Decline In Glucose Research Articles

Glucocorticoid and glycemic responses to immune challenge in a viviparous snake afflicted with an emerging mycosis.

Disease may be both a cause and consequence of stress, and physiological responses to infectious disease may involve stress coping mechanisms that have important fitness consequences. For example, glucocorticoid and glycemic responses may affect host fitness by altering resource allocation and use in hosts, and these responses may be affected by competing stressors. To better understand the factors that affect host responses to infection, we challenged the immune system of field acclimatized pygmy rattlesnakes, Sistrurus miliarius, with a sterile antigen, lipopolysaccharide (LPS), and measured the glucocorticoid and glycemic response in healthy non-reproductive snakes, snakes afflicted with an emerging mycosis (ophidiomycosis), and pregnant snakes. We hypothesized that LPS challenge would result in a glucocorticoid and glycemic response typical of the vertebrate acute phase response (APR), and therefore predicted that LPS challenge would result in an acute increase in plasma corticosterone (CORT) and a decline in plasma glucose in all individuals. Additionally, we hypothesized that the APR would be attenuated in individuals simultaneously coping with additional challenges to homeostasis (i.e., disease or reproduction). As predicted, immune challenge elicited an acute increase in plasma CORT and a decrease in plasma glucose. Snakes coping with ophidiomycosis and pregnant snakes were able to mount a robust glucocorticoid and hypoglycemic response to LPS challenge, which was contrary to our hypothesis. Our findings clarify directions of causality linking infection, glucocorticoids, and glucose, and emphasize the importance of future research examining the fitness consequences of interactions between stress and disease in wildlife threatened by emerging pathogens.

Chemical Characterization, Evaluation of Acute Oral Toxicity, and Anti-Diabetic Activity of Aloe sabaea Flowers Extract on Alloxan-Induced Diabetic Rats.

The study aimed to conduct chemical profiling, acute in-vivo toxicity evaluation, and the potential anti-diabetic effect of standardized Aloe sabaea flowers ethanolic extracts (ASFEE) on alloxan-induced diabetic rats. The chemical composition was analyzed using GC-MS and TLC techniques. The oral acute toxicity study was performed according to the WHO 2000 and the OECD 420 guidelines. Furthermore, anti-diabetic activity was investigated using two doses of ASFEE (0.2 and 0.5 g/kg/day BW, p.o.) compared with glibenclamide (5 mg/kg/day, p.o.). A molecular docking investigation of the identified components with the PTPN9 enzyme was performed to figure out the proposed anti-diabetic mechanism. GC-MS analysis displayed the existence of 18 compounds; mostof the compoundswere fatty acids and theiresters, and phytosterols. Total phenolic and flavonoid contents were 42.00±1.26 mg GAE/g DW and 22.21±1.55 mg QE/g DW, respectively. The results of the in-vivo toxicity study revealed the absence of noticeable signs of toxicity or mortality at various doses establishing the safety of the tested extract. The estimated LD50 value was higher than 10 g/kg. Antidiabetic action exhibited a noticeable decline in fasting blood glucose (FBG) levels comparable to glibenclamide with no inducing intense hypoglycemia and considerable excess weight.

Therapeutic Potential of Fecal Microbiota Transplantation in Type 2 Diabetes Mellitus: A Systematic Review.

Diabetes mellitus is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. It can cause various complications, which result in significant morbidity and mortality. There are multiple treatment options available to combat this disease; however, despite this, the incidence of type 2 diabetes mellitus is continuously increasing. Some promising results have shown that dysbiosis has a role in the pathogenesis of type 2 diabetes mellitus and fecal microbiota transplantation (FMT) in animals; however, the usage of FMT in humans needs further clarification and review. We explored PubMed, Popline, and Cochrane Library to identify relevant papers. Eight articles were then finalized after screening and applying eligibility criteria. These articles explored the role of the therapeutic efficacy of FMT in insulin resistance and hyperglycemia. The studies showed that the FMT had a positive impact on managing hyperglycemia and insulin resistance, which is evident in the decline of blood glucose and HBA1c levels and the rise of insulin and C-peptides. In addition, FMT also helped to control other risk factors such as hyperlipidemia and blood pressure; however, the impact on weight loss is not convincing. FMT also influenced the levels of some microbiota, which could be involved in controlling hyperglycemia and insulin resistance. Due to limited control trials and study periods and the small sample size of diabetic patients, more research is needed to explore the impact of FMT in controlling type 2 diabetes mellitus.

Potential hepato-protective effect of Salvia hispanica (chia) and Chenopodium quinoa (quinoa) in diabetic male albino rats

Chia and quinoa seeds are novel sources of bioactive compounds that may improve lipid profile, blood glucose homeostasis, and body weight in diabetic rats. This work aims to study the effect of different percentages of chia and quinoa consumption, alone or in a mixture, compared to Metformin drug on regulating lipid profile, blood glucose level, and weight of male diabetic rats. The consumption of quinoa and chia seeds showed a significant decline in fasting blood glucose (FBG), fasting insulin level, Hemoglobin A1C (HbA1c), and Homeostatic Model Assessment for Insulin (HOMA-IR), while the best results were obtained with Metformin and chia seeds. A decrease in mean body weight, triglycerides, total cholesterol, low density lipoprotein (LDL-C), and very low-density lipoprotein (VLDL-C), and an increase in high density lipoprotein (HDL-C) occurred, which was significant when consuming chia and quinoa seeds rather than treatment with metformin. Chia and quinoa seeds could improve blood glucose homeostasis and lipid profile in diabetic rats. These research findings could promote the daily consumption of quinoa and chia as great functional foods that could improve blood glucose homeostasis and lipid profile.

X-ray irradiation maintains soluble sugar content and regulates expression of genes related to sugar metabolism of figs (Ficus carica L. ‘Siluhongyu’)

Fig is susceptible to lose fruit sensory quality due to its delicate skin and the natural bottom fruit pore. X-ray irradiation is an effective strategy for fruit preservation. This study investigated appearance and basic quality attributes of ‘Siluhongyu’ fig and evaluated the effects of X-ray on fig sugar metabolism and relative expression of genes. Results indicated that ‘Siluhongyu’ fig could be accepted by consumers with suitable overall dimension, soluble sugar, titratable acidity (TA), soluble protein, and dietary fiber contents. Sugar metabolism assay revealed that 3.0 kGy X-ray effectively inhibited the decline of glucose, fructose and sucrose contents. The starch degradation and the increase of amylase activity of figs were alleviated. In addition, the neutral invertase (NI), sucrose phosphate synthase (SPS), sucrose synthase (SS) and phosphofructokinase (PFK) activities in figs were activated by 3.0 kGy X-ray. About 22 % higher hexokinase (HK) activity was found in 3.0 kGy irradiated fruit than non-irradiated figs. Furthermore, 3.0 kGy X-ray upregulated gene expressions of NI, SS, HK, and PFK. The study proves that 3.0 kGy X-ray could be used as the feasible preservation means to regulate sugar metabolism and maintain quality of figs.

Investigation of Factors Influencing the Effectiveness of Deformable Nanovesicles for Insulin Nebulization Inhalation.

Nebulized inhalation offers a noninvasive method for delivering drugs to treat both local respiratory and systemic diseases. In this study, insulin was used as a model drug to design a series of deformable nanovesicles (DNVs) with key quality attributes, including particle size, deformability, and drug load capacity. We investigated the effects of these properties on aerosol generation, macrophage phagocytosis, and bloodstream penetration. The results showed that deformability improved nebulization performance and reduced macrophage phagocytosis, benefiting local and systemic delivery. However, the advantage of DNVs for transmembrane penetration was not evident in the alveolar epithelium. Within the size range of 80-490 nm, the smaller the particle size of IPC-DNVs, the easier it is to evade clearance by macrophages and the more effective the in vivo hypoglycemic efficacy will be. In the drug load range of 3-5 mg/mL, a lower drug load resulted in better hypoglycemic efficacy. The area above the blood glucose decline curve with time (AAC) of nebulized DNVs was 2.32 times higher than that of the insulin solution, demonstrating the feasibility and advantages of DNVs in the pulmonary delivery of biomacromolecule drugs. This study provides insights into the construction and formulation optimization of pulmonary delivery carriers.

Accuracy of continuous glucose monitoring during exercise-related hypoglycemia in individuals with type 1 diabetes.

Hypoglycemia is common in individuals with type 1 diabetes, especially during exercise. We investigated the accuracy of two different continuous glucose monitoring systems during exercise-related hypoglycemia in an experimental setting. Fifteen individuals with type 1 diabetes participated in two separate euglycemic-hypoglycemic clamp days (Clamp-exercise and Clamp-rest) including five phases: 1) baseline euglycemia, 2) plasma glucose (PG) decline ± exercise, 3) 15-minute hypoglycemia ± exercise, 4) 45-minute hypoglycemia, and 5) recovery euglycemia. Interstitial PG levels were measured every five minutes, using Dexcom G6 (DG6) and FreeStyle Libre 1 (FSL1). Yellow Springs Instruments 2900 was used as PG reference method, enabling mean absolute relative difference (MARD) assessment for each phase and Clarke error grid analysis for each day. Exercise had a negative effect on FSL1 accuracy in phase 2 and 3 compared to rest (ΔMARD = +5.3 percentage points [(95% CI): 1.6, 9.1] and +13.5 percentage points [6.4, 20.5], respectively). In contrast, exercise had a positive effect on DG6 accuracy during phase 2 and 4 compared to rest (ΔMARD = -6.2 percentage points [-11.2, -1.2] and -8.4 percentage points [-12.4, -4.3], respectively). Clarke error grid analysis showed a decrease in clinically acceptable treatment decisions during Clamp-exercise for FSL1 while a contrary increase was observed for DG6. Physical exercise had clinically relevant impact on the accuracy of the investigated continuous glucose monitoring systems and their ability to accurately detect hypoglycemia.

Variations in Management and Clinical Outcomes for Children With Diabetic Ketoacidosis in an Academic Pediatric Versus Community Emergency Department Setting.

Our objectives were to characterize variations from standardized, evidence-based guidelines in the management of pediatric patients with diabetic ketoacidosis (DKA) based on initial presentation to a tertiary pediatric emergency department (PED) versus a community emergency department (OSH) and compare clinical outcomes. We conducted a retrospective study on children 18 years and younger with DKA who presented to an OSH or PED over a 3-year period. Treatments monitored for variation included intravenous fluid management, insulin delivery, and sodium bicarbonate administrations. Clinical outcomes included time to anion gap correction and on insulin infusion, hypokalemia, hypoglycemia, rapid serum glucose decline, cerebral edema, mechanical ventilation, mortality, and time from initial presentation to hospital discharge. Children with DKA who presented to an OSH (n = 250) were more acidotic (pH 7.11 vs. 7.13, P = 0.001) and had larger anion gaps (28.8 vs. 25.5, P < 0.001) compared with children presenting to the PED (n = 237). The OSH patients were more likely to receive larger fluid boluses (>20 cc/kg or >1000 ml, 43% vs. 4%, P < 0.001), sodium bicarbonate (5% vs. 0%, P < 0.001), and intravenous bolus insulin (28% vs. 0%, P < 0.001). The OSH group were less likely to be started on maintenance intravenous fluids (70% vs. 99%, P < 0.001) or receive potassium in maintenance intravenous fluids (14% vs. 42%, P < 0.001). The OSH group had longer anion gap correction times (754 vs. 541 mins, P < 0.001), insulin infusion times (1018 vs. 854 min, P = 0.003), and times to hospital discharge (3358 vs. 3045 mins, P < 0.001). Incidence of hypokalemia, hypoglycemia, rapid glucose decline, cerebral edema, and deaths were similar between the 2 groups. Our study demonstrated significant variations in the initial management of pediatric DKA patients by OSH facilities that deviated from an evidence-based treatment pathway utilized by a PED. Statewide quality improvement initiatives could help improve the overall clinical care provided to pediatric DKA patients.

Effect of Impaired Awareness of Hypoglycemia on Glucose Decline During and After Exercise in the T1DEXI Study.

Adults with type 1 diabetes (T1D) face the necessity of balancing the benefits of exercise with the potential hazards of hypoglycemia. This work aimed to assess whether impaired awareness of hypoglycemia (IAH) affects exercise-associated hypoglycemia in adults with T1D. We compared continuous glucose monitoring (CGM)-measured glucose during exercise and for 24 hours following exercise from 95 adults with T1D and IAH (Clarke score ≥4 or ≥1 severe hypoglycemic event within the past year) to 95 "aware" adults (Clarke score ≤2 and no severe hypoglycemic event within the past year) matched on sex, age, insulin delivery modality, and glycated hemoglobin A1c. A total of 4236 exercise sessions, and 1794 exercise days and 839 sedentary days, defined as 24 hours following exercise or a day without exercise, respectively, were available for analysis. Participants with IAH exhibited a nonsignificant trend toward greater decline in glucose during exercise compared to "aware" (-21 ± 44 vs -19 ± 43 mg/dL [-1.17 ± 2.44 vs -1.05 ± 2.39 mmol/L], adjusted group difference of -4.2 [95% CI, -8.4 to 0.05] mg/dL [-0.23 95% CI, -.47 to 0.003 mmol/L]; P = .051). Individuals with IAH had a higher proportion of days with hypoglycemic events below 70 mg/dL [3.89 mmol/L] (≥15 minutes <70 mg/dL [<3.89 mmol/L]) both on exercise days (51% vs 43%; P = .006) and sedentary days (48% vs 30%; P = .001). The increased odds of experiencing a hypoglycemic event below 70 mg/dL (<3.89 mmol/L) for individuals with IAH compared to "aware" did not differ significantly between exercise and sedentary days (interaction P = .36). Individuals with IAH have a higher underlying risk of hypoglycemia than "aware" individuals. Exercise does not appear to differentially increase risk for hypoglycemia during the activity, or in the subsequent 24 hours for IAH compared to aware individuals with T1D.

Insulin sensitivity and beta cell function after duodenal mucosal resurfacing: an open-label, mechanistic, pilot study

Background and AimsThe duodenum has been shown to play a key role in glucose homeostasis. Duodenal mucosal resurfacing (DMR) is an endoscopic procedure for patients with type 2 diabetes (T2D) in which the duodenal mucosa is hydrothermally ablated. DMR improves glycemic control, but the underlying mechanisms remain unclear. Here, we report changes in glucoregulatory hormones and indices of insulin sensitivity and beta cell function after DMR. MethodsWe included 28 patients on non-insulin glucose lowering medications who underwent open-label DMR and a mixed meal test (MMT) in Revita-1 or Revita-2. Inclusion criteria were hemoglobin A1c (HbA1c) 7.6-10.4% and BMI 24-40kg/m2. Baseline and 3-months MMT data included plasma glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), and gastric inhibitory polypeptide (GIP) concentrations. Glucoregulatory hormones, insulin sensitivity indices (homeostatic model assessment for insulin resistance [HOMA-IR], Matsuda index [MI] and hepatic insulin resistance [HIR]), and beta cell function (insulinogenic index [IGI], disposition index [DI] and insulin secretion rate [ISR]) were assessed. ResultsFasting insulin, glucagon, and C-peptide decreased significantly. Insulin sensitivity (HOMA-IR, MI, and HIR) and beta cell function (DI and ISR) all improved significantly. Decline in postprandial glucose, mainly driven by a decrease in fasting levels, was observed, as well as a decline in postprandial glucagon whereas GLP-1 and GIP did not change. ConclusionsInsulin sensitivity and insulin secretion improved 3 months after DMR. It is unlikely that incretin changes are responsible for improved glucose control after DMR. These data add to the growing evidence validating the duodenum as a therapeutic target for patients with T2D.

Addressing the impact of high glucose microenvironment on the immunosuppressive characteristics of human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are a therapeutically efficient type of stem cells validated by their ability to treat many inflammatory and chronic conditions. The biological and therapeutic characteristics of MSCs can be modified depending on the type of microenvironment at the site of transplantation. Diabetes mellitus (DM) is a commonly diagnosed metabolic disease characterized by hyperglycemia, which alters over time the cellular and molecular functions of many cells and causes their damage. Hyperglycemia can also impact the success rate of MSCs transplantation; therefore, it is extremely significant to investigate the effect of high glucose on the biological and therapeutic attributes of MSCs, particularly their immunomodulatory abilities. Thus, in this study, we explored the effect of high glucose on the immunosuppressive characteristics of human adipose tissue-derived mesenchymal stem cells (hAD-MSCs). We found that hAD-MSCs cultured in high glucose lost their immunomodulatory abilities and became detectable by immune cells. The decline in the immunosuppressive capabilities of hAD-MSCs was mediated by significant decrease in the levels of IDO, IL-10, and complement factor H and substantial increase in the activity of immunoproteasome. The protein levels of AMP-activated protein kinase (AMPK) and phosphofructokinase-1 (PFK-1), which are integral regulators of glycolysis, revealed a marked decline in high glucose exposed MSCs. The findings of our study indicated the possibility of immunomodulatory shift in MSCs after being cultured in high glucose, which can be translationally employed to explain their poor survival and short-lived therapeutic outcomes in diabetic patients.

Bone marrow stem cell-derived β-cells: New issue for diabetes cell therapy

This investigation aimed to establish the promising role of insulin-producing cells (IPCs) growing from bone marrow-mesenchymal stem cells (BM-MSCs) in relieving hyperglycemia induced in rats. BM-MSCs were differentiated into IPCs using three different protocols. The efficiency of BM-MSCs differentiation into IPCs in vitro was confirmed by detecting IPCs specific gene expression (Foxa-2, PDX-1 and Ngn-3) and insulin release assay. The in vivo study design included 3 groups of male Wistar rats; negative control group, diabetic group and IPCs-transfused group (5 ×106 cells of the most functional IPCs/rat). One month after IPCs infusion, serum glucose, insulin, c-peptide and visfatin levels as well as pancreatic glucagon level were quantified. Gene expression analysis of pancreatic Foxa-2 and Sox-17, IGF-1 and FGF-10 was done. Additionally, histological investigation of pancreatic tissue sections was performed. Our data clarified that, the most functional IPCs are those generated from BM-MSCs using differentiation protocol 3 as indicated by the significant up-regulation of Foxa-2, PDX-1 and Ngn-3 gene expression levels. These findings were further emphasized by releasing of a significant amount of insulin in response to glucose load. The transplantation of the IPCs in diabetic rats elicited significant decline in serum glucose, visfatin and pancreatic glucagon levels along with significant rise in serum insulin and c-peptide levels. Moreover, it triggered significant up-regulation in the expression levels of pancreatic Foxa-2, Sox-17, IGF-1 and FGF-10 genes versus the untreated diabetic counterpart. The histopathological examination of pancreatic tissue almost assisted the biochemical and molecular genetic analyses. These results disclose that the cell therapy holds potential to develop a new cure for DM based on the capability of BM-MSCs to generate β-cell phenotype using specific protocol.

Pediatric Hyperglycemic Hyperosmolar Syndrome: A Comprehensive Approach to Diagnosis, Management, and Complications Utilizing Novel Summarizing Acronyms.

This paper focuses on hyperglycemic hyperosmolar syndrome (HHS), a unique hyperglycemic state requiring divergent diagnosis and treatment approaches from diabetic ketoacidosis (DKA) despite some shared characteristics. We introduce the mnemonic DI-FF-ER-EN-CE-S to encapsulate unique HHS management and complications. 'DI' emphasizes the need to delay and decrease initial insulin therapy until serum glucose decline is managed by fluid resuscitation alone. 'FF' stresses the importance of double fluid replacement compared to DKA due to severe dehydration and 'ER' electrolyte replacement due to profound losses and imbalances. 'EN' denotes the potential for encephalopathy and the requirement for a controlled serum osmolality reduction. 'CE' indicates cerebral edema, a rare complication in HHS. 'S' signifies systemic multiorgan failure. We categorize the associated risks into three mnemonic groups: the 3Rs (renal failure, respiratory distress, rhabdomyolysis), the 3Hs (heart failure, hypercoagulation, hyperthermia), and AP (arrhythmias, pancreatitis) to facilitate awareness and screening of HHS.

Construction of a 10rolGLP-1-expressing glucose-lowing Saccharomyces cerevisiae by CRISPR/Cas9 technique

To develop a novel glucose-lowering biomedicine with potential benefits in the treatment of type 2 diabetes, we used the 10rolGLP-1 gene previously constructed in our laboratory and the CRISPR/Cas9 genome editing technique to create an engineered Saccharomyces cerevisiae strain. The gRNA expression vector pYES2-gRNA, the donor vector pNK1-L-PGK-10rolGLP-1-R and the Cas9 expression vector pGADT7-Cas9 were constructed and co-transformed into S. cerevisiae INVSc1 strain, with the PGK-10rolGLP-1 expressing unit specifically knocked in through homologous recombination. Finally, an S. cerevisiae strain highly expressing the 10rolGLP-1 with glucose-lowering activity was obtained. SDS-PAGE and Western blotting results confirmed that two recombinant strains of S. cerevisiae stably expressed the 10rolGLP-1 and exhibited the desired glucose-lowering property when orally administered to mice. Hypoglycemic experiment results showed that the recombinant hypoglycemic S. cerevisiae strain offered a highly hypoglycemic effect on the diabetic mouse model, and the blood glucose decline was adagio, which can avoid the dangerous consequences caused by rapid decline in blood glucose. Moreover, the body weight and other symptoms such as polyuria also improved significantly, indicating that the orally hypoglycemic S. cerevisiae strain that we constructed may develop into an effective, safe, economic, practical and ideal functional food for type 2 diabetes mellitus treatment.

Pharmacological Evaluation of Antidiabetic Activity of Hydroethanolic Seeds Extract of Peganum Harmala in Streptozotocin Induced Diabetes in Albino Rats

Using streptozotocin to artificially induce diabetes in rats, this study aimed to assess the potential effects of a hydroalcoholic extract of Peganum harmala on blood sugar levels. For this experiment, five groups of male Wistar albino rats (weighing 200-230 g each) were randomly allocated. Oral administration of two doses of Peganum harmala hydroalcoholic seed extract, along with normal saline, was given to diabetic and control rats. Two hundred and fifty milligrams per kilogram were administered. Blood samples were taken at the end of therapy to determine measures of glucose, triglycerides, total cholesterol, LDL, HDL, Malondialdehyde (MDA), total antioxidant capacity (TCA), ALT, AST, bilirubin, and glycosylated haemoglobin (HbA1C). Compared to normal rats, STZ-induced diabetic rats had substantially different levels of glucose, triglycerides, total cholesterol, LDL-c, MDA, TAC, ALT, AST, GGT, bilirubin, and HbA1C. Rats with diabetes showed a considerable improvement in lipid profile, glucose, bilirubin, AST, GGT, and TAC levels after receiving the extract, but a marked decline in glucose, MDA, ALT, and HbA1C. According to the results of this investigation, hydroalcoholic seed extract of Peganum harmala possesses antidiabetic activity and might be useful in treating diabetes mellitus. Recent studies have demonstrated that P. harmala and its active alkaloids, especially harmine and harmaline, have a wide range of pharmacological and therapeutic actions. Chemical analyses have shown that harmalol, harmaline, and harmine are the principal components of this plant. These are beta-carboline alkaloids. There has been a disproportionate amount of focus on harmine among these naturally occurring alkaloids.

573-P: Impact of Impaired Awareness of Hypoglycemia on Glucose Changes During and After Exercise in Type 1 Diabetes—Results from the T1DEXI Study Cohort

Prior exposure to hypoglycemia and exercise may each dampen the sympathoadrenal response to subsequent hypoglycemia, leading to impaired awareness of hypoglycemia (IAH) and increased risk for experiencing clinically significant hypoglycemia. Whether glucose changes during exercise differ in those with IAH vs. intact awareness of hypoglycemia (Aware) has not been assessed in a large sample of ambulatory adults with type 1 diabetes, nor is the risk for hypoglycemia events in the next 24 hours known in such individuals. Using a case-control design, we compared participants with IAH (Clarke score ≥4 or ≥1 severe hypoglycemic event [SHE] within the past year) to Aware participants (Clarke score of ≤2 and no SHE within the past year), matching on sex, insulin modality, baseline HbA1c, and age. The analysis cohort included 95 adults with IAH matched to 95 Aware adults (in both groups, 74% female, mean ± SD age of 43 ± 14 yr, and HbA1c of 6.5 ± 0.7%) with a total of 4,236 exercise sessions and 1,794 post-exercise and 839 sedentary days available for analysis. IAH had a trend toward a greater but not clinically significant decline in glucose during exercise compared to Aware (−21 ± 44 vs. −19 ± 43 mg/dL, adjusted group difference of −4.2 [95% CI: −8.7 to 0.3] mg/dL, p=0.06). IAH had a higher proportion of hypoglycemic events (≥15 minutes &amp;lt;70 mg/dL) vs. Aware on both post-exercise days (51% vs. 43%, p=0.008) and sedentary days (48% vs. 30%, p=0.002). There was no evidence that the increased odds of hypoglycemia for IAH compared with Aware differed between post-exercise and sedentary days (interaction p=0.36). In summary, participants with IAH have an overall higher baseline risk of hypoglycemia than Aware participants. However, for those with IAH exercise itself does not appear to differentially increase the risk for hypoglycemia during the activity, or in the subsequent 24 hours compared to Aware individuals with type 1 diabetes. Disclosure J.L. Jo Kamimoto: None. Z. Li: None. R.L. Gal: None. J.R. Castle: Research Support; Dexcom, Inc. Advisory Panel; Novo Nordisk. Stock/Shareholder; Pacific Diabetes Technologies. Advisory Panel; Zealand Pharma A/S. F.J. Doyle: Stock/Shareholder; Mode AGC. Other Relationship; Insulet Corporation, Roche Diabetes Care, Dexcom, Inc. P.G. Jacobs: Other Relationship; Pacific Diabetes Technologies. Board Member; Pacific Diabetes Technologies. Research Support; Dexcom, Inc. C.K. Martin: Research Support; Pack Health, Evidation Health, Lilly. Board Member; EHE Health, Wondr Health. Other Relationship; ABGIL. Research Support; WW International, Inc. R. Beck: Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company. Consultant; Eli Lilly and Company. Research Support; Novo Nordisk. Consultant; Novo Nordisk, Diasome, Insulet Corporation. P. Calhoun: None. M. Riddell: Stock/Shareholder; Supersapiens. Advisory Panel; Zealand Pharma A/S. Speaker's Bureau; Dexcom, Inc. Consultant; Lilly Diabetes. Speaker's Bureau; Novo Nordisk, Sanofi. Stock/Shareholder; Zucara Therapeutics. Advisory Panel; Zucara Therapeutics, Indigo Diabetes. Consultant; Eli Lilly and Company, Jaeb Center for Health Research. M.R. Rickels: Consultant; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S. Research Support; Dompé. Funding The Leona M. and Harry B. Helmsley Charitable Trust; Verily Life Sciences; Dexcom, Inc.

A Comparison of Variable Versus Fixed Insulin Infusion Rate on Resolution of Diabetic Ketoacidosis.

Diabetic ketoacidosis (DKA) is a well-known, potentially fatal complication of diabetes. The American Diabetes Association hyperglycemic crises guidelines suggest the use of intravenous insulin in patients presenting with DKA, along with a recommended rate of glucose reduction of 50-75 mg/dL/h. However, no specific guidance is provided regarding how to best achieve this rate of glucose decline. Is there a difference in time to DKA resolution between a variable intravenous insulin infusion strategy and a fixed infusion strategy in the absence of an institutional protocol? Single-center, retrospective cohort study of DKA patient encounters in 2018. Insulin infusion strategy was considered to be variable if the infusion rate changed within the first 8 hours of therapy or was considered fixed if the rate remained unchanged for the same period. The primary outcome was time to resolution of DKA. Secondary outcomes were hospital length of stay, intensive care unit length of stay, hypoglycemia, mortality, and DKA recurrence. The median time to resolution of DKA was 9.3 hours in the variable infusion group compared with 7.8 hours in the fixed infusion group (HR, 0.82; 95% CI, 0.43-1.5, P = 0.5360). Severe hypoglycemia was observed in 13% of patients in the variable infusion group and in 50% of patients in the fixed infusion group ( P = 0.006). In this analysis, insulin infusion strategy (variable vs. fixed) was not associated with a significant difference in the time to resolution of DKA in the absence of an institutional protocol. The fixed infusion strategy was associated with a higher incidence of severe hypoglycemia.

Antidiabetic activity of Berberis brandisiana is possibly mediated through modulation of insulin signaling pathway, inflammatory cytokines and adipocytokines in high fat diet and streptozotocin-administered rats.

Medicinal plants play a key role in protection of chronic non-communicable ailments like diabetes, hypertension and dyslipidemia. Berberis brandisiana Ahrendt (Berberidaceae) is traditionally used to treat diabetes, liver problems, wounds, arthritis, infections, swelling and tumors. It is also known to be enriched with multiple phytoconstituents including berbamine, berberine, quercetin, gallic acid, caffeic acid, vanillic acid, benzoic acid, chlorogenic acid, syringic acid, p-coumaric acid, m-coumaric acid and ferulic acid. The efficacy of B. brandisiana has not been established yet in diabetes. This study has been planned to assess the antidiabetic activity of B. brandisiana in high fat diet and streptozotocin (HFD/STZ)-induced diabetes using animals. Administration of aqueous methanolic extract of B. brandisiana (AMEBB) and berbamine (Berb) for 8 weeks caused a dose dependent marked (p < 0.01) rise in serum insulin and HDL levels with a significant decline (p < 0.01) in glucose, triglycerides, glycosylated hemoglobin (HbA1c), cholesterol, LDL, LFTs and RFTs levels when compared with only HFD/STZ-administered rats. AMEBB and Berb also modulated inflammatory biomarkers (TNF-α, IL-6) and adipocytokines (leptin, adiponectin and chemerin). AMEBB (150mg/kg and 300mg/kg) and Berb (80mg/kg and 160mg/kg) treated rats showed a marked increase (p < 0.001) in catalase levels (Units/mg) in pancreas (42.4 ± 0.24, 47.4 ± 0.51), (38.2 ± 0.583, 48.6 ± 1.03) and liver (52 ± 1.41, 63.2 ± 0.51), (57.2 ± 0.58, 61.6 ± 1.24) and superoxide dismutase levels (Units/mg) in pancreas (34.8 ± 1.46, 38.2 ± 0.58), (33.2 ± 0.80, 40.4 ± 1.96) and liver (31.8 ± 1.52, 36.8 ± 0.96), (30 ± 0.70, 38.4 ± 0.81),respectively while a significant (p < 0.01) decrease in serum melondialdehyde levels (nmol/g) in pancreas (7.34 ± 0.17, 6.22 ± 0.22), (7.34 ± 0.20, 6.34 ± 0.11) and liver (9.08 ± 0.31,8.18 ± 0.29), (9.34 ± 0.10, 8.86 ± 0.24) compared to the data of only HFD/STZ-fed rats. Histopathological studies of pancreas, liver, kidney, heart and aorta revealed restoration of normal tissue architect in AMEBB and Berb treated rats. When mRNA expressions of candidate genes were assessed, AMEBB and Berb showed upregulation of IRS-1, SIRT1, GLUT-4 and downregulation of ADAM17. These findings suggest that AMEBB and Berb possess antidiabetic activity, possibly due to its effect on oxidative stress, glucose metabolism, inflammatory biomarkers and adipocytokines levels. Further upregulation of IRS-1, SIRT1, GLUT-4 and downregulation of ADAM17, demonstrated its potential impact on glucose homeostasis, insulin resistance and chronic inflammatory markers. Thus, this study provides support to the medicinal use of B. brandisiana and berbamine in diabetes.

Feeding Status Affects Glucose Metabolism in Exercising Horses

Four standardbred horses were used in a Latin square design experiment to evaluate the effects of feeding status on metabolic response to exercise. Horses were deprived of food overnight and then fed 0 (control condition), 1, 2 or 3 kg of corn grain approximately 2.5-3 h before exercise. The exercise test consisted of a warm-up phase (heart rate mean = 144 beats/min) followed by 800 m of walking and then a high intensity work bout for 1600 m (heart rate mean = 206 beats/min). All tests were conducted on a high speed equine treadmill on which the horses had been previously conditioned. During exercise, the control treatment resulted in steady plasma glucose concentrations, whereas all other treatments (1, 2 or 3 kg corn) caused a decline in plasma glucose. Liver glycogen concentration was decreased by exercise in the horses only when they received the control treatment. Plasma lactate concentration was increased by exercise but was not affected by feeding state. Plasma free fatty acid concentrations were highest when the horses received the control treatment. In addition, when horses received the control treatment, plasma free fatty acid concentrations decreased during the warm-up and high intensity phases of the test and increased during the walk phase. Free fatty acid concentrations changed in the horses receiving 1, 2 or 3 kg of corn grain only during the high intensity phase of the exercise test. Feeding status affects the metabolic response of horses to exercise thus further studies are necessary to evaluate the effect of feeding status on exercise performance.

Discovery of IHMT-MST1-58 as a Novel, Potent, and Selective MST1 Inhibitor for the Treatment of Type 1/2 Diabetes.

The critical pathogenesis of type 1 diabetes (T1D)/type 2 diabetes (T2D) is the physical status, mass, and function of pancreatic β cells. Mammalian STE20-like protein 1 kinase (MST1) plays vital roles in the apoptosis and insulin secretion of β cells. Here, we discovered a novel, potent, and selective MST1 inhibitor 19 (IC50 = 23 nM), which inhibited the phosphorylation of MST1-protected β cells from the damage of inflammatory cytokines in vitro. In vivo, it displayed acceptable pharmacokinetic properties in different species. In the STZ-induced T1D/T2D mouse models, both monotherapy of 19 and in combination with metformin led to the decline of fasting blood glucose and showed protective effect of β cells. In addition, the combination of 19 and metformin decreased the hemoglobin A1c level. Together, our study suggested that 19 might be a useful pharmacological tool to study MST1-mediated physiology and pathology as well as a potential drug candidate for diabetes.