Retinal microcirculation changes in prediabetic patients with short-term increased blood glucose using optical coherence tomography angiography.

BACKGROUND: Retinal microcirculation alterations are early indicators of diabetic microvascular complications. Optical coherence tomography angiography (OCTA) is a noninvasive method to assess these changes. This study analyzes changes in retinal microcirculation in prediabetic patients during short-term increases in blood glucose using OCTA. AIM: To investigate the changes in retinal microcirculation in prediabetic patients experiencing short-term increases in blood glucose levels using OCTA. METHODS: Fifty volunteers were divided into three groups: Group 1 [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)], Group 2 (both IFG and IGT), and a control group. Retinal microcirculation parameters, including vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) metrics, were measured using OCTA. Correlations between these parameters and blood glucose levels were analyzed in both the fasting and postprandial states. RESULTS: One hour after glucose intake, the central VD (P = 0.023), central PD (P = 0.026), and parafoveal PD (P < 0.001) were significantly greater in the control group than in the fasting group. In Group 1, parafoveal PD (P < 0.001) and FAZ circularity (P = 0.023) also increased one hour after glucose intake. However, no significant changes were observed in the retinal microcirculation parameters of Group 2 before or after glucose intake (P > 0.05). Compared with the control group, Group 1 had a larger FAZ area (P = 0.032) and perimeter (P = 0.018), whereas Group 2 had no significant differences in retinal microcirculation parameters compared with the control group (P > 0.05). Compared with Group 1, Group 2 had greater central VD (P = 0.013) and PD (P = 0.008) and a smaller FAZ area (P = 0.012) and perimeter (P = 0.010). One hour after glucose intake, Group 1 had a larger FAZ area (P = 0.044) and perimeter (P = 0.038) than did the control group, whereas Group 2 showed no significant differences in retinal microcirculation parameters compared with the control group (P > 0.05). Group 2 had greater central VD (P = 0.042) and PD (P = 0.022) and a smaller FAZ area (P = 0.015) and perimeter (P = 0.016) than Group 1. At fasting, central PD was significantly positively correlated with blood glucose levels (P = 0.044), whereas no significant correlations were found between blood glucose levels and OCTA parameters one hour after glucose intake. CONCLUSION: A short-term increase in blood glucose has a more pronounced effect on retinal microcirculation in prediabetic patients with either IFG or IGT.

Exploring the Association of VEGF-A and ANGPTL2 with the Prognosis of Non-proliferative and Proliferative Diabetic Retinopathy.

Introduction Diabetic retinopathy (DR) is a microvascular ailment that can arise from the long-term effects of diabetes mellitus. It can potentially cause retinal damage that could endanger vision and cause blindness. The worsening of DR is mainly linked to poor glycemic control, uncontrolled hypertension, and dyslipidemia. There is a need for alternative and clinically significant novel molecules involved in the pathogenesis of DR because the diagnostic and prognostic markers have reached a limit. Materials and method This study included sex and age-matched diabetic patients with proliferative stage (N = 70), non-proliferative stage (N = 80), and control (N = 80, without the sign of DR). These patients were recruited from outpatients in the Department of Ophthalmology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India. A random blood sample was collected from each study participant, and the serum was separated after centrifugation and stored at -80 °C for batch analysis. The biomarkers vascular endothelial growth factor (VEGF-A) and angiopoietin-like protein-2 (ANGPTL2) were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) technique, and the laboratory parameters such as fasting blood sugar (FBS), lipid profile, blood urea nitrogen (BUN), creatine, and glycated hemoglobin (HbA1C) were also assessed. Results We observed statistically significant differences in the duration of diabetes, FBS, total cholesterol (TC), triglyceride level (TGL), BUN, and creatine (p<0.05), and the mean age of study participants was 52.95±8.20 years in the control group, 53.85±10.20 years in the proliferative diabetic retinopathy (PDR) group, and 55.02±7.65 in the non-proliferative diabetic retinopathy (NPDR) group. Furthermore, ANGPTL2 levels were statistically significant according to the severity of the disease (p<0.001*), and they were also linked (p<0.05) with established markers such as VEGF-A. Conclusion Thus, our research implies that the up-regulated markers might be linked to the disease's advancement and could serve as a prognostic indicator or therapeutic target for DR.

Effect of Continuous Infusion vs Bolus Dose of Hydrocortisone in Septic Shock: A Prospective Randomized Study.

Aim and background: Corticosteroids are recommended for use in adult patients with septic shock requiring vasopressors for blood pressure maintenance. However, this predisposes them to hyperglycemia, which is associated with a poor outcome. This prospective randomized study compares the effect of continuous infusion with bolus hydrocortisone on blood glucose levels in septic shock. Materials and methods: Forty adult patients with sepsis and septic shock requiring vasopressor support were randomly allocated to either group C (continuous infusion of hydrocortisone 200 mg/day) or group B (intermittent bolus dose of hydrocortisone 50 mg IV 6 hourly). Blood glucose level (primary objective), number of hyperglycemic and hypoglycemic episodes, daily insulin requirement, shock reversal incidence, time to shock reversal, and nursing workload required to maintain blood glucose within the target range (82-180 mg/dL) were compared. Results: The mean blood glucose level was comparable in the two groups (136.5 ± 22.08 mg/dL in group C vs 135.85 ± 19.06 mg/dL in group B; p = 0.921). The number of hyperglycemic and hypoglycemic episodes (p = 1.000 each), insulin requirement/day (p = 1.000), and nursing workload (p = 0.751) were also comparable among groups. Shock reversal was seen in 7/20 (35%) patients in continuous group and 12/20 (60%) patients in bolus group (p = 0.113). Time to shock reversal (p = 0.917) and duration of ICU stay (p = 0.751) were also statistically comparable. Conclusion: Both the regimes of hydrocortisone, continuous infusion, and bolus dose, have comparable effects on blood glucose levels in patients with septic shock.The study was registered prospectively with ctri.nic.in (Ref. No. CTRI/2021/01/030342; registered on 8/1/2021). How to cite this article: Salhotra R, Sharahudeen A, Tyagi A, Rautela RS, Kemprai R. Effect of Continuous Infusion vs Bolus Dose of Hydrocortisone in Septic Shock: A Prospective Randomized Study. Indian J Crit Care Med 2024;28(9):837-841.

Impact of risk factors on intervened and non-intervened coronary lesions.

INTRODUCTION: In-stent restenosis (ISR) and aggravated non-intervened coronary lesions (ANL) are two pivotal aspects of disease progression in patients with coronary artery disease (CAD). Established risk factors for both include hyperlipidemia, hypertension, diabetes, chronic kidney disease, and smoking. However, there is limited research on the comparative risk factors for the progression of these two aspects of progression. The aim of this study was to analyze and compare the different impacts of identical risk factors on ISR and ANL. METHODS: This study enrolled a total of 510 patients with multiple coronary artery lesions who underwent repeated coronary angiography (CAG). All patients had previously undergone percutaneous coronary intervention (PCI) and presented non-intervened coronary lesions in addition to the previously intervened vessels. RESULTS: After data analysis, it was determined that HbA1c (OR 1.229, 95% CI 1.022-1.477, P=0.028) and UA (OR 1.003, 95% CI 1.000-1.005, P=0.024) were identified as independent risk factors for ISR. Furthermore, HbA1c (OR 1.215, 95% CI 1.010-1.460, P=0.039), Scr (OR 1.007, 95% CI 1.003-1.017, P=0.009), and ApoB (OR 1.017, 95% CI 1.006-1.029, P=0.004) were identified as independent risk factors for ANL. The distribution of multiple blood lipid levels differed between the ANL only group and the ISR only group. Non-HDL-C (2.17 mmol/L vs. 2.44 mmol/L, P=0.007) and ApoB (63.5 mg/dL vs. 71.0 mg/dL, P=0.011) exhibited significantly higher values in the ANL only group compared to the ISR only group. CONCLUSIONS: Blood glucose levels and chronic kidney disease were identified as independent risk factors for both ISR and ANL, while elevated lipid levels were only significantly associated with ANL. In patients with non-intervened coronary lesions following PCI, it is crucial to assess the concentration of non-HDL-C and ApoB as they serve as significant risk factors.

A new classification method for gestational diabetes mellitus: a study on the relationship between abnormal blood glucose values at different time points in oral glucose tolerance test and adverse maternal and neonatal outcomes in pregnant women with gestational diabetes mellitus.

Background: Gestational diabetes mellitus (GDM) can lead to various adverse pregnancy outcomes for both mothers and infants, including gestational hypertension, premature rupture of membranes, preterm birth, macrosomia, large for gestational age (LGA) infants, and neonatal hypoglycemia. Previous studies have mainly focused on the overall risk of GDM for adverse maternal and neonatal outcomes, but there has been limited research specifically investigating the relationship between different patterns of abnormal oral glucose tolerance test (OGTT) results and adverse maternal and neonatal outcomes. Objective: The study aimed to analyze the maternal and neonatal outcomes among GDM women with different OGTT patterns and to explore a new classification method capable of stratifying GDM into high-risk (GDM-HR) and low-risk subtypes based on OGTT results. Study Design: We conducted a retrospective cohort study at the Women's Hospital, School of Medicine, Zhejiang University, spanning from November 1, 2015, to April 30, 2018. During the study period, a total of 3268 cases of GDM were enrolled. Based on the results of the OGTT, these GDM cases were classified into 7 subtypes, and the composition ratio of each subtype and their maternal and neonatal outcomes were analyzed. Innovatively, we proposed to categorize GDM-HR (characterized by elevated fasting blood glucose [FBG] levels, including T0, T0+1, T0+2, and T0+1+2) and low-risk GDM (GDM-LR, without elevated FBG, including T1, T2, and T1+2) and compared the maternal and neonatal outcomes between the two subtypes. Results: (1) In this cohort of 3268 GDM cases, the composition ratios of the 7 GDM subtypes were as follows: T0 (7.9%, n=260), T1 (24.2%, n=791), T2 (27.4%, n=897), T0+1 (5.4%, n=175), T0+2 (1.7%, n=56), T1+2 (26.2%, n=855), and T0+1+2 (7.2%, n=234). (2) GDM subtypes with elevated FBG levels (GDM-HR) exhibit more severe adverse prognostic outcomes compared to those without elevated FBG levels (GDM-LR). (3) Multiple logistic regression analysis revealed that compared to the GDM-LR group, the GDM-HR group showed increased fetal birth weight (by approximately 150 grams), and had higher rates of cesarean section (adjusted odds ratio [aOR]: 1.45, 95% confidence interval [CI]: 1.19-1.76), hypertensive disorders of pregnancy (aOR: 1.78, 95% CI: 1.35-2.35), preterm birth (aOR: 1.59, 95% CI: 1.17-2.16), macrosomia (aOR: 2.66, 95% CI: 2.07-3.43), LGA infants (aOR: 2.46, 95% CI: 2.05-2.97), and neonatal hypoglycemia (aOR: 2.00, 95% CI: 1.37-2.91). Partial correlation analysis shows a positive correlation between fetal birth weight and FBG levels, with r=0.222, P<.001. Multiple linear regression indicates that for every 1 mmol/L increase in FBG, the fetal weight is estimated to increase by approximately 188 grams. Conclusion: The composition ratio of GDM subtypes with elevated FBG (GDM-HR) is relatively low within GDM cases, yet it presents with a higher risk of adverse outcomes compared to subtypes without elevated FBG (GDM-LR), warranting increased attention from obstetricians. Applying this new classification method in clinical practice enables better differentiation and individualized management of GDM.

Exploring the Initial Encounter with Continuous Glucose Monitoring among Individuals with Type 2 Diabetes: A Two-Week Trip.

Purpose: This study aimed to explore the inaugural experience of using a continuous glucose monitoring (CGM) system in patients with type 2 diabetes. Patients and Methods: This study employed a qualitative design. Thirty-one patients with type 2 diabetes were recruited from a national university hospital and underwent CGM for two weeks. Individual interviews with 28 participants were conducted between August 1 and October 17, 2022, after the CGM. Thematic analysis was used to examine the data. Results: The results revealed transformative shifts in aspects of participants' lives due to CGM use, including alterations in dietary management and interpersonal relationships. During the two-week journey with CGM, participants were able to visually observe exercise effects and other benefits, leading to the discovery of a new utility for this innovative medical device. However, unavoidable drawbacks such as high cost, inaccurate results, and skin irritation have been identified, prompting suggestions for improvement. Conclusion: This study determined that CGM is both feasible and valuable for facilitating lifestyle adjustments to manage diabetes. Nevertheless, the challenge of discomfort associated with CGM use should be addressed in the future. To ensure effective utilization and overcome potential obstacles, it is recommended that a comprehensive and user-friendly CGM education manual be created, with the scope of CGM insurance coverage extended to include this research in the future.

[Characterization and expression optimization of a highly thermostable hexokinase in Escherichia coli].

Hexokinase is a crucial diagnostic reagent in blood glucose testing, which has high requirements for the enzyme activity and thermal stability. The hexokinases in China mainly rely on imports and are primarily sourced from yeast, with high costs and poor thermal stability, which limit the development of blood glucose diagnostic reagents. Therefore, there is an urgent need for the efficient expression of highly active and thermally stable hexokinases. In this study, an ATP-dependent hexokinase (glucokinase, Glk) from a thermophilic bacterium Glk was heterologously expressed in Escherichia coli BL21(DE3). Glk exhibited high specificity for glucose, dependence on Mg2+, and the highest activity at pH 8.5 and 80 ℃. It retained over 90% activity after storage at 30-37 ℃ for 7 days, demonstrating thermal stability as an alkaline glucose kinase. Subsequently, the factors influencing Glk expression, including culture medium, OD600, final concentration of the inducer, induction temperature, and induction duration, were systematically optimized. The optimization increased the Glk expression by 4.71 folds Glk compared with non-optimized conditions. After purification, Glk exhibited a specific activity of (43.05±2.00) U/mg and the purity ≥98%. In conclusion, the developed expression and purification method for the highly thermostable hexokinase provides more possibilities for overcoming the shortcomings in the preparation of blood glucose diagnostic reagents in China.

Prediction of People With Type 2 Diabetes Not Achieving HbA1c Target After Initiation of Fast-Acting Insulin Therapy: Using Machine Learning Framework on Clinical Trial Data.

BACKGROUND AND AIMS: Glycemic control is crucial for people with type 2 diabetes. However, only about half achieve the advocated HbA1c target of ≤7%. Identifying those who will probably struggle to reach this target may be valuable as they require additional support. Thus, the aim of this study was to develop a model to predict people with type 2 diabetes not achieving HbA1c target after initiating fast-acting insulin. METHODS: Data from a randomized controlled trial (NCT01819129) of participants with type 2 diabetes initiating fast-acting insulin were used. Data included demographics, clinical laboratory values, self-monitored blood glucose (SMBG), health-related quality of life (SF-36), and body measurements. A logistic regression was developed to predict HbA1c target nonachievers. A potential of 196 features was input for a forward feature selection. To assess the performance, a 20-repeated stratified 5-fold cross-validation with area under the receiver operating characteristics curve (AUROC) was used. RESULTS: Out of the 467 included participants, 98 (21%) did not achieve HbA1c target of ≤7%. The forward selection identified 7 features: baseline HbA1c (%), mean postprandial SMBG at all meals 3 consecutive days before baseline (mmol/L), sex, no ketones in urine, baseline albumin (g/dL), baseline low-density lipoprotein cholesterol (mmol/L), and traces of protein in urine. The model had an AUROC of 0.745 [95% CI = 0.734, 0.756]. CONCLUSIONS: The model was able to predict those who did not achieve HbA1c target with promising performance, potentially enabling early identification of people with type 2 diabetes who require additional support to reach glycemic control.

An evaluation of the quality care for type 2 diabetes patients in the primary healthcare using the lot quality assurance sampling technique.

BACKGROUND: Diabetes is the most prevalent metabolic disease globally. Correct and effective healthcare management requires up-to-date and accurate information at the local level. This level of information allows managers to determine whether the health system has achieved its desired goals in this area. This study aimed to evaluate the adequacy and quality of care for Type 2 diabetes mellitus (T2DM) patients using the Lot quality assurance sampling (LQAS) technique to provide evidence for decision-making at the local level, prioritizing and allocating resources. METHODS: A descriptive-analytical study was conducted in 12 supervision areas (SAs)/health facilities in northwestern Iran involving 240 patients with T2DM in primary health care. The selection of patients and determination of SAs were done randomly using the LQAS technique. Glycated Hemoglobin (HbA1c) was used to evaluate patients' blood sugar control in each SA. Multiple linear regression analysis was used to estimate predictors of HbA1c in T2DM. RESULTS: The overall average of HbA1c value was 7.84%. The HbA1c level was > 7% in 148 (61.6%) of the patients. Among the 12 SAs, the LQAS identified unacceptable quality of care in 5 SAs. In the final analysis, each unit increase in fasting blood sugar (FBS), High-density lipoprotein (HDL), Low-density lipoprotein (LDL), and Thyroglobulin (TG) values resulted in an increased in HbA1c levels by 0.43, 0.183, 0.124, and 0.182 times, respectively. However, with a one-unit increase in the care of a family physician and nutritionist, along with regular physical activity, HbA1c levels decreased by - 0.162, -0.74, and - 0.11 times, respectively. CONCLUSIONS: The quality of care for diabetic patients needs improvement in some SAs. Findings indicated that the LQAS technique effectively identifies centers/areas with substandard diabetes care quality and efficiently allocates resources to those in need. It is recommended to implement corrective measures in areas with inadequate care quality.

Correlation between ratio of fasting blood glucose to high density lipoprotein cholesterol in serum and non-alcoholic fatty liver disease in American adults: a population based analysis.

Background: Based on previous research, elevated fasting blood glucose (FBG) and decreased high-density lipoprotein cholesterol (HDL-C) levels are associated with non-alcoholic fatty liver disease (NAFLD). It is hypothesized that the prevalence of NAFLD may be proportional to the FBG-to-HDL-C ratio (GHR). Methods: In this study, 3,842 participants from the National Health and Nutrition Examination Survey (NHANES) (2013-2020) were investigated. Liver steatosis was assessed using vibration-controlled transient elastography (VCTE). NAFLD was defined as controlled attenuation parameter (CAP) ≥288 dB/m. Results: After adjusting for race, gender, age, diabetes, BMI, moderate activities, uric acid, albumin, ALT, GGT, ALP, total bilirubin and creatinine, multiple logistic regression analysis indicated a positive correlation between GHR and the prevalence of NAFLD (OR = 1.22, 95% CI = 1.17-1.28). Additionally, multiple linear regression analysis showed a positive correlation between GHR and the severity of liver steatosis according to CA p-values (ß = 4.97, 95% CI: 4.28, 5.66). According to the subgroup analysis, the correlation was stronger in other race, participants at the age <50 years old and those with non-diabetes. In this study, a non-linear relationship and saturation effect between GHR and the prevalence of NAFLD was also revealed, characterized by an inverted L-shaped curve, with an inflection point of 7.443. Finally, the receiver operating characteristic (ROC) analysis suggested that the area under the curve (AUC) of GHR (AUC = 0.731) significantly exceeded that of FBG and HDL-C. Conclusion: Elevated GHR levels are independently associated with the severity of liver steatosis and the increased prevalence of NAFLD in American adults.

Low-Carbohydrate Dietary Interventions for Metabolic Control in Individuals With Type 2 Diabetes Mellitus: An Overview of Systematic Reviews.

CONTEXT: Dietary interventions providing different amounts of carbohydrates have been proposed as a means of achieving glycemic control and weight loss in type 2 diabetes mellitus (T2DM); however, the supporting evidence is heterogeneous, making this recommendation difficult to apply in nutritional clinical practice. OBJECTIVE: The aim was to assess the quality of evidence from meta-analyses on low-carbohydrate (LC) dietary interventions for glycemic control, weight loss, and lipid profile in individuals with T2DM. DATA SOURCES: The MEDLINE, Web of Science, and Scopus databases were searched until September 2023. DATA EXTRACTION: A systematic review was conducted. Systematic reviews with meta-analysis of randomized clinical trials designed to assess glycated hemoglobin (HbA1c) reductions in individuals with T2DM were eligible. The AMSTAR-2 critical appraisal tool was used to evaluate the methodological aspects of all included studies. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to assess the certainty of the evidence. DATA ANALYSIS: The LC interventions were associated with a reduction in HbA1c (%) of -0.42 (-1.45 to -0.09; high certainty of evidence) without considering follow-up time; at up to 3 months of follow-up of -0.28 (-0.13 to -0.43); at up to 6 months of follow-up of -0.40 (-0.61 to -0.09); at 6 to 12 months of follow-up of -0.32 (-0.49 to 0.11); and at >12 months of follow-up time of -0.31 (-0.14 to -0.65) compared with control diets. CONCLUSION: LC diets can help reduce HbA1c in individuals with T2DM in the short term (up to 3 months). However, dietary recommendations must always be individualized, as the studies reviewed herein analyzed different populations and used different definitions of what constitutes an LC diet. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42023404197.

Effects of night-to-night variations in objectively measured sleep on blood glucose in healthy university students.

STUDY OBJECTIVES: We examined associations between daily variations in objectively measured sleep and blood glucose in a sample of non-diabetic young adults to complement laboratory studies on how sleep affects blood glucose levels. METHODS: 119 university students underwent sleep measurement using an Oura Ring 2 and continuous glucose monitoring (CGM) for up to 14 days. In 69 individuals who consumed a standardised diet across the study, multilevel models examined associations between sleep duration, timing and efficiency and daily CGM profiles. Separately, in 58 individuals, multilevel models were used to evaluate postprandial glycaemic responses to a test meal challenge on 7 days. Participants also underwent oral glucose tolerance testing once after a night of ad libitum sleep, and again following a night of sleep restriction by 1-2 hours relative to that individual's habitual sleep duration. Between-condition glucose and insulin excursions, HOMA-IR and Matsuda index were compared. RESULTS: Nocturnal sleep did not significantly influence following-day CGM profiles, postprandial glucose, or nocturnal mean glucose levels (all Ps>0.05). Longer sleep durations were associated with lower same-night glucose variability (all Ps<0.001). However, the range of variation of sugar levels was small and unlikely to be of functional significance. Considering naps in the analysis did not alter the findings. Sleep restriction by an average of 1.73 hours (SD=0.97) did not significantly impact excursions in glucose or insulin or insulin sensitivity the following morning (all Ps>0.05). CONCLUSIONS: Glucose handling in young, healthy adults may be more resilient to real-life fluctuations in sleep patterns than previously thought.

Impact of Microplastic Exposure on Blood Glucose Levels and Gut Microbiota: Differential Effects under Normal or High-Fat Diet Conditions.

Microplastics are emerging pollutants that have garnered significant attention, with evidence suggesting their association with the pathogenesis of type 2 diabetes mellitus. In order to assess the impact of polystyrene microplastic exposure on alterations in the gut microbiota and the subsequent implications for glucose dysregulation under different dietary conditions in mice, we investigated the effects and disparities in the blood glucose levels induced by polystyrene microplastic exposure in mice fed a high-fat diet versus those fed a normal diet. Using 16S rRNA sequencing and bioinformatics analyses, we explored the dynamic changes and discrepancies in the gut microbiota stability induced by polystyrene microplastic exposure under varied dietary conditions, and we screened for gut genera associated with the potential of polystyrene microplastics to disrupt glucose homeostasis. Our findings indicate that a high-fat diet resulted in abnormal mouse body weight, energy intake, blood glucose levels and related metabolic parameters. Additionally, polystyrene microplastic exposure exacerbated the glucose metabolism disorders induced by a high-fat diet. Furthermore, the composition and diversity of the mouse gut microbiota were significantly altered following microplastic exposure, with 11 gut genera exhibiting a differential presence between mice fed a high-fat diet combined with microplastic exposure compared to those fed a normal diet with microplastic exposure. Moreover, Ucg-009 played an intermediary role in the association between a high-fat diet and the fasting blood glucose. Hence, our study demonstrates that polystyrene microplastic exposure exacerbates high-fat diet-induced glucose metabolism disorders, whereas its impact on the blood glucose under normal dietary conditions is not significant, highlighting the differential influence attributable to distinct alterations in characteristic gut genera.

Quantitative brain [18F]FDG PET beyond normal blood glucose levels.

Introduction SUV measurements from static brain [18F]FDG PET acquisitions are a commonly used tool in preclinical research, providing a simple alternative for kinetic modelling, which requires complex and time-consuming dynamic acquisitions. However, SUV can be severely affected by the animal handling and preconditioning protocols, primarily by those that may induce changes in blood glucose levels (BGL). Here, we aimed at developing and investigating the feasibility of SUV-based approaches for a wide range of BGL far beyond normal values, and consequently, to develop and validate a new model to generate standardized and reproducible SUV measurements for any BGL. Material and methods We performed dynamic and static brain [18F]FDG PET acquisitions in 52 male Sprague-Dawley rats sorted into control (n = 10), non-fasting (n = 14), insulin-induced hypoglycemia (n = 12) and glucagon-induced hyperglycemia (n = 16) groups. Brain [18F]FDG PET images were cropped, aligned and co-registered to a standard template to calculate whole-brain and regional SUV. Cerebral Metabolic Rate of Glucose (CMRglc) was also estimated from 2-Tissue Compartment Model (2TCM) and Patlak plot for validation purposes. Results Our results showed that BGL=100±6 mg/dL can be considered a reproducible reference value for normoglycemia. Furthermore, we successfully established a 2nd-degree polynomial model (C1=0.66E-4, C2=-0.0408 and C3=7.298) relying exclusively on BGL measures at pre-[18F]FDG injection time, that characterizes more precisely the relationship between SUV and BGL for a wide range of BGL values (from 10 to 338 mg/dL). We confirmed the ability of this model to generate corrected SUV estimations that are highly correlated to CMRglc estimations (R2= 0.54 2TCM CMRgluc and R2= 0.49 Patlak CMRgluc). Besides, slight regional differences in SUV were found in animals from extreme BGL groups, showing that [18F]FDG uptake is mostly directed toward central regions of the brain when BGLs are significantly decreased. Conclusion Our study successfully established a non-linear model that relies exclusively on pre-scan BGL measurements to characterize the relationship between [18F]FDG SUV and BGL. The extensive validation confirmed its ability to generate SUV-based surrogates of CMRglu along a wide range of BGL and it holds the potential to be adopted as a standard protocol by the preclinical neuroimaging community using brain [18F]FDG PET imaging.

Value of Glycemic Indices for Delayed Cerebral Ischemia after Aneurysmal Subarachnoid Hemorrhage: A Retrospective Single-Center Study.

Delayed cerebral ischemia (DCI) is a severe complication following aneurysmal subarachnoid hemorrhage (aSAH), linked to poor functional outcomes and prolonged intensive care unit (ICU) stays. Timely DCI diagnosis is crucial but remains challenging. Dysregulated blood glucose, commonly observed after aSAH, may impair the constant glucose supply that is vital for brain function, potentially contributing to DCI. This study aimed to assess whether glucose indices could help identify at-risk patients and improve DCI detection. This retrospective, single-center observational study examined 151 aSAH patients between 2016 and 2019. Additionally, 70 of these (46.4%) developed DCI and 81 did not (no-DCI). To determine the value of glycemic indices for DCI, they were analyzed separately in patients in the period before (pre-DCI) and after DCI (post-DCI). The time-weighted average glucose (TWAG, p = 0.024), mean blood glucose (p = 0.033), and novel time-unified dysglycemic rate (TUDR140, calculated as the ratio of dysglycemic to total periods within a glucose target range of 70-140 mg/dL, p = 0.042), showed significantly higher values in the pre-DCI period of the DCI group than in the no-DCI group. In the time-series analysis, significant increases in TWAG and TUDR140 were observed at the DCI onset. In conclusion, DCI patients showed elevated blood glucose levels before and a further increase at the DCI onset. Prospective studies are needed to confirm these findings, as this retrospective, single-center study cannot completely exclude confounders and limitations. In the future blood glucose indices might become valuable parameters in multiparametric models to identify patients at risk and detect DCI onset earlier.

Reinforcement Learning: A Paradigm Shift in Personalized Blood Glucose Management for Diabetes.

Background/Objectives: Managing blood glucose levels effectively remains a significant challenge for individuals with diabetes. Traditional methods often lack the flexibility needed for personalized care. This study explores the potential of reinforcement learning-based approaches, which mimic human learning and adapt strategies through ongoing interactions, in creating dynamic and personalized blood glucose management plans. Methods: We developed a mathematical model specifically for patients with type IVP diabetes, validated with data from 10 patients and 17 key parameters. The model includes continuous glucose monitoring (CGM) noise and random carbohydrate intake to simulate real-life conditions. A closed-loop system was designed to enable the application of reinforcement learning algorithms. Results: By implementing a Policy Optimization (PPO) branch, we achieved an average Time in Range (TIR) metric of 73%, indicating improved blood glucose control. Conclusions: This study presents a personalized insulin therapy solution using reinforcement learning. Our closed-loop model offers a promising approach for improving blood glucose regulation, with potential applications in personalized diabetes management.

Perioperative glucose monitoring with continuous glucose monitors identifies risk factors for post-transplant diabetes mellitus in kidney transplant recipients.

Post-transplantation diabetes mellitus (PTDM) negatively affects graft and patient survival after kidney transplantation (KT). This prospective study used continuous glucose monitoring (CGM) to evaluate perioperative blood glucose dynamics, identify PTDM risk factors, and compare predictive accuracy with capillary blood glucose monitoring (CBGM) in 60 non-diabetic living-donor KT recipients. Patients underwent 2-week pre- and postoperative CGM, including routine CBGM during their in-hospital stays. PTDM-related risk factors and glucose profiles were analyzed with postoperative CGM and CBG. PTDM developed in 14 (23.3%) patients and was associated with older age, male sex, higher baseline HbA1c, high-density lipoprotein cholesterol, and 3-month cumulative tacrolimus exposure levels. Male sex and postoperative time above the range (TAR) of 180 mg/dL by CGM were PTDM-related risk factors in the multivariate analysis. For predictive power, the CGM model with postoperative glucose profiles exhibited higher accuracy compared with the CBGM model (areas under the curves of 0.916, and 0.865, respectively). Therefore, we found that male patients with a higher postoperative TAR of 180 mg/dL have an increased risk of PTDM. Postoperative CGM provides detailed glucose dynamics and demonstrates superior predictive potential for PTDM than CBGM.

The Role and Mechanism of Probiotics Supplementation in Blood Glucose Regulation: A Review.

With economic growth and improved living standards, the incidence of metabolic diseases such as diabetes mellitus caused by over-nutrition has risen sharply worldwide. Elevated blood glucose and complications in patients seriously affect the quality of life and increase the economic burden. There are limitations and side effects of current hypoglycemic drugs, while probiotics, which are safe, economical, and effective, have good application prospects in disease prevention and remodeling of intestinal microecological health and are gradually becoming a research hotspot for diabetes prevention and treatment, capable of lowering blood glucose and alleviating complications, among other things. Probiotic supplementation is a microbiologically based approach to the treatment of type 2 diabetes mellitus (T2DM), which can achieve anti-diabetic efficacy through the regulation of different tissues and metabolic pathways. In this study, we summarize recent findings that probiotic intake can achieve blood glucose regulation by modulating intestinal flora, decreasing chronic low-grade inflammation, modulating glucagon-like peptide-1 (GLP-1), decreasing oxidative stress, ameliorating insulin resistance, and increasing short-chain fatty acids (SCFAs) content. Moreover, the mechanism, application, development prospect, and challenges of probiotics regulating blood glucose were discussed to provide theoretical references and a guiding basis for the development of probiotic preparations and related functional foods regulating blood glucose.

Angiotensin in the Arcuate: Mechanisms Integrating Cardiometabolic Control.

BACKGROUND: The American Heart Association has identified obesity as a primary impediment to ongoing improvements in cardiovascular diseases, including hypertension. Although drugs, exercise, diets, and surgeries can each cause weight loss, few subjects maintain a reduced weight over the long term. Dysfunctional integrative control (ie, adaptation) of resting metabolic rate (RMR) appears to underlie this failed weight maintenance, yet the neurobiology of physiological and pathophysiological RMR control is poorly understood. METHODS: Recent insights into the cellular and molecular control of RMR by Ang-II (angiotensin II) signaling within the arcuate nucleus of the hypothalamus are reviewed. RESULTS: Within a unique subset of AgRP (agouti-related peptide) neurons, AT1Rs (Ang-II type 1 receptors) are implicated in the integrative control of RMR. Furthermore, a spontaneous G protein signal switch of AT1R within this neuron type appears to underlie the pathogenesis of RMR adaptation by qualitatively changing the cellular response to AT1R activation from a ß-arrestin-1/Gαi-mediated inhibitory response to a Gαq-mediated stimulatory response. CONCLUSIONS: Therapeutic approaches to obesity are likely hampered by the plasticity of the signaling mechanisms that mediate the normal integrative control of energy balance. The same stimulus that would increase RMR in the normal physiological state may decrease RMR during obesity due to qualitative changes in second-messenger coupling. Understanding the mechanisms that regulate interactions between receptors such as AT1R and its various second-messenger signaling cascades will provide novel insights into the pathogenesis of RMR adaptation and potentially point toward new therapeutic approaches for obesity and hypertension.

Fasting blood glucose level and risk of all-cause and cause-specific mortality in peritoneal dialysis patients.

BACKGROUND: Glycemic control is crucial in peritoneal dialysis (PD) patients with diabetes. Although fasting blood glucose (FBG) is the most commonly used index to measure blood glucose levels, there is currently no evidence supporting the association between FBG level and mortality risk in PD patients. METHODS: A total of 3548 diabetic PD patients between 2002 and 2018 were enrolled from the National Health Insurance Service database of Korea. We investigated the association between FBG levels and the risk of all-cause and cause-specific mortality. RESULTS: Patients with FBG levels 80-99 mg/dL exhibited the highest survival rates, whereas those with FBG levels ≥180 mg/dL had the lowest survival rates. Compared with FBG levels 80-99 mg/dL, the adjusted hazard ratios and 95% confidence interval for all-cause mortality significantly increased as follows: 1.02 (0.87-1.21), 1.41 (1.17-1.70), 1.44 (1.18-2.75), and 2.05 (1.73-2.42) for patients with FBG 100-124 mg/dL, FBG 125-149 mg/dL, FBG 150-179 mg/dL, and FBG ≥180 mg/dL, respectively. The risk for all-cause mortality also showed an increasing pattern in patients with FBG levels <80 mg/L. The risk of cardiovascular death significantly increased as FBG levels exceeded 125 mg/dL. However, the risk of infection-related and malignancy-related deaths did not show a significant increase with increasing FBG levels. CONCLUSION: There was an increase in the risk of all-cause mortality as FBG levels exceeded 125 mg/dL in PD patients with diabetes, and the risk of cardiovascular death showed a strong correlation with FBG levels compared with other causes of death.