Hyperglycemia Research Articles

Sex sifferences in lifes essential eight and its association with mortality among adults without known CVD

Abstract Background The American Heart Association’s Life’s Essential 8 (LE8) score is a helpful tool to quantify cardiovascular health (CVH) metrics. Sex differences in relation to LE8 and its association with mortality are not known. Methods The National Health and Nutrition Examination Survey (NHANES) between 2009 and 2018 was utilized to evaluate the prevalence of health metrics included in LE8 among adult patients, stratified by sex. Health metrics were further subdivided into health behaviors (diet, physical activity, nicotine exposure, and sleep) and health factors (body mass index, non–high density lipoprotein cholesterol, blood glucose, and blood pressure). LE8 scores were also evaluated based on age, race/ethnicity, and socioeconomic status. Cox proportional hazard models were used to evaluate the association between the levels of CVH and risk of all-cause and cardiovascular mortality. Results Among 22,761 participants, 52% were female. Overall CVH score was similar in both females and males (65.8 vs. 65.9). Females had higher health factors score (64.3 vs. 63.1, p <0.001) and lower health behaviors score (67.2 vs 68.6, p <0.001). Amongst individual metrics, blood pressure score was higher in females (73.2 vs. 67.7, p <0.001) while males had higher physical activity score (70.6 vs. 54.9, p <0.001). For individuals under 65 years of age, overall CVH and health factors scores were higher in females while in those age 65 or older, males had higher scores. The most prominent sex differences were noted in non-Hispanic Black females who had significantly lower CVH scores than Black males. High or moderate LE8 scores vs. low LE8 scores demonstrated lower all-cause and CV mortality in both sexes (p-interaction 0.98 and 0.9). High or moderate health behaviors scores also demonstrated a significant association with lower all-cause and CV mortality, with the reduction in mortality being more prominent in females (p-interaction 0.01 and 0.03). Conclusions We demonstrate important sex differences in CVH metrics along with notable variations based on age and race/ethnicity. Furthermore, we highlight sex differences in the association of CVH metrics with mortality. These findings underscore the importance of designing and implementing effective strategies for both sexes, aimed at targeting these specific factors.

Association of risk factors on mortality in ST-elevation myocardial infarction patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies

Abstract Introduction Despite advancements in medical therapy and revascularization strategies for ST-elevation myocardial infarction (STEMI), diabetes mellitus (DM) remains independently associated with enhanced morbidity and mortality in STEMI. The causes for this are still unknown. Therefore, we aimed to summarise and quantify existing evidence in a systematic review and meta-analysis on the association between risk factors and mortality in STEMI patients with DM from prospective and retrospective cohort studies. Methods The systematic literature search was performed on the database of PubMed, Scopus and the Cochrane library up to July 2022. Relevant data were extracted and the risk of bias (RoB) of each study was assessed by using the Quality In Prognosis Studies (QUIPS) tool. All steps were conducted by two researchers independently. Summarised relative risks (SRR) and 95% confidence interval (CI) were estimated using a random effects model. I² was calculated as a measure of inconsistency. Results Out of 7601 studies, 18 were included after full-text screening, meeting our inclusion criteria. The RoB was moderate for 6 and high for 12 studies. Results of 7 studies reported on in-hospital mortality, 7 on all-cause-mortality up to 72 months, 3 on both outcomes, and 1 on cardiac death followed-up for 3.5 years. We found an increased risk of mortality for female compared to male sex (SRR [95% CI]: 1.56 [1.20; 2.01], n = 3 studies), age per 5 year increase (SRR [95% CI]: 1.26 [1.23; 1.30], n = 10 studies), admission blood glucose ≥ 7,8 mmol/l (SRR [95% CI]: 2.54 [1.60; 4.04], n = 3 studies), insulin treatment (SRR [95% CI]: 1.72 [1.33; 2.21], n = 2 studies), and dedicated Killip classification III-IV (SRR [95% CI]: 2.97 [2.58; 3.41], n = 3 studies) in STEMI patients with DM. Similar findings were observed for pre-existing comorbidities: prior myocardial infarction (SRR [95% CI]: 1.25 [1.06; 1.47], n = 3 studies), and heart failure (SRR [95% CI]: 2.68 [1.83; 3.93], n = 2 studies). Current smoking (SRR [95% CI]: 0.68 [0.52; 0.88], n = 3 studies) and hypercholesterinemia (SRR [95% CI]: 0.67 [0.57; 0.79], n = 2 studies) showed a reduced risk for mortality, while no association was found for multivessel disease (SRR [95% CI]: 1.03 [0.55; 1.92], n = 3 studies). Conclusion We identified specific risk factors of diabetes for mortality after STEMI. Our results confirm higher risk of mortality among STEMI patients with DM, particularly in women, older individuals, those with high admission blood glucose or insulin-dependent diabetes, and cardiac comorbidities. The role of smoking and hypercholesterinemia as a predictor for mortality might be explained by reverse causality and warrants further investigation.

A mathematical model of glomerular fibrosis in diabetic kidney disease to predict therapeutic efficacy

BackgroundGlomerular fibrosis is a tissue damage that occurs within the kidneys of chronic and diabetic kidney disease patients. Effective treatments are lacking, and the mechanism of glomerular damage reversal is poorly understood.MethodsA mathematical model suitable for hypothesis-driven systems pharmacology of glomerular fibrosis in diabetes was developed from a previous model of interstitial fibrosis. The adapted model consists of a system of ordinary differential equations that models the complex disease etiology and progression of glomerular fibrosis in diabetes.ResultsWithin the scope of the mechanism incorporated, advanced glycation end products (AGE)—matrix proteins that are modified due to high blood glucose—were identified as major contributors to the delay in the recovery from glomerular fibrosis after glucose control. The model predicted that inhibition of AGE production is not an effective approach for accelerating the recovery from glomerular fibrosis. Further, the model predicted that treatment breaking down accumulated AGE is the most productive at reversing glomerular fibrosis. The use of the model led to the identification that glucose control and aminoguanidine are ineffective treatments for reversing advanced glomerular fibrosis because they do not remove accumulated AGE. Additionally, using the model, a potential explanation was generated for the lack of efficacy of alagebrium in treating advanced glomerular fibrosis, which is due to the inability of alagebrium to reduce TGF-β.ImpactUsing the mathematical model, a mechanistic understanding of disease etiology and complexity of glomerular fibrosis in diabetes was illuminated, and then hypothesis-driven explanations for the lack of efficacy of different pharmacological agents for treating glomerular fibrosis were provided. This understanding can enable the development of more efficacious therapeutics for treating kidney damage in diabetes.

Sodium-Glucose Cotransporter-2 Inhibitors in Diabetic Patients with Heart Failure: An Update

Diabetes mellitus and heart failure are two diseases that are commonly found together, in particular in older patients. High blood glucose has a detrimental effect on the cardiovascular system, and worse glycemic control contributes to the onset and the recrudesce of heart failure. Therefore, any specific treatment aimed to reduce glycated hemoglobin may, in turn, have a beneficial effect on heart failure. Sodium-glucose cotransporter-2 inhibitors have been initially developed for the treatment of type 2 diabetes mellitus, and their significant action is to increase glycosuria, which in turn causes a reduction in glucose blood level and contributes to the reduction of cardiovascular risk. However, recent clinical trials have progressively demonstrated that the glycosuric effect of the sodium-glucose cotransporter-2 inhibitors also have a diuretic effect, which is a crucial target in the management of patients with heart failure. Additional studies also documented that sodium-glucose cotransporter-2 inhibitors improve the therapeutical management of heart failure, independently by the glycemic control and, therefore, by the presence of diabetes mellitus. In this review, we analyzed studies and trials demonstrating the efficacy of sodium-glucose cotransporter-2 inhibitors in treating chronic and acute heart failure.

Sex differences in the prevalence of metabolic syndrome and associated factors in the general population of Mongolia: A nationwide study.

The prevalence and factors associated with metabolic syndrome (MetS) between men and women in Mongolia were compared using secondary data from the STEPwise approach to non-communicable disease risk factor surveillance conducted in 2019. In total, 5,695 participants (2,577 males and 3,118 females) aged 18-69 years old were enrolled in the study. The prevalence of MetS was 37.4% in total and the prevalence was significantly higher in women (39.2%) than men (35.2%, P = 0.002). The most prevalent MetS components were abdominal obesity in women (74.2%) and high blood glucose levels in men (58.7%). All of the 2,128 participants who were categorized into MetS met the criteria of abdominal obesity. Factors associated with MetS included being 30-69 years old compared to 18-29 years old, low and moderate physical activity levels compared to high levels, history of hypertension and diabetes mellitus, and a high body mass index (overweight and obesity) compared to a normal body mass index in both sexes. Additional factors included Buryat ethnicity compared to Khalkh ethnicity, living in Ulaanbaatar, no education compared to primary education, higher monthly income, and currently drinking in men; and smoking and sufficient fruit and vegetable intake in women. Significant differences were observed between men and women in terms of the prevalence of MetS, components of MetS, and factors associated with MetS. To reduce MetS prevalence in Mongolia, sex-specific programs should be designed to promote health behavior, such as reducing alcohol consumption in men and smoking in women.

Association between blood glucose level trajectories and 30-day mortality risk in patients with acute ischemic stroke: analysis of the MIMIC database 2001–2019

BackgroundHyperglycemia is one of the most common comorbidities in patients with acute ischemic stroke (AIS). This study aimed to assess the impact of short-term longitudinal blood glucose level change trajectories on the 30-day mortality risk in patients with AIS.MethodsData for AIS patients were obtained from the 2001–2019 Medical Information Mart for Intensive Care (MIMIC) database. The latent growth mixture modeling (LGMM) was utilized to classify a patient’s blood glucose level trajectory within 24 h of admission. Cox regression analyses were applied to examine the relationship between blood glucose levels at admission and blood glucose level trajectories and the risk of 30-day mortality in patients with AIS.ResultsA total of 2,432 patients with AIS were included in this retrospective cohort study, with 30-day mortality occurring in 574 (23.60%) patients. The median glucose levels of all patients were 136.00 (110.00, 178.00) mg/dL. Four blood glucose level trajectories were identified: low level-stable trend (type 1), moderate level-stable trend (type 2), high level-decreasing-increasing trend (type 3), and moderate level-increasing-decreasing trend (type 4). Type 2 blood glucose level trajectory was associated with an increased risk of 30-day mortality compared with type 1 blood glucose level trajectory [hazard ratio (HR) = 1.28, 95% confidence interval (CI): 1.03–1.59), but there were no significant associations between type 3 (HR = 1.16, 95%CI: 0.77–1.74) and type 4 (HR = 1.44, 95%CI: 0.84–2.45) trajectories and 30-day mortality risk. Subgroup analysis demonstrated that the association between type 2 trajectory and 30-day mortality risk was observed in patients aged ≥ 65 years (HR = 1.37, 95%CI: 1.05–1.79), female (HR = 1.42, 95%CI: 1.05–1.94), with (HR = 1.44, 95%CI: 1.02–2.02) or without (HR = 1.42, 95%CI: 1.01–1.99) diabetes, and not using insulin (HR = 2.80, 95%CI: 1.43–5.49).ConclusionAIS patients with consistently high blood glucose levels within 24 h of admission increased the risk of 30-day mortality.

Can a mobile application improve glucose-related and patient-reported outcome measures (PROMs) in people with type 1 diabetes mellitus? A randomized controlled trial using the mySugr® app.

Mobile applications (apps) have proven to be highly effective tools to empower patients with type 1 diabetes mellitus (T1DM) and enable them to achieve better self-care, quality of life (QOL), and glycemic control. The aim of the study is to examine whether mySugr®, an app for diabetes management, together with teleconsultations, can have a positive impact on these factors and, thereby, replace current clinical care. This study concerns an exploratory randomized clinical trial of 12 months' duration. People with T1DM using multiple daily injections were randomized to usual care (bolus calculator, five face-to-face visits) or intervention (mySugr® app, three face-to-face visits, and two teleconsultations). The main outcome was increase in empowerment assessed with the Diabetes Empowerment Scale Short Form questionnaire (DES-SF-S). Secondary outcomes were change in additional glucose-related (blood glucose monitoring, mean blood glucose, standard deviation, coefficient of variation (CV), and high and low blood glucose index) and patient-reported outcome measures (PROMs) (self-management, QOL, and distress). A total of 25 out of 28 participants completed the study (52% men, age 44.52 years, diabetes duration 21.28 years). At 12 months, no significant differences were identified in the change of DES-SF-S and additional PROMs between arms. Similarly, no differences were observed in glucose-related outcomes except for the change in CV at 9 (control - 1.87 ± 4.98 vs. intervention 5.89 ± 11.33, p = 0.008) and 12 months (control - 2.33 ± 3.54 vs. intervention 5.12 ± 11.32, p = 0.018). Adherence to and satisfaction with the app were high. Patients with diabetes using the mySugr® app and teleconsultation achieved similar results to those following usual care in empowerment, other PROMs, and most glucose-related outcomes, thus supporting its use in combination with face-to-face visits. The RCT was registered with ClinicalTrials.gov (NCT03819335, first registration 28/01/2019).

Euglycemic Diabetic Ketoacidosis Presenting as Chest Pain and Vomiting in a Patient taking SGLT-2 inhibitor

Empagliflozin-induced Euglycemic Diabetic Ketoacidosis (EDKA) is a life-threatening metabolic emergency of Diabetes Mellitus. It is characterized by metabolic acidosis (i.e., pH <7.3 and Serum bicarbonate <15mEq/dl) with an increased anion gap, ketonemia and relatively normal serum glucose level. EDKA resembles Diabetic Keto Acidosis (DKA) but does not exhibit the typical high blood sugar levels. In EDKA, blood glucose is usually below 200 mg/dL. This condition is a diagnostic challenge as euglycemia masks the underlying diabetic ketoacidosis. Here we present a case of Empagliflozin-induced Euglycemic Diabetic Ketoacidosis presented with palpitation and several episodes of vomiting. The aim of this article is to create awareness among clinicians to consider this diagnosis in the differential, especially in the patients taking SGLT-2 inhibitors. Bangladesh Crit Care J September 2024; 12 (2): 172-174

Terazosin, a repurposed GPR119 agonist, ameliorates mitophagy and β-cell function in NAFPD by inhibiting MST1-Foxo3a signalling pathway.

GPR119 agonists are being developed to safeguard the function of pancreatic β-cells, especially in the context of non-alcoholic fatty pancreas disease (NAFPD) that is closely associated with β-cell dysfunction. This study aims to employ a drug repurposing strategy to screen GPR119 agonists and explore their potential molecular mechanisms for enhancing β-cell function in the context of NAFPD. MIN6 cells were stimulated with palmitic acid (PA), and a NAFPD model was established in GPR119-/- mice fed with a high-fat diet (HFD). Terazosin, identified through screening, was utilized to assess its impact on enhancing β-cell function via the MST1-Foxo3a pathway and mitophagy. Terazosin selectively activated GPR119, leading to increased cAMP and ATP synthesis, consequently enhancing insulin secretion. Terazosin administration improved high blood glucose, obesity, and impaired pancreatic β-cell function in NAFPD mice. It inhibited the upregulation of MST1-Foxo3a expression in pancreatic tissue and enhanced damaged mitophagy clearance, restoring autophagic flux, and improving mitochondrial quantity and structure in β-cells. Nevertheless, GPR119 deficiency negated the positive impact of terazosin on pancreatic β-cell function in NAFPD mice and abolished its inhibitory effect on the MST1-Foxo3a pathway. Terazosin activates GPR119 on the surface of pancreatic β-cells, enhancing mitophagy and alleviating β-cell dysfunction in the context of NAFPD by suppressing the MST1-Foxo3a signalling pathway. Terazosin could be considered a priority treatment for patients with concomitant NAFPD and hypertension.

Multifunctional Hydrogel Containing Oxygen Vacancy‐Rich WOx for Synergistic Photocatalytic O2 Production and Photothermal Therapy Promoting Bacteria‐Infected Diabetic Wound Healing

AbstractAn effective method capable of simultaneously providing antibacterial activity, blood glucose regulation, and angiogenesis promotion for healing bacteria‐infected diabetic wounds is not reported to date, but urgently required. In this study, a hydrogel composite (γ‐PGA/PDA/GOx/WOx (PPGW)), endowed with these desired attributes is fabricated by incorporating polydopamine (PDA), glucose oxidase (GOx), and tungsten oxide (WOx) nanowires into the poly(γ‐glutamic acid) (γ‐PGA) framework. The exceptional photothermal conversion properties of PDA facilitated notable antibacterial effects on bacteria‐infected diabetic wounds; GOx regulated high blood glucose by consuming glucose and generating hydrogen peroxide (H2O2); while WOx nanowires displayed remarkable photocatalytic abilities, converting H2O2 into oxygen (O2) when exposed to 808‐nm near‐infrared radiation. Density functional theory calculations and experiments are conducted to confirm the mechanism of WOx‐mediated photocatalytic degradation of H2O2 to produce O2. These transformations aided in alleviating the hypoxic conditions in wounds associated with diabetes, expediting angiogenesis, and fostering cell crawling and proliferation. Consequently, the multifunctional hydrogel dressing PPGW, featuring photothermal, antibacterial, and enzyme‐catalyzed activity reduces hyperglycemia at the wound site. Moreover, photocatalytic O2 production represents a promising strategy for addressing chronic bacteria‐infected diabetic wounds.

Study of indications, associated comorbid condi-tions and outcome of patients requiring Bilevel type of Non Inva-sive Positive Pressure Ventilation in a tertiary care hospital

BiLevel non-invasive positive pressure ventilation (BiPAP) is the most utilised supportive treatment in the world of medicine for respiratory failure. COPD is the most common indication for its use. We in-vestigated the indications and effects of comorbidities on BiPAP outcomes because there have been few studies on it. It is a descriptive, observational, cross-sectional study conducted over period of 12 months, wherein 60 patients fulfilling the inclusion criteria for the requirement of BiPAP were includ-ed in the study and evaluated. The indications, associated comorbid conditions and the outcomes of NIV therapy were studied. COPD exacerbation with Type II Respiratory failure was the most common indication (71.4%), followed by asthma [near fatal/severe] (21.4%). Success with BiPAP in COPD was 67.6% . In COPD patients with co-morbidities, success came down to 47.4%. Pneumonia, ILD & Cardiogenic Pulmonary Edema (CPE) had success rates of 0%, 16.7% and 66.7% respectively with BiPAP therapy,with higher mortality rates for pneumonia and ILD. Comorbidities were present in 51.7% of patients and Hypertension (35%) and Diabetes Mellitus (21.7%) were the most common. In patients who had co-morbidities, the mean hospital stay was 12 days, which was higher than the mean hospital stay of 9.3 days in patient with no co-morbidities. The presence of co-morbidities was associated with higher failures with BiPAP (51.6%) comapred to ones with no co-morbidities (13.8%) (p value <0.05). Higher respiratory rate (>28/min), lower ABG pO2, pCO2 and bicarbonate levels and higher blood glucose and total leucocyte counts were associated with higher BiPAP failures and mortality. The conclusion was that the most common indication of BiPAP was a COPD exacerbation with type II respiratory failure and presence of comorbidities led to a poorer outcome with prolonged hospital stay. ABG parameters, blood glucose levels and total leucocyte counts has an effect on NIV outcome and mortality.

Smart photonic crystal hydrogels for visual glucose monitoring in diabetic wound healing

Diabetes is a global chronic disease that seriously endangers human health and characterized by abnormally high blood glucose levels in the body. Diabetic wounds are common complications which associate with impaired healing process. Biomarkers monitoring of diabetic wounds is of great importance in the diabetes management. However, actual monitoring of biomarkers still largely relies on the complex process and additional sophisticated analytical instruments. In this work, we prepared hydrogels composed of different modules, which were designed to monitor different physiological indicators in diabetic wounds, including glucose levels, pH, and temperature. Glucose monitoring was achieved based on the combination of photonic crystal (PC) structure and glucose-responsive hydrogels. The obtained photonic crystal hydrogels (PCHs) allowed visual monitoring of glucose levels in physiological ranges by readout of intuitive structural color changes of PCHs during glucose-induced swelling and shrinkage. Interestingly, the glucose response of double network PCHs was completed in 15 min, which was twice as fast as single network PCHs, due to the higher volume fraction of glucose-responsive motifs. Moreover, pH sensing was achieved by incorporation of acid-base indicator dyes into hydrogels; and temperature monitoring was obtained by integration of thermochromic powders in hydrogels. These hydrogel modules effectively monitored the physiological levels and dynamic changes of three physiological biomarkers, both in vitro and in vivo during diabetic wound healing process. The multifunctional hydrogels with visual monitoring of biomarkers have great potential in wound-related monitoring and treatment.Graphical abstract

Quercetin: Potential antidiabetic effects through enzyme inhibition and starch digestibility

AbstractDiabetes mellitus involves high blood sugar levels due to insufficient insulin action. Furthermore, enzymes such as α‐amylase and α‐glucosidase break down carbohydrates into glucose, leading to postprandial hyperglycemia. Flavonoids, particularly quercetin, inhibit these enzymes, slowing carbohydrate digestion and reducing glucose absorption. Quercetin has significant hypoglycemic effects with inhibitory concentration (IC50) values comparable to acarbose, a standard inhibitor, suggesting its potential as a natural alternative for diabetes management. In silico models, including molecular docking, molecular dynamics (MD) simulations, and quantitative structure‐activity relationship (QSAR) approaches, help researchers understand the molecular interactions of therapeutic agents. These techniques identify potential inhibitors, determine enzyme‐inhibitor structures, and calculate binding energies, correlating findings with in vitro or in vivo data. Molecular docking predicts molecular orientations, MD simulations offer insights into enzyme–inhibitor dynamics, and QSAR models predict inhibitory potential based on structural properties. Studies have shown that quercetin effectively inhibits α‐glucosidase and α‐amylase by forming hydrogen bonds with specific amino acid residues. Quercetin interacts with starches and reduces their digestibility, increases the formation of resistant starch, lowers the glycemic index, and inhibits digestive enzymes. Studies show that the effects of quercetin on starch digestion vary with concentration and type of starch, and its incorporation into foods such as bakery products, pasta, etc. can significantly decrease starch hydrolysis. The incorporation of quercetin into starch matrices may aid in the development of functional foods aimed at improving glycemic control.

Investigation of Biochemical and Inflammatory Markers in COVID-19 Patients Hospitalized in the Intensive Care Unit: An Observational Study in Northern Iran

Background: Since the first documentation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there has been a notable emphasis on it in a brief period, especially as the mortality rate and confirmed cases steadily rise. The rapid and accurate laboratory identification of an ongoing COVID-19 infection is essential for efficient pandemic control. For diagnostic purposes, various testing methods have been developed to detect the severity of COVID-19. These diagnostic methods play a crucial role in identifying and managing the spread of the virus within communities worldwide. Methods: This cross-sectional observational study was conducted from February to June 2020, spanning four months. Patient clinical records and laboratory biomarkers data were collected. Results: In this study, 263 patients were involved, with an average age of 59.38 ± 15.26 years, and 51.3% of them (135 patients) were male. The typical hospital stay was 9.25 ± 6.9 days. The patients were divided into three groups: Those who survived (49.4%), those receiving treatment (4.9%), and those who did not survive (45.6%), with all treated patients surviving. An important connection was observed between serum lactate dehydrogenase (LDH), creatine phosphokinase (CPK), urea, leukocytosis, lymphopenia, high polymorphonuclear neutrophil (PMN) counts, and poor patient outcomes (P-value < 0.05). Elevated aspartate transaminase (AST) levels also showed a close relationship with adverse outcomes (P-value = 0.05). Furthermore, most patients with hyponatremia, high fasting blood glucose, and elevated serum creatinine levels did not survive, despite lacking statistical significance. Conclusions: Serum biomarkers serve as prognostic indicators for the severity of COVID-19 patients. Leveraging these markers aids in promptly diagnosing patients at high mortality risk and facilitates more effective treatments in the disease's initial phases. These biomarkers can help healthcare providers identify patients at higher risk of complications and guide the implementation of targeted interventions to improve patient outcomes.

Combination of anlotinib and sintilimab for the treatment of recurrent or metastatic head and neck squamous cell carcinoma: a single-arm prospective study

To investigate whether blocking both programmed cell death protein and vascular endothelial growth factor receptor could offer superior anticancer activity in these patients without compromising safety. In this study, patients were administered oral anlotinib (12 mg/day) on days 1–14 and intravenous sintilimab (200 mg) on day 1 of a 3-weekly cycle. The primary endpoints included the objective response rate and disease control rate. The secondary endpoints included overall survival (OS) and safety. Ten eligible patients were enrolled between June 2019 and May 2022, and eight patients underwent radiographic assessments. The results showed an objective response rate of 50% (partial and complete response in four and zero patients, respectively) and a disease control rate of 100%; four patients demonstrated stable disease for at least 8 weeks. The median OS was 4.37 (in our study, the score was 7), and the OS rate at 12 months was 37.5%. The Kaplan–Meier survival curve showed that the group with high blood glucose levels had a significantly shorter duration of survival than those with normal blood glucose levels. Adverse events of grade 3 and higher occurred in 50% of patients, and the most common severe adverse events included tumor pain (50%), hypertension (37.5%), tumor hemorrhage (25%), and decreased appetite (25%). The combination of anlotinib and sintilimab showed promising efficacy in controlling tumor size. However, the disappointing OS rate suggests that anti-vascular endothelial growth factor receptor agents should be used cautiously after radical radiation therapy. The combination used in this study demonstrated a toxicity profile comparable to that of other agents used in this setting. These findings warrant further investigation into the potential clinical utility of this combination.

Ayurveda’s Role in Managing Diabetes: A Case Study

Diabetes is also known as Diabetes mellitus (DM) which is characterised by high blood sugar levels over a long period. The raised level of Blood Glucose leads to frequent urination. This may occur when the pancreas is unable to produce the proper level of insulin or the inability of body cells to absorb the glucose properly. Insulin regulates the level of glucose in the bloodstream, so its deficiency leads to a rise in the glucose levels in the bloodstream. The condition of Diabetes may lead to various complications if it is not managed properly. A 50-year-old male patient presented with complaints of frequent urination, increased thirst and hunger. The clinical findings and symptoms of the patient are related to Type 2 Diabetes. Diabetes is correlated to Madhumeha in Ayurveda. The patient was given Dia-Beta Plus capsules, Karela capsules, Madhumehantak churna, Fenugreek capsules and Diaplan tea. After 2 months, the patient feels some relief in his symptoms. The random sugar levels of the patient decreased from 240 mg/dL to 130 mg/dL. After the complete course of Ayurveda medication, the blood sugar level of the patient was managed effectively.

6938 An Unusual Case of New-onset autoimmune insulin dependent Diabetes Mellitus Complicating Gestational Diabetes Mellitus in A Pregnant Female Diagnosed Early Postpartum - The Enigma of Autoimmunity and Diabetes During Pregnancy

Abstract Disclosure: R. Abdelmasih: None. W. Pan: None. Introduction: Gestation diabetes is the most common metabolic disorder in pregnancy affecting 25% of pregnancies. T1DM accounts for 0.2-0.5% of all pregnancies in the United States yearly. New-onset autoimmune insulin-dependent diabetes mellitus during pregnancy is very uncommon and it might be overlooked. Diabetes-related autoantibodies have been studied in women with GDM with prevalence of 0-10%. There is controversial data regarding the clinical significance of checking diabetes antibodies in pregnancy. Case Presentation: A 22-year-old G1P1 female with history of Hashimoto hypothyroidism presented during early second trimester for evaluation of GDM with serum glucose of 300s mg/dl in a random blood sample with multiple subsequent high values, hemoglobin A1C of 9.4% (prepartum value was 5.3%). Patient was started on insulin during pregnancy. Pregnancy was complicated with cesarian section and macrosomia. 1 week postpartum, A1c was 5.4%, Insulin was discontinued, and patient was continued on Metformin. 2 months Postpartum, patient presented with persistent high blood glucose values of 300-400 mg/dl with no signs of DKA. Glipizide and Glargine 15 units daily were added though patient continued to have hyperglycemia. Laboratory workup were remarkable for high blood glucose of 342 mg/dl, low C peptide of 0.6 ng/dl, and positive glutamic acid decarboxylase antibodies (GAD Ab) 38.8 U/ml. oral antidiabetics were discontinued and prandial insulin was added. Discussion: GDM is a risk factor for DMII after pregnancy given high insulin resistance postpartum, Data regarding new-onset DMI and diabetes autoimmunity during pregnancy is lacking. About 0-10% of women with gestational diabetes develop DM autoantibodies. GAD Ab exhibits the highest sensitivity of 63% for type 1 diabetes prediction compared to Islet cell antibodies (48%), and tyrosine phosphatase-related islet antigen 2 (34%). Pathophysiology of autoimmune DM during pregnancy is not quite understood; It is thought that when autoimmune tendency is present, GDM causes β-cells to deteriorate due to excessive insulin production in setting of insulin resistance, and the burden of third-trimester gestation may cause the insulin deficiency to be expressed sooner than non-pregnant female. So far, Literature about the predictive value or specific clinical features of checking diabetes autoantibodies is discordant and inconclusive. It is suggested to screen for autoantibodies only when array of clinical hallmarks suggestive of an autoimmune DM form of GDM present as young age, low BMI, need for insulin therapy early in pregnancy, presence of ketones, concurrent other autoimmune conditions (e.g., thyroiditis). This case is to shed light on autoimmunity in pregnancy. More data is needed with longer follow-up to better identify women at risk, their characteristics, indications for autoantibodies testing, follow and prognosis. Presentation: 6/2/2024

UJI AKTIVITAS ANTIDIABETES EKSTRAK DAUN PACAR AIR (Impatiens balsamina L.) TERHADAP GINJAL TIKUS WISTAR (Rattus novergicus L.) YANG DIINDUKSI ALOKSAN

Background: Diabetes mellitus is a serious, "chronic" condition that occurs when there is an increase in a person's blood sugar levels because the body is unable to produce enough insulin hormones/cannot effectively use the insulin produced. A lack of insulin, or the inability of cells to respond to it, causes high blood glucose levels (hyperglycemia), which causes clinical indicators of diabetes. Methods: This research is an experimental study using a completely randomized design. Twenty-four male white rats were divided into 6 groups consisting of normal controls (KN) who received no treatment, negative controls (K-) who were injected with alloxan at a dose of 150 mg/kg BW, positive controls (K+) who were injected with alloxan at a dose of 150 mg/kg BW. kg BW and glibenclamide at a dose of 0.09 mg/200 g BW, Treatment 1 (P1) was injected with alloxan at a dose of 150 mg/kg BW and ethanol extract of water henna leaves at a dose of 450 mg/KG BW, Treatment 2 (P2) was injected with alloxan with a dose of 150 mg/kg BW and ethanol extract of water henna leaves with a dose of 500 mg/KG BW, Treatment 3 (P3) was injected with alloxan at a dose of 150 mg/kg BW and ethanol extract of water henna leaves with a dose of 550 mg/KG BW. Mice blood glucose levels were measured on days 0 (after alloxan induction), 3, 7, and 14. Before the measurements, the mice were fasted for 8 hours. Results: Research shows that administration of water henna leaf extract has a significant effect in reducing urea and creatinine levels, as well as improving kidney morphology. However, it could not prevent the alloxan-induced increase in kidney weight in white mice. Conclusion: Administration of henna leaf extract (Impatiens balsamina L.) at a dose of 500 mg/kg BW had a significant effect on reducing urea and creatinine levels in white rats induced by alloxan. Administration of water henna leaf extract (Impatiens balsamina L.) at a dose of 450 mg/kg BW had a significant effect in improving kidney morphology in alloxan-induced white rats, whereas the organ index of water henna leaf extract could not prevent the increase in kidney weight in white mice induced alloxan

A-064 Improved Insulin production in Advanced glycation end-products (AGEs)-induced RIN-m5F pancreatic β-cells by using a Flavonoid-Rich Medicinal Plant, Kaempferia parviflora treatment

Abstract Background Advanced glycation end-products (AGEs) are glycated proteins that react with reducing sugar which causes the damages of function and cellular signaling of insulin production in insulinoma cells. AGEs also contribute to hyperglycemia-induced insulin resistance in type 2 diabetes. AGEs gradually form during the chronic high blood glucose condition, which is a major risk factor and harmful to β-cells function and survival, and could alter the insulin signaling and downregulate the insulin-responsive transcription factors including PDX-1, Glut-2, GCK, and Pre-INS. Kaempferia parviflora, also known as black ginger and flavonoid-rich medicinal plant, has beneficial properties for type 2 diabetes patients as a counteracts the detrimental effects of AGEs and improves the insulin production in pancreatic β-cells. Thus, we hypothesize that treated β-cells with K. parviflora, which is the most effective flavonoid-containing plant might protect against the damage of AGEs-induced insulin impairment, and these effects are also responsible for improved insulin synthesis and the essential transcription factors in pancreatic β-cells. Methods Rat pancreatic β-cell line RIN-m5F (ATCC CRL-2058) were maintained and cultured in RPMI 1640 medium containing 10% (v/v) FBS, 1% penicillin-streptomycin at 37◦C in a humidified atmosphere containing 5% CO2. RIN-m5F cells were pre-treated with the K. parviflora at concentrations 0, 25, and 50 µg/ml for 48 hours, and afterward, exposure to 250 µg/ml AGEs treatment. To quantify the bioactive compound of K. parviflora, total phenolic and flavonoid content assays were performed and the transcriptional changes of insulin-related genes (PDX-1, Glut-2, GCK, and Pre-INS) were determined by using real-time qRT-PCR. Results K. parviflora has shown a high phenolic content and flavonoid content was 50.43 ± 1.74, 26.66 ± 1.18 mg GAE/g Dry weight of sample, respectively. For the transcriptional changes of insulin-related genes, the levels of gene expression in the regulators of insulin secreting pathway (PDX-1, Glut-2, GCK, and Pre-INS) were significantly downregulated after exposure to AGEs-treated, while the pre-treatment of K. parviflora was showed statistically difference. PDX-1, Glut-2, GCK, and Pre-INS expressions were significantly upregulated after pre-treated with 50 µg/ml K. parviflora. However, under the AGEs-treated alone condition, the transcriptional levels were significantly decreased as compared to the control (untreated). Taken together, these results suggest K. parviflora could be a potential natural medicine to ameliorate the damage of insulin production in AGEs-induced β-cell damage and highlight promising alternatives for therapeutic avenue against diabetes. Conclusions Treated RIN-m5F pancreatic β-cells with K. parviflora, a flavonoid-rich medicinal plant, could upregulate the insulin-responsive transcription factors and improve the insulin production in damaging AGEs-induced pancreatic β-cells. Our findings provide a novel strategy related metabolic disease and insights into the regulation of insulin synthesis by using K. parviflora treatment as a therapeutic agent against type 2 diabetes.

Association between child marriage and high blood glucose level in women: A birth cohort analysis

ObjectivesChild marriage prematurely forces girls (<18 years of age) to perform adult roles prior to physical and psychological maturity. Such precocious transitions to young adulthood can have consequences on their long-term health, however, limited work has examined such relationships to date. As such, this study examines whether child marriage is associated with the risk of having hyperglycemia, or high blood glucose, in adulthood. Study designObservational study using repeated cross-sectional data. MethodsUsing data from the 2015-16 and 2019-21 waves of the India National Family Health Survey, we matched 432,080 and 418,409 women, aged 20 to 49 years, by birth year and month to create birth cohorts. Fitting multivariable binomial and multinomial logistic models, we compared the odds of having hyperglycemia across groups by marriage age (i.e., before or after age 18 years) within respective birth cohorts. ResultsWe found that the adjusted odds of having high blood glucose among women married as children were 1.12 (95% CI: 1.07 – 1.16) times that of their peers married as adults in the full-sample. The adjusted relative risks of having blood glucose levels higher than normal but lower than diabetic and diabetic ranges were 1.09 (95% CI: 1.04 – 1.14) and 1.23 (95% CI: 1.15 – 1.31), respectively, in comparison to blood glucose within normal range. These results were persistent across sub-groups of different birth cohorts. ConclusionOur findings suggest that child marriage was associated with higher risk of having high blood glucose in women, later in life.