Plasma Glucose Levels Research Articles

Effects of dietary carbohydrate levels on growth performance, feed utilization, liver histology and intestinal microflora of juvenile tiger puffer, Takifugu rubripes

An 8-week feeding trial was conducted to investigate the effects of dietary carbohydrate levels on growth performance, body composition, and plasma biochemical parameters, liver and gut histology, and intestinal microbiota of Takifugu rubripes. Five isonitrogenous and isolipidic experimental diets were formulated with graded levels of cassava starch: 0% (C0), 8% (C8), 16% (C16), 24% (C24), and 32% (C32). The results showed that weight gain rate, specific growth rate (SGR) and protein efficiency ratio significantly increased in C16 and C24 groups (P < 0.05), while the feed conversion ratio expressed an opposite trend. Feeding rate is decreased with the increasing of carbohydrate levels (P < 0.05). Liver lipid content was dramatically increased in C24 treatment (P < 0.05). The intestinal amylase activity and muscle glycogen content were higher than other groups (P < 0.05). Plasma glucose levels were increased in C24 and C32 groups (P < 0.05). In addition, the abundance of intestinal potentially pathogenic bacteria (Staphylococcus) decreased, and the intestinal probiotics (Lactobacillus) increased with the increasing of dietary carbohydrate level (P < 0.05). The intestinal bacteria, indicated by Sobs, Chao and Shannon indexes, were more diverse with the increasing of the carbohydrate level (P < 0.05), meanwhile the abundance of transport and metabolism of carbohydrate, lipid and amino acid were enhanced with the increasing of carbohydrate levels (P < 0.05). In conclusion, appropriate supplementation of carbohydrate in diet promoted growth performance and feed utilization of juvenile Takifugu rubripes, and increased the liver lipid and muscle glycogen content, as well as intestinal microbial diversity. Based on the quadratic regression between SGR and carbohydrate levels, the optimal dietary carbohydrate level of juvenile Takifugu rubripes is 21.6%.

Analytical Method Development and Optimization on High Performance Liquid Chromatography for Related Substances Test of Gliclazide Drug as Active Pharmaceutical Ingredient

Diabetes mellitus, particularly Type 2 Diabetes Mellitus (T2DM), presents a significant global health challenge, necessitating continuous advancements in therapeutic strategies. Gliclazide, an oral selective inhibitor of sodium glucose co-transporter-2 (SGLT2), has emerged as a promising agent for managing T2DM by facilitating urinary glucose excretion and reducing plasma glucose levels. However, ensuring the quality and efficacy of pharmaceutical formulations remains crucial for regulatory approval and clinical effectiveness. In this study, we present the development of an improved stability-indicating Reverse Phase-High Performance Liquid Chromatography (RP-HPLC) method for the precise quantification of Gliclazide. The novel analytical method employs 0.1% Potassium Phosphate in water 0.1% Potassium Phosphate in methanol (MeOH) as the mobile phase, demonstrating enhanced sensitivity, cost-effectiveness, and reduced reliance on organic chemicals. Through rigorous validation following International Conference on Harmonisation (ICH) guidelines, the developed method exhibited superior performance in terms of retention times compared to existing methodologies. The proposed analytical approach holds promise for routine analysis of Gliclazide in both bulk and tablet formulations, offering a valuable tool for pharmaceutical quality control and clinical research in the management of T2DM.

Analysis of non-physiological shear stress-induced red blood cell trauma across different clinical support conditions of the blood pump.

Systematic research into device-induced red blood cell (RBC) damage beyond hemolysis, including correlations between hemolysis and RBC-derived extracellular vesicles, remains limited. This study investigated non-physiological shear stress-induced RBC damage and changes in related biochemical indicators under two blood pump clinical support conditions. Pressure heads of 100 and 350mmHg, numerical simulation methods, and two in vitro loops were utilized to analyze the shear stress and changes in RBC morphology, hemolysis, biochemistry, metabolism, and oxidative stress. The blood pump created higher shear stress in the 350-mmHg condition than in the 100-mmHg condition. With prolonged blood pump operation, plasma-free hemoglobin and cholesterol increased, whereas plasma glucose and nitric oxide decreased in both loops. Notably, plasma iron and triglyceride concentrations increased only in the 350-mmHg condition. The RBC count and morphology, plasma lactic dehydrogenase, and oxidative stress across loops did not differ significantly. Plasma extracellular vesicles, including RBC-derived microparticles, increased significantly at 600min in both loops. Hemolysis correlated with plasma triglyceride, cholesterol, glucose, and nitric oxide levels. Shear stress, but not oxidative stress, was the main cause of RBC damage. Hemolysis alone inadequately reflects overall blood pump-induced RBC damage, suggesting the need for additional biomarkers for comprehensive assessments.

Assessing the Features of Diabetic Foot Ulcers among Individuals with Type 2 Diabetes Mellitus in Thi Qar, Iraq

Background This study aimed to evaluate the characteristics of diabetic foot ulcers in individuals with type 2 diabetes mellitus (T2DM) in Iraq. Methods The study included 881 participants with T2DM and different types of foot ulcers, who attended a specialized diabetes center. Data on demographics, clinical characteristics, biochemical investigations, comorbidities, and treatment regimens were collected and analyzed. Results The majority of the cases (96.8%) were due to T2DM, with an average age of 58 years and a mean BMI of 30 kg/m2. Participants had elevated serum creatinine, blood urea, and glucose levels, with uncontrolled HbA1c levels. Comorbidities included hypertension, ischemic heart disease, diabetic neuropathy, and retinopathy. Most participants were on insulin and statins. Diabetic foot ulcers were mainly on the right foot (48%) and classified as Grade 2 in Wagner's system. Some participants had Charcot deformity or stages of amputation. Conclusions Random plasma glucose levels and diabetic retinopathy were significantly associated with the classification of foot ulcers. Further research is needed to explore additional variables related to T2DM and foot ulcers, emphasizing the importance of glucose control and retinopathy in ulcer classification.

Eating Patterns, Chronotypes, and Their Relationship with Metabolic Health in the Early Postpartum Period in Women after Gestational Diabetes Mellitus

Observational studies have shown a relationship between eating patterns and chronotypes with metabolic health in the general population and in healthy pregnancies. Data are lacking in the postpartum period, which is characterized by an externally driven misalignment of sleep and food intake. We investigated the associations between eating patterns, chronotypes, and metabolic health in the early postpartum period in women who had gestational diabetes mellitus (GDM). We prospectively included 313 women who completed their 6–8 weeks postpartum visit between January 2021 and March 2023 at the Lausanne University Hospital. Women filled questionnaires on the timing of food intake, sleep (a shortened Pittsburgh Sleep Quality Questionnaire), and the chronotype (the Morningness–Eveningness Questionnaire) and underwent HbA1c and fasting plasma glucose measurements. After adjustments for weight, sleep quality, or breastfeeding, the later timing of the first and last food intake were associated with higher fasting plasma glucose and HbA1c levels 6–8 weeks postpartum (all p ≤ 0.046). A higher number of breakfasts per week and longer eating durations were associated with lower fasting plasma glucose levels (all p ≤ 0.028). The chronotype was not associated with metabolic health outcomes. Eating patterns, but not the chronotype, were associated with worsened metabolic health in the early postpartum period in women with previous GDM.

#2209 Hypoglycemia induced by hemodialysis in diabetic and non-diabetic patients, how to prevent it? A prospective study

Abstract Background and Aims Hemodialysis-induced hypoglycemia, a documented complication associated with adverse clinical outcomes, including mortality, is linked to factors such as impaired gluconeogenesis, inadequate nutritional status, reduced insulin clearance, glucose loss to the dialysate, and autonomic neuropathy. Glycemic variability is recognized as an independent risk factor for morbidity and mortality. This study aims to investigate the incidence of hypoglycemia during hemodialysis (HD) by exploring protocol-related factors and their impact, such as in-nutrition during HD. Additionally, the study seeks to examine the relationship between nutritional and inflammatory statuses and variations in intradialytic glycemia in both diabetic and non-diabetic patients. Method This prospective study, conducted between September and December 2023, examined the glycemic profiles of HD patients at a hospital HD program. All patients undergo hemodialysis with a dialysate containing 100 mg/dL of glucose. Plasma glucose levels were assessed at the start, 2:30 hours post-initiation, and the end of sessions. Following the 2:30-hour mark, patients received a meal (523 Kcal). Glycose variability was computed by averaging blood glucose differences across all sessions. Data collected included demographics, hemodialysis specifics, and lab results. Inflammatory and nutritional statuses were evaluated using lab tests at the study's beginning and conclusion [ferritin, protein C reactive (PCR), interleukin 6 (IL-6) and albuminemia, urea, creatinemia, cholesterol, respectively]. Anthropometric measurements and bioimpedance assessments were performed, with values averaged for better representation. Categorical variables are shown with frequencies/percentages, and continuous variables with means/standard deviations or medians/interquartile ranges for skewed distributions. The study used repeated measures ANOVA for glycemic profiles, correlation analyses for outcome influences on glycemia, and parametric/non-parametric tests for relations in diabetic and non-diabetic groups. Significance was set at p&amp;lt;0.05, analyzed with SPSS version 29 for Mac OS 13. Results 63 patients, 67.2% (n=43) were males, the medium age was 72.0±11.8 and 50.8% (n=32) had diabetes. Among 9072 measurements, hypoglycemia was observed in 0.07% (n=6) of diabetic patients and 0.01% (n=1) in non-diabetic individual. The initial blood glucose measurement was 139.5±260.0 mg/dL, the second was 117.05±35 mg/dL, and the third was 132.8±21.3 mg/dL. Significant differences were observed in all measurements [F (1.17, 73.58)=23.62; p&amp;lt;0.001]. The mean glycemic variation between the first and second measurements was 23.8±46.0 mg/dL, and for the third measurement was 5.5±71.5 mg/dL. There was no significant correlation found between glycemic and nutritional parameters neither between inflammatory parameters. In the subgroup analysis comparing diabetic and non-diabetic patients, the diabetic group demonstrated lower serum creatinine levels (6.8±2.7 mg/dL) and total cholesterol (137.4±35.6 mg/dL), coupled with a higher Charlson Index (8.2±1.7). These differences were statistically significant (p=0.055, p=0.035, p&amp;lt;0.001). In the subsequent analysis, no other statistically significant associations were observed. Conclusion Contrary to what is described in the literature, the studied population exhibited a very low incidence of hypoglycemic events. This underscores the importance of nutrition during HD, along with the use of a glucose-containing dialysate, as an effective preventive measure against intradialytic hypoglycemia. Careful consideration of these factors is warranted to prevent adverse health consequences for our patients. It is plausible that diabetic patients may face an elevated risk of malnutrition, necessitating heightened concern and a more proactive preventive approach.

Mediterranean Diet Combined with Regular Aerobic Exercise and Hemp Protein Supplementation Modulates Plasma Circulating Amino Acids and Improves the Health Status of Overweight Individuals

Plant protein is considered a sustainable health-promoting strategy to prevent metabolic syndrome. Lifestyle changes (including dietary patterns and exercise) have been demonstrated to exert an effect on human health by modulating the biochemical status in humans. The objective of this study was to assess whether supplementation with hemp protein within a Mediterranean diet context together with exercise could help to ameliorate the metabolic statuses of patients prone to developing metabolic syndrome. For this study, 23 patients followed with Mediterranean diet and engaged in aerobic exercise according to the WHO’s recommendations, while also being supplemented with hemp protein, for 12 weeks. A comparison of anthropometric, biochemical, and mineral data as well as amino acid values was made between the start and the end of the study, with the subjects acting as their own control group. Statistical analyses included a paired t-test, Wilcoxon paired test, Pearson correlation coefficient, and Sparse Partial Least Squares Discriminant Analysis to evaluate significant differences and correlations among parameters. There were statistically significant changes in total cholesterol, HDL-C (+52.3%), LDL-C (−54.0%), and TAG levels (−49.8%), but not in glucose plasma levels. Following the intervention, plasma concentrations of some amino acids, including α-aminoadipic acid, phosphoethanolamine, and 1-metylhistidine, increased, whereas those of asparagine and alanine declined. Different correlations between amino acids and the other parameters evaluated were reported and discussed. A Mediterranean diet combined with regular aerobic exercise, together with protein supplementation, can highly improve the metabolic parameters and anthropometric parameters of subjects with obesity and impaired glucose levels, ameliorating their health status and likely delaying the development of metabolic syndrome.

Temporal trends in the visual impairment burden attributable to high fasting plasma glucose levels: a population-based study.

Elevated fasting plasma glucose (FPG) levels have been associated with visual impairment. Recognising global patterns of high FPG level exposure can facilitate the prevention and treatment of related visual impairment. We aimed to assessthe trendsof the visual impairmentburden attributable to high FPG levels globally, regionally, nationally, and by income level. We obtained data on the visual impairment burden attributable to high FPG levels from the Global Burden of Disease Study 2019. We evaluated the trends of related disability-adjusted life-years (DALYs) from 1990 to 2019 through joinpoint regression analysis and calculated the annual percentage change (APC) and average APC (AAPC). Countries/territories were categorised into high-, upper-middle-, lower-middle-, and low-income groups based on the 2019 World Bank criteria. The age-standardised rate of DALYs due to visual impairment attributable to high FPG levels significantly increased globally, from 6.75 (95% uncertainty interval [UI], 1.55-15.79) in 1990 to 8.44 per 100,000 population (95% UI, 2.00-19.63) in 2019 (AAPC, 0.79; 95% confidence interval [CI], 0.69-0.89; p < 0.001). The largest increases were observed in high-income (AAPC, 0.73; 95% CI, 0.60-0.85) and lower-middle-income countries/territories (AAPC, 0.68; 95% CI, 0.62-0.73). In 2019, lower-middle-income countries/territories had the highest age-standardised DALY rate (18.94 per 100,000 population; 95% UI, 4.39-43.98), whereas high-income countries/territories had the lowest (2.97 per 100,000 population; 95% UI, 0.75-6.74). The visual impairment burden associated with elevated FPG levels has increased significantly, necessitating enhanced public health prevention measures, clinical management, and treatment to mitigate adverse outcomes.

Long-term effects of ipragliflozin and pioglitazone on metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes: 5 year observational follow-up of a randomized, 24 week, active-controlled trial: Effect of ipragliflozin in MASLD.

We conducted a 5 year post-trial monitoring study of our previous randomized 24 week, open-label, active-controlled trial that showed beneficial effects of ipragliflozin on metabolic dysfunction-associated steatotic liver disease (MASLD), identical to those of pioglitazone. In our previous trial, 66 patients with MASLD and type 2 diabetes were randomly assigned to receive either ipragliflozin (n = 32) or pioglitazone (n = 34). Upon its conclusion, 61 patients were monitored for 5 years for outcome measures of MASLD, glycemic, and metabolic parameters. Differences between the two groups were analyzed at baseline, 24 weeks, and 5 years; changes in outcome measures from baseline were also evaluated. At 5 years, the mean liver-to-spleen attenuation ratio increased by 0.20 (from 0.78 ± 0.24 to 0.98 ± 0.20) in the ipragliflozin group and by 0.26 (from 0.76 ± 0.26 to 1.02 ± 0.20) in the pioglitazone group (P = 0.363). Similarly, ipragliflozin and pioglitazone significantly improved serum aminotransferase, HbA1c, and fasting plasma glucose levels over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat area observed at 24 weeks were sustained throughout the 5 years (-4.0%, P = 0.0075 and -7.6%, P = 0.045, respectively). Moreover, ipragliflozin significantly reduced the values of fibrosis markers (serum ferritin and FIB-4 index), was well tolerated, and had a higher continuation rate for 5 years compared with pioglitazone. Ipragliflozin and pioglitazone improved MASLD and glycemic parameters over 5 years. In the ipragliflozin group, significant reductions in body weight and visceral fat mass persisted for 5 years.

Phytosterol supplementation enhances the growth performance, feed utilization, antioxidant status and glucose metabolism of juvenile largemouth bass (Micropterus salmoides) fed a high-starch diet

IntroductionPrevious studies found that phytosterols could influence growth performance, feed utilization and lipid metabolism as well as improve the antioxidant capacity of animals.MethodsTo investigate the effects of dietary phytosterol supplementation on juvenile largemouth bass (Micropterus salmoides) fed a high-starch diet, a 56- day feedingtrial was conducted with four dietary feeds for juvenile largemouth bass: extruded floating feed isonitrogenous and isoenergetic diets were formulated to contain 10% and 15% α-starch; on the basis of a 15% α-starch diet, two other diets were formulated with supplementation of 0.1% and 0.5% phytosterol, respectively. After the feeding trials, the survival rate, weight gain and specific growth rate, feed conversion ratio, intraperitoneal fat ratio, feed intake, protein efficiency ratio and activities of three digestive enzymes, as well as the concentrations of nine plasma biochemical indices, hepatic enzyme activities and glycogen contents, were measured and calculated, and the data were statistically analyzed.ResultsThe results of the present study showed that the survival rate, weight gain and specificgrowthrates were significantly greater in plants fed high-starch diets supplemented with phytosterols. As the supplemental phytosterol concentration increased, the feed conversion ratio and intraperitoneal fat ratio significantly decreased; the protease and lipase levels in the pyloric zone markedly increased; the plasma cholesterol, triglyceride, glucose, malondialdehyde, aspartate transaminase and alanin transaminase levels significantly decreased; the glucokinase and pyruvate kinase levelsmarkedly increased; and the hepatic glycogen content significantly decreased.DiscussionIn summary, dietary phytosterol supplementation promoted the growth performance, feed utilization and antioxidant status of juvenile largemouth bass fed a highstarch diet; enhanced glucose utilization and metabolism; and alleviated the negative stimulation of glycemia stress in M. salmoide fed a high-starch diet.

Long-term prognostic significance of stress hyperglycemia in patients with ST-elevation myocardial infarction

Abstract Funding Acknowledgements None. Background/aim Stress hyperglycemia is defined as hyperglycemia that occurs in critically ill patients without diabetes mellitus (DM). It is associated with adverse in-hospital outcomes in patients with ST elevation myocardial infarction (STEMI). The aim of the present study is to evaluate short- and long-term prognostic impact of stress hyperglycemia in STEMI patients. Method We analysed 2505 consecutive STEMI patients treated with successful primary PCI (pPCI) without previous DM and without cardiogenic shock at admission. Successful pPCI was defined as post-procedural flow TIMI 3. Stress hyperglycemia was defined as plasma glucose level above 7.8mmol/L at any time during hospitalization. The follow-up period was 6 years. Results Stress hyperglycemia at admission was registered in 685 (27.3%) patients. Compared with patients without stress hyperglycemia, patients with stress hyperglycemia were older and presented more often with heart failure (Killip class II and III); they were more likely to have hypertension, chronic kidney disease, three vessel coronary disease (at initial angiogram) and lower predischarge left ventricular ejection fraction (EF). In-hospital, 30-day and 6-year mortality were significantly higher in patients with stress hyperglycemia vs patients without stress hyperglycemia: 7.1% vs 1.5%, 7.5% vs 1.7% and 12.5% vs 4.6% (p&amp;lt;0.001), respectively as shown in Figure 1. In Cox regression analysis stress hyperglycemia was an independent predictor for in-hospital, 30-days and 6-year mortality- HR 2.19 (95% 1.49-3.94), p=0.018, HR 1,58(95%CI 1.15-2.85), p=0.020 and HR 1.52 (95%CI 1.32-2.17), p=0.030, respectively. Conclusion In STEMI patients without diabetes mellitus treated with successful primary PCI stress hyperglycemia is an independent predictor for short- and long-term mortality (up to 6-years). These findings emphasize the importance of close monitoring of blood glucose level in STEMI patients regardless of diabetic status.

Weight loss, glycolipid profile changes in type 2 diabetes patients after esophagectomy: a propensity score matching analysis

BackgroundType 2 diabetes mellitus (T2DM) is a common co-morbidity in patients who receive esophagectomy and has unfavorable effects on glucose and lipid metabolism in patients. This study examines how weight and glycolipid metabolism change in patients with T2DM following esophagectomy.MethodsThis retrospective, one-center, observational analysis with a propensity score matching analysis (PSM) included 114 patients who underwent esophageal surgery in the Department of Cardiothoracic Surgery, the 900th Hospital of Joint Logistic Support Force from 2017 to 2020, which were separated into T2DM group and Non-T2DM group. Weight, body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured and analyzed before and after the operation.ResultsTwo groups showed similar reductions in weight and BMI after surgery. In the T2DM group, weight decreased from 63.10(10.31) before surgery to 55.10(11.60) kg at 6 months (P < 0.001) with BMI decreasing from 22.67 (2.90) to 19.77 (3.48); While in the Non-T2DM group, weight decreased from 61.42 (8.46) to 53.19 (9.26) kg at 6 months after surgery with BMI decline from 22.49 (2.77) before operation to 19.45 (3.08) at 6 months after surgery. Fasting plasma glucose levels showed a significant decrease (P = 0.035) in the T2DM group at a six-month point of 7.00 (2.21) mmol/L compared to preoperative levels of 7.67 (2.32) mmol/L. HDL levels increased significantly in the Non-T2DM group at six months postoperatively at 1.52 (0.05) with P < 0.001 compared to preoperative levels of 1.22(0.04) mmol/L. TG, LDL, and TC levels decreased significantly in both groups from the preoperative to the 6-month point.ConclusionsEsophagectomy induces weight loss in T2DM and Non-T2DM groups, improves long-term glucose metabolism in the T2DM group, and enhances lipid metabolism in both groups. Further research is needed to understand their mechanisms.

Integrated mRNA and miRNA analysis reveals the regulatory network of oxidative stress and inflammation in Coilia nasus brains during air exposure and salinity mitigation

BackgroundAir exposure is an inevitable source of stress that leads to significant mortality in Coilia nasus. Our previous research demonstrated that adding 10‰ NaCl to aquatic water could enhance survival rates, albeit the molecular mechanisms involved in air exposure and salinity mitigation remained unclear. Conversely, salinity mitigation resulted in decreased plasma glucose levels and improved antioxidative activity. To shed light on this phenomenon, we characterized the transcriptomic changes in the C. nasus brain upon air exposure and salinity mitigation by integrated miRNA-mRNA analysis.ResultsThe plasma glucose level was elevated during air exposure, whereas it decreased during salinity mitigation. Antioxidant activity was suppressed during air exposure, but was enhanced during salinity mitigation. A total of 629 differentially expressed miRNAs (DEMs) and 791 differentially expressed genes (DEGs) were detected during air exposure, while 429 DEMs and 1016 DEGs were identified during salinity mitigation. GO analysis revealed that the target genes of DEMs and DEGs were enriched in biological process and cellular component during air exposure and salinity mitigation. KEGG analysis revealed that the target genes of DEMs and DEGs were enriched in metabolism. Integrated analysis showed that 24 and 36 predicted miRNA-mRNA regulatory pairs participating in regulating glucose metabolism, Ca2+ transport, inflammation, and oxidative stress. Interestingly, most of these miRNAs were novel miRNAs.ConclusionIn this study, substantial miRNA-mRNA regulation pairs were predicted via integrated analysis of small RNA sequencing and RNA-Seq. Based on predicted miRNA-mRNA regulation and potential function of DEGs, miRNA-mRNA regulatory network involved in glucose metabolism and Ca2+ transport, inflammation, and oxidative stress in C. nasus brain during air exposure and salinity mitigation. They regulated the increased/decreased plasma glucose and inhibited/promoted antioxidant activity during air exposure and salinity mitigation. Our findings would propose novel insights to the mechanisms underlying fish responses to air exposure and salinity mitigation.

The proteomic profile is altered but not repaired after bariatric surgery in type 2 diabetes pigs

To reveal the sources of obesity and type 2 diabetes (T2D) in humans, animal models, mainly rodents, have been used. Here, we propose a pig model of T2D. Weaned piglets were fed high fat/high sugar diet suppling 150% of metabolizable energy. Measurements of weight gain, blood morphology, glucose plasma levels, cholesterol, and triglycerides, as well as glucose tolerance (oral glucose tolerance test, OGTT) were employed to observe T2D development. The histology and mass spectrometry analyses were made post mortem. Within 6 months, the high fat-high sugar (HFHS) fed pigs showed gradual and significant increase in plasma triglycerides and glucose levels in comparison to the controls. Using OGTT test, we found stable glucose intolerance in 10 out of 14 HFHS pigs. Mass spectrometry analysis indicated significant changes in 330 proteins in the intestine, liver, and pancreas of the HFHS pigs. These pigs showed also an increase in DNA base modifications and elevated level of the ALKBH proteins in the tissues. Six diabetic HFHS pigs underwent Scopinaro bariatric surgery restoring glycaemia one month after surgery. In conclusion, a high energy diet applied to piglets resulted in the development of hyperlipidaemia, hyperglycaemia, and type 2 diabetes being reversed by a bariatric procedure, excluding the proteomic profile utill one month after the surgery.

Abstract PO4-12-12: An Updated analysis of risk factor identification and Hyperglycemia prevention with alpelisib + fulvestrant in PIKC3A-mutated, hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer

Abstract Background: SOLAR-1 investigated use of alpelisib (ALP) + fulvestrant (FLV) in patients (pts) with hormone-receptor positive (HR+)/human epidermal growth factor-2 negative (HER2-), PIK3CA-mutated advanced breast cancer (ABC) after progression on endocrine-based therapy and demonstrated a clinically significant increase in all-grade (G) and G3-4 hyperglycemia (HG) compared to placebo + FLV. Current guidance recommends an insulin sensitizer (metformin, thiazolidinedione, SGLT2i) at HG onset. Given high rates of HG, a preventative protocol and identification (ID) of associated risk factors (RFs) was implemented to minimize HG, dose reductions and discontinuation. Although METALLICA investigated the implementation of metformin for hyperglycemia prophylaxis, there is limited data for alpelisib use and hyperglycemia prevention in high risk or controlled type 2 diabetic patients. Duke Breast Oncology Clinic (DBOC) implemented a preventive strategy to minimize HG and treatment disruptions in patients receiving alpelisib, including pre-diabetic and controlled-diabetic patients. Methods: This single-center, retrospective study included pts receiving at least one 28-day cycle of ALP+FLV between June 2019 and April 2023. One week prior to ALP initiation, pts initiated an insulin-sensitizer. Pts had fasting plasma glucose (FPG) levels drawn on day 8, 15, 28, and monthly while on ALP. The primary outcome was incidence of G2-4 HG. Descriptive statistics were used to summarize results. Number of RFs for HG (age ≥ 65 years, BMI ≥ 25 kg/m2, baseline FPG ≥ 100 mg/dL, and A1c ≥ 5.7%) were compared between pts with and without HG using Wilcoxon rank-sum test. Results A total of 30 pts (29 females; 1 male) were included with a median age of 60 years. The cohort was 70% White, 23% Black, while 67% were overweight/obese, and 50% had a history of type 2 diabetes mellitus (T2DM), gestational diabetes, or pre-diabetes. 29 pts received a CDK4/6 inhibitor prior to starting ALP. By day 28, 13 pts (43%) had G2-4 HG, with only 4 (13%) having G3 HG and zero having grade 4. Pts with G2-4 HG had a median of 2 RFs compared to only 1 RF if no HG. 8 pts (27%) required a temporary hold of ALP and 5 pts (17%) required a dose reduction in ALP due to HG. 25 pts permanently discontinued ALP; 14 due to disease progression and 8 due to an adverse event with only 3 due to HG. Median duration of ALP was 86 days (range 24-442), with 5 pts continuing to receive ALP at time of analysis. Patients with grade 2-4 HG by day 28 after ALP initiation had an older median age (66 years), higher BMI (median 28.1 kg/m2), higher baseline FPG (median 100 mg/dL), and higher baseline HbA1c (median 5.6%) compared to those without grade 2-4 HG (Table). Conclusions: Implementation of a HG prevention protocol with ALP in the real-world setting demonstrated fewer G3-4 HG events compared to that seen in SOLAR-1 (13% vs 36.6%) but slightly higher than METALLICA (6%) although we included a higher risk patient population. An increase in HG-associated RFs correlated with a higher incidence of G2-4 HG. Early risk identification and optimization of prophylactic antihyperglycemics can reduce ALP dose reductions and discontinuations secondary to HG. ALP use in higher-risk patients can be considered with a HG prevention protocol. Table 1. Hyperglycemia outcomes Citation Format: Heather Moore, Sarah Burnette, Emily Poehlein, Hui-Jie Lee, Kelly Westbrook, Thomas Bagwell, Kervin Novido, Susan Dent. An Updated analysis of risk factor identification and Hyperglycemia prevention with alpelisib + fulvestrant in PIKC3A-mutated, hormone-receptor positive, human epidermal growth factor-2 negative advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-12-12.

Insulin and glucose tolerance assessment in guanylyl cyclase/natriuretic peptide receptor-A gene-targeted mutant mice

Atrial natriuretic peptide (ANP), acting through guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) regulates blood pressure and cardiac homeostasis. The disruption of Npr1 (encoding NPRA) in mice exhibits hypertension and provokes renal and cardiac disorder. However, the underlying mechanisms are not yet precisely determined. The objective of this study was to determine whether Npr1 plays a role in regulating glucose homeostasis in global Npr1 gene-disrupted mice. The adult male (14-18 wks) Npr1 haplotype gene-knockout ( Npr1+/-, 1-copy), wild-type ( Npr1+/+, 2-copy), and gene-duplicated ( Npr1+ +/+ +, 4-copy) mice were fasted overnight (16 h) and given free access to water. The mice were administered with glucose both orally and intraperitoneally (2 g/kg body weight) to determine the oral glucose tolerance test (OGTT) and intraperitoneal glucose tolerance test (IPGTT). For the insulin tolerance test (ITT), mice were also fasted for 16 h and then received an ip-injection of insulin (1.0 UI/kg body weight). Blood glucose levels were determined by performing tail bleeds at 0, 15, 30, 60, 90, and 120 min using the AlphaTRAK blood glucose monitoring system. The results showed that administration of glucose resulted in a greater increases in blood glucose levels at 120 mins in 1-copy mice (OGTT: 237 ± 5 mg/dL, IPGT: 246 ± 6 mg/dL, ITT; 239 ± 7 mg/dL) than 2-copy male (OGTT: 131 ± 3 mg/dL, IPGT: 126 ± 6 mg/dL, ITT; 127 ± 6 mg/dL), respectively. The blood glucose was also significantly lower in 4-copy mice (OGTT: 113 ± 5 mg/dL, IPGT: 108 ± 7 mg/dL, ITT; 107 ± 3 mg/dL) than in 2-copy mice. Systolic blood pressure (SBP) was determined by non-invasive tail-cuff method (Visitech 2000). SBP was significantly greater in 1-copy mice (130 ± 4 mmHg) than 2-copy mice (100 ± 3 mmHg). Similarly, SBP was also significantly lower in 4-copy mice (90 ± 2) than 2-copy mice. The increase in plasma glucose levels was significantly lower in OGTT than in IPGTT. The present results suggest that decreased Npr1 gene copy number predisposes to hyperglycemia, insulin resistance, and hypertension. These results indicate that the Npr1 gene might regulate blood glucose homeostasis. This work was supported by the NIH grant (DK133833). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Effect of aerobic exercise (skipping) on the levels of fasting plasma glucose, lipid profile and some apolipoproteins in male students at Nnamdi Azikiwe University, Nigeria

Effect of aerobic exercise (skipping) on the levels of fasting plasma glucose, lipid profile and some apolipoproteins in male students at Nnamdi Azikiwe University, Nigeria

Does Serum Uric Acid to Creatinine Ratio Predict Mortality Risk in Patients With Heart Failure?

Previous studies have established a positive correlation between serum uric acid to creatinine (SUA/Cr) ratio and cardiovascular disease, but the relationship between SUA/Cr ratio and the prognosis of heart failure (HF) remains unknown. This study investigated the potential of SUA/Cr ratio as a prognostic predictor for patients with HF. This single-center prospective cohort study enrolled 2,122 patients with HF between March 2013 and June 2017. All patients were divided into 3 groups according to SUA/Cr ratio tertiles and were followed up with until December 31, 2022. The association between SUA/Cr ratio and the prognosis of HF was assessed using the Cox proportional hazards model. The mean (SD) age and mean (SD) SUA/Cr ratio of the study cohort (66% male) were 59.3 (14.7) years and 4.71 (2.09), respectively. During a median follow-up period of 15 months (range, 11-26 months), 390 end-point events were observed. Prognosis analysis revealed that a high SUA/Cr ratio was associated with an increased mortality risk of HF (hazard ratio, 1.62 [95% CI, 1.26-2.09]; P < .001) compared with the SUA/Cr ratio in the lowest tertile. After adjusting for covariates, the hazard ratio for mortality risk of HF was 1.71 (95% CI, 1.23-2.37; P = .001). Subgroup analysis showed that mortality risk increased in direct proportion with the SUA/Cr ratio in female patients, patients with a history of hypertension and β-blocker use, and patients with UA levels below 428 μmol/L and creatinine levels less than 97 mg/dL. Stratification by age; by history of diabetes, hyperlipidemia, and smoking; and by level of fasting plasma glucose, however, had no obvious effect on the association between SUA/Cr ratio and HF prognosis. Patients with higher SUA/Cr ratios had reduced left ventricular ejection fraction and increased left ventricular end-diastolic diameter. A high SUA/Cr ratio was an independent risk factor for the mortality risk of HF.

First-trimester fasting plasma glucose level is also associated with post-partum frank type 2 diabetes not just gestational diabetes mellitus

First-trimester fasting plasma glucose level is also associated with post-partum frank type 2 diabetes not just gestational diabetes mellitus

A potential role for GPR107 in the development of Hypoglycemia Unawareness

Diabetes remains one of the largest health burdens in modern society and while an estimated 37.3 million people suffer from either type 1 or type 2 diabetes worldwide, a further 96 million people are currently estimated to be prediabetic. So far, most efforts for diabetic therapies have been focused on insulin-replacement therapies and secretagogues; however, a common risk associated with these therapies is hypoglycemia. Hypoglycemia is defined as low plasma glucose levels (&lt; 70 mg/dl) and can lead to loss of consciousness and death. Recently, it has been established that repeated exposure to bouts of hypoglycemia in diabetic individuals likely impairs sympathoadrenal counter regulation, and shifts the glycemic threshold for symptoms to lower plasma glucose concentrations, close to levels which result in cognitive failure. This pathology has been titled hypoglycemia unawareness (HU) and constitutes a major risk factor for developing severe hypoglycemia. The development of severe hypoglycemia in diabetics accounts for a six-fold increase in mortality, compared to diabetic individuals who do not experience severe hypoglycemia. Thus, it is important to understand how to prevent and reverse its development. We have developed a novel rat model of HU in which rats are exposed to insulin-induced recurrent hypoglycemia for five consecutive days. In this model of HU, we found that GPR107 expression is dramatically increased in the hypothalamus of rats exhibiting loss of hypoglycemia-induced food intake. Our group previously identified GPR107 as a receptor for neuronostatin (NST), a 13 amino acid peptide derived from the somatostatin prepro-hormone, which can exert anorexigenic actions in the hypothalamus. Using a GPR107-flox rat model we are currently evaluating the effect of hypothalamic knock-down of GPR107 on the development of HU and basal feeding behavior. We anticipate that if knock-down of GPR107 reverses HU, the development of NST antagonists could potentially be useful therapeutically for diabetic patients who experience recurrent hypoglycemia. Our GPR107-flox rat model will enable us to identify upstream and downstream interacting partners of GPR107/NST. This could reveal hypothalamic pathways involved in the development of HU that also could serve as potential therapeutic targets for this devastation consequence of iatrogenic hypoglycemia. Internal Funds St. Louis University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.