Fasting Blood Glucose Research Articles

7216 Absence Of Weight Gain In C57Bl/67 Female Mice On A High-Fat Diet Protects The Skeleton From Bone Loss

Abstract Disclosure: C. McAndrews: None. C. Chlebek: None. S. Costa: None. C.J. Rosen: None. Background: Obesity is associated with both systemic metabolic changes that increase the risk of comorbidities and reduced bone quality that increases the risk of fracture. The effects of high-fat diet consumption have been well studied in preclinical models where high-fat diet-feeding induces obesity, but there have been no studies to investigate the effects of high-fat diet-feeding in animals that do not become obese. Therefore, we characterized components of systemic metabolism and bone mineral content in non-obese C57Bl/6J mice that were fed a high-fat diet. Methods: Female C57Bl/6J mice aged 8 weeks received either a high-fat (60% kcal fat, n = 31) or control (10% kcal fat, n = 17) diet for 12 weeks. Body composition, areal bone mineral density (BMD) and bone mineral composition (BMC) were assessed after the feeding period using dual energy x-ray absorptiometry (Faxitron UltraFocus-DXA). Glucose (GTT) and insulin (ITT) tolerance testing were performed at the conclusion of the study. Changes in body weight were calculated as the difference between baseline and experiment end. High-fat diet-fed animals were classified as obese (HFD-O, n = 24) if they weighed more than 25 g or had greater than 25% body fat as evaluated via DXA, and were otherwise considered non-obese (HFD-NO, n = 7). In a small subset of animals, subcutaneous inguinal fat pads were harvested and weighed (n=5-7/group). Differences between groups were assessed with one-way ANOVAs and Tukey post-hoc analyses. Results: HFD-O mice weighed more than HFD-NO and control animals, whereas the body weights of HFD-NO mice were not significantly different from control (p < 0.001). Fat percent was increased in HFD-O mice compared to HFD-NO and control animals (p < 0.001). Subcutaneous inguinal fat mass was increased in both HFD-O and HFD-NO mice compared to control (p < 0.001). Fasting blood glucose did not significantly differ between groups. Glucose tolerance was worsened in both HFD-O and HFD-NO mice compared to control (p < 0.001), but there were no significant differences in insulin tolerance between groups. BMD was decreased in HFD-O mice compared to HFD-NO and control animals (p < 0.001). DISCUSSION: The consumption of a high-fat diet in mice induces deleterious metabolic changes irrespective of weight gain. However, high-fat diet-induced bone loss does not occur in the absence of weight gain. These findings suggest that certain adipokines derived from larger adipose depots may drive high-fat diet-induced bone loss and warrant further investigation. Acknowledgements: This work was supported by the 2023 Endocrine Society Research Experiences for Graduate and Medical Students (REGMS) Program. Presentation: 6/1/2024

12505 Prevalence Of Mody Diabetes Polymorphism Of Thai Urban Families By Targeted Next Generation Sequencing Of Diabetes Polymorphism

Abstract Disclosure: S. Niramitmahapanya: None. Prevalence of MODY diabetes polymorphism of Thai Urban families by targeted next-generation sequencing in diabetes polymorphismObjective: To study the prevalence between single nucleotide polymorphism of urban diabetes (UD) and non-diabetes (noD) in Thai population. Method: Cross-sectional study was collected 240 participant samples; 60 from UD, 60 from RnoD, 60 from non-relative, non-diabetes (noRnoD) and 60 diabetes, non-relatives (noRD). And generated diabetes variant frequency in Thai population by targeted next-generation sequencing. Result; Among group of UD and RnoD found that age, fasting blood glucose (FBG), HbA1c and LDL level were statistic significant all parameter by p<0.001. Age in UD was 64.15±10.74 vs. 43.43±12.46 in RnoD, FBs in UD was 129.39±44.91 vs. 99.74±39.75 in RnoD, A1c in UD was 8.26±4.76 vs. 6.17±1.35 in RnoD and LDL level in UD was 98.28±38.52 vs. 129.35±39.75 in RnoD.In subgroup analysis of diabetes variant, we designed Ion AmpliSeq On-Demand Panels (25 genes related diabetes) for targeted sequencing. We didn’t found statistic significant between UD and RnoD group by p-value =0.998 (23 genes; ABCC8, FGA, SELE, PAX4, HNF1A, BLK, LOC10028732, NEUROD1, KCNJ11, MMP2, APPL1, LPL, CAT, CEL, HNF1A, HNF1B, ICAM1, INSR, SOD, GCK, INS and UCP3). We identified 12 mutations of MODY in UD, the most polymorphism was HNF1a and ABCC8 that found 16.4%, PAX4 found 13.1%, APPL1 found 11.5%, KCNJ11 and NEUROD1 found 8.2%, BLK 6.6% and other less polymorphism that found <5% (HNF1B, HNF4a, CEL, GCK, INS). Conclusion; From the study, we analyzed genetic data from 12 genes that involved pathogenesis for diabetes polymorphism between UD and noD groups. We focus on diabetes variant frequency. We found that 5 pathogenic polymorphism such as HNF1a, GCK, CEL, INS and APPL1. Further study needs to evaluate correlation diabetes polymorphism and their treatment protocols. Keywords; Thai urban diabetes, first degree relatives and MODY diabetes polymorphism 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

6923 Case Report: Long Standing Type 2 Diabetes with TOFI Phenotype Successfully Weaned Off One Hundred Units of Basal-Bolus Insulin Therapy With Glucagon-Like Peptide 1 Receptor Agonist Therapy

Abstract Disclosure: Y.C. Kon: None. A 60-year-old Indian male was diagnosed with type 2 diabetes in 1997. In July 2017, his fasting blood glucose level (FBGL) was 10.3 mM, paired C-peptide 719 pM, eGFR measured as more than 60 ml/min. Since Sep 2017, he had been compliant on the same stable regimen of sc insulatard 20 units om and 20 units at 10 pm, sc actrapid 20 units t.i.d premeal, PO metformin 850 mg t.i.d and PO dapagliflozin 10 mg om. In the past, he had suffered myocardial infarction, with left ventricular ejection fraction 35%, and had left anterior descending coronary artery stenting. In 2017, he had automatic cardioverter defibrillator implanted for primary arrhythmia prevention. His cardiac medications included bisoprolol fumarate 5 mg om, losartan 25 mg om, spironolactone 25 mg om, aspirin 100 mg om and high intensity statin therapy. Since 2020, his HbA1c had measured 8% to 9% with FBGL at 6 mM to 11 mM. Hence he was referred by his cardiologist in Oct 2022 to optimize glycaemic control. Once every few months, he experienced hypoglycaemic symptoms with corresponding low capillary blood glucose (CBG) of 3 mM, reversed with glucose intake. On physical examination, he weighed 81.6 kg, BMI was 25.4 kg/m2, BP 110/67 mmHg, pulse rate 69/min regular, waist circumference 106 cm. There was no acanthosis nigricans. He did not appear Cushingoid nor acromegalic. As he had “thin outside, fat inside (TOFI)” type 2 diabetes phenotype, he was started on sc liraglutide 1.8 mg om. His actrapid dose was halved to 10 units premeal, and insulatard dose halved to 10 units bid. His dapagliflozin was switched to subsidised empagliflozin 25 mg om. Subsequently, his premeal CBG measured 4 to 7 mM, bedtime CBG 4-6 mM, with occasional minor hypoglycaemic episodes with CBG at 3-4 mM. In July 2023, HbA1c measured 6.3%, FBGL was 5.5 mM and paired C-peptide measured as 554 pM. Basal insulatard was discontinued and he was switched from liraglutide to sc dulaglutide 1.5 mg once weekly. In Oct 2023, his FBGL was 5.2 mM and HbA1c had improved markedly to 5.7%. His weight had reduced from 81.6 kg to 70.0 kg, BMI decreased from 25.4 kg/m2 to 22.9 kg/m2 and waist circumference reduced from 106 cm to 97 cm. As he continued to experience occasional minor hypoglycemic episodes, actrapid insulin was discontinued. On his current therapy of sc dulaglutide 1.5 mg once weekly, PO empagliflozin 25 mg om, PO metformin 850 mg tid, and PO acarbose 50 mg t.i.d, his fasting CBG measured 6.7-7.7 mM, premeal CBG 6.4 to 10.1 mM, off all insulins and without further episodes hypoglycaemia. Conclusion: Patients with long standing “TOFI” type 2 diabetes and robust C-peptide may be trialled on GLP1-receptor agonist therapy to wean off high daily doses of insulin, thus avoiding hypoglycaemia, achieving weight and abdominal fat loss, whilst maintaining glycaemic control. This is especially important in patients with established coronary artery disease. Presentation: 6/3/2024

8638 NEGR1 is a Mediator of Exercise-Induced Neuritogenesis in Subcutaneous White Adipose Tissue, Implications for Improved Systemic Metabolism

Abstract Disclosure: P. Nigro: None. N.P. Carbone: None. T. Caputo: None. M. Vamvini: None. M.M. Columbus: None. M.F. Hirshman: None. R. Middelbeek: None. L.J. Goodyear: None. Emerging research shows that exercise training results in robust and beneficial adaptions to subcutaneous white adipose tissue (scWAT), leading to improved systemic metabolism. The mechanisms for these benefits of exercise on are not fully understood, but we have recently demonstrated that training in mouse scWAT refines nerve connections in scWAT promoting neurite outgrowth (neuritogenesis). Our multi-omics and advanced microscopy data identifies Neuronal Growth Regulator 1 (NEGR1) as a potential player in this process. Here, we determine the role of NEGR1 as a mediator of scWAT neuritogenesis and regulator of systemic metabolism. Exercise training in mice for 11 days significantly increased NEGR1 protein expression by 35% (p<0.05). Next, we directly injected NEGR1 AAV into the inguinal scWAT of untrained male mice for three weeks resulting in a 43% increase in NEGR1 protein (p<0.05). Overexpression of NEGR1 led to an increase in the innervation markers tyrosine hydroxylase (+38%, p<0.01) and synaptophysin (+39%, p<0.01), and remarkably, a 16% decrease in adipocyte cell size (p<0.05), and a 15% reduction in fasting blood glucose levels (p<0.05). This suggests that NEGR1 plays a fundamental role in regulating scWAT morphology and function, adaptations that improve systemic glucose homeostasis. To determine mechanisms for exercise training-induced increases in NEGR1 expression, we used in silico and cell culture experiments and found that NEGR1 is under the regulation of the Peroxisome Proliferator-Activated Receptor gamma (PPARg) transcription factor. Given that numerous natural and synthetic PPARg ligands are lipids, we used targeted lipidomics to identify exercise-induced lipids capable of binding and inducing PPARg expression in inguinal scWAT. We identified 13-oxo-octadecadienoic acid (13-oxo-ODE), an oxylipin derived from linoleic acid, as a potent agonist and inducer of PPARg expression. Exercise training increased 13-oxo-ODE by 3-fold (p<0.05), and 13-hydroxyoctadecadienoic acid (13-HODE), the 13-oxo-ODE precursor was also increased by 3-fold (p<0.01). To validate that 13-oxo-ODE increases NEGR1, adipocytes were incubated with 2μM of 13-oxo-ODE for 48 hours. 13-oxo-ODE increased NEGR1 expression by 27-fold (p<0.0001) and NEGR1 protein by 2-fold (p<0.01). In summary, NEGR1 is a novel exercise-induced molecule that regulates neuronal refinement in scWAT. Our data also suggest that the synthesis of 13-oxo-ODE leads to PPARγ activation that in turn promotes NEGR1 expression in scWAT. NEGR1 has beneficial effects on scWAT that are associated with improved systemic metabolism, making NEGR1 a novel target for treatment of obesity and cardiometabolic diseases. Presentation: 6/1/2024

7288 A Preclinical Mouse Model of Gender-Affirming Hormone Therapy: Metabolic and Behavioral Outcomes

Abstract Disclosure: A. Yasrebi: None. K. Otersen: None. O. Groh: None. E. Guthman: None. I. Shmarakov: None. S. Campbell: None. T.A. Roepke: None. The long-term metabolic effects of gender-affirming hormone therapy (GAHT) is largely unknown, in part, due to the lack of properly designed preclinical animal models. Here we propose a rodent study design, beyond the classical endocrine model of gonadectomy and steroid treatment, to accurately reflect the reality of the trans experience. Specifically, trans women do not all seek or undergo orchidectomy (ORX) instead take estrogen supplementation along with an androgen blocker such as finasteride. In this study, 40 WT C57 male mice were divided into 4 groups of 10 mice - 1) intact with oil vehicle, 2) intact with estradiol benzoate (EB, 150 μg/kg/d) and finasteride (F, 0.25 mg/kg/d), 3) ORX with oil; and ORX with EB (150 μg/kg/d). Each mouse was dosed daily for 8 weeks while on a standard chow diet. Mice were pair housed and food intake and body weight were collected weekly prior to behavioral (open field, elevated plus, Y-maze) and metabolic (body composition, metabolic rates, activity, tolerance testing) phenotyping. Intact mice treated with EB+F exhibited less avoidance behaviors, potentially due to differences in movement, with no differences between treatments in the Y-maze. Cumulatively, Intact:EB+F gained less weight than Intact:oil (3.4 ± 0.4 g vs 5.3 ± 0.4 g), while ORX:oil mice gained less than ORX:EB (2.2 ± 0.5 g vs 5.5 ± 0.7 g). These interactive effects were due to differences in the gain of fat or lean mass between ORX and intact and lower cumulative food intake in ORX:oil mice (136 ± 3.8 g vs Intact:oil: 159 ± 4.9 g; Intact:EB+F: 167 ± 6.1 g; ORX:EB: 171 ± 3.4 g). Metabolic assessments found that Intact:EB+F exhibited elevated V.O2, V.CO2, and heat production in the light and dark cycle compared to Intact:oil, while ORX:EB only exhibited elevated heat production compared to ORX:oil. Similarly, Intact:EB+F and ORX:EB moved more than their counterparts during the dark cycle; however, only Intact:EB+F exhibited elevated wheel running. Tolerance tests (i.p.) found that glucose clearance was augmented in ORX:EB mice while insulin-induced glucose clearance was lower in Intact:EB+F compared to Intact:oil but modestly elevated by EB in ORX mice. These data, along with suppressed fasting blood glucose in ORX:EB mice, suggest that glucose homeostasis is differentially modulated by GAHT paradigms in mice. Analysis of hypothalamic, hepatic, adipose, and intestinal gene expression is currently underway. Collectively, these data, generated by using a translationally-relevant preclinical animal model, are the first to establish that metabolism is differentially affected by both steroid treatments and ORX and suggesting that the long-term metabolic effects of GAHT are dependent on the type of treatment. The underlying mechanisms and sites of action remain to be investigated. Presentation: 6/3/2024

6984 New Onset Diabetes After Transplant: Need for Strict Glucose Monitoring

Abstract Disclosure: T. Chaudhary: None. O. Syed: None. M. Nawaz: None. R. Kaur: None. Introduction: Immunosuppressant use comes at a cost of challenging side effects, which are being discovered more as its use increases. One such example is our case of new-onset diabetes after transplant (NODAT).Patient presentation: A 36-year-old male with a past medical history of end-stage renal disease status post renal transplant (6/2023), hypertension, and hyperlipidemia who presented to the hospital in 10/2023 with fever, chills, and diarrhea. His vitals at that time were as follows: temperature 36.1C, blood pressure 148/84 mmHg, pulse 87 bpm, and a respiratory rate of 22. Lab work was significant for blood glucose 1144, anion gap 22, bicarbonate 13, potassium 7.3, Sodium 135, lipase 427, pH 7.3, urine ketones 80, HbA1C 11.5 %. CT scan of the abdomen revealed loss of peripancreatic fat and inflammatory changes surrounding the pancreas. His medication review included Tacrolimus 12 mg daily, Mycophenolate 500 mg BID, Valtrex 500mg daily, and fluconazole 200mg every other day. He was treated with 2 liters of normal saline bolus and started on maintenance fluid, and insulin drip as per DKA protocol. Calcium gluconate and an albuterol nebulizer were given for hyperkalemia. Tacrolimus and prednisone were held. Endocrinology and Nephrology were consulted. The patient was thought to have diabetes due to steroid use which were discontinued and the patient was discharged on subcutaneous insulin regimen and lower dose of tacrolimus. Despite discontinuation of steroids, patients continued to have raised glucose readings confirming the causative agent as tacrolimus. Conclusion: The current guidelines for post-kidney transplant patients recommend checking fasting blood glucose weekly for the first four weeks, then biweekly for two months, and then monthly thereafter. HbA1C should be checked every 3 months and if it is >6% then home glucose monitoring should be done as well. Although the frequency of these check-ups decreases, it is imperative for physicians to remember that patients can still develop NODAT months post-transplant. It is also essential to reinforce the importance of these glucose checks for the patient as missed diagnosis can lead to dangerous complications such as DKA. Presentation: 6/2/2024

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

In vivo and in silico insights into the antidiabetic efficacy of EVOO and hydroxytyrosol in a rat model

Extra virgin olive oil (EVOO) has a putative antidiabetic activity mostly attributed to its polyphenol Hydroxytyrosol. In this study, we explored the antidiabetic effects of EVOO and Hydroxytyrosol on an in vivo T2D-simulated rat model as well as in in silico study. Wistar rats were divided into four groups. The first group served as a normal control (NC), while type 2 diabetes (T2D) was induced in the remaining groups using a high-fat diet (HFD) for 12 weeks followed by a single dose of streptozotocin (STZ, 30 mg/kg). One diabetic group remained untreated (DC), while the other two groups received an 8-week treatment with either EVOO (90 g/kg of the diet) (DO) or Hydroxytyrosol (17.3 mg/kg of the diet) (DH). The DC group exhibited hallmark features of established T2D, including elevated fasting blood glucose levels, impaired glucose tolerance, increased HOMA-IR, widespread downregulation of insulin receptor expression, heightened oxidative stress, and impaired β-cell function. In contrast, treatments with EVOO and Hydroxytyrosol elicited an antidiabetic response, characterized by improved glucose tolerance, as indicated by accelerated blood glucose clearance. Systematic analysis revealed the underlying antidiabetic mechanisms: both treatments enhanced insulin receptor expression in the liver and skeletal muscles, increased adiponectin levels, and mitigated oxidative stress. Moreover, while EVOO reduced intramyocellular lipids, Hydroxytyrosol restored adipose tissue insulin sensitivity and enhanced β-cell survival. Molecular docking and dynamics confirm Hydroxytyrosol's high affinity binding to PGC-1α, IRE-1α, and PPAR-γ, particularly IRE-1α, highlighting its potential to modulate diabetic signaling pathways. Collectively, these mechanisms highlight the putative antidiabetic role of EVOO and Hydroxytyrosol. Moreover, the favorable docking scores of Hydroxytyrosol with PGC-1α, IRE-1α, and PPAR-γ support the antidiabetic potential and offer promising avenues for further research and the development of novel antidiabetic therapies.

5180 Atypical Presentation of Type 2 Diabetes Mellitus in a 72Year Old Caucasian Male with Hemoglobin J-Baltimore Variant: A Case Report

Abstract Disclosure: C. Muojieje: None. M. Luzuriaga: None. Objective: This case report discusses the unusual manifestation of Type 2 Diabetes Mellitus (T2DM) in a 72-year-old Caucasian male possessing a rare Hemoglobin variant, Hemoglobin J-Baltimore. It emphasizes the importance of recognizing how hemoglobin variants can impact HbA1c measurements. Alternative markers, such as fructosamine and HbA1c measurement using turbidimetric inhibition immunoassay (TINIA), are discussed as potential tools for a more precise assessment of glycemic control. Furthermore, it accentuates the effectiveness of tailored treatment strategies in such cases. Methods: A 72-year-old Caucasian male with a history of T2DM was referred to an endocrinology clinic due to substantial discordance between the blood glucose (BG) values when self-monitoring and HbA1c. The patient was diagnosed with T2DM a decade ago due to fasting hyperglycemia. His HbA1c levels had remained within normal range. He exhibited signs of diabetic nephropathy with moderately increased albuminuria. He was never prescribed an oral hypoglycemic agent. He reported polyuria, weight loss, and fatigue, prompting him to monitor his BG at home twice daily, revealing readings > 200 mg/dl. HbA1c measurement using high-performance liquid chromatography (HPLC) was 4.8%. His fasting plasma glucose was 190 mg/dl, and fructosamine levels were 292 umol/L (205 - 285 umol/L). An HbA1c level via TINIA was 6.4%. Hemoglobin electrophoresis unveiled the presence of Hemoglobin J-Baltimore. We started metformin, resulting in an improvement in HbA1c from 6.4% to 5.8%. Fructosamine levels improved from 292 umol/L to 210 umol/L. Fasting blood glucose remained > 150 mg/dl. Dulaglutide was introduced. Follow-up analysis showed an improvement in FBS to < 120 mg/dl. HbA1c remained unchanged at 5.9%. Conclusion: The significance of hemoglobin variants, exemplified by Hemoglobin J-Baltimore, cannot be overstated in the context of patients with T2DM, especially within populations where these variants are uncommon. This case underscores the need for a nuanced approach to glycemic control assessment in such individuals. The utilization of alternative markers, such as HbA1c values obtained through TINIA, emerges as a valuable strategy. The role of continuous glucose monitoring (CGM) is crucial, providing real-time and comprehensive data, which enhances the quality of care and contributes to more tailored and effective treatment strategies. Presentation: 6/1/2024

7484 Pseudohypoglycemia In A Patient With Raynaud’s Phenomenon

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

Homeostatic Effect of Phoenix Dactylifera on Alloxan-Induced Diabetes and Aluminium-Induced Neurotoxicity in Male Wistar Rats

Introduction: This study assessed homeostatic effect of Phoenix dactylifera on alloxan-induced diabetes and aluminium-induced neurotoxicity in male wistar rats divided into 5 groups of 5 rats each. Methods: Group A; control, Group B; diabetic group, Group C; AlCl3, Group D Alloxan+ P. dactylifera, Group E; AlCl3 + P. dactylifera (0.5ml each). Diabetes was experimentally induced in groups B-D. The animals were left to acclimatize for 2 weeks and treatments were dissolved in distilled water and given orally for 2 weeks (4weeks). Blood sample was collected via ocular puncture for analysis of fasting blood glucose level. At the end of 4 weeks, the animals were sacrificed and blood samples taken for estimation of oxidative stress markers. Blood and brain samples were collected for neuromuscular function markers. Results: The results were statistically significant at 95% confidence interval. The results obtained when compared to control from showed group D and E exhibited decrease levels of lipid peroxidation (MDA), increased levels of antioxidant enzymes (SOD, CAT, GPx and GSH). There was also decrease BGL2, indicating positive glycemic control. When compared to the diabetic group, the treatment group showed a significant reduction in MDA levels and significant increase in the levels of GSH, CAT, SOD, and GPX. It also showed significant decrease in CKMM levels (less muscle activity and damage), and increase in AChE indicating nerve activity and stress was observed in control group too. Significant reduction in FBGL2 were shown. There was no significant difference in FBG1 levels. Conclusion: P. dactylifera aqueous extract exhibits potential antidiabetic and antioxidant effect in Alloxan-induced diabetic and aluminium-induced toxicity in male wistar rats. Keywords: Phoenix dactylifera; Neurologic; Diabetes; Phytochemical; Therapy

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

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

Investigation of the risk factors associated with prediabetes in normal-weight Qatari adults: a cross-sectional study

Type 2 diabetes is one of the most prevalent chronic diseases in the world, and more people than ever before have impaired glucose tolereance, or prediabetes. Many patients with impaired glucose tolerance and undiagnosed diabetes do not know that their glucose metabolism system has been in a state of disorder. Every year, about 5-10% of prediabetics develop diabetes. One of the important achieving factors may be the increase in blood lipids. However, it is not clear whether triglyceride is associated with impaired glucose tolerance and prediabetes in the Qatari population. Therefore, we investigated the relationship between the first several clinical variables and prediabetes status in normal and overweight populations. We conducted a cross-sectional study using data from the Qatar Biobank program. The study included 5,996 participants who were adults over the age of 20. We collected information about participants’ fasting blood glucose levels with other clinical measurements and used various machine learning models and logistic regression to study the association between the clinical measurements and prediabetes for normal and overobese weight groups. The use of several machine learning models showed that, after adjusting the potential confounding factors such as age and sex, Triglyceride has been demonstrated to be positively correlated with prediabetes, and there was a special population dependence phenomenon. Among them, nonobese people (p < 0.05). The effect value and 95% confidence interval and OR of triglyceride on prediabetes was 2.79 and (e0.78, e1.28), respectively.

Correlation Analysis of Traditional Chinese Medicine Constitution and Metabolic Indexes in General Physical Examination People.

Analysis of Traditional Chinese Medicine (TCM) constitution type general medical patients and the relationship between the metabolic index. A cohort of 1,029 general individuals who underwent a physical examination at the Affiliated Hospital of Changchun University of Chinese Medicine for identification of their TCM constitution between January 2021 and April 2023 were included in this study. Their data were sorted and analyzed using Microsoft Excel and SPSS26.0 statistical software. Among the 1029 study participants, the balanced constitution (BC) type was the most prevalent (33.24%), and the blood stasis constitution (BSC) type was the least prevalent (2.62%). Compared with BC, phlegm-dampness constitution (PDC) (P=0.000), yang-deficiency constitution (YADC) (P=0.000) and BSC (P=0.008) had significant differences in body mass index (BMI) (P<α). The systolic blood pressure (SBP) of PDC was different (P=0.042, P<α). There was a significant difference in diastolic blood pressure (P=0.001, P<α). The diastolic blood pressure (DBP) of YADC was significantly different (P=0.001, P<α). Yin-deficiency constitution (YIDC) (P = 0.007) and YADC differences between fasting blood glucose (FBG) (P = 0.025) were significantly (P<α). There were significant differences in uric acid (UA) of YADC (P=0.000), BSC (P=0.004), PDC (P=0.007) and qi-stagnation constitution (QSC) (P=0.012, P<α). The triglyceride (TG) of YADC (P=0.000) and PDC (P=0.005) were significantly different (P<α). There was a difference in total cholesterol (TC) between PDC (P=0.046) and BC (P<α). BSC (P = 0.028) and PDC (P = 0.023) of low-density lipoprotein cholesterol (LDL-C) also had a significant difference (P<α). People with PDC, YADC and BSC had more abnormal metabolic indexes than people with BC, and the metabolic indexes of people with YIDC constitution were different from those with BC. Individuals with these four TCM constitution types should pay attention to making appropriate changes in lifestyles and dietary habits and take required measures to prevent the incidence and development of metabolic diseases.

New peripherally-restricted CB1 receptor antagonists, PMG-505–010 and −013 ameliorate obesity-associated NAFLD and fibrosis

The endocannabinoid system plays a crucial role in metabolic regulation, prompting the investigation of cannabinoid type 1 receptor (CB1R) antagonists for obesity and its complications like non-alcoholic fatty liver disease (NAFLD). Concerns over psychiatric side effects led to the development of peripheral CB1R antagonists that circumvent the blood-brain barrier (BBB). In this study, we synthesized PMG-505–010 and PMG-505–013 as peripherally restricted CB1 receptor antagonists by modifying rimonabant to minimize BBB penetration. Physicochemical analysis confirmed their reduced lipophilicity and increased polarity compared to rimonabant, indicating limited brain exposure. Molecular docking studies revealed similar binding modes to rimonabant at CB1R, characterized by robust hydrophobic interactions. Functionally, they acted as CB1R antagonists and inverse agonists, effectively reversing CP55,940-induced cAMP inhibition. In a murine model of obesity-related NAFLD, PMG-505–010 and −013 improved metabolic profiles, including fasting blood glucose levels and dyslipidemia. They also ameliorated hepatic injury, steatosis, and inflammation, evidenced by reduced liver enzymes, lipid peroxidation, hepatic lipid levels, and inflammatory cytokine levels. Notably, these compounds inhibited hepatic fibrosis by reducing extracellular matrix (ECM) deposition and altering fibrosis-related gene and protein expressions. In conclusion, PMG-505–010 and PMG-505–013 hold promise for treating obesity-related liver diseases, including NAFLD and fibrosis, through selective peripheral CB1R targeting, potentially avoiding CNS-related side effects seen with earlier CB1R antagonists.

Low-carbohydrate diets in East Asians with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials.

Despite the reported success of low-carbohydrate diets in improving glycemic control in the Western countries, no studies have investigated the effects of such diets in Asians. We aimed to conduct a systematic review and meta-analysis of randomized controlled trials to examine the effects of low-carbohydrate diets on glycemic control in East Asian adults. We systematically searched the PubMed, Cochrane Library, and Embase databases from inception to June 28, 2023, to identify randomized controlled trials examining the efficacy of low-carbohydrate diets in patients with type 2 diabetes (PROSPERO number CRD 42023453007). The primary outcome was the difference in glycated hemoglobin levels between the low-carbohydrate diet and control groups. The secondary outcome was the difference in body mass index, fasting blood glucose level, blood pressure, and lipid profile. Six randomized controlled trials met the eligibility criteria. The study duration ranged from 3 to 18 months, with five studies conducted within 6 months. The results showed that low-carbohydrate diets were more beneficial in lowering glycated hemoglobin levels and body mass index than control diets. The risk of bias for the six studies was minimal for two and moderate for four. The heterogeneity among the studies was low. Low-carbohydrate diets improved glycated hemoglobin levels and body mass index in East Asians compared with control diets. Therefore, carbohydrate restriction may be effective for glycemic management in East Asians with type 2 diabetes for at least 6 months.

The association of plasma asprosin with anthropometric and metabolic parameters in Korean children and adolescents.

This study aimed to determine the correlation of plasma asprosin with anthropometric and metabolic parameters in Korean children and adolescents. This single-center study included 109 Korean children and adolescents: 62 (56.9%) obese participants with a body mass index (BMI) ≥95th percentile and 47 (43.1%) healthy controls with BMI between the 15th and 85th percentile. Metabolic parameters were measured, including fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride and glucose (TyG) index, and lipid profiles. Plasma asprosin levels were higher in the obese group than in the control group (mean 87.0 vs. 69.3 ng/mL; p = 0.001) and in the IR group than in the non-IR group (mean 98.6 vs. 70.2 ng/mL; p < 0.001). Plasma asprosin levels were not associated with sex or pubertal stage. Plasma asprosin levels were positively correlated with BMI SDS (r = 0.34; p = 0.002), glycated hemoglobin (HbA1c) (r = 0.25; p = 0.02), glucose (r = 0.33; p = 0.002), insulin (r = 0.44; p < 0.001), HOMA-IR (r = 0.47; p < 0.001), triglyceride (TG) (r = 0.33; p = 0.003), high-density lipoprotein (HDL) cholesterol (r = -0.29; p = 0.008), and TyG index (r = 0.38; p < 0.001). Multiple linear regression analysis indicated that plasma asprosin levels were independently associated with HOMA-IR (p < 0.001) and TG/HDL cholesterol ratio (p < 0.001). This study demonstrated an association between plasma asprosin levels and obesity and insulin resistance in Korean children and adolescents.

Relationship between dietary sialic acid intake and serum HbA1c: a population-based study in Xiamen, China

This study investigates the correlation between dietary sialic acid intake which mainly come from eggs, red meat, and dairy products and serum HbA1c levels. A survey among Xiamen’s general population, China, collected dietary data from 2,908 participants over the past year. A semi-quantitative food frequency questionnaire (FFQ) was employed. Sialic acid intake was calculated, along with measurements of biochemical indicators, including fasting blood glucose, HbA1c, blood lipids, and insulin. Sociodemographic and physical data were also collected. Logistic regression models evaluated the relationship between dietary sialic acid and HbA1c levels. The daily sialic acid intake in Xiamen’s general population was 48.55 (21.68, 65.23) mg/1000Kcal, accompanied by a 1.96% rate of high HbA1c. A significant negative correlation between dietary sialic acid and HbA1c was observed. Individuals in the highest quartile of sialic acid intake (> 65.48 mg/1000 kcal) had a lower risk of high HbA1c compared to those in the lowest quartile (< 23.63 mg/1000 kcal) [OR: 0.123 (0.022, 0.689)]. A high dietary sialic acid intake within a specific range may reduce the risk of elevated HbA1c levels, suggesting a potential preventive effect. Note that this effect is limited to specific intake ranges.

Efficacy of vitamin D supplementation on glycaemic control in type 2 diabetes: An updated systematic review and meta-analysis of randomized controlled trials.

To assess the effects of vitamin D interventions on glycaemic control in subjects with type 2 diabetes (T2D). We searched PubMed, EMBASE, Web of Science and the Cochrane Library for relevant studies. Serum 25(OH)D, fasting blood glucose (FBG), HbA1c, fasting insulin and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) were analysed. We identified 39 randomized controlled trials involving 2982 subjects. Results showed a significant decline in the vitamin D group, as shown by the FBG weighted mean difference (WMD; -0.49 [95% confidence interval {CI}: -0.69 to -0.28] mmol/L), HbA1c (WMD -0.30% [95% CI: -0.43 to -0.18]), HOMA-IR (WMD -0.39 [95% CI -0.64 to -0.14]) and insulin (WMD -1.31 [95% CI: -2.06 to -0.56] μIU/mL). Subgroup analyses indicated that the effects of vitamin D supplementation on glycaemic control depend on the dosage and duration of supplementation, baseline 25(OH)D levels and the body mass index of patients with T2D. Vitamin D supplementation can significantly reduce serum FBG, HbA1c, HOMA-IR and fasting insulin levels in T2D patients; the effects were especially prominent when vitamin D was given in a short-term, high dosage to patients with a vitamin D deficiency, who were overweight, or had an HbA1c of 8% or higher at baseline. Our study suggests that vitamin D supplements can be recommended as complementary treatment for T2D patients.