Risk Factors For Hyperglycemia Research Articles

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.

Efficacy of alpelisib (ALP) + fulvestrant (FUL) with rational use of metformin (MET) in patients with HR+/HER2- advanced breast cancer (ABC).

1049 Background: Hyperglycemia (HG) is an on-target effect of ALP, and prophylactic with metformin was shown to decrease the rate and severity of HG. Here we present efficacy and safety of ALP in a large cohort of patients with rational approach to metformin usage based on risk factors of HG. Methods: Patients (pts) with HR+/HER2- PIK3CAmut ABC were treated with ALP 300mg orally and FUL 500mg IM until disease progression or intolerance. The primary endpoints were progression free survival (PFS) and rate of grade 3/4 HG in different risk groups. Pts were stratified to risk groups of HG based on the algorithm (table 1) before starting ALP and received MET for prevention of HG. Results: A cohort comprised 139 pts, median lines of previous treatment in ABC was 3 (1-9): 88% received CDK4/6i, 60% - FUL, and 55% - chemotherapy (77) prior to ALP. The median PFS (mPFS) on ALP - was 7.0 (CI 95%: 5.0-8.9). The risk of HG was assessed in 138 pts: low (47), moderate (46), and high (42) risk, and 3 pts with type 2 diabetes mellitus. Any grade HG was reported in 62% pts, no cases HG G4 were detected. HG G3 was reported in 13% pts; 10% pts required ALP dose reduction to 250 mg due to HG G3; 3 pts (2%) discontinued ALP due to HG. The mPFS in our analysis was longer than in BYlieve trial in cohort C: 7.0 vs 5.6 mo. We suggest that prophylactic of HG allowed maintenance of full dose of ALP in most patients and thus increased the efficacy of ALP. Furthermore, in contrast to the METALLICA trial we distinguished a low risk group (33%) of pts who don’t need the prophylactic use of MET. Conclusions: Rational use of MET in pts with moderate and high risk of HG reduces the frequency and severity of HG, decreases the rate of ALP dose reductions and as a result may increase the efficacy of ALP. Pts with low risk of HG don’t need MET for HG prevention. [Table: see text]

Abstract PO4-12-12: An Updated analysis of risk factor identification and Hyperglycemia prevention with alpelisib + fulvestrant in PIKC3A-mutated, hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer

Abstract Background: SOLAR-1 investigated use of alpelisib (ALP) + fulvestrant (FLV) in patients (pts) with hormone-receptor positive (HR+)/human epidermal growth factor-2 negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) after progression on endocrine-based therapy and demonstrated a clinically significant increase in all-grade (G) and G3-4 hyperglycemia (HG) compared to placebo + FLV. Current guidance recommends an insulin sensitizer (metformin, thiazolidinedione, SGLT2i) at HG onset. Given high rates of HG, a preventative protocol and identification (ID) of associated risk factors (RFs) was implemented to minimize HG, dose reductions and discontinuation. Although METALLICA investigated the implementation of metformin for hyperglycemia prophylaxis, there is limited data for alpelisib use and hyperglycemia prevention in high risk or controlled type 2 diabetic patients. Duke Breast Oncology Clinic (DBOC) implemented a preventive strategy to minimize HG and treatment disruptions in patients receiving alpelisib, including pre-diabetic and controlled-diabetic patients. Methods: This single-center, retrospective study included pts receiving at least one 28-day cycle of ALP+FLV between June 2019 and April 2023. One week prior to ALP initiation, pts initiated an insulin-sensitizer. Pts had fasting plasma glucose (FPG) levels drawn on day 8, 15, 28, and monthly while on ALP. The primary outcome was incidence of G2-4 HG. Descriptive statistics were used to summarize results. Number of RFs for HG (age ≥ 65 years, BMI ≥ 25 kg/m2, baseline FPG ≥ 100 mg/dL, and A1c ≥ 5.7%) were compared between pts with and without HG using Wilcoxon rank-sum test. Results A total of 30 pts (29 females; 1 male) were included with a median age of 60 years. The cohort was 70% White, 23% Black, while 67% were overweight/obese, and 50% had a history of type 2 diabetes mellitus (T2DM), gestational diabetes, or pre-diabetes. 29 pts received a CDK4/6 inhibitor prior to starting ALP. By day 28, 13 pts (43%) had G2-4 HG, with only 4 (13%) having G3 HG and zero having grade 4. Pts with G2-4 HG had a median of 2 RFs compared to only 1 RF if no HG. 8 pts (27%) required a temporary hold of ALP and 5 pts (17%) required a dose reduction in ALP due to HG. 25 pts permanently discontinued ALP; 14 due to disease progression and 8 due to an adverse event with only 3 due to HG. Median duration of ALP was 86 days (range 24-442), with 5 pts continuing to receive ALP at time of analysis. Patients with grade 2-4 HG by day 28 after ALP initiation had an older median age (66 years), higher BMI (median 28.1 kg/m2), higher baseline FPG (median 100 mg/dL), and higher baseline HbA1c (median 5.6%) compared to those without grade 2-4 HG (Table). Conclusions: Implementation of a HG prevention protocol with ALP in the real-world setting demonstrated fewer G3-4 HG events compared to that seen in SOLAR-1 (13% vs 36.6%) but slightly higher than METALLICA (6%) although we included a higher risk patient population. An increase in HG-associated RFs correlated with a higher incidence of G2-4 HG. Early risk identification and optimization of prophylactic antihyperglycemics can reduce ALP dose reductions and discontinuations secondary to HG. ALP use in higher-risk patients can be considered with a HG prevention protocol. Table 1. Hyperglycemia outcomes Citation Format: Heather Moore, Sarah Burnette, Emily Poehlein, Hui-Jie Lee, Kelly Westbrook, Thomas Bagwell, Kervin Novido, Susan Dent. An Updated analysis of risk factor identification and Hyperglycemia prevention with alpelisib + fulvestrant in PIKC3A-mutated, hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-12.

Cost-effectiveness of diagnosis and treatment of early gestational diabetes mellitus: economic evaluation of the TOBOGM study, an international multicenter randomized controlled trial

A recently undertaken multicenter randomized controlled trial (RCT) "Treatment Of BOoking Gestational diabetes Mellitus" (TOBOGM: 2017-2022) found that the diagnosis and treatment of pregnant women with early gestational diabetes mellitus (GDM) improved pregnancy outcomes. Based on data from the trial, this study aimed to assess the cost-effectiveness of diagnosis and treatment of early GDM (from <20 weeks') among women with risk factors for hyperglycemia in pregnancy compared with usual care (no treatment until 24-28 weeks') from a healthcare perspective. Participants' healthcare resource utilization data were collected from their self-reported questionnaires and hospital records, and valued using the unit costs obtained from standard Australian national sources. Costs were reported in US dollars ($) using the purchasing power parity (PPP) estimates to facilitate comparison of costs across countries. Intention-to-treat (ITT) principle was followed. Missing cost data were replaced using multiple imputations. Bootstrapping method was used to estimate the uncertainty around mean cost difference and cost-effectiveness results. Bootstrapped cost-effect pairs were used to plot the cost-effectiveness (CE) plane and cost-effectiveness acceptability curve (CEAC). Diagnosis and treatment of early GDM was more effective and tended to be less costly, i.e., dominant (cost-saving) [-5.6% composite adverse pregnancy outcome (95% CI:-10.1%,-1.2%),-$1373 (95% CI:-$3,749, $642)] compared with usual care. Our findings were confirmed by both the CE plane (88% of the bootstrapped cost-effect pairs fall in the south-west quadrant), and CEAC (the probability of the intervention being cost-effective ranged from 84% at a willingness-to-pay (WTP) threshold value of $10,000-99% at a WTP threshold value of $100,000 per composite adverse pregnancy outcome prevented). Sub-group analyses demonstrated that diagnosis and treatment of early GDM among women in the higher glycemic range (fasting blood glucose 95-109mg/dl [5.3-6.0mmol/L], 1-h blood glucose ≥191mg/dl [10.6mmol/L] and/or 2-h blood glucose 162-199mg/dl [9.0-11.0mmol/L]) was more effective and less costly (dominant) [-7.8% composite adverse pregnancy outcome (95% CI:-14.6%,-0.9%),-$2795 (95% CI:-$6,638,-$533)]; the intervention was more effective and tended to be less costly [-8.9% composite adverse pregnancy outcome (95% CI:-15.1%,-2.6%),-$5548 (95% CI:-$16,740, $1547)] among women diagnosed before 14 weeks' gestation as well. Our findings highlight the potential health and economic benefits from the diagnosis and treatment of early GDM among women with risk factors for hyperglycemia in pregnancy and supports its implementation. Long-term follow-up studies are recommended as a key future area of research to assess the potential long-term health benefits and economic consequences of the intervention. National Health and Medical Research Council (grants 1104231 and 2009326), Region O¨rebro Research Committee (grants Dnr OLL-970566 and OLL-942177), Medical Scientific Fund of the Mayor of Vienna (project 15,205 and project 23,026), South Western Sydney Local Health District Academic Unit (grant 2016), and Western Sydney University Ainsworth Trust Grant (2019).

The predictive ability of the triglyceride glucose index, fasting glucose and oral glucose tolerance test for postpartum hyperglycemia in women with a GDM history

Objective This study aimed to determine the likelihood of hyperglycemia postpartum in women with gestational diabetes mellitus (GDM) and to identify the predictors. Methods The retrospective cohort study involved 1 527 GDM patients who delivered at Peking University First Hospital from 1 January 2021, to 31 December 2021. According to the blood glucose level of postpartum oral glucose tolerance test (OGTT), women were divided into a normal glucose tolerance (NGT) group and a hyperglycemia group, and their characteristics and risk factors of hyperglycemia were compared. Results The prevalence of hyperglycemia was 33.9% (184/543) at 6–12 weeks postpartum. Compared with the NGT group, the fasting plasma glucose (FPG) of hyperglycemia group increased significantly during pregnancy and postpartum, the OGTT 1h postprandial glucose (PG) and 2hPG increased in the second trimester of pregnancy, the triglyceride (TG) increased in the first trimester of pregnancy and postpartum, the triglyceride glucose (TyG) index increased in the first trimester of pregnancy and postpartum, and the total cholesterol (TCHO) and low density lipoprotein cholesterol (LDL-C) decreased in the second trimester (p < 0.05). Fasting plasma glucose (FPG) in the first trimester [odds ratio (OR) = 3.583, p < 0.001], OGTT 2hPG in the second trimester (OR = 1.604, p < 0.001), the TyG index in the first trimester (OR = 1.863, p = 0.045) and FPG in third trimester (OR = 1.985, p = 0.024) were independent risk factors for postpartum hyperglycemia. Conclusions Approximately one-third of women with GDM have hyperglycemia 6–12 weeks after delivery. FPG and the TyG index in the first trimester, OGTT 2hPG in the second trimester and FPG in third trimester are risk factors for postpartum hyperglycemia.

Risk factors for hyperglycemia in COVID-19 patients treated with remdesivir.

The primary objective of this study was to investigate the factors contributing to hyperglycemic adverse events (AEs) associated with the administration of remdesivir in hospitalized patients diagnosed with coronavirus disease 2019 (COVID-19). Furthermore, the study aimed to develop a risk score model employing various machine learning approaches. A total of 1262 patients were enrolled in this investigation. The relationship between covariates and hyperglycemic AEs was assessed through logistic regression analysis. Diverse machine learning algorithms were employed for the purpose of forecasting hyperglycemia-related complications. After adjusting for covariates, individuals with a body mass index ≥23 kg/m2 , those using proton pump inhibitors, cholinergic medications, or individuals with cardiovascular diseases exhibited approximately 2.41-, 2.73-, 2.65-, and 1.97-fold higher risks of experiencing hyperglycemic AEs (95% CI 1.271-4.577, 1.223-6.081, 1.168-5.989, and 1.119-3.472, respectively). Multivariate logistic regression, elastic net, and random forest models displayed area under the receiver operating characteristic curve values of 0.65, 0.66, and 0.60, respectively (95% CI 0.572-0.719, 0.640-0.671, and 0.583-0.611, respectively). This study comprehensively explored factors associated with hyperglycemic complications arising from remdesivir administration and, concurrently, leveraged a range of machine learning methodologies to construct a risk scoring model, thereby facilitating the tailoring of individualized remdesivir treatment regimens for patients with COVID-19.

Abstract 12516: Explaining the Increase Mortality From Cardiovascular Disease in Indonesia: Unraveling the Trends in the Influence of Metabolic and Behavioral Risk Factors (2000-2019)

Background: CVD burden has shifted from developed to developing countries; it decreased from 48% in 1990 to 43% in 2010, while in developing countries, it increased from 18% to 25%. According to several studies, current behavioural and metabolic risk factors enhance the risk of cardiovascular disease risk. Aims: We investigated whether changes in the risk factors—hyperglycemia, obesity, dyslipidemia, hypertension, and smoking—caused the rise in CVD mortality and incidence from 2000 to 2019 in Indonesia. Methods: Data from 34 province-year observations for CVD outcomes and changes in risk factors between 2000 and 2019 in Indonesia were obtained from IHME. A statistical model calculated risk factor fatalities using population-attributable fractions and baseline year death data. Multivariate regression on Summary Exposure Values of risk factors with mortality and incidence rates and lag year analysis was performed using R, measuring heteroscedasticity-consistent standard errors. Covariates, including the Socio-demographic Index, Primary healthcare, and GDP per capita, were added. Results: The age-standardized mortality rate per 100,000 for CVD from 2000 to 2019 in Indonesia increased from 356 to 412 among men and decreased from 357 to 354 among women. There was an increase in exposure to risk factors; obesity by 9%, smoking by 1%, dyslipidemia by 1.3%, hyperglycemia by 2%, and hypertension by 1.2%. An additional 14,517 men and 17,917 women died from CVD, attributable to obesity. Multivariate regression with province-fixed and year-fixed analysis shows a strong correlation between hyperglycemia in women (6;95% CI 0 to 12) with an increasing death rate in IHD. Notably, the association between hyperglycemia and IHD mortality was regardless of socioeconomic class and healthcare coverage. The association between a 10-year lag of high LDL and incidence of IHD was five times stronger compared to other risk factors, particularly in men (5;95%CI 2 to 8, incidence per 1-point increase). Conclusion: Female hyperglycemia increases CVD mortality risk. However, the prior-year analysis showed that high LDL levels increase incidence in men and women. These findings imply policymakers should prevent high LDL risk factors and hyperglycemia 10 years earlier.

Intensive Care Unit Hyperglycemia After Cardiac Surgery: Risk Factors and Clinical Outcomes

Patients with hyperglycemia after cardiac surgery face increased morbidity and mortality due to postoperative complications. The main purpose of this study was to evaluate the incidence of postoperative hyperglycemia, the hyperglycemia risk factors, and its association with clinical outcomes in patients admitted to the cardiac surgery intensive care unit after cardiac surgery. Prospective, observational study. Single-center hospital. Two hundred ten consecutive postoperative cardiac surgery patients admitted to the cardiac surgery intensive care unit. Patients' blood glucose levels were evaluated immediately after cardiac surgery and every 3 hours daily for 7 days or earlier upon discharge. Intravenous insulin was administered as per the institution's protocol. Perioperative predisposing risk factors for hyperglycemia and clinical outcomes were assessed. Postoperative hyperglycemia, defined as glucose level ≥180 mg/dL, occurred in 30% of cardiac surgery patients. Diabetes mellitus (odds ratio [OR] 6.73; 95% CI [3.2-14.3]; p < 0.001), white blood cell count (OR 1.28; 95% CI [1.1-1.4]; p < 0.001), and EuroSCORE II (OR 1.20; 95% CI [1.1-1.4]; p=0.004) emerged as independent prognostic factors for hyperglycemia. Moreover, patients with glucose ≥180 mg/dL had higher rates of acute kidney injury (34.9% v 18.9%, p=0.013), longer duration of mechanical ventilation (959 v 720 min, p=0.019), and sedation (711 v 574 min, p=0.034), and higher levels of intensive care unit (ICU)-acquired weakness (14% v 5.5%, p=0.027) and rate of multiorgan failure (6.3% v 0.7%, p=0.02) compared with patients with glucose levels <180 mg/dL. In the intensive care unit, hyperglycemia occurs frequently in patients immediately after cardiac surgery. Diabetes, high EuroSCORE II, and preoperative leukocytosis are independent risk factors for postoperative hyperglycemia. Hyperglycemia is associated with worse clinical outcomes, including a higher rate of acute kidney injury and ICU-acquired weakness, greater duration of mechanical ventilation, and a higher rate of multiorgan failure.

The incidence of and risk factors for hyperglycemia and hypoglycemia in preterm infants receiving early-aggressive parenteral nutrition

IntroductionOptimizing nutritional support helps prevent extra uterine growth restriction and adverse long-term outcomes in preterm infants. ObjectivesThis study aimed to analyze the incidence of and risk factors for hyperglycemia and hypoglycemia in preterm infants receiving early-aggressive parenteral nutrition (PN). MethodsThis prospective observational study included preterm infants receiving PN at the Neonatal Intensive Care Unit of Dr. Soetomo General Hospital between April 2018 and May 2019. Potential risk factors analyzed included asphyxia, sepsis, respiratory distress syndrome, multiple congenital anomalies, mortality, necrotizing enterocolitis, retinopathy of prematurity, the postoperative period, inotropic administration, glucose infusion rate (GIR) > 10–12 mg/kg/min, GIR 4–<5.5 mg/kg/min, and increase in GIR <1 mg/kg/min. ResultsOf the 105 preterm infants included, hyperglycemia and hypoglycemia were found in 14 (13.3%) and 26 (24.8%) infants, respectively, with most incidents occurring in the first week (hyperglycemia: 85.7%; hypoglycemia: 88.5%). Sepsis was an independent risk factor for hyperglycemia (odds ratio [OR]: 8.743, 95% confidence interval [CI]: 2.392–31.959; P = 0.001). Hypoglycemia independent risk factors included the postoperative period (OR: 4.425, 95% CI: 1.218–16.073; P = 0.024) and use of GIR 4–<5.5 mg/kg/min (OR: 2.950, 95% CI: 1.035–8.405; P = 0.043). ConclusionHyperglycemia and hypoglycemia can occur in preterm infants receiving early-aggressive PN; most cases occur within the first week of life. Hypoglycemia correlated with low glucose intake, and hyperglycemia correlated with sepsis. Monitoring blood glucose levels in preterm infants receiving PN, especially in the first weeks of life, may decrease morbidity associated with hyperglycemia or hypoglycemia.

Incidence and Factors Associated with Hyperglycemia in Patients with First Hospitalization for Major Depression Disorder: A Large Cross-Sectional Sample.

Major depressive disorder (MDD) is a mood disorder characterized by persistent spontaneous depression and has a high rate of disability and mortality. There is a complex relationship between MDD and disorders of glucose metabolism, and our study aimed to investigate the prevalence and risk factors for hyperglycemia in patients with MDD who were hospitalized for the first times. A total of 981 first-time inpatients with MDD were recruited, socio-demographic information, anthropometric data, and biochemical parameters were collected for each participant. The 17-item Hamilton Assessment Scale for Depression (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive Syndrome Scale (PSS), and Clinical General Impressions Inventory-Severity of Illness (CGI-SI) scores were used to assess patients' clinical symptoms. The prevalence of hyperglycemia was 9.28% among patients with MDD who were hospitalized for the first time. Compared to the non-hyperglycemic subgroup, patients in the hyperglycemic subgroup were found to have more extensive and significant demographic and clinical characteristics, higher levels of metabolism-related parameters, and more severe psychological and psycho-pathological symptoms. Age, thyroid stimulating hormone (TSH), triglycerides (TG) were risk factors for hyperglycemia in MDD patients, while course of disease was a protective factor. The study findings suggest that the prevalence of hyperglycemia is not high in patients with MDD who are hospitalized for the first time. The risk variables for predicting hyperglycemia include age, TSH and TG. The above three factors and course of disease have good combined diagnostic ability for hyperglycemia.

Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy

BackgroundWhether treatment of gestational diabetes before 20 weeks’ gestation improves maternal and infant health is unclear.MethodsWe randomly assigned, in a 1:1 ratio, women between 4 weeks’ and 19 weeks 6 days’ gestation who had a risk factor for hyperglycemia and a diagnosis of gestational diabetes (World Health Organization 2013 criteria) to receive immediate treatment for gestational diabetes or deferred or no treatment, depending on the results of a repeat oral glucose-tolerance test [OGTT] at 24 to 28 weeks’ gestation (control). The trial included three primary outcomes: a composite of adverse neonatal outcomes (birth at <37 weeks’ gestation, birth trauma, birth weight of ≥4500 g, respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia), pregnancy-related hypertension (preeclampsia, eclampsia, or gestational hypertension), and neonatal lean body mass.ResultsA total of 802 women underwent randomization; 406 were assigned to the immediate-treatment group and 396 to the control group; follow-up data were available for 793 women (98.9%). An initial OGTT was performed at a mean (±SD) gestation of 15.6±2.5 weeks. An adverse neonatal outcome event occurred in 94 of 378 women (24.9%) in the immediate-treatment group and in 113 of 370 women (30.5%) in the control group (adjusted risk difference, −5.6 percentage points; 95% confidence interval [CI], −10.1 to −1.2). Pregnancy-related hypertension occurred in 40 of 378 women (10.6%) in the immediate-treatment group and in 37 of 372 women (9.9%) in the control group (adjusted risk difference, 0.7 percentage points; 95% CI, −1.6 to 2.9). The mean neonatal lean body mass was 2.86 kg in the immediate-treatment group and 2.91 kg in the control group (adjusted mean difference, −0.04 kg; 95% CI, −0.09 to 0.02). No between-group differences were observed with respect to serious adverse events associated with screening and treatment.ConclusionsImmediate treatment of gestational diabetes before 20 weeks’ gestation led to a modestly lower incidence of a composite of adverse neonatal outcomes than no immediate treatment; no material differences were observed for pregnancy-related hypertension or neonatal lean body mass. (Funded by the National Health and Medical Research Council and others; TOBOGM Australian New Zealand Clinical Trials Registry number, ACTRN12616000924459.)

Association between poor parent-daughter relationships and the risk of hyperglycemia in pregnancy: a hospital-based prospective cohort study in Japan

BackgroundAdverse child experiences (ACEs), childhood maltreatment and household dysfunction, are risk factors of hyperglycemia in pregnancy (HIP), including diabetes before pregnancy, gestational diabetes (GDM), and overt diabetes in pregnancy, through increased risk of unhealthy behaviors, obesity, and stress response system dysfunction. While ACEs are often difficult to be assessed in hospital settings, parent-daughter relationship, that is, pregnant women’s relationship with their parents can be considered as a measurable maker for ACEs that may be associated with HIP. The purpose of this study is to examine the association between poor parent-daughter relationship and HIP.MethodsHospital-based prospective cohort study was conducted in Japan (N = 6,264). Women visiting participating 58 facilities for delivery between April 2019 and March 2020 were included. Parent-daughter relationship was assessed by a questionnaire asking whether participants were satisfied with their relationship with their parents. HIP was diagnosed based on the criteria used in Japan. A multiple logistic regression model was applied to adjust for covariates.ResultsPregnant women who were not very satisfied and not satisfied at all with the relationship with their parents, and HIP were 343 (5.5%), 74 (1.2%), and 274 (4.4%), respectively. Pregnant women who were not very satisfied with their parent-daughter relationship showed a significant positive association with HIP in the crude model (odds ratio (OR): 1.71, 95% confidence interval (CI): 1.11–2.63). When stratified by psychiatric disease history, we found a significant positive association among those without psychiatric disease history (OR: 1.77, 95% CI: 1.11–2.84), but not among those with psychiatric disease history (OR: 0.61, 95% CI: 0.16–2.28).ConclusionsPoor parent-daughter relationship was associated with the risk of HIP among pregnant women without psychiatric disease history, suggesting that this simple question could be used to estimate the risk of HIP when it was challenging to inquire directly about ACEs. Further research is needed to elucidate the mechanism of the association.

Risk Factors of Hyperglycemia After Treatment With the AKT Inhibitor Ipatasertib in the Prostate Cancer Setting: A Machine Learning-Based Investigation.

Hyperglycemia is a major adverse event of phosphatidylinositol 3-kinase/AKT inhibitor class of cancer therapeutics. Machine learning (ML) methodologies can identify and highlight how explanatory variables affect hyperglycemia risk. Using data from clinical trials of the AKT inhibitor ipatasertib (IPAT) in the metastatic castrate-resistant prostate cancer setting, we trained an XGBoost ML model to predict the incidence of grade ≥2 hyperglycemia (HGLY ≥ 2). Of the 1,364 patients included in our analysis, 19.4% (n = 265) of patients had HGLY ≥2 events with a median time of first onset of 28 days (range, 0-753 days), and 30.0% (n = 221) of patients on an IPAT regimen had at least one HGLY ≥2 event compared with 7.0% (n = 44) of patients on placebo. An 11-variable XGBoost model predicted HGLY ≥2 events well with an AUROC of 0.83 ± 0.02 (mean ± standard deviation). Using SHapley Additive exPlanations analysis, we found IPAT exposure and baseline HbA1c levels to be the strongest predictors of HGLY ≥2, with additional predictivity of baseline measurements of fasting glucose, magnesium, and high-density lipoproteins. The findings support using patients' prediabetic status as a key factor for hyperglycemia monitoring and/or trial exclusion criteria. Additionally, the model and relationships between explanatory variables and HGLY ≥2 described herein can help identify patients at high risk for hyperglycemia and develop rational risk mitigation strategies.

The Relationship Between Basal Metabolism Index and Blood Sugar Levels Among Farmers: a Secondary Data Analysis of Non-Communicable Disease in Public Health Center of Pakusari, Jember Regency, Indonesia

Obesity is a risk factor for hyperglycemia. Farmers are a group of people at risk of obesity and hyperglycemia due to a lifestyle that consumes foods high in fat and carbohydrates. The aim of this study wants to analyze the relationship between body mass index and blood sugar levels of farmers in the report of Integrated Development Post of Non-Communicable Disease (Posbindu PTM) Pakusari Jember Health Center. The survey analysis study used a retrospective cohort study. A design was used to analyze secondary data of Posbindu PTM Pakusari Jember Health Center registered from January to October 2020 among 345 farmers. A population of 345 farmers was selected by purposive sampling to be used as research samples. Characteristics of participants, height and weight, and random blood sugar levels were measured through a health monitoring book (KMS Posbindu PTM). The chi-Square test was used to answer the objective of the study. Among 146 farmers identified that 46.6% were obese and 45.9% were hyperglycemia. There was a relationship between body mass index and blood sugar levels in farmers (p-value = 0.000). Indirectly, body mass index affects blood sugar levels, manifesting as diabetes mellitus and other complications. Therefore, obesity should be identified as a risk factor associated with farmers' blood sugar levels.

The predictors of hyperglycemia and its effects on neurological outcome in the patients with aneurysmal subarachnoid hemorrhage undergoing surgical clipping: A prospective observational study.

Following intracranial aneurysm rupture, 70-90% of patients have hyperglycemia as a stressful response. Uncontrolled hyperglycemia is deleterious if not controlled well. The objectives of the study were to assess the prevalence, risk factors of hyperglycemia, and its effect on outcome in aneurysmal subarachnoid hemorrhage (aSAH) patients who underwent aneurysmal clipping. Following intracranial aneurysm rupture, 70-90% of patients have hyperglycemia as a stressful response. Uncontrolled hyperglycemia is deleterious if not controlled well. The objectives of the study were to assess the prevalence, risk factors of hyperglycemia, and its effect on outcome in aSAH patients who underwent aneurysmal clipping. At admission, the prevalence of hyperglycemia and severe hyperglycemia was 31.8% and 6.8%, respectively. Perioperative hyperglycemia and severe hyperglycemia were seen in 75.7% and 27%, respectively. History of diabetes mellitus (DM), higher admission random blood sugar, and higher admission mean blood pressure were predictors of perioperative hyperglycemia (P- 0.046, 0.00, and 0.004, respectively) and severe hyperglycemia (P- 0.048, 0.00, and 0.031). In addition, female sex, prolonged duration of anesthesia, and surgery were also found to be the predictors of hyperglycemia (P- 0.025, 0.07, and 0.012). Increased ventilator, intensive care unit, and hospital days were associated with perioperative hyperglycemia and severe hyperglycemia, respectively (P ≤ 0.006/0.00, P ≤ 0.007/0.00, and P ≤ 0.038/0.00). Poor Glasgow Outcome Score at 1 and 3 months after discharge was associated with admission and perioperative hyperglycemia ([P ≤ 0.000/0.000 and P ≤ 0.000/0.000], respectively). However, no association was seen between mortality and hyperglycemia or severe hyperglycemia. A higher prevalence of hyperglycemia is present in aSAH patients. A higher incidence of perioperative hyperglycemia is associated with poor neurological outcomes. Hence, the identification of risk factors and meticulous perioperative control of hyperglycemia will help in preventing poor neurological outcomes.

Incidence and risk factors of intraoperative hyperglycemia in non-diabetic patients: a prospective observational study

BackgroundIntraoperative hyperglycemia has been associated with multiple postoperative complications such as surgical site infection, myocardial infarction, stroke, and death. These complications are not confined to only diabetic patients. However, the incidence of intraoperative hyperglycemia in non-diabetic patients has not been fully elucidated. Additionally, these patients’ risk factors were not well established in previous studies.MethodsFour hundred forty non-diabetic patients who underwent intermediate- to high-risk surgery were included in the study. We prospectively measured the capillary blood glucose level in all patients during surgery. The incidence of intraoperative hyperglycemia was defined as at least one episode of blood glucose level of more than 180 mg/dL. Risk factors for hyperglycemia were assessed using multivariable logistic regression analysis.ResultsSixty-five (14.7%) patients developed hyperglycemia during surgery. The independent risk factors for intraoperative hyperglycemia were an American Society of Anesthesiologists status ≥ 3 (odds ratio [OR] 6.09, 95% confidence interval [CI]: 2.67–13.89, p < 0.001), preoperative impaired fasting blood sugar (OR 2.28, 95%CI:1.13–4.61, p = 0.021), duration of anesthesia ≥ 3 h (OR 4.06, 95%CI: 1.23–13.45, p = 0.021), intraoperative hypotension (OR 5.37, 95%CI: 2.35–12.29, p < 0.001), intraoperative blood transfusion (OR 4.35, 95%CI: 2.15–8.79, p < 0.001), and steroid use (OR 2.39, 95%CI: 1.20–4.76, p = 0.013). Surgical site infection was higher in patients with intraoperative hyperglycemia compared with patients without intraoperative hyperglycemia (4 [6.1%] vs. 6 [1.6%], respectively, p = 0.035).ConclusionThe incidence of intraoperative hyperglycemia was significant in non-diabetic patients during intermediate- to high-risk surgery. Risk factors should be identified to prevent intraoperative hyperglycemia.Trial registrationThe study was prospectively registered at https://www.thaiclinicaltrials.org (TCTR20191114001).

Hyperglycemia in Severe and Critical COVID-19 Patients: Risk Factors and Outcomes.

Background: Hyperglycemia is commonly seen in critically ill patients. This disorder was also seen in coronavirus disease 2019 (COVID-19) patients and was associated with a worse prognosis. The current study determined the prevalence, risk factors, and prognostic implications of hyperglycemia in COVID-19 patients.Method: This was a retrospective observational study performed in an intensive care unit for COVID-19 patients. Electronic data of COVID-19 patients admitted to the intensive care unit from August 2nd to October 15th, 2021, were collected. Patients were divided into non-hyperglycemia, hyperglycemia in diabetic patients, and hyperglycemia in non-diabetic patients. Primary outcomes were 28-day and in-hospital mortalities. Multinomial logistic regression and multivariable Cox regression models were used to determine the risk factors for hyperglycemia and mortality, respectively.Results: Hyperglycemia was documented in 65.6% of patients: diabetic patients (44.8%) and new-onset hyperglycemia (20.8%). In-hospital and 28-day mortality rates were 30.2% and 26.1%, respectively. Respiratory failure, corticosteroid therapy, and a higher level of procalcitonin were risk factors for hyperglycemia in diabetic patients, whereas cardiovascular diseases, respiratory failure, and higher aspartate aminotransferase/glutamate aminotransferase ratio were risk factors for hyperglycemia in non-diabetic patients. The risk of the 28-day mortality rate was highest in the new-onset hyperglycemia (hazard ratio [HR] 3.535, 95% confidence interval [CI] 1.338-9.338, p=0.011), which was higher than hyperglycemia in type 2 diabetes mellitus patients (HR 1.408, 95% CI 0.513-3.862, p=0.506).Conclusion: Hyperglycemia was common in COVID-19 patients in the intensive care unit. Hyperglycemia reflected the disease severity but was also secondary to therapeutic intervention. New-onset hyperglycemia was associated with poorer outcomes than that in diabetic patients.

Characterization, management, and risk factors of hyperglycemia during PI3K or AKT inhibitor treatment.

PurposeThe phosphoinositide 3‐kinase (PI3K)/protein kinase B (AKT) pathway controls insulin sensitivity and glucose metabolism. Hyperglycemia is one of the most common on‐target adverse effects (AEs) of PI3K/AKT inhibitors. As several PI3K and AKT inhibitors are approved by the United States Food and Drug Administration or are being studied in clinical trials, characterizing this AE and developing a management strategy is essential.MethodsPatients with hematologic or solid malignancies treated at Memorial Sloan Kettering Cancer Center with a PI3K or AKT inhibitor were included in this retrospective analysis. A search for patients experiencing hyperglycemia was performed. The frequency, management interventions and outcomes were characterized.ResultsFour hundred and ninety‐one patients with 10 unique cancer types who received a PI3K or AKT inhibitor were included. Twelve percent of patients required a dose interruption, 6% of patients required a dose reduction and 2% of patients were hospitalized to manage hyperglycemia. No events occurred among patients receiving β‐, γ‐, or δ‐ specific PI3K inhibitor. There was one case where the PI3K or AKT inhibitor was permanently discontinued due to hyperglycemia. Metformin was the most commonly used antidiabetic medication, followed by insulin, sodium‐glucose transport protein 2 (SGLT2) inhibitors, and sulfonylurea. SGLT2 inhibitors were associated with the greatest reductions in blood sugar, followed by metformin. At least one case of euglycemic diabetic ketoacidosis (DKA) occurred in a patient on PI3K inhibitor and SGLT2 inhibitor. Body mass index ≥ 25 and HbA1c ≥ 5.7 are were independently significant predictors of developing hyperglycemia.ConclusionHyperglycemia is one of the major on‐target side effects of PI3K and AKT inhibitors. It is manageable with antidiabetic medications, treatment interruption and/or dose modification. We summarize pharmacological interventions that may be considered for PI3K/AKT inhibitor induced hyperglycemia. SGLT2‐inhibitor may be a particularly effective second‐line option after metformin but there is a low risk of euglycemic DKA, which can be deadly. To our knowledge, our report is the largest study of hyperglycemia in patients receiving PI3K/AKT inhibitors.

-2548G>A LEP Polymorphism Is Positively Associated with Increased Leptin and Glucose Levels in Obese Saudi Patients Irrespective of Blood Pressure Status

Background and Objectives: In this study, we aimed to investigate the link between common -2548G>A (rs7799039) promoter variant of the human leptin gene (LEP) with leptin and serum glucose leptin levels in obese Saudi patients. Materials and Methods: A total of 206 Saudi adults (80 obese normotensive nondiabetics, 76 obese hypertensive with Type 2 Diabetes and 50 normotensive nondiabetic controls) were genotyped for -2548G>A LEP polymorphism using the polymerase chain reaction-restriction fragment-length polymorphism technique. Results: Participants with minor AA genotype had significantly higher blood glucose levels (6.8 ± 0.55 mmol/L vs. 5.8 ± 0.30 mmol/L; p < 0.04) and HOMA-IR (4.1 ± 0.84 vs. 2.6 ± 0.67; p = 0.03) against those carrying major GG genotype. Participants with heterozygous GA genotype had significantly higher serum leptin levels against those carrying major GG genotype (40.0 ± 2.6 ng/mL vs. 29.6 ± 2.6 ng/mL; p = 0.04). Further investigation showed that individuals with AA, GA, GA + AA genotypes are at greater risk of developing hyperglycemia compared to those with GG genotype [OR 3.7(1.6–8.4), p = 0.001; 3.2 (1.2–8.6), p = 0.03; 3.5 (1.6–7.7), p = 0.001, respectively]. Additionally, the -2548AA allele was shown to be a risk factor for hyperglycemia [OR 1.9 (1.2–3.0), p = 0.006]. Our data revealed no relationship between this variant of the LEP gene with systolic and diastolic BP, signifying that this genetic variant is not a significant marker of obesity and hypertension in the Saudi population. Conclusions: AA and GA genotypes and LEP gene -2548AA alleles may signify potent risk factors predisposing healthy individuals to develop T2DM regardless of blood-pressure profile.

Medicinal plants in Sabah (North Borneo) exhibit anti-pancreatic lipase, anti-amylase, and antioxidant properties

Medicinal plants have been widely used for their notable health benefits and help in disease prevention for generations. In recent years, obesity has become among the risk factors of hyperglycemia and oxidation stress. This study aims to investigate the potential of plants in Sabah, North Borneo to inhibit the key enzymes involved in obesity, hyperglycemia and oxidative stress. A total of 46 plant extracts were subjected to anti-pancreatic lipase, α-amylase inhibition and antioxidant assays. It was observed that S43 (Lantana camara) exhibited the greatest IC50 of anti-pancreatic lipase activity (mean of IC50 (±S.D.) = 0.20 mg mL-1 ± 0.010). Cinnamomum sp. (S42) has the most substantial α-amylase activity with a mean IC50 (±S.D.) = 2.68 mg mL-1 ± 0.471. S19 (Glochidion rubrum) was the most effective antioxidants (mean of IC50 (±S.D.) = 0.011 mg mL-1 ± 0.004) among all the investigated samples. Interestingly, three plant extracts were found (S6-Buchanania sp.; S22-Vitex negundo and S42-Cinnamomum sp.) to exhibit inhibition activity in anti-pancreatic lipase, α-amylase and antioxidant assays. The bioactivities of plant extracts have been closely related to the content of phytochemicals, as in earlier studies. Thus, plants have the potential to serve as supplements and nutraceuticals for obesity and other related complications.