Rise In Glucose Research Articles

Effect of Sevoflurane, Isoflurane, and Desflurane on the Random Blood Glucose Levels in Non-diabetic Patients Undergoing General Anesthesia: A Randomized, Single-Blind Study.

Volatile anesthetic agents like sevoflurane, isoflurane, and desflurane are widely used for maintaining general anesthesia (GA). Their effect on the autonomic system is different and can impact the blood sugar homeostasis. This study compares the intraoperative blood glucose levels in non-diabetic patients undergoing non-cardiac surgery under GA with the three volatile agents. A randomized, single-blind, parallel-arm study recruited 105 non-diabetic patients into three groups. GA induction and maintenance were standardized except for the volatile agent. Capillary blood sugar levels were measured at different time points and compared between and within the groups. A p-value of <0.05 was considered significant. Entire participants completed the study, and their baseline characteristics were statistically indifferent. Intraoperative blood glucose rise and variation were the highest in the desflurane group and the lowest in the isoflurane group; the differences were statistically significant at 15, 30, and 45 minutes. The highest blood sugar level was noted at 60 minutes in all groups; after that, the level started falling. However, none of the raises were beyond 140 mg% to categorize them as hyperglycemia. Intraoperative glycemic variation was evident with isoflurane, sevoflurane, and desflurane. The maximum increase from the pre-induction level was noted at 60 minutes. However, none of the readings reached the hyperglycemia level. The rise was significantly higher in desflurane-based anesthesia than in isoflurane. This study was, however, conducted in non-diabetic patients; hence, results might not be extrapolated to diabetic patients.

A probabilistic computation framework to estimate the dawn phenomenon in type 2 diabetes using continuous glucose monitoring.

In type 2 diabetes (T2D), the dawn phenomenon is an overnight glucose rise recognized to contribute to overall glycemia and is a potential target for therapeutic intervention. Existing CGM-based approaches do not account for sensor error, which can mask the true extent of the dawn phenomenon. To address this challenge, we developed a probabilistic framework that incorporates sensor error to assign a probability to the occurrence of dawn phenomenon. In contrast, the current approaches label glucose fluctuations as dawn phenomena as a binary yes/no. We compared the proposed probabilistic model with a standard binary model on CGM data from 173 participants (71% female, 87% Hispanic/Latino, 54 ± 12years, with either a diagnosis of T2D for six months or with an elevated risk of T2D) stratified by HbA1c levels into normal but at risk for T2D, with pre-T2D, or with non-insulin-treated T2D. The probabilistic model revealed a higher dawn phenomenon frequency in T2D [49% (95% CI 37-63%)] compared to pre-T2D [36% (95% CI 31-48%), p = 0.01] and at-risk participants [34% (95% CI 27-39%), p < 0.0001]. While these trends were also found using the binary approach, the probabilistic model identified significantly greater dawn phenomenon frequency than the traditional binary model across all three HbA1c sub-groups (p < 0.0001), indicating its potential to detect the dawn phenomenon earlier across diabetes risk categories.

Molecular interactions between polyphenols and porcine α-amylase: An inhibition study on starch granules probed by kinetic, spectroscopic, calorimetric and in silico techniques

Inhibition of α-amylase activity to limit the rise in postprandial glucose is one of the most notable effects of dietary plant (poly)phenols. The rate and extent of inhibition depend on many factors, including the structure of (poly)phenols and the substrate used for the inhibition study. While soluble/gelatinised starch is widely used as a substrate for studying inhibition mechanisms, the formation of (poly)phenol-amylose complexes can reduce susceptibility to α-amylase catalysis. Therefore, the extent of inhibition may not truly represent the inhibition of α-amylase by (poly)phenols. To elucidate mechanisms of interactions between a (poly)phenol and the enzyme, this study compared the inhibition of porcine pancreatic α-amylase (PPA) by three differently structured (poly)phenols: p-coumaric acid, quercetin, and cyanidin-3-glucoside, using solid maize starch as a substrate, that limits the formation of starch-(poly)phenol complexes due to the compact structure of starch granules. The inhibition kinetics were investigated and supported by complementary techniques: in silico analysis (molecular docking and molecular dynamic simulation), fluorescence quenching, circular dichroism and differential scanning calorimetry. Quercetin exhibited the strongest inhibition, followed by cyanidin-3-glucoside and p-coumaric acid, with apparent modes of mixed, mixed, and competitive inhibition, respectively. The specific binding of (poly)phenols to PPA involved hydrogen bonds and hydrophobic interactions, as indicated by in-silico studies. Multi-spectroscopic analysis of the PPA structure unveiled changes or peak shifts due to ligand binding, resulting in structural alterations. These findings were consistent with the kinetic data, emphasising the importance of the structural aspects of each individual (poly)phenol in relation to their interaction with PPA. The study articulated the in-depth mechanism of molecular interaction mechanism between (poly)phenols and enzymes and provided evidence that the structural alterations of enzymes are not a strong indicator of inhibition efficacy, but rather inhibition is due to the binding of (poly)phenols to the enzyme structure limiting the catalysis.

Outcome of hospitalized patients with COVID-19 and predictors at the Buea Regional Hospital, South West region of Cameroon.

there is a paucity of data on the epidemiology of COVID-19 infection in Cameroon with a few studies limited to big urban cities. The objective of this study was to describe the clinical characteristics and outcomes of hospitalized patients with COVID-19 at the Buea Regional Hospital, in the South West region of Cameroon. this was a retrospective cross-sectional study. The medical records of hospitalized patients with COVID-19 were reviewed from 2020 to 2021. Hospitalized patients with laboratory-confirmed COVID-19 were included. Binary logistic regression was used to identify factors associated with mortality. two hundred and ten (210) patients were included in this cohort. There were 114 (54.7%) men. The mean age was 60±17.1 years. The common co-morbidities were hypertension (46.7%), diabetes mellitus (31%), and HIV infection (5.7%). The most common symptoms were dyspnea (93.3%), fatigue (93.8%), cough (77.6%), and fever (71.4%). The median oxygen saturation was 85% and the median respiratory rate was 24 cycles per minute. More than 80% had crackles on lung examination. Death occurred in 57 (27.1%) patients. In binary logistic regression, the factors independently associated with mortality were heart failure (aOR: 6.7, p=0.034), SBP < 100 mmHg (aOR: 8.1, p<0.001), RR > 24 cpm (aOR: 3, p=0.016), SaO2<90% (aOR: 6.2, p=0.031), blood glucose > 150mg/dL (aOR: 3.3, p=0.02), and CRP > 50 mg/L (aOR: 3.3, p=0.036). For every 1 mg/dL rise in blood glucose, the odds of death increased by 1% (p=0.011). For every 1 mg/L rise in the C-reactive protein (CRP), the odds of death increased by 1% (p=0.054). over half of hospitalized patients with laboratory-confirmed COVID-19 infection in the South West Region of Cameroon were males. Hypertension and diabetes were common co-morbidities. More than a quarter of these patients died. Furthermore, having heart failure, low systolic blood pressure (SBP), low oxygen saturation, elevated respiratory rate, high CRP and blood glucose levels on admission were associated with poor prognosis.

Body fluid kinetics is changed by a rise in plasma glucose

Glucose is an osmotically active molecule and, therefore, rapid changes in plasma glucose might redistribute water volume between the body fluid compartments in a yet unknown way. To study this issue, population volume kinetic analysis was applied to repeated measurements of plasma glucose, blood hemoglobin, and urine output during and after 84 intravenous infusions of 2.5 % glucose with 70 mmol of sodium and in 9 control experiments using Ringer's solution. Forty-nine infusions were given to healthy volunteers, 11 to patients undergoing surgery, and 24 to patients with type 2 diabetes. The results showed that a rise in plasma glucose without marked glucosuria accelerated the distribution of fluid while the return of extravascular fluid to the plasma was strongly retarded. High plasma glucose also decreased the urine output, which was probably due to sodium retention. The summary effect was that fluid-induced plasma volume expansion subsided within 30 min after an infusion ended while extracellular fluid volume remained increased for several hours. Accumulation of fluid was most pronounced in the patients with type 2 diabetes and in the surgical patients. Plasma glucose, HOMA-IR, and Ouicki values did not correlate with any of the kinetic parameters. In conclusion, a rise in plasma glucose conserved infused fluid in the body and promoted peripheral accumulation. A specific effect of type 2 diabetes further decreased the urine flow.

Effect of dietary fiber-enriched brown rice crackers on suppressing elevation of blood glucose level

Background: Rice crackers are composed of carbohydrates refined from rice and enjoyed as a snack in Japan. Most rice crackers are crafted from white rice, and the potential postprandial blood glucose rise following their consumption may pose a clinical concern. Brown rice contains more dietary fiber than white rice and has been reported to suppress elevations of blood glucose. Dietary fiber-enhanced brown rice crackers have a significantly higher dietary fiber content than regular brown rice crackers and can be expected to suppress blood glucose elevations more reliably.Methods: We conducted a crossover trial in humans using white rice crackers and dietary fiber-enhanced brown rice crackers to investigate the effect of dietary fiber-enhanced brown rice crackers on postprandial blood glucose elevations. Participants ingested the 100 g rice crackers with 200 mL water for 10 min, and blood was collected from the fingertip at 7 time points: baseline, and at 15, 30, 45, 60, 90, and 120 min after ingestion of the rice cracker. The primary outcome measure was the blood glucose levels, and the secondary outcome measure was the incremental area under curve of blood glucose.Results: Glucose levels and incremental areas under curve at 60 min and 120 min after intake were significantly lower with dietary fiber-enhanced brown rice crackers than with white rice crackers. Incremental area under curves at 60 min and 120 min after intake of rice crackers were also significantly lower in dietary fiber-enhanced brown rice crackers than white rice crackers.Conclusions: Ingesting dietary fiber-enhanced brown rice crackers instead of white rice crackers could be useful for achieving better glycemic control.Keywords: Brown rice crackers, Dietary fiber, Postprandial blood glucose

Serum MMP3 Correlates with Renal Function Tests and Insulin Resistance Parameters in Patients with End-stage Renal Disease

End-stage renal disease (ESRD) is associated with changes in serum biomarkers. However, except for the renal function test, there is no definite useful biomarker correlated with the disease and its consequences, such as insulin resistance (IR). In the present study, matrix metalloproteinases-3 (MMP3) and its inhibitor, the tissue inhibitor of metalloproteinase-1 (TIMP1) were examined and correlated with IR parameters. MMP3, TIMP1, renal function tests, and IR parameters were measured in 60 ESRD patients and the results were compared with thirty healthy controls. After controlling for all cofounders, ESRD patients showed a substantial rise in serum MMP3, glucose, insulin, and beta-cell function percentage compared to the control group. While the patients had a lower insulin sensitivity percentage when compared to the controls. TIMP1, insulin/glucose ratio, and insulin resistance index did not vary significantly across groups. MMP3 had a strong relationship with serum creatinine, urea, and eGFR. TIMP1 had a strong relationship with height and weight. High serum MMP3 is associated with increased renal function tests and with changes in the IR parameters in ESRD patients.

Functional insulin aspart/insulin degludec-based microneedles for promoting postprandial glycemic control.

Insulin aspart (IAsp) and insulin degludec (IDeg), as the third generation of insulin, have a faster onset time or a more durable action period, which may simulate the secretion of insulin under physiological conditions. Microneedles (MNs) are transdermal delivery devices that may allow diabetic patients to easily deploy transdermal insulin therapy while considerably reducing injection pain. In this study, we investigated the combination of dissolving MNs with IAsp or IDeg therapy as an alternative to daily multiple insulin injections, aiming to improve glycemic control and patient compliance. Mechanical properties of the MNs, structural stability of insulin encapsulated in the MNs, and transdermal application characteristics were studied to assess the practicality of insulin-loaded MNs for diabetes therapy. In vivo experiments conducted on diabetic rats demonstrated that the IAsp- and IDeg-loaded MNs have comparable blood glucose control abilities to that of subcutaneous injections. In addition, the therapeutic properties of insulin-loaded MNs under diverse dietary conditions and application strategies were further investigated to provide new information to support future clinical trials. Taken together, the proposed MNs have the potential to improve balances between glycemic control, hypoglycemia risk, and convenience, providing patients with simpler regimens. STATEMENT OF SIGNIFICANCE: 1. The fabricated functional insulin-loaded dissolving microneedles closely matched the glucose rise that occurs in response to meals, demonstrating promising alternatives for multiple daily insulin injections. 2. The hypoglycemic properties of insulin microneedles were investigated under diverse dietary conditions and application strategies, yielding new information to support future clinical trials. 3. Molecular dynamics simulations were utilized to study the interactions between the insulin and microneedle matrix materials, providing a strategy for theoretically understanding drug stability as well as the release mechanism of drug-loaded microneedles.

Potassium Magnesium Citrate Is Superior to Potassium Chloride in Reversing Metabolic Side Effects of Chlorthalidone.

Thiazide diuretics (TD) are the first-line treatment of hypertension because of its consistent benefit in lowering blood pressure and cardiovascular risk. TD is also known to cause an excess risk of diabetes, which may limit long-term use. Although potassium (K) depletion was thought to be the main mechanism of TD-induced hyperglycemia, TD also triggers magnesium (Mg) depletion. However, the role of Mg supplementation in modulating metabolic side effects of TD has not been investigated. Therefore, we aim to determine the effect of potassium magnesium citrate (KMgCit) on fasting plasma glucose and liver fat by magnetic resonance imaging during TD therapy. Accordingly, we conducted a double-blinded RCT in 60 nondiabetic hypertension patients to compare the effects of KCl versus KMgCit during chlorthalidone treatment. Each patient received chlorthalidone alone for 3 weeks before randomization. Primary end point was the change in fasting plasma glucose after 16 weeks of KCl or KMgCit supplementation from chlorthalidone alone. The mean age of subjects was 59±11 years (30% Black participants). Chlorthalidone alone induced a significant rise in fasting plasma glucose, and a significant fall in serum K, serum Mg, and 24-hour urinary citrate excretion (all P<0.05). KMgCit attenuated the rise in fasting plasma glucose by 7.9 mg/dL versus KCl (P<0.05), which was not observed with KCl. There were no significant differences in liver fat between the 2 groups. KMgCit is superior to KCl, the common form of K supplement used in clinical practice, in preventing TD-induced hyperglycemia. This action may improve tolerability and cardiovascular safety in patients with hypertension treated with this drug class.

Effects of milling on texture and in vitro starch digestibility of oat rice.

Compared with other oat products, consumers in China prefer oat rice and porridge made from naked oat. However, this oat product usually has poor sensory acceptance, which is directly related to the texture properties. This study aimed to use the milling method to improve the oat rice texture. The nutrient component, microstructure, pasting, and thermal properties of oat treated with different degrees of milling (0s, 20s, 40s, 60s, and 80s) were researched. The results showed that milling would damage the bran layer of oat rice, increasing starch, β-glucan, total leached solids content, and the gelatinization enthalpy (ΔH). Meanwhile, oil, protein content, the pasting viscosity, and the pasting temperature were decreased. Milling made oat rice sticky and soft, and the bound water and non-flowing water migrated like flowing water. The cross-section of oat rice showed that milling damaged the surface of oat rice, which was beneficial to water entry and starch dissolution, and increased the viscosity of oat rice. When the milling time was 40s and 60s, the appearance, aroma, taste, texture, and overall acceptability of oat porridge were better. Moreover, rapid digestion fraction (k1) and slow digestion fraction (k2) are the lowest and have the effect of low blood glucose rise rate.

Effect of meal time on postprandial glycemia in patients with type 2 diabetes mellitus and obesity not receiving insulin

BACKGROUND: Postprandial hyperglycemia (PPG) is associated with micro- and macrovascular diseases in patients with T2DM. Severity of postprandial peaks depends on composition and amount of food. Circadian rhythms can influence PPG, which may determine variability of glycemia during day. According to literature, in persons without T2DM, PPG is maximum after dinner. Features of the postprandial response in patients with T2DM are not effective enough.AIM: To assess variability of postprandial glycemia based on flash glucose monitoring (FGM) depending on meal times in patients with T2DM not receiving insulin.MATERIALS AND METHODS: Open prospective study. T2DM patients were managed on FMG FreeStyle Libre. Each patient carried out 9 tests with three types of food loads: boiled buckwheat (250 grams), apple (200 grams) and white bread (30 grams) for breakfast, lunch and dinner.Statistical analysis of PPG by area under glycemic curve (AUC) and area under glycemic curve excluding starting glycemia (delta AUC), analysis of glycemia before meals (Start_gly) was carried out. Effect of time of food intake and food type was assessed with a two-way RM ANOVA using R 4.1.2. for quantitative variables, arithmetic means and standard deviations (M±SD) are presented.RESULTS: A total of 29 patients were included. Data from 17 patients, 153 food loading tests, were included in analysis. Both food type (p=0.037) and time of food intake (p=0.003) were shown to have a significant effect on the AUC. Maximum AUC values were observed after breakfast (p=0.005 vs supper, p&lt;0.001 vs dinner), and buckwheat intake (p=0.01 vs apple).For the delta AUC only type of food (p=0.003) had significant influence. Delta AUC was higher for buckwheat than for apple (p=0.001) and wheat bread (p=0.012).CONCLUSION: Patients with T2DM who do not receive insulin have higher PCG levels after breakfast compared to lunch and dinner, regardless of the type of food load. Rise in glucose after a food load relative to initial values does not significantly differ from time of a meal, which does not coincide with known data on the maximum rise in glycemia on a food stimulus after dinner, which is observed in individuals without DM2.

The impact of mulberry leaf extract at three different levels on reducing the glycemic index of white bread.

In this study, the influences of mulberry leaf extract (MLE) addition on the physicochemical properties including the specific volume, texture and sensory features of white bread (WB) were evaluated by the sensory analysis technology. A double-blind, randomised, repeat-measure design was used to study the impact of MLE addition on the postprandial blood glucose response as well as the satiety index of WB. Results showed that the addition of MLE showed no significant effects on the physicochemical properties of WB except for the slight changes of color and bitterness. The addition of MLE significantly reduced the total blood glucose rise after ingestion of WB over 120 minutes, and reduced the GI value of WB in a dose-effect relationship. When the concentration of MLE reached 1.5 g per 100 g available carbohydrate, the GI value of WB could be reduced from 77 to 43. This study provides important information in terms of the appropriateness of MLE when added to more complex real food, the dose-dependent relationship could supply a reference for the application of MLE.

ER stress increases expression of intracellular calcium channel RyR1 to modify Ca2+ homeostasis in pancreatic beta cells

Pancreatic beta cells maintain glucose homeostasis by secreting pulses of insulin in response to a rise in plasma glucose. Pulsatile insulin secretion occurs as a result of glucose-induced oscillations in beta-cell cytosolic Ca2+. The endoplasmic reticulum (ER) helps regulate beta-cell cytosolic Ca2+, and ER stress can lead to ER Ca2+ reduction, beta-cell dysfunction, and an increased risk of type 2 diabetes. However, the mechanistic effects of ER stress on individual calcium channels are not well understood. To determine the effects oftunicamycin-induced ER stress on ER inositol 1,4,5-triphosphate receptors (IP3Rs) and ryanodine receptors (RyRs) and their involvement in subsequent Ca2+ dysregulation, we treated INS-1 832/13cells and primary mouse islets with ER stress inducer tunicamycin (TM). We showed TM treatment increased RyR1 mRNA without affecting RyR2 mRNA and decreased both IP3R1 and IP3R3 mRNA. Furthermore, we found stress reduced ER Ca2+ levels, triggered oscillations in cytosolic Ca2+ under subthreshold glucose conditions, and increased apoptosis and that these changes were prevented by cotreatment with the RyR1 inhibitor dantrolene. In addition, we demonstrated silencing RyR1-suppressed TM-induced subthreshold cytosolic Ca2+ oscillations, but silencing RyR2 did not affect these oscillations. In contrast, inhibiting IP3Rs with xestospongin-C failed to suppress the TM-induced cytosolic Ca2+ oscillations and did not protect beta cells from TM-induced apoptosis although xestospongin-C inclusion did prevent ER Ca2+ reduction. Taken together, these resultsshowchanges in RyR1 play a critical role in ER stress-induced Ca2+ dysfunction and beta-cell apoptosis.

Elevated CO2 increases biomass of Sorghum bicolor green prop roots under drought conditions via soluble sugar accumulation and photosynthetic activity.

Elevated [CO2 ] (E[CO2 ]) mitigates agricultural losses of C4 plants under drought. Although several studies have described the molecular responses of the C4 plant species Sorghum bicolor during drought exposure, few have reported the combined effects of drought and E[CO2 ] (E[CO2 ]/D) on the roots. A previous study showed that, among plant organs, green prop roots (GPRs) under E[CO2 ]/D presented the second highest increase in biomass after leaves compared with ambient [CO2 ]/D. GPRs are photosynthetically active and sensitive to drought. To understand which mechanisms are involved in the increase in biomass of GPRs, we performed transcriptome analyses of GPRs under E[CO2 ]/D. Whole-transcriptome analysis revealed several pathways altered under E[CO2 ]/D, among which photosynthesis was strongly affected. We also used previous metabolome data to support our transcriptome data. Activities associated with photosynthesis and central metabolism increased, as seen by the upregulation of photosynthesis-related genes, a rise in glucose and polyol contents, and increased contents of chlorophyll a and carotenoids. Protein-protein interaction networks revealed that proliferation, biogenesis, and homeostasis categories were enriched and contained mainly upregulated genes. The findings suggest that the previously reported increase in GPR biomass of plants grown under E[CO2 ]/D is mainly attributed to glucose and polyol accumulation, as well as photosynthesis activity and carbon provided by respiratory CO2 refixation. Our findings reveal that an intriguing and complex metabolic process occurs in GPRs under E[CO2 ]/D, showing the crucial role of these organs in plant drought /tolerance.

Plasma insulin is required for the increase in plasma angiopoietin-like protein 8 in response to nutrient ingestion.

Plasma levels of angiopoietin-like protein 8 (ANGPTL8) are regulated by feeding and they increase following glucose ingestion. Because both plasma glucose and insulin increase following food ingestion, we aimed to determine whether the increase in plasma insulin and glucose or both are responsible for the increase in ANGPTL8 levels. ANGPTL8 levels were measured in 30 subjects, 14 with impaired fasting glucose (IFG), and 16 with normal fasting glucose (NFG); the subjectsreceived 75g glucose oral Glucose tolerance test (OGTT), multistep euglycaemic hyperinsulinemic clamp and hyperglycaemic clamp with pancreatic clamp. Subjects with IFG had significantly higher ANGPTL8 than NGT subjects during the fasting state (p<0.05). During the OGTT, plasma ANGPTL8 concentration increased by 62% above the fasting level (p<0.0001), and the increase above fasting in ANGPTL8 levels was similar in NFG and IFG individuals. During the multistep insulin clamp, there was a dose-dependent increase in plasma ANGPTL8 concentration. During the 2-step hyperglycaemic clamp, the rise in plasma glucose concentration failed to cause any change in the plasma ANGPTL8 concentration from baseline. In response to nutrient ingestion, ANGPTL8 level increased due to increased plasma insulin concentration, not to the rise in plasma glucose. The incremental increase above baseline in plasma ANGLPTL8 during OGTT was comparable between people with normal glucose tolerance and IFG.

538-P: Use of Real-Time Continuous Glucose Monitoring Supports Behavior Modification in Gestational Diabetes Mellitus—Results from an Ongoing Pilot Study

Gestational diabetes mellitus (GDM) is common, with 14% of women developing GDM. Although real-time continuous glucose monitoring (RT-CGM) has been shown to support behavioral/lifestyle modifications in patients living with type 1 and type 2 diabetes, no studies to date have assessed RT-CGM as a behavior modification tool for patients with GDM. Participants diagnosed with GDM [prior to gestational age 24 weeks (early) or between 24-30 weeks (typical)] were randomized to use RT-CGM or continue self-monitoring of blood glucose (SMBG) using finger-sticks and wore 3 serial blinded CGM over the remainder of the pregnancy. Both groups continued their routine obstetric care. After delivery, RT-CGM participants completed a 44-question survey adapted from the Joslin Diabetes Center CGM questionnaire plus our published 8-question survey on behavior modification and CGM use. To date, 70 participants have enrolled; 31 were randomized to RT-CGM. Twenty-four (4 early and 20 typical) have completed the post-delivery surveys. Demographics: 42% were Caucasian, 63% reported annual incomes of &amp;gt;$50,000, and 79% had achieved at least a bachelor’s degree. From RT-CGM use: 71% excluded or limited sugared beverages (29% never drank sugared beverages), 78% excluded or limited white rice (13% never ate white rice), 67% started reading labels for fiber content (17% of participants already read labels for fiber content), and 92% would walk or increase activity after a meal if they saw their glucose rising. Overall, 92% of participants felt like RT-CGM contributed to a healthier lifestyle during pregnancy. Sixty-three percent wanted to continue using RT-CGM. Our study suggests that women with GDM perceive that RT-CGM supports improved lifestyle choices during pregnancy. Studies are ongoing to assess whether RT-CGM improves maternal and/or fetal outcomes, but advocacy is needed now to improve accessibility of RT-CGM in GDM. Disclosure B.Cedeno: None. E.Fay: None. N.M.Ehrhardt: Advisory Panel; Novo Nordisk, Dexcom, Inc., Consultant; Nestlé Health Science. S.J.Fonda: Research Support; Dexcom, Inc. Funding Dexcom, Inc. (IIS-2019-101)

219-OR: Glucagon Counterregulation in a Hypoglycemic Clamp in Type 1 Diabetes Is Increased by ZT-01, a Novel Somatostatin Receptor 2 Antagonist—A Phase 1b Study

This study evaluated the effect of ZT-01 on glucagon counterregulation during hypoglycemia in adults with type 1 diabetes, in a Phase 1b randomized, three-arm, double-blind crossover trial in 23 hypoglycemia aware adults with T1D. Participants underwent three hypoglycemic clamp procedures with 3 or 20 mg ZT-01 or placebo dosed 1 h prior to stepwise glucose clamp conditions using variable rate IV insulin infusion: euglycemia (5.0 ± 0.5 mmol/L), level 1 (3.5 ± 0.3 mmol/L, L1), and level 2 hypoglycemia (2.6 ± 0.2 mmol/L, L2). With ZT-01, peak glucagon increased by up to 15.1 ± 10.5 and 27.1 ± 17.3 pg/mL, in L1 and L2 hypoglycemia, respectively, compared with no increase in L1 and an 8.4 ± 8.4 pg/mL increase in L2 hypoglycemia with placebo (p&amp;lt;0.0001, figure). A counterregulatory response of increased glucose level coinciding with an increased glucagon level was observed more frequently with ZT-01 than placebo. No clinically significant effects on other counterregulatory hormones or hypoglycemia symptom scores were observed with ZT-01. A transient rise in glucagon and blood glucose was observed with ZT-01 post-dose prior to hypoglycemia. No SAEs were reported and no TEAEs were observed with ZT-01. This study demonstrates proof-of-concept that ZT-01 significantly enhances the defective counterregulatory response in people with T1D during L1 and L2 hypoglycemia. Disclosure A.Abitbol: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Dexcom, Inc., Novo Nordisk Canada Inc., Janssen Pharmaceuticals, Inc., Research Support; Abbott Diabetes, Lilly Diabetes, Zucara Therapeutics, Novo Nordisk Canada Inc., Moderna, Inc., Senseonics, Speaker's Bureau; Boehringer Ingelheim (Canada) Ltd., Lilly Diabetes, Amgen Canada, Dexcom, Inc., Novo Nordisk Canada Inc., HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Sanofi. S.Peers: Employee; Zucara Therapeutics. E.Simonson: None. M.Midmer: Board Member; Zucara Therapeutics, Employee; Zucara Therapeutics, Stock/Shareholder; Zucara Therapeutics. M.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. R.Liggins: Employee; Zucara Therapeutics, Stock/Shareholder; Zucara Therapeutics.

1559-P: Glucagon Receptor–Mediated Improvements in Glycemia Are Dependent on Agonist Pharmacodynamics

Glucagon is considered the main glucose counter-regulatory hormone to insulin. Although, chronic glucagon receptor (GCGR) agonism induces hyperglycemia and glucose intolerance, it also improves insulin secretion and action. Surprisingly, we found chronic treatment with the selective, long-acting GCGR agonist, IUB288, improves ad libitum glycemia and glucose tolerance 4h after treatment. These glycemic improvements were associated with enhanced AKT phosphorylation, despite control-like insulin levels. We next tested if these results could be replicated with a short acting GCGR agonist. IUB94 displays improved aqueous solubility but maintains the short half-life and potency of native glucagon. 4h glucose excursion was monitored in lean mice after injection of IUB288, IUB94, or vehicle. We observed a transient rise in blood glucose (BG) 15min after either IUB288 or IUB94 compared to vehicle. Intriguingly, IUB288-treated mice exhibited improved BG from 120-240min, while BG in IUB94-treated mice was similar to vehicle controls. These data suggest that acute BG regulation is agonist-dependent yet, it remains unclear if pharmacodynamics or some inherent difference in potency is influencing the 4h BG. We next treated lean mice for 4d with vehicle or IUB288, measuring ad libitum glycemia over the final 24h period. IUB288-treated mice displayed improved glycemia 4h after the last injection and hyperglycemia after 12h, compared to vehicle-treated controls, suggesting chronic GCGR agonism is not exclusively hyperglycemic. Surprisingly, 4d IUB288 treatment in diet-induced obese (DIO) mice reduced ad libitum glycemia for a longer duration than observed in chow IUB288-treated mice. IUB288 treatment also increased glucose infusion rate, suppression of endogenous glucose production, and AKT phosphorylation during hyperinsulinemic-euglycemic clamps. These data provide insight into the potential therapeutic use of sustained-acting GCGR agonists against diabetes and obesity. Disclosure S.Nason: None. T.Kim: None. J.Antipenko: None. B.Yang: None. R.Dimarchi: None. K.M.Habegger: Consultant; Glyscend Inc., Research Support; Eli Lilly and Company, Novo Nordisk, Glyscend Inc., Stock/Shareholder; Glyscend Inc. Funding National Institutes of Health

Phenolic Composition, Antioxidant, and α-Glucosidase Inhibitory Activities of Extracts from Polygonatum sibiricum

As a traditional Chinese medicine and functional food, Polygonatum sibiricum contains many bioactive compounds with multiple biological activities. Presently, we obtained three extracts from Polygonatum sibiricum by different solvents and comparably analyzed their total phenols, flavonoids, and chemical compositions. Meanwhile, the antioxidant activity and the attenuation of palmitic acid (PA)-induced hepatic oxidative stress of these extracts were further investigated. The results showed that the active substances in Polygonatum sibiricum were inclined to dissolve in ethanol (EE), and twenty compounds were identified. EE exhibited the best antioxidant activity to scavenging DPPH and ABTS free radicals, as well as reducing power. Meanwhile, extracts from Polygonatum sibiricum, especially EE, could significantly increase the activity of SOD and HO-1 and ameliorate PA-induced oxidative stress in HepG2 cells through Nrf2-related pathways. Furthermore, EE could significantly inhibit the activity of α-glucosidase and effectively reduce the rapid rise of blood glucose induced by sucrose loading.

Black garlic melanoidins inhibit in vitro α-amylase and α-glucosidase activity: the role of high-molecular-weight fluorescent compounds.

Black garlic (Allium sativum L.) melanoidins (MLDs) are produced by Maillard reaction under high temperature and high humidity, and has a variety of biological activities. The aim of this study was to analyze the structural characteristics and investigate α-amylase and α-glucosidase in vitro inhibitory activity of black garlic MLDs. Spectroscopic and chemical analysis revealed that black garlic MLDs were heterogeneous macromolecular polymers with a skeletal structure similar to sugar chains. Molecular weight distribution and 3DEEM fluorescence showed that black garlic MLDs were composed of high-molecular-weight colorants with strong fluorescence properties. The polarity of black garlic MLDs was related to the fluorescence groups. The results of physicochemical properties proved that the polarity difference of black garlic MLDs was related to the elemental composition, resulting in differences in fluorescence, thermodynamic and apparent characteristics. MLDs with higher levels of fluorescent intensity (BG20 and BG40) had stronger inhibitory effects on α-amylase and α-glucosidase than BGW, and hydrolysis of fluorescent groups attenuated the inhibitory activity. The median inhibitory concentration (IC50 ) of black garlic MLDs against enzymes was positively correlated with the concentration, and the kinetic results detected non-competitive and mixed types of inhibition. High-molecular-weight fluorescent components of black garlic MLDs played a crucial role in the inhibitory activities of α-amylase and α-glucosidase, and the inhibitory ability was positively correlated with concentration. Black garlic MLDs had the potential to block postprandial glucose rise. © 2023 Society of Chemical Industry.