Lower Blood Glucose Levels Research Articles

Randomized trial of early exercise rehabilitation and its effects on patients with acute coronary syndrome

To assess the psychological and physiological benefits of early exercise rehabilitation in patients with acute coronary syndrome (ACS). Among 559 ACS-diagnosed patients at Fuzhou University Affiliated Provincial Hospital from January to December 2021, 200 eligible participants were assigned to two groups. The control group received standard care, while the experimental group received early exercise rehabilitation in addition to standard care. The outcomes measured included changes in depression levels (PHQ-9), fasting blood glucose, and troponin I (TnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. Data were analyzed using SPSS, with t tests and chi-square tests for group comparisons. In comparison to the control group, the experimental group demonstrated significant improvements in PHQ-9 scores (P < 0.001) and lower fasting blood glucose levels before discharge (P = 0.046). Additionally, the experimental group had notably reduced TnI levels at 72 h after admission (P = 0.001), especially among non-diabetic NSTEMI patients over 60 years old, who showed decreased TnI levels at the 48-hour mark (P = 0.016). However, there were no significant differences in NT-ProBNP change values between the two groups (P > 0.05). Subgroup analysis revealed enhanced outcomes in the intervention group for ACS patients without smoking or drinking history and no heart failure (P = 0.025,P = 0.014,P = 0.018). Early exercise rehabilitation has notable benefits for ACS patients, including reduced depression, improved blood glucose control, and enhanced myocardial protection, especially in nondiabetic NSTEMI patients aged 60 and above.

Effects of Ovariectomy on Kidney Injury in SDT Fatty Rats

Postmenopausal women are at a higher risk of developing diabetes, and estrogen can lower blood glucose levels. The purpose of this study was to investigate the effect of ovariectomy (OVX) on the pathology of diabetic nephropathy. Female SD rats and SDT fatty rat underwent bilateral OVX or sham treatment at 6 weeks of age, and their blood and kidneys were collected at 40 weeks of age for blood biochemical and histopathological analyses. OVX treatment resulted in a decrease in blood estradiol levels at 24 and 40 weeks of age. Histopathological analysis revealed that Sham-treated SDT fatty rats showed glomerular atrophy, adhesions, enlargement, mesangial cell proliferation, regenerated tubules, hyaline casts, Armani-Ebstein lesions, tubular dilatation, interstitial inflammatory cell infiltration, and fibrosis. OVX treatment slightly reduced glomerular atrophy and enlargement, renal tubular dilatation, and interstitial inflammatory cell infiltration, while slightly increased or exacerbated mesangial cell hyperplasia, tubular regeneration, and Armani-Ebstein lesions. The above findings suggest that SDT fatty rats are not a practical model to study postmenopausal diabetic nephropathy.

Hypoglycaemia Prevention, Awareness of Symptoms, and Treatment (HypoPAST): protocol for a 24-week hybrid type 1 randomised controlled trial of a fully online psycho-educational programme for adults with type 1 diabetes

BackgroundManagement of type 1 diabetes (T1D) requires the use of insulin, which can cause hypoglycaemia (low blood glucose levels). While most hypoglycaemic episodes can be self-treated, all episodes can be sudden, inconvenient, challenging to prevent or manage, unpleasant and/or cause unwanted attention or embarrassment. Severe hypoglycaemic episodes, requiring assistance from others for recovery, are rare but potentially dangerous. Repeated exposure to hypoglycaemia can reduce classic warning symptoms (‘awareness’), thereby increasing risk of severe episodes. Thus, fear of hypoglycaemia is common among adults with T1D and can have a negative impact on how they manage their diabetes, as well as on daily functioning, well-being and quality of life. While advances in glycaemic technologies and group-based psycho-educational programmes can reduce fear, frequency and impact of hypoglycaemia, they are not universally or freely available, nor do they fully resolve problematic hypoglycaemia or associated worries. This study aims to determine the effectiveness of a fully online, self-directed, scalable, psycho-educational intervention for reducing fear of hypoglycaemia: the Hypoglycaemia Prevention, Awareness of Symptoms, and Treatment (HypoPAST) programme.MethodsA 24-week, two-arm, parallel-group, hybrid type 1 randomised controlled trial, conducted remotely (online and telephone). Australian adults (≥ 18 years) with self-reported T1D and fear of hypoglycaemia will be recruited, and allocated at random (1:1) to HypoPAST or control (usual care). The primary outcome is the between-group difference in fear of hypoglycaemia (assessed using HFS-II Worry score) at 24 weeks. A sample size of N = 196 is required to detect a 9-point difference, with 90% power and allowing for 30% attrition. Multiple secondary outcomes include self-reported psychological, behavioural, biomedical, health economic, and process evaluation data. Data will be collected at baseline, 12 and 24 weeks using online surveys, 2-week ecological momentary assessments, website analytics and semi-structured interviews.DiscussionThis study will provide evidence regarding the effectiveness, cost-effectiveness and acceptability of a novel, online psycho-educational programme: HypoPAST. Due to the fully online format, HypoPAST is expected to provide an inexpensive, convenient, accessible and scalable solution for reducing fear of hypoglycaemia among adults with T1D.Trial registrationAustralian and New Zealand Clinical Trials Registry (ANZCTR): ACTRN12623000894695 (21 August 2023).

The Triglycerides - Glucose Index: An independent predictor of late subclinical cardiotoxicity in adult survivors of childhood, adolescent and young adult cancer

Abstract Introduction The Triglycerides - Glucose index (TyG index) has been identified as a reliable alternative for estimating insulin resistance (IR). Numerous recent studies have provided strong statistical evidence suggesting that this index is associated with the development and prognosis of cardiovascular pathologies. Objectives The aim of this study was to investigate the predictive role of the TyG index on the decrease in left ventricular longitudinal global strain (GLS) assessed on two-dimensional echocardiography in asymptomatic adult survivors of childhood, adolescent and young adult cancer. Methods The study included patients aged 18 years and older, asymptomatic cardiovascular survivors of childhood, adolescent and young adult cancer treated with anthracyclines with or without mediastinal radiotherapy. Anthropometric characteristics, cardiovascular risk factors and cancer treatment-related characteristics were collected. The TyG index was calculated using the formula: ln [fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2]. GLS was assessed and expressed as an absolute value. A GLS equal to 17.3% was retained as the threshold value after calculation in a referent group matched to patients according to age and gender. Cardiac biomarkers GDF 15, ultra-sensitive troponin I and NT-proBNP levels were measured in addition to fasting blood glucose and lipid profiles. Multivariate analysis using linear regression was performed to identify associations between these different parameters. Results A total of 105 cancer survivors from childhood, adolescence and young adulthood were included. The sex ratio was 1.3. The mean age of the patients was 25 years, the mean time since completion of cancer treatment was 10.6 years, the mean cumulative doses of anthracyclines and mediastinal radiotherapy were successively 245.75 ± 75.14 mg/m2 and 34.6 ± 6.19 Gy. Mean GLS was 18.5 ± 2.83%, mean LVEF 60.6 ± 5.69%. None of the patients had any known diabetes or treatment to lower blood glucose or triglyceride levels. No patient had a history of cardiovascular disease. In the univariate study, the factors associated with lower GLS were patient age at recruitment (p = 0.03), mean time since completion of cancer treatment when this was greater than ten years (p = 0.005), dyslipidemia (p = 0.012), obesity (p = 0.037) and TyG (p = 0.037). In multivariate analysis, lower GLS was related to mean time since completion of cancer treatment (p = 0.015) and TyG index (p = 0.002). Conclusion Our results suggest that the TyG index, as a simple and inexpensive marker of insulin resistance, could help identify cancer survivors from childhood, adolescence and young adulthood who would be at risk of subclinical cardiac dysfunction. Prospective studies with larger numbers are needed to confirm these findings.

Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review

The history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria resulted from inhibition by phlorizin of glucose reabsorption by the renal tubules, which lowered blood glucose levels in diabetic rats. Nowadays, beyond their glucose-lowering effects, growing evidence suggests significant cardiorenal benefits associated with SGLT2i therapy. Indeed, several clinical trials, including landmark studies such as EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, have demonstrated robust reductions in cardiovascular events, particularly heart failure hospitalizations and cardiovascular mortality, among patients treated with SGLT2i. However, subsequent trials showed that SGLT2i benefits extend beyond the diabetic population, encompassing individuals with and without diabetes. Additionally, SGLT2i exhibit nephroprotective effects, manifesting as a slowing of the progression of chronic kidney disease and a reduction in the risk of end-stage kidney disease. The mechanisms underlying the cardiorenal benefits of SGLT2i are multifactorial and include improvements in glycemic control, reduction in arterial stiffness, modulation of inflammation and oxidative stress, reduction of intraglomerular pression and promotion of natriuresis and diuresis through inhibition of SGLT2 in the luminal brush border of the first segments of the proximal kidney tubule. This narrative review aims to explore the cardiorenal outcomes of SGLT2i, encompassing their mechanisms of action, clinical evidence, safety profile, and implications for clinical practice.

In Vivo Differentiation of Endogenous Bone Marrow-Derived Cells into Insulin-Producing Cells Using Four Soluble Factors.

Four soluble factors-putrescine, glucosamine, nicotinamide, and signal transducer and activator of transcription 3 (STAT3) inhibitor BP-1-102-were shown to differentiate bone marrow mononucleated cells (BMNCs) into functional insulin-producing cells (IPCs) in vitro. Transplantation of these IPCs improved hyperglycemia in diabetic mice. However, the role of endogenous BMNC regeneration in this effect was unclear. This study aimed to evaluate the effect of these factors on in vivo BMNC differentiation into IPCs in diabetic mice. Mice were orally administered the factors for 5 days, twice at 2-week intervals, and monitored for 45-55 days. Glucose tolerance, glucose-stimulated insulin secretion, and pancreatic insulin content were measured. Chimeric mice harboring BMNCs from insulin promoter luciferase/green fluorescent protein (GFP) transgenic mice were used to track endogenous BMNC fate. These factors lowered blood glucose levels, improved glucose tolerance, and enhanced insulin secretion. Immunostaining confirmed IPCs in the pancreas, showing the potential of these factors to induce β-cell regeneration and improve diabetes treatment.

Metabolic Effects of Medium-Chain Triacylglycerol Consumption are Preserved in Obesity.

Several health beneficial effects are associated with intake of medium-chain triacylglycerol (MCT), however, the underlying mechanisms are unknown. Furthermore, it remains uncertain whether the acute metabolic effects of MCT differ between lean individuals and individuals with obesity - and whether these effects are sustained following chronic intake. This study aimed to elucidate the postprandial physiological and metabolic effects of MCT before and after eight days intake compared to intake of energy-matched triacylglycerol consisting of long-chain fatty acids (LCT) using a randomized cross-over design in lean individuals (n=8) and individuals with obesity (n=8). The study revealed that consumption of MCT increased ketogenesis and metabolic rate, while lowering blood glucose levels over five hours. The hypoglycemic action of MCT intake was accompanied by a concomitant transient increase in plasma insulin and glucagon levels. Interestingly, the effects on ketogenesis, metabolic rate, and glycemia were preserved in individuals with obesity and sustained after eight days of daily supplementation. Lipidomic plasma analysis in lean individuals (n=4) showed that a part of the ingested MCT bypasses the liver and entered the systemic circulation as medium-chain fatty acids (MCFA). The findings suggest that MCFA, along with ketone bodies from the liver, may act as signaling molecules and/or substrates in the peripheral tissues, thereby contributing to the effects of MCT intake. In summary, these findings underscore the health benefits of MCT in metabolically compromised individuals after daily supplementation. Moreover, we uncover novel aspects of MCFA biology, providing insights into how these fatty acids orchestrate physiological effects in humans.

The Therapeutic Potential of GLP-1 Receptor Agonists in the Management of Hidradenitis Suppurativa: A Systematic Review of Anti-Inflammatory and Metabolic Effects

Background: Glucagon-like peptide-1 receptor agonists (GLP1-RAs) are synthetic peptides that mimic the natural activity of GLP-1, widely known for lowering blood glucose levels and promoting weight reduction. These characteristics make them a valuable tool in managing type 2 diabetes and obesity-related conditions. Recent findings indicate that GLP1-RAs may also offer therapeutic benefits in managing hidradenitis suppurativa (HS), a chronic inflammatory skin disorder closely associated with metabolic abnormalities, including obesity, diabetes, and dyslipidemia. This review explores the potential role of GLP1-RAs in managing HS. Methods: A systematic review was conducted by searching electronic databases, including MEDLINE and Google Scholar, without date limitations. Key search terms included “GLP-1” or “GLP-1 agonists” combined with “hidradenitis suppurativa” or “acne inversa”. Inclusion criteria were set for studies reporting on the use of GLP1-RAs as a treatment for HS, with articles discussing theoretical applications excluded. Data synthesis included findings from 25 relevant studies. Results: The analysis revealed that GLP1-RAs, specifically liraglutide and semaglutide, led to significant reductions in weight and systemic inflammation in HS patients. Notably, improvements in lesion severity and quality of life were reported. The anti-inflammatory effects of GLP1-RAs were attributed to the suppression of key inflammatory pathways involving TNF-α, IL-17, and NF-κB. Conclusions: GLP1-RAs demonstrate significant potential as an adjunct therapy for HS, addressing both the metabolic and inflammatory aspects of the condition. While early results are promising, further research is necessary to determine their long-term efficacy in managing HS.

In vivo functional profiling and structural characterisation of the human Glp1r A316T variant.

Glucagon-like peptide-1 receptor (GLP-1R) agonists are a highly effective therapy class for type 2 diabetes (T2D) and obesity, yet there are variable patient responses. Variation in the human Glp1r gene leading to altered receptor structure, signal transduction, and function might be directly linked to therapeutic responses in patients. A naturally occurring, low-frequency, gain-of-function missense variant, rs10305492 G>A (A316T), protects against T2D and cardiovascular disease. Here we employ CRISPR/Cas9 technology to generate a humanised knock-in mouse model bearing the homozygous Glp1r A316T substitution. Human Glp1r A316T/A316T mice displayed lower fasting blood glucose levels and improved glucose tolerance, as well as increased plasma insulin levels and insulin secretion responses, even under metabolic stress. They also exhibited alterations in islet cytoarchitecture and β-cell identity indicative of compensatory mechanisms under a high-fat, high-sucrose (HFHS) diet challenge. Across all models investigated, the human Glp1r A316T variant exhibited characteristics of constitutive activation but blunted incretin-induced responses. Our results are further supported by cryo-EM analysis and molecular dynamics (MD) simulations of the GLP-1R A316T structure, demonstrating that the A316T Glp1r variant governs basal receptor activity and pharmacological responses to GLP-1R-targeting anti-diabetic therapies, highlighting the importance of the precise molecular characterisation of human Glp1r variants to predict individual therapy responses.

Anti-Hyperglycemic Effects of Thai Herbal Medicines

This study aims to investigate selected medicinal plants’ anti-oxidative and antihyperglycemic activities to develop an effective remedy for lowering blood glucose levels and/or reducing diabetes complications. Thai medicinal plants, reported to have blood sugar-lowering effects, were selected for the study: Coccinia grandis, Gymnema inodorum, Gynostemma pentaphyllum, Hibiscus sabdariffa, Momordica charantia, Morus alba, and Zingiber officinale. Each species was extracted by Soxhlet’s extraction using ethanol as solvent. The ethanolic crude extract of each species was then evaluated for its phytochemicals, anti-oxidant, and antihyperglycemic activities. The results showed that the extract of Z. officinale gave the highest values of total phenolic and total flavonoid content (167.95 mg gallic acid equivalents (GAE)/g and 81.70 mg CE/g, respectively). Anti-oxidant activity was determined using DPPH and ABTS radical scavenging activity. Among the ethanolic extracts, Z. officinale exhibited the highest anti-oxidant activity with IC50 values of 19.16 and 8.53 µg/mL, respectively. The antihyperglycemic activity was assessed using α-glucosidase inhibitory and glucose consumption activities. M. alba and G. pentaphyllum demonstrated the highest α-glucosidase inhibitory activity among the ethanolic extracts, with IC50 values of 134.40 and 329.97 µg/mL, respectively. Z. officinale and H. sabdariffa showed the highest percentage of glucose consumption activity in induced insulin-resistant HepG2 cells at a concentration of 50 µg/mL with 145.16 and 107.03%, respectively. The results from α-glucosidase inhibitory and glucose consumption activities were developed as an effective antihyperglycemic remedy. Among the remedies tested, the R1 remedy exhibited the highest potential for reducing blood glucose levels, with an IC50 value of 122.10 µg/mL. Therefore, the R1 remedy should be further studied for its effects on animals.

Gut Microbiome and Metabolome Alterations in Overweight or Obese Adult Population after Weight-Loss Bifidobacterium breve BBr60 Intervention: A Randomized Controlled Trial.

Probiotics, known for regulating gut microbiota, may aid those with overweight or obesity, but their mechanisms require more research. This study involved 75 overweight or obese young adults, randomly assigned to either a Bifidobacterium breve BBr60 (BBr60) group or a placebo group. Both groups received diet guidance and took either BBr60 (1 × 1010 CFU/day) or a placebo for 12 weeks. Researchers analyzed body composition, serum glucose, lipids, liver and kidney function, comprehensive metabolome, and intestinal homeostasis before and after the intervention. After 12 weeks, BBr60 significantly reduced weight and BMI compared to pretreatment levels and outperformed the placebo. The BBr60 group also showed improved blood biochemistry, with notably lower fasting blood glucose (FBG) levels than the placebo group (p < 0.05). Additionally, BBr60 influenced vital serum and fecal metabolites related to three amino acid metabolic pathways and regulated the bacteria Dialister, Klebsiella, and Bacteroides, which correlated strongly with serum metabolites. These findings indicate that BBr60 can safely and effectively regulate BMI, body weight, serum glucose, lipids, and liver function markers, which may involve BBr60's impact on key gut bacteria, which influence metabolites related to the valine, leucine, and isoleucine biosynthesis; glycine, serine, and threonine metabolism; and alanine, aspartate, and glutamate metabolism.

Growth, biochemical indexes, and intestinal microbiota response of red tilapia (Oreochromis spp.) under different densities and feeding frequencies in the land-based aquaculture tank

Red tilapia (Oreochromis spp.) has been favored by farmers in recent years because of its superior growth performance and competitive market price, but there is a lack of experimental data related to growth and health of red tilapia in land-based aquaculture tanks. In this study, red tilapia (initial weight 27.62 ± 2.43 g) was cultured with three stocking densities (30, 40, or 50 fish/m3, named 30F,40F and 50F) in the culture mode for 60 days, including two feeding frequencies (2 or 3 times/day, named 2 T and 3 T), and various growth and metabolic parameters were assessed along with the intestinal microbiome analysis. The 30 fish/m3 groups achieved the better weigh gain rate and specific growth rate (p < 0.05). The growth rate and condition factor of 40F groups were close to those of 30F groups, the yield of 40F groups were not significantly different from that of 50F groups (p > 0.05), and it had the highest survival rate (p < 0.05). The 3 T groups has a higher growth rate and yield but also has a higher rate of feed conversion (p < 0.05). The 30F groups had higher lipase levels, but a higher fat content in this group, more lipids were observed in the liver, and resulted in higher blood glucose levels (p < 0.05). The 40F groups showed healthier physiological and biochemical indicators, as its total cholesterol, lysozyme and antioxidant enzymes levels were similar to those of the 30F groups (p > 0.05), alkaline phosphatase, amylase and trypsin levels were higher than those of the other groups, and aspartate transaminase levels were the lowest (p < 0.05). The 50F groups had higher cortisol, alanine transaminase and malondialdehyde levels, lower lysozyme and digestive enzyme activities, and blood cell infiltration in the liver (p < 0.05). In terms of different feeding frequencies, the 3 T groups had higher crude protein content, catalase and total superoxide dismutase levels, wider villus width and lower blood glucose level, while the 2 T groups had higher triglyceride, total cholesterol, lysozyme, alkaline phosphatase and some digestive enzymes activities (p < 0.05). From the perspective of intestinal microbiota. The 40F groups had a better intestinal flora, and 40F-3T groups observed a better balance of flora, while 40F-2T groups had more digestion-related flora. Considering the growth rate, health status, and yield, the optimum culture condition was determined to be stocking density of 40 fish/m3, and feedings 3 times/day were recommended. The experiment provided theoretical basis and experimental data for red tilapia culture in land-based aquaculture tank mode.

7574 Diabetes Stem Cells: A Common Target for Abnormal Insulin Secretion and Insulin Resistance

Abstract Disclosure: H. Kojima: None. M. Katagi: None. J. Okano: None. T. Nakagawa: None. Diabetes is based on chronic inflammation and cannot be cured using only drugs that lower blood glucose levels. A culprit was lurking there that was hindering healing. We discovered abnormal hematopoietic stem cells that caused persistent chronic inflammation in the bone marrow of diabetic model animals. The real culprit is born after several days of hyperglycemia, never dies, and each time glycemic control deteriorates, it moves its progeny in large numbers throughout the body, fusing with unique cells in various organs and producing TNF-α from the organ cells. We have named these worst stem cells, which resemble cancer stem cells, "diabetes stem cells," and attempted to induce complete remission in diabetic model animals by eliminating them with drugs. In this study, we used streptozotocin (STZ)-induced insulin-deficient diabetes model mice. "Diabetes stem cells" were included in the CD106-positive short-term hematopoietic stem cell fraction, in which progenitor cells that play an important role in the regeneration of the thymus and peripheral tissues, and were characterized by abnormal expression of proinsulin and TNF-α. Furthermore, like cancer cells, the expression of histone deacetylases (HDACs) increased, and once the cells were born, they would not disappear. Therefore, we aimed to eliminate diabetes by administering an HDAC inhibitor and subcutaneously injecting insulin pellets to temporarily correct blood glucose levels. We treated diabetic mice with HDAC inhibitor for 8 weeks, along with several weeks of insulin therapy. Insulin aims to prevent the formation of new abnormal cells in the bone marrow and to prevent the inhibition of pancreatic islet wasting due to the forced insulin secretion caused by hyperglycemia. The combination therapy allowed the beta cells to regenerate and produce enough insulin to normalize blood glucose levels and maintain them even after treatment was discontinued. It also solved the mystery of how the abnormal cell population evades attacks from the T cells. In STZ diabetes, the supply of normal CD106-positive progenitor cells from the bone marrow for thymic regeneration was completely blocked, resulting in marked thymic atrophy. As a result, the thymus, which had lost its progenitor cells, was unable to establish an immune surveillance system to eliminate mutated cells throughout the body. In other words, the combination therapy completely broke the vicious cycle caused by atrophies in both the islet and the thymus. Moreover, when the thymus was surgically removed along with the adventitia to prevent regeneration, diabetes remission was completely inhibited, supporting the importance of thymic normalization. Diabetes is a hematopoietic stem cell disease accompanied by thymic dysfunction, and the removal of "diabetes stem cells" paves the way for the cure of diabetes. Presentation: 6/2/2024

7484 Pseudohypoglycemia In A Patient With Raynaud’s Phenomenon

Abstract Disclosure: J. Fedorko: None. P. Subarajan: None. A.P. Amblee: None. C.A. Poku: None. Background: The term ‘pseudohypoglycemia’ is used to describe the disparity between actual and measured capillary glucose and clinical presentation. It has been used to describe situations when a patient has the characteristic symptoms of low blood glucose (BG) Whipple’s triad), but the patient’s BG levels are within normal limits. Alternatively, this term can also be used to describe falsely low BG levels on finger-stick (capillary) readings in a patient with normal serum glucose levels and without the characteristic Whipple’s triad. Case: A 55-year-old female with Raynaud’s phenomenon was seen in Endocrine clinic with persistent hypoglycemia noted on finger-stick glucose readings. Her finger-stick glucose reading was 43, and was subsequently given 24 grams of glucose gel. Ten minutes later, a repeat finger stick BG was 44. She had no weakness, tremors, shakiness, vision changes, confusion, seizures, lightheadedness, dizziness, tachycardia, palpitations, nervousness, hunger, paresthesias irritability, confusion, seizures, loss of consciousness, or any other symptoms or signs of hypoglycemia. She had no such previous episodes and her fasting BG ranged from mid-70s to 80, with post-meal BG ranging from 100 to mid-100’s. Her most recent hemoglobin A1c was 5.5. She regularly experiences cyanosis of fingers consistent with Raynaud’s phenomenon, triggered by cold air in winter and air conditioners in summer. She does not take any medications for these episodes. Given the absence of classic Whipple triad and normal BG from peripheral blood draw, the patient’s low finger stick BG readings were attributable to Raynaud’s phenomenon. It is postulated to be secondary to decreased perfusion in the digital microcirculation and increased blood transit time in the fingers, resulting in a local increase in glucose consumption and thus low capillary finger stick BG levels. Simultaneously done serum glucose levels are usually normal. Conclusion: Pseudohypoglycemia can occur in patients with impaired peripheral circulation such as Raynaud’s phenomenon, acrocyanosis, peripheral vascular disease, shock, or with increased glycolysis by blood cells like in leukemia, polycythemia and rare infections like African trypanosomiasis, hyperviscosity syndromes like Waldenstrom’s and monoclonal gammopathy of undetermined significance. In patients with low finger-stick (capillary) glucose levels who do not display Whipple’s triad, and have comorbid conditions that might interfere with the BG reading, it is important for clinicians to recognize the difference between true and pseudohypoglycemia. This can be confirmed with a simultaneously done normal serum glucose level and will prevent unnecessary investigations or excessive treatment. Presentation: 6/3/2024

8227 Complex Case of Myxedema Coma Complicated by Cardiac Arrest in a Geriatric Patient with Multiple Comorbidities

Abstract Disclosure: M. Parvez: None. L. Makahleh: None. S. Nagpal: None. A. Kavarthapu: None. V. Vedantam: None. Introduction: This case report details a rare instance of cardiac arrest in a patient with myxedema coma, a severe form of hypothyroidism. It highlights the diagnostic and therapeutic challenges in managing such complex endocrine emergencies. Case Presentation: A 70-year-old female with a history of hypothyroidism, type 2 diabetes, atrial fibrillation, pacemaker implantation, and COPD presented with a 3 day history of progressive lethargy and weakness. EMS found her with critically low blood glucose level of 20. History and Examination revealed non-compliance with thyroid medication and myxedematous features including moon-like facies, periorbital edema, generalized edema, elevated JVP, and cold extremities with sluggish capillary refill. In the ER, she was hypotensive, labs showed a significantly elevated TSH level of 30.55 (0.45-4.5), free T3 level of 1.2 (2.3-4.2), free T4 level of 1.12 (0.93-1.70), high lactate, metabolic acidosis, renal impairment, and liver enzyme elevation. These findings, coupled with the clinical presentation, led to the diagnosis of myxedema coma. The patient's critical state was further complicated by distributive shock, shock liver and oliguric AKI. Management included sodium bicarbonate infusion for severe acidosis, IV hydrocortisone, IV levothyroxine, and broad-spectrum antibiotics. Amiodarone was discontinued due to its potential contribution to acute liver injury and hypothyroidism. Despite interventions, she developed acute respiratory failure, requiring intubation and norepinephrine for low mean arterial pressure. Her renal function improved with pressor support, and her lactic acidosis resolved. She recovered quickly and was subsequently extubated. After stabilization, she was switched to oral levothyroxine and discharged. Shortly after discharge, she returned again with generalized weakness, confusion, and dysuria. ER evaluation revealed lethargy, hypotension, hypoglycemia, severe metabolic acidosis, and a UTI. She tested positive for Influenza. While in the ER, she had cardiac arrest, presenting with agonal breathing and PEA. CPR was initiated, achieving ROSC after two rounds and one dose of epinephrine. She was treated again with IV levothyroxine, and IV antibiotics. She recovered well and was discharged to rehab facility with re-education on compliance. Conclusion: This case exemplifies the complexity and challenges in managing a geriatric patient with multiple comorbidities, particularly in the context of myxedema coma. The intricate interplay of endocrine, cardiovascular, respiratory, and infectious complications necessitated a multifaceted and dynamic therapeutic approach. This case underscores the importance of compliance, vigilant monitoring, prompt recognition of complicating factors, and the need for a coordinated multidisciplinary approach in managing similar cases. Presentation: 6/2/2024

Metabolomics Revealed the Effects of Momordica charantia L. Saponins on Diabetic Hyperglycemia and Wound Healing in Mice.

Momordica charantia L. saponins (MCS) may promote wound-healing properties but the underlying mechanisms are unclear. This study aimed to examine the effects and mechanisms of MCS on diabetic wounds. The results have shown that higher MCS intake lowered fasting blood glucose levels, serum lipids, and lipopolysaccharides in diabetic mice. MCS-treated diabetic mice exhibited faster wound healing than the diabetic control groups. After three days, the diabetic control groups exhibited a wound area reduction of only 19.3%, while a 39.75% reduction was observed following high-dose MCS treatment. Five potential biomarkers were screened in the metabolomics study. The results revealed that MCS mainly regulated glycerophospholipid metabolism, fructose and mannose metabolism, steroid hormone biosynthesis, pyrimidine metabolism, and the Krebs cycle, thus affecting wound healing. Overall, MCS could not only exert a hypoglycemic effect but also promote diabetic wound healing, making it a potential treatment option for diabetes-related wounds.

B-150 Chromatographic Separation and Quantitation of Human Insulin and Lispro Analog in Serum Using Liquid Chromatography High-Resolution Mass Spectrometry

Abstract Background Factitious hypoglycemia, a deliberate attempt to induce low blood glucose levels occurring secondary to the surreptitious administration of exogenous insulin, can be difficult to diagnose due to a variety of factors including the increased use of synthetic insulin analogs in clinical practice. Traditional insulin immunoassays demonstrate variable cross-reactivity with commonly prescribed insulin analogues and their metabolites, making it difficult to measure specific analogs. The development of liquid chromatography high resolution accurate mass (LC-HRAM)-mass spectrometry (MS) assays has largely circumvented the limitations of traditional immunoassays for detection and quantitation of insulin analogs. Analytical challenges remain, however, specifically in differentiating lispro, an isomeric human insulin analog formed by the transposition of proline and lysine near the C-terminal end of the B chain, from human insulin in patient samples due to the equivalent mass-to-charge ratios of their precursor ions. Methods Immunoaffinity purification of insulin from calibrators and quality control material prepared by spiking insulin-depleted serum with pharmaceutical insulin preparations, as well as patient samples, was performed using tips coupled with anti-insulin monoclonal antibody. An automated liquid handler was programmed to perform aspiration and dispense cycles. Eluate from the purification protocol was submitted for analysis using a TLX-2 multiplex LC system paired with a Thermo Scientific Q Exactive Plus mass spectrometer. Various HPLC column chemistries were evaluated, a column passivation procedure was established, and column heater temperature was optimized to identify a combination of parameters yielding the best chromatographic separation of human insulin and lispro. Additionally, parallel reaction monitoring (PRM) targeted tandem mass spectrometry (MS/MS) analysis was utilized in combination with the full scan data to increase specificity through the monitoring of fragment ions produced from human insulin and each insulin analog. Results We found that a 1000 Å Diphenyl, 2.7 µm, 2.1 x 100 mm analytical column in a column heater maintained at a temperature of 80°C allowed for human insulin and lispro to be differentiated as two chromatographically separated extracted ion chromatographic peaks (XICs) and quantified down to 2.5 mcIU/mL with near-baseline separation. Before use, the column required passivation with a high protein buffer (0.05% bovine serum albumin in 20% acetonitrile [ACN] + 0.2% acetic acid) followed by increasingly organic buffers (20% ACN + 0.2% acetic acid and 50% ACN + 0.2% acetic acid). MS/MS was used to confirm the presence of analogs detected. Conclusions The LC-HRAM-MS method described here, coupled with optimized column chemistry, column passivation, and proper column temperature control allows for chromatographic separation of human insulin and lispro. Incorporating a PRM scan into the mass spectrometry full scan method provides confirmation of the insulin detected in the XICs. The results obtained from preliminary studies suggest this method is appropriate for use to facilitate the clinical investigation of suspected factitious hypoglycemia with the ability to differentiate isomeric compounds, such as human insulin and lispro.

Management Strategies for Obese Diabetes

In recent years, there has been a growing emphasis on the relationship between obesity and diabetes. An analysis of Korean data revealed that more than 75% of diabetic patients were overweight or obese, with two-thirds having abdominal obesity. Traditional treatment goals for diabetes have primarily focused on lowering blood glucose levels to prevent and treat microvascular and macrovascular complications, which is known as the glucocentric approach. However, with the recognition of the shared pathophysiology of insulin resistance in both diabetes and obesity, a weight-centric approach has emerged, particularly beneficial for patients in whom insulin resistance is a primary driver of type 2 diabetes. Of note, the overlap of various physiological aspects in diabetic patients necessitates a multicentric approach for effective type 2 diabetes management. Recent guidelines now recommend weight loss as a primary treatment goal alongside blood glucose control for overweight and obese diabetic patients, highlighting the significance of weight management in diabetes care. Medications such as glucagon-like peptide-1 (GLP-1) receptor agonist or dual glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonist with weight-loss effects are recommended for this patient population. Ongoing research is exploring the potential of various gut hormone-based therapies, offering hope for effective weight management and improved diabetes outcomes in the growing population of obese diabetic individuals.

Combined Anti-Diabetic and Wound Healing Effects of Binahung Leaf (Basella rubra L.) and Snakehead Fish (Channa striata) Extracts in Alloxan-Induced High-Fat Diet Rats

Diabetes mellitus is a metabolic disease that continues to increase in the world. Lifestyle factors cause diabetes cases to increase uncontrollably. The development of medicines based on natural ingredients has become a subject of study for researchers throughout the world. Meanwhile, binahong leaf extract contains flavonoids and saponins, which can reduce the absorption of glucose. Snakehead fish extract containing albumin also influences the reduction of diabetic wounds. The combination of binahong and snakehead fish extract is expected to synergistically lower blood glucose levels and cure diabetic wounds. Therefore, this study aimed to determine the anti-diabetic and wound healing activity resulting from the combination of binahong leaf and snakehead fish extract in rat models of diabetes induced with alloxan and fat diet. The test animals were divided into six groups with five per group, namely normal, positive, and negative control, as well as dose 1 (snakehead fish 250 mg/kg and binahong extract 100 mg/kg), dose 2 (snakehead fish 250 mg/kg and binahong extract 300 mg/kg), and a single dose of snakehead fish extract 500 mg/kg. The experiment was conducted for 21 days by administering the test solution once a day. The results showed that administering a combination of binahong extract at a dose of 100 mg/kg and snakehead fish at a dose of 500 mg/kg significantly reduced blood glucose levels in diabetic rats (p≤0.05). Treatment using a combination of the two extracts was more effective in lowering blood sugar levels compared to a single dose of snakehead fish extract.

Chondroitin Sulfate from Halaelurus burgeri Skin Inhibits Hepatic Endoplasmic Reticulum Stress and Inflammation, and Regulates Gut Microbiota.

Previous study has demonstrated the chemical structure of chondroitin sulfate (CHS) from Halaelurus burgeri skin and its effects on insulin resistance. However, the precise impact of this phenomenon on endoplasmic reticulum (ER) stress and inflammation, which contribute to insulin resistance, remains unclear. This study is to investigate the impact of CHS on ER stress, inflammatory response and signaling, and gut microbiota in high-fat diet (HFD)-fed mice. HFD-fed C57BL/6J mice receive dietary gavage intervention of CHS for 18 weeks. Blood, liver tissue, and feces are harvested for further investigation. Results show that CHS inhibits ER stress, accompanied by lowered blood glucose, nitric oxide (NO), reactive oxygen (ROS), and free fatty acids (FFA) levels, and increases hepatic glycogen accumulation. Moreover, hepatic inflammation is improved by CHS treatment via inactivation of Toll-like receptor 4 (TLR4) signaling and its downstream c-jun N-terminal kinase (JNK) and nuclear factor kappa B (NFκB) pathways. Additionally, CHS regulates gut microbiota, particularly the decline in the Firmicutes to Bacteroidetes ratio. CHS also lowers fecal lipopolysaccharide and elevates several fecal short chain fatty acids. These findings suggest that CHS from H. burgeri skin may be an alternative functional food supplement for anti-ER stress, anti-inflammtion, and regulation of gut microbiota.