Plasma Glucose Concentrations Research Articles

Associations of retinal microvascular alterations with diabetes mellitus: an OCTA-based cross-sectional study

BackgroundDiabetes, a health crisis afflicting millions worldwide, is increasing rapidly in prevalence. The microvascular complications triggered by diabetes have emerged as the principal cause of renal disease and blindness. The retinal microvascular network may be sensitive to early systemic vascular structural and functional changes. Therefore, this research endeavored to discern the systemic determinants influencing the retinal microvascular network in patients with and without diabetes.MethodsThe Kailuan Eye Study is a cross-sectional study based on the community-based cohort Kailuan Study. Participants underwent optical coherence tomography angiography (OCTA) (Zeiss Cirrus 5000; Carl Zeiss Meditec) and comprehensive systemic examination. Metrics such as perfusion density (PD), vascular density (VD), foveal avascular zone (FAZ) parameters of the superficial capillary plexus (SCP) in the macula were assessed.ResultsThis study included 860 eligible participants (average age = 62.75 ± 6.52 years; 21.9% female), of which 449 were diabetics. People with diabetes had diminished PD and VD in the entire macular and parafoveal regions compared to people without diabetes. Reduced PD in the whole macular region was correlated with higher fasting plasma glucose (FPG, mmol/L) concentration (Beta = -0.19, 95% CI = -0.42 to -0.36, P < 0.001), longer axial length (AL, mm) (Beta = -0.13, 95%CI = -0.48 to -0.25, P = 0.002), and elevated heart rate (Beta = -0.10, 95%CI = -0.14 to -0.19, P = 0.014), after adjusting for younger age (Beta = -0.18, 95%CI = -0.24 to -0.35, P < 0.001), consistent with VD of the whole macular region. A higher FPG level was significantly correlated with lower SCP density of both PD and VD in the macular and parafoveal region (P < 0.05 for all), as well as increased systolic blood pressure and low-density lipoprotein cholesterol concentration (P < 0.01 for all).ConclusionsIn this large-sample cross-sectional study, OCTA evaluation revealed that high prevalence of diabetes and elevated FPG levels were correlated with reduced retinal VD and PD. Hypertension and hyperlipidemia are important risk factors for the development of atherosclerotic cardiovascular disease but have no significant effect on retinal microvascular abnormalities.

Effects of exercise modality combined with moderate hypoxia on blood glucose regulation in adults with overweight.

Purpose: This study aimed to investigate the combined effects of moderate hypoxia with three different exercise modes on glucose regulation in healthy overweight adults. Methods: Thirteen overweight males (age: 31 ± 4years; body fat 26.3 ± 3.2%) completed three exercise trials in a randomized crossover design involving 60min cycling exercise at 90% lactate threshold (LOW), sprint interval training (20 × 4s all-out; SIT) and lower limb functional bodyweight exercises (8 sets of 4 × 20s; FEX) under moderate hypoxia (FiO2 = 16.5%). Post-exercise oral glucose tolerance test (OGTT) was performed following each trial. Heart rate, oxygen saturation (SpO2), physical activity enjoyment scale (PACES), and perceptual measures were recorded during each exercise session. Venous blood was collected pre-, immediately post-, and 24h post-exercise and analysed for plasma glucose and insulin, incremental area under curve (iAUC), and circulating microRNA expression (c-miRs-486-5p, -126-5p, and -21-5p). Interstitial glucose concentrations were measured using continuous glucose monitoring (CGM). Results: Post-exercise OGTT iAUC for plasma glucose and insulin concentration were lower in SIT and LOW vs. control (p < 0.05) while post-exercise interstitial glucose iAUC and c-miRs were not different between exercise modes. Heart rate was greater in SIT vs. LOW and FEX, and FEX vs. LOW (p < 0.05), SpO2 was lower in SIT, while PACES was not different between exercise modes. Perceptual measures were greater in SIT vs. LOW and FEX. Conclusion: Acute SIT and LOW under moderate hypoxia improved post-exercise plasma insulin compared to FEX exercises. Considering SIT was also time-efficient, well tolerated, and enjoyable for participants, this may be the preferred exercise modality for improving glucose regulation in adult males with overweight when combined with moderate hypoxia.

Variations of blood metabolites in single‐ and multiple‐bearing Ossimi ewes during the transition period

AbstractEvaluation of the metabolic profile indices allows early detection and treatment of various metabolic disorders during the transition period in ewes. This study aimed to determine the variations in the blood metabolites around lambing in Ossimi ewes. The blood metabolites were investigated in ewes with single (n = 27) and multiple (n = 9) lambs at 3‐ and 1‐week pre‐lambing and 3‐week post‐lambing. The plasma concentrations of glucose were higher in single‐bearing ewes than those in multiple‐bearing ewes (p &lt; .05), moreover, its lowest value was measured at 1‐week prepartum in both groups. Throughout the study period, the serum concentrations of non‐esterified fatty acids (NEFA) were significantly increased in ewes with multiple lambs compared to ewes with single lambs (p &lt; .05), and the highest value was found at 1‐week before parturition in both groups. In addition, the serum level of beta‐hydroxybutyric acid (BHBA) was higher at 3‐week postpartum, and it was significantly increased in multiple‐bearing ewes than that in single‐bearing ones (p &lt; .05) at 3‐week pre‐lambing. In both groups, the lowest values of total proteins were determined 1‐week before lambing, and its concentrations, at 3‐ and 1‐week prepartum, were higher in ewes with single lambs than those with multiple lambs (p &lt; .05). In contrast, the serum concentrations of albumin were significantly lowered 1‐week postpartum (p &lt; .05), and without significant differences between both groups (p &gt; .05). The serum activities of aspartate aminotransferase (AST) and gamma‐glutamyltransferase (GGT) were significantly increased at 1‐week after parturition in both groups (p &lt; .05). Furthermore, the serum activities of AST were higher in multiple‐bearing ewes than those in single‐bearing ones at 3‐week pre‐lambing and 3‐week post‐lambing (p &lt; .05). Variable positive and negative correlations were determined among the blood metabolites. In conclusion, physiological adaptations are associated with the fluctuation of the blood metabolites around lambing. The higher the number of foetuses the higher the metabolic variations in Ossimi ewes. Therefore, regular metabolic profiling for health monitoring may be necessary to avoid disease development during the transition period.

Local variation in stress response of juvenile anadromous brown trout, Salmo trutta.

Habitat fragmentation may cut off anadromous salmonids from parts of their potential native habitat and separate previously connected populations. Understanding the consequences of this is vital for fish management and prioritization of restoration activities. Here, we show that there is a significant difference in the body morphology, physiological stress response, and aspects contributing to aerobic capacity between juvenile anadromous brown trout, Salmo trutta, collected at a downstream site and an upstream site, separated by 2 km and several challenging stream sections, in a small unfragmented stream system in western Sweden. Following a standardized stress test, there were significant differences between fish from the upstream and downstream sites (plasma cortisol concentration, plasma osmolality, hematocrit, hemoglobin concentration, and mean corpuscular hemoglobin concentration). Plasma glucose concentration did not significantly differ between fish from the two sites. Fish from the upstream site had larger spleen mass, although there was no evidence of differences in ventricle mass or proportion of compact ventricular myocardium. These physiological differences indicate local variation in stress response and highlight the importance of considering local trait variation in river management. If a section of the river becomes fragmented or degraded, and there are differences in the juveniles in different parts of the river, the consequence for the population might be larger than the proportional loss of habitat.

Postprandial effects following a semielemental critical-care diet lead to changes in uric acid, bile acids, and glucose in the central bearded dragon (Pogona vitticeps).

To assess the prandial effects of a semielemental diet on plasma uric acid, bile acid, and glucose concentrations in the central bearded dragon (Pogona vitticeps). 13 healthy adult male bearded dragons. Following a 72-hour fasting period, blood was collected to measure preprandial uric acid, bile acid, and glucose concentrations. The animals were then gavage fed 1.2% body weight of an omnivore critical-care diet containing 20% protein, 9.5% fat, 2.5% fiber, and 2.39 kcal/mL. Blood was collected for repeat concentrations at 4 and 24 hours. Median (IQR) uric acid concentration (mg/dL) increased from 3.8 preprandial (2.8 to 4.3) to 4.7 4 hours postprandial (4 to 7; P = .0001). Median (IQR) bile acid concentration (mg/dL) increased from 1.8 preprandial (1 to 3.4) to 9.5 24 hours postprandial (5.6 to 10.4; P = .004). Median (IQR) glucose concentration (mg/dL) was 209 at time 0 (193 to 216), 287 at 4 hours (258 to 312), and 393 at 24 hours (361 to 464). Significant increases were seen between pre- and 4-hours-postprandial (P < .0001), pre- and 24-hours-postprandial (P < .0001), and 4-hours- and 24-hours-postprandial (P < .0001) glucose concentrations. Results suggest that postprandial status and diet composition should be considered during the interpretation of some biochemical analytes in the bearded dragon.

Dietary cooking oils and cardiometabolic measurements in an elderly Chinese population.

To investigate three features of dietary cooking oil intake, namely, the consumption, cooking style, and composition of fatty acids in relation to several cardiometabolic measurements in an elderly Chinese population. The elderly (≥ 65 years) participants for this study were recruited from two community health centers in the urban area of Shanghai. A questionnaire was administered to collect information on dietary oil consumption (low, medium and high) and cooking styles (fry or stir-fry vs. others) and the composition of fatty acids (poly-unsaturated vs. mono-unsaturated). The cardiometabolic measurements included anthropometry, blood pressure, fasting plasma glucose and serum lipids. The 1186 study participants had a mean age of 70.9 ± 5.4 years. The mean dietary oil consumption was 35.0 g/d, being low (< 25 g/d), medium (25-49 g/d) and high (≥ 50 g/d) in 485,467 and 234 participants, respectively. The proportion of the fry or stir-fry cooking style and oils rich in mono-unsaturated fatty acids was 30.4% and 27.4%, respectively. Both before and after adjustment for sex, age, current smoking and alcohol intake, dietary oil consumption was significantly (P ≤ 0.02) and positively associated with the prevalence of treated hypertension and fasting plasma glucose concentration. With similar adjustments as above and additional adjustment for dietary oil consumption, the fry or stir-fry cooking style was significantly (P ≤ 0.048) and positively associated with body mass index, but inversely with systolic and diastolic blood pressure and serum low-density lipoprotein cholesterol, and the dietary intake of oils rich in mono-unsaturated fat acids was significantly (P ≤ 0.02) and positively associated with diastolic blood pressure, serum triglycerides, total cholesterol and low-density lipoprotein cholesterol, and the prevalence of hypertriglyceridemia and hypercholesterolemia. This study showed that both the consumption and composition of fatty acids of the dietary oils mattered with regard to several cardiometabolic measurements in an elderly Chinese population.

Prediabetes: prevalence, associations with cardiovascular risk factors and contribution to survival in the Russian population

Aim. To assess the prevalence of type 2 diabetes (T2D) and prediabetes in the Russian population aged 25-64 years, as well as the association of prediabetes with risk factors (RFs) of noncommunicable disease. To study the contribution of carbohydrate metabolism disorders to mortality and the occurrence of cardiovascular events.Material and methods. We included data from cross-sectional studies ESSE-RF and ESSE-RF2. The final sample included 26418 people (10268 men and 16150 women) who signed informed consent. A modular questionnaire was used. Biochemical parameters were determined in the National Medical Research Center for Therapy and Preventive Medicine with an Abbott Architect c8000 autoanalyzer using diagnostic kits from Abbott Diagnostics (USA). Impaired fasting glycemia (IFG) was defined as a fasting plasma glucose concentration of 6,1-6,99 mmol/L. The presence of T2D was determined by interview and/or fasting plasma glucose ≥7,0 mmol/L. Obesity was defined as a body mass index of ≥30,0 kg/m2. Abdominal obesity was defined as a waist circumference of ≥102 cm in men and ≥88 cm in women. A prospective observation cohort was formed from 14 regions of ESSE-RF and ESSE-RF2 (n=22812). The vital status of each examined person was clarified once every 2 years. Information on fatal and non-fatal events was collected. Statistical processing was performed using the open-source statistical programming language and R environment (version 4.1). Associations were assessed using logistic regression. Kaplan-Meier curves were used to estimate survival. Associations with endpoints were assessed using Cox proportional hazards models.Results. In the Russian population aged 25-64 years, the prevalence of T2D and prediabetes, assessed by IFG, was 6,9% (men — 7,1%, women — 6,7%) and 6,2% (men — 7,7, women — 5,0% (p&lt;0,001)), respectively. Age, low level of education, obesity, including abdominal obesity, hypertension, tachycardia, hyperuricemia and lipid metabolism disorders were significantly associated with prediabetes, and for men, additionally, stress. Prediabetes and T2D demonstrated a significant decrease of survival, including cardiovascular survival, and the occurrence of a composite endpoint. However, multivariate analysis adjusted for sex, age, and region of residence indicates a significant contribution of T2D, but not IFG.Conclusion. To reduce the T2D burden in the Russian Federation, patients with T2D should be identified early and RFs should be controled. Early detection of prediabetes plays a significant role in the prevention of T2D. In addition, T2D and prediabetes have common risk factors, and therefore common ways of prevention.

Influence of epinephrine reactivity to stress on meat quality in goats.

The magnitude of physiological responses to a stressor can vary among individual goats within a herd; however, whether these differences can differentially affect meat quality is not known. This study was conducted to determine the influence of the magnitude of epinephrine response (ER) to acute stress on muscle metabolome and meat quality in goats. Male Spanish goats (6 mo old) were transported for 180min. (N = 75 goats; 25 goats/d) to impose stress. Blood samples were obtained after transport for analysis of physiological responses. Goats were slaughtered using humane procedures and samples were collected for muscle metabolomics and meat quality analyses. The data obtained from blood and muscle/meat analysis were then categorized based on epinephrine concentrations into low (LE), medium (ME), and high (HE) ER groups (n = 12/ER group). The physiological and meat quality variables were analyzed as a Completely Randomized Design in SAS, and metabolomics data were analyzed using R software. Plasma glucose concentrations were significantly high in the HE group, low in the LE group, and intermediate in the ME group (P < 0.05). However, leukocyte counts and cortisol, norepinephrine, blood urea nitrogen, and creatine concentrations were not different among the ER groups. Muscle (Longissimus dorsi) glycogen concentrations (15min postmortem) were significantly higher (P < 0.05) in the ME and LE groups than in the HE group. However, postmortem Longissimus muscle pH and temperature (15min and 24h), 24h calpastatin and desmin levels, and rib chop color (L*, a*, and b*), cooking loss, and Warner-Bratzler shear force values were unaffected by ER. Targeted metabolomics analysis of Longissimus muscle (15min) revealed that diacyl phosphatidylcholines (C38:0; 40:6) and sphingomyelin (C20:2) were significantly different (P < 0.05) among the ER groups, with the concentrations of these metabolites being consistently high in the LE group. These differential muscle metabolite concentrations suggest that ER can influence biochemical pathways associated with cell membrane integrity and signaling. ER had a significant effect on dopamine concentrations, with the levels increasing with increasing levels of ER. The results indicate that differences in epinephrine reactivity can influence selected physiological responses and muscle metabolites; however, it does not significantly influence meat quality attributes.

Burden of liver cancer attributable to high fasting plasma glucose: a global analysis based on the global burden of disease study 2019

ObjectiveLiver cancer is the world’s sixth most prevalent cancer and the third most frequent cause of cancer-related mortality. Glucose metabolic disorders, indicated by a high fasting plasma glucose (HFPG) concentration, is a contributor to the etiology of liver cancer. With the rising prevalence of glucose metabolic disorders, an assessment of the global burden of liver cancer attributable to HFPG is warranted to inform global liver cancer prevention and control strategies. Methods and analysisWe evaluated the global death and disability-adjusted life years (DALYs) of liver cancer and its subtypes attributable to HFPG at global, regional, and country level. The temporal trend and disparity across geographic regions, social development level, age groups and sex were assessed. ResultsIn 2019, HFPG-attributable liver cancer was estimated to have caused 4,729.49 deaths and to be responsible for 99,302.25 DALYs. The age-standardized mortality and DALY rate were 0.06 and 1.20 per 100,000 population, and displayed a significantly increasing temporal trend from 1990 to 2019. The age-standardized mortality rate of patients with liver cancer that was attributable to HFPG was higher in men than women. Sex-based disparity narrowed after the women reached menopause, but increased between 1990 and 2019. ConclusionThe burden of liver cancer that are attributable to HFPG has been influenced by longitudinal changes in lifestyle, the etiology of liver disease, age demographics, and hormonal status in women. These findings suggest that comprehensive strategies could be implemented, especially for patients with NASH and hyperglycemia, to prevent liver cancer.

Morphology and metabolic traits related to swimming performance in Australasian snapper (Chrysophrys auratus) selected for fast growth.

Changes in body shape are linked to swimming performance and become relevant for selective breeding programmes in cultured finfish. We studied how the selection for fast growth could affect phenotypes by investigating the relationship between swimming performance and body shape. We also investigated how swimming might affect plasma metabolite concentrations. Critical swimming speed (UCrit), body traits (e.g., BW, body weight; BL, body length; K, condition factor), and plasma lactate and glucose concentrations were evaluated in two cohorts of Australasian snapper (Chrysophrys auratus): one derived from wild broodstock (F1), and the other selected for fast growth (F4). UCrit tests (n = 8) were applied in groups of 10 snapper of similar BW (71.7 g) and BL (14.6 cm). The absolute or relative UCrit values of both cohorts were similar (0.702 m⋅s-1 and 4.795 BL⋅s-1, respectively), despite the F4 cohort displaying a higher K. A positive correlation between K and absolute UCrit (Pearson's r = 0.414) was detected in the F4 cohort, but not in the F1 cohort, which may be linked to differences in body shape. A negative correlation between relative UCrit and body size (Pearson's r between -0.682 and -0.501), but no correlation between absolute UCrit and body size, was displayed in both cohorts. Plasma lactate and glucose concentrations were higher in the F4 cohort at UCrit. Whether a longer selective breeding programme could result in more changes in body shape, potentially affecting swimming performance, should be explored, along with the potential outcomes of the differences in metabolic traits detected.

#976 Empagliflozin limits AKI incidence and severity following cardiac surgery: an open-label phase IV randomized pilot study

Abstract Background and Aims Cardiac surgery-associated acute kidney injury (CSA-AKI) is a frequent complication of cardiac surgery assisted by cardiopulmonary bypass (CPB). Currently, no effective preventative strategies exist to reduce the incidence of acute kidney injury (AKI). Sodium-glucose transport protein 2 (SGLT2) inhibitors are effective in reducing the incidence of AKI in studies conducted in patients with chronic kidney disease. Therefore, we hypothesized that perioperative SGLT2 inhibition could reduce the incidence of CSA-AKI. Method In this open-label phase IV, randomized, parallel-group, balanced (1:1), pilot study, adult patients undergoing elective cardiac surgery with CPB were randomized to receive 10 mg empagliflozin per os once daily three days before surgery until two days after surgery, or standard care. The primary outcome was AKI incidence according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Other outcomes included hypoxia-inducible factor 1 alpha (HIF1A) and urinary Kidney Injury Molecule (KIM-1), urinary neutrophil gelatinase associated lipocalin (NGAL) and metabolic parameters such as plasma ketone and glucose concentrations. Results Between March 2022 and April 2023, 60 patients were randomized to empagliflozin (n = 29) or control (n = 31). All patients who underwent cardiac surgery with CPB were included in the intention-to-treat analysis (n = 25; empagliflozin group, n = 30; control group). SGLT2 inhibition significantly reduced the incidence of all stages of AKI (20% vs 66.7%; absolute difference 46%, 95% CI .13 to .63, P &amp;lt; .001). This decline in AKI incidence was reflected in the kidney biomarkers. SGLT2 inhibition also significantly reduced the number of patients with postoperative hyperglycemia (28% vs 60%; absolute difference 32%, 95% CI −56.8 to −7.2, P = .029). We observed no differences in the incidence of neither ketoacidosis nor hypoglycemic events. Conclusion Perioperative SGLT2 inhibition, compared with standard of care, demonstrated a significant reduction in AKI incidence rates. These findings merit validation in a larger placebo-controlled trial which is currently ongoing. Supplementary figures:

Good Handling Practices Have Positive Impacts on Dairy Calf Welfare

The objective was to evaluate the effects of good handling practices on dairy calf welfare. Forty-eight crossbred dairy calves were assigned to two treatments: conventional handling (CH): calves kept in individual pens, fed milk replacer in buckets without nipples and abruptly weaned; or good handling practices (GHP): calves kept in group pens, fed milk replacer in buckets with nipples, given daily tactile stimulation during feeding, and progressive weaning. Calf welfare was assessed from birth to 120 days of age, based on: health (plasma concentrations of glucose and IgG, and occurrences of diarrhea, pneumonia, tick-borne disease, or death); physiology (heart rate [HR], respiratory rate [RR], and rectal temperature [RT]); behavior (flight distance [FD], latencies for first movement [LM] and to hold the calf in a pen corner [LH], and total time a calf allowed touching [TTT]); and performance indicators (body weight, average daily gain, and weaning success at 70 days of age). Calves in the GHP treatment had a lower HR at 30 days of age, shorter FD and LH, longer TTT, and lower RR and RT than CH (p &lt; 0.05). However, health, deaths and performance indicators did not differ (p &gt; 0.05) between treatments. Based on various indicators, GHP improved dairy calf welfare.

Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies

ObjectiveTo investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related.Research design and methodsObservational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC.ResultsObservationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (β-coefficient: 0.02 (0.02, 0.03), p = 3 × 10− 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (−0.04 (−0.12, 0.32) and − 0.03 (−0.13, 0.06)), nor of glucose on CRP (−0.01 (−0.08, 0.07) and − 0.00 (−0.14, 0.13)).ConclusionsElevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.

Risk assessment by acute bedside echocardiography prior to acute coronary angiography in patients with ST-elevation myocardial infarction: a feasibility study

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): Novo Nordisk Foundation. Background Early risk assessment by hemodynamic measurements in patients with ST-elevation myocardial infarction (STEMI) could be useful for early detection of patients at risk of developing hemodynamic instability after primary percutaneous coronary intervention (pPCI). Anterior STEMI patients have larger infarct size and may be of particular interest. Transthoracic echocardiography (TTE) is a quick, non-invasive, and available tool, however, evidence regarding the use of acute TTE prior to acute coronary angiography (CAG) is limited. Purpose To assess the feasibility of acute bedside hemodynamic assessment in the cath. lab. by TTE in addition to clinical examination, and blood samples in STEMI patients without CS at arrival in the cath. lab. Methods STEMI patients without CS at hospital arrival and treated with pPCI were included in the study during a five week period. Clinical examination (Killip class), blood sampling (lactate, troponin T (TNT), proB-type natriuretic peptide (proBNP), and focused bedside 2D TTE with Doppler were performed prior to the acute CAG. The TTE protocol was focused (approx. 5 minutes) on hemodynamic measurements, infarction related complications, and differential diagnoses e.g. aortic dissection. The TTE was performed during preparation for the acute CAG. Patients were stratified in anterior- vs. non-anterior STEMI based on the culprit artery and prehospital ECG. Feasibility was estimated by all of the following echocardiographic parameters; left ventricular ejection fraction (LVEF), left ventricular outflow tract (LVOT) velocity time integral (VTI), and right ventricular function (tricuspid annular plane systolic excursion (TAPSE)). Results A total of 60 STEMI patients (aged mean 63 years, 18% female) were included, and 47% had an anterior STEMI. No differences in baseline characteristics between the two groups were found including comorbidities, clinical parameters, and time from cath. lab. arrival to first wire over the culprit lesion (median (IQR) 28 (23; 38) vs 32 (24; 40) minutes). Admission biomarkers of blood glucose, lactate, and proBNP plasma concentrations were similar between the two groups. Whereas admission TNT were higher for patients with anterior STEMI (median (IQR) 110 (37; 449) vs. 37 (20; 94) ng/L, p=0.01). The feasibility of TTE-study protocol was 93%. Patients with anterior STEMI had lower LVEF (mean: 36±11 vs. 48±9%, p=0.0003; missing: n=0), and a trend to lower LVOT VTI (19 (6.4) vs. 22 (5.0) cm, p=0.06; missing: n=4). No difference in parameters of diastolic function or TAPSE (missing: n=0) were found. None of the included patients had echocardiographic visible complications related to the infarction. Conclusion Acute TTE is to a high degree feasible and does not delay time to acute revascularization in STEMI patients. Patients with anterior STEMI have significantly higher admission TNT levels, lower LVEF, and a trend to lower LVOT VTI compared with non-anterior STEMI patients.

144 Bioavailability of calcium salt of hydroxy analogue of methionine relative to DL-methionine to support growth performance of 11 to 20 kg pigs

Abstract Methionine (Met) is typically the third limiting AA in commercial swine diets and is commonly supplied as dry DL-Met (99% pure) or DL-Met hydroxy analogue. Data on the relative bioavailability (RBV) of calcium salt of hydroxy analogue of DL-Met (MHA-Ca; 84%) compared with DL-Met in weaned pigs is scarce. The objective of the experiment was to determine the RBV of MHA-Ca compared with DL-Met to support growth performance of 11 to 20 kg pigs. A total of 504 piglets [DNA x Pietrain pigs; approximately 42 d of age and 11 kg body weight (BW)] were used in two blocks of 252 pigs each with 6 pigs (3 entire males and 3 gilts) per pen and 12 replicate pens per treatment. Within each block, pigs were randomly allotted to 7 diets for 21 d. A basal diet (BD) was formulated to be adequate in all essential nutrients except for Met (0.22% standardized ileal digestible Met), which was 61% of the SID Met requirement of 0.36% recommended by NRC (2012) for 10 to 25 kg pigs. The Met-deficient BD was then supplemented with 3 graded levels of DL-Met (0.05, 0.10, and 0.15%) or MHA-Ca (0.077, 0.154, and 0.231%) at the expense of corn. Pigs had ad libitum access to feed (mash) and water. Individual pigs and pen feed disappearance were weighed on d 0 and d 21 to calculate average daily gain (ADG), average daily feed intake (ADFI) and feed conversion rate (FCR). On d 21, blood samples were collected from 1 pig per pen after 8 h fasting to determine total protein, albumin and glucose. Data were analyzed as a randomized complete block design using GLM procedure of SAS 9.4 (SAS Inst. Inc.). Orthogonal-polynomial contrasts were used to determine linear and quadratic effects of increasing levels of DL-Met and MHA-Ca, and the effect of Met sources. The final BW at d 21 and overall average daily gain (ADG; 375, 401, 429, 430, 402, 431, and 428 g/d for diets 1 to 7, respectively) increased linearly (P &amp;lt; 0.01) by graded additions with both Met sources. The ADFI was not different but the overall FCR (1.64, 1.55, 1.51, 1.45, 1.59, 1.46, and 1.50 for diets 1 to 7, respectively) improved linearly (P &amp;lt; 0.01) by supplementation with DL-Met or MHA-Ca. Pig performance responses (ADG, ADFI and FCR) was not different (P ≥ 0.15) when Met was supplemented in the Met-deficient diet at a DL-Met to MHA-Ca ratio of 65:100 on a product basis. Plasma concentrations of total protein, albumin and glucose on d 21 were not affected (P &amp;gt;0.05) by dietary treatments or Met sources. Based on ADG as a response of Met supplementation level, the linear and exponential regressions estimated the RBV of 64 and 65%, respectively for MHA-Ca relative to DL-Met (product-to-product basis) in 11 to 20 kg pigs.

Circulating Extracellular Vesicles Are Elevated with Prediabetes and Adversely Affect Cerebral Endothelial Nitric Oxide and Endothelin-1 Production

Experimental and clinical studies indicate that a proatherogenic endothelial phenotype develops in the prediabetic, hyperglycemic state providing the platform for accelerated vascular disease with prediabetes and, in turn, type 2 diabetes. Prediabetes (fasting plasma glucose concentrations: 100-125 mg/dL) is associated with an increased risk of stroke. Circulating endothelial cell-derived microvesicles (EMVs) are now recognized as both a biomarker and mediator of vascular health and disease. In fact, EMVs have been shown to be involved in the pathogenesis of cerebrovascular dysfunction leading to increased stroke risk. Circulating EMVs are elevated in adults with prediabetes; whether EMVs associated with the prediabetic state promote endothelial abnormalities known to increase stroke risk is unknown. The experimental aim of this study was to determine the effect of EMVs isolated from adults with prediabetes on brain endothelial cell nitric oxide (NO) and endothelin (ET)-1 production. Circulating EMVs (CD144-PE) were isolated (flow cytometry) from 20 mid-life adults (age:44-69 yr): 10 normoglycemic (NG; 8M/2F; age: 55±2 yr; BMI: 25.7±0.8 kg/m2; fasting plasma glucose: 87±2 mg/dL) and 10 prediabetic (PreD: 8M/2F; 55±2 yr; 27.1±1.5 kg/m2; 107±2 mg/dL). Human cerebral microvascular endothelial cells (hCMECs) were cultured and separately treated with EMVs from each subject. Expression of intracellular proteins of interest was determined by capillary electrophoresis immunoassay. Circulating EMV concentrations were significantly higher (~65%) in PreD vs NG (180±25 vs 110±13 EMV/μL) and significantly associated with plasma glucose concentrations (r=0.48; P=0.03). Phosphorylation is the primary posttranslational modification regulating eNOS enzyme activity. Phosphorylation of Ser1177 confers the greatest activation of eNOS; whereas, phosphorylation at Thr495 reduces eNOS activation. Expression of p-eNOS (Ser1177) was lower (47.6±2.6 vs 58.6±3.5 AU; P=0.02) and p-eNOS (Thr495) higher (82.6±4.4 vs 31.1±2.5 AU; p&lt;0.001) in cells treated with EMVs from PreD vs NG. Concordantly, NO production was ~20% lower (6.0±0.2 vs 7.2±0.4 μmol/L; p&lt;0.05) in cells treated with EMVs from PreD adults. PreD-associated EMVs also significantly increased (~25-70%) the expression of Big ET-1 (804.4±47.7 vs 656.7±30.7 AU) and endothelin converting enzyme (290.0±24.6 vs 169.6±19.0 AU) as well as ET-1 production (30.2±4.3 vs 24.2±2.0 pg/mL) in hCMECs. In summary, EMVs harvested from adults with PreD reduced endothelial nitric oxide synthase (eNOS) activation and NO production and increased ET-1 synthesis and release in brain endothelial cells in vitro. Increased risk and incidence of stroke associated with prediabetes may be mediated by circulating EMVs. 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.

Neonatal Hypoglycemia.

Neonatal hypoglycemia (NH) is broadly defined as a low plasma glucose concentration that elicits hypoglycemia-induced impaired brain function. To date, no universally accepted threshold (reference range) for plasma glucose levels in newborns has been published, as data consistently indicate that neurologic responses to hypoglycemia differ at various plasma glucose concentrations. Infants at risk for NH include infants of diabetic mothers, small or large for gestational age, and premature infants. Common manifestations include jitteriness, poor feeding, irritability, and encephalopathy. Neurodevelopmental morbidities associated with NH include cognitive and motor delays, cerebral palsy, vision and hearing impairment, and poor school performance. This article offers a timely discussion of the state of the science of NH and recommendations for neonatal providers focused on early identification and disease prevention.

Impaired exercise-induced increase in serum IGF-1 in humans with obesity

Changes in circulating insulin-like growth factor 1 (IGF-1) implicate regulation of skeletal muscle metabolism, including protein and glucose metabolism. Previous studies have shown that an acute bout of exercise increases serum IGF-1 concentrations in healthy, lean humans. However, exercise-induced changes in serum IGF-1 concentrations in humans with obesity remain unknown. We compared changes in plasma IGF-1 during and after an acute bout of endurance exercise between humans with and without obesity. Eight subjects with obesity (i.e., OB: BMI = 34.48 ± 2.96) and eight subjects without obesity (i.e., LN: BMI = 24.45 ± 2.43 kg/m2) exercised for 45 min in a cycle ergometer at 65% of their maximum oxygen uptake, after an overnight 10-h fast. Blood draws were taken immediately before exercise, at 15 and 30 minutes (i.e., during exercise), and at 55, 75, 95, and 115 minutes after the start of the exercise. Serum concentrations of total IGF-1 and insulin were determined using commercially available ELISA assays (Alpco 22-IGFHU-E01 and 80-INSHU-E10.1, respectively). Plasma glucose concentrations were determined using an automatic analyzer (YSI glucose analyzer). One-way repeated measures analyses of variance were carried out to detect significant changes over time within each group. Independent t tests were used to determine group differences at each time point. Alpha level was set at p ≤ 0.05 and data are reported as mean ± SD. There were no significant ( p &gt; 0.05) differences between groups for IGF-1 serum concentrations at baseline (LN = 205.61 ± 40.07 ng/mL, OB = 200.89 ± 80.40 ng/mL) nor during or after exercise. Significant increases from baseline in serum IGF-1 concentrations were detected in the LN group at 15 min (231.30 ± 50.47 ng/mL, p = 0.007) and 30 min (227.94 ± 49.02 ng/mL, p = 0.04) during exercise, followed by significant decreases from baseline at 95 min (189.99 ± 34.73 ng/mL, p = 0.052) and 115 min (196.42 ± 40.39 ng/mL, p = 0.023). No significant ( p &gt; 0.05) differences from baseline were observed in the obese group neither during nor after exercise. Higher serum insulin concentrations were observed in the OB group at baseline (LN = 5.55 ± 2.62 μIU/mL, OB = 11.07 ± 5.76 μIU/mL, p = 0.027) but significant group differences no longer existed ( p &gt; 0.05) during exercise and up to 55 min after exercise; however, insulin concentrations for the OB group were significantly greater than those measured in the LN group at 75 min ( p = 0.028), 95 min ( p = 0.008), and 115 min ( p = 0.007) after exercise. Moreover, a significant increase from baseline was measured 55 min after exercise in the lean group (8.22 ± 3.13 μIU/mL, p = 0.005), whereas no significant changes were observed in the OB groups at any time point ( p &gt; 0.05). No significant ( p &gt; 0.05) group differences were detected for plasma glucose concentrations at any time point, and despite a significant decrease from baseline observed in the LN group at 115 min after exercise (baseline = 83.32 ± 7.66 mg/dL, 115 min = 81.02 ± 7.00 mg/dL, p = 0.044). In conclusion, endurance exercise increases serum IGF-1 concentrations in humans without obesity, but this response is impaired in humans with obesity. National Institute of Health (NIH)\National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Grant/Award Number: R01DK123441. 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 intermittent hypoxia on glucose tolerance in adults with type 2 diabetes

Hypoxia stimulates glucose uptake through an insulin-independent pathway. The purpose of this single-blind randomized study was to determine the acute effect of intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and normoxic air, on glucose and insulin concentrations during an oral glucose tolerance test in adults with type 2 diabetes. It was hypothesized that intermittent hypoxia would attenuate the increase in glucose and insulin concentrations during an oral glucose tolerance test. Six adults with type 2 diabetes (5 men, age: 51±15 years, HbA1c: 7.3±1.5%) visited the laboratory on two occasions. On both visits, a 2-hour oral glucose tolerance test was performed, with venous blood samples collected 0, 30, 60, 90, and 120 min after ingestion of a high-glucose drink. Following ingestion of the drink, participants were exposed to either an intermittent hypoxia (IH) protocol, consisting of eight 4-min hypoxic cycles at a targeted arterial oxygen saturation of 80% interspersed with breathing room air to resaturation, or an intermittent normoxia (IN) protocol consisting of eight 4-min normoxic cycles interspersed with breathing room air. By design, oxygen saturation was lower during intermittent hypoxia than intermittent normoxia (81±3 vs. 97±1%, p&lt;0.01). Relative changes in plasma glucose concentrations in response to the oral glucose tolerance tests were not different between conditions (IH vs. IN: 30: 42±15 vs. 35±15; 60: 57±26 vs. 65±30; 90: 73±32 vs. 88±30; and 120: 78±26 vs. 83±29 mg/dl, interaction effect: p=0.13). Similarly, the relative changes in insulin concentrations in response to the oral glucose tolerance tests were not different between conditions (IH vs. IN: 30: 14±17 vs. 25±17; 60: 42±36 vs. 48±35; 90: 70±58 vs. 86±60; and 120: 103±72 vs. 125±94 ulU/ml, main effect for condition: p=0.12). While these preliminary results did not reach statistical significance, the observed trends for reduced glucose concentrations in combination with lower insulin concentrations during intermittent hypoxia suggest that short bouts of hypoxia improve glucose tolerance by stimulating glucose uptake independently from the action of insulin. Data from a larger sample size of adults with type 2 diabetes are needed to confirm these preliminary findings. None. 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.

Abstract 2047: Pioglitazone Improves Apolipoprotein A1-associated Proteomic Composition More Than Weight Loss In Insulin Resistance

Insulin resistance (IR) is linked to an atherogenic dyslipidemia and an increased risk of ASCVD. Apolipoprotein A1 (ApoA1)-associated lipoproteins exert varying anti-atherogenic functions and have a large diverse proteome. It is, however, unknown whether IR contributes to atherogenic perturbations in these ApoA1-associated proteins. We thus tested the hypothesis that IR is associated with an atherogenic ApoA1 proteome and that insulin-sensitizing interventions improve the proteome to a more anti-atherogenic composition. The study included 861 participants without diabetes (age 48 ± 12 years, female = 65.5 %). We measured IR directly using the steady-state plasma glucose (SSPG) concentration during the insulin suppression test, where a higher SSPG indicates greater IR. The ApoA1-associated proteome lipoproteins were measured by mass spectrometry. A subgroup of participants underwent pioglitazone treatment (PIO; n = 38) or weight loss (WL; n = 70) for 3 months. Paired t-testing was used to quantify within-subject changes in outcomes of interest pre- to post-treatment. At baseline, several components of ApoA1-associated proteome significantly correlated with SSPG concentration ( Figure ). Both PIO and WL significantly improved IR (p&lt;0.01). PIO led to significant increases in several ApoA1-associated proteins: ApoC1; ApoC2; ApoC3; ApoC4; ApoA2; ApoA4; ApoD; ApoE; ApoM; LCAT; LpPLA2; PLTP; PON1; and PON3. WL also led to significant increases in ApoA1-associated proteins: ANGT; ApoA4; ApoD; ApoM; LpPLA2; PLTP; PON1; and PON3. In conclusion, IR correlates with an atherogenic ApoA1-associated proteome. Both PIO and WL improve IR and the composition of the ApoA1-associated proteome, but PIO has a more pronounced effect on the proteome compared to WL. These findings support further exploration into the ApoA1-associated proteome for both understanding residual lipid-related ASCVD risk and targeted therapeutics for ASCVD reduction.