Elevated Blood Glucose Research Articles

The Relationship Between Lycopene and Metabolic Diseases

Background: Metabolic syndrome, obesity, and type 2 diabetes are closely related. They are characterized by chronic inflammation and oxidative stress. Obesity is the most important risk factor for metabolic syndrome and type 2 diabetes. Metabolic syndrome is characterized by insulin resistance and elevated blood glucose levels, among other conditions. These disorders contribute to the development of type 2 diabetes, which can exacerbate other metabolic problems. Methods: Numerous studies indicate that diet and nutrients can have a major impact on preventing and treating these conditions. One such ingredient is lycopene. It is a naturally occurring carotenoid with a unique chemical structure. It exhibits strong antioxidant and anti-inflammatory properties due to its conjugated double bonds and its ability to neutralize reactive oxygen species. Its properties make lycopene indirectly affect many cellular processes. The article presents studies in animal models and humans on the activity of this carotenoid in metabolic problems. Results: The findings suggest that lycopene’s antioxidant and anti-inflammatory activities make it a promising candidate for the prevention and treatment of metabolic syndrome, obesity, and type 2 diabetes. Conclusions: This review underscores the potential of lycopene as a beneficial dietary supplement in improving metabolic health and reducing the risk of associated chronic diseases. The conditions described are population diseases, so research into compounds with properties such as lycopene is growing in popularity.

Impact of systemic diseases on oral health and facial surgery outcomes

Systemic diseases have a profound influence on oral health and maxillofacial surgical outcomes, presenting challenges that require comprehensive management. Diabetes mellitus is a prominent example, with its impact on periodontal health and healing processes being well-established. Elevated blood glucose levels in diabetic patients impair immune response, reduce collagen synthesis, and delay wound healing, increasing the risk of periodontitis and postoperative complications following surgical interventions such as dental implants. Similarly, cardiovascular diseases exacerbate the inflammatory response linked to periodontal disease, potentially worsening both oral health and systemic conditions, thus complicating the recovery process after maxillofacial surgery. These patients often face heightened risks of infections and slower healing, partly due to the frequent use of anticoagulant medications, which can interfere with surgical procedures. Immunocompromised individuals, such as those with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) or undergoing chemotherapy, also experience significant oral health challenges, including higher susceptibility to oral infections and delayed tissue repair. Reduced immune function and mucosal integrity make it difficult for these patients to recover effectively after maxillofacial surgery, increasing the risk of complications such as infection and wound dehiscence. Moreover, osteoporosis, a systemic condition characterized by reduced bone density, affects the success of dental implants and bone grafting procedures. The decreased bone quality in osteoporotic patients compromises the ability to achieve stable osseointegration, leading to higher implant failure rates and additional surgical challenges. Addressing these complex interactions between systemic health and oral conditions requires an interdisciplinary approach, integrating medical and dental care to enhance treatment outcomes. Proper management of systemic diseases, along with individualized dental and surgical protocols, is essential to improving the prognosis for patients with concurrent systemic and oral health issues.

The relationship between daily blood glucose fluctuation and readmission in patients with acute coronary syndrome

Abstract Background Although the comprehensive diagnos and treatment of patients with acute coronary syndrome(ACS) has been greatly improved,the morbidity and mortality are still high. Previous literature has reported that about 70-75% of patients diagnosed with acute coronary syndrome have abnormal blood glucose metabolism1,and there existed gender differences. At present, most research results showed that elevated blood glucose is related to the prognosis of ACS. However, further intervention studies indicated that simply strengthen the reducement of blood glucose did not improve prognosis of these patients2. Glucose fluctuations, another dimension of blood glucose, reflect acute changes in blood glucose. However, there are few studies on the effect of blood glucose fluctuation on the prognosis of patients with ACS. Purpose This study aimed to explore the relationship between seven daily fluctuations of blood glucose and readmission in ACS patients. Methods In this study, a total of 664 patients admitted to our University from January 1, 2019 to December 31, 2019 were included and their blood glucose was monitored seven times a day during their hospitalization. The coefficient of variation of blood glucose (CV) was calculated from the results of seven daily blood glucose monitoring to represent the daily fluctuation of blood glucose. Univariate and multivariate regression analyses were performed to determine whether CV was an independent risk factor for re-hospitalization. In addition, the area under the curve (AUC) was used to evaluate the predictive efficacy of CV for outcome events. Finally, we performed a subgroup analysis based on gender and diabetes status to assess the association between CV and readmission in each subgroup. Results After a median follow-up of 21 months, the rate of readmission was 38.4%. Unstable angina pectoris (71.4%) and heart failure (16.4%) were the most common reasons for readmission. Patients with greater CV levels typically exhibited lower fasting blood glucose, higher post breakfast blood glucose, and higher admission blood glucose.The readmission rate increased with the increasing blood glucose variability after the cox regression analysis. Moreover, independent of glycated hemoglobin,CV could predict the risk of readmission in patients with ACS.When using 26.66% as the cutoff point of CV, the study population was divided into two groups and showed a significant differentiation for rehospitalization.In subgroup analysis, there was no significant association between seven daily blood glucose fluctuations and readmission in female and non-diabetes mellitus patients with acute coronary syndrome. Conclusions Besides some normal blood glucose index,seven daily fluctuations of blood glucose was associated with readmission in ACS patients. ACS patients who were male and combined with diabetes were more likely to be readmitted if their CV levels were greater.

The Potential Role of Beetroot Juice in Hyperglycemia Management: A Review of Mechanisms and Clinical Outcomes

Hyperglycemia, characterized by elevated blood glucose levels, is a significant health concern that affects millions of individuals worldwide. It has been associated with long-term complications affecting the cardiovascular, renal, and nervous systems. Beetroot juice (BRJ), rich in nitrates, betalains, and antioxidants, has gained attention for its potential role in mitigating hyperglycemia and improving insulin sensitivity. This review evaluates the available scientific evidence on the hypoglycemic effects of beetroot juice, explores its proposed mechanisms of action, and discusses its potential as a complementary therapy for diabetes management. By analyzing studies, we found that beetroot juice may help manage hyperglycemia by enhancing insulin sensitivity through its nitrate content, which converts to nitric oxide. Clinical evidence indicates it may lower fasting blood glucose and improve glycated hemoglobin A1c (HbA1c) levels, though results vary. While beetroot juice shows promise as a supplementary treatment for hyperglycemia, more research is needed to determine the optimal dosage, long-term effects, and interactions with other diabetes management strategies.

MELAS Presenting as Bilateral Symmetric Occipital and Temporal Cortices Lesions: A Case Report and Literature Review.

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS) is one of the most common maternally inherited mitochondrial diseases. The stroke-like episode affecting the cortical cortex is the hallmark of MELAS; however, it rarely presents as simultaneously bilateral symmetric cortices lesions. We reported a case of MELAS in a 46-year-old female patient with bilateral symmetric occipital and internal temporal cortices involvements on brain magnetic resonance imaging (MRI). A literature review of MELAS patients and a retrospective analysis were performed. She had a family history of diabetes. Although she denied a history of diabetes, elevated blood glucose was noted after admission, and diabetes was diagnosed. Laboratory examination revealed elevated lactate acid and creatine kinase levels in blood. Cranial computed tomography (CT) image demonstrated basal ganglia calcification, as well as subtle decreased attenuation in bilateral symmetric occipital and internal temporal cortices. Brain magnetic resonance imaging (MRI) demonstrated symmetric gyriform hyperintensity in bilateral occipital lobes and internal temporal lobes in both grey and white matter on fluid-attenuated inversion recovery (FLAIR) images with restricted diffusion on diffusion weighted images (DWI). A genetic test revealed a point mutation in the mtDNA(3243A > G) by blood examination. Literature review showed that there were 231 eligible patients with MELAS identified from 212 published papers. Symmetric cortical involvements were seen in 15 (6.5%) patients on brain MRI. MELAS should be considered as a potential diagnosis in the patients with bilateral symmetric stroke-like cortices lesions.

Dynamics of Blood Lipids Before, During, and After Diurnal Fasting in Inactive Men: Quasi-Experimental Study.

There is a lack of investigation into the dynamics of blood lipids before, during, and after diurnal fasting, especially in inactive men. This study determined dynamic changes in blood lipids in inactive men before, during, and after they underwent diurnal fasting. A total of 44 young men aged a mean 27.6 (SD 5.8) years were recruited to evaluate their habitual physical activity and diet using a questionnaire developed for this study. Body composition was evaluated using a bioelectrical impedance analysis machine (Tanita BC-980). An 8-ml blood sample was collected to evaluate blood lipids and glucose. All measurements were taken 2-3 days before Ramadan, during Ramadan (at week 2 and week 3), and 1 month after Ramadan. A 1-way repeated measures ANOVA was used to compare the measured variables before, during, and after the month of Ramadan. When a significant difference was found, post hoc testing was used. Differences were considered significant at P<.05. There was a significant reduction in low-density lipoprotein during Ramadan compared to before and after Ramadan (83.49 mg/dl at week 3 vs 93.11 mg/dl before Ramadan [P=.02] and 101.59 mg/dl after Ramadan [P=.007]). There were significant elevations in fasting blood glucose (74.60 mmol/L before Ramadan vs 81.52 mmol/L at week 3 [P=.03] and 86.51 mmol/L after Ramadan [P=.01]) and blood pressure (109 mm Hg before Ramadan vs 114 mm Hg after Ramadan; P=.02) reported during and even after the month of Ramadan, although both fasting blood glucose and blood pressure were within normal levels. Ramadan fasting could be an independent factor in reducing low-density lipoprotein. Further investigations are encouraged to clarify the impact of diurnal fasting on blood lipids in people with special conditions.

The relationship between metabolic syndrome and intestinal microbiota: a review of the literature

Metabolic syndrome is a pathological condition that includes obesity, elevated blood glucose levels, hypertension and dyslipidemia. This comorbid condition is a global problem of our time. According to the INTERHEART study, metabolic syndrome occurs in more than 26% of the world’s population. In the Russian Federation, 40% of residents have 2 components of the metabolic syndrome, 11% have 3 or more of its components. In addition to well-known risk factors for the development of metabolic syndrome, such as genetic predisposition, overeating, physical inactivity, hormonal disorders and others, in recent years, increasing attention has been paid to the study of the intestinal microbiota and its effect on the metabolic syndrome. For example, a comparison of the intestinal microbiota of people with normal BMI and obesity showed different species of microorganisms inhabiting our gastrointestinal tract. Analyzing patients diagnosed with type 2 diabetes mellitus we can note a decrease in butyrate-producing bacteria (Faecalibacterium prausnitzii and Roseburia) that modify insulin sensitivity to body tissues. Some species of Lactobacillus are able to normalize lipid metabolism, reduce the number of adipocytes, reduce the absorption of cholesterol by converting it into insoluble coprostanol. In patients with arterial hypertension there is dysbacteriosis of I and II degree, in arterial hypertension with metabolic syndrome – absence of dysbacteriosis of I degree and presence of dysbacteriosis of II and III degrees, with prevalence of opportunistic forms. Understanding the role of intestinal microbiota becomes a key element not only in diagnosis, but also in the development of effective treatment methods and their application in complex treatment of metabolic syndrome.

Asiaticoside improves diabetic nephropathy by reducing inflammation, oxidative stress, and fibrosis: An in vitro and in vivo study

BACKGROUND Diabetic nephropathy (DN) is a severe microvascular complication of diabetes characterized by inflammation, oxidative stress, and renal fibrosis. Asiaticoside (AC) exhibits anti-inflammatory, antioxidant, and anti-fibrotic properties, suggesting potential therapeutic benefits for DN. This study aimed to investigate the protective effects of AC against DN and elucidate the underlying mechanisms involving the nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) antioxidant pathway. AIM To investigate the renoprotective effects of AC against DN and elucidate the role of the NRF2/HO-1 pathway. METHODS The effects of AC on high glucose (HG)-induced proliferation, inflammation, oxidative stress, and fibrosis were evaluated in rat glomerular mesangial cells (HBZY-1) in vitro . A streptozotocin-induced DN rat model was established to assess the in vivo impact of AC on renal injury, inflammation, oxidative stress, and fibrosis. The involvement of the NRF2/HO-1 pathway was examined using pharmacological inhibition studies in the cell model. RESULTS AC inhibited HG-induced HBZY-1 cell proliferation and significantly improved various indicators of DN in rats, including reduced body weight, and elevated blood glucose, serum creatinine, blood urea nitrogen, and 24-h urine protein. Both in vitro and in vivo studies demonstrated that AC decreased inflammation and oxidative stress by reducing interleukin (IL)-6, IL-8, tumor necrosis factor-alpha, reactive oxygen species, and malondialdehyde levels while increasing superoxide dismutase activity. Additionally, AC suppressed the expression of fibrogenic markers such as collagen I, collagen IV, and fibronectin. AC activated NRF2 expression in the nucleus and increased HO-1 and NAD(P)H dehydrogenase (Quinone) 1 protein expression in renal tissues and HG-induced HBZY-1 cells. CONCLUSION AC improves DN by reducing inflammation, oxidative stress, and fibrosis through the activation of the NRF2/HO-1 signaling pathway. These findings not only highlight AC as a promising therapeutic candidate for DN but also underscore the potential of targeting the NRF2/HO-1 pathway in developing novel treatments for other chronic kidney diseases characterized by oxidative stress and inflammation.

Identification of Candida albicans in the Urine of Type 2 Diabetes Mellitus Patiens at Puskesmas Jaten 2, Karanganyar Regency

Background: Candida albicans is an opportunistic fungus that thrives in environments with high glucose concentrations, which makes patients with Diabetes Mellitus (DM) especially vulnerable to infection. Elevated blood glucose levels in DM can lead to glycosuria, providing a rich nutrient source for fungal growth. This research is critical because there is a lack of specific studies focusing on fungal infections in diabetic patients in Indonesia, despite the increasing prevalence of DM. This research provides a new perspective by highlighting a local diabetic population that has not been extensively studied before. Objective: The objective of this study is to identify the presence of Candida albicans in the urine of Type 2 Diabetes Mellitus patients at Puskesmas Jaten 2 in Karanganyar Regency. Materials and Methods: This descriptive study included 20 urine samples from Type 2 Diabetes Mellitus patients. The inclusion criteria were fasting blood glucose levels of 200 mg/dl or higher, and all patients were enrolled in the chronic disease management program (Prolanis) at Puskesmas Jaten 2. The samples were collected and examined macroscopically in February 2024 to detect the presence of Candida albicans. Results: The results showed that Candida albicans was found in 6 out of 20 urine samples (30%), while the fungus was not detected in 14 samples (70%). The majority of positive cases occurred in patients aged 50 and older, suggesting an age-related susceptibility to fungal infection in this population. Patients with higher glucose levels also showed a greater tendency for Candida growth. Conclusions: Based on the results of this study, it can be concluded that Candida albicans is present in the urine of Type 2 Diabetes Mellitus patients at Puskesmas Jaten 2, with a notable prevalence of 30%. This finding highlights an increased susceptibility to fungal infections in older patients and those with elevated glucose levels, suggesting the need for careful monitoring and potential intervention in this population. Further studies with larger sample sizes are suggested to confirm these results and explore additional preventive measures.

Toxic Metals Impact Gut Microbiota and Metabolic Risk in Five African-Origin Populations.

Exposure to toxic metals impacts obesity and type 2 diabetes (T2DM) risk. Yet, the underlying mechanisms remain largely unknown. Gut microbiota has been strongly associated with progression of cardiometabolic risk. To determine whether high metal exposures and gut dysbiosis interact to promote metabolic dysregulation and cardiometabolic risk, we assessed relationships between these factors. We analyzed cross-sectional associations between arsenic, lead, mercury, cadmium, and cardiometabolic health markers in 178 randomly selected African-origin adults (52% female, 51% obese, mean age=43.0±6.4 years) from Ghana, South Africa, Seychelles, Jamaica, and USA. Metal levels were dichotomized to high or low at the median level of each metal. We analyzed associations between gut microbiome taxa, metal levels, clinical measures (BMI, fasting blood glucose, and blood pressure) and diagnoses (hypertension, obesity, and diabetes status). High vs. low lead and arsenic exposures had a significant effect on beta diversity (p <0.05). 71 taxa were associated with high lead levels: 30 with elevated BMI, 22 with T2DM, and 23 with elevated fasting blood glucose (p<0.05). 115 taxa were associated with high arsenic levels: 32 with elevated BMI, 33 with T2DM, and 26 with elevated blood glucose (p<0.05). Of the taxa associated with high lead and arsenic exposure and either elevated BMI or fasting blood glucose, porphyrin metabolism was the most enriched metabolic pathway. These data collectively provide the first findings in a human study that the gut microbiome may drive the association between lead and arsenic exposure and obesity and T2DM risk.

HUBUNGAN SENAM PROLANIS TERHADAP PENURUNAN KADAR GULA DARAH SEWAKTU PADA PASIEN DIABETES MELLITUS TIPE 2 DI PUSKESMAS SEI LEKOP

Background : Type 2 diabetes mellitus is a chronic metabolic disease characterized by elevated blood glucose levels in the body due to insulin resistance or inadequate insulin production. The purpose of this study is to investigatethe relationship between physical activity and blood sugar levels in patients with type 2 Diabetes Mellitus who participated in the PROLANIS program at the Sei Lekop Community Health Center in 2023. Methods : This study is an observational research with an analytical cohort design. Data collection was obtained from the medical records of patients with type 2 diabetes mellitus who are registered under BPJS. The data analysis methods include univariate analysis and bivariate analysis, with a standard error of estimate set at 5% or 0.05 Results : The results of the Wilcoxon test showed that PROLANIS exercise had a relationship with reducing blood sugar levels during type 2 diabetes mellitus patients at the Sei Lekop Community Health Center in 2023. The results of the Wilcoxon test were p = 0.001. Conclusion : Based on the results of this study, it can be concluded that there is a relationship between PROLANIS exercise and random blood sugar levels in patients with type 2 diabetes mellitus at Sei Lekop Health Center in 2023 Keywords : Diabetes Mellitus, Blood Glucose Levels, and PROLANIS Exercise.

Analysis of the Setomimycin Biosynthetic Gene Cluster from Streptomyces nojiriensis JCM3382 and Evaluation of Its α-Glucosidase Inhibitory Activity Using Molecular Docking and Molecular Dynamics Simulations.

The formation of atroposelective biaryl compounds in plants and fungi is well understood; however, polyketide aglycone synthesis and dimerization in bacteria remain unclear. Thus, the biosynthetic gene cluster (BGC) responsible for antibacterial setomimycin production from Streptomyces nojiriensis JCM3382 was examined in comparison with the BGCs of spectomycin, julichromes, lincolnenins, and huanglongmycin. The setomimycin BGC includes post-polyketide synthase (PKS) assembly/cycling enzymes StmD (C-9 ketoreductase), StmE (aromatase), and StmF (thioesterase) as key components. The heterodimeric TcmI-like cyclases StmH and StmK are proposed to aid in forming the setomimycin monomer. In addition, StmI (P-450) is predicted to catalyze the biaryl coupling of two monomeric setomimycin units, with StmM (ferredoxin) specific to the setomimycin BGC. The roles of StmL and StmN, part of the nuclear transport factor 2 (NTF-2)-like protein family and unique to setomimycin BGCs, could particularly interest biochemists and combinatorial biologists. α-Glucosidase, a key enzyme in type 2 diabetes, hydrolyzes carbohydrates into glucose, thereby elevating blood glucose levels. This study aimed to assess the α-glucosidase inhibitory activity of EtOAc extracts of JCM 3382 and setomimycin. The JCM 3382 EtOAc extract and setomimycin exhibited greater potency than the standard inhibitor, acarbose, with IC50 values of 285.14 ± 2.04 μg/mL and 231.26 ± 0.41 μM, respectively. Molecular docking demonstrated two hydrogen bonds with maltase-glucoamylase chain A residues Thr205 and Lys480 (binding energy = -6.8 kcal·mol-1), two π-π interactions with Trp406 and Phe450, and one π-cation interaction with Asp542. Residue-energy analysis highlighted Trp406 and Phe450 as key in setomimycin's binding to maltase-glucoamylase. These findings suggest that setomimycin is a promising candidate for further enzymological research and potential antidiabetic therapy.

12614 Induction Of Gpt2 During Metabolic Stress Is Associated With Reduced Incretin Responsiveness And Decreased β-cell Resilience To Metabolic Stress

Abstract Disclosure: S. Sen: None. A.V. Rozo: None. M. Haemmerle: None. J. Roman: None. A.V. Scota: None. J.A. Christine: None. E.M. Morrow: None. S.A. Tersey: None. C.B. Newgard: None. N.M. Doliba: None. D.A. Stoffers: None. Elevated blood glucose and lipids compromise pancreatic β-cell survival and function, but the underlying molecular mechanisms are ill-understood. We previously found that mitochondrial glutamate-pyruvate transaminase 2 (GPT2) is induced by ER and glucolipotoxic (GLT) stress. Here, we find that islets from type 2 diabetic donors exhibited markedly elevated levels of GPT2 compared to those of non-diabetic donors. GLT stress induced GPT2 in MIN6 cells, primary murine, and human non-diabetic islets. We generated β-cell specific Gpt2-deficient (Gpt2βKO) and Gpt2 floxed control (Gpt2f/f) mice to study the in vivo role of Gpt2 in β-cells. Intraperitoneal (IP) glucose tolerance (GTT) of Gpt2βKO mice was minimally affected on chow diet; therefore, we placed Gpt2f/f and Gpt2βKO mice on 45 kcal% high-fat and matched control diets. At 1 week, HFD-fed Gpt2βKO mice exhibited reduced β-cell death, measured by droplet digital PCR of circulating unmethylated preproinsulin DNA and by TUNEL analysis. Over 37 weeks, HFD-fed Gpt2βKO mice showed lower random blood glucose similar to Gpt2f/f mice under a control diet. While IPGTT was modestly improved in HFD-fed Gpt2βKO compared to HFD-fed Gpt2f/f mice, insulin secretion was not enhanced. Remarkably, oral glucose administration markedly improved glucose tolerance and enhanced insulin secretion of control- and HFD-fed Gpt2βKO mice compared to Gpt2f/f mice, while GLP-1 and GIP levels were unaltered, suggesting enhanced incretin action on the β-cell. Indeed, Gpt2βKO mice (under both control and high-fat diets) were more responsive to administration of GLP1R agonist Exendin-4 (Ex4) than Gpt2f/f mice. Isolated Gpt2βKO islets secreted more insulin when stimulated by Ex4 and GIP but not acetylcholine. Perifusion assay revealed markedly enhanced insulin secretion of Gpt2βKO islets in response to a stepwise exposure to increasing Ex4 doses, indicating enhanced incretin sensitivity. Metabolic flux analysis of Gpt2βKO and Gpt2f/f islets exposed to uniformly labeled glucose (U-13C glucose) under low (2.8mM), high (12mM) glucose, and high glucose with Ex4 conditions revealed elevated levels of key TCA cycle intermediates in Gpt2βKO islets under high glucose and high glucose+Ex4 conditions, indicating increased TCA cycle flux that likely enhances insulin secretion. Gpt2βKO mice had higher β cell mass than Gpt2f/f littermates under control diet and HFD feeding. Bulk islet RNA-seq from Gpt2f/f and Gpt2βKO mice exposed to GLT revealed upregulation of genes responsible for cell cycle and division pathways and downregulation of apoptosis and ER stress genes, consistent with enhanced survival of Gpt2βKO islets under stress conditions. In summary, β-cell GPT2 is increased during metabolic stress and T2D. Its deficiency induces a metabolic reprogramming that improves incretin sensitivity and protects pancreatic β-cells from metabolic stress. Presentation: 6/2/2024

12201 Ketogenic-diet As A Trigger Of First Episode Diabetic Ketoacidosis In A Woman Living With Type 1 Diabetes Mellitus

Abstract Disclosure: M.E. Chacon Cruz: None. A.N. Gonzalez Bossolo: None. G.J. Mora Osoria: None. A number of dietary patterns have been proposed as an effective method for weight reduction. A keto diet is a strict low-carbohydrate and high-fat diet. The reduction in carbohydrates enables the body to rely on fat as a predominant energy source leading to a state of ketosis. However, a serious but rare complication of the ketogenic diet is ketoacidosis associated with low carbohydrate intake, which should be cautiously monitored in people with a predisposition to the condition, such patient with diabetes mellitus type 1. We report the case of a female patient living with type 1 diabetes mellitus female who developed her first episodes of diabetic ketoacidosis (DKA) as the following the course of ketogenic diet. A 53 y/o Female patient with past medical history diabetes mellitus type 1 and pernicious anemia went emergency department complaining pelvic pain associated with weakness, nausea and vomiting for about 1 day of evolution. Patient also refers that during the past 2 weeks she has been doing a detox and taking some herbal and tea. Other physical examinations were unremarkable except for moderate dehydration. The initial testing revealed patients meet criteria for severe diabetes ketoacidosis (DKA) with a pH: 7.04, CO2 15, serum central bicarbonate in 6 mmol/L and elevated blood glucose in 504 mg/dl and positive urine and serum ketones, C-Peptide less than 0.02 ng/ml. and glycosylated hemoglobin in 8.25%. She was admitted to the intensive care unit and treated with intravenous saline, intravenous insulin infusion, and electrolyte repletion. Blood glucose levels and metabolic acidosis improved. After DKA resolved patient refers that week started with Keto-diet and was restricting carbohydrates. Patient was discharge home with multiple injection insulin and followed by Endocrinologist services in the external clinic for a follow up. This case illustrates the challenges and the importance of dietary history providing clues to the diagnosis. If we had never asked her about her diet, we would not have found the reason that brought her to the DKA. This case demonstrates the development of DKA following ketogenic diet in a patient with type 1 diabetes. It is important for physicians to be aware of this rare potential complication of ketogenic diet which is infrequently reported in literature. Therefore, physicians should be cognizant of the complications and risks, and benefits of the ketogenic diet. Risks and benefits of the ketogenic diet should be discussed with patients before initiation of this diet. The patient was followed in an outpatient clinic with Endocrinologist service for evaluation for an insulin pump. Presentation: 6/1/2024

7657 Single Cell RNAseq And Omics Revealed Novel Role Of Liver Group 2 Innate Lymphocytes In Regulation Of Hepatic Gluconeogenesis

Abstract Disclosure: M. Fujimoto: None. T. Tanaka: None. Background: The liver is an important organ that maintains homeostasis of glucose metabolism in the body through gluconeogenesis. It is considered that gluconeogenesis in hepatocytes is particularly active around the portal vein. However, since excessive gluconeogenesis aggravates the pathogenesis of diabetes, it is necessary to elucidate the regulatory mechanism of gluconeogenesis. Although several studies revealed that group 2 innate lymphocytes (ILC2) contribute to blood glucose maintenance in adipose and pancreatic tissues, the contribution of liver ILC2s to glucose metabolism is unknown. This study aims to elucidate the contribution of liver ILC2s to glucose metabolism and its molecular mechanism. Methods: We administered IL-33, an endogenous ILC2 activator, to BALB/c and NSG mice, and measured fasting blood glucose levels and blood glucose elevation by gluconeogenic substrate pyruvate, and blood glucose levels in liver ILC2s transplanted NSG mice. Molecular mechanisms were analyzed by single cell-RNAseq (scRNA-seq) of liver ILC2s, lung ILC2s and hepatocytes, GATA3 transcription complex, ATAC-seq, GATA3-ChIP-seq, and Metabolomics of primary hepatocytes. Results: IL-33 strongly induced IL-13 production by liver ILC2s, lowered fasting blood glucose, and suppressed pyruvate-induced glucose elevation; these effects were not observed in NSG mice lacking immune cells including ILC2s. A hypoglycemic effect of IL-33 was observed in liver ILC2-transplanted NSG mice, but not in mice transplanted with IL-13-deficient ILC2s, suggesting the effect is IL-13-dependent. scRNA-seq results showed that liver ILC2s showed higher IL-13 expression than lung ILC2s, and IL-33 treatment suppressed the expression of gluconeogenic enzymes in the G6pc-high hepatocyte population. The interaction between liver ILC2s and G6pc-high hepatocytes via IL-13/IL-13 receptors was also demonstrated; co-culture of ILC2s with primary cultured hepatocytes resulted in decreased expression of hepatocyte gluconeogenic enzymes and accumulation of multiple gluconeogenic substrates. In addition, IL-13 neutralizing antibody treatment attenuated the effect of the decreased expression of gluconeogenic enzymes in hepatocytes. Transcription factor GATA3 complex analysis and GATA3-ChIPseq suggested binding of GATA3 of the AP-1 family (JunB) in liver ILC2s. Overexpression, knockdown, and scRNA-seq results suggest that AP1 may act in a GATA3-repressive manner in liver ILC2s. Discussion The functional characteristics of liver ILC2s, hepatocyte heterogeneity and subcluster were demonstrated by scRNA-seq, suggesting that liver ILC2s may directly suppress hepatocyte gluconeogenesis via IL-13. This may play a novel role in the homeostasis of hepatic glucose metabolism. Presentation: 6/1/2024

8243 Euglycemic Diabetic Ketoacidosis Unveiled: Delayed Presentation and Complications of SGLT-2 Inhibitor Therapy in a Multimorbid Patient - A Case Report

Abstract Disclosure: T. Amin: None. A.K. Bala: None. M.A. Jones: None. M.S. Akula: None. K. Chalasani: None. M. Patel: None. J. Cheng: None. Introduction: Normal serum glucose levels (&amp;lt;200 mg/dL) in euglycemic diabetic ketoacidosis (EDKA) can complicate the typical clinical presentation of diabetic ketoacidosis (DKA), posing a diagnostic challenge. SGLT-2 inhibitors, a class of antihyperglycemic drugs, have been rarely but significantly associated with EDKA. These inhibitors enhance renal glucose clearance by preventing glucose reabsorption via sodium-glucose cotransport. The increased renal clearance may contribute to the euglycemic picture, potentially leading to an underestimation of required insulin dosage, thereby precipitating ketoacidosis in EDKA. Although the mechanisms of EDKA are not fully understood, the association with SGLT-2 inhibitors is becoming increasingly evident. Case A 53-year-old male with a medical history of type 2 Diabetes Mellitus, coronary artery disease, chronic kidney disease, hyperlipidemia, was admitted to the trauma bay after a fall. Medications included empagliflozin, metformin, aspirin, amlodipine, spironolactone, and carvedilol. Upon presentation, he had a brief loss of consciousness, complained of headache and chest pain, and was found to have an epidural hematoma with regional brain compression on the CT head. Admission labs showed a blood glucose level of 172, an unremarkable anion gap, and normal renal and liver function tests. Due to traumatic brain injury, he was admitted to the ICU for neurological monitoring. Despite remaining neurologically stable, he developed hypoxia, necessitating intubation. After successful extubation, he exhibited worsening metabolic acidosis on the fourth day, with an elevated anion gap of 22 and a blood glucose level of 174. Arterial blood gas analysis revealed a pH of 7.3 (and elevated beta-hydroxybutyrate (&amp;gt;4), while lactic acid levels remained normal. Urine analysis showed elevated blood glucose (&amp;gt;1000) and ketones (&amp;gt;40). Home medications, metformin, and empagliflozin were appropriately withheld, but euglycemic DKA attributed to empagliflozin was diagnosed. Treatment included intravenous fluid resuscitation and insulin infusion, leading to resolution of acidosis and improved mentation within 24 hours. Conclusion: EDKA is a diagnosis of exclusion often overlooked in ICU patients due to diverse causes of high-anion gap metabolic acidosis. Typical cases occur while the patient is using the drug, often associated with triggers like illness, alcohol use, surgery, or starvation. SGLT2 inhibitors, such as empagliflozin, with a half-life of 12.4 hours, are expected to clear the bloodstream in about 48 hours, yet this case suggests an association with EDKA both during use and after drug cessation. This delayed presentation highlights additional risk considerations associated with SGLT2 inhibitors, guiding future clinical diagnoses of EDKA even several days post discontinuation. Presentation: 6/3/2024

9179 Type 2 Diabetes Alters Metabolic Fuel Selection During Intermittent Fasting

Abstract Disclosure: M.O. Conn: None. D.M. Marko: None. J.D. Schertzer: None. Type 2 Diabetes Alters Metabolic Fuel Selection During Intermittent Fasting Diabetes is characterized by elevated blood glucose resulting from defective insulin secretion and/or insulin resistance. Intermittent fasting, a popular weight loss strategy involving periodic reduction of caloric intake, can improve glycemia. Fasting shifts metabolism from carbohydrates to free fatty acids and ketones. However, high blood insulin can inhibit lipolysis and alter metabolic substrate selection in prediabetes, resulting in muscle catabolism to maintain energy homeostasis. Clinical studies have observed a significant decrease in muscle mass in subjects with obesity and diabetes. Our research aims to characterize lean mass versus fat loss after intermittent fasting in a mouse model of obesity and type 2 diabetes (T2D) and investigate the role of muscle alanine catabolism. We hypothesized that intermittent fasting would promote less lipolysis and more muscle alanine catabolism, causing more muscle loss in diabetic mice than controls. We compared male db/db mice manifesting obesity, hyperglycemia, and hyperinsulinemia to age-matched db/+ (control) mice. Our lab established a 5:2 repeated fasting protocol of ad-libitum access to food for 5 days a week and 2 days of fasting on non-consecutive days. Blood glucose was monitored weekly in fed and fasted states to assess glycemic control. While intermittent fasting lowered fasted blood glucose in both groups, no significant body weight or metabolic tissue mass changes were observed. Metabolic cage data demonstrated increased reliance on fat-based substrates for energy in control mice that underwent intermittent fasting during feeding and fasting periods. Diabetic mice did not show significant changes in the fasted state, but intermittent fasting led to increased reliance on carbohydrate oxidation during re-feeding periods, indicating impaired metabolic flexibility. After 10 weeks, the mice were sacrificed, and metabolic tissue histology (adipose, liver, skeletal muscle) will be performed. We will also analyze serum markers (alanine, fatty acids, glycerol, glucose, insulin) and the activity of the metabolic enzyme alanine transaminase (ALT) in the muscle and liver. This experiment will improve our understanding of how lipolysis and protein breakdown in muscle regulate lean mass versus fat mass loss in obesity and T2D, leading to more effective tailoring of fasting to specific populations. Presentation: 6/3/2024

Comorbidity profiles among sputum-positive tuberculosis patients in Cameroon.

Comorbid non-communicable diseases (NCDs) like diabetes, cardiovascular diseases (CVD), kidney diseases, and hypertension, could have implications for tuberculosis (TB) treatment management and increase the disease burden amongst active TB patients. This cross-sectional study aimed at profiling comorbidities amongst sputum-positive TB patients in the South West and Littoral regions of Cameroon and was relevant for improving disease management and public health interventions. Diabetes was defined by elevated blood glucose, body mass index (underweight: <18.5 kg/m2, normal: 18.5-<25.0 kg/m2, overweight: 25-<30 kg/m2 and obese: ≥30.0 kg/m2) and hypertension by elevated blood pressure levels (i.e., systolic ≥130 mmHg or diastolic ≥80 mmHg). Socio-demographic and clinical data were collected using case report forms. Descriptive analysis was performed, bivariate logistic regression analysis was computed with at least one comorbidity as the dependent variable (global model) and a multivariable logistic regression analysis was done to provide adjusted odds ratios (final model). The covariate with the highest p-value was removed until p < 0.25 cut-off, using R software version 4.3.1. p-value <0.05 at 95% confidence interval was considered statistically significant. Five hundred and forty-nine sputum-positive microscopically confirmed active TB patients were enrolled into this study. Two-thirds (65.8%) of the total patients were male. Overall, 56 sputum-positive TB patients had at least one non-communicable disease, thus a prevalence of 10.2% (95% CI = 7.9-13.0). The most frequently recorded NCD was diabetes 4.4% (95% CI = 3.1-6.7) followed by kidney disease 2% (95% CI = 1.1-3.6), hypertension 0.9% (95% CI = 0.4-2.2), and CVD 0.91% (95% CI = 0.4-2.2). Three TB patients (0.6%) had all four comorbidities examined. Age group (p < 0.001), and level of education (p = 0.049) were factors significantly associated with having at least one comorbidity. Our findings showed that diabetes was significantly the most prevalent comorbid NCD amongst sputum-positive TB patients (p < 0.001). HIV status, occupation, body mass index (BMI), and alcohol intake were not significantly associated with having at least one comorbidity. Implementing public health intervention programmes such as systematic screening of TB patients for NCDs especially diabetes is highly recommended for better control of these diseases.

Household food insecurity and elevated blood glucose among filipino adults aged 30-65 years in highly urbanized cities

Household food insecurity and elevated blood glucose among filipino adults aged 30-65 years in highly urbanized cities

Clinical phenotype of ARDS based on K-means cluster analysis: a study from the eICU database

PurposeTo explore the characteristics of the clinical phenotype of ARDS based on Machine Learning. MethodsThis is a study on Machine Learning. Screened cases of acute respiratory distress syndrome (ARDS) in the eICU database collected basic information in the cases and clinical data on the Day 1, Day 3, and Day 7 after the diagnosis of ARDS, respectively. Using the Calinski-Harabasz criterion, Gap Statistic, and Silhouette Coefficient, we determine the optimal clustering number k value. By the K-means cluster analysis to derive clinical phenotype, we analyzed the data collected within the first 24 hours. We compared it with the survival of cases under the Berlin standard classification, and also examined the phenotypic conversion within the first 24 hours, on day 3, and on day 7 after the diagnosis of ARDS. ResultsWe collected 5,054 cases and derived three clinical phenotypes using K-means cluster analysis. Phenotype-I is characterized by fewer abnormal laboratory indicators, higher oxygen partial pressure, oxygenation index, APACHE IV score, systolic and diastolic blood pressure, and lower respiratory rate and heart rate. Phenotype-II is characterized by elevated white blood cell count, blood glucose, creatinine, temperature, heart rate, and respiratory rate. Phenotype-III is characterized by elevated age, partial pressure of carbon dioxide, bicarbonate, GCS score, albumin. The differences in ICU length of stay and in-hospital mortality were significantly different between the three phenotypes (P<0.05), with phenotype I having the lowest in-hospital mortality (10%) and phenotype II having the highest (31.8%). To compare the survival analysis of ARDS patients classified by phenotype and those classified according to Berlin criteria. The results showed that the differences in survival between phenotypes were statistically significant (P<0.05) under phenotypic classification. ConclusionsThe clinical classification of ARDS based on K-means clustering analysis is beneficial for further identifying ARDS patients with different characteristics. Compared to the Berlin standard, the new clinical classification of ARDS provides a clearer display of the survival status of different types of patients, which helps to predict patient prognosis.