Lower Glucose Levels Research Articles

IOT Based Continuous Glucose Monitoring for Diabetes Mellitus using Deep Siamese Domain Adaptation Convolutional Neural Network

The phrase "Internet of Things" (IoT) refers to the forthcoming generation of the Internet, which facilitates interaction among networked devices. IoT functions as an assistant in medicine and is critical to a variety of uses that monitor healthcare facilities. The pattern of observed parameters can be used to predict the type of the disease. Health experts and technologists have developed an excellent system that employs commonly utilized technologies like wearable technology, wireless channels, and other remote devices to deliver cost-effective medical surveillance for people suffering from a range of diseases. Network-connected sensors worn on the body or put in living areas collect large amounts of data to assess the patient's physical and mental wellbeing. In this Manuscript, IoT -based Continuous Glucose Monitoring for Diabetes Mellitus using Deep Siamese Domain Adaptation Convolutional Neural Networ k (CGM-DM- DSDACNN) is proposed. The goal of the work that has been described to investigate whether Continuous Glucose Monitoring System (CGMS) on the basis of IoT is both intrusive also secure. The job at hand is for making an architecture based on IoT that extends from the sensor model to the back-end and displays blood glucose level, body temperature, and contextual data to final users like patients and doctors in graphical and text formats. A higher level of energy economy is also attained by tailoring the Long range Sigfox communication protocol to the glucose monitoring device. Additionally, analyse the energy usage of a sensor device and create energy collecting components for it. Present a Deep Siamese Domain Adaptation Convolutional Neural Network (DSDACNN) as a last resort for alerting patients and medical professionals in the event of anomalous circumstances, like a too -low or too-high glucose level.

Diagnostic challenges in tuberculous meningitis: a case report with negative genexpert result.

Tuberculous meningitis (TBM) is a severe form of tuberculosis affecting the meninges, primarily caused by Mycobacterium tuberculosis. Diagnosis of TBM poses numerous challenges due to its nonspecific clinical presentation and the limitations of diagnostic tests like GeneXpert. The authors report a case of a 22-year-old female from Eastern Nepal presenting with acute-onset fever, headache, vomiting, and neck pain. Cerebrospinal fluid (CSF) analysis showed lymphocytic pleocytosis, elevated protein, low glucose levels, and cobweb coagulum indicative of TBM. However, the GeneXpert test revealed negative results. In resource-limited settings like Nepal, where access to GeneXpert MTB/Rif is limited, CSF analysis and clinical algorithms play a crucial role in diagnosing TBM. Relying solely on GeneXpert results may lead to false negatives, so a high level of suspicion based on patient risk factors is essential. Prompt initiation of empirical antitubercular therapy is vital for a favorable outcome in TBM cases. Negative MTB PCR results from CSF can be misleading in diagnosis of tubercular meningitis. Therefore, comprehensive evaluations, including detailed patient history, physical examination, and CSF fluid analysis, are crucial in high tuberculous prevalence countries to ensure accurate and timely diagnosis.

Growth, body composition, digestive enzyme activity, blood biochemical parameters, and immune antioxidant indices of red tilapia fish (Oreochromis mossambicus × Oreochromis niloticus) reared in mixed cell and rectangular raceways

In this study, growth performance, body composition, digestive enzyme activity, blood biochemical parameters, immune-antioxidant indices of red tilapia fish (Oreochromis mossambicus × Oreochromis niloticus), and water quality parameters were investigated in mixed cell (MCR) and rectangular raceways. Fish with an initial weight of 1 ± 0.03 g were reared in mixed cell and rectangular raceways at a density of 150 g/m3 and fed a commercial diet as a percentage of their body weight for 60 days. The MCR groups had significant improvements in water quality parameters and had higher final weight, specific growth rate, and lower feed conversion ratio compared to the rectangular raceway groups. The MCR groups also had higher ash content and lower body moisture content. In addition, the MCR groups had improved digestive enzyme activity and better fish health, with lower cortisol and glucose levels and higher antioxidant competence. These results suggest that MCR is a beneficial alternative to rectangular raceways in terms of water quality, growth performance, and fish health.

Neonatal hypoglycemia and associated factors at Wangaya General Hospital

In the early hours to early days of life, managing low blood glucose levels and screening infants at risk are common problems in the care of newborns. Still missing, though, is a precise definition of newborn hypoglycemia. The purpose of this study is knowing that pregnancy hypertension/preeclampsia/eclampsia, prematurity, small-gestational-weight (SGA), large-gestational-weight (LGA), asphyxia, and sepsis are risk factors associated with neonatal hypoglycemia. The type of research conducted was a cross-sectional retrospective analytic study on infants in the perinatology room at Wangaya Hospital in 2022. The sample in this study consisted of 18 hypoglycemia babies and 18 normoglycemia babies taken by purposive sampling with matching hypertension/preeclampsia/eclampsia pregnancy, prematurity, SGA, LGA, asphyxia and sepsis. Data collection used medical record data and perinatology register data. Statistical tests used were Chi-Square and logistic regression with a 95% confidence interval. The results showed that prematurity was an associated risk factor (OR=2.78; 95% CI=1.437-5.379), asphyxia and sepsis also showed statistical significance (OR=2.07; 95% CI=1.221-3.513) (OR=2.27; 95% CI=1.257-4.109). In multivariate analysis, there was no statistical significance among other factors (p-value 0.019). Prematurity, asphyxia, and sepsis were risk factors associated with the incidence of neonatal hypoglycemia with odds of 2.78 times, 2.07 times and 2.27 times respectively compared to the control population. However, in the multivariate analysis, there was no relationship between one factor to another factor that influenced each other in being a risk factor associated with hypoglycemia at Wangaya Hospital.

The Effect of Glycemic Control on Morbidity and Mortality in Critically Ill COVID-19 Patients.

Background COVID-19 infection has caused a global pandemic affecting a group of patients with chronic conditions including diabetes with exacerbating insulin resistance and hyperglycemia. Investigators noted that pre-existing diabetes and newly diagnosed diabetes are associated with an increased risk of all-cause mortality in hospitalized patients with COVID-19 infection. Aim To evaluate the relationship between ICU patients infected with COVID-19 and mortality among those with high versus low glucose levels. Methods This is a retrospective study of critically ill adult patients infected with COVID-19 who were admitted to the ICU from April 5, 2020, to October 14, 2020. The participants were from San Bernardino County which is a diverse and underserved community. Overall, 84 patients were included in the final analysis. The average age was 59.67 (standard deviation=15.55) with 59.5% being males. Overall mortality was 44.1%. Results Around one-fifth of patients had glucose under control as measured by peak glucose level of <180 mg/dL during hospital stay. A statistically significant association was seen between tighter serum glucose control and mortality (p=0.0354). Patients with serum glucose maintained <180 mg/dL were associated with significantly lower mortality than their counterparts (22.2% vs. 50%). Conclusions This study suggests that maintaining a tighter control of the glycemic index in critically ill COVID-19 patients will improve morbidity and mortality.

Increased insulin resistance with reduced beta cell function in recovered COVID-19 Ghanaians

AimThis study compares levels of insulin resistance and beta-cell function and their relationship with liver enzymes in recovered COVID-19 participants and their uninfected counterparts in a cross-sectional study design in the Tamale metropolis of Ghana. MethodsBiochemical indices for liver function, lipid metabolism, inflammation and oxidative stress were assessed under fasting state in 110 recovered COVID-19 and 116 uninfected participants. The homeostatic model assessment of insulin resistance (HOMA-IR) and the triglyceride-glucose index (TyG) were employed for the assessment of insulin resistance. ResultsRecovered COVID-19 participants presented lower (P < 0.05) levels of fasting glucose, insulin, alkaline phosphatase, creatinine and beta-cell function but higher (P < 0.05) levels of alanine/aspartate transferase, total bilirubin, direct bilirubin, total cholesterol, high-density lipoprotein cholesterol and HOMA-IR than their uninfected counterparts. The mean levels of the remaining indices were comparable (P > 0.05) between the study groups. Prevalence of insulin resistance ranged from 61 % (71/116) to 81 % (89/110) for the uninfected and recovered COVID-19 participants respectively. Selected liver enzymes associated with HOMA-IR and TyG. ConclusionThe risk of developing type 2 diabetes mellitus appears higher in recovered COVID-19 participants than their uninfected counterparts despite the high prevalence of insulin resistance in both groups.

Combining wavelet transform with convolutional neural networks for hypoglycemia events prediction from CGM data

Estimating future blood glucose levels is an essential and challenging task for people with diabetes. It must be carried out based on variables such as current glucose, carbohydrate intake, physical activity, and insulin dosing. Accurate estimation is essential to maintain glucose values in a healthy range and avoid dangerous events of low glucose levels (hypoglycemia) and extremely high glucose values (hyperglycemia). Those situations maintained in time can cause not only permanent long-term damage but also short-term complications and even the death of the person. This paper proposes a new method to predict and detect hypoglycemic events over a 24-h time horizon. The technique combines applying the wavelet transform to glucose time series and deep learning convolutional neural networks. We have experimented with real data collected from 20 different people with type 1 diabetes. Our technique can also be applied to predict hyperglycemia. We incorporate a data augmentation technique consisting of a rolling windows system that improves the accuracy of the prediction. The uncertainty of the data is considered by the addition of controlled noise. The results show that the predictions obtained are accurate (higher than 88% of accuracy, sensitivity, specificity, and precision), confirming the effectiveness of the proposed method.

The role of diabetes in metastatic melanoma patients treated with nivolumab plus relatlimab

BackgroundThe combination of nivolumab + relatlimab is superior to nivolumab alone in the treatment of naive patients and has activity in PD-1 refractory melanoma. We had previously observed a reduced expression of LAG3 in melanoma tissue from patients with type 2 diabetes.MethodTo evaluate the impact of diabetes on oncological outcomes of patients with advanced melanoma treated with nivolumab plus the LAG3 inhibitor relatlimab we performed a retrospective multicenter study.ResultsOverall, 129 patients were included: 88 without diabetes before the treatment, 37 who were diagnosed with type 2 diabetes before the start of treatment, and 4 without diabetes before treatment who developed immune checkpoint inhibitor-induced diabetes (ICI-DM). PFS was 21.71 months (95% CI: 15.61–27.81) in patients without diabetes, 10.23 months (95% CI: 5.81–14.66) in patients with type 2 diabetes, and 50.85 months (95% CI: 23.04–78.65) in patients who developed ICI-DM. OS was 37.94 months (95% CI: 31.02–44.85) in patients without diabetes, 22.12 months (95% CI: 14.41–29.85) in those with type 2 diabetes and 57.64 months (95% CI: 42.29–72.99) in those who developed ICI-DM. Multivariate analysis showed that the presence of diabetes and LDH was correlated with OS and PFS. The mean OS was 64.63 months in subjects with low levels of glucose (< 137 mg/dl) and 36.27 months in those with high levels (hazard ratio 0.16, 95% CI: 0.04–0.58; p = 0.005). The patients whose glucose blood level increased after 3 months of treatment with nivolumab + relatinib compared to baseline (ratio of blood level at baseline/after 3 months > 1.5) had a worse prognosis than those whose glucose level had not increased. This result was observed also in subgroups treated either in first line or further lines. Patients who developed ICI-DM during the study period had better outcomes than the overall population and patients without diabetes.ConclusionsLAG3 inhibition for treating metastatic or unresectable melanoma has a reduced efficacy in patients with type 2 diabetes, possibly due to a low expression of LAG3 in tumor tissue. Higher level evidence should be obtained.

Rare Variant in Metallothionein 1E Increases the Risk of Type 2 Diabetes in a Chinese Population.

To uncover novel targets for the treatment of type 2 diabetes (T2D) by investigating rare variants with large effects in monogenic forms of the disease. We performed whole-exome sequencing in a family with diabetes. We validated the identified gene using Sanger sequencing in additional families and diabetes- and community-based cohorts. Wild-type and variant gene transgenic mouse models were used to study the gene function. Our analysis revealed a rare variant of the metallothionein 1E (MT1E) gene, p.C36Y, in a three-generation family with diabetes. This risk allele was associated with T2D or prediabetes in a community-based cohort. MT1E p.C36 carriers had higher HbA1c levels and greater BMI than those carrying the wild-type allele. Mice with forced expression of MT1E p.C36Y demonstrated increased weight gain, elevated postchallenge serum glucose and liver enzyme levels, and hepatic steatosis, similar to the phenotypes observed in human carriers of MT1E p.C36Y. In contrast, mice with forced expression of MT1E p.C36C displayed reduced weight and lower serum glucose and serum triglyceride levels. Forced expression of wild-type and variant MT1E demonstrated differential expression of genes related to lipid metabolism. Our results suggest that MT1E could be a promising target for drug development, because forced expression of MT1E p.C36C stabilized glucose metabolism and reduced body weight, whereas MT1E p.C36Y expression had the opposite effect. These findings highlight the importance of considering the impact of rare variants in the development of new T2D treatments.

Зависимость биохимических показателей крови беременных и веса новорожденных от количества глюкозы в крови матери

The aim of the study is to identify the relationship between glucose levels and biochemical parameters of the blood of pregnant women and between glucose levels and the weight of newborns. Material and methods. The work was carried out in the Samara region State Medical Institution ‘Samara City Consultative and Diagnostic Polyclinic No. 14’ on the basis of the results of a blood test of the patients of the women's consultation. The studies were conducted in the biochemical department of the clinical diagnostic laboratory. The patients were divided into four groups depending on the blood glucose level: ≤ 4.0 mmol/l (n = 178), &gt; 4.1 mmol/l (n = 200), 5.0–6.1 mmol/l (n = 115), &gt; 6.1 mmol/l (n = 18). Results. The greatest severity of differences in the biochemical parameters of the blood of pregnant women, depending on the glucose level, was noted when determining cholesterol and total protein. The maximum cholesterol index of 7.1 mmol/l was recorded in the group with the lowest glucose level

A synbiotic made of an autochthonous Enterococcus durans strain and microbial polysaccharides improves broiler chicken health

PurposeThe gastrointestinal tract (GI) of organically fed desi chickens fosters a microbiota that can exclude pathogens and be potentially probiotic for improving the gut health of commercial chickens. MethodsA panel of strains were selectively cultured from desi chicken intestine and screened for their antagonism towards specific pathogens. Treating the culture free supernatant (CFS) of such strains with NaOH and proteases gives a picture of the antibacterial compound's biochemistry and determining its minimum inhibitory concentration (MIC) provides a measure of potency. The most strongly antagonistic strains were tested in vitro for surviving the chicken GIT. Safety was examined using mucin degradation, gelatin liquefaction, hemolysis, antibiotic susceptibility and biogenic amine production. An in vivo trial was done on young male Ross chickens to evaluate the performance of a bespoke synbiotic formulation comprising of an Enterococcus durans strain (1x108 CFUg−1) with prebiotics Dextran or Levan (0.1% w/v) and with both and assessing its impact on broiler gut microbiota, body and carcass weight, histopathology of organ tissues, and biochemical markers. ResultsA panel of Enterococcus spp. (NPL1315-NPL1334) was obtained and the selected strains (NLP-1319, 20, 24, 27, 34) showed good bile, acid and phenol survival, and cell surface hydrophobicity but not autoaggregation and none of them were deemed unsafe. The synbiotic-fed chickens were significantly heavier, with lowered serum cholesterol, triglycerides and glucose levels and a lesser load of pathogens than the controls. ConclusionDesi chicken intestine can be a viable source of probiotics with good antagonistic potential capable of replacing antibiotics in poultry feed.

ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon

Raynaud’s phenomenon (RP) is a common vasospastic disorder that causes severe pain and ulcers, but despite its high reported heritability, no causal genes have been robustly identified. We conducted a genome-wide association study including 5,147 RP cases and 439,294 controls, based on diagnoses from electronic health records, and identified three unreported genomic regions associated with the risk of RP (p < 5 × 10−8). We prioritized ADRA2A (rs7090046, odds ratio (OR) per allele: 1.26; 95%-CI: 1.20-1.31; p < 9.6 × 10−27) and IRX1 (rs12653958, OR: 1.17; 95%-CI: 1.12–1.22, p < 4.8 × 10−13) as candidate causal genes through integration of gene expression in disease relevant tissues. We further identified a likely causal detrimental effect of low fasting glucose levels on RP risk (rG = −0.21; p-value = 2.3 × 10−3), and systematically highlighted drug repurposing opportunities, like the antidepressant mirtazapine. Our results provide the first robust evidence for a strong genetic contribution to RP and highlight a so far underrated role of α2A-adrenoreceptor signalling, encoded at ADRA2A, as a possible mechanism for hypersensitivity to catecholamine-induced vasospasms.

Acute repeated cage exchange stress modifies urinary stress and plasma metabolic profiles in male mice.

Exposure to a novel environment is psychologically and physically stressful for humans and animals. The response has been reported to involve enhanced sympathetic nervous system activity, but changes in nutrient levels under stress are not fully understood. As a form of exposure to a novel environment, repeated cage exchange (CE, four times at 2-h intervals for 8 h from 08:00 h) during the light phase with no restraint on movement was applied to A/J mice, a strain particularly prone to stress. Body temperature was measured with a temperature-sensing microchip implanted in the interscapular region. The stress conditions and anxiety level were evaluated by measuring urinary catecholamines and corticosterone and by performing an anxiety-like behavior test, respectively. Major nutrients such as glucose, fatty acids, and amino acids in the plasma were also examined. CE mice showed a significant increase in body temperature with each CE. They also showed a significantly greater reduction of body weight change, more water intake, and higher levels of urinary catecholamines and corticosterone and anxiety-like behavior score than control mice. The model revealed a significantly lower plasma glucose level and higher levels of several essential amino acids, such as branched-chain amino acids and phenylalanine, than those of control mice. Meanwhile, free fatty acids and several amino acids such as arginine, aspartic acid, proline, threonine, and tryptophan in both sets of mice were significantly decreased from the corresponding levels at 08:00 h, while similar plasma levels were exhibited between mice with and without CE. In conclusion, repeated CE stress was associated with changes in glucose and amino acids in plasma. Although further study is needed to clarify how these changes are specifically linked to anxiety-like behavior, this study suggests the potential for nutritional intervention to counter stress in humans exposed to novel environments.

FRI109 D-Allulose Inhibits NF-kB- And AP1-Mediated Inflammatory Pathways In HepG2 Cells

Abstract Disclosure: N. Gupta: None. J. Batch-Joudi: None. L.D. Graham: None. K. Champagne: None. F. Warda: None. M.J. Haas: None. A. Mooridian: None. Nothing to Disclose: NG, J B-J, LG, KC, FW, MJH, ADM. Source of Research Support: No outside funding was used for this research. Rare sugars such as D-allulose and its derivatives are defined as monosaccharides that are rare in nature. D-allulose is an epimer of D-fructose and is used primarily as a non-nutritive sweetener. D-allulose is also a functional food due to its ability to lower fasting plasma glucose and post-prandial glucose levels in both normoglycemic and diabetics, most likely due to its insulin-mimetic properties as well as its ability to enhance glucagon-like peptide 1. D-alluose has also been shown to possess anti-inflammatory and immunosuppressant activity in allogenic orthotopic liver transportation, neutrophil activation, and monocyte chemoattractant protein-1 expression in endothelial cells. We examined the effects of D-allulose on two well characterized pathways that promote inflammation in HepG2 hepatoblastoma cells, specifically nuclear factor κB (NF-κB) and activator protein 1 (AP1). HepG2 cells were exposed to tumor necrosis factor α (TNFα) (10 ng/ml), lipopolysaccharide (LPS) (10 nM), and high dextrose (27.5 mM). Treatment with 0, 2.8, 5.5, 11, 22, and 27.5 mM D-allulose decreased TNFα-dependent NF-κB and AP1 reporter plasmid activity and 2.8- and 5.5-mM D-alluose decreased NF-κB p50 and p65 subunit expression, measured by Western blot. D-allulose treatment increased IκB expression in TNFα treated cells. D-alluose also suppressed c-jun, phospho-c-jun, and c-fos AP1 subunit expression in TNFα treated cells. Similar effects were observed in D-allulose-treated cells (2.8 and 5.5 mM) exposed to high dextrose and LPS. These results suggest that D-allulose mediates some of its anti-inflammatory effects via suppressing NF-κB and AP1 activity. Presentation: Friday, June 16, 2023

SAT151 Assessments Of Body Composition In Women With Reactive Hypoglycemia

Abstract Disclosure: A. Adamska: None. A. Buczyńska: None. K. Łuka: None. A. Wiatr: None. K. Siewko: None. E. Duraj: None. A. Krętowski: None. A. Popławska-Kita: None. Introduction: Reactive hypoglycemia is characterized by low blood glucose level in non-diabetic patients. It manifests as a syndrome of adrenergic and neuroglycopenic symptoms in the postprandial period, and their resolution occurs after consuming carbohydrates. Reactive hypoglycaemia can also be seen in patients with insulin resistance and hyperinsulinism. In patients with reactive hypoglycemia can be observed disturbances in body composition. The aim of this study was to asses of body composition in women with reactive hypoglycaemia vs control group. Subjects and Methods: We examined 103 women: 49 subjects with RH and 54 control women matched for age and BMI. Four hours oral glucose tolerance test (OGTT) with 75 grams of glucose with estimation of serum glucose and insulin was performed. Body composition was analysed by dual-energy X-ray absorptiometry (DXA). Results: We did not observe differences in fat mass, fat free mass, android fat mass and fat free mass, gynoid fat mass and fat free mass and visceral adipose tissue estimated with DXA method between studied groups (all p&amp;gt;0.05). However, we have found positive relationship between fat mass and serum glucose concentration at 3rd hour of OGTT (r=0.29, p= 0.03) in the group of reactive hypoglycaemia. In the control group be observe relationships between android fat-free mass and serum glucose concentration at 3rd hour of OGTT (r=-0.3, p=0.02) and gynoid fat-free mass and serum glucose concentration at 3rd hour of OGTT (r=-0.27, p=0.04). Conclusions: Women with reactive hypoglycaemia is not differ in body composition estimated with DXA methods. However RH is connected in different manner with glucose homeostasis and fat and lean mass in comparison to control group. Presentation: Saturday, June 17, 2023

SAT167 Risk Of Life Threatening Hypoglycemia When Using U-100 Insulin Syringes To Administer R U-500 Insulin

Abstract Disclosure: T. Rizwan: None. M. Alchalabi: None. G. Arora: None. U.N. Qureshi: None. F. Qureshi: None. Background: Humulin R U-500 is a concentrated human insulin indicated to improve glycemic control in adults and children with diabetes mellitus requiring more than 200 units of insulin per day. R U-500 insulin is five times more concentrated than U-100 insulin. Clinical Case: A 42-Year-old woman with medical history of depression, hidradenitis, morbid obesity, hypertension, hyperlipidemia, chronic headache, and type 2 diabetes mellitus was on R U-500 insulin, Jardiance, and Victoza. Patient presented with low blood glucose levels. Patient reported that her home insulin regimen is 20 units of R U-500 insulin with meals. Her home glucose diary showed blood glucose levels as low as 30-50 mg/dL. Recent hemoglobin A1c was 6.5%. Of note, the patient was unaware of hypoglycemic symptoms. Upon taking detailed history, and discussing insulin injection technique, it was apparent that the patient was administering insulin correctly. Upon further inquiry, the patient reported not being aware of the specialized R U-500 syringe. Patient expressed unfamiliarity after being shown images of the correct R U-500 syringe. It became apparent that the patient was using a U-100 insulin syringe to draw from R U-500 insulin vial which means she was receiving an incorrect dosage. Filling the U-100 syringe to the 20-unit mark with R U-500 insulin will deliver 100 units of R U-500 insulin which puts the patient at risk of severe hypoglycemia. During hospital stay, U-500 R insulin, Victoza, and Jardiance were stopped, the patient was started on basal and bolus insulin regimen, and blood glucose levels were monitored with meals and at bedtime. Blood glucose levels improved to 140-180 mg/dL. Upon hospital discharge, the patient was encouraged to switch to R U-500 KwikPen as this will be more accurate and safe. Conclusion: The U.S. Food and Drug Administration approved a dedicated syringe for the administration of Humulin R U-500 insulin, which is now the only device approved for use with U-500 insulin vial. Do not switch between types of syringes because it may increase the risk of dosing errors. Presentation: Saturday, June 17, 2023

SAT163 Title: Adult-onset Hyperinsulinemic Hypoglycemia Due To An Activating Mutation In Glucokinase

Abstract Disclosure: S. Vaid: None. R. Ghosh: None. H. Elenius: None. C. Cochran: None. R. Chang: None. N. Nilubol: None. R. Muniyappa: None. Introduction: Glucokinase (GK), the key β-cell glucose sensor, determines the threshold for glucose-stimulated insulin secretion. Activating mutations of GK are infrequent causes (prevalence of 1.2%) of congenital hyperinsulinemic hypoglycemia (HH). Adult-onset of severe hypoglycemia due to GK-HH is extremely rare. Clinical Case: A 26-year-old well-nourished female (BMI, 27 kg/m2) with a recent history of dizziness, tremulousness, fatigue, sweating, and hunger, associated with weight gain presented for further workup. Hypoglycemia was noted, and Whipple's triad was confirmed. She had no family history of endocrine disease or hypoglycemia. Supervised fasting promptly produced symptomatic hypoglycemia with hyperinsulinemia. Laboratory studies revealed a low glucose level at 44 mg/dL; a plasma insulin level at 93 μIU/mL (&amp;lt;3 μIU/ml); a C-peptide level at 8.1 ng/mL (&amp;lt;0.6 ng/mL); pro-insulin at 266 pmol/L (&amp;lt;5 pmol/L); and beta-hydroxybutyrate &amp;lt;2.7 mmol/L. IGF2/IGF-1 ratio was 3.1 (&amp;lt;10) and renal and liver function was normal. Interestingly, a mixed meal also provoked significant hypoglycemia within an hour of consumption of a meal. Urine for sulfonylurea screen was negative, and so were anti-insulin antibodies. Imaging of the pancreas with computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound revealed a 1.2x0.8cm nodule on the superior margin of the body of the pancreas. 68Ga-DOTATATE​​ PET/CT (targeting somatostatin receptors) showed mild uptake coinciding with the nodule on the CT scan. Arteriography with calcium stimulation and venous sampling (ASVS) was non-localizing. The patient subsequently underwent laparoscopic exploration with intraoperative ultrasound (IOUS) of the pancreas followed by the enucleation of the pancreatic nodule. Histopathology of the nodule revealed a normal pancreatic tissue with no evidence of a neuroendocrine tumor. Change to multiple small meals, addition of cornstarch to diet, continuous blood glucose monitoring (CGM), diazoxide (70 mg oral, three times a day), and monthly octreotide LAR (30 mg) has allowed the patient to avoid hypoglycemia. Genetic testing by analysis of the genes known to cause hypoglycemia revealed a heterozygous GCK variant [c.1367C&amp;gt;T (p.Ala456Val), which was predicted to be a pathological mutation. This mutation is known to increase affinity for glucose, which leads to exaggerated insulin secretion. Conclusion: Our study highlights that in adults with non-insulinoma pancreatogenous hypoglycemia, genetic causes of HH should be considered in the differential diagnosis. Presentation: Saturday, June 17, 2023

Association of serum 25-hydroxyvitamin D concentrations with all-cause mortality among individuals with kidney stone disease: the NHANES database prospective cohort study.

The purpose of this study was to investigate the correlation between serum 25(OH)D concentrations and all-cause mortality in patients with kidney stone disease (KSD) as the effects of a deficiency in 25-hydroxyvitamin D on KSD patients are currently unclear. For our prospective cohort study, we included 2,916 participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. The National Death Index (NDI) was utilized to identify all causes of death and cause-specific mortality until December 31, 2018. We calculated hazard ratios (HR) and 95% confidence intervals (CIs) using multivariate Cox regression models. During the 18,859 person-years of follow-up, a total of 375 fatalities occurred, including 83 deaths from cardiovascular disease (CVD) and 79 deaths from cancer. At baseline, individuals with higher blood 25(OH)D concentrations had lower levels of glucose, glycohemoglobin, CRP, and insulin, as well as higher levels of HDL cholesterol (P < 0.01). In the fully adjusted model (Model 3), compared to the group with the lowest 25(OH)D concentrations, those with serum 25(OH)D concentrations ≥75 nmol/L had hazard ratios (HRs) and 95% confidence intervals (CIs) of 0.48 (0.26, 0.87) for all-cause mortality (P=0.02, P for trend = 0.02). The association between serum 25(OH)D concentrations and all-cause mortality in KSD patients was found to be significantly non-linear. A 7% decrease in the risk of death from all causes was observed for each unit-nmol/L increase in serum 25(OH)D concentrations when the concentrations were below 27.7 nmol/L (P < 0.05). Based on the findings, KSD patients with insufficient serum 25(OH)D concentrations were at a higher risk of all-cause mortality. Therefore, it is crucial to maintain sufficient blood 25(OH)D concentrations and prevent 25(OH)D insufficiency in order to extend the lifespan of KSD patients.

Genetic and Functional Modifications Associated with Ovarian Cancer Cell Aggregation and Limited Culture Conditions.

The aggregation of cancer cells provides a survival signal for disseminating cancer cells; however, the underlying molecular mechanisms have yet to be elucidated. Using qPCR gene arrays, this study investigated the changes in cancer-specific genes as well as genes regulating mitochondrial quality control, metabolism, and oxidative stress in response to aggregation and hypoxia in our progressive ovarian cancer models representing slow- and fast-developing ovarian cancer. Aggregation increased the expression of anti-apoptotic, stemness, epithelial-mesenchymal transition (EMT), angiogenic, mitophagic, and reactive oxygen species (ROS) scavenging genes and functions, and decreased proliferation, apoptosis, metabolism, and mitochondrial content genes and functions. The incorporation of stromal vascular cells (SVF) from obese mice into the spheroids increased DNA repair and telomere regulatory genes that may represent a link between obesity and ovarian cancer risk. While glucose had no effect, glutamine was essential for aggregation and supported proliferation of the spheroid. In contrast, low glucose and hypoxic culture conditions delayed adhesion and outgrowth capacity of the spheroids independent of their phenotype, decreased mitochondrial mass and polarity, and induced a shift of mitochondrial dynamics towards mitophagy. However, these conditions did not reduce the appearance of polarized mitochondria at adhesion sites, suggesting that adhesion signals that either reversed mitochondrial fragmentation or induced mitobiogenesis can override the impact of low glucose and oxygen levels. Thus, the plasticity of the spheroids' phenotype supports viability during dissemination, allows for the adaptation to changing conditions such as oxygen and nutrient availability. This may be critical for the development of an aggressive cancer phenotype and, therefore, could represent druggable targets for clinical interventions.

Association between plant-based or animal-based dietary pattern and plasma glucose during oral glucose tolerance test among Chinese women with gestational diabetes mellitus: a prospective cohort study

ObjectiveThis study explored whether plant-based and animal-based dietary patterns are associated with plasma glucose levels during oral glucose tolerance test in women with gestational diabetes mellitus (GDM).DesignA prospective cohort study...