 criteria) treatment trial. A 2-h 75-g OGTT was performed at <20 weeks' gestation. Individuals with early treated hyperglycemia in pregnancy were excluded from the primary analysis. Early OGTT glucose concentrations were analyzed continuously and in glycemic categories (normal, low band, and high band). Overall, 3,645 individuals had an OGTT at (mean ± SD) 15.6 ± 2.5 weeks. For each 1-SD increase in fasting, 1-h, and 2-h glucose values, there were continuous positive associations with late GDM: adjusted odds ratio (aOR) 2.04 (95% CI 1.82-2.27), 3.05 (2.72-3.43), and 2.21 (1.99-2.45), respectively. There were continuous positive associations between 1-h and 2-h glucose and the perinatal composite (birth <37 + 0 weeks, birth trauma, birth weight ≥4,500 g, respiratory distress, phototherapy requirement, stillbirth/neonatal death, and shoulder dystocia), with aOR 1.15 (95% CI 1.04-1.26) and 1.14 (1.04-1.25), respectively, and with large-for-gestational-age offspring, with aOR 1.18 (1.06-1.31) and 1.26 (1.01-1.25), respectively. Significant associations were also observed between 1-h glucose and cesarean section and between fasting and 2-h glucose and neonatal hypoglycemia. In categorical analysis, only the high-band 1-h glucose (≥10.6 mmol/L [191 mg/dL]) predicted the perinatal composite. There is a continuous positive association between early-pregnancy OGTT glucose and complications. In individuals with hyperglycemia risk factors, only the high-glycemic-band 1-h glucose corresponded to increased risk of major perinatal complications.

Relationship between Hyperglycemia and Retinopathy of Prematurity in Very Low Birth Weight Infants: A Systematic Review

Background: Retinopathy of prematurity (ROP) is the major cause of neonatal blindness and may account for up to 10% of juvenile blindness. This systematic review evaluates the relationship between hyperglycemia and ROP in VLBW infants. Methods: PRISMA guidelines were used to conduct a systematic review using an online database: Google Scholar, PubMed, and the Wiley Online Library. Original research studies examining the association between hyperglycemia and ROP were the inclusion criteria. Animal studies, a letter to the editor, a commentary report, a review, a meta-analysis not available in full text in English or Bahasa Indonesia, and data in the study insufficient for analysis were all excluded. Results: This systematic review includes nine studies, six cohorts and three case-control studies, involving a total of 1,566 infants. Six studies indicated that newborns in the ROP group had lower mean gestational age and birthweight than those in the non-ROP group. Five investigations found that the mean glucose level in the ROP group was greater than in the non-ROP group. Six studies found that the prevalence of glycemia was much higher than in the non-ROP group. Eight of the nine studies found a significant relationship between hyperglycemia in VLBW infants, and only one found no significant relationship between them. The highest odds ratio and relative risk of hyperglycemia causing ROP were 14.27 (5.16–39.50); p-value &lt;0.001 and 28.062 (7.881–99.924); p-value &lt;0.001, respectively. The overall range of values found across the studies was also considered. Conclusion: Hyperglycemia has a significant relationship with ROP and is also a risk factor for ROP in VLBW infants.

Prenatal exposure to polycyclic aromatic hydrocarbons and phthalate acid esters and gestational diabetes mellitus: A prospective cohort study

BackgroundPolycyclic aromatic hydrocarbons and phthalate acid esters (PAHs & PAEs), known as endocrine disrupting chemicals (EDCs), widely exist in daily life and industrial production. Previous studies have suggested that PAHs & PAEs may modify the intrauterine homeostasis and have adverse effects on fetal development. However, epidemiological evidence on the associations between PAHs & PAEs and gestational diabetes mellitus (GDM) is still limited. ObjectiveTo investigate the effects of prenatal PAHs &PAEs exposure on the risk of GDM and hyperglycemia in pregnant women. MethodsThe study population was a total of 725 pregnant women from a prospective birth cohort study conducted from December 2019 to December 2021. Blood glucose levels were collected by the hospital information system. Urinary PAHs & PAEs concentrations were determined by gas chromatography tandem mass spectrometry. The Poisson regression in a generalized linear model (GLM), multiple linear regression, quantile-based g-computation method (qgcomp), and Bayesian kernel machine regression (BKMR) were applied to explore and verify the individual and overall effects of PAHs & PAEs on glucose homeostasis. Potential confounders were adjusted in all statistical models. ResultsA total of 179 (24.69%) women were diagnosed with GDM. The Poisson regression suggested that a ln-unit increment of 4-OHPHE (4-hydroxyphenanthrene) (adjusted Risk Ratio (aRR) = 1.13; 1.02–1.26) was associated with the increased GDM risk. Mixed-exposure models showed similar results. We additionally found that MBZP (mono-benzyl phthalate) (aRR = 1.19; 1.02–1.39) was positively related to GDM risk in qgcomp model. Although neither model demonstrated that 2-OHNAP (2-hydroxynaphthalene) and 9-OHFLU (9-hydroxyfluorene) increased the risk of GDM, 2-OHNAP and 9-OHFLU exposure significantly increased blood glucose levels. BKMR model further confirmed that overall effects of PAHs & PAEs were significantly associated with the gestational hyperglycemia and GDM risk. ConclusionsOur study presents that environmental exposure to PAHs & PAEs was positively associated with gestational glucose levels and the risks of developing GDM. In particular, 2-OHNAP, 9-OHFLU, 4-OHPHE and MBZP may serve as important surveillance markers to prevent the development of GDM.

Dietary quality and its relationship with metabolic syndrome in the population aged 45 to 59 in Zhejiang Province in 2022

To explore the relationship between dietary quality and metabolic syndrome(MS) in the population aged 45 to 59 in Zhejiang Province. Selecting the 45-59 year old population as the research object from the 2022 nutrition and health monitoring data of residents in Zhejiang Province. Dietary data was obtained by the 24-hour dietary review method on 3 consecutive days and the weighing method of household cooking oil and condiments, and dietary quality was evaluated using the China health diet index(CHDI), which was categorized into four groups according to quartiles of CHDI scores. Multivariate logistic regression model was used to analyze the relationship between different CHDI score groups and MS and its components. A total of 1421 study participants were included, with a mean CHDI score of(56.83±11.80) and a prevalence of MS of 24.5%. After adjusting for gender, age, smoking, and physical activity, the Q4 group with the highest CHDI score had a decreased risk of developing MS(OR=0.57, 95%CI 0.40-0.82), hypertension(OR=0.60, 95% CI 0.44-0.81), and elevated fasting blood glucose(OR=0.41, 95%CI 0.26-0.65) compared to the Q1 group with the lowest CHDI score. After conducting gender subgroup analysis, it was found that: the risk of developing MS, hypertension and high triglycerides was decreased in the Q4 group of CHDI scores in females compared with the Q1 group(P&lt;0.05), whereas in males only high CHDI scores were found to be a protective factor for elevated fasting blood glucose(P&lt;0.05). The quality of diet is negatively associated with the risk of MS, hypertension and hyperglycemia in people aged 45-59 years in Zhejiang Province, and there are gender differences in the relationship between CHDI and MS and its components.

Association of serum irisin levels with glucose and lipid metabolism among adolescents in Yinchuan City from 2017 to 2020

To explore the relationship between serum irisin levels and glucose and lipid metabolism among adolescents in Yinchuan City. From 2017 to 2020, a conbination of convenient sampling and stratified cluster random sampling method were used to select 1219 adolescents aged 12 to 18 years old in Yinchuan City as research subjects. The height and weight were measured using the height and sitting height meter and the bioelectrical impedance analyzer. Blood indicators such as fasting plasma glucose(FPG), totalcholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) were measured using fully automatic biochemical analyzer. Serum irisin levels were measured by enzyme-linked immunosorbent assay(ELISA). Binary logistic regression was used to analyze the correlation between irisin and abnormal glucose and lipid metabolism. The FPG, TC, HDL-C and LDL-C levels of subjects in the highest tertile of irisin levels were significantly lower than those of subjects in the lowest tertile of irisin levels(F values were 5.13, 3.15, 3.07 and 5.01, P&lt;0.05), and the differences were statistically significant(all P&lt;0.05). The serum irisin levels in the hyperglycemia group(t=2.87, P&lt;0.01), hypercholesterolemia group(t=2.36, P=0.02) and hyperLDL-Cemia group(t=2.34, P=0.02) were significantly lower than those in the normoglycemia group, normal TC group and normal LDL-C group. Meanwhile, the irisin level in the low HDL-Cemia group(t=-2.57, P=0.01) was significantly higher than that in the normal HDL-C group, and the differences were statistically significant(P&lt;0.05). Participants in the highest tertile of irisin had 0.51, 0.49 and 0.50 times the risk of hyperglycemia(OR=0.51, 95%CI 0.29-0.87), hypercholesterolemia(OR=0.49, 95%CI 0.27-0.89) and hyperLDL-cemia(OR=0.50, 95%CI 0.25-0.99) compared with those in the lowest tertile. Low levels of irisin are associated with the occurrence of hyperglycemia, hypercholesterolemia, and hyperLDL-Cemia in adolescents.