Overnight Fasting Research Articles

Study on the effective control of postpreal blood glucose of resistant starch cakes in patients with type 2 diabetes

Background: This study was conducted on 93 volunteers with type 2 diabetes to investigate the ability of acetylated wheat starch cake containing 32.1% resistant starch to control postprandial blood glucose levels. Material and methods: The study was designed using a crossover, double-blind trial method. During each testing day, after a minimum of 12 hours of overnight fasting, each participant consumed two identical cakes containing either 80 g of acetylated wheat starch or 80 g natural wheat starch with 330ml of water within 15 minutes. Blood glucose levels were measured at baseline, 60 mins (G1), and 120 mins (G2) after ingestion. The predictive value of factors that contribute to the ability of resistant starch to control postprandial blood glucose was determined by the area under the receiver operating characteristic (ROC) curve based on the combined effect of the cake weight-to-BMI ratio (g/m²BMI) and HbA1c. Results: 60 mins and 120 mins postprandial capillary glucose levels after consuming acetylated wheat starch cake (10.4 ± 1.2 và 9.2 ± 1.2 mmol/L, respectively) were significantly lower compared with natural wheat starch cake (13.3 ± 1.8 và 11.2 ± 1.8 mmol/L, respectively) (p < 0.05). For good control of postprandial blood glucose levels, a maximum of 80 g of acetylated wheat starch can be used per serving for patients with type 2 diabetes with HbA1c ≤ 7.25 without blood glucose-lowering medication is required. Conclusion: acetylated wheat starch has better ontroled of postprandial blood glucose compared with natural wheat starch in patients with type 2 diabetes. This is very suitable in the processing of diets including resistant starch for patients with type 2 diabetes for the purpose of both supporting treatment and improving quality of life. Key words: resistant starch, blood glucose, HbA1c, ROC, volunteers.

Biomarkers - Part 1.

The CSF amyloid to tau ratio can isolate cognitively healthy participants into normal Aβ42/tau (CH-NAT) or a pathological Aβ42/tau (CH-PAT) with a low or high risk of cognitive decline, respectively. We aim to determine if plasma Aβ42/tau ratios can differentiate CH-NAT from CH-PAT participants. Study participants (> 65 years of age) were recruited, and demographic, neurological, and neuropsychological data were obtained in an ongoing HMRI Brain Aging study. Overnight fasting plasma and CSF were collected within a month of examination, and the levels of Aβ38, Aβ40, Aβ42 (MSD 6E10 kit), and total tau were quantified using the MSD electrochemiluminescence platform. Differences in fluid biomarker levels and the plasma ratios (n = 55) and CSF ratios (Aβ42/Aβ40, n = 41, Aβ42/tau, n = 55) were determined using nonparametric student t-test and correlations using a Spearman test. Aβ40 and Aβ42 levels were higher (15-18-fold, and 10-14-fold, respectively), while tau levels are 8-13-fold higher in CSF than in plasma. Plasma and CSF Aβ40 were not distinct in CH-NAT compared with CH-PAT. In contrast, Aβ42 levels were 30.9% lower in CH-PAT (16.3 ± 18.3 pg/ml) compared with CH-NAT plasma (23.6 ± 26.4 pg/mL) (p < 0.05). CSF Aβ42 levels in CH-PAT (171.6 ± 124.6 pg/mL) were lower by 47.6% compared with CH-NAT (327.6 ± 182.6 pg/ml) (p < 0.0001). The Aβ42/Aβ40 ratio was significantly lower in both plasma and CSF (Table 1A). Similarly, the Aβ42/tau ratio was significantly lower in plasma and CSF (Table 1B). Individually, plasma levels of Aβ42 and tau did not correlate with CSF levels. However, the ratio of Aβ42 to total tau in plasma significantly correlated with the CSF ratios (Spearman r = 0.36, p = 0.0071). Finally, CSF Aβ42/Aβ40 ratio correlated with Aβ42/tau ratio for all samples, CH (n = 100) and MCI (n = 35) (Fig. 1). While not as robust as CSF ratios, plasma Aβ42/Aβ40 and Aβ42/tau ratios can isolate cognitively healthy participants with lower risk from participants with a higher risk of cognitive decline. Thus, plasma represents a less invasive medium for the biomarker classification of aging participants.

Acute changes in the metabolome following resistance exercise combined with intake of different protein sources (cricket, pea, whey).

Separately, both exercise and protein ingestion have been shown to alter the blood and urine metabolome. This study goes a step further and examines changes in the metabolome derived from blood, urine and muscle tissue extracts in response to resistance exercise combined with ingestion of three different protein sources. In an acute parallel study, 52 young males performed one-legged resistance exercise (leg extension, 4 × 10 repetitions at 10 repetition maximum) followed by ingestion of either cricket (insect), pea or whey protein (0.25g protein/kg fat free mass). Blood and muscle tissue were collected at baseline and three hours after protein ingestion. Urine was collected at baseline and four hours after protein ingestion. Mixed-effects analyses were applied to examine the effect of the time (baseline vs. post), protein (cricket, pea, whey), and time x protein interaction. Nuclear magnetic resonance (NMR)-based metabolomics resulted in the annotation and quantification of 25 metabolites in blood, 35 in urine and 21 in muscle tissue. Changes in the muscle metabolome after combined exercise and protein intake indicated effects related to the protein source ingested. Muscle concentrations of leucine, methionine, glutamate and myo-inositol were higher after intake of whey protein compared to both cricket and pea protein. The blood metabolome revealed changes in a more ketogenic direction three hours after exercise reflecting that the trial was conducted after overnight fasting. Urinary concentration of trimethylamine N-oxide was significantly higher after ingestion of cricket than pea and whey protein. The blood, urine and muscle metabolome showed different and supplementary responses to exercise and ingestion of the different protein sources, and in synergy the summarized results provided a more complete picture of the metabolic state of the body.

HPB P28 Continuous glucose monitoring improves the diagnosis of insulinoma and surveillance after endoscopic ablation therapy

Abstract Background Insulinomas are the most common functioning pancreatic neuroendocrine tumours (PNET) and are classically diagnosed according to Whipple’s triad. The gold-standard diagnostic test (72 hour fasting glucose/C-peptide) is difficult for patients, and risks mis-diagnosing patients who only experience post-prandial symptoms. Moreover, the advent of endoscopic ablative techniques means that confirming successful treatment can be challenging when compared with surgical resection. This study aimed to investigate the value of continuous glucose monitoring (CGM) to: a) confirm the diagnosis of insulinoma; b) guide symptom management whilst awaiting definitive treatment; and c) as a surveillance tool in patients electing for non-surgical interventions. Methods A 61-year-old healthy male presented with post-prandial sweating, vacant episodes and reduced exercise tolerance which resolved upon consuming glucose. Computed Tomography demonstrated a 2cm exophytic hypervascular lesion in the pancreatic body, consistent with a NET, and correlated with an Octreotide avid lesion upon SPECT/CT. Overnight fasting glucose/c-peptide was not confirmatory. The target glucose range was defined as 4.0-9.9 mmol/L and critical hypoglycaemia as ≤2.9mmol/L. Data from CGM were analysed (Time in range and critical hypoglycaemia [Chi2]; glycaemic control and glycaemic variability [T-test]) during diagnosis, in the first week post-ablation, and the recovery phase beyond 3 weeks. Results Data from 22,008 glucose levels were analysed over a 90 day period. Time in range during diagnosis was 67.25%, 82.8% (p&amp;lt;0.0001) post-ablation, and 98.9% (P&amp;lt;0.0001) during recovery. Critical hypoglycaemia occurred in 5.2% of measurements during diagnosis, 1.9% (p&amp;lt;0.0001) post-ablation, and 0.1% (p&amp;lt;0.0001) during recovery. Glucose levels (mean [SD] mmol/L) were 4.4 (0.47) during diagnosis, 4.9 (0.29) (p=0.0001) post-ablation, and 5.7 (0.42) (p&amp;lt;0.0001) during recovery. Glycaemic variability (mean [SD] %CV) was 19.4 (5.09) during diagnosis, 20.17 (5.60) post-ablation (p=0.630), and 11.3 (5.53) (p&amp;lt;0.0001) during recovery. Temporal changes identifying post-prandial hypoglycaemia during diagnosis, and resolution during recovery, are illustrated (Figure 1). Conclusions CGM has utility to accurately diagnose insulinoma when standard tests are negative, and to improve quality of life by alerting patients to life-threatening critical hypoglycaemia. As parenchymal preserving non-operative therapies increase in popularity, especially for patients with small PNETs, sensitive, reliable, and acceptable surveillance techniques are required in order to confirm treatment success and monitor for recurrence. Proactive engagement with commissioning and regulatory bodies is necessary in order to harness the potential from emerging technologies, so that PNET patients can benefit in a similar manner as those with type 1 Diabetes Mellitus.

E47 as a novel glucocorticoid-dependent gene mediating lipid metabolism in patients with endogenous glucocorticoid excess.

E47 has been identified as a modulating transcription factor of glucocorticoid receptor target genes, its loss protecting mice from metabolic adverse effects of glucocorticoids. We aimed to analyze the role of E47 in patients with endogenous glucocorticoid excess [Cushing's syndrome (CS)] and its association with disorders of lipid and glucose metabolism. This is a prospective cohort study including 120 female patients with CS (ACTH-dependent = 79; ACTH-independent = 41) and 26 healthy female controls. Morning whole blood samples after an overnight fast were used to determine E47 mRNA expression levels in patients with overt CS before and 6-12 months after curative surgery. Expression levels were correlated with the clinical phenotype of the patients. Control subjects underwent ACTH stimulation tests and dexamethasone suppression tests to analyze short-term regulation of E47. E47 gene expression showed significant differences in patient cohorts with overt CS vs. patients in remission (p = 0.0474) and in direct intraindividual comparisons pre- vs. post-surgery (p = 0.0353). ACTH stimulation of controls resulted in a significant decrease of E47 mRNA expression 30min after i.v. injection compared to baseline measurements. Administration of 1 mg of dexamethasone overnight in controls did not change E47 mRNA expression. E47 gene expression showed a positive correlation with total serum cholesterol (p = 0.0036), low-density lipoprotein cholesterol (p = 0.0157), and waist-arm ratio (p = 0.0138) in patients with CS in remission. E47 is a GC-dependent gene that is upregulated in GC excess potentially aiming at reducing metabolic glucocorticoid side effects such asdyslipidemia.

Habitual carbohydrate intake is not correlated with circulating β-hydroxybutyrate levels in pregnant women with overweight and obesity at 28 weeks' gestation

Aims/hypothesisPregnant women are advised to consume a minimum of 175 g per day of carbohydrate to meet maternal and fetal brain glucose requirements. This recommendation comes from a theoretical calculation of carbohydrate requirements in pregnancy, rather than from clinical data. This study aimed to determine whether fasting maternal ketone levels are associated with habitual carbohydrate intake in a subset of participants of the Study of PRobiotics IN Gestational diabetes (SPRING) randomised controlled trial.MethodsFood frequency questionnaires on dietary intake during pregnancy were completed by pregnant women with overweight or obesity at 28 weeks’ gestation (considering their intake from the beginning of pregnancy). Dietary intake from early pregnancy through to 28 weeks was analysed for macronutrient intake. At the same time, overnight fasting serum samples were obtained and analysed for metabolic parameters including serum β-hydroxybutyrate, OGTTs, insulin and C-peptide.ResultsFasting serum β-hydroxybutyrate levels amongst 108 women (mean BMI 34.7 ± 6.3 kg/m2) ranged from 22.2 to 296.5 μmol/l. Median fasting β-hydroxybutyrate levels were not different between women with high (median [IQR] 68.4 [49.1–109.2 μmol/l]) and low (65.4 [43.6–138.0 μmol/l]) carbohydrate intake in pregnancy. Fasting β-hydroxybutyrate levels were not correlated with habitual carbohydrate intake (median 155 [126–189] g/day). The only metabolic parameter with which fasting β-hydroxybutyrate levels were correlated was 1 h venous plasma glucose (ρ=0.23, p=0.03) during a 75 g OGTT.Conclusions/interpretationFasting serum β-hydroxybutyrate levels are not associated with habitual carbohydrate intake at 28 weeks’ gestation in pregnant women with overweight and obesity.Graphical

Comparative Bioavailability of DFD-29 (Minocycline Hydrochloride Modified Release Capsules, 40 mg) Vs. Minocycline Hydrochloride Extended Release 105-mg tablets After a Single Oral Dose: A Randomized, 3-way Crossover Study

Background: A low-dose formulation (DFD-29) of minocycline hydrochloride (HCl) is under evaluation for the treatment of moderate-to-severe papulopustular rosacea. The objective of this phase 1 study is to compare the bioavailability of DFD-29 to that of the currently available Solodyn® (minocycline HCl extended release) 105-mg formulation. Methods: This single-center, randomized, open-label, laboratory-blinded, 3-way, 6-sequence crossover study compared the pharmacokinetics of a single dose of DFD-29 40 mg after an overnight fast, DFD-29 40 mg after a high-fat meal, and minocycline HCl extended release 105-mg tablet (minocycline HCl ER 105 mg) after an overnight fast in healthy adult volunteers. Blood samples were collected for PK assessments prior to and up to 72 hours after each drug dose, with a washout period of 7 calendar days between doses. Safety was evaluated by monitoring adverse events (AEs), vital signs, and laboratory tests. Results: A total of 24 subjects were randomized and 23 subjects completed the study. Mean plasma minocycline Cmax levels were 243.9 ng/mL for DFD-29 (fasting), 225.0 ng/mL for DFD-29 (fed), and 497.3 ng/mL for minocycline HCl ER 105 mg (fasting). The geometric least squares (LS) mean ratios for Cmax, AUC0-T, and AUC0-∞ of DFD-29 to minocycline HCl ER 105 mg when administered after fasting were 47.97%, 36.55%, and 38.35%, respectively. When comparing fasting vs fed administration of DFD-29, geometric LS mean ratios for Cmax, AUC0-T, and AUC0-∞ were 97.48%, 116.84%, and 115.26% respectively. Tmax was 1.5 h for DFD-29 (fasting), 4.5 h for DFD-29 (fed), and 4.0 h for minocycline HCl ER 105 mg (fasting). Treatment-emergent AEs (TEAEs) were reported in 17.4%, 13.0%, and 21.7% after administration of DFD-29 (fasting), DFD-29 (fed), and minocycline HCl ER 105 mg, respectively. Most TEAEs were mild in severity (21/22; 95.5%). Conclusion: Bioavailability was significantly lower after a single dose of DFD-29 40 mg vs minocycline HCl ER 105 mg following a single dose under fasting and fed conditions. Food intake had no impact on Cmax but may delay absorption and may slightly increase exposure. Overall, single oral doses of DFD-29 40 mg and minocycline HCl ER 105 mg were generally safe and well tolerated. This study and abstract are funded by Journey Medical Corporation.

Association of Serum Magnesium with Preterm Labor

In recent years preterm labor is a significant obstetric concern. Alteration of basic biochemical function at cellular level is one of the etiologies of preterm labor. Several trace elements including magnesium are associated with normal cellular function. Magnesium sulfate is used as a tocolytic agent because high magnesium level causes relaxation of smooth muscle. Hypomagnesaemia leads to neuromuscular irritability leading to uterine hyperactivity which leads to cervical dilation. Therefore, this study was performed to find out the association of hypomagnesemia with preterm labor. This cross-sectional study was conducted in 100 women in labor, of them 50 were diagnosed case of preterm labor and 50 women were in labor at term attended in BSMMCH, Faridpur during July 2021 to December 2021. After overnight fasting 5ml blood sample was collected and was analyzed for serum magnesium using standard enzymatic method. Mean value of serum magnesium was compared between two groups by student unpaired t-test. A p-value was considered to be statistically significant at 0.05 at the 95% confidence interval. The mean serum magnesium was found 1.44±0.36 mg/dl in preterm labor and 2.0±0.27 mg/dl in term labor. Low serum magnesium level was significantly higher in preterm labor. Bangabandhu Sheikh Mujib Med. Coll. J. 2023;2(1): 45-48

Effects of an Impaired Fasting Glucose on the Left Atrial Strain Evaluated by Speckle Tracking Echocardiography.

Background and Objectives: Similar to diabetes, the presence of left ventricular (LV) diastolic function (DD) has been reported in various studies which were conducted with people with a diagnosis of an impaired fasting blood glucose (FBG). This study aimed to examine the effects of the fasting blood glucose (FBG) levels on the left atrial strain (LAS) estimated by two-dimensional echocardiography speckle tracking analyses in patients without known diabetes. Material and Methods: The study included 148 participants (74 female and 74 male) without a history of diabetes mellitus or chronic disease. The patients were divided into two groups as follows: individuals with an FBG < 100 mg/dL and those with an FBG between 100 and 125 mg/dL after at least 8 h of overnight fasting. According to these FBG levels, speckle tracking echocardiography (STE) measures were compared. Results: There was a significant decrease in the LA reservoir (52.3 ± 15 vs. 44.5 ± 10.7; p = 0.001) and conduit strain (36.9 ± 11.7 vs. 28.4 ± 9.7; p = 0.001) in the impaired FBG group. When the STE findings of both ventricles were compared, no significant difference was observed between the groups in right and left ventricular strain imaging. Conclusions: In the earliest stage of LVDD, changes in atrial functional parameters become particularly evident. Echocardiographic analyses of these parameters can help to diagnose and determine the degree of LVDD while the morphological parameters are still normal. The addition of LAS imaging to routine transthoracic echocardiography (TTE) studies in patients with an impaired FBG but without a DM diagnosis may be helpful in demonstrating subclinical LVDD or identifying patients at risk for LVDD in this patient group.

High dose NAD+ boosting as pan-sirtuin activation increases atherosclerotic plaques and systemic inflammation in Apoe knockout mice

Abstract Background NAD+ (nicotinamide adenine diphosphate) is a cosubstrate of sirtuins (SIRT) that are activated upon caloric restriction. The nuclear SIRT1 and SIRT6 exert protective effects on atherothrombosis through immunometabolic pathways. By supplementing its precursors, an increase in the NAD+ pool has been reported to extend life span in mice. However, supplementing NAD+ precursors may also stimulate inflammation depending on the context. Nicotinamide riboside (NR) is a precursor of NAD+, whose supplementation has been used to combat metabolic syndromes and liver steatosis. Notably, the effects of pan-sirtuin activation using NR on atherosclerosis remain unknown. Purpose We hypothesized that NR supplementation confers atheroprotection by activating the NAD+ sirtuin axis. We aimed to test this hypothesis by investigating the effects of NR supplementation on plaque formation using an atherosclerosis-prone mouse model. Methods 8-week-old male apolipoprotein E (ApoE) knockout (KO) mice were fed for 12 weeks a high-cholesterol diet (HCD, 1.25 wt%) supplemented with three NR doses: 0, 1.2, and 2.4 g/kg diet. The groups were designated as NR-, NR+, and NR++, respectively (n=14/group). After overnight fasting, aortae, liver, and blood were collected. Cytokines were analyzed using a multiplex ELISA. Triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels were determined by colorimetry and the Friedewald equation. Cross sections of the aortic root were stained with Oil-Red O. Results High-dose (HD) NR supplementation increased plaque thickness in NR++ ApoE KO mice, compared with NR+ mice (Figure 1A and B). In parallel, plasma expression levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 as well as TG and LDL-C levels were increased in NR++ mice (Figure 1C-F) suggesting that NR supplementation induced systemic inflammation and disturbed lipid metabolism. Analyses of liver lysates showed that expression levels of SIRT1 were decreased and CD38 increased in NR++ mice. Full length PARP1 remained unchanged, while both cleaved PARP1 and total PARylation in liver decreased. NAD+ concentrations in liver and plasma remained unchanged. These data suggest that an increase in hepatic CD38 might consume more NAD+ in the atherosclerotic environment and could be the culprits for worsening atherosclerotic progression and systemic inflammation (Figure 2). Conclusions HD NR supplementation increased plaque thickness, as well as IL-6 and LDL-C plasma levels, moderate NR dose had neutral effects. Elevated hepatic expression levels of CD38 and decreased SIRT1 may at least in part explain the atherosclerotic phenotype. Thus, HD NR supplementation in mice does not decrease but worsen atherosclerosis and induce systemic inflammation. A cautious approach should be considered when applying NAD+ boosting in patients with atherosclerotic disease.

Left atrial glucose metabolism by 18F-FDG PET/CT in persistent atrial fibrillation and after return to sinus rhythm

Abstract Background Atrial Fibrillation (AF) is strongly associated with the development of Left Atrial (LA) remodeling. Animal studies pointed to an important role of metabolic deregulation in AF, yet few studies have assessed LA myocardial metabolism in vivo in patients with AF. 18-fluorodeoxyglucose (FDG) Positron Emission tomography (PET) has been widely used for evaluation of left ventricular (LV) metabolism, but its application to study metabolism of LA has not yet been explored. Purpose The aim of this study was to evaluate LA glucose metabolism and contractile efficiency in patients with persistent AF, following our successful implementation of a protocol enabling the acquisition of high-resolution PET images of the LA. Methods 36 nondiabetic patients (64±7 years, 29 men) with persistent non valvular AF (peAF) undergoing a first AF ablation and 5 healthy age matched volunteers (69±5 years, 3 men, p=0.114) without AF underwent FDG PET, speckle tracking echocardiography (STE) and cardiac MRI (cMR). PET was performed after overnight fasting and after administration of a nicotinic acid derivative (Acipimox 250 mg) to maximally stimulate myocardial glucose uptake. The 3 tests were repeated 3 months later in 26 patients in whom return to permanent sinus rhythm (SR) could be obtained after the ablation procedure. PET images were registered with cMR LA angiography, and the mean partial volume and spillover corrected standardized FDG uptake (SUV) in the whole LA, the left atrial appendage (LAA), and the left ventricle (LV) were computed. Measurements were compared to global Peak Atrial Longitudinal Strain (GPALS) and to left atrial ejection fraction (LAEF) measured by STE and LA contractile efficiency was computed as the ratio of LA SUV to LAEF. Results Hemodynamics (syst. BP mmHg: 128±11 vs 129±5 mmHg, p=0.663) and metabolic parameters (glycemia: 99±14 vs 96±7 mg/dl, p=0.480) were similar in peAF patients and healthy controls. While 18F-FDG SUV in the LV was comparable between pEAF patients and healthy controls, patients in peAF exhibited significantly increased SUV in LA and LAA compared to controls. Following a return to SR, LA-SUVmean and LAA-SUVmean in patients peAF decreased significantly after 3 months (20.3%, p&amp;lt;0.002 and 34.1%, p&amp;lt;0.001), whereas the LV-SUVmean remained unchanged (p=0.847). The Global Peak Atrial Longitudinal Strain (GPALS) increased by 54.2%(p&amp;lt;0.001), and the Left Atrial Ejection Fraction (LAEF) by 39.2% (p&amp;lt;0.001), post-restoration of SR. (Figure 1). Accordingly contractile efficiency of LA SUV/LAEF in peAF patients improved significantly upon their return to SR (47%, p&amp;lt;0.001). Conclusion LA glucose metabolism is significantly increased in peAF and return after restoration of SR. This could indicate oxygen wasting and reduced contractile efficiency of AF or metabolic shift towards preferred glucose metabolism in AF. These findings support the notion that LA glucose metabolism plays a role in the pathophysiology of AF.Figure 1Figure 2

Circulating beta-hydroxybutyrate levels in advanced HFrEF: the determinants and prognostic impact

Abstract Background Beta-hydroxybutyrate (BOHB) is the main ketone body and is generated mainly in the liver during states of exessive fatty acid (FA) utilisation, such as starvation or diabetic ketosis. BOHB serves as a metabolic substrate to heart. Mild ketosis or enahancement of BOHB utilisation may favorably affect cardiac function in preclinical HF models. Patients with HF have increased BOHB levels, but regulation of ketosis in HF is poorly understood. Purpose To investigate the determinants and prognostic implact of circulating BOHB levels in patients with advanced HFrEF. Methods We examined 847 pts with symptomatic HFrEF (age 57±11y, 50% CAD, 82% males, NYHA 2.7±0.6, LVEF 22±5%, BNP 802±850 pg/ml), referred to IKEM for TX or device (ICD/CRT/LVAD) implant. Patients underwent clinical and echocardiographic examination, MLHFQ questionnaire, circulating metabolite assessment, body composition (DEXA, n=150) and right heart catheterisation (n=383). BOHB in peripheral vein was measured in all subjects after overnight fasting by an enzymatic metod (Autokit 3-HB, Wako). Patients were followed for occurrence of an event (death/urgent Tx/LVAD). Results Median BOHB level was 64 (IQR: 33-161) mmol/l. BOHB was higher in DM patients (111 vs 163, &amp;lt;0.001) and inreased with age. Body composition, congestion status, insulin resistance (HOMA-IR), liver function tests, weight loss history, HF symptoms (NYHA, MLHFQ), gender, HF etiology or HF therapy (BB, ACE/ARB) were unrelated to BOHB levels. BOHB strongly correlated with markers of lipolysis (free FA, BNP) and GDF15, less strongly with pulmonary hypertension (PA systolic pressure, pulmonary vascular resistance-PVR), inflammation (CRP level, leukocytes%) and humoral regulators of ketogenesis in the liver (insulin/glucagon ratio). After median follow-up of 1126 days (IQR: 410; 1781), 60% patients experienced an event. In Cox analysis, Increased BOHB levels predicted worse survival (RR: 1.001, 95%CI: 1.0005-1.001, p&amp;lt;0.0001), particularly in the upper BOHB tercile. Impaired survival was also associated with elevated free FA (RR: 1.78 (1.23-2.51, p= 0.002). In bivariate Cox analysis of free FA and BOHB levels, only free FA, but not BOHB, remained significantly asccociated with adverse outcome. Conclusion Increased BOHB levels in HFrEF correlate with free FA levels, likely due to sympatetic activation-driven and BNP-driven lipolysis. The association of increased BOHB with adverse outcome dissapears after adjustment to free FA level. Other notable associations of BOHB were diabetic status, GDF15 level, systemic inflammation and pulmonary hypertension.

HDLc levels have a protective effect for in-hospital mortality in Non-STEMI but not in STEMI patients

Abstract Background High-density lipoprotein cholesterol (HDLc) has been associated to lower myocardial infarction size although it is not considered a primary target in cardiovascular prevention or as treatment target in patients with cardiovascular disease. The role of HDLc on in-hospital mortality in acute coronary syndrome (ACS) patients could be influenced by many variables. Methods We performed and observational and cross-sectional analysis of all patients admitted for an ACS in 2 tertiary hospitals in Spain between 2006 and 2016. HDL was measured in the first 24 of the admission in the first overnight fasting state. Results We included 8,684 patients, mean (standard deviation) age 66.88 (12.90), 27.5% women, mean GRACE score 143.13 (40.27), and 35.09% admitted for ST-elevation myocardial infarction (STEMI). Mean HDLc levels were 35.90 (13.64) mg/dL in whole cohort and were significantly lower in patients presenting as non-STEMI (35.53±13.62 vs. 36.55± 13.65 mg/dL), those with GRACE score &amp;lt;140 (35.09±13.00 vs. 36.78±14.24 mg/dL) and women (34.28±12.81 vs. 40.21±14.80 mg/dL) but not in patients who died or not (p=0.43). From these variables, we observed a significant interaction of HDLc levels and STEMI presentation (p=0.03) for in-hospital mortality risk and, thus, results were analyzed separately. After natural logarithm transformation, in-hospital mortality risk had a "U-shaped" distribution in STEMI patients compared to the linear trend in Non-STEMI patients (figure 1). Multivariate analysis, adjusted by age, gender, risk factors, hemoglobin, revascularization and GRACE score, verified the interaction and the protective effect of HDLc in Non-STEMI patients (OR: 0.48 95% CI 0.28-0.80; p=0.005) but not in STEMI patients (OR: 0.96 95% CI 0.55-1.67; p=0.887) (figure 2). Conclusions Clinical presentation of STEMI vs. non-STEMI modifies the effect of HDLc on in-hospital mortality. HDLc might have a protective effect in patients presenting with non-STEMI only.

Abstract 18692: Relationship Between Fasting Time on Ketogenic Diet and Myocardial Glucose Suppression in Patients Referred for Cardiac Sarcoidosis Evaluation on FDG-PET Imaging

Introduction: FDG-PET imaging is standard for assessing myocardial inflammation for cardiac sarcoidosis (CS). Preparation with the ketogenic diet (KD) is required to suppress physiologic myocardial glucose uptake (MGU), thereby highlighting pathologic MGU. Incomplete physiologic myocardial glucose suppression (MGS) continues to limit FDG-PET. The effect of fasting time (FT) on MSG remains unexplored. Goal: To identify if FT is an independent predictor of MGS following a KD in patients undergoing FDG-PET imaging. Methods: We prospectively included 442 consecutive patients (59.2 ± 10.9 yrs, 39% female, 55% white) who underwent 590 FDG-PET scans for the evaluation of CS after following a KD at our institution between 2021 and 2023. Time from last meal to FDG injection was documented in all patients. Serum BHB levels were measured in 516 scans. FDG PET images were classified as 1) diagnostic (complete MGS) when there was either no MGU (negative) or multifocal uptake (positive), or 2) nondiagnostic (incomplete MGS) when there was either diffuse left ventricular or nonspecific uptake. Results: The KD was followed for 1, 2 or ≥3 days in 127 (22%), 61 (10%), and 402 (68%) of cases respectively. FDG-PET scans were interpreted as the following: 436 (74%) negative; 109 (18.3%) positive; 13 (2.2%) diffuse; 32 (5.4%) nonspecific uptake. Patients on the KD for only 1 day had higher rates of MGS with increased FT (β = 0.33 ± 0.11, p &lt;0.01); this correlation did not hold true for patients on KD for 2 days (β = -0.005 ± 0.09, p = 0.96) whereas, patients on the KD for 3 or more days showed lower rates of MGS with increased FT (β = -0.18 ±0.07, p&lt;0.01) ( Figure 1 ). When adjusting for BHB level, the correlation between MGS and FT held true (1 day: β = 0.35 ± 0.13, p &lt;0.01; 2 days: β = 0.26 ± 0.28, p = 0.35; 3 days: β = -0.17 ± 0.07, p = 0.02). Conclusion: Fasting time appears to be most beneficial in patients following the KD for 1-day only. Patients following the KD for 2 days or longer may not require overnight fasting.

Energy and macronutrient restriction regulate bile acid homeostasis

As we reported previously, caloric restriction (CR) results in an increased concentration of bile acids (BA) in the intestinal mucosa. We now investigated the background of this phenotype, trying to identify nutrition-related factors modulating BA levels. Male mice were submitted to various types of restrictive diets and BA levels and expression of associated factors were measured. We found that BA concentration is increased in the liver of CR mice, which corresponds to reduced expression of the Shp gene and elevated mRNA levels of Cyp27a1, Bal, and Ntcp, as well as CYP7A1 protein and gene expression. Correlation between decreased concentration of BAs in the feces, increased BAs levels in plasma, and elevated gene expression of BAs transporters in the ileum mucosa suggests enhanced BA uptake in the intestine of CR mice. Corresponding to CR upregulation of liver and ileum mucosa, BA concentration was found in animals submitted to other types of prolonged energy-restricting dietary protocols, including intermittent fasting and fasting-mimicking diet. While over-night fasting had negligible impact on BAs levels. Manipulation of macronutrient levels partly affected BA balance. Low-carbohydrate and ketogenic diet increased BAs in the liver but not in the intestine. Carbohydrate restriction stimulates BA synthesis in the liver, but energy restriction is required for the increase in BA levels in the intestine and its uptake.

Consensus on criteria for acromegaly diagnosis and remission

PurposeThe 14th Acromegaly Consensus Conference was convened to consider biochemical criteria for acromegaly diagnosis and evaluation of therapeutic efficacy.MethodsFifty-six acromegaly experts from 16 countries reviewed and discussed current evidence focused on biochemical assays; criteria for diagnosis and the role of imaging, pathology, and clinical assessments; consequences of diagnostic delay; criteria for remission and recommendations for follow up; and the value of assessment and monitoring in defining disease progression, selecting appropriate treatments, and maximizing patient outcomes.ResultsIn a patient with typical acromegaly features, insulin-like growth factor (IGF)-I > 1.3 times the upper limit of normal for age confirms the diagnosis. Random growth hormone (GH) measured after overnight fasting may be useful for informing prognosis, but is not required for diagnosis. For patients with equivocal results, IGF-I measurements using the same validated assay can be repeated, and oral glucose tolerance testing might also be useful. Although biochemical remission is the primary assessment of treatment outcome, biochemical findings should be interpreted within the clinical context of acromegaly. Follow up assessments should consider biochemical evaluation of treatment effectiveness, imaging studies evaluating residual/recurrent adenoma mass, and clinical signs and symptoms of acromegaly, its complications, and comorbidities. Referral to a multidisciplinary pituitary center should be considered for patients with equivocal biochemical, pathology, or imaging findings at diagnosis, and for patients insufficiently responsive to standard treatment approaches.ConclusionConsensus recommendations highlight new understandings of disordered GH and IGF-I in patients with acromegaly and the importance of expert management for this rare disease.

The use of overnight fasting copeptin and glucagon stimulated copeptin to diagnose arginine vasopressin deficiency in a tertiary centre

The use of overnight fasting copeptin and glucagon stimulated copeptin to diagnose arginine vasopressin deficiency in a tertiary centre

The Effects of Overnight Fasting Duration on Glucose and Lipid Metabolism in a Sprague-Dawley Rat Model of Nonalcoholic Steatohepatitis with Advanced Fibrosis.

Nonalcoholic steatohepatitis (NASH) can progress to hepatic fibrosis, and is associated with cardiovascular and liver-related mortality. To understand the pathogenesis of NASH, reliable animal models of the disease are useful. In animal studies, the animals are usually fasted overnight before biospecimens are taken, but little is known about the effects of fasting. Here, we investigated the impact of overnight fasting for approximately 9 to 17 h on glucose and lipid metabolism in a Sprague-Dawley (SD) rat model of diet-induced moderate and advanced NASH in comparison to normal SD rats. Our results revealed that in the moderate NASH model rats, the fasting duration did not affect glucose and lipid metabolism, the histopathological findings, or the hepatic mRNA expression levels of genes related to lipid metabolism, cholesterol metabolism, inflammation, fibrosis, and oxidative stress. In contrast, in the normal rats, significant fasting time-dependent reductions were observed in the epididymal fat pad weight and the hepatic mRNA expression levels of adipose differentiation-related protein and heme oxygenase-1. Moreover, in the advanced NASH model rats, a significant fasting time-dependent reduction and increase were observed in the serum insulin level and mRNA expression level of alpha-smooth muscle actin, respectively. Our present results suggest that the influence of the overnight fasting duration differs among the healthy condition, moderate NASH, and advanced NASH statuses. Further studies are needed in humans to determine the appropriate overnight fasting duration for the accurate evaluation of glucose and lipid metabolism in NASH patients.

Optimal Bowel Preparation Method to Visualize the Distal Ileum via Small Bowel Capsule Endoscopy.

Small bowel capsule endoscopy (SBCE) is a convenient and minimally invasive method widely used to evaluate the small intestine. However, especially in the distal ileum, visualization of the intestinal mucosa is frequently hampered by the remaining intestinal contents, making it difficult to detect critical lesions. Although several studies have reported on the efficacy of bowel preparation before SBCE, no standardized protocol has been established. Herein, we determined the optimal preparation method for better visualization of the distal ileum using SBCE. We retrospectively analyzed 259 consecutive patients who had undergone SBCE between July 2009 and December 2019, divided into three groups: Group A (no preparation except overnight fasting), Group B (ingestion of 1-2 L polyethylene glycol 4 h before colonoscopy after overnight fasting and performing SBCE immediately after colonoscopy), and Group C (ingestion of 0.9 L magnesium citrate [MC] before SBCE after overnight fasting). The visibility of the intestinal mucosa in the first 10 min and at the last 10 min during the period of observation of the distal ileum was examined using a scoring system and compared. The visibility of the images captured by SBCE was assessed based on the scoring of the degree of bile/chyme staining, residual fluid and debris, brightness, bubble reduction, and visualized mucosa. The status of intestinal collapse was also assessed. In the first 10 min of observation of the distal ileum, no significant differences were detected among the groups. In the last 10 min, significantly better images were acquired in Group C in terms of bile/chyme staining, brightness, bubble reduction, and visualized mucosa. Bowel preparation using a low-dose MC solution 2 h before SBCE provided significantly higher-quality images of the distal ileum. Further optimization, such as the timing of initiating the preparation, is necessary to determine the optimal regimen for bowel preparation prior to SBCE.

Adrenergic modulation of melanocortin pathway by hunger signals

Norepinephrine (NE) is a well-known appetite regulator, and the nor/adrenergic system is targeted by several anti-obesity drugs. To better understand the circuitry underlying adrenergic appetite control, here we investigated the paraventricular hypothalamic nucleus (PVN), a key brain region that integrates energy signals and receives dense nor/adrenergic input, using a mouse model. We found that PVN NE level increases with signals of energy deficit and decreases with food access. This pattern is recapitulated by the innervating catecholaminergic axon terminals originating from NTSTH-neurons. Optogenetic activation of rostral-NTSTH → PVN projection elicited strong motivation to eat comparable to overnight fasting whereas its inhibition attenuated both fasting-induced & hypoglycemic feeding. We found that NTSTH-axons functionally targeted PVNMC4R-neurons by predominantly inhibiting them, in part, through α1-AR mediated potentiation of GABA release from ARCAgRP presynaptic terminals. Furthermore, glucoprivation suppressed PVNMC4R activity, which was required for hypoglycemic feeding response. These results define an ascending nor/adrenergic circuit, NTSTH → PVNMC4R, that conveys peripheral hunger signals to melanocortin pathway.