Plasma Glucose Concentrations Research Articles

The glucagon-receptor antagonist MK-3577 reduces glucagon-stimulated plasma glucose and insulin concentrations in metabolically healthy overweight cats

The role of glucagon disturbances in diabetes mellitus is increasingly recognized and, hence, glucagon antagonism might aid in treatment of hyperglycemia and other metabolic disturbances. The aim of this study was to assess the pharmacokinetics of the glucagon receptor antagonist MK-3577 and its effect on plasma glucose, insulin, and glucagon concentrations in healthy cats. In a cross-over placebo-controlled study, 5 purpose-bred cats were treated with either Placebo, MK-3577 (1 mg/kg), or MK-3577 (3 mg/kg). Glucose, insulin and glucagon concentrations were measured at 0, 15, 225, 240 min post-treatment administration. Glucagon (20 mcg/kg, IM) was administered at 240 min and glucose and insulin were measured at 255, 265, 275, 285 and 300 min. Plasma MK-3577 concentrations peaked at 4.2 and 3.2 hours after 1 and 3 mg/kg dosing with a half-life of 14.8h and 15.5h respectively. Baseline glucose, insulin and glucagon concentrations did not differ significantly between treatment groups. At a dose of 3 mg/kg, MK-3577 blunted the glucagon-stimulated rise of glucose (p=0.0089) and insulin (p=0.02). Similar trends were observed with MK-3577 at the 1 mg/kg dose but the effect was smaller, and not significant. In conclusion, the GRA MK-3577 has a pharmacokinetic profile suitable for diminishing the glucagon-induced rise of glucose and insulin in healthy cats.

A New Alternative Nutritional Source Hawthorn Vinegar: How It Interacts with Protein, Glucose and GLP-1.

(1) Background: There is a balance between nutrition, glycemic control, and immune response. Their roles in physiological mechanisms are essential for maintaining life quality. This study aimed to evaluate hawthorn vinegar's metabolic effects, and describe its possible mechanism. We also pointed out several vinegar production methods to clarify the antioxidant features. (2) Methods: In the study, three vinegar techniques were applied to vinegar: traditional production of hawthorn vinegar (N), thermal pasteurization (P), and ultrasound method (U). Thirty-two female adult Wistar albino rats were randomly separated into four groups: Control, N1 (regular vinegar; 1 mL/kg bw), P1 (pasteurized vinegar; 1 mL/kg bw), and U1(ultrasound treated vinegar; 1 mL/kg bw). Vinegar was administered by oral gavage daily for 45 days. Initial and final weights, the percentage changes of body weight gains, and Gamma-Glutamyl Transferase (GGT) values of plasma and liver were measured. The total protein, globulin, and albumin values of plasma, liver, and intestinal tissue were determined. In addition, plasma glucagon-like peptide-1 (GLP-1) and glucose concentrations were evaluated. (3) Results: There was a statistical increase in total intestinal protein value and an increasing tendency in total protein in plasma and liver in group U1 compared to group Control. However, the GGT concentrations in plasma and liver were slightly lower in group U1 than in group Control. In addition, there were significant increases in plasma GLP-1 values in all experimental groups compared to the Control group (p: 0.015; 576.80 ± 56.06, 773.10 ± 28.92, 700.70 ± 17.05 and 735.00 ± 40.70; respectively groups control, N1, P1, and U1). Also, liver GLP-1 concentrations in groups P1 and U1 were higher than in group Control (p: 0.005; 968.00 ± 25.54, 1176 ± 17.54 and 1174.00 ± 44.06, respectively groups control, P1 and U1). On the other hand, significant decreases were found in plasma glucose concentrations in groups N1 and U1 as to the Control group (p: 0.02; Control: 189.90 ± 15.22, N1: 133.10 ± 7.32 and U1: 142.30 ± 4.14). Besides, liver glucose levels were lower in all experimental groups than in group Control statistically (p: 0.010; 53.47 ± 0.97, 37.99 ± 1.46, 44.52 ± 4.05 and 44.57 ± 2.39, respectively groups control, N1, P1, and U1). (4) Conclusions: The findings suggest that hawthorn vinegar can balance normal physiological conditions via intestinal health, protein profiles, and glycemic control. Additionally, ultrasound application of vinegar may improve the ability of hawthorn vinegar, and have positive effects on general health.

Triglyceride glucose index as a predictor for non-alcoholic fatty liver disease: insights from a longitudinal analysis in non-obese individuals.

A substantial portion of non-obese population is afflicted with Non-alcoholic Fatty Liver Disease (NAFLD). The Triglyceride Glucose (TyG) index, a quantifier of insulin resistance magnitude, is determined by the product of fasting plasma glucose and triglyceride concentrations. The relationship between the TyG index and NAFLD within this cohort remains ambiguous. We conducted a retrospective analysis utilizing datasets acquired from the Dryad digital repository. Non-obese participants (BMI < 25 kg/m2) were enrolled at the Wenzhou Medical Center of Wenzhou People's Hospital between January 2010 and December 2014. Demographic information and biochemical parameters were systematically compiled, and the diagnosis of NAFLD was established through ultrasonographic evidence. This study cohort included 16,172 non-obese participants with a 5-year follow-up, among whom 2,322 (14.36%) developed NAFLD. The disparity between TyG index quartiles in the accumulative incidence of new-onset NAFLD was distinct, with an increasing risk of new-onset NAFLD as the TyG index increased. Participants in highest quartile exhibited the maximum risk of NAFLD. In the fully adjusted model 3, the hazard ratios for NAFLD in Q2, Q3, and Q4 were 2.15 (1.62, 2.87), 2.89 (2.20, 3.80) and 4.58 (3.48, 6.02), respectively. Meanwhile, the TyG index and NAFLD risk showed a highly significant overall correlation (p < 0.0001) and nonlinearity (p < 0.0001) according to the limited cubic splines. In subgroup analysis, a significant interaction was noted between new-onset NAFLD and SBP (<140 mmHg vs. ≥140 mmHg; P for interaction = 0.0114). The SBP < 140 mmHg subgroup demonstrated an enhanced TyG index influence on NAFLD risk (HR = 2.83, 95% CI: 2.48-3.23, p < 0.0001). The TyG index serves as a straightforward instrument for assessing NAFLD risk in non-obese individuals, enabling prompt identification and management in this population segment.

Impairments of insulin and glucagon sensitivity in Chinese women with gestational diabetes mellitus.

To evaluate insulin and glucagon sensitivity in Han Chinese women with and without gestational diabetes mellitus (GDM). In total, 81 women with GDM and 81 age-matched healthy controls were evaluated with a 75 g oral glucose tolerance test (OGTT) at gestational weeks 24-28. Plasma glucose concentrations were measured at fasting and 1 h and 2 h post-OGTT. Fasting plasma insulin, glucagon and amino acids were also measured. Insulin and glucagon sensitivity were assessed by the homeostatic model assessment of insulin resistance (HOMA-IR) and glucagon-alanine index, respectively. As expected, plasma glucose concentrations were higher at fasting and 1 h and 2 h post-OGTT in GDM participants (p < .001 each). Both the HOMA-IR and the glucagon-alanine index were higher in GDM participants. There was a weak positive correlation between HOMA-IR and glucagon-alanine index (r = 0.24, p = .0024). Combining the HOMA-IR and the glucagon-alanine index yielded better capacity (area under the curve = 0.878) than either alone (area under the curve = 0.828 for HOMA-IR and 0.751 for glucagon-alanine index, respectively) in differentiating GDM from healthy participants. While the majority of GDM participants (64%) exhibited both reduced insulin and glucagon sensitivity, a third of them presented either reduced insulin (20%) or glucagon (14%) sensitivity alone. HOMA-IR and glucagon-alanine index correlated differentially with fasting glucose, triglycerides, low-density lipoprotein cholesterol, sum of amino acids and hepatic steatosis index. Impairments of both insulin and glucagon sensitivity occur frequently in Chinese women with GDM, which may, individually or together, drive metabolic derangements in GDM. These observations provide new insights into the pathophysiology of GDM and support the need to target insulin or glucagon resistance, or both, in the management of GDM.

P-633 Impact of insulin resistance on reproductive medicine outcomes

Abstract Study question Does Homeostasis Model Assessment for insulin resistance (HOMA-IR) have an influence in reproductive medicine outcomes? Summary answer HOMA-IR is associated with fertility treatment parameters and has a significant influence on reproductive medicine outcomes. What is known already The HOMA model is used to yield an estimate of insulin sensitivity from basal (fasting) plasma insulin and glucose concentrations. Currently, the model has become a widely used clinical tool to evaluate glucose metabolism. Regarding fertility, the relation between polycystic ovary syndrome (PCOS) and insulin resistance (IR) has been studied. Insulin resistance may be potential contributor to impaired treatment outcomes in artificial reproductive technology (ART). Although a few studies have recently been published on the topic the association of HOMA-IR with fertility treatment parameters remains a black box in reproductive medicine research. Study design, size, duration The observational study was designed and conducted at the Kinderwunsch Institut Schenk GmbH (Dobl, Austria). The study included 175 patients (25 men and 150 women), aged 18-45. HOMA-IR was determined for each patient and then correlated with patient’s medical history, fertility treatment parameters and outcomes. Participants/materials, setting, methods HOMA-IR was determined by taking a blood sample during fasting state and measuring plasma values of glucose (mg/dl) and insulin (mU/ml). A HOMA-IR of ≥ 2 was considered as insulin resistance. HOMA-IR was correlated with medical history (polycystic ovarian syndrome (PCOS), endometriosis, Body-Mass-Index (BMI), nicotine abuse) and fertility treatment parameters (sperm quality, number of retrieved oocytes after controlled ovarian stimulation, number of mature and fertilized oocytes, embryo quality and pregnancy rate). Main results and the role of chance An increased HOMA-IR (³2) was observed in 90 patients (51.4%). They suffered from obesity (n = 36; 80%), PCOS (n = 22; 70.97%), ovarian hyperstimulation syndrome (n = 17; 77.27%) and experienced poor embryo quality (n = 249; 91.54%). A significant positive correlation was found between HOMA-IR and PCOS (p &amp;lt; 0.001), obesity (p &amp;lt; 0.001) and number of retrieved oocytes (p &amp;lt; 0.05). The pregnancy rate correlated negatively with the HOMA-IR (p &amp;lt; 0.001). Furthermore, trends of positive correlations of high HOMA-IR in endometriosis, BMI, pathological spermiogram, nicotine abuse and increased number of mature oocytes were determined. The relation between HOMA-IR and the number of retrieved and mature oocytes is consistent with its relation to PCOS. The data show that HOMA-IR is associated with fertility treatment parameters and has a significant influence on ART outcome. Limitations, reasons for caution The number of patients may be seen as a study limitation. Results should be confirmed with a bigger sample size. An interventional study should confirm the role of HOMA-IR in IVF outcomes. Wider implications of the findings These findings may help to better understand the importance of glucose and insulin metabolism in reproduction and suggest that evaluation of HOMA-IR may be a valuable parameter to be considered when collecting patients’ anamnesis prior to starting ART treatment. Trial registration number not applicable

Insulinoma presenting with anti-insulin antibodies.

An 89-year-old woman presented with a 6-year history of occasional episodes of impaired consciousness that were relieved by ingestion of a snack. Three months before presenting to our hospital, she had been hospitalized in a local hospital with subdural hematoma caused by a head contusion, where previously unrecognized hypoglycemia was discovered. Fasting plasma glucose concentration was 37 mg/dL, with a relatively high serum level of insulin (34.9 µU/mL). Computed tomography showed a 14 mm hyperenhancing tumor in the tail of the pancreas and she was referred to our hospital for further investigation. A prolonged fasting test revealed the plasma glucose concentration reduced to 43 mg/dL (2.4 mmol/L) at 8 h after the last meal. Serum insulin, proinsulin, and C-peptide concentrations were 21.1 µU/mL, 16.9 pmol/L, and 2.72 ng/mL, respectively. Subsequent intravenous administration of 1 mg of glucagon increased the plasma glucose concentration to 76 mg/dL (4.2 mmol/L). Moreover, the insulin-to-C-peptide molar ratio was 0.14. These data indicated the presence of insulinoma. Interestingly, serum anti-insulin antibodies were elevated (21.1 U/mL), although she had no history of taking exogenous insulin injection, alpha lipoic acid, or sulfhydryl group-containing agents. Human leukocyte antigen (HLA) typing revealed HLA-DRB1*0407 and HLA-DRB1*1405 alleles. Treatment with diazoxide prevented hypoglycemia, but was discontinued due to weight gain and leg edema. Elevated serum anti-insulin antibodies persisted almost 1 year after the diagnosis of insulinoma. We present a rare case of insulinoma concomitant with serum anti-insulin antibodies. Insulinoma presenting with concomitant anti-insulin antibodies appears rare. Insulin/C-peptide molar ratio and serum insulin concentration are useful for differentiating insulinoma and autoimmune syndrome. Flash glucose monitoring systems appear suitable for evaluating treatment outcomes.

Acute Consumption of Cooked Green Banana Pulp Beverage (Musa cavendishii) Decreases Plasma Glucose in Healthy Women: A Cross-Sectional Controlled Study.

This study aimed at comparing the carbohydrate composition of three banana varieties (cv. Nanica, Nanicão, and Prata) and investigating the effect of a single dose of cooked green banana pulp beverage (GBPd) on plasma glycemic homeostasis indexes (glucose, PYY, GIP, insulin) and hunger and satiety sensation (visual analog scale-VAS). The bananas were classified according to the color scale. The fiber, total carbohydrate, and resistant starch (RS) were determined using validated methods. Glucose homeostasis indexes and hunger/satiety sensation were determined in ten healthy women in two stages before and after intake: (1) glucose solution (250g/L); (2) one week later, consumption of the glucose solution plus 75g/L of GBPd. Blood samples were collected twice in stage-1 and every 15min for 2h in stage-2. Cv. Nanicão was selected, because it presented a higher content in RS and dietary fiber on dry base than the other cultivars. Thus, it was used to test glycemic response. After 2h of GBPd intake, no difference was observed in hunger/satiety sensation and plasma glycemic homeostasis indexes, except for a decrease in plasma glucose concentration (-15%, p = 0.0232) compared to stage-1. These results suggest that cv. Nanicão has a higher potential as a functional ingredient and can influence the reduction in the glycemic index of a meal compared to other cultivars. However, it had not a short-term effect on hormones GIP and PYY in healthy women. Further research is needed to understand the long-term effects and mechanisms of green banana on glycemic control and satiety.

Effects of postbiotic products from Saccharomyces cerevisiae fermentation on lactation performance, antioxidant capacities, and blood immunity in transition dairy cows

This study aimed to evaluate the effects of dietary supplementation with different types of Saccharomyces cerevisiae fermentation products (SCFP) on lactational performance, metabolism, acute phase protein response, and antioxidant capacities in dairy cows from -21 to 56 d in milk (DIM). One hundred and 80 multiparous Holstein dairy cows were blocked by parity, expected calving date, pre-trial body condition score, and previous 305-d ME yield, and then randomly assigned to 1 of 3 dietary treatments: basal diet (CON; n = 60), basal diet supplemented with 40 g/d of SCFP1 (XPC; n = 60; XPC, Diamond V, Cedar Rapids, IA), and basal diet supplemented with 19 g/d of SCFP2 (NTK; n = 60, NutriTek®, Diamond V, Cedar Rapids, IA). Blood (n = 15, 13 and 12 in the CON, XPC and NTK groups, respectively) was sampled at -7 ± 3, + 3, + 7, + 21, and + 28 d, and milk samples (n = 19, 18 and 15 in the CON, XPC and NTK groups, respectively) was sampled during 1-8 wk from a subset of cows from -21 to 56 d relative to calving. Data were analyzed using the MIXED procedure in SAS (SAS Institute Inc.). All data were subjected to repeated measures ANOVA. Dietary treatment (TRT), time, and their interaction (TRT × time) were considered as fixed effects and cow as the random effect. Cows fed XPC and NTK had greater energy-corrected milk (ECM). Supplementing NTK increased milk fat content and yield, and 3.5% fat-corrected milk (FCM) yield compared with CON. Milk urea nitrogen (MUN) was lower in XPC cows than CON. SCFP supplementation decreased plasma β-hydroxybutyrate (BHB), ceruloplasmin (CER), haptoglobin (HPT), and interleukin-1β (IL-1β) concentrations, whereas increased plasma phosphorus (P) concentrations. In addition, cows fed NTK showed lower creatinine (CR) and cortisol (COR) concentrations but increased plasma calcium (Ca) and myeloperoxidase (MPO) concentrations than those in the CON cows. In addition, cows fed NTK and XPC both had reduced plasma concentrations of serum amyloid-A (SAA) at 3 DIM of lactation compared with CON fed cows. Furthermore, SCFP cows had greater concentrations of plasma glucose (GLU) and calcium (Ca) than CON cows at 7 DIM, and greater concentrations of plasma phosphorus (P) at 21 DIM. Between different SCFP type fed groups, plasma concentrations of nonesterified fatty acids (NEFA), MDA, creatinine (CR), SAA, and HPT were lower in cows fed NTK compared with cows fed XPC at 7 DIM. Overall, our results indicate the potential benefits of supplementing SCFP in transition dairy cows by modulating immunity, liver metabolic function and supporting ECM yield. The results also suggest that NutriTek at 19 g/d appears to support the performance and health of dairy cows better compared with XPC at 40 g/d, based on improved metabolic and inflammatory status during the transition period.

The Role of Piromelatine on Peripheral and Hippocampal Insulin Resistance in Rat Offspring Exposed to Chronic Maternal Stress.

Prenatal stress (PNS), which alters the hypothalamic-pituitary-adrenal axis function in the offspring, predisposes to insulin resistance (IR) in later life and is associated with numerous disorders, including cognitive and memory impairments. At present, our main goal is to assess the effects of chronic piromelatine (Pir) administration, a melatonin analogue, on PNS-provoked IR in the periphery and the hippocampus in male and female offspring. Pregnant Sprague-Dawley rats were exposed to chronic stress (one short-term stressor on a daily basis and one long-term stressor on a nightly basis) from the first gestation week until birth. Vehicle or Pir 20 mg/kg were administered intraperitoneally for 21 days. Plasma glucose, serum insulin levels, and the homeostasis model assessment of insulin resistance (HOMA-IR) were determined as markers of peripheral IR. For the hippocampal IR assessment, insulin receptors (IRs) and glucose transporter 4 (GLUT4) were examined. Prenatally stressed offspring of both sexes indicated enhanced plasma glucose and serum insulin concentrations, increased HOMA-IR, and decreased hippocampal GLUT4 only in male rats. The PNS-induced changes were corrected by chronic treatment with Pir. The present results suggest that the melatoninergic compound Pir exerts beneficial effects on altered glucose/insulin homeostasis in PNS-exposed offspring.

The substitute ENSO 16 has low impact on glucose metabolism in healthy humans: a randomized, double-blind, active-controlled, cross-over trial

High sugar consumption is associated with cardiovascular diseases and diabetes. Current sugar substitutes may cause taste sensations and gastrointestinal symptoms. ENSO 16 is a combination of 16 different sugar substitutes and plant fibers and has been designed as a sugar alternative. The impact on plasma glucose metabolism as well as on gastrointestinal tolerance has not been investigated yet. 17 healthy participants were enrolled in this randomized, double-blind trial. Participants received a single oral dose of 30 g glucose or 30 g ENSO 16 and crossed over to the alternate treatment after a 7 day wash out period. The study endpoint was the effect on plasma glucose, insulin, C-peptide concentrations and gastrointestinal disorders. A questionnaire regarding gastrointestinal symptoms was used for individual subjective scoring. The mean baseline adjusted plasma glucose AUC0–180 min was significantly greater after glucose administration compared to ENSO 16 (n = 15, p = 0.0128, paired t-test). Maximum plasma glucose elevation over baseline was 117 mg*dl−1 and 20 mg*dl−1 after oral glucose or ENSO 16, respectively. Insulin and C-peptide AUC0−180 min were significantly greater after glucose compared to ENSO 16 intake (p < 0.01, Wilcoxon rank sum test). The mean maximal concentrations of plasma glucose, insulin and C-peptide after glucose intake were 1.5, 4.6 and 2.7-fold greater after glucose intake compared to ENSO 16 intake, respectively. Adverse reactions were mostly mild and not different between treatments. Conclusion. ENSO 16 has only a small impact on plasma glucose metabolism. This may be of interest in a dietary context and may help to reduce calory intake.Trail registration NCT05457400. First registration: 14/07/2022. https://clinicaltrials.gov/study/NCT05457400.

Relative merits of offering a milk replacer, glucose-electrolyte or whey-based diet on the blood composition and health of unweaned calves after transport

The objective of this randomized controlled trial was to assess the relative merits of offering unweaned calves 3 different types of diets to meet energy and water deficits that can occur during journeys. Six young unweaned male Holstein calves were randomly selected from within 2 body weight ranges (median 48 and 42 kg) from each of 29 loads (total n = 174 calves) transported from an auction market or a collection center to a calf sorting center before transport to a veal unit. The calves were then randomly allocated to one of 3 dietary treatments (n = 58 calves/dietary treatment). They were offered either a milk replacer diet (M), a glucose-electrolyte diet (G) or a whey-based diet with added electrolytes (W). The ability of these diets to provide sufficient nutrient energy to restore vigor, avoid hypoglycaemia and clinical signs of dehydration without increasing the risk of diarrhea was assessed. A clinical assessment of dehydration, health and vigor was made, and the calves were blood sampled before feeding, then 2 h and 4 h after feeding. The plasma glucose concentration was increased 2 h and 4 h after feeding the M and W diets. The increases in plasma glucose concentration were greater 2 and 4 h after (a) feeding the M than after the W diet and (b) feeding the M and W diets than after the G diet. Back-transformed means and 95% Confidence Intervals (CI) for the ratio of the plasma glucose concentration at 4 h compared with 0 h for the milk replacer, glucose-electrolytes and whey-based diets were 1.2 mM CI 1.21, 1.35; 0.95 mM CI 0.92, 0.97; and 1.09 mM CI 1.06, 1.14, respectively. There was no effect of diet on the change in serum total protein concentration between before feeding and 2 and 4 h after feeding. The serum osmolality was lower 2 h after feeding the G diet. The fall in serum osmolality was greater 2 h after feeding the G diet than after feeding the M and W diets. The changes in the serum osmolality between before feeding and 2 h after feeding for the milk replacer, glucose-electrolytes and whey-based diets were -0.68 mosmol CI -3.27, 1.91; -5.23 mosmol CI -7.82, and -2.64; -0.13 mosmol CI -2.77, 2.51, respectively. The diet offered at the sorting center had no effect on subsequent growth on the veal rearing farm between arrival and slaughter (milk replacer 1.22 kg/d, CI 1.17, 1.28; glucose-electrolyte diet 1.23 kg/d. CI 1.18, 1.28; whey-based diet 1.28 kg/d CI 1.23, 1.33). The M diet provided the calves with nutrients and water to replace energy and water deficits that had accumulated before arrival at the sorting center, and these dietary benefits were still apparent 4 h after feeding. The benefits of the W diet were similar to those of the M diet, but the M diet was better able to assist the calves in maintaining their plasma glucose concentration 4 h after feeding than the W diet. The G diet had some short-term benefits in providing energy and assistance to the calves to recover from dehydration, as indicated by a decrease in serum osmolality. However, the G diet was clearly inferior to the M and W diets in providing sufficient energy to assist the calves in recovering from the effects of transport and fasting. During the 4-h after feeding, no adverse effects of offering the calves the M or W diets were observed. The benefits of the W diet in replacing energy and water deficits were similar to those of the M diet, but the M diet was better able to assist the calves in maintaining their blood glucose concentration 4 h after feeding than the W diet.

Altered bile acid and correlations with gut microbiome in transition dairy cows with different glucose and lipid metabolism status

The transition from pregnancy to lactation is critical in dairy cows. Among others, dairy cows experience a metabolic stress due to a large change in glucose and lipid metabolism. Recent studies revealed that bile acids (BA), besides being involved in both the emulsification and solubilization of fats during intestinal absorption, can also affect the metabolism of glucose and lipids, both directly or indirectly by affecting the gut microbiota. Thus, we used untargeted and targeted metabolomics and 16S rRNA sequencing approaches to investigate the concentration of plasma metabolites and BA, the composition of the rectum microbial community, and assess their interaction in transition dairy cows. In Experiment 1, we investigated BA and other blood parameters and gut microbiota in dairy cows without clinical diseases during the transition period, which can be seen as well adapted to the challenge of changed glucose and lipid metabolism. As expected, we detected an increased plasma concentration of β-hydroxybutyrate (BHBA) and nonesterified fatty acids (NEFA) but decreased concentration of glucose, cholesterol, and triglycerides (TG). Untargeted metabolomic analysis of the plasma revealed primary BA biosynthesis was one of the affected pathways, and was consistent with the increased concentration of BA in the plasma. A correlation approach revealed a complex association between BA and microbiota with the host plasma concentration of glucose and lipid metabolites. Among BA, chenodeoxycholic acid derivates such as glycolithocholic acid, taurolithocholic acid, lithocholic acid, taurochenodeoxycholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites (such as glucose, TG, and NEFA). In Experiment 2, we investigated early postpartum dairy cows with or without hyperketonemia (HPK). As expected, HPK cows had increased concentration of NEFA and decreased concentrations of glucose and triglycerides. The untargeted metabolomic analysis of the plasma revealed that primary BA biosynthesis was also one of the affected pathways. Even though the BA concentration was similar among the 2 groups, the profiles of taurine conjugated BA changed significantly. A correlation analysis also revealed an association between BA and microbiota with the concentration in plasma of glucose and lipid metabolites (such as BHBA). Among BA, cholic acid and its derivates such as taurocholic acid, tauro α-muricholic acid, and taurodeoxycholic acid were the main hub nodes connecting microbe and blood metabolites. Our results indicated an association between BA, intestinal microbe, and glucose and lipid metabolism in transition dairy cows. These findings provide new insight into the adaptation mechanisms of dairy cows during the transition period.

Effects of rumen-protected niacin on inflammatory response to repeated intramammary lipopolysaccharide challenges

Nutritional strategies that improve an animal's resilience to various challenges may improve animal health and welfare. One such nutrient is niacin which has reduced inflammation in mice, humans, and swine; however, niacin's anti-inflammatory effects have not been investigated in cattle. Our objective was to determine whether rumen-protected niacin (RPN) alters lactating dairy cows' inflammatory response to intramammary lipopolysaccharide (LPS) challenges, whether RPN resulted in any carry-over effects, and whether repeated LPS challenges result in signs of immune tolerance or innate immune training. Twenty healthy, late-lactation Holstein cows (232 ± 65 d in milk; 39 ± 5.8 kg/d of milk) were enrolled in a randomized complete block experiment which lasted 70 d. Cows received 26 g/d of RPN or no top-dress (CON) for the first 42 d of the experiment. During the final milking of d 27 and 55, cows were challenged in their rear-right mammary gland (RR) with 100 µg of LPS suspended in 5 mL of phosphate buffered saline. Milk yield, milk conductivity, and feed intake were measured daily. Milk composition was measured on d 14, 23, 24, 30, 37, 45, and 52. Blood samples were collected at 0, 8, 12, 24, 48, 72, 96, and 120 h after each LPS challenge, whereas RR quarter milk samples were collected at 0, 8, 16, 24, 48, 72, 96, 120, 144, and 168 h after each LPS challenge. Body temperature was measured continuously during each challenge with an intravaginal thermometer. Linear mixed models with repeated measures were used to analyze the results. Before LPS challenge, RPN did not affect feed intake or milk production, but it reduced SCS (1.24 ± 0.41 vs. 0.05 ± 0.45). After challenge, RPN did not affect feed intake, milk production, milk composition, SCS, body temperature, plasma glucose, or plasma insulin concentrations. Our results suggest RPN reduced peak plasma haptoglobin and lipopolysaccharide binding protein (LBP) during the 1st LPS challenge. Plasma haptoglobin tended to be less after the 2nd challenge for cows previously supplemented RPN while LBP was similar for each treatment group after the 2nd challenge. The 2nd LPS challenge resulted in decreased plasma haptoglobin compared with the 1st LPS challenge, suggestive of tolerance but it also induced a greater peak SCS than the 1st LPS challenge. Our results suggest that repeated LPS challenges promote a systemic tolerance but heightened local response to LPS-induced mastitis. Feeding RPN reduced SCS before challenge and reduced plasma acute phase proteins after challenge suggesting that RPN may reduce systemic inflammation without altering the local inflammatory responses.

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.