Stable Glucose Research Articles

ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes.

ISPAD Clinical Practice Consensus Guidelines 2022: Glycemic targets and glucose monitoring for children, adolescents, and young people with diabetes.

Differential regulation of nucleus accumbens glutamate and GABA in obesity-prone and obesity-resistant rats.

Obesity is one of the leading health concerns in the United States. Studies from human and rodent models suggest that inherent differences in the function of brain motivation centers, including the nucleus accumbens (NAc), contribute to overeating and thus obesity. For example, there are basal enhancements in the excitability of NAc GABAergic medium spiny neurons (MSN) and reductions in basal expression of AMPA-type glutamate receptors in obesity-prone vs obesity-resistant rats. However, very little is known about the regulation of extracellular glutamate and GABA within the NAc of these models. Here we gave obesity-prone and obesity-resistant rats stable isotope-labeled glucose (13 C6 -glucose) and used liquid chromatography mass spectrometry (LC-MS) analysis of NAc dialysate to examine the real-time incorporation of 13 C6 -glucose into glutamate, glutamine, and GABA. This novel approach allowed us to identify differences in glucose utilization for neurotransmitter production between these selectively bred lines. We found that voluntarily ingested or gastrically infused 13 C6 -glucose rapidly enters the NAc and is incorporated into 13 C2 -glutamine, 13 C2 -glutamate, and 13 C2 -GABA in both groups within minutes. However, the magnitude of increases in NAc 13 C2 -glutamine and 13 C2 -GABA were lower in obesity-prone than in obesity-resistant rats, while basal levels of glutamate were elevated. This suggested that there may be differences in the astrocytic regulation of these analytes. Thus, we next examined NAc glutamine synthetase, GAD67, and GLT-1 protein expression. Consistent with reduced 13 C2 -glutamine and 13 C2 -GABA, NAc glutamine synthetase and GLT-1 protein expression were reduced in obesity-prone vs obesity-resistant groups. Taken together, these data show that NAc glucose utilization differs dramatically between obesity-prone and obesity-resistant rats, favoring glutamate over GABA production in obesity-prone rats and that reductions in NAc astrocytic recycling of glutamate contribute to these differences. These data are discussed in light of established differences in NAc function between these models and the role of the NAc in feeding behavior.

Corn Stover Pretreatment with Na2CO3 Solution from Absorption of Recovered CO2

Renewable resources such as lignocellulosic biomass are effective at producing fermentable sugars during enzymatic hydrolysis when pretreated. Optimizing pretreatment methods for delignification while maintaining sustainability and low processing costs requires innovative strategies such as reusing greenhouse gas emissions for materials processing. Corn stover, an agricultural waste residue, was pretreated with 2.2 M Na2CO3 produced from CO2 captured via absorption in a 5 M NaOH solution. Composition analysis of the pretreated corn stover exhibited higher cellulose content (40.96%) and less lignin (16.50%) than the untreated biomass. Changes in the chemical structures are visible in the FTIR-ATR spectra, particularly in the cellulose and lignin-related absorption bands. The sugar release from hydrolysis was evaluated at different time intervals and by varying two enzyme ratios of CTec2-to-HTec2 (2:1 and 3:1). Enzymatic hydrolysis produced higher and more stable glucose yields for the pretreated biomass, surpassing 90% after 24 h using the 3:1 enzyme ratio. Sugar concentrations notably increased after pretreatment and even more when using the cellulase-rich enzyme solution. The maximum glucose, xylose, and arabinose recovered were 44, 19, and 2.3 g L−1. These results demonstrate the viability of capturing CO2 and converting it into an efficient Na2CO3 pretreatment for corn stover biomass. Additional processing optimizations depend on the combination of physicochemical parameters selected.

Effects of structure and physical chemistry of resistant starch on short-term satiety

The present study investigated the effects of structure and physical chemistry and of resistant starch on short-term satiety in mice using three types of resistant starch (RS): high-amylose maize starch (HMS, RS2), retrograded HMS (RS3), and octenyl succinic anhydride (OSA)-modified HMS (RS4). RS3 resulted in the greatest satiety, as indicated by the lowest food intake over 4 h, followed by RS4 and RS2. RS3 also yielded the lowest postprandial blood glucose peak, blood glucose fluctuation, and gastric emptying rate, which was conducive to the continuation of satiety. Structural and physicochemical analysis revealed that the three resistant starches differed significantly in terms of particle size, chain-length distribution, and swelling power, which were all significantly associated with short-term satiety (Pearson correlation analysis). These findings could provide a theoretical basis for designing raw materials for high-satiety-inducing foods for patients with type 2 diabetes and obesity. • Type Ⅲ resistant starch (RS3) resulted in greater satiety than RS4 and RS2. • RS3 caused stable postprandial blood glucose and the lowest insulin level. • Satiety was positively correlated with the swelling power of resistant starch.

OR30-2 Targeting Succinate Metabolism in Endocrine Therapy Resistant, ER Positive, Breast Cancer Cells

Abstract Estrogen receptor positive (ER+) breast cancer is the most common subtype among all breast cancers and is responsible for most breast cancer related deaths. Endocrine therapies, such as selective estrogen receptor modulators (SERM) and aromatase inhibitors (AI), often given in combination with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, are initially effective but the majority of advanced ER+ breast cancers eventually become refractory to endocrine therapies. Therefore, understanding the underlying molecular mechanisms that enable or promote resistance to endocrine therapies may lead to novel therapeutic targets.Cancer cells have a high energy demand and as a result consume greater quantities of glucose to meet their energy and anabolic demands to support cell growth and proliferation. In this study, we used breast cancer cell models that are endocrine therapy sensitive and resistant and investigated the metabolic flux of glucose by growing the cells in the presence of the stable glucose isotope, UC13-Glucose. We measured the C13-labelled metabolites of glycolysis and the TCA cycle. Glucose consumption was higher in endocrine therapy resistant MCF7/LCC9 (LCC9) cells compared with parental MCF7 (MCF7) and estrogen independent, endocrine therapy sensitive MCF7/LCC1 (LCC1) cells. Notably, in LCC9 cells the m+4 and m+6 isotopomer of C-13 labelled citrate was absent. Further, in LCC9 cells, C-13 labelled fumarate was very low while the succinate: fumarate ratio was markedly higher. These results suggest that the TCA cycle is impaired in LCC9 cells and the conversion of succinate to fumarate is dysregulated. Succinate dehydrogenase (SDH) enzyme is responsible for catalytic conversion of succinate to fumarate. SDH is a multimeric protein comprised of four different subunits and SDH assembly factor 2 (SDHAF2), which is a tumor suppressor gene. Our study further showed that SDHAF2 protein was under expressed in LCC9 cells compared with LCC1 cells, likely contributing to lower SDH activity. Intriguingly, when SDH activity was inhibited using dimethylmalonate, the LCC9 were re-sensitized to both Fulvestrant and 4-hydroxytamoxifen. Data analysis of clinical samples shows that poor relapse free survival in ER+ breast cancer patients is correlated with lower expression levels of SDHAF2. Overall, this study suggests that targeting succinate metabolism may help to restore sensitivity to Fulvestrant and tamoxifen in endocrine therapy resistance in ER+ breast cancer cells. Presentation: Tuesday, June 14, 2022 10:00 a.m. - 10:15 a.m.

LBODP086 An Unusual Infant Case Of Gastric Volvulus Presenting With Dumping Syndrome

Abstract An 18-day female infant, born preterm small for gestational age (SGA), developed fasting hypoglycemia. A critical sample revealed an insulin level of 4.7 μIU/mL at the time of hyloglycemia (39 mg/dL) without ketoacidosis. Diazoxide therapy was started under the impression of transient neonatal hyperinsulinemia related to SGA, however, hypogycemia was developed on the 21st day of life. Targeted next generation sequencing (NGS) was performed for possible congenital hyperinuslinism. During octreotide therapy, postprandial hyperglycemia was incidentally detected at 27 days. Continuous glucose monitoring (CGM; Dexcom G6, San Diego, California) revealed postprandial hyperglycemia and subsequent hypoglycemia suggestive of dumping syndrome, although she had no prior history of surgery. An upper gastrointestinal series revealed the anomalous rotation of the stomach along the mesenteroaxial axis perpendicular to its longitudinal axis, implying gastric volvulus. The possibility of dumping syndrome caused by gastric volvulus was confirmed by stable glucose level in the euglucemic range using CGM after continuous nasojejunal feeding. She received laparoscopic gastropexy to anchor the stomach. Euglycemia was maintained after surgery and octreotide therapy was successfully discontinued. NGS identified no pathogenic variant for congenital hyperinsulinism. At 8 months of age, she exhibited catch-up growth and normal development. This is the first infant case of gastric volvulus presenting with dumping syndrome during diazoxide therapy for transient neonatal hyperinsulinism. Presentation: No date and time listed

Diabetic ketoacidosis induced by nivolumab in invasive mucinous adenocarcinoma of the lung: a case report and review of the literature

Nivolumab is the first programmed cell death receptor 1 (PD-1) inhibitor approved in China. Compared with chemotherapy, nivolumab has shown advantages of good efficacy and safety in the treatment of a variety of tumors. However, due to its short time of use in China and lack of safety experience, clinical understanding of its adverse reactions has not been sufficiently elucidated. In recent years, cases of diabetic ketoacidosis caused by nivolumab have been reported in the emergency department, which has aroused our concern. Here we present a serious case of diabetic ketoacidosis in a 69-year-old woman with invasive mucinous adenocarcinoma of the lung, which occurred following therapy with the PD-1 inhibitor nivolumab and dendritic cell/cytokine-induced killer cell (DC/CIK) immunotherapy. She presented with diabetic ketoacidosis 5 days after the second cycle of nivolumab administration. The patient presented with dry mouth symptoms, a maximum blood glucose of 511.2 mg/dL, hemoglobin A1c (HbA1c) level of 7.4%, urine ketone body value of 3+, and extracellular fluid residual alkali level of -3.8 mmol/L. Normal saline and insulin was initiated. The patient had no history of obesity or family history of diabetes. She received a single dose of 3.75 mg of dexamethasone treatment during this period of time which resulted in cough improvement, but did not explain the onset of the diabetes. She was treated with insulin, sitagliptin phosphate tablets and acarbose tablets. Diabetic ketoacidosis was considered an immune-related toxicity caused by nivolumab, and consequently, treatment with nivolumab was suspended. Patient was maintained under insulin treatment with a blood glucose levels normalization. The incubation period of nivolumab-induced diabetic ketoacidosis is dispersive and the clinical risk is high. Patients need life-long insulin therapy. Blood glucose and HbA1c should be monitored routinely before and during nivolumab immunotherapy to avoid the occurrence of diabetic ketoacidosis. After the occurrence of diabetic ketoacidosis, insulin should be used to actively control blood glucose and do a good job in medication education to ensure long-term compliance of patients. Nivolumab should only be initiated if the patient has a clinical benefit under stable glucose control.

Sandwich structure confined gold as highly sensitive and stable electrochemical non-enzymatic glucose sensor with low oxidation potential

• Fe 3 O 4 @Au@CoFe-LDH is prepared through a spontaneous galvanic displacement reaction. • In Fe 3 O 4 @Au@CoFe-LDH, the metallic Au intercalates between Fe 3 O 4 and LDH forming the sandwich structure. • Fe 3 O 4 @Au@CoFe-LDH possesses high sensitivity of 6342 μA mM −1 cm −2 , broad linear detection range of 0.0375 to 15.64 mM and low limit of detection of 12.7 μM, with an extremely low oxidation potential of 0.82 V vs. RHE. • The small quantity of Au laying between LDH and Fe 3 O 4 is the active part of glucose oxidation and the existence of Fe 3 O 4 nanoparticles significantly improves the stability of the electrocatalyst. The preparation of highly sensitive and stable non-enzymatic glucose sensors is critical to the prevention and treatment of diabetes. Fe 3 O 4 @Au@CoFe-LDH is prepared through a spontaneous galvanic displacement reaction. A series of structural characterizations testify the successful formation of Fe 3 O 4 @Au@CoFe-LDH electrocatalyst, with the Au intercalating between Fe 3 O 4 and LDH to form the sandwich structure. Cyclic voltammetry tests indicate that Au is responsible for the electrocatalytic oxidation of glucose. The characterizations of the electrochemical sensor for glucose detection indicate that Fe 3 O 4 @Au@CoFe-LDH possesses high sensitivity of 6342 μA mM −1 cm −2 , with an extremely low oxidation potential of 0.82 V vs. RHE. Even with the high glucose concentration of 15 mM, the sensitivity remains at 4359 μA mM −1 cm −2 . Due to the broad linear detection range (0.0375 to 15.64 mM) and the low limit of detection (12.7 μM), Fe 3 O 4 @Au@CoFe-LDH is applicable towards practical application. Thanks to the sandwich structure, which confines the Au in between Fe 3 O 4 and CoFe-LDH, the Fe 3 O 4 @Au@CoFe-LDH glucose sensor shows high long-term stability and satisfactory selectivity. The successful synthesis of the sandwich-structured Fe 3 O 4 @Au@CoFe-LDH provides a new conception for the design of highly sensitive and stable non-enzymatic glucose electrodes.

A physical activity-intensity driven glycemic model for type 1 diabetes

Background and ObjectiveThe glucose response to physical activity for a person with type 1 diabetes (T1D) depends upon the intensity and duration of the physical activity, plasma insulin concentrations, and the individual physical fitness level. To accurately model the glycemic response to physical activity, these factors must be considered. MethodsSeveral physiological models describing the glycemic response to physical activity are proposed by incorporating model terms proportional to the physical activity intensity and duration describing endogenous glucose production (EGP), glucose utilization, and glucose transfer from the plasma to tissues. Leveraging clinical data of T1D during physical activity, each model fit is assessed. ResultsThe proposed model with terms accommodating EGP, glucose transfer, and insulin-independent glucose utilization allow for an improved simulation of physical activity glycemic responses with the greatest reduction in model error (mean absolute percentage error: 16.11 ± 4.82 vs. 19.49 ± 5.87, p = 0.002). ConclusionsThe development of a physiologically plausible model with model terms representing each major contributor to glucose metabolism during physical activity can outperform traditional models with physical activity described through glucose utilization alone. This model accurately describes the relation of plasma insulin and physical activity intensity on glucose production and glucose utilization to generate the appropriately increasing, decreasing or stable glucose response for each physical activity condition. The proposed model will enable the in silico evaluation of automated insulin dosing algorithms designed to mitigate the effects of physical activity with the appropriate relationship between the reduction in basal insulin and the corresponding glycemic excursion.

A stable glucose sensor with direct electron transfer, based on glucose dehydrogenase and chitosan hydro bonded multi-walled carbon nanotubes

Direct electron transfer (DET) glucose sensors are third-generation biosensors, which allow the enzyme to directly transfer electrons by glucose oxidation without a mediator. In previous studies, many researchers have focused on the glucose oxidase (GOx)-based DET glucose sensor; however, an efficient DET glucose sensor using flavin adenine dinucleotide (FAD)-glucose dehydrogenase (GDH) has not been developed. In the present study, we bound FAD-GDH and multi-walled carbon nanotubes (MWCNT), using chitosan (CS) compounds that support hydrogen bonding, van der Waals forces, and 3D structural adsorption. The GDH/CS-MWCNT-5 composite, which had a GDH concentration of 75 wt%, was physically adsorbed on screen-printed carbon electrodes (SPCEs), and cyclic voltammetry indicated that its oxidation and reduction peaks were at − 0.422 V and − 0.543 V (vs Ag/AgCl), respectively. In addition, the electrochemical results confirmed that the prepared GDH/CS-MWCNT/SPCEs were not affected by other interfering substances or oxygen at pH of 7. The GDH/CS-MWCNT/SPCEs displayed oxidation catalytic currents, which increased according to glucose concentrations across a range of 0–5.5 mM. Finally, the short-term stability of glucose, assessed for 10 days, was maintained at 80% of the GDH enzyme activity for 6 days, and it reduced to 50% of the initial activity for the remaining 4 days. Here, we illustrate the potential utility of the FAD-GDH-based DET method in continuous glucose monitoring sensors.

Separate and combined effect of visit-to-visit glycaemic variability and mean fasting blood glucose level on all-cause mortality in patients with type 2 diabetes: A population-based cohort study.

To assess the independent and combined impacts of visit-to-visit fasting blood glucose variability (VVV-FBG) and mean fasting blood glucose level (M-FBG) on all-cause mortality. This prospective cohort study included 48 843 Chinese patients with type 2 diabetes. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to evaluate the association of VVV-FBG and M-FBG with all-cause mortality. The potential nonlinear associations were examined using restricted cubic splines, and additive interaction was evaluated using relative excess risk due to interaction (RERI). Cox generalized additive models (CGAMs) and bivariate response surface models were further used to assess the combined effects of VVV-FBG and M-FBG. A total of 4087 deaths were observed during a median follow-up of 6.99 years. Compared with patients with values at the 5th percentile of average real variability (ARV) and M-FBG, we observed a 23% and 38% increased risk of premature deaths among those with values at the 95th percentile of ARV (HR 1.23, 95% CI 1.10, 1.37) and M-FBG (HR 1.38, 95% CI 1.26, 1.51), respectively. The interaction between glycaemic variability (ARV) and M-FBG was significant on both the additive scale (RERI 0.80 [0.29, 1.32]) and the multiplicative scale (HR 1.90 [1.10, 3.28]). High VVV-FBG and high M-FBG conferred the highest risk of all-cause mortality (HR 1.89, 95% CI 1.64, 2.17), compared to low VVV-FBG and low M-FBG. The CGAMs showed significant synergistic effects between glycaemic variability and M-FBG (P < 0.05). Moreover, a bivariate surface plot showed that risk of death increased more rapidly in type 2 diabetes patients with lower M-FBG combined with lower VVV-FBG. The coexistence of high glycaemic variability and high glucose level might exacerbate the independent risk of premature mortality in type 2 diabetes patients, highlighting the importance of achieving normal and stable glucose levels simultaneously in the management of glucose.

Electrospun nanofiber-based glucose sensors for glucose detection.

Diabetes is a chronic, systemic metabolic disease that leads to multiple complications, even death. Meanwhile, the number of people with diabetes worldwide is increasing year by year. Sensors play an important role in the development of biomedical devices. The development of efficient, stable, and inexpensive glucose sensors for the continuous monitoring of blood glucose levels has received widespread attention because they can provide reliable data for diabetes prevention and diagnosis. Electrospun nanofibers are new kinds of functional nanocomposites that show incredible capabilities for high-level biosensing. This article reviews glucose sensors based on electrospun nanofibers. The principles of the glucose sensor, the types of glucose measurement, and the glucose detection methods are briefly discussed. The principle of electrospinning and its applications and advantages in glucose sensors are then introduced. This article provides a comprehensive summary of the applications and advantages of polymers and nanomaterials in electrospun nanofiber-based glucose sensors. The relevant applications and comparisons of enzymatic and non-enzymatic nanofiber-based glucose sensors are discussed in detail. The main advantages and disadvantages of glucose sensors based on electrospun nanofibers are evaluated, and some solutions are proposed. Finally, potential commercial development and improved methods for glucose sensors based on electrospinning nanofibers are discussed.

The Effect Of Moringa Leaf Extract On Hyperglycemic Rat Liver Function

One of the management of diabetics is to maintain stable glucose levels. Often diabetes treatment combines chemical drugs with medicinal plants. People have consumed a lot of Moringa leaves which are believed to be able to maintain body condition. One of the benefits of Moringa leaves with phytochemical components in it is as a hepatoprotector. The aim of this study was to analyze the role of Moringa leaf extract on liver function parameters of hyperglycemic rats. There were 4 groups, normal control (K0), hyperglycemic rats with induction of alloxan 125 mg/kg bw and divided into three groups treated with moringa leaf extract at a dose of 0 mg (K1), 200 mg (T1) and 400 mg/kg bw (T2 ) for 21 days. The variables measured were aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, total cholesterol. Data were analyzed with Anova P0.05 and Least Significance Different (LSD) follow-up test. The results showed that the levels of AST and ALT were highest in the K1 group which then decreased significantly in the group that received Moringa extract (T1 and T2). Statistically there was a significant difference (p0.05) between the control and treatment groups. Cholesterol levels in the control group were significantly lower than the diabetes and treatment groups, but there was no significant difference between the treatment groups. The conclusion is that Moringa leaf extract has an effect on reducing liver enzyme levels and cholesterol in hyperglycemic rats. This research adds to the study of the hepatoprotective potential of Moringa leaf extract in hyperglycemic rats.

Update on glycogen storage disease: primary hepatic involvement.

Glycogen storage disease is a group of disorders primarily characterized by hepatomegaly and fasting hypoglycemia. This group of disorders may also affect the muscle, kidneys, and neurodevelopment. With an overall prevalence of 1 : 20 000, GSDs are disorders that clinicians should diagnose in a timely manner because adequate management can prevent complications, such as neurodevelopmental delay and liver disease [1] . As there are numerous types of GSDs, being able to distinguish one type from another can be overwhelming. In this review, we focus on hepatic GSDs to provide a concise review of clinical presentation, diagnosis, and current management. GSDs are considered rare disorders, and one of the main challenges is the delay in diagnosis, misdiagnosis, or under diagnosis. However, with molecular genetic testing now readily available, confirming the diagnosis is no longer as difficult or invasive as it was in the past. Current therapy for this group of disorders requires maintaining stable glucose levels. Avoiding hypoglycemia, as well as hyperglycemia, is critical in managing these patients. Being able to distinguish the types of GSDs and understanding the specific treatments for each enzymatic defect will optimize patient care.

Successful treatment of hyperglycemia with liraglutide in a hospitalized 27-year-old patient with schizophrenia: A case report

BACKGROUNDAntipsychotics are associated with abnormalities in glucose metabolism in patients with schizophrenia. Liraglutide, a GLP-1 receptor agonist, is Food and Drug Administration approved for the treatment of type 2 diabetes mellitus. However, ways to maintain the long-term stability of psychotic symptoms and balance the disadvantages of obesity, diabetes, and other metabolic disorders caused by antipsychotic medications remain unclear. In this study, we present a case of weight gain and hyperglycemia in a schizophrenia patient who received antipsychotic polypharmacy for 6 years.CASE SUMMARYA 27-year-old man with olanzapine and sodium valproate-treated disorganized schizophrenia was admitted to a diabetes outpatient clinic. He was diagnosed with type 2 diabetes (fasting blood glucose, 20 mmol/L) and obesity (body mass index, 38.58 kg/m2). The patient had been treated with glargine (40 IU/d) and metformin (1.5 g/d) and showed a poor response for 2 mo. Two years of liraglutide treatment resulted in stable blood glucose levels and weight loss in addition to a maintained stable mental status for a long time. The biological activities of GLP-1 significantly improved glucose levels and body weight in the schizophrenia patient treated with antipsychotic medications.CONCLUSIONLiraglutide administration can be considered an effective alternative treatment for abnormalities in glucose metabolism in schizophrenia patients receiving antipsychotics.

Reaction kinetics study and the estimation of thermodynamic parameters for the conversion of glucose to 5-hydroxymethylfurfural (5-HMF) in a dimethyl sulfoxide (DMSO) medium in the presence of a mesoporous TiO2 catalyst

BackgroundsGlucose is a potential feedstock for the production of 5-HMF, a top ten platform chemical. The kinetics of glucose conversion to 5-HMF in organic dimethylsulfoxide (DMSO) medium is not known. In this study, glucose dehydration kinetics is performed over TiO2 catalyst in the DMSO medium. MethodsThe kinetic experiments were performed in a 15 mL screw tight glass vial at 100-180 °C. A first-order kinetic model was developed by assuming a four steps process including (1) glucose conversion to 5-HMF via dehydration, (2) direct glucose decomposition to FA and polymerization to humin or polymeric products, (3) 5-HMF conversion to LA and FA via rehydration and (4) 5-HMF decomposition to humin and FA. The obtained models were solved by non-linear regression techniques by minimizing the sum of the square using Polymath. Further, the thermodynamic parameters (∆H‡, ∆S‡, and ∆G‡) of activation for all the probable reaction steps were calculated. Significant findingsThe model was fitted very well with the experimental data with an R2 value of > 0.97. The calculated activation energy for glucose dehydration to 5-HMF was 66.2 kJ mol−1 and for 5-HMF rehydration to LA and FA was (51 kJ mol−1), respectively. The higher value (∼63 kJ mol−1) of the enthalpy of activation (∆H‡) for glucose conversion to 5-HMF depicted the higher energy required to break the stable pyranose glucose ring, and the obtained positive ∆G‡ value suggested that the reactions were non-spontaneous.

Relationships Among Perception of Cognitive Function, Diabetes Self-Management, and Glucose Variability in Older Adults: A Mixed Methods Study.

The aim of the current study was to explore relationships among perceived cognitive function, glucose variability, and self-management in older adults with type 2 diabetes mellitus (T2DM). A mixed methods design was used with data from: (a) questionnaires on perceived cognitive function and diabetes self-management; (b) continuous glucose monitoring (CGM) reports; and (c) semi-structured interviews. Thirty adults with T2DM (47% female; mean age = 68.5 [SD = 5.2] years) participated. Those who exercised more days per week had more stable glucose. Those who reported fewer days of diet adherence had more hypoglycemia. Participants who reported higher levels of memory dissatisfaction exhibited higher levels of glucose variability. Findings point to the potential of glucose variability as a target to reduce the effect of diabetes on cognitive function. Instruction in recognition of glucose patterns found via CGM can be integrated into self-management education to improve self-management and subsequent glucose control and cognitive function. [Research in Gerontological Nursing, 15(4), 203-212.].

Abstract 2327: Dysregulated TCA cycle is associated with endocrine therapy resistance in ER+ breast cancer cells

Abstract Estrogen receptor positive (ER+) breast cancer is the most common breast cancer subtype. Endocrine therapies, such as selective estrogen receptor modulators (SERM) and aromatase inhibitors (AI), along with cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, are the current mainstays of treatment. Despite being initially effective, the majority of advanced ER+ breast cancers become resistant to the endocrine therapies. Therefore, it is important to understand the underlying molecular mechanisms that enable or promote resistance to endocrine therapies. Rapidly proliferating cells have a high energy demand and consequently consume greater quantities of glucose to fulfill their energy and anabolic demands to support cell growth. Using endocrine therapy sensitive and resistant breast cancer cell models we investigated the metabolic flux of glucose by growing the cells in the presence of the stable glucose isotope, UC13-Glucose and measured the C13-labelled metabolites of glycolysis and the TCA cycle. Glucose consumption was higher in endocrine therapy resistant MCF7/LCC9 (LCC9) cells compared with parental MCF7 (MCF7) and estrogen independent, endocrine therapy sensitive MCF7/LCC1 (LCC1) cells. The TCA cycle was noticeably impaired in LCC9 cells as the C-13 labelled citrate (m+4 and m+6) isotopomer was absent in these cells. In addition, C-13 labelled fumarate was very low in LCC9 cells with a concurrent increase in the succinate:fumarate ratio. These observations show that in LCC9 cells the TCA cycle is dysregulated at the succinate to fumarate conversion step, which is catalyzed by the succinate dehydrogenase (SDH) enzyme. SDH is a multimeric protein comprised of four different subunits and SDH assembly factor 2 (SDHAF2), which is a tumor suppressor gene. Further investigation revealed that SDHAF2 was under expressed in LCC9 cells compared with LCC1 cells, likely contributing to lower SDH activity. Intriguingly, SDH inhibition by dimethyl-malonate re-sensitized LCC9 cells to both Fulvestrant and 4-hydroxytamoxifen. Clinically, lower expression levels of SDHAF2 correlates with poor relapse free survival in ER+ breast cancer patients. In summary, our study suggests that accumulation of succinate driven by deficient SDH activity is functionally associated with endocrine therapy resistance in ER+ breast cancer cells. Citation Format: Surojeet Sengupta, Karla Andrade de Oliviera, Lu Jin, Robert Clarke. Dysregulated TCA cycle is associated with endocrine therapy resistance in ER+ breast cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2327.

Bioactive spermidine nanoparticles for effective cardiovascular recovery and diabetic therapy

Cardiovascular complications account for more than 80% of type II diabetes (T2D)-related mortality every year. Although glucagon-like peptide 1 receptor agonists (GLP-1RA) can effectively maintain the glycemic level, their efficacy and related cardiovascular benefits are significantly limited owing to their short half-life. Hence, in this study, on the basis of calorie restriction theory, spermidine containing bioactive polymers have been developed to deliver liraglutide with sustained release kinetics. Calorie restrictive and cardiovascular beneficial spermidine (SPM) was conjugated to oxidized dextran to synthesize bioactive SPM-DEX polymer and the SPM-DEX/Liraglutide nanoparticles were successfully prepared using the flash nanocomplexation (FNC) technique via electrostatic polyelectrolyte complexation. Single administration of these sub-100 nm liraglutide nanoparticles efficiently prolonged the hypoglycemic efficacy of liraglutide for more than 4 days. Moreover, through modulating glucose metabolism dysfunction and excessive lipid metabolism, these long-acting liraglutide and SPM containing nanoparticles efficiently maintained a stable blood glucose level (BGL) and body weight in 30 days as biochemical indices, such as HbA1c and triglycerides, were all reduced to the normal range. In addition, by downregulating the Wnt/β-catenin signaling pathway, SPM containing nanoparticles effectively postponed the progression of myocardial fibrosis and systemically improved the systolic function of the cardiac left ventricle. We believe this highly biocompatible, bioactive and calorie restrictive spermidine-containing liraglutide nanoparticles with long-term hypoglycemic efficacy and cardiovascular benefits may hold great clinical potentials.

670-P: Iron-Deficiency Anemia Case Report Showing the Clinical Relevance of RBC-Lifespan–Adjusted A1C

Laboratory A1C does not precisely reflect glycemic control in those with altered RBC lifespan and our aim was to evaluate an adjusted A1C, a glycemic measure that adjusts A1C to a reference RBC lifespan. By removing the individual RBC lifespan variation, adjusted A1C better reflects intracellular glucose exposure in RBCs and perhaps other organs susceptible to complications. Iron-deficiency anemia and treatment is known to affect RBC lifespan and therefore provides opportunity to evaluate the model. The patient was a 53-year-old woman with iron-deficiency anemia and type 1 diabetes utilizing sensor-augmented pump therapy. Longitudinal A1C and CGM were evaluated with a novel kinetic model to estimate RBC lifespan and glucose uptake rate. During the six months before iron therapy, the RBC lifespan was estimated at 151 days and 93% of a reference glucose uptake. During six months of iron therapy, the RBC lifespan decreased to 122 days, while the RBC glucose uptake increased slightly to 101% of reference value. The RBC lifespan change explains the observed laboratory A1C change (Figure) and can be attribute to the iron therapy and supported by Hb, RDW and Ferritin data. The adjusted A1C based on these two different RBC lifespans agree with the stable CGM mean glucose of this patient. In this case study, we confirmed the clinical relevance of adjusted A1C to account for variations in RBC lifespan. Disclosure Y.Hirota: Speaker's Bureau; Abbott Japan Co., Ltd., Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Kirin Co., Ltd., Lilly, Medtronic, Mochida Pharmaceutical Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited, Terumo Corporation. Y.Xu: Employee; Abbott Diabetes. A.Yamamoto: None. A.Matsuoka: None. T.Dunn: Employee; Abbott. W.Ogawa: Advisory Panel; Abbott Japan Co., Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk, Other Relationship; Abbott Japan Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Nippon Boehringer Ingelheim Co. Ltd., Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Research Support; Abbott, Astellas Pharma Inc., Eli Lilly and Company, Kowa Company, Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Funding Abbott Diabetes Care