Postprandial Levels Research Articles

Predictors of New Onset Dysglycemia Post COVID-19

Abstract Background: Hyperglycemia postcoronavirus disease 2019 (COVID-19) infection is multifactorial and warrants serial monitoring of blood glucose. Aims: The aim of the study was to assess the incidence of glucose intolerance and new-onset diabetes in patients who have recovered from COVID-19 and to correlate the risk factors for dysglycemia. Materials and Methods: Participants who were admitted for COVID-19 infection at St John’s Hospital, Bangalore, India, at least 6 months previously were enrolled in the study using telephonic interviews. Details regarding age, gender, weight, and history were obtained. Laboratory parameters such as fasting blood sugar, postprandial blood sugar, and glycated hemoglobin (HbA1c) were obtained. The comparison between the dysglycemia and normoglycemia groups was conducted using either independent samples t-test or Mann–Whitney U test and using the Chi-squared test or Fisher’s exact test, as appropriate. Multivariate logistic regression was employed to determine the adjusted effect of multiple variables on dysglycemia. Results: The overall mean age of the study group was 40 ± 13 years with 68 (52%) male patients. Of the 131 patients, 93 had mild, 32 had moderate, and 6 had severe COVID-19. Thirty-nine percent of patients who were previously infected with COVID-19 were found to have elevated fasting, postprandial, or HbA1c levels. Of these, 3.1% were diagnosed as having type 2 diabetes mellitus and 9.9% had prediabetes. On excluding those with an isolated HbA1c elevation and comparing prediabetes and diabetes with normoglycemia, age, overweight and obese range body mass index (BMI), and the presence of comorbidities showed significant association (P < 0.05). Age (odds ratio [OR] 1.06, 95% confidence interval [CI] 1.02–1.11), the presence of comorbidities (OR 4.84, 95% CI 1.49–15.5), and overweight and obese range BMI (OR 3.48, 95% CI 1.13–13.1) were associated with dysglycemia on multivariate logistic regression analysis. Conclusion: A high incidence of dysglycemia over 6 months post-COVID-19 infection, especially in those with higher BMI, comorbidities, and in those in the middle age group warrants serial long-term monitoring of glucose levels in view of the high background risk of diabetes in the Asian population.

Diagnostic accuracy of DIPSI criteria for diagnosing gestational diabetes mellitus in Puducherry

ABSTRACT Context: Gestational diabetes mellitus (GDM) is a major concern in recent years. During pregnancy, it is difficult to consume 75 g of glucose in the fasting state as pregnant women may experience symptoms such as vomiting. The Diabetes in Pregnancy Study Group India (DIPSI) criterion requires a single prick in the non-fasting state to collect the sample for diagnosing GDM. Aims: This study aimed to assess the diagnostic accuracy of DIPSI criteria compared to the WHO criteria for GDM diagnosis. Settings and Design: A community-based cross-sectional study was conducted among pregnant mothers attending the primary health centers in Puducherry from August 2022 to November 2022. Methods and Material: A total of 384 samples were selected, and 75 g of anhydrous glucose was given after 8 hours of overnight fasting. Both fasting and postprandial venous blood sugar levels were measured to determine the prevalence of GDM as per the WHO 2013 criteria. After 2 days, GDM was diagnosed among all study participants based on the DIPSI criteria. Further analysis was done. Results: The prevalence of GDM was 14.1% and 12.8% per the WHO 2013 and DIPSI criteria, respectively. In comparison to the WHO 2013 criteria, DIPSI had 79.63% sensitivity, 98.18% specificity, 87.76% positive predictive value, and 96.72% negative predictive value. The results of kappa statistics showed that there was almost perfect agreement between the WHO 2013 criteria and DIPSI criteria. Conclusions: The present study shows that the DIPSI criteria can be used to screen and diagnose GDM as there is no need for overnight fasting. The blood glucose value can be measured easily with a single prick, which is comfortable for both pregnant women and treating doctors.

Anti-Obesity Effects of a Collagen with Low Digestibility and High Swelling Capacity: A Human Randomized Control Trial.

Collagen is a protein formed by very long amino acid chains. When conveniently treated, it can incorporate water into the net, thus increasing its volume and mass. The present work aimed to evaluate the potential anti-obesity effects of bovine collagen that has been technologically treated to increase its water retention capacity in an acid pH medium, with the objective of inducing satiation. Collagen's digestibility was tested with a pepsin digestion test. Its swelling capacity was tested in an acid pH medium simulating gastric conditions. Postprandial levels of ghrelin in response to collagen supplementation were tested in rats. In a randomized control trial, 64 subjects with overweight/obesity were allocated in two groups: supplemented daily with two protein bars enriched with collagen (20 g per day) for 12 weeks, or control group. Anthropometric and biochemical measurements were assessed in all the participants. This collagen showed a low digestibility (<60%) and high swelling capacity (>1900%) in vitro. In humans with overweight and obesity, this collagen significantly reduced body weight, body mass index (BMI), systolic blood pressure (SBP), and fatty liver index (FLI) and increased fat-free mass when compared with the control group. A significant reduction in the sarcopenic index; total, troncular, and visceral fat (measured by DEXA); and serum leptin levels were observed in the collagen group at the end of the intervention, with no differences with respect to controls. Collagen reduced the sensation of hunger and increased fullness and satisfaction. In male Wistar rats, collagen decreased postprandial blood ghrelin levels. Collagen supplementation (20 g per day for 12 weeks) reduced body weight, BMI, waist circumference, fat mass, FLI, and SBP in humans with overweight and obesity, which might be related to the increased sensation of fullness and satisfaction reported by the volunteers after the intake.

Proposed mechanisms of action participating in the hypoglycemic effect of the traditionally used Croton guatemalensis Lotsy and junceic acid, its main compound.

Croton guatemalensis Lotsy (Euphorbiaceae) is an important traditional medicine that is used by the Cakchiquels of Guatemala to control hyperglycemia in patients with type 2 diabetes. Previous studies have shown that administration of this plant induces an acute hypoglycemic effect during fasting and that the main compound is junceic acid, a diterpenoid with a clerodane skeleton; however, junceic acid has not been reported to have hypoglycemic activity in the literature. As the mechanisms involved in the hypoglycemic effect of C. guatemalensis remain unknown, the objective of the present investigation was to elucidate the hypoglycemic mechanisms of this species, as well as its major compound, junceic acid. The results indicated that, similar to complete extract, junceic acid exhibited a hypoglycemic effect in hyperglycemic rats. Both C. guatemalensis extract and junceic acid inhibited the activity of two rate-limiting enzymes involved in hepatic glucose production; however, compared with chlorogenic acid, junceic acid had a more potent effect on glucose-6-phosphatase levels than chlorogenic acid, which was used as a positive control. Furthermore, both fasting and postprandial insulin levels decreased in healthy and hyperglycemic rats despite reduced blood glucose levels in both metabolic states, suggesting a potential insulin-sensitizing effect. However, neither of these compounds potentiated the effect of insulin in insulin tolerance tests nor inhibited the enzyme activity of protein tyrosine phosphatase 1B, a negative regulator of the insulin pathway. Therefore, the insulin-sensitizing effect is thought to be independent of insulin and mediated by potential activation of the AMP-activated protein kinase pathway. The specific activation of this master regulator in β-cells results in the inhibition of insulin secretion in a healthy state and the restoration of the insulin response under conditions of glucotoxicity; these effects were observed after the administration of the extract and junceic acid in healthy and hyperglycemic rats. Overall, the main findings of this study establish a basis of the mechanisms of action of C. guatemalensis and its main compound, junceic acid, in terms of their hypoglycemic effect.

Dietary superdosing of phytase positively affects growth, mineral utilization and amino acid availability of channel catfish (Ictalurus punctatus)

The present study investigated the effects of supplementing high levels (superdosing) of dietary phytase on growth performance, mineral utilization and digestibility of amino acids in different regions of the gastrointestinal (GI) tract of fingerling channel catfish. The negative control (NC) diet was formulated with primarily soybean meal as a protein feedstuff which contributed 0.61 % total phosphorus (P) but was deficient in available P at 0.11 % of diet. Five other diets were formulated either with supplemental monocalcium phosphate at 1 % of diet in the positive control (PC), or supplemented with Quantum Blue phytase (AB Vista, Plantation, Florida) at 1000, 2000, 4000, or 8000 phytase units (FTU)/kg of diet. Groups of 20 catfish were each stocked into 24 aquaria operated as a closed, recirculating system with biological and mechanical filtration. All dietary treatments were assigned randomly to quadruplicate aquaria and initially fed at 6 % of total body weight per day. Feed quantities were adjusted weekly after weighing all fish in each aquarium as a group, and feeding levels were maintained close to apparent satiation throughout the 8-week feeding trial. Phytase supplementation significantly (P < 0.05) increased various responses of channel catfish including weight gain, feed efficiency, and protein retention compared to catfish fed the NC diet, resulting in values that were similar to catfish fed the PC diet. Moreover, catfish fed the phytase-supplemented diets had higher bone ash, calcium (Ca), magnesium (Mg), P, manganese (Mn), and zinc (Zn), as well as retention of Ca, Mg, P, iron (Fe), Mn, and Zn in whole-body tissues. Additionally, apparent availability of P from the posterior intestinal region increased with dietary phytase supplementation, with reduced excretion of nitrogen, Ca, Mg, P, copper (Cu), Mn, and Zn observed in comparison to fish fed the NC diet. Apparent digestibility coefficients for many of the indispensable and dispensable amino acids were increased by phytase supplementation, except for histidine, methionine, threonine, and taurine. This improvement in amino acid availability occurred only in the posterior region of the gastrointestinal tract. Channel catfish fed the diet containing 4000 FTU/kg diet had the highest postprandial plasma phosphorus level most of the time, except at 24 h after feeding. Based on these various responses, the optimal dietary phytase dosage was determined to average 5492 FTU/kg diet.

7814 Non-fasting and Fasting Mixed Meal Tolerance Tests Equally Capture the Triglyceride Response in Participants With and Without MASLD

Abstract Disclosure: L.A. Gonzalez Ramirez: None. Z. He: None. J.N. Binongo: None. H.E. Huneault: None. A. Ramirez Tovar: None. J.A. Welsh: None. M.B. Vos: Consulting Fee; Self; Boehringer Ingelheim, Prosciento, Target Real World Solutions, Intercept Pharmaceuticals, INC, Novo Nordisk. Grant Recipient; Self; Target Real World Solutions. Mixed meal tolerance tests (MMTTs) are functional assessments that may identify metabolic dysregulation earlier than fasting tests during the progression to metabolic dysfunction-associated steatotic liver disease (MASLD). Although standards to conduct MMTTs in adults are readily available, the knowledge gap for children is quite large. Furthermore, conducting this type of study in children is challenging because they are less tolerant of long fasting intervals, long periods of testing, and early morning visits that interrupt school attendance. The objective of this study was to assess if conducting an MMTT in a non-fasting state will equally identify variance in the metabolic response of triglycerides (TG) between healthy children and those living with MASLD when compared to a 12-hour fasting MMTT. We collected blood samples every two hours in our 2-day randomized crossover feeding study. During each visit, 9 children with MASLD and 10 healthy controls aged 10 to 18 y underwent 1 standardized MMTT after a 12-hour overnight fasting (breakfast), followed by 2 standardized MMTTs in a non-fasting state (lunch and dinner). Participants were randomized to receive a glucose or fructose beverage at visit 1 and the other at visit 2. For uniformity, we only used data from the glucose beverage visit. We found that TG levels were statistically higher in the MASLD participants when compared to the non-MASLD group at each time point (p= 0.01). The maximum TG metabolic response peak for each MMTT was higher and more delayed in the MASLD group compared to the non-MASLD group. Within groups, postprandial TG level patterns were not significantly different when comparing breakfast, lunch, and dinner. Although TG levels varied throughout the day, the pattern after every meal was similar. These findings suggest that it is possible to identify differences in the TG metabolic response between children living with MASLD and healthy participants in the postprandial state. The results from our study also support the use of non-fasting MMTTs when examining TG metabolism in children, though further research to validate these findings is needed. Presentation: 6/1/2024

8616 A Novel Mutation of Maturity Onset Diabetes of the Young

Abstract Disclosure: K.H. Weerasinghe: None. N. Branis: None. Background: Maturity onset diabetes of the young (MODY) is an autosomal dominant condition characterized by various subsets (Nkonge et al., 2020). A mutation in the glucokinase gene (GCK), otherwise known as MODY type 2, is often characterized by mild hyperglycemia managed with lifestyle modifications (Nkonge et al., 2020). Novel mutations in this gene may differ in their clinical course and need close clinical monitoring. Clinical Case: A 19 year old male presented for evaluation of his diabetes mellitus. In 2020, the patient was hyperglycemic on routine blood work, with asymptomatic features. His condition was managed with lifestyle modifications. The HbA1c was 6.8 and 7; while fructosamine was 338 mmol/L (normal 205-285 mmol/L). Subsequent workup revealed GAD 65 to be less than 5 U/ml(normal range being 0-5 U/ml) with negative islet antibodies. C-peptide was similarly measured and found to be 1.5 ng/ml, within the limits of 1.1-4.4 ng/ml, demonstrating a good pancreatic reserve. A MODY genetic profile was then conducted which revealed a novel mutation in the GCK gene, variant c.1064T&amp;gt;C (p.L355P). As this is a novel mutation, the probability of MODY was calculated, and found to be 75% using the Exeter maturity-onset diabetes of the young (MODY) probability calculator (EMPC).The patient’s clinical course thus far has been managed conservatively as his hyperglycemia has been mild. However, recently the patient’s post prandial sugars were found to be persistently elevated. Pharmacotherapy such as sulfonylureas was discussed however, as per the patient’s wishes, stricter dietary modifications will be applied prior to the initiation of medication. Conclusion: Patients with novel mutations should be closely monitored as the general expected clinical course may vary. These changes are demonstrated in this case report as the patient started developing elevation in postprandial sugar levels uncharacteristically. Close monitoring of the patient’s future clinical status will be essential in learning more about the differences in prognosis and long term management.

7424 Measurements of Key Regulators of Energy Intake in Young and Midlife Women with Overweight or Obesity

Abstract Disclosure: E. Tama: None. R. Rivera: None. S. Fansa: None. D. Anazco: None. W. Ghusn: None. S. Faubion: None. A. Acosta: Consulting Fee; Self; Amgen Inc. Grant Recipient; Self; Vivus USA, Novo Nordisk. C. Shufelt: None. M.D. Hurtado: None. Introduction: Midlife women (ages 40 to 65) experience age-related weight gain (0.4-0.7 kg/year) due to physiologic and psychosocial changes. Evidence supports that age-related decrease in lean mass and its subsequent effect on energy expenditure are key physiologic factors. To date, the are no data describing if changes in the main regulators of energy intake (i.e., hunger, satiation, and satiety) across women’s lifespan play a role in weight gain during midlife. The aim of this study is to characterize measurements of satiation, satiety, and appetite sensations through early adulthood and midlife in women with obesity. Methods: This is a cross sectional study of women aged 19-65 with overweight or obesity who have undergone measurements of (i) body composition by DXA scan; (ii) resting energy expenditure (REE) by indirect calorimetry; (iii) satiation by calories consumed to satiation (CTS) during an ad libitum meal test; (iv) satiety by time needed to empty 50% of the stomach content (GEt1/2) in a gastric emptying study and plasma satiety hormone levels (PYY, GLP-1, and CCK); and (v) appetite sensations by visual analog scales (VAS) for hunger and fullness. We present data as mean ± standard deviation. We performed simple correlations between these variables and age. We performed multiple regression analyses to adjust for body composition and REE. Results: Our cohort included 552 mostly white (93%) women, with a mean age of 41±11 years and a mean BMI of 37±7 kg/m2. Increased age significantly correlated with higher waist circumference (r=0.1, p=0.006), waist/hip ratio (r=0.1, p=0.01), and total fat mass % (r=0.1, p=0.04); and with lower lean mass % (r=-0.1, p=0.04) and REE (r=-0.3, p&amp;lt;0.0001). Increased age was associated with decreased hunger sensation (i.e., lower preprandial VAShunger after an overnight fast, r=-0.1, p=0.04; and lower postprandial VAShunger 4hr after a standardized 320-kcal breakfast, r=-0.1, p=0.001), stronger satiation (i.e., lower CTS, r=-0.1, p=0.001), and more prolonged satiety (i.e., higher GEt1/2, r=0.1, p=0.02; higher postprandial GLP-1 levels, r=0.1, p=0.03; and higher postprandial VASfullness after and ad libitum meal, p=0.1, p=0.008). After adjusting for lean mass % and REE, the correlations between age and hunger sensations and satiation measurement, but not satiety measurements, were maintained. Conclusion: Our results show that older women have lower lean mass % and REE. After adjusting for these variables, older women experience decreased hunger sensation and achieve satiation with a lower number of calories. As these changes in theory would protect against midlife weight gain, the differences in body composition and REE remain the most likely culprit. Further research is necessary to investigate if there are other key factors that may contribute to weight gain such as the hedonic or emotional components of food intake. Presentation: 6/2/2024

A-001 The Postprandial Levels of the Metabolites in the Metaorganismal Trimethylamine N-Oxide (TMAO) Pathway are Altered in A Diet-, Microbe-, and Sex-Specific Manner

Abstract Background Cardiovascular disease (CVD) remains the leading cause of death in developed countries. Elevated levels of the gut-microbe-associated metabolite trimethylamine-N-oxide (TMAO) have been associated with increased risk for CVD mortality in many large independent studies. In fact, large laboratory corporations such as Labcorp and Quest Diagnostic now offer TMAO diagnostic tests for the assessment of CVD risk and as a marker for disease-associated dysbiosis, using samples obtained from fasting patients. Although the strong association between TMAO levels and CVD risk has been established in fasting blood samples, here we are investigating the potential for a single meal to dynamically alter TMAO-related metabolites based on sex, diverse dietary substrates, and microbial influences. Methods 35 healthy participants were randomized to one of four study groups with approximately 8-9 subjects in each arm. Half of the participants were randomly assigned to receive a three-day broad spectrum antibiotic regimen (ciprofloxacin, metronidazole, and vancomycin) while the others received no antibiotics. These two groups were further subdivided into a group consuming a highly processed meal (originating from local fast food restaurants) or alternatively a whole food meal (containing a variety of fruits, vegetables, and healthy fiber). Blood samples were taken at baseline (after an overnight fast), and then postprandially at 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, and 6 hours after meal ingestion. Targeted plasma metabolites were quantified using a stable isotope dilution, liquid chromatography - tandem mass spectrometry (LC-MS/MS) method Results While plasma TMAO levels between food groups did not change significantly within the total cohort, there were clear individualized responses to either highly processed or whole food meals. Separation based on sex showed that TMAO levels were significantly reduced in females at 6 hours but remained steady in males for both food groups. Particularly, in the processed food group, TMAO levels were significantly lower in females than males at the 6-hour time point. Neither of these observations held true for TMAO precursors choline, carnitine, or betaine. However, plasma levels of a dietary precursor for TMAO, γ-butyrobetaine, showed clear diet-microbe-host interactions. For males in the processed food group, plasma γ-butyrobetaine levels were significantly increased in subjects on broad spectrum antibiotics. Conclusions Our results show the postprandial levels of TMAO, and its nutrient precursors dynamically change in a diet-, microbe-, and sex-dependent manner. These findings provide new insights into the postprandial levels of TMAO-related metabolites and may inform precision nutritional approaches in those who could benefit from TMAO-lowering strategies.

Buckwheat containing-bread: a scientific inquiry into insulin, polyphenols, antioxidants status, and oxidative stress markers in type-II diabetic individuals

Buckwheat grains contain bioactive components with known effects on cardio-metabolic biomarkers. Previous research on oxidative stress markers made exclusively from wheat flour or two-hour postprandial levels of antioxidant status, plasma total polyphenols, and advanced glycation end products (AGEs) were considerably higher than fasting values after consuming buckwheat-incorporated bread (BWB), including clinical, animal, and epidemiological studies, suggesting the potential of buckwheat intake to influence parameters such as polyphenol intake, antioxidant status, insulin levels, and oxidative stress markers. However, the specific impact of buckwheat-containing bread on these biomarkers in individuals with type-II diabetes remains a significant gap in our understanding. Our current work aims to address this gap by exploring the effects of buckwheat-containing bread on insulin levels, polyphenol intake, antioxidant status, and markers of oxidative stress. In a randomized crossover study, 16 individuals with type-II diabetes were assigned to consume control bread made exclusively from wheat flour or bread incorporating 50% buckwheat flour. The research followed a crossover design, with a period of one to two washout interventions. Test breads were given at breakfast following a 12 h fast the previous night. After 2 h of bread intake, blood samples were collected at baseline (fasting). The two-hour postprandial levels of antioxidant status, plasma total polyphenols, and advanced glycation end products (AGEs) were significantly higher than fasting values after consuming buckwheat-incorporated bread (BWB). This suggests that the buckwheat-containing bread improved plasma total polyphenol levels and total antioxidant status. Our research concludes that the intake of bread containing buckwheat positively influences polyphenols in plasma and the status of antioxidants. This suggests that incorporating buckwheat into bread may have favorable effects on biomarkers associated with cardio-metabolic health in individuals with type-II diabetes. By addressing these knowledge gaps, our research aims to inform and engage the scientific community in further exploration of the potential health benefits of buckwheat-containing bread.

Prevalence and influencing factors of pulmonary nodules in hospitalized patients with diabetes.

Pulmonary nodules are an early manifestation of many lung cancers, and patients with diabetes are at high risk for lung cancer. However, there is a lack of epidemiological data on pulmonary nodules in patients with diabetes. This study investigated the prevalence rate of pulmonary nodules in hospitalized patients with diabetes and analyzed its influencing factors, with the aim of generating data to inform the management of pulmonary nodules in patients with diabetes. This retrospective study included 1,864 patients with diabetes admitted to the Department of Endocrinology and Metabolism in the North District of Suzhou City Hospital from January 2020 to November 2022. According to the chest computed tomography (CT) examination, the patients were divided into two groups: a no pulmonary nodules group and a pulmonary nodules group. The prevalence rate of pulmonary nodules was calculated, and the number, size, nature, and other imaging characteristics of pulmonary nodules were compared. The pulmonary nodule group was divided into three subgroups according to the following nodule diameters: <5, ≥5 and <10, and ≥10 and ≤30 mm. The clinical data, blood biochemistry, insulin resistance index, and serum tumor marker levels were recorded. A multinomial logistic regression model was used to analyze the influencing factors of pulmonary nodule in diabetic patients. Among the 1,864 hospitalized patients with diabetes, 1,407 were found to have pulmonary nodules, representing a total prevalence rate of 75.48%. Compared with the pulmonary nodules subgroups, the no pulmonary nodules group had a higher proportion of males, a lower smoking rate, and higher incidence of proteinuria (all P values <0.05). Compared with the group with a nodule diameter ≥5 and <10 mm and that with a nodule diameter ≥10 and ≤30 mm, the no pulmonary nodules group had a lower age, insulin use rate, and homocysteine (Hcy) levels but higher fasting and 2-hour postprandial C-peptide level, low-density lipoprotein cholesterol (LDL-C) level and insulin resistance index [Homeostatic Model Assessment for Insulin Resistance 2 (HOMA2IR)] (all P values <0.05). The usage rate of dipeptidyl peptidase 4 (DPP4) inhibitor in the no pulmonary nodules group was lower than that in the subgroup with a nodule diameter ≥5 and <10 mm (P<0.05). Multinomial logistic regression analysis showed that age, smoking, and use of DPP4 inhibitors were independent risk factors for pulmonary nodules. DPP4 inhibitors increased the risk of nodules ≥5 and <10 mm in size, while older age and smoking increased the risk of nodules ≥5 mm in size (all P values <0.05). The prevalence of pulmonary nodules in hospitalized patients with diabetes is up to 75.48%. Older age, smoking, and use of DPP4 inhibitors were found to be independent risk factors for pulmonary nodule development in diabetic patients.

Global 13C tracing and metabolic flux analysis of intact human liver tissue ex vivo.

Liver metabolism is central to human physiology and influences the pathogenesis of common metabolic diseases. Yet, our understanding of human liver metabolism remains incomplete, with much of current knowledge based on animal or cell culture models that do not fully recapitulate human physiology. Here, we perform in-depth measurement of metabolism in intact human liver tissue ex vivo using global 13C tracing, non-targeted mass spectrometry and model-based metabolic flux analysis. Isotope tracing allowed qualitative assessment of a wide range of metabolic pathways within a single experiment, confirming well-known features of liver metabolism but also revealing unexpected metabolic activities such as de novo creatine synthesis and branched-chain amino acid transamination, where human liver appears to differ from rodent models. Glucose production ex vivo correlated with donor plasma glucose, suggesting that cultured liver tissue retains individual metabolic phenotypes, and could be suppressed by postprandial levels of nutrients and insulin, and also by pharmacological inhibition of glycogen utilization. Isotope tracing ex vivo allows measuring human liver metabolism with great depth and resolution in an experimentally tractable system.

Plasma Endocannabinoids Are Independently Associated With the Metabolic Function of White Adipose Tissue

Abstract Context Little is known about the link between the endocannabinoid (EC) system and the in vivo metabolic function of white adipose tissue (WAT). Objective We aimed to evaluate whether ECs are linked to postprandial fatty acid metabolism and WAT metabolic function. Methods Men and women, with (IGT, n = 20) or without impaired glucose tolerance (NGT, n = 20) underwent meal testing with oral and intravenous stable isotope palmitate tracers and positron emission tomography with intravenous [11C]-palmitate and oral [18F]-fluoro-thia-heptadecanoic acid to determine systemic and organ-specific dietary fatty acid (DFA) and nonesterified fatty acid (NEFA) metabolism and partitioning. We determined fasting and postprandial plasma levels of EC by ultra-high performance liquid chromatography–tandem mass spectrometry. Results All ECs of the 2-monoacylglycerol (2-MAG) family displayed a progressive postprandial increase up to 360 minutes after meal intake that was more pronounced in women with IGT. N-acylethanolamine (NAE) levels decreased between fasting and 180 minutes, followed by a return to preprandial values at 360 minutes and were also increased in women with IGT. Postprandial area under the curve (AUC) of palmitate appearance rate was significantly and independently associated with postprandial AUC of anandamide (AEA; P = .0003) and total energy expenditure (P = .0009). DFA storage in abdominal subcutaneous adipose tissue was positively predicted by fasting 2-arachidonoylglycerol (2-AG; P &amp;lt; .04). Conclusion EC levels of the NAE family independently follow plasma NEFA metabolism, whereas 2-MAG closely follow the spillover of triglyceride-rich lipoprotein intravascular lipolytic products. Whether these associations are causal requires further investigation.

Postprandial metabolomics analysis reveals disordered serotonin metabolism in post-bariatric hypoglycemia.

BACKGROUNDBariatric surgery is a potent therapeutic approach for obesity and type 2 diabetes but can be complicated by post-bariatric hypoglycemia (PBH). PBH typically occurs 1-3 hours after meals, in association with exaggerated postprandial levels of incretins and insulin.METHODSTo identify mediators of disordered metabolism in PBH, we analyzed the plasma metabolome in the fasting state and 30 and 120 minutes after mixed meal in 3 groups: PBH (n = 13), asymptomatic post-Roux-en-Y gastric bypass (post-RYGB) (n = 10), and nonsurgical controls (n = 8).RESULTSIn the fasting state, multiple tricarboxylic acid cycle intermediates and the ketone β-hydroxybutyrate were increased by 30%-80% in PBH versus asymptomatic. Conversely, multiple amino acids (branched-chain amino acids, tryptophan) and polyunsaturated lipids were reduced by 20%-50% in PBH versus asymptomatic. Tryptophan-related metabolites, including kynurenate, xanthurenate, and serotonin, were reduced 2- to 10-fold in PBH in the fasting state. Postprandially, plasma serotonin was uniquely increased 1.9-fold in PBH versus asymptomatic post-RYGB. In mice, serotonin administration lowered glucose and increased plasma insulin and GLP-1. Moreover, serotonin-induced hypoglycemia in mice was blocked by the nonspecific serotonin receptor antagonist cyproheptadine and the specific serotonin receptor 2 antagonist ketanserin.CONCLUSIONTogether these data suggest that increased postprandial serotonin may contribute to the pathophysiology of PBH and provide a potential therapeutic target.FUNDINGNational Institutes of Health (NIH) grant R01-DK121995, NIH grant P30-DK036836 (Diabetes Research Center grant, Joslin Diabetes Center), and Fundação de Amparo à Pesquisa do Estado de São Paulo grant 2018/22111-2.

Evaluating Blood Pressure Variability in Type 2 Diabetic Patients: An Insight into Non-Dipping Patterns and Their Clinical Implications.

Hypertension (HTN) is prevalent in individuals with type 2 Diabetes Mellitus (T2DM), doubling the risk of developing chronic complications. Despite normal routine checks, many patients with diabetes exhibit abnormal blood pressure (BP) profiles identified by 24-hour ambulatory Blood Pressure monitoring (ABPM). This study aimed to analyse blood pressure variability in patients with diabetes to enhance current knowledge and improve clinical practice. This cross-sectional study obtained ethical approval from Jazan University and involved 58 patients with type 2 Diabetes Mellitus (T2DM) who adhered to the strict inclusion and exclusion criteria. Comprehensive clinical and laboratory data, including demographic, clinical, and essential laboratory parameters, were collected using a standardized form. Blood Pressure (BP) was meticulously monitored using the Sun Tech Oscar 2 ABPMR device, with measurements commencing between 8 am and 10 am, extending over 24hours. The study calculated averages and evaluated systolic and diastolic percentage dipping during 24-hour, daytime, and night-time intervals. Participants classified as "dippers" experienced a BP reductions of at least 10%. Fifty-eight normotensive T2DM patients, with a mean age of 45.51 ± 6.7 years, were monitored over 24 months. Among the 58 individuals assessed using ABPM, a non-dipping pattern was observed in 45 participants (77.58%), whereas 13 (22.41%) exhibited a dipping pattern. Postprandial and fasting blood sugar levels were distinct; the dipper group demonstrated better post-meal glucose control (p=0.02), whereas the non-dipper group had superior fasting glucose control (p=0.04). The dipper group showed a higher 24-hour average systolic BP (p=0.00) and increased dipping percentages for systolic and diastolic BP during sleep. Over 77% of ABPM-evaluated individuals showed non-dipping patterns, with a higher BMI being strongly associated. Laboratory findings revealed distinct variations in the postprandial and fasting blood sugar levels, suggesting a potential genetic predisposition.

Exploring Factors Influencing Stroke Risk: Insights From a Predictive Analysis.

Introduction Stroke is a serious medical condition characterized by the sudden interruption of blood flow to the brain, resulting in the death of brain cells. It is a leading cause of long-term disability and mortality worldwide. Stroke has some associated risk factors, both modifiable and non-modifiable ones.As for non-modifiable risk factors, these are age, gender (men are more vulnerable), and family history of stroke.The controllable or adjustable risk factors include hypertension (high blood pressure), diabetes, smoking, high cholesterol levels, obesity, and insulin resistance. Methods In our study, we collected data from 229 patients which were originally collected for clinical purposes and were retrospectively analyzed. These data contain features such assex and age, the presence of ischemic heart disease (IHD) or stroke history, and different blood sugar readings. These measurements include fasting blood sugar (FBS), postprandial blood sugar (PPBS), HbA1c%, and insulin levels (fasting and postprandial).Furthermore, cholesterol was also tested, such as total cholesterol, triglycerides (TGL), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL). Surprisingly, stroke was observed in 24of the 205 patients. This contrast permits us to be concerned with the chance of the association between stroke and insulin levels. Given the imbalanced nature of our outcome variable (stroke occurrence), the primary analytical method will be logistic regression. Results In this cross-sectional study, we investigated the association between high insulin levels (both fasting and postprandial) and the occurrence of stroke within a dataset of 229 patients. Out of the 229 included cases, 102 individuals were female (44.5%) and 127 individuals were male (55.5%). Twenty-four cases have ischemic heart disease (10.5%). Among the analyzed cases, 24 individuals have a history of stroke. The average age of the sample is approximately 57 years ± 14.87. There was no significant difference between the males and females in most of the descriptive statistics. However, females experienced significantly higher levels of postprandial glucose level and significantly lower levels of postprandial insulin. According to our predictive model, we found that an increase in fasting insulin levels was linked to a lower risk of stroke occurrence. On the other hand, increasing insulin postprandial levels and age were associated with an increased risk of stroke. Conclusion Our study identified age, fasting insulin, and postprandial insulin as key factors influencing stroke risk. Higher fasting insulin levels were associated with reduced risk, while increased postprandial insulin and age were linked to higher risk. Blood glucose, cholesterol, and triglycerides had minor effects. Notably, higher total cholesterol and triglyceride levels were slightly associated with lower stroke occurrence. Further research with larger samples is needed for validation.

Effectiveness of serological markers of gastric mucosal atrophy in the gastric precancer screening and in cancer prevention.

New markers are needed to improve the effectiveness of serological screening for atrophic gastritis. To develop a cost-effective method for serological screening of atrophic gastritis with a high level of sensitivity. Of the 169 patients with atrophic gastritis, selected by the visual endoscopic Kimura-Takemoto method, 165 showed histological mucosal atrophy using the updated Kimura-Takemoto method. All 169 patients were examined for postprandial levels of gastrin-17 (G17) and pepsinogen-1 (PG1) using GastroPanel® (Biohit Plc, Helsinki, Finland). We used the histological standard of five biopsies of the gastric mucosa, in accordance with the Kimura-Takemoto classification system to assess the sensitivity of G17 in detecting gastric mucosal atrophy. We also compared the morpho-functional relationships between the detected histological degree of gastric mucosal atrophy and the serological levels of G17 and PG1, as the markers of atrophic gastritis. The sensitivity of postprandial G17 was 62.2% for serological levels of G17 (range: 0-4 pmol/L) and 100% for serological G17 (range: 0-10 pmol/L) for the detection of monofocal severe atrophic gastritis. No strong correlation was found between the levels of PG1 and degree of histological atrophy determined by the Kimura-Takemoto classification system to identify the severity of mucosal atrophy of the gastric corpus. In the presented clinical case of a 63-year-old man with multifocal atrophic gastritis, there is a pronounced positive long-term dynamics of the serological marker of atrophy - postprandial G17, after five months of rennet replacement therapy. Serological screening of multifocal atrophic gastritis by assessment of postprandial G17 is a cost-effective method with high sensitivity. Postprandial G17 is an earlier marker of regression of atrophic gastritis than a morphological examination of a gastric biopsy in accordance with the Sydney system. Therefore, postprandial G17 is recommended for dynamic monitoring of atrophic gastritis after treatment.

Gut-muscle communication links FGF19 levels to the loss of lean muscle mass following rapid weight loss

ObjectiveOptimal weight loss involves decreasing adipose tissue while preserving lean muscle mass. Identifying molecular mediators that preserve lean muscle mass is therefore a clinically important goal. We have shown that circulating, postprandial FGF19 levels are lower in patients with obesity and decrease further with comorbidities such as type 2 diabetes and MASLD. Preclinical studies have shown that FGF15 (mouse ortholog of human FGF19) is necessary to protect against lean muscle mass loss following metabolic surgery-induced weight loss in a mouse model of diet-induced obesity. We evaluated if non-surgical weight loss interventions also lead to increased systemic levels of FGF19 and whether FGF19 levels are predictive of lean muscle mass following rapid weight loss in human subjects with obesity. Research design and methodsWeight loss was induced in 176 subjects with obesity via a very low-energy diet, VLED (800 kcal/d) in the form of total liquid meal replacement for 3-4 months. We measured plasma FGF19 levels at baseline and following VLED-induced weight loss. Multiple linear regression was performed to assess if FGF19 levels were predictive of lean mass at baseline (obesity) and following VLED. ResultsPostprandial levels of FGF19 increased significantly following VLED-weight loss. Multiple linear regression analysis showed that baseline (obesity) FGF19 levels, but not post VLED FGF19 levels, significantly predicted the percent of lean muscle mass after VLED-induced weight loss, while controlling for age, sex, and the baseline percent lean mass. ConclusionThese data identify gut-muscle communication and FGF19 as a potentially important mediator of the preservation of lean muscle mass during rapid weight loss.

Validation of a Hand-Held Point-of-Care Device to Measure Breath Hydrogen and Its Utility in Detecting Response to Antibiotic Treatment.

Breath testing for small intestinal bacterial overgrowth (SIBO) is typically performed using clinic-based equipment or single-use test kits. This study aimed to evaluate the utility of a portable, point-of-care breath analysis device (AIRE®, FoodMarble) in patients suspected to have SIBO. A technical assessment including a comparison to existing mail-in kits was first performed. Then, postprandial breath hydrogen levels of patients before and after antibiotic treatment were gathered and compared to levels seen in a healthy cohort. For the comparison, 50 patients suspected of having SIBO were provided with an AIRE device and performed concurrent LHBTs at-home with a mail-in breath test kit. For the postprandial analysis, twenty-four patients with chronic GI symptoms measured their postprandial hydrogen for 7days prior to antibiotic treatment and for 7days after treatment. 10 healthy controls also measured their postprandial hydrogen for 7days. Substantial agreement was demonstrated between AIRE and the mail-in kits for the performance of lactulose hydrogen breath tests (κ = 0.8). Prior to treatment, patients had significantly greater daily postprandial hydrogen than healthy controls (p < 0.001). The mean postprandial hydrogen of patients reduced significantly after treatment (p < 0.001). Measuring postprandial hydrogen shows potential as a means of differentiating patients with chronic GI symptoms from healthy controls and may be useful in monitoring patients before, during, and after treatment. Future studies could help determine if pre-treatment breath gas levels are predictive of response to antibiotic treatment.

Impacts of different pancreatic resection ranges on endocrine function in Suncus murinus.

Surgical intervention involving the pancreas can lead to impaired glucose tolerance and other types of endocrine dysfunction. The scope of pancreatectomy and whether it includes the ventral pancreas are the key factors in the development of postoperative diabetes. The ventral and dorsal pancreases are almost separated in Suncus murinus (S. murinus). To investigate the effects of different extents of pancreatic resection on endocrine function in S. murinus. Eight-week-old male S. murinus shrews were randomly divided into three experimental groups according to different pancreatic resection ranges as follows: ventral pancreatectomy (VPx) group; partial pancreatectomy (PPx) group; subtotal pancreatectomy (SPx) group; and a sham-operated group. Postprandial serum insulin, glucagon-like peptide-1 (GLP-1), pancreatic polypeptide (PP), and somatostatin (SST) levels, as well as food intake, weight, blood glucose, and glucose tolerance were regularly measured for each animal. S. murinus treated with PPx and SPx suffered from varying degrees of impaired glucose tolerance, but only a small proportion of the SPx group developed diabetes. Only S. murinus in the SPx group showed a significant decrease in food intake accompanied by severe weight loss, as well as a significant increase in postprandial serum GLP-1 levels. Postprandial serum PP levels decreased in both the VPx and PPx groups, but not in the SPx group. Postprandial serum SST levels decreased in both VPx and PPx groups, but the decrease was marginal. Severe weight loss after pancreatectomy may be related to loss of appetite caused by compensatory elevation of GLP-1. PP and GLP-1 may play a role in resisting blood glucose imbalance.