Glucose Variability Research Articles

What is the Relationship Between Time in Range, Time in Tight Range, and HbA1c in Youth and Young Adults With Type 1 Diabetes? Results From the German/Austrian/Luxembourgian/Swiss Diabetes Prospective Follow-Up Registry.

Time in range (TIR, 70-180 mg/dL) is an established marker of glycemic control. More recently, time in tight range (TTR, 70-140 mg/dL) has been proposed as well. The aim of this study was to examine the relationship between TIR, TTR, and HbA1c in youth and young adults with type 1 diabetes (T1D) in the German/Austrian/Luxembourgian/Swiss Diabetes Prospective Follow-up (DPV) registry. Data of youth and young adults aged ≤25 years with T1D for >3 months, documented in the DPV registry between 2019 and 2022 were analyzed. The most recent available HbA1c and corresponding continuous glucose monitoring (CGM) profiles in the 12 preceding weeks with at least 80% completeness were included. Associations were investigated using correlation and adjusted regression models. 1901 individuals (median age 14.0 years [IQR 10.4-16.9]) were included in the analysis. TIR and TTR correlated strongly, r = 0.965 (95% CI [0.962, 0.968]), P < .001. TTR estimates predicted from TIR were significantly higher in the group with high coefficient of variation (CV group ≥ 36%), P < .001. Correlations between TIR or TTR and HbA1c were both strong, r = -0.764 (95% CI [-0.782, -0.745]) and r = -0.777 (95% CI [-0.795, -0.759]), both P < .001, with no significant difference (P = .312) However, adjusted regression models indicated a slightly better fit for the prediction of HbA1c from TIR compared with TTR. Based on large, real-world data from a multinational registry, TIR and TTR correlated strongly, and both showed a good prediction of HbA1c. TTR estimates predicted from TIR were significantly higher in people with high glucose variability (CV).

The metabolic and circadian signatures of gestational diabetes in the postpartum period characterised using multiple wearable devices.

Gestational diabetes mellitus (GDM) affects 14% of all pregnancies worldwide and is associated with cardiometabolic risk. We aimed to exploit high-resolution wearable device time-series data to create a fine-grained physiological characterisation of the postpartum GDM state in free-living conditions, including clinical variables, daily glucose dynamics, food and drink consumption, physical activity, sleep patterns and heart rate. In a prospective observational study, we employed continuous glucose monitors (CGMs), a smartphone food diary, triaxial accelerometers and heart rate and heart rate variability monitors over a 2 week period to compare women who had GDM in the previous pregnancy (GDM group) and women who had a pregnancy with normal glucose metabolism (non-GDM group) at 1-2 months after delivery (baseline) and 6 months later (follow-up). We integrated CGM data with ingestion events recorded with the smartphone app MyFoodRepo to quantify the rapidity of returning to preprandial glucose levels after meal consumption. We inferred the properties of the underlying 24 h rhythm in the baseline glucose. Aggregating the baseline and follow-up data in a linear mixed model, we quantified the relationships between glycaemic variables and wearable device-derived markers of circadian timing. Compared with the non-GDM group (n=15), the GDM group (n=22, including five with prediabetes defined based on fasting plasma glucose [5.6-6.9 mmol/l (100-125 mg/dl)] and/or HbA1c [39-47 mmol/mol (5.7-6.4%)]) had a higher BMI, HbA1c and mean amplitude of glycaemic excursion at baseline (all p≤0.05). Integrating CGM data and ingestion events showed that the GDM group had a slower postprandial glucose decrease (p=0.01) despite having a lower proportion of carbohydrate intake, similar mean glucose levels and a reduced amplitude of the underlying glucose 24 h rhythm (p=0.005). Differences in CGM-derived variables persisted when the five women with prediabetes were removed from the comparison. Longitudinal analysis from baseline to follow-up showed a significant increase in fasting plasma glucose across both groups. The CGM-derived metrics showed no differences from baseline to follow-up. Late circadian timing (i.e. sleep midpoint, eating midpoint and peak time of heart rate) was correlated with higher fasting plasma glucose and reduced amplitudes of the underlying glucose 24 h rhythm (all p≤0.05). We reveal GDM-related postpartum differences in glucose variability and 24 h rhythms, even among women clinically considered to be normoglycaemic. Our results provide a rationale for future interventions aimed at improving glucose variability and encouraging earlier daily behavioural patterns to mitigate the long-term cardiometabolic risk of GDM. ClinicalTrials.gov no. NCT04642534.

Safety of a Novel Continuous Glucose Monitoring–Informed Insulin Bolus Calculator Mobile Application for People With Type 1 or Type 2 Diabetes

BACKGROUND Managing bolus insulin dosing can be a significant burden for people with diabetes, many of whom have limited numeracy skills. Insulin bolus calculators (IBCs) may improve glycemia as well as treatment satisfaction. OBJECTIVE The purpose of this study was to demonstrate the safety of a novel, continuous glucose monitoring (CGM)-informed IBC mobile device app that applies trend arrow adjustments to bolus insulin dose recommendations. RESEARCH DESIGN AND METHODS This clinical trial was an open-label, industry-sponsored single-arm study conducted at two sites. Fifty-four participants with type 1 or type 2 diabetes were enrolled and used the IBC app on their mobile device for 30 days. Study participants were adults who were already using CGM and dosing bolus insulin. The analysis examined both noninferiority and superiority of time in range (TIR) during the study period compared with baseline. Other important end points included hypoglycemia, glucose variability, nocturnal and diurnal TIR, and diabetes distress. The per-protocol (PP) group was defined as participants who used the IBC &amp;gt;30 times during the study. RESULTS Mean TIR improved by 3.8% (95% CI 0.7–6.9%) from 69.2 to 73.0% (P = 0.017) in the PP group. This TIR corresponds to a mean of 0.9 more hours per day spent in range, and the improvement was driven by those with type 2 diabetes. There was no increase in measures of hypoglycemia or diabetes distress. Exploratory analysis revealed a reduction in measures of glucose variability. In addition, individuals with type 1 diabetes had greater improvements in diurnal TIR than in nocturnal TIR. CONCLUSION A CGM-informed IBC app that applies trend arrow adjustments to bolus insulin dose recommendations improved TIR without increasing hypoglycemia or diabetes distress in individuals with type 1 or type 2 diabetes.

Increased FT3/FT4 ratio in a certain range is associated with decreased glycemic variability in patients with type 2 diabetes

Thyroid hormone (TH) plays a crucial role in regulating glucose metabolism. However, the potential impact of the FT3/FT4 ratio, which reflects peripheral sensitivity to thyroid hormones, on glycemic variability in patients with type 2 diabetes (T2DM), has not been previously reported. To investigate the correlation between the FT3/FT4 ratio and glycemic variability in individuals with T2DM. In this retrospective analysis, a total of 468 inpatients with T2DM underwent continuous glucose monitoring (CGM) systems for a period of 6–14 days. Baseline clinical characteristics, laboratory tests, and CGM parameters were documented to investigate the correlation between FT3/FT4 ratio and CGM parameters. The levels of HBA, MG, SD, CV, LAGE, MODD and TAR2Scale were all higher in FT3/FT4Q1 compared with FT3/FT4Q2, FT3/FT4Q3 and FT3/FT4Q4 (all P < 0.01). Additionally, TIR was lower in FT3/FT4Q1 compared with the other quartiles (P < 0.01). Smooth curve fitting and saturation effect analysis revealed that there are curve-like relationships between the FT3/FT4 ratio and SD, MAGE, MODD and TAR2Scale. The inflection points of the fitted curves were found to be at FT3/FT4 = 0.279, 0.237, 0.253 and 0.282 respectively (all P < 0.05). Prior to the inflection point, the FT3/FT4 ratio was negatively related to SD, MAGE, MODD and TAR2Scale (all P < 0.05). Furthermore, The FT3/FT4 ratio exhibits a negative linear correlation with HBA and MG, while demonstrating a positive linear relationship with TIR (all P < 0.05). Binary logistic regression demonstrated that the FT3/FT4 ratio was independently related to HBA (P = 0.001), MG (P = 0.01), TAR2Scale (P = 0.003), LAGE (P = 0.014) and MAGE (P < 0.001). The increased FT3/FT4 ratio within a certain range (FT3/FT4 ≤ 0.282) is associated with decreased blood glucose variability and increased TIR. The FT3/FT4 ratio may act as a potential independent protective factor for glycemic fluctuation and glycemic control in patients with T2DM when it increases within a specific range.

Regulatory roles of histamine receptor in astrocytic glutamate clearance under conditions of increased glucose variability

In diabetic patients, repeated episodes of hypoglycemia can increase glucose variability (GV), which may lead to glutamate neurotoxicity in the brain and consequently affect cognitive functions. Astrocytes play a crucial role in regulating the balance of glutamate within the brain, and their function is influenced by the histamine receptor (HR) signaling pathway. However, the specific role of this mechanism under conditions of high GV is not yet clear. The results showed that increased GV resulted in decreased expression of HRs in mice hippocampus and astrocytes cultured in vitro. Additionally, a decrease in the expression of proteins related to glutamate metabolic clearance was observed, accompanied by a reduction in glutamate reuptake capacity. Notably, the intervention with histidine/histamine was able to reverse the above changes. Further mechanistic studies showed that inhibition of HRs that increased GV led to significant disturbances in astrocytic mitochondrial function. These abnormalities encompassed increased fragmentation morphology and the accumulation of reactive oxygen species, accompanied by decreased mitochondrial respiratory capacity and dysregulation of dynamics. Distinct HR subtypes exhibited variations in the modulation of mitochondrial function, with H3R demonstrating the most pronounced impact. The overexpression of H3R could enhance glutamate metabolic by reversing disturbances in mitochondrial dynamics. Therefore, this study suggests that H3R is able to maintain glutamate metabolic clearance capacity and exert neuroprotective effects in astrocytes that increased GV by regulating mitochondrial dynamic balance. This provides an important basis for potential therapeutic targets for diabetes-related cognitive dysfunction.

Biological variation of capillary blood glucose: A systematic review

Biological variation of capillary blood glucose: A systematic review

Association between average glucose concentration or glucose variability and acute kidney injury among CAD patients with prediabetes

Abstract Background Prediabetes, impacting approximately 10% of adults, lacks comprehensive attention, and there is limited data on effective glycemic control strategies. Meta-analysis suggests that intensive glycemic control is linked to a lower incidence of major adverse cardiovascular events, mainly driven by decreased reinfarction and reduced microvascular complications in coronary artery disease (CAD) patients. However, despite these associations, existing evidence does not conclusively establish the efficacy of intensive glycemic control in enhancing cardio-renal outcomes. Purpose In the present study, we aimed to validate the utility of intensive glycaemic control on acute kidney injury (AKI) prevention using a prospective, pragmatic clinical data of patients with CAD. Methods This study utilized data from the Prospective Registry of the Current Status of Care for Patients with Coronary Artery Disease database, a nationwide and pragmatic registry project initiated on January 17th, 2022. Data, including demographics, medical history, and lab results, were collected from electronic medical records. The time-weighted average glucose (TWAG) and glucose variability (CV) for each patient to assess glycaemic control, and outcomes including AKI were assessed. Statistical analysis involved logistic models and sensitivity analyses. SAS 9.4 and R software were used, with p&amp;lt;0.05 considered significant. Results Between January 2022 and June 2023, 2,454 CAD patients with prediabetes were included for final analysis. Among them, the average age was 62.6 ± 10.3 years, of whom 27.1% were females. In univariate model, the incidence of AKI was 1.51 (1.36,1.68) times higher in patients with an increasing TWAG per mmol/L. After the stepwise adjusting of covariates, the OR was 1.50 (1.35,1.67). CV of glucose also had positive association with AKI. An increasing of 0.1 unit of CV increased the risk of about 44%. When adjusting the TWAG and CV of glucose at the same time, both still had positive association with AKI. A restricted cubic splines plot showed an increasing trend of the ORs for AKI as both TWAG and CV of glucose increased. Subgroups analyses also showed stable positive association between TWAG, CV and AKI. Conclusions Our study reveals an association between TWAG or CV and AKI in individuals with both CAD and prediabetes. These findings underscore the importance of continuous glucose monitoring and the implementation of intensive glycaemic control for CAD patients coexistence of prediabetes.Restricted cubic splines function

Association of long-term visit-to-visit glycemic variability with risk of adverse clinical outcomes in diabetic patients with heart failure with preserved ejection fraction

Abstract Background Previous research has linked glycemic variability (GV) with cardiovascular issues in type 2 diabetes mellitus. However, its impact on patients with heart failure with preserved ejection fraction (HFpEF) remains understudied. Purpose In this study, we aim to examine how glycemic variability influences on clinical cardiovascular outcomes in diabetic HFpEF patients. Methods We conducted a retrospective cohort analysis utilizing the electronic medical records of a tertiary medical center in Taiwan between 2014 and 2019. Diabetic patients diagnosed with HFpEF were included in the study. The coefficient of variability of fasting glucose (FGCV) was determined for each individual, and the FGCVs were categorized into tertiles. We analyzed the association between FGCV and the risks of hospitalization for heart failure (HHF), atrial fibrillation (AF), cardiac mortality, and overall mortality. Results A total of 74,835 patients were enrolled in this study. Among them, 753 diabetic patients with concomitant with HFpEF and measured FGCV were identified, with a median follow-up duration of 38.1 months. In the multivariable regression model, the third tertile of FGCV demonstrated a significant association with an elevated risk of HHF and overall mortality compared to the first tertile (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.03-1.50, p = 0.026; HR 1.64 [1.15-2.26], p = 0.006). Although a higher FGCV exhibited a trend towards increased AF and cardiac mortality, statistical significance was not reached (HR 1.19 [0.91-1.56], p=0.208; HR 1.64 [0.87-3.12], p=0.129). The Kaplan-Meier analyses revealed a significant association between higher FGCV and both HHF and overall mortality (log-rank p = 0.022 and &amp;lt;0.001, respectively). Conclusions Our study highlights a significant association between increased GV and a higher incidence of HHF as well as an overall mortality rate in diabetic individuals with HFpEF.

The relationship between daily blood glucose fluctuation and readmission in patients with acute coronary syndrome

Abstract Background Although the comprehensive diagnos and treatment of patients with acute coronary syndrome(ACS) has been greatly improved,the morbidity and mortality are still high. Previous literature has reported that about 70-75% of patients diagnosed with acute coronary syndrome have abnormal blood glucose metabolism1,and there existed gender differences. At present, most research results showed that elevated blood glucose is related to the prognosis of ACS. However, further intervention studies indicated that simply strengthen the reducement of blood glucose did not improve prognosis of these patients2. Glucose fluctuations, another dimension of blood glucose, reflect acute changes in blood glucose. However, there are few studies on the effect of blood glucose fluctuation on the prognosis of patients with ACS. Purpose This study aimed to explore the relationship between seven daily fluctuations of blood glucose and readmission in ACS patients. Methods In this study, a total of 664 patients admitted to our University from January 1, 2019 to December 31, 2019 were included and their blood glucose was monitored seven times a day during their hospitalization. The coefficient of variation of blood glucose (CV) was calculated from the results of seven daily blood glucose monitoring to represent the daily fluctuation of blood glucose. Univariate and multivariate regression analyses were performed to determine whether CV was an independent risk factor for re-hospitalization. In addition, the area under the curve (AUC) was used to evaluate the predictive efficacy of CV for outcome events. Finally, we performed a subgroup analysis based on gender and diabetes status to assess the association between CV and readmission in each subgroup. Results After a median follow-up of 21 months, the rate of readmission was 38.4%. Unstable angina pectoris (71.4%) and heart failure (16.4%) were the most common reasons for readmission. Patients with greater CV levels typically exhibited lower fasting blood glucose, higher post breakfast blood glucose, and higher admission blood glucose.The readmission rate increased with the increasing blood glucose variability after the cox regression analysis. Moreover, independent of glycated hemoglobin,CV could predict the risk of readmission in patients with ACS.When using 26.66% as the cutoff point of CV, the study population was divided into two groups and showed a significant differentiation for rehospitalization.In subgroup analysis, there was no significant association between seven daily blood glucose fluctuations and readmission in female and non-diabetes mellitus patients with acute coronary syndrome. Conclusions Besides some normal blood glucose index,seven daily fluctuations of blood glucose was associated with readmission in ACS patients. ACS patients who were male and combined with diabetes were more likely to be readmitted if their CV levels were greater.

Mediation analysis of brain magnetic resonance imaging variables with all-cause and cardiovascular disease-specific mortalities in persons with type 2 diabetes.

Glucose variation (GV) has emerged as a predictor of morbidity and mortality in persons with diabetes. However, no study has examined whether brain magnetic resonance imaging (MRI) variables mediated the association between mortality and GV. This study was a retrospective cohort comprising 3,961 individuals with type 2 diabetes (T2D), whose electronic medical records were retrieved from a medical center between January 2001 and October 2021. GV was quantified using coefficient of variation of fasting plasma glucose (FPG-CV) and glycated hemoglobin (HbA1c). The MRI variables included the presence or absence of cerebrovascular abnormality and white matter hyperintensity (WMH). All deaths and deaths resulting from expanded cardiovascular disease (CVD) were identified through annual record linkage with National Death Datasets. Cox proportional hazards models were applied to evaluate associations of MRI variable or GV with mortality. Mediation analyses were performed to assess the relative contributions of MRI variables for GV on mortality. Among 3,961 patients, 2,114 patients (53.4%) had cerebrovascular abnormality and 1,888 patients (47.7%) had WMH. The results showed cerebrovascular abnormality and WMHs were significantly associated with all-cause and expanded CVD mortality after considering GV. The largest mediated effects of GV on all-cause and expanded CVD mortality were observed by cerebrovascular abnormality (5.26% and 8.49%, respectively). Our study suggests cerebrovascular abnormality and WMHs are important predictors of mortality in patients with T2D after considering GV. In addition, MRI variables of cerebrovascular abnormality expressed weak but significant mediation effect on the associations between GV and mortality.

The Relation of Diabetes Complications to a New Interpretation of Glycaemic Variability from Continuous Glucose Monitoring in People with Type 1 Diabetes.

Microvascular and macrovascular complications in type 1 diabetes (T1D) may be linked to endothelial stress due to glycaemic variability. Continuous glucose monitoring systems (CGMs) provide new opportunities to quantify this variability, utilising the amplitude of glucose change summated over time. The aim of this study was to examine whether this determination of glucose variability (GV) is associated with microvascular clinical sequelae. Continuous glucose monitoring values were downloaded for 89 type 1 diabetes mellitus (T1D) individuals for up to 18 months from 2021 to 2023. Data for patient demographics was also taken from the patient record which included Sex, Date of Birth, and Date of Diagnosis. The recorded laboratory glycated haemoglobin (HbA1c) test results were also recorded. The glucose management index (GMI) was calculated from average glucose readings for 18 months using the formula GMI (%) = (0.82-(Average glucose/100)). This was then adjusted to give GMI (mmol/mol) = 10.929 * (GMI (%) - 2.15). Average Glucose Fluctuation (AGF) was calculated by adding up the total absolute change value between all recorded results over 18 months and dividing by the number of results minus one. The % Above Critical Threshold (ACT) was calculated by summing the total number of occurrences for each result value. A cumulative 95% limit was then applied to identify the glucose value that only 5% of results exceeded in the overall population. Using this value, we estimated the percentage of total tests that were above the Critical Threshold (ACT). Results for the 89 individuals (44 men and 45 women) were analysed over 18months. The mean age of participants was 43 years and the mean duration of diabetes was 18years. A total of 3.22 million readings were analysed, giving an average of 10.3mmol/L blood glucose. Those with the largest change in glucose from reading to reading, summated over time, showed the greatest change in eGFR of 3.12ml/min/1.73 m2 (p = 0.007). People with a higher proportion of glucose readings > 18mmol/L showed a fall in eGFR of 2.8ml/min/1.73 m2 (p = 0.009) and experienced higher rates of sight-threatening retinopathy (44% of these individuals) (p = 0.01) as did 39% of individuals in the highest tertile of glucose levels (p = 0.008). Those individuals with T1D in the highest tertile of reading-to-reading glucose change showed the greatest change in eGFR. Those with a higher proportion of glucose readings > 18mmol/L also showed a fall in eGFR and experienced higher rates of sight-threatening retinopathy, as did people with higher mean glucose. Discussions with T1D individuals could reflect on how the percentage recorded glucose above a critical level and degree of change in glucose are important in avoiding future tissue complications.

31 Impact of the amount of intravenous glucose administration on hospitalization for acute gastroenteritis in a paediatric emergency department

Abstract Background In case of failure of oral rehydration, children with acute gastroenteritis can be hydrated using intravenous (IV) solution. The choice of the intravenous solution itself (solutions containing dextrose versus crystalloids alone) and the glucose quantities to administer are not well established. Objectives The main objective of this study was to evaluate the impact of the amount of intravenous glucose provided to children treated for acute gastroenteritis on hospitalizations. Other objectives were to evaluate practice variation regarding the amount of glucose and liquid provided for IV rehydration in a paediatric emergency department (ED). Design/Methods We conducted a retrospective cohort study from 2019-2022 in a Canadian paediatric ED. We included children with acute gastroenteritis undergoing IV rehydration. Patient with hypoglycemia, metabolic disease or diabetes were excluded. The IV glucose administered during the initial four hours of rehydration was quantified. The primary outcome was hospitalization and return visit in the following seven days was a secondary outcome. 10% of the charts were evaluated in duplicate to assess inter-rater reliability. We examined glucose distribution at one and four hours, and utilized multiple logistic regression to relate glucose amounts with hospitalization and second visit, accounting for age, weight, bicarbonate levels, ondansetron use, and amount of liquid infused. It was estimated that the evaluation of 250 cases would have at least 50 admissions. Results Among 6,939 children evaluated for potential acute gastroenteritis, 250 met our inclusion/exclusion criteria. All variables included in the analysis had excellent inter-rater reliability. Notable variations existed in glucose quantities provided, both at one hour (first quartile: 87 mg/Kg; third quartile: 294 mg/Kg) and four hours (first quartile: 681 mg/Kg; third quartile: 1174 mg/kg) of rehydration. Multiple logistic regression showed a greater hospitalization risk with smaller amount of glucose administered during the initial hour (OR for each 100mg/kg increment: 0.60; 95%CI: 0.42-0.84) and four hours (OR: 0.76; 95%CI: 0.63-0.91) of rehydration. Moreover, children who received more dextrose during the first hour of rehydration were at lower risk of return visit (OR for each 100mg/kg increment: 0.52; 95%CI: 0.35-0.78), as well as during the first four hours (OR for each 100 mg/kg increment: 0.83; 95%CI: 0.73-0.94). Conclusion There was a wide practice variation in intravenous glucose provided to children with acute gastroenteritis. In this population, higher intravenous glucose amount was associated to a lower risk of hospitalization and lower risk of return visit.

Impact of Hypoglycemia on Glucose Variability over Time for Individuals with Open-Source Automated Insulin Delivery Systems

This study investigates glucose conditions preceding and following various hypoglycemia levels in individuals with type 1 diabetes using open-source automated insulin delivery (AID) systems. It also seeks to evaluate relationships between hypoglycemia and subsequent glycemic variability. Methods: Analysis of continuous glucose monitor (CGM) data from 122 adults with type 1 diabetes using open-source AID from the OpenAPS Data Commons was conducted. This study comprehensively analyzed the effects of hypoglycemia on glycemic variability, covering time periods before and after hypoglycemia. Results: Glucose variability normalization post-hypoglycemia can take up to 48 h, with severe hypoglycemia (41–50 mg/dL) linked to prolonged normalization. A cyclical pattern was observed where hypoglycemia predisposes individuals to further hypoglycemia, even with AID system use. A rise in glucose levels often precedes hypoglycemia, followed by an elevated mean time above range (TAR) post-hypoglycemia, indicating a ‘rebound’ effect. The experimental results are further validated on T1DEXI data (n = 222), originating from commercial AID systems. Different hypoglycemia categorization approaches did not show significant differences in glycemic variability outcomes. The level of hypoglycemia does influence the pattern of subsequent glucose fluctuations. Conclusion: Hypoglycemia, especially at lower levels, significantly impacts subsequent glycemic variability, even with the use of open-source AID systems. This should be studied further with a broader set of commercial AID systems to understand if these patterns are true of all types of AID systems. If these patterns occur in all types of AID systems, it underscores potential opportunities for enhancements in AID algorithms and highlights the importance of educating healthcare providers and people with diabetes about post-hypoglycemia glucose variability.

Variation in blood glucose, cholesterol, urea and calcium levels according to the physiological stage in Ouled-Djellal ewes in Algerian arid zone. Technical note

Sheep farming in arid and semi-arid regions of Algeria is confronted with large fluctuations in the availability of fodder, which is all the more restrictive for pregnant ewes whose needs are at a maximum and constitute a major obstacle to the development of this sector. This study aims to evaluate the influence of the physiological stage on the energy, nitrogen and mineral status of Ouled-Djellal ewes living in arid zones (Biskra), by determining the plasma levels of glucose, cholesterol, urea and calcium. Blood samples were taken from 40 ewes divided into two groups according to their physiological stage (pregnant and empty). The obtained results showed that the physiological stage had a significant influence only on blood glucose, being higher in empty sheep than in pregnant sheep (P&lt;0.05), whereas for the other blood parameters: cholesterol, urea, and the plasma concentrations of calcium do not seem to be influenced by the physiological stage.

Imaging Glucose Metabolism and Dopaminergic Dysfunction in Sheep (Ovis aries) Brain Using Positron Emission Tomography Imaging Reveals Abnormalities in OVT73 Huntington's Disease Sheep.

Huntington's disease (HD) is a neurodegenerative disease that causes cognitive, movement, behavioral, and sleep disturbances, which over time result in progressive disability and eventually death. Clinical translation of novel therapeutics and imaging probes could be accelerated by additional testing in well-characterized large animal models of HD. The major goal of our preliminary cross-sectional study is to demonstrate the feasibility and utility of the unique transgenic sheep model of HD (OVT73) in positron emission tomography (PET) imaging. PET imaging studies were performed in healthy merino sheep (6 year old, n = 3) and OVT73 HD sheep (5.5 year old, n = 3, and 11 year old, n = 3). Region-of-interest and brain atlas labels were defined for regional analyses by using a sheep brain template. [18F]fluorodeoxyglucose ([18F]FDG) was employed to compare the regional brain glucose metabolism and variations in FDG uptake between control and HD sheep. We also used [18F]fluoro-3,4-dihydroxyphenylalanine ([18F]FDOPA) to compare the extent of striatal dysfunction and evaluated the binding potential (BPND) in key brain regions between the groups. Compared with healthy controls and 11 year old HD sheep, the 5.5 year old HD sheep exhibited significantly increased [18F]FDG uptake in several cortical and subcortical brain regions (P < 0.05-0.01). No difference in [18F]FDG uptake was observed between healthy controls and 11 year old HD sheep. Analysis of the [18F]FDOPA BPND parametric maps revealed clusters of reduced binding potential in the 5.5 year old and 11 year old HD sheep compared to the 6 year old control sheep. In this first-of-its-kind study, we showed the usefulness and validity of HD sheep model in imaging cerebral glucose metabolism and dopamine uptake using PET imaging. The identification of discrete patterns of metabolic abnormality using [18F]FDG and decline of [18F]FDOPA uptake may provide a useful means of quantifying early HD-related changes in these models, particularly in the transition from presymptomatic to early symptomatic phases of HD.

Improved Glucose Variability in Elderly Case of Type 2 Diabetes (T2D) With Retinopathy by Vildagliptin/Metformin (Equmet)

Improved Glucose Variability in Elderly Case of Type 2 Diabetes (T2D) With Retinopathy by Vildagliptin/Metformin (Equmet)

The Association of Glycemic Control Medication Regimens and Preoperative Fructosamine Among Total Joint Artrhoplasty Patients.

Although glycated hemoglobin A1C (HbA1c) has classically been used for glycemic control screening before surgery, fructosamine, a short-term glucose variability indicator, has been reported to be a more accurate predictor of postoperative periprosthetic joint infection among patients with diabetes mellitus (DM). Given the variability of diabetic medication management, this study aims to identify the associated effect of glycemic control medication regimen (GCMR) on the incidence rate and associated odds of abnormal preoperative fructosamine levels among diabetic primary total knee arthroplasty or total hip arthroplasty patients. Between 2017 and 2018, consecutive series of total hip arthroplasty and total knee arthroplasty patients were identified, and the final cohort included only diabetic patients. All patients reported preoperative HbA1c and fructosamine levels. GCMR categories included insulin, metformin, and other. Independent risk of GCMR and abnormal fructosamine levels (>293 µmol/L) were identified using multivariable logistic regression, while controlling for preoperative baseline factors including HbA1C. Among 420 patients, 15.7% (66/420) were diabetic, of whom 22.7% (15/66) reported an abnormal fructosamine level. Among patients requiring GCMR, 24.0% (18/75), 56.0% (42/75), and 77.7% (58/75) reported using insulin, other, and metformin, respectively. Multivariable logistic regressions demonstrated that insulin-dependent patients with DM reported a 1.71 (95% confidence interval [CI], 0.096 to 30.213, P = 0.716) increased odds of abnormal fructosamine levels compared with nonactive GCMR patients, whereas patients managed with metformin and other glycemic control medications reported a protective 0.48 (95% CI, 0.418 to 5.407, P = 0.549) and 0.32 (95% CI, 0.216 to 4.508, P = 0.393) decreased odds of abnormal fructosamine levels, respectively. In this study, insulin and other GCMR medications exhibited a trend for increased and decreased odds of having abnormal preoperative fructosamine levels while controlling for baseline HbA1c level compared with patients with DM without active GCMR. This association may be explained by multifactorial short-term glucose variability in insulin users, indicating the continued need and optimization of short-term glycemic variations instead of HbA1c.

Predictive value of stress hyperglycemia ratio on one-year mortality in chronic kidney disease patients admitted to intensive care unit

BackgroundStress Hyperglycemia Ratio (SHR) reflects the acute blood glucose variation in critically ill conditions. However, its prognostic value in chronic kidney disease (CKD) remains understudied. This study aimed to investigate the association between SHR and one-year mortality in CKD patients hospitalized in the Intensive Care Unit (ICU).MethodsPatients with diagnosis of CKD in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were enrolled. Incidence of all-cause mortality within one-year follow-up was used as the primary endpoint.Results1825 CKD patients were included in the study. A “U-shaped” relationship between SHR and one-year mortality as identified using multivariate restricted cubic spline (RCS) analysis. Then study population were categorized into three groups: Group 1 (SHR < 0.70), Group 2 (0.70 ≤ SHR ≤ 0.95) and Group 3 (SHR > 0.95). Group 2 showed significantly better one-year outcomes compared to the other two groups (p = 0.0031). This survival benefit persisted across subgroup analyses stratified by age, sex, CKD stage, anemia and various clinical conditions.ConclusionSHR proved to be a meaningful biomarker for predicting one-year mortality in ICU-admitted CKD patients, with a “U-shaped” correlation. The identification of the optimal SHR range (0.70–0.95) provided clinicians with a valuable tool for detecting high-risk populations.

Identification and Characterization of a Novel Insulin-like Receptor (LvRTK2) Involved in Regulating Growth and Glucose Metabolism of the Pacific White Shrimp Litopenaeus vannamei.

The insulin receptor (IR) plays a crucial role in the growth and metabolism of animals. However, there are still many questions regarding the IR in crustaceans, particularly their role in shrimp growth and glucose metabolism. In this study, we identified a novel insulin-like receptor gene in Litopenaeus vannamei and cloned its full length of 6439 bp. This gene exhibited a highly conserved sequence and structural characteristics. Phylogenetic analysis confirmed it as an unreported RTK2-type IR, namely, LvRTK2. Expression pattern analysis showed that LvRTK2 is primarily expressed in female reproductive and digestive organs. Through a series of in vivo and in vitro experiments, including glucose treatment, exogenous insulin treatment, and starvation treatment, LvRTK2 was confirmed to be involved in the endogenous glucose metabolic pathway of shrimp under different glucose variations. Moreover, long-term and short-term interference experiments with LvRTK2 revealed that the interference significantly reduced the shrimp growth rate and serum glucose clearance rate. Further studies indicated that LvRTK2 may regulate shrimp growth by modulating the downstream PI3K/AKT signaling pathway and a series of glucose metabolism events, such as glycolysis, gluconeogenesis, glycogen synthesis, and glycogenolysis. This report on the characteristics and functions of LvRTK2 confirms the important role of RTK2-type IRs in regulating shrimp growth and glucose metabolism.

Insulin requirement trajectories during COVID-19 versus non-COVID-19 critical illness-A retrospective cohort study.

The glycemic response to critical COVID-19 remains uncertain. We aimed to assess the association between COVID-19, insulin requirements, glycemic control, and mortality in intensive care unit (ICU) patients. We conducted a retrospective observational study of 350 COVID-19 patients and 1067 non-COVID-19 patients admitted to the ICU. Insulin requirement was defined as the total units of exogenous insulin required to cover one gram of administered carbohydrates (insulin-to-carbohydrate ratio, ICR). We used multivariable generalized linear mixed-model (GLMM) analysis to assess the association of the interaction between COVID-19 and ICU-day with daily ICR, adjusted for fixed and time-dependent covariates. Glycemic control was assessed after stratification on diabetes and COVID-19. We used multivariable logistic regression analysis to assess the association between ICR and 90-day mortality. The mean (95% CI) of the mean daily ICR among patients without diabetes was 0.09 (0.08-0.11) U/g and 0.15 (0.11-0.18) U/g in the non-COVID-19 group and COVID-19 group (p = .01), respectively. In diabetes patients, the corresponding ICRs were 0.52 (0.43-0.62) U/g and 0.59 (0.50-0.68) U/g (p = .32). In multivariable GLMM analysis, the interaction between COVID-19 and ICU-day was independently associated with ICR (risk estimate 1.22, 95% CI 1.15-1.31, p < .001). COVID-19 was associated with higher hypoglycemia prevalence irrespective of diabetes status, higher average glucose levels, more pronounced glucose variability, and a lower proportion of glucose values within target range among patients without diabetes. On multivariable logistic regression analysis, the adjusted odds ratio for 90-day mortality was 1.77 (95% CI 0.94-3.34, p = .076) per one unit increase in mean ICR. In our cohort of ICU patients, COVID-19 was associated with higher daily insulin requirements per gram of administered carbohydrates, and worse glycemic control. We found no robust association between ICR and increased odds of death at 90 days.