Baseline Glucose Levels Research Articles

EFFICACY, SAFETY, AND PATIENT OUTCOMES OF EMERGENCY TREATMENT WITH IV INSULIN-DEXTROSE IN PATIENTS WITH HYPERKALEMIA

Hyperkalemia is a potentially life-threatening condition often encountered in emergency settings. Insulin-dextrose infusion is a common treatment to rapidly lower serum potassium levels, but this approach carries risks, particularly related to glucose imbalances. Objective: To evaluate the efficacy, safety, and clinical outcomes of insulin-dextrose infusion in the emergency treatment of patients with hyperkalemia. Methods: This retrospective study was conducted in the Emergency Department of Shifa International Hospital Islamabad from June 2023 to June 2024. The study included 400 patients with recorded potassium levels. Patients were categorized into non-hyperkalemic (K+ <5.5 mmol/L) and hyperkalemic (K+ ≥ 5.5 mmol/L) groups. Hyperkalemic patients received an insulin-dextrose infusion consisting of an average of 10 units of Actrapid insulin and 50 milliliters of 50% dextrose. Clinical outcomes, including efficacy and safety, were compared between treated hyperkalemic patients and those with moderate-severe hyperkalemia who did not receive the treatment. Statistical analysis was performed using odds ratios (OR) and 95% confidence intervals (CI) to assess the association between treatment variables and outcomes. Results: Glucose imbalances were observed in 60% of patients treated with insulin, with 50% developing hyperglycemia and 20% experiencing hypoglycemia, including 5% with severe hypoglycemia six hours post-treatment. Factors significantly associated with hypoglycemia included multiple insulin doses (OR: 2.9, 95% CI: 2.0-3.9), chronic kidney disease (CKD) (OR: 1.3, 95% CI: 1.0-2.1), and baseline glucose levels below seven mmol/L (OR: 3.0, 95% CI: 2.2-4.2). Hypoglycemic patients had a higher risk of mortality (OR: 1.49, 95% CI: 1.11-2.11). ICU admission occurred in three patients treated with insulin, with a higher risk associated with multiple doses (OR: 1.8, 95% CI: 1.4-2.9) and insulin doses greater than ten units (OR: 5.3, 95% CI: 2.9-10). Conclusion: The use of insulin-dextrose infusion in the emergency management of hyperkalemia is associated with a significant risk of hypoglycemia, ICU admission, and prolonged hospital stay. These findings suggest the need for improved treatment protocols to enhance patient safety in emergency settings.

Associations of retinal neurovascular dysfunction with inner retinal layer thickness in non-proliferative diabetic retinopathy.

Neurovascular coupling impairment and inner retinal layer thinning are early detectable retinal changes in diabetes, and both worsen during progression of diabetic retinopathy (DR). However, direct interactions between these features have not been investigated so far. Therefore, we aimed to analyze associations between the retinal functional hyperemic response to light stimulation and the thickness of individual neuroretinal layers in eyes with early non-proliferative DR. Thirty patients with type 1 diabetes featuring mild (n = 15) or moderate (n = 15) non-proliferative DR and 14 healthy subjects were included in this cross-sectional study. Retinal vessel diameters were measured before and during illumination with flickering light using a dynamic vessel analyzer. Individual layer thickness in the macula was analyzed from spectral domain optical coherence tomography. Flicker light-induced vessel dilation was significantly reduced in patients compared to healthy controls (veins: 3.0% vs. 6.1%, p < 0.001; arteries: 1.3% vs. 5.1%, p = 0.005). Univariately, the response in retinal veins of diabetes patients correlated significantly with ganglion cell layer (GCL) thickness (r = 0.46, p = 0.010), and negatively with hemoglobin A1c (HbA1c) levels (r=-0.41, p = 0.023) and age (r=-0.38, p = 0.037), but not with baseline diameters, glucose levels, or diabetes duration. In a multiple regression model only GCL thickness (p = 0.017, β = 0.42) and HbA1c (p = 0.045, β=-0.35) remained significantly associated with the vascular flicker light response. The results indicate that thinner GCL and worse glycemic control both contribute to reduced retinal neurovascular coupling in patients with clinical signs of DR. Progression of neurovascular dysfunction in DR might be related to structural degeneration of the neurovascular complex in the inner retina.

Triglyceride-Glucose Index Associated with Future Renal Function Decline in the General Population.

The triglyceride-glucose index (TyG index), calculated as the logarithmic product of fasting triglyceride and glucose concentrations, is recognized as a simple marker of insulin resistance. However, the association between the TyG index and future decline of renal function remains unclear in the general population. To investigate whether the TyG index was associated with future decline of renal function in the general population who had not progressed to chronic kidney disease stage G2. Retrospective longitudinal observational cohort study. Individuals who received a population-based health checkup at JA Ehime Kouseiren Checkup Center from 2010 to 2019 (n = 134,007). Individuals without data of baseline fasting triglyceride or glucose levels, or baseline and follow-up data of estimated glomerular filtration rate (eGFR), or those with baseline eGFR < 60mL/min/1.73 m2 were excluded. Future renal function decline, defined as a ≥ 25% decrease in eGFR from baseline. Of 10,758 participants, 8,076 were classified into the low TyG index group (TyG index < 8.76, 1st to 3rd quartiles) and 2,682 into the high TyG index group (TyG index ≥ 8.76, 4th quartile). The mean follow-up period was 37.8 ± 23.6months. The incidence rates of renal function decline were 0.31 and 0.69 per 100 person-years in the low and high TyG index groups, respectively. In multivariate Cox proportional hazard models, high TyG index was significantly associated with future renal function decline (hazard ratio 2.25, 95% CI 1.40-3.60). This association was consistent across subgroups stratified by age, sex, body mass index, baseline eGFR, and diagnosed hypertension, diabetes, or dyslipidemia. In the general population, high TyG index was associated with future renal function decline. The TyG index may be useful in identifying individuals at high risk for future renal function decline in the setting of health checkups.

Arthrospira platensis enriched with Cr(III), Mg(II), and Mn(II) ions improves insulin sensitivity and reduces systemic inflammation in equine metabolic affected horses.

Equine metabolic syndrome (EMS) is a critical endocrine condition in horses, characterized by hyperinsulinemia, hyperlipidemia, and insulin resistance, posing a significant threat to their health. This study investigates the efficacy of supplementing EMS-affected horses with Arthrospira platensis enriched with Cr(III), Mg(II), and Mn(II) ions using biosorption process in improving insulin sensitivity and glucose tolerance, reducing inflammation, and mitigating obesity-related fat accumulation. Our results demonstrate that Arthrospira supplementation reduces baseline insulin and glucose levels, contributing to decreased adipose tissue inflammation. Furthermore, Arthrospira supplementation results in a decrease in body weight and improvements in overall body condition scores and cresty neck scores. Additionally, administration of Arthrospira leads to reduced levels of triglycerides and aspartate aminotransferase, indicating a decrease in hepatic adiposity and inflammation. These findings suggest that Arthrospira, enriched with essential micro- and macroelements, can be an advanced feed additive to enhance insulin sensitivity, promote weight reduction, and alleviate inflammatory processes, thereby improving the overall condition of horses affected by EMS. The use of Arthrospira as a feed additive has the potential to complement conventional management strategies for EMS.

Intestinal alterations and mild glucose homeostasis impairments in the offspring born to overweight rats

The gut plays a crucial role in metabolism by regulating the passage of nutrients, water and microbial-derived substances to the portal circulation. Additionally, it produces incretins, such as glucose-insulinotropic releasing peptide (GIP) and glucagon-like derived peptide 1 (GLP1, encoded by gcg gene) in response to nutrient uptake. We aimed to investigate whether offspring from overweight rats develop anomalies in the barrier function and incretin transcription. We observed pro-inflammatory related changes along with a reduction in Claudin-3 levels resulting in increased gut-permeability in fetuses and offspring from overweight rats. Importantly, we found decreased gip mRNA levels in both fetuses and offspring from overweight rats. Differently, gcg mRNA levels were upregulated in fetuses, downregulated in female offspring and unchanged in male offspring from overweight rats. When cultured with high glucose, intestinal explants showed an increase in gip and gcg mRNA levels in control offspring. In contrast, offspring from overweight rats did not exhibit any response in gip mRNA levels. Additionally, while females showed no response, male offspring from overweight rats did exhibit an upregulation in gcg mRNA levels. Furthermore, female and male offspring from overweight rats showed sex-dependent anomalies when orally challenged with a glucose overload, returning to baseline glucose levels after 120 min.These results open new research questions about the role of the adverse maternal metabolic condition in the programming of impairments in glucose homeostasis, enteroendocrine function and gut barrier function in the offspring from overweight mothers and highlight the importance of a perinatal maternal healthy metabolism.

Evaluating the effectiveness of a novel somatostatin receptor 2 antagonist, ZT-01, for hypoglycemia prevention in a rodent model of type 2 diabetes.

Background: Elevated levels of somatostatin blunt glucagon counterregulation during hypoglycemia in type 1 diabetes (T1D) and this can be improved using somatostatin receptor 2 (SSTR2) antagonists. Hypoglycemia also occurs in late-stage type 2 diabetes (T2D), particularly when insulin therapy is initiated, but the utility of SSTR2 antagonists in ameliorating hypoglycemia in this disease state is unknown. We examined the efficacy of a single-dose of SSTR2 antagonists in a rodent model of T2D. Methods: High-fat fed (HFF), low dose streptozotocin (STZ, 35mg/kg)-induced T2D and HFF only, nondiabetic (controls-no STZ) rats were treated with the SSTR2 antagonists ZT-01/PRL-2903 or vehicle (n = 9-11/group) 60min before an insulin tolerance test (ITT; 2-12U/kg insulin aspart) or an oral glucose tolerance test (OGTT; 2g/kg glucose via oral gavage) on separate days. Results: This rodent model of T2D is characterized by higher baseline glucose and HbA1c levels relative to HFF controls. T2D rats also had lower c-peptide levels at baseline and a blunted glucagon counterregulatory response to hypoglycemia when subjected to the ITT. SSTR2 antagonists increased the glucagon response and reduced incidence of hypoglycemia, which was more pronounced with ZT-01 than PRL-2903. ZT-01 treatment in the T2D rats increased glucagon levels above the control response within 60min of dosing, and values remained elevated during the ITT (glucagon Cmax: 156 ± 50 vs. 77 ± 46pg/mL, p < 0.01). Hypoglycemia incidence was attenuated with ZT-01 vs. controls (63% vs. 100%) and average time to hypoglycemia onset was also delayed (103.1 ± 24.6 vs. 66.1 ± 23.6min, p < 0.05). ZT-01 administration at the OGTT onset increased the glucagon response without exacerbating hyperglycemia (2877 ± 806 vs. 2982 ± 781), potentially due to the corresponding increase in c-peptide levels (6251 ± 5463 vs. 14008 ± 5495, p = 0.013). Conclusion: Treatment with SSTR2 antagonists increases glucagon responses in a rat model of T2D and results in less hypoglycemia exposure. Future studies are required to determine the best dosing periods for chronic SSTR2 antagonism treatment in T2D.

Songbirds avoid the oxidative stress costs of high blood glucose levels: a comparative study.

Chronically high blood glucose levels (hyperglycaemia) can compromise healthy ageing and lifespan at the individual level. Elevated oxidative stress can play a central role in hyperglycaemia-induced pathologies. Nevertheless, the lifespan of birds shows no species-level association with blood glucose. This suggests that the potential pathologies of high blood glucose levels can be avoided by adaptations in oxidative physiology at the macroevolutionary scale. However, this hypothesis remains unexplored. Here, we examined this hypothesis using comparative analyses controlled for phylogeny, allometry and fecundity based on data from 51 songbird species (681 individuals with blood glucose data and 1021 individuals with oxidative state data). We measured blood glucose at baseline and after stress stimulus and computed glucose stress reactivity as the magnitude of change between the two time points. We also measured three parameters of non-enzymatic antioxidants (uric acid, total antioxidants and glutathione) and a marker of oxidative lipid damage (malondialdehyde). We found no clear evidence for blood glucose concentration being correlated with either antioxidant or lipid damage levels at the macroevolutionary scale, as opposed to the hypothesis postulating that high blood glucose levels entail oxidative costs. The only exception was the moderate evidence for species with a stronger stress-induced increase in blood glucose concentration evolving moderately lower investment into antioxidant defence (uric acid and glutathione). Neither baseline nor stress-induced glucose levels were associated with oxidative physiology. Our findings support the hypothesis that birds evolved adaptations preventing the (glyc)oxidative costs of high blood glucose observed at the within-species level. Such adaptations may explain the decoupled evolution of glycaemia and lifespan in birds and possibly the paradoxical combination of long lifespan and high blood glucose levels relative to mammals.

Associations of neurovascular dysfunction with inner retinal layer thickness in non‐proliferative diabetic retinopathy

Aims/Purpose: Neurovascular dysfunction and inner retinal layer thinning are among the earliest detectable retinal changes in diabetes, and both worsen during development and progression of diabetic retinopathy (DR). However, direct interactions between these features have not been investigated so far. Therefore, we aimed to analyse associations between the retinal functional hyperaemic response and thickness of the individual neuroretinal layers in eyes with non‐proliferative DR.Methods: Thirty patients with Type 1 diabetes featuring mild (n = 15) or moderate (n = 15) non‐proliferative DR and 14 healthy subjects were included in this cross‐sectional study. Retinal vessel diameters were measured before and during illumination with flickering light using a dynamic vessel analyser. Individual retinal layer thickness in the macula was analysed from spectral domain optical coherence tomography.Results: Flicker light‐induced vessel dilation was significantly reduced in diabetes patients compared to healthy controls (veins: 3.0% vs. 6.1%, p &lt; 0.001; arteries: 1.3% vs. 5.1%, p = 0.005). Univariately, the response in retinal veins of diabetes patients correlated significantly with ganglion cell layer (GCL) thickness (r = 0.46, p = 0.010) and inner plexiform layer thickness (r = 0.40, p = 0.027), and negatively with haemoglobin A1c (HbA1c) levels (r = −0.41, p = 0.023) and age (r = −0.38, p = 0.037), but not with baseline diameters, glucose levels, or diabetes duration. In a multiple regression model only HbA1c (p = 0.027, β = −0.40) and GCL thickness (p = 0.030, β = 0.39) remained significantly associated with the vascular flicker light response.Conclusions: The results indicate that thinner GCL and worse glycaemic control both contribute to reduced neurovascular coupling in patients with clinical signs of DR. Progression of neurovascular dysfunction in DR might be related to structural degeneration of the neurovascular complex in the inner retina.

A Non-invasive Blood Glucose Detection System Based on Photoplethysmogram with Multiple Near-infrared Sensors.

Recent advancements in non-invasive blood glucose detection have seen progress in both photoplethysmogram and multiple near-infrared methods. While the former shows better predictability of baseline glucose levels, it lacks sensitivity to daily fluctuations. Near-infrared methods respond well to short-term changes but face challenges due to individual and environmental factors. To address this, we developed a novel fingertip blood glucose detection system combining both methods. Using multiple light sensors and a lightweight deep learning model, our system achieved promising results in oral glucose tolerance tests. A total of 10 participants were involved in the study, each providing approximately 700 data segments of about 10 seconds each. With a root mean squared error of 0.242 mmol/L and 100% accuracy in zone A of the Parkes error grid, our approach demonstrates the potential of multiple near-infrared sensors for non-invasive glucose detection.

Impaired Glucose Tolerance and Risk for Mild Cognitive Impairment and Dementia:Results from the SPRINT‐MIND Trial

AbstractBackgroundIn epidemiological studies, persons with a diagnosis of diabetes mellitus (DM), especially those with coexisting hypertension, have been shown to be at increased risk for dementia.[1‐3] However, the relationship between impaired glucose tolerance (IGT) and future risk of Mild Cognitive Impairment (MCI) and dementia is less clear, especially in persons without diagnosed DM . The SPRINT‐MIND trial (4) provides an opportunity to assess the relationship between baseline glucose level and risk for transition to mild cognitive impairment in the context of hypertension control.MethodRandomized clinical trial (n = 9,361) conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diagnosed diabetes or history of stroke. Baseline serum glucose obtained fasting and incidence of adjudicated MCI and probable dementia (PD) was calculated. Results were also stratified by age, baseline cardiovascular disease risk, and baseline systolic blood pressure.ResultAt baseline, 4398 participants (58%) had a serum glucose &amp;lt; 100 mg/dl and 3606 (42%) had a serum glucose &amp;gt;100. Overall, 389 (7.9%) of participants in the normoglycemic group and 250 (6.9%) of participants in the impaired glucose tolerance group developed MCI. For incident PD, 204 (4.1%) and 118 (3.3%) cases occurred in in persons with normal vs. impaired glucose tolerance. Incidence MCI or Dementia did not significantly differ when the results were stratified by baseline age or blood pressure.ConclusionIn persons with hypertension but without diagnosed diabetes, baseline impaired glucose tolerance does not confer elevated risk for MCI or dementia.

Psychosocial and sociodemographic factors associated with gestational blood glucose levels in women attending public hospitals: Results from baseline of MAASTHI cohort.

Understanding psychosocial environment is important for improving maternal and fetal health outcomes during pregnancy. We aimed to identify the association between gestational blood glucose levels and psychosocial and demographic factors in pregnant women. In the MAASTHI pregnancy cohort in Bengaluru, we assessed depressive symptoms, and social support using validated scales at baseline in first trimester. A 2-hour 75 g oral glucose tolerance test (OGTT) was administered between 24-36 weeks of gestation. We examined the relation between psychosocial factors assessed at baseline and gestational blood glucose levels in second/third trimester using multivariate linear regression and explored association between serum cortisol and gestational blood glucose levels in subgroup samples. We found that 9% of pregnant women had depressive symptoms and 14.3% had Gestational Diabetes Mellitus (GDM). Psychosocial factors, including depressive symptoms, have a significant correlation with gestational fasting(β = 0.12, p-value<0.05) and postprandial blood sugar level(β = 0.23, p-value<0.05) and poor social support were found to have a significant association with gestational fasting blood glucose levels(β = 1.45, p-value <0.05) and postprandial blood sugar levels(β = 2.60, p-value <0.05). The sociodemographic factors such as respondent education, occupation, social and economic status were associated with gestational blood sugar after adjusting for potential confounder variables. Depressive symptoms and poor social support earlier in pregnancy were significantly associated with increased gestational blood glucose levels. Early detection and recognition of modifiable psychosocial risk factors can reduce glucose intolerance during pregnancy. Evaluating the benefits of screening for psychosocial factors and timely management of gestational diabetes mellitus can be helpful in India.

Ectopic expression of insulin in a type 1 diabetic rat model by injection of manipulated mesenchymal stem cells with an insulin construct driven by a glucose-sensitive promoter in the port vein.

The treatment of type 1 diabetes through islet cell transplantation is a complex process, facing challenges such as allograft rejections and a limited supply of donors. One potential solution is to utilize the liver as an alternative for natural insulin production, as hepatocytes can secrete proteins and respond to glucose levels. Recent research has shown promising results in using mesenchymal stem cells as a potential cure for diabetes. The study utilized a diabetic rat model, confirmed through blood sugar measurement. A plasmid vector was designed with specific genetic components, synthesized by biotech company, and then Inserted vector into a plasmid with resistance genes and bacterial origin. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were cultured and transfected with the plasmid using Lipofectamine 3000. Polymerase chain reaction wasemployed to confirm successful transfection using specific primers. For the animal study, 30 male Wistar rats were divided into six groups, each comprising five rats. The control group did not receive any treatment, while the second group received MSCs via Portal Vein Injection. The third group received MSCs transfected with a specific construct via Portal Vein Injection. The fourth group was induced to develop diabetes through streptozotocin(STZ) injection, the fifth group developed diabetes and received untransfected MSCs via Portal Vein Injection, and the sixth group received MSCs transfected with the specific construct via Portal Vein Injection. To manage Pain, appropriate pain control was administered to the rats for 3 days after the surgery. Fixed liver tissues obtained from the euthanized rats were utilized for immunohistochemistry. In this study, immunohistochemical techniques were used to examine insulin expression in different groups of rats. The control groups showed high levels of insulin expression, while the diabetic groups exhibited lower expression. However, there was a significant difference between the diabetic groups treated with MSC and transgenic MSC cells. All groups had similar baseline glucose levels, but the diabetic groups showed a significant increase after STZ injection, whereas the control and MSC groups did not. Postintervention, both the control and MSC groups had similar glucose levels to the post-STZ levels. However, diabetes-induced groups experienced a significant decrease in glucose levels, with the transfected MSCs showing a greater decrease than the untransfected MSCs. The study suggested that treatment with MSCs, especially transfected ones, can effectively reduce glucose levels in rats with diabetes. In this research, rat BM-MSCs were utilized to create insulin-producing mesenchymal cells with glucose-sensitive insulin expression. The cells were transferred to the liver of diabetic rats via portal vein injection, leading to an increase in insulin expression. This study proposes a novel approach for cell therapy and delivery in the treatment of type 1 diabetes.

Association of urinary arsenic metabolism with type 2 diabetes and glucose homeostasis: Cross-sectional and longitudinal associations.

BackgroundPrevious researches have assessed the relationships of urinary arsenic metabolism with type 2 diabetes (T2D) and glucose-insulin homeostasis, but the results were controversial, and potential mechanisms remain largely unclear. ObjectivesThis study aimed to investigate the cross-sectional and longitudinal associations of urinary arsenic metabolism with T2D prevalence and glucose changes in relatively higher arsenic exposure, and further to evaluate the underlying roles of oxidative damage in these relationships. MethodsWe included 796 participants at baseline, among them 509 participants were followed up after 2 years. Logistic regression model and leave-one-out approach were applied to evaluate the associations of arsenic metabolism with T2D prevalence. Linear mixed model was conducted to estimate the relationship of arsenic metabolism with glycemic changes over two years. The associations between arsenic metabolism and indicators of oxidative stress were assessed with a linear regression model. We further performed mediation analysis to investigate the role of oxidative stress in the associations of arsenic metabolism with 2-year change of glucose levels. ResultsHigher urinary MMA% increased T2D prevalence and baseline glucose levels. MMA% was positively associated with 2-year change of glucose levels. Moreover, we observed significant dose-response relationship between MMA% and 8-hydroxy-2-deoxyguanosine (8-OHdG). However, the mediating role of 8-OHdG in the association of MMA% and 2-year change of glucose levels was not observed in this population. ConclusionsIn this population exposure to relatively higher arsenic levels, higher MMA% contributed to increased T2D prevalence and glucose homeostasis disorder. Arsenic metabolism also affected oxidative stress levels, especially 8-OHdG. Further studies are required to investigate the potential mechanisms.

1-LB: Evaluating the Effectiveness of the Novel Somatostatin Receptor Antagonist (SSTR2a) ZT-01 for Hypoglycemia Prevention in a Rodent Model of Type 2 Diabetes

Background: Few pharmacological strategies exist to prevent hypoglycemia in diabetes, other than reducing the intensity of glucose-lowering therapy. SSTR2a treatment increases glucagon counterregulation and reduces the time spent in hypoglycemia in rodent models of type 1 diabetes (T1D), but the utility of this approach in type 2 diabetes (T2D) is unclear. The purpose of this study was to test the effect of acute SSTR2a treatment in a rodent model of hypoglycemia in T2D. Methods: High fat fed (HFF), low dose streptozotocin (35 mg/kg) T2D rats received SSTR2a treatment (subcutaneous ZT-01 3 mg/kg) or vehicle (N=9-11/group) 60 min before the induction of hypoglycemia using rapid-acting insulin (12 U/kg). Glycemia, glucagon and c-peptide levels were measured intermittently pre- and post-dosing. Results: T2D in the rats was characterized by significantly higher baseline glucose (21.8 ± 4.7 vs 6.5 ± 0.7 mmol/L, p&amp;lt;0.05) and HbA1c (8.6 ± 0.6% vs 5.5 ± 0.5%; p&amp;lt;0.0001) levels relative to HFF controls (n=3). T2D rats also displayed reduced c-peptide levels relative to controls (3.1 ± 1.3 vs 6.1 ± 1.2 ng/ml, p&amp;lt;0.05). During hypoglycemic challenge (T2D rats only), SSTR2a elevated glucagon levels relative to vehicle treatment (glucagon Cmax: 156 ± 50 vs 77 ± 46 pg/ml, p&amp;lt;0.01) and reduced the incidence of hypoglycemia by ~40% (5/8 SSTR2a treated vs 9/9 vehicle treated rats). In those that developed hypoglycemia, the average time to hypoglycemia onset was delayed (103.1± 24.6 vs 66.1 ± 23.6 min, p&amp;lt;0.05) with SSTR2a compared to vehicle. Conclusion: SSTR2a treatment increases glucagon levels in this rodent model of T2D, which appears to reduce the risk for hypoglycemia following bolus insulin dosing. Disclosure N. C. D'souza: None. M. Nejad-mansouri: None. R. Liggins: Employee; Zucara Therapeutics, Stock/Shareholder; Zucara Therapeutics. O. Chan: None. M. C. Riddell: Advisory Panel; Zealand Pharma A/S, Zucara Therapeutics, Indigo Diabetes, Consultant; Lilly Diabetes, Eli Lilly and Company, Jaeb Center for Health Research, Speaker's Bureau; Dexcom, Inc., Novo Nordisk, Sanofi, Stock/Shareholder; Supersapiens, Zucara Therapeutics. P. Zaree bavani: None. J. Aiken: None. E. G. Hoffman: None. S. C. Atherley: None. S. Champsi: None. N. Aleali: None. D. Shakeri: None. M. El-zahed: None. N. Akbarian: None. Funding GlycoNet (CD-85)

1533-P: Mind over Metabolism—A Molecular Subtype of Vagal Neurons That Can Improve Glucose Tolerance

Parasympathetic neurons of the dorsal motor nucleus of the vagus (DMV) control glucose metabolism through the vagus nerve and so are potential targets for diabetes treatment. Currently, little is known about the molecular identity or organization of the glucose-regulating DMV neurons. To identify these neurons for further study, we optogenetically activated them in awake mice during a glucose tolerance test (GTT). We transgenically targeted a blue light-sensitive ion channel, CaTCh, selectively to all DMV neurons based on co-expression of Chat - and Phox2b- driven recombinases (Chat-Cre::Phox2b-Flp::CaTCh mice). We implanted optical fibers over the DMV in these adult mice (2 females, 1 male), acclimated them to the test environment and procedure, and then fasted them overnight. After recording baseline glucose levels, we administered intraperitoneal glucose (20% glucose, 10uL/g) and concurrently began photostimulation (time=0-30min; 5Hz, 1ms pulse, 2.5s off, 1s on) or sham stimulation. We performed tail blood glucometry at 5-min increments from -20-120min and compared average readings between stimulation and sham trials. Results: sham 0-30min 472.6 ± 74mg/dL, stim 0-30min 352 ± 48mg/dL (p=0.0005, paired t-test); other timepoints, p&amp;gt;0.05 between conditions. Our results indicate that activating DMV neurons can significantly improve glucose tolerance. To identify specific DMV neurons controlling glucose tolerance, we optogenetically activated a molecular subtype of DMV neurons defined by co-expression of Calb2 and Chat (2 female Calb2-Cre::Chat-Flp::CaTCh adult mice). We photostimulated Calb2+ DMV neurons while performing GTT as described above. Results: sham 0-30min 493 ± 90mg/dL, stim 0-30min 407 ± 69mg/dL (p=0.0390, paired t-test); other timepoints, p&amp;gt;0.05 between conditions. Together our data indicates that activating DMV neurons generally or Calb2+ DMV neurons specifically improves glucose tolerance. Disclosure N.J.Conley: None. L.S.Kauffman: None. J.Campbell: None. Funding American Diabetes Association (1-18-INI-14 to J.C.)

Stress, glucose metabolism and the HPA axis: Early life adversity-the missing piece of the puzzle?

Physiological stress prompts metabolic reactions aimed at increasing glucose supply, to initiate a fight/flight response in a healthy individual. The quality of the first 1000 days of life is a critical period which impacts the overall metabolic trajectory. Exposure to stress in early life increases the risk of developing cardiometabolic disorders. This may be due to epigenetic programming of cardiometabolic and stress response mechanisms. The objective of this study was to investigate both stress induced and baseline glucose levels in different models of early life adversity, in addition to dissecting mechanisms that drive these changes. We determined baseline and stress mediated blood glucose release in 3 different early life adversity models. Furthermore, we administered an escalating cortisol dose to an adversity negative cohort, to dissect the gluconeogenic driving mechanism and checked glucocorticoid driven gene expression to confirm GC-GR binding. Our study showed an impairment of stress response along with sex dependent differences in basal glucose levels in early life adversity models. The human institutionalisation/adoption and mice infection models showed higher baseline glucose levels in females, while the rat maternal deprivated males showed lower baseline glucose levels compared to the control group. Additionally, we established the stress mediated glucose release as a glucocorticoid independent process. Our study proposes a new outlook on potential mechanisms that may drive stress mediated metabolic changes. Additionally, we emphasise quality of early life as the missing piece of the puzzle to get a better understanding of the adult metabolic profile.

Baseline glucose levels moderate the association between burn-related mortality inpatients with obesity

BackgroundDiffering findings concerning outcomes for burn patients with obesity indicate additional factors at play. One possible explanation could lie in determining metabolically healthy versus unhealthy obesity, which necessitates further study. MethodsA retrospective study was conducted using the Cerner Health Facts® Database. Deidentified patient data from 2014 to 2018 with second or third-degree burn injuries were retrieved. A moderator analysis was conducted to determine if the association between increased body mass index (BMI) and mortality is moderated by baseline glucose level, a surrogate marker associated with metabolically unhealthy obesity. ResultsThe study included 4682 adult burn patients. BMI alone was not associated with higher mortality (β = 0.106, p = 0.331). Moderation analysis revealed that baseline glucose level significantly modulated the impact of BMI on burn-related obesity; patients with higher BMI and higher baseline blood glucose levels had higher mortality than those with lower baseline blood glucose levels (β = 0.277, p = 0.009). These results remained unchanged after adjusting for additional covariates (β = 0.285, p = 0.025) and inthe sensitivity analysis. ConclusionsIncreased baseline glucose levels indicate increased mortality in obese patients with burn injuries, emphasizing the differentiation between metabolically unhealthy versus healthy obesity.

Effects of Neuromuscular Electrical Stimulation on Fasting Blood Glucose

Muscle contraction during physical activity improves glucose metabolism and glycemic control by facilitating muscle glucose uptake and utilization. Neuromuscular electrical stimulation (NMES) is an involuntary alternative mode of muscle contraction and is widely applicable and suitable for individuals with sedentary lifestyle including people with physical functional limitations and other mobility impairments. Use of NMES has the potential to improve metabolic health analogous to voluntary exercise. Purpose: To determine the acute effect of 30 mins of NMES on energy metabolism and fasting blood glucose level. Methods: Fifteen participants without diabetes participated in the study (Males: 6; Females: 9; Age: 33.80 ± 12.99 years; BMI: 32.59 ± 9.17 kg/m2). Each participant underwent 30 mins of cyclical NMES on the quadricep muscles of both legs while lying supine on a bed. NMES was applied at a frequency of 50Hz with a pulse width of 300μs up to maximum tolerable intensity. Blood glucose and lactate levels were determined at baseline and at 5 mins intervals during the stimulation. Energy expenditure and substrate utilization were measured at baseline and monitored continuously during the NMES via indirect calorimetry. The experimental procedure was performed in a fasting condition and was directly preceded by a day of dietary control. Results: A decreasing blood glucose effect of NMES was observed between baseline glucose level (95.94 ± 7.81 mg/dL) and after 25 mins (92.85 ± 8.82 mg/dL) and 30 mins (91.79 ± 9.00 mg/dL) of NMES (p&lt;0.05). Average energy expenditure rate during the 30min of NMES (19.37 ± 4.49 Kcal/kg/day) was relatively higher than that of the resting baseline rate (19.24 ± 3.57 Kcal/kg/day) (p&lt;0.05). Blood lactate level and respiratory exchange ratio (substrate utilization) however, remained unaffected throughout the experimental procedure. Conclusion: Neuromuscular electrical stimulation is effective in decreasing blood glucose level and hence could serve as a beneficial intervention for blood glucose management. Supported by NIH Grant R01 DK132430 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A Histological Study on the Effect of Aqueous Extract of Cactus on Frontal Cortex of Diabetes Mellitus Wistar Rat

The cactus plant is one of the most common plants used in treatment all kinds of ailment. Studies have shown that the cactus extract has both antihyperglycemic and neuroprotective effects. This research will focus on some of the effect of an aqueous extract of cactus on the cytoarchitecture of the frontal cortex of the diabetic Wistar rats. Thirty (30) male Wistar rats were randomly selected and placed into five (5) groups of 6 Wistar rats each. These include the control group A, diabetic only group B, diabetic+cactus group C, diabetic+metformin group D, and cactus only group E. The animals were acclimatized for one week. The Rats were weighed, and a baseline glucose level established after the overnight fasting period. The animals were injected with streptozotocin calculated at a dose of 70 mg/kg body weight and reintroduced to the normal feeding cycle. After about 72 hours, diabetes was established (blood glucose≥ 7 mmol). The administration of Cactus extract of 100 mg/kg BW and Metformin of 100 mg/kg BW commenced for four weeks. After fourth week the animals were sacrificed by euthanasia and the brain was harvested and fixed in 10 % formal saline for H and E and PTAH staining. At the end of the four weeks experiments the results shows, the average body weight of the rats in the diabetic+cactus group showed an increase by the end of the four-week experiment which was not significantly different to the normal control group, while the diabetic+metformin group was significantly different to the control group and also diabetic control group was significant to normal control group. The relative brain weight of the diabetic+cactus and diabetic+metformin group were not significantly different to the normal control (p&gt;0.05). The blood glucose levels of the diabetic+cactus and diabetic+metformin group at the end of the fourth week were not significant different from Group A (p&gt;0.05). The H and E photomicrographs of diabetic group show that most cells were necrotic, and the normal pyramidal cells present were scanty. The diabetic+cactus group showed presence of more normal pyramidal cells than necrotic cells. The diabetic+metformin group showed presence of both normal and necrotic pyramidal cells. The PTAH staining in the diabetic group, there were astrocytes present with degenerated neuron. Diabetic+cactus and diabetic+metformin groups showed some neurons were degenerated while some appeared normal with astrocytes while the cytoarchitecture of cactus only group are similar to that of normal control group. Aqueous extract of cactus possesses anti hyperglycemic effects and can be a potential and effective therapy for the management of diabetes due to its ameliorative properties as shown in the findings of this research.

Cold temperatures induce priming of the glucose stress response in tree swallows

Capricious environments often present wild animals with challenges that coincide or occur in sequence. Conceptual models of the stress response predict that one threat may prime or dampen the response to another. Although evidence has supported this for glucocorticoid responses, much less is known about the effects of previous challenges on energy mobilization. Food limitation may have a particularly important effect, by altering the ability to mobilize energy when faced with a subsequent challenge. We tested the prediction that challenging weather conditions, which reduce food availability, alter the energetic response to a subsequent acute challenge (capture and restraint). Using a three-year dataset from female tree swallows measured during three substages of breeding, we used a model comparison approach to test if weather (temperature, wind speed, and precipitation) over 3- or 72-hour timescales predicted baseline and post-restraint glucose levels, and if so which environmental factors were the strongest predictors. Contrary to our predictions, weather conditions did not affect baseline glucose; however, birds that had experienced lower temperatures over the preceding 72 h tended to have higher stress-induced glucose when faced with an acute stressor. We also saw some support for an effect of rainfall on stress-induced glucose: around the time that eggs hatched, birds that had experienced more rainfall over the preceding 72 h mounted lower responses. Overall, we find support in a wild animal for the idea that the glucose stress response may be primed by exposure to prior challenges.