Lower Glucose Research Articles

Mechanisms by which sheep milk consumption ameliorates insulin resistance in high-fat diet-fed mice

Sheep milk is rich in fat, protein, vitamins and minerals and is also one of the most important sources of natural bioactives. Several biopeptides in sheep milk have been reported to possess antibacterial, antiviral and anti-inflammatory properties, and they may prevent type 2 diabetes (T2D), disease and cancer. However, the precise mechanism(s) underlying the protective role of sheep milk against T2D development remains unclear. Therefore, in the current study, we investigated the effect of sheep milk on insulin resistance and glucose intolerance in high-fat diet (HFD)-fed mice, by conducting intraperitoneal glucose tolerance tests, metabolic cage studies, genomic sequencing, polymerase chain reaction, and biochemical assays. Hyperinsulinemic–euglycemic clamp-based experiments revealed that mice consuming sheep milk exhibited lower hepatic glucose production than mice in the control group. These findings further elucidate the mechanism by which dietary supplementation with sheep milk alleviates HFD-induced systemic glucose intolerance.

Liver-derived extracellular vesicles improve whole-body glycaemic control via inter-organ communication.

Small extracellular vesicles (EVs) are signalling messengers that regulate inter-tissue communication through delivery of their molecular cargo. Here, we show that liver-derived EVs are acute regulators of whole-body glycaemic control in mice. Liver EV secretion into the circulation is increased in response to hyperglycaemia, resulting in increased glucose effectiveness and insulin secretion through direct inter-organ EV signalling to skeletal muscle and the pancreas, respectively. This acute blood glucose lowering effect occurs in healthy and obese mice with non-alcoholic fatty liver disease, despite marked remodelling of the liver-derived EV proteome in obese mice. The EV-mediated blood glucose lowering effects were recapitulated by administration of liver EVs derived from humans with or without progressive non-alcoholic fatty liver disease, suggesting broad functional conservation of liver EV signalling and potential therapeutic utility. Taken together, this work reveals a mechanism whereby liver EVs act on peripheral tissues via endocrine signalling to restore euglycaemia in the postprandial state.

Computational Design of a Truncated Javan Spitting Cobra (Naja sputatrix) Venom Cardiotoxin Analogue as a Promising Insulinotropic Agent

Treatment options for diabetes may vary widely, however, around 50% of all diabetic patients do not reach the minimum glycemic target. Therefore, drugs that are able to lower glucose levels through unconventional targets are still needed for the treatment of type 2 diabetes. This study aimed to investigate the activity of cardiotoxins from N. sputatrix towards Kv channels as potential targets for glucose level reduction. Molecular docking analysis was conducted using the ClusPro web server, and the resulting protein-ligand interactions were visualized using BioVia Discovery Studio and LigPlus v.4.5.3. The stability of the docking structures was further examined through molecular dynamics simulations. The CTX-1, CTX-3, CTX-4, CTX-5, and CTX-KJC3 sequences from N. sputatrix were aligned and modeled, focusing on the 62-81 amino acid residues. The models of CTX-3, CTX-4, and CTX-5 demonstrated interactions with the binding site of the KcsA receptor. Additionally, substituting the Val74 residue in the CTX62-81 fragment with Lys74 resulted in reduced binding energy and mitigated the cytotoxic effects of CTX, while maintaining its insulinotropic activity

A gluco-mindful approach to diabetic gastroparesis.

Diabetes gastroparesis is a common manifestation of autonomic neuropathy in persons with long-standing, uncontrolled diabetes. Most discussion about its management revolves around the mitigation of symptoms. Here, we share tips on choosing the right glucose-lowering medication, based upon predominant symptomatology of gastroparesis. We highlight about insulin preparations, and their timing of administration, can be tailored according to need. We also emphasize the need to choose oral glucose lowering drugs with care.

Association of Christian Orthodox Fasting with Sociodemographic, Anthropometric and Lifestyle Factors and Serum Biochemical Indices: A Cross-Sectional Study on Patients with Metabolic Diseases.

Christian Orthodox fasting, a type of time-restricted diet, which presents some similarities to the Mediterranean Diet, also including certain similarities with periodic vegetarianism or other time-restricted diets (e.g., intermittent diet and Ramadan fasting), may cumulatively be related to the same or even better beneficial healthy effects as these well-recognized dietary patterns. The present study aimed to explore the potential beneficial impact of Christian Orthodox fasting in patients with metabolic disorders, such as diabetes mellitus type 2, excessive obesity, hypothyroidism and osteoporosis. This was a cross-sectional study, including 135 patients with metabolic disorders (67 fasters and 68 non-fasters). The enrolled fasters had adapted Christian Orthodox fasting recommendations for at least twelve consecutive years or even from childhood. Relevant questionnaires were used to record sociodemographic, anthropometric and lifestyle data of the study population through face-to-face interviews between the enrolled individuals and qualified personnel during a non-fasting period. Christian Orthodox fasting patients showed a significantly and independently lower prevalence of overweight/obesity and abdominal obesity, which is highly associated with cardiometabolic disease risks, as well as a significantly and independently lower incidence of hypertension, including separately lower systolic and diastolic pressure, than non-fasting patients. Fasters also had a significantly and independently increased prevalence of an advanced educational level and no smoking history, as well as a lower incidence of sedentary behavior, and a trend of a correlation with reduced c-reactive protein (CRP), an indicator of inflammation, compared to non-fasters. Fasters also exhibited higher serum albumin and high-density lipoprotein (HDL) levels, as well as lower glucose levels, than non-fasters. This is one of the few cross-sectional studies demonstrating that Christian Orthodox fasting may promote metabolic health by improving several aspects of metabolic disorders, being associated with specific sociodemographic, anthropometric and lifestyle factors. Further studies conducted on larger sample sizes from different countries and different ethnicities that include Christian Orthodox fasters are recommended to evaluate the impact of long-term religious fasting effects on human health, either as a preventative factor reducing the risk of chronic diseases and especially cardiometabolic disorders or as a nutritional intervention to ameliorate symptom severity.

Absolute treatment effects of novel antidiabetic drugs on a composite renal outcome: meta-analysis of digitalized individual patient data

BackgroundAbsolute treatment benefits—expressed as numbers needed to treat—of the glucose lowering and cardiovascular drugs, glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose transporter 2 (SGLT2) inhibitors on renal outcomes remain uncertain. With the present meta-analysis of digitalized individual patient data, we aimed to display and compare numbers needed to treat of both drugs on a composite renal outcome.MethodsFrom Kaplan–Meier plots of major cardiovascular outcome trials of GLP-1 receptor agonists and SGLT2 inhibitors vs. placebo, we digitalized individual patient time-to-event information on composite renal outcomes with WebPlotDigitizer 4.2; numbers needed to treat from individual cardiovascular outcome trials were estimated using parametric Weibull regression models and compared to original data. Random-effects meta-analysis generated meta-numbers needed to treat with 95% confidence intervals (CI).ResultsTwelve cardiovascular outcome trials (three for GLP-1 receptor agonists, nine for SGLT2 inhibitors) comprising 90,865 participants were included. Eight trials were conducted in primary type 2 diabetes populations, two in a primary heart failure and two in a primary chronic kidney disease population. Mean estimated glomerular filtration rate at baseline ranged between 37.3 and 85.3 ml/min/1.73 m2. Meta-analyses estimated meta-numbers needed to treat of 85 (95% CI 60; 145) for GLP-1 receptor agonists and 104 (95% CI 81; 147) for SGLT2 inhibitors for the composite renal outcome at the overall median follow-up time of 36 months.ConclusionThe present meta-analysis of digitalized individual patient data revealed moderate and similar absolute treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors compared to placebo for a composite renal outcome.Graphical

More Similar than Different: Memory, Executive Functions, Cortical Thickness, and Glucose Metabolism in Biomarker-Positive Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are typically associated with very different clinical and neuroanatomical presentations; however, there is increasing recognition of similarities. To examine memory and executive functions, as well as cortical thickness, and glucose metabolism in AD and bvFTD signature brain regions. We compared differences in a group of biomarker-defined participants with Alzheimer's disease and a group of clinically diagnosed participants with bvFTD. These groups were also contrasted with healthy controls (HC). As expected, memory functions were generally more impaired in AD, followed by bvFTD, and both clinical groups performed more poorly than the HC group. Executive function measures were similar in AD compared to bvFTD for motor sequencing and go/no-go, but bvFTD had more difficulty with a set shifting task. Participants with AD showed thinner cortex and lower glucose metabolism in the angular gyrus compared to bvFTD. Participants with bvFTD had thinner cortex in the insula and temporal pole relative to AD and healthy controls, but otherwise the two clinical groups were similar for other frontal and temporal signature regions. Overall, the results of this study highlight more similarities than differences between AD and bvFTD in terms of cognitive functions, cortical thickness, and glucose metabolism. Further research is needed to better understand the mechanisms mediating this overlap and how these relationships evolve longitudinally.

Tandem T:Slim X2 Insulin Pump Use in Clinical Practice Among Pregnant Individuals With Type 1 Diabetes: A Retrospective Observational Cohort Study.

Insulin pump use is increasing in frequency among pregnant individuals with type 1 diabetes (T1D). Automated insulin delivery (AID) technologies have not been studied extensively in pregnancy. We present a retrospective case series of eight individuals with T1D who used the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, Inc., CA, USA) during pregnancy. Weekly continuous glucose monitor and insulin pump data were analyzed from electronic medical records and data-sharing portals. Safety, glycemic control, and pregnancy outcomes were examined with both the control IQ (CIQ) and basal IQ (BIQ) algorithms. Six CIQ and two BIQ users were studied. The mean glycated hemoglobin (A1C) during pregnancy was 6.1%, and the average time in pregnancy-recommended glycemic range (TIR; 63-140mg/dL) was 67.9%. There were no instances of diabetic ketoacidosis or severe hypoglycemia. CIQ users had a higher mean sensor glucose (127.6 mg/dL) compared to BIQ participants (118.4 mg/dL). However, the average time below range (<63 mg/dL) was 6.1% in BIQ participants compared to 1.5% in CIQ participants. CIQ participants used several strategies to achieve glycemic targets, including daytime use of sleep activity. An increased basal-to-bolus insulin ratio was negatively correlated with TIR (r=-0.415). Tandem t:slim X2 insulin pumps were safely used during pregnancy in eight individuals with T1D, with variable success in achieving recommended glycemic targets. Further research is needed to understand differences in CIQ and BIQ use in pregnancy. AID device manufacturers must additionally develop further methods to target lower glucose for pregnant users.

Effect of sodium-glucose cotransporter-2 inhibitors on continuous glucose monitoring metrics, as adjunctive to insulin in adults with type 1 diabetes mellitus: a meta-analysis of randomized controlled trials

AimsThis meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on continuous glucose monitoring metrics as adjunctive to insulin in adults with type 1 diabetes mellitus (T1D). MethodsA systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until October 25, 2023. Dual-independent study selection, data extraction and quality assessment were conducted. Results were summarized with random effects meta-analysis. ResultsEight RCTs were identified, involving a total of 2310 T1D patients. The use of SGLT2is on top of standard insulin therapy was associated with a significantly higher time in range (TIR) compared to placebo (mean difference (MD) 9.7 %; 95 % confidence interval (CI) [8.3, 1.11]; P < 0.001). The time above range was significantly lower in patients receiving SGLT2is (MD -8.71 %; 95 % CI [−11.62, −5.79]; P < 0.001), whereas no difference was observed regarding the time below range (TBR) (MD 0.34 %; 95 % CI [−0.17, 0.85]; P = 0.19). A significantly lower sensor-recorded mean daily glucose was noted in the group receiving SGLT2is (MD -16.55 mg/dL; 95 % CI [−19.82, −13.29]; P < 0.001). When considering the metrics of glucose variability, SGLT2is demonstrated a significant favorable effect on the mean amplitude of glucose excursions (MD -16.92 mg/dL; 95 % CI [−25.31, −8.13]; P < 0.001) and the mean standard deviation of weekly glucose levels (MD -7.67 mg/dL; 95 % CI [−11, −4.35]; P < 0.001). No significant effect was observed concerning the coefficient of variation (MD -1 %; 95 % CI [−2.39, 0.4]; P = 0.16). Regarding safety outcomes, SGLT2is were significantly linked to higher odds of diabetic ketoacidosis compared to insulin alone (OR 3.18; 95 % CI [1.79, 5.66]; P < 0.001), with no significant impact on severe hypoglycemia events (OR 1; 95 % CI [0.54, 1.85]; P = 0.1). ConclusionOur findings suggest that in individuals with T1D, adjunct therapy with SGLT2is provides a significant benefit in terms of TIR and reduced glucose variability, without an increase in TBR.

Gene polymorphisms of IL-17A and bacterial meningitis in Angolan children

Interleukin (IL)-17 A plays a crucial role in protecting hosts from invading bacterial pathogens. In this study, we investigated if single nucleotide polymorphisms (SNPs) in IL-17A are associated with susceptibility and outcome of bacterial meningitis (BM) in Angolan children. The study sample comprised 241 confirmed BM patients and 265 controls, which were matched for age and ethnicity. Three IL-17A SNPs – rs2275913 (−197G > A), rs8193036 (-737C > T) and rs4711998 (−877 A > G) – were determined by high-resolution melting analysis (HRMA). The frequency of variant genotype rs4711998 was significantly higher in patients with BM caused by Haemophilus influenzae (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.49–8.23; P = 0.0025) than in controls. Also, patients with BM caused by Gram-negative bacteria and who carried the variant genotype rs2275913 had a lower glucose level (P = 0.0051) in cerebrospinal fluid (CSF). Patients with BM caused by Streptococcus pneumoniae who carried the variant type rs8193036 had a reduced risk for severe neurological sequelae (OR: 0.14; 95% CI: 0.029–0.68; P = 0.0079), blindness (OR: 0.012; 95% CI: 0.012–0.87; P = 0.017) and ataxia (OR: 0.28; 95% CI: 0.091–0.83; P = 0.023). This study suggests an association of IL-17A genetic variations with susceptibility and outcome of bacterial meningitis in Angolan children.

Habitual coffee drinking and the chance of prediabetes remission: findings from a population with low coffee consumption.

We aimed to investigate the association between coffee drinking and total caffeine intakes with the chance of prediabetes (Pre-DM) regression and progression over 9-years of follow-up. This cohort study included 334 Pre-DM individuals (mean age of 49.4 ± 12.8 years and 51.5% men) who participated in the third phase of the Tehran Lipid and Glucose Study (2006-2008). A validated food frequency questionnaire at baseline assessed habitual coffee consumption. All measurements were done at baseline and all subsequent examinations with 3-year follow-up intervals. The odds ratios (OR) and 95% confidence intervals (CIs) of Pre-DM regression to normal glycemia or progression to type 2 diabetes (T2D) in coffee drinkers/non-drinkers were estimated using multinomial logistic regression analysis. During the study follow-up 39.8% of the study participants were progressed to T2D and 39.8% returned to normal glycemia. Coffee consumption nearly doubled the chance of returning to normal (OR = 2.26, 95% CI = 1.03-4.97). Total caffeine intake was not related to Pre-DM progression and regression. Compared to non-drinkers, coffee drinkers had significantly lower 2-hour serum glucose concentrations over time (152, 95% CI = 144-159 vs. 162, 95% CI = 155-169mg/dL, P = 0.05). Habitual coffee drinking may increase the chance of returning to normal glycemia in Pre-DM subjects.

Glucose uptake from the rhizosphere mediated by MdDOF3-MdHT1.2 regulates drought resistance in apple.

In plants under drought stress, sugar content in roots increases, which is important for drought resistance. However, the molecular mechanisms for controlling the sugar content in roots during response to drought remain elusive. Here, we found that the MdDOF3-MdHT1.2 module-mediated glucose influx into the root is essential for drought resistance in apple (Malus × domestica). Drought induced glucose uptake from the rhizosphere and up-regulated the transcription of hexose transporter MdHT1.2. Compared with the wild-type plants, overexpression of MdHT1.2 promoted glucose uptake from the rhizosphere, thereby facilitating sugar accumulation in root and enhancing drought resistance, whereas silenced plants showed the opposite phenotype. Furthermore, ATAC-seq, RNA-seq and biochemical analysis demonstrated that MdDOF3 directly bound to the promoter of MdHT1.2 and was strongly up-regulated under drought. Overexpression of MdDOF3 in roots improved MdHT1.2-mediated glucose transport capacity and enhanced plant resistance to drought, but MdDOF3-RNAihr apple plants showed the opposite phenotype. Moreover, overexpression of MdDOF3 in roots did not attenuate drought sensitivity in MdHT1.2-RNAi plants, which was correlated with a lower glucose uptake capacity and glucose content in root. Collectively, our findings deciphered the molecular mechanism through which glucose uptake from the rhizosphere is mediated by MdDOF3-MdHT1.2, which acts to modulate sugar content in root and promote drought resistance.

Automated Insulin Delivery for Pregnant Women With Type 1 Diabetes: Where Do We Stand?

Automated insulin delivery (AID) systems mimic an artificial pancreas via a predictive algorithm integrated with continuous glucose monitoring (CGM) and an insulin pump, thereby providing AID. Outside of pregnancy, AID has led to a paradigm shift in the management of people with type 1 diabetes (T1D), leading to improvements in glycemic control with lower risk for hypoglycemia and improved quality of life. As the use of AID in clinical practice is increasing, the number of women of reproductive age becoming pregnant while using AID is also expected to increase. The requirement for lower glucose targets than outside of pregnancy and for frequent adjustments of insulin doses during pregnancy may impact the effectiveness and safety of AID when using algorithms for non-pregnant populations with T1D. Currently, the CamAPS® FX is the only AID approved for use in pregnancy. A recent randomized controlled trial (RCT) with CamAPS® FX demonstrated a 10% increase in time in range in a pregnant population with T1D and a baseline glycated hemoglobin (HbA1c) ≥ 48 mmol/mol (6.5%). Off-label use of AID not approved for pregnancy are currently also being evaluated in ongoing RCTs. More evidence is needed on the impact of AID on maternal and neonatal outcomes. We review the current evidence on the use of AID in pregnancy and provide an overview of the completed and ongoing RCTs evaluating AID in pregnancy. In addition, we discuss the advantages and challenges of the use of current AID in pregnancy and future directions for research.

Resistant starch and type 2 diabetes mellitus: Clinical perspective.

The immediate and well-documented benefits of carbohydrate restriction include improved glycemic control in individuals with diabetes mellitus. Starch, a significant source of carbohydrates, is categorized as rapidly digestible, slowly digestible, or resistant starch (RS). RS, which is a non-viscous fermentable fiber, has shown promise in animal studies for antidiabetic effects by improving glucose metabolism. Although the exact mechanism by which RS affects glucose metabolism remains unclear, it is expected to positively impact glucose tolerance and insulin sensitivity. The fermentation of RS by colonic microbiota in the large bowel produces short-chain fatty acids, which exert multiple metabolic effects on glucose regulation and homeostasis. Moreover, RS may influence glucose metabolism via bile acid modulation, independent of its fermentation. Diets rich in RS could aid in blood glucose homeostasis. However, it is uncertain whether they can alter the metabolic pathology associated with glucose regulation. In essence, RS has the potential to lower postprandial glucose levels similarly to a low-glycemic index diet. Yet, its efficacy as a medical nutrition therapy for type 2 diabetes needs further investigation. To confirm the role of RS in glycemic control and to possibly recommend it as an additional dietary approach for people with type 2 diabetes mellitus, a well-designed, large-scale intervention is required.

The Effect of Diet Composition on the Post-operative Outcomes of Roux-en-Y Gastric Bypass in Mice.

Roux-en-Y gastric bypass (RYGB) leads to the improvement of many obesity-associated conditions. The degree to which post-operative macronutrient composition contributes to metabolic improvement after RYGB is understudied. A mouse model of RYGB was used to examine the effects of diet on the post-operative outcomes of RYGB. Obese mice underwent either Sham or RYGB surgery and were administered either chow or HFD and then monitored for an additional 8weeks. After RYGB, reductions to body weight, fat mass, and lean mass were similar regardless of diet. RYGB and HFD were independently detrimental to bone mineral density and plasma vitamin D levels. Independent of surgery, HFD accelerated hematopoietic stem and progenitor cell proliferation and differentiation and exhibited greater myeloid lineage commitment. Independent of diet, systemic iron deficiency was present after RYGB. In both Sham and RYGB groups, HFD increased energy expenditure. RYGB increased fecal energy loss, and HFD after RYGB increased fecal lipid content. RYGB lowered fasting glucose and liver glycogen levels but HFD had an opposing effect. Indices of insulin sensitivity improved independent of diet. HFD impaired improvements to dyslipidemia, NAFLD, and fibrosis. Post-operative diet plays a significant role in determining the degree to which RYGB reverses obesity-induced metabolic abnormalities such as hyperglycemia, dyslipidemia, and NAFLD. Diet composition may be targeted in order to assist in the treatment of post-RYGB bone mineral density loss and vitamin D deficiency as well as to reverse myeloid lineage commitment. HFD after RYGB continues to pose a significant multidimensional health risk.

The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator

BackgroundMetabolic effects of empagliflozin treatment include lowered glucose and insulin concentrations, elevated free fatty acids and ketone bodies and have been suggested to contribute to the cardiovascular benefits of empagliflozin treatment, possibly through an improved cardiac function. We aimed to evaluate the influence of these metabolic changes on cardiac function in patients with T2D.MethodsIn a randomized cross-over design, the SGLT2 inhibitor empagliflozin (E) was compared with insulin (I) treatment titrated to the same level of glycemic control in 17 patients with type 2 diabetes, BMI of > 28 kg/m2, C-peptide > 500 pM. Treatments lasted 5 weeks and were preceded by 3-week washouts (WO). At the end of treatments and washouts, cardiac diastolic function was determined with magnetic resonance imaging from left ventricle early peak-filling rate and left atrial passive emptying fraction (primary and key secondary endpoints); systolic function from left ventricle ejection fraction (secondary endpoint). Coupling between cardiac function and fatty acid concentrations, was studied on a separate day with a second scan after reduction of plasma fatty acids with acipimox. Data are Mean ± standard error. Between treatment difference (ΔT: E–I) and treatments effects (ΔE: E-WO or ΔI: I -WO) were evaluated using Students’ t-test or Wilcoxon signed rank test as appropriate.ResultsGlucose concentrations were similar, fatty acids, ketone bodies and lipid oxidation increased while insulin concentrations decreased on empagliflozin compared with insulin treatment. Cardiac diastolic and systolic function were unchanged by either treatment. Acipimox decreased fatty acids with 35% at all visits, and this led to reduced cardiac diastolic (ΔT: −51 ± 22 ml/s (p < 0.05); ΔE: −33 ± 26 ml/s (ns); ΔI: 37 ± 26 (ns, p < 0.05 vs ΔE)) and systolic function (ΔT: -3 ± 1% (p < 0.05); ΔE: −3 ± 1% (p < 0.05): ΔI: 1 ± 2 (ns, ns vs ΔE)) under chronotropic stress during empagliflozin compared to insulin treatment.ConclusionsDespite significant metabolic differences, cardiac function did not differ on empagliflozin compared with insulin treatment. Impaired cardiac function during acipimox treatment, could suggest greater cardiac reliance on lipid metabolism for proper function during empagliflozin treatment in patients with type 2 diabetes.Trial registration: EudraCT 2017-002101-35, August 2017.

Modulatory effects of dietary prickly pear (Opuntia ficus-indica) peel on high salinity tolerance, growth rate, immunity and antioxidant capacity of Nile tilapia (Oreochromis niloticus)

This study evaluated the effects of prickly pear (Opuntia ficus-indica) peel (PPP) on salinity tolerance, growth, feed utilization, digestive enzymes, antioxidant capacity, and immunity of Nile tilapia (Oreochromis niloticus). PPP was incorporated into four iso-nitrogenous (280 g kg−1 protein) and iso-energetic (18.62 MJ kg−1) diets at 0 (PPP0), 1 (PPP1), 2 (PPP2), and 4 (PPP4) g kg−1. Fish (9.69 ± 0.2 g) (mean ± SD) were fed the diets for 75 days. Following the feeding experiment, fish were exposed to a salinity challenge (25‰) for 24 h. Fish survival was not affected by the dietary PPP inclusion either before or after the salinity challenge. Fish fed the PPP-supplemented diets showed lower aspartate aminotransferase, alanine aminotransferase, cortisol, and glucose levels compared to PPP0, with the lowest values being observed in PPP1. Fish fed dietary PPP had higher growth rates and feed utilization than PPP0. Quadratic regression analysis revealed that the best weight gain was obtained at 2.13 g PPP kg−1 diet. The highest activities of protease and lipase enzymes were recorded in PPP1, while the best value of amylase was recorded in PPP2, and all PPP values were higher than PPP0. Similarly, PPP1 showed higher activities of lysozyme, alternative complement, phagocytic cells, respiratory burst, superoxide dismutase, glutathione peroxidase and catalase, and lower activity of malondialdehyde than in PPP0. Further increases in PPP levels above 2 g kg−1 diet led to significant retardation in the immune and antioxidant parameters. Thus, the inclusion of PPP at about 1 to or 2 g kg−1 diet can improve stress tolerance, immunity, and antioxidant capacity in Nile tilapia.

Effects of Acacia mearnsii tannins on growth performance, footpad dermatitis, nutrient digestibility, intestinal permeability, and meat quality of broiler chickens

An experiment was conducted to evaluate the effects of increasing dietary supplementation of tannins from Acacia mearnsii on broiler growth performance, footpad dermatitis, litter moisture, and ileal digestibility as well as on intestinal permeability, jejunal morphometric, and lipid oxidation measurements. A total of 1620 Cobb 500 one-day-old male chicks were fed 6 experimental diets with 10 replicate pens of 27 birds each in a 4-phase feeding program. Dietary treatments were as follow: non-challenged control, challenged control, and challenged supplemented with 300, 500, 700, or 900 mg/kg tannin from Acacia mearnsii. All birds on challenged groups were challenged with Eimeria spp. on day 1 and Clostridium perfringens on days 11, 12, and 13. Performance was evaluated weekly until day 43. On day 21, blood samples were collected for biochemistry analyses and the intestinal permeability was evaluated using FITC-d as marker. Ileal digestibility and jejunal morphometric were also determined on day 21. Footpad dermatitis, litter moisture, and litter pH were evaluated on days 28, 35, and 43. On day 44, carcass and commercial cuts weights were evaluated and thigh samples were collected for lipid oxidation (TBARS) through a 6 months storage period. Broilers under intestinal challenge had lower growth performance, higher intestinal permeability, and lower serum albumin, cholesterol, glucose, and triglycerides compared to non-challenged birds (P < 0.05). From day 1 to 43, increasing tannin supplementation for broilers under intestinal challenge led to quadratic increases (P < 0.05) in body weight gain, with optimal supplementation at 310 mg/kg as well as optimized estimations for feed conversion ratio at 444 mg/kg tannin. Dietary tannin supplementation that reduced intestinal permeability at 21 days was 466 mg/kg (P < 0.05). Tannin supplementation that improved protein and energy digestibility were at 374 and 294 mg/kg, respectively (P < 0.05). No effects of tannin were observed on blood biochemistry, crypt depth, litter pH, carcass measurements, and lipid oxidation until the storage day 60. However, increasing levels of tannin supplementation led to a linear (P < 0.05) decrease on lipid oxidation of broiler meat after 90 days of storage. In conclusion, low levels of supplemental tannins from Acacia mearnsii improved growth performance, nutrient digestibility, and intestinal permeability in broilers under an intestinal challenge.

Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model

Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponectin is reported to be anxiolytic. Here we test the hypothesis that elevated adiponectin levels protect against the development of androgen-induced anxiety-like behavior. Pregnant mice overexpressing adiponectin (APNtg) and wildtypes were injected with vehicle or dihydrotestosterone to induce prenatal androgenization (PNA) in the offspring. Metabolic profiling and behavioral tests were performed in 4-month-old female offspring. PNA offspring spent more time in the closed arms of the elevated plus maze, indicating anxiety-like behavior. Intriguingly, neither maternal nor offspring adiponectin overexpression prevented an anxiety-like behavior in PNA-exposed offspring. However, adiponectin overexpression in dams had metabolic imprinting effects, shown as lower fat mass and glucose levels in their offspring. While serum adiponectin levels were elevated in APNtg mice, cerebrospinal fluid levels were similar between genotypes. Adiponectin overexpression improved metabolic functions but did not elicit anxiolytic effects in PNA-exposed offspring. These observations might be attributed to increased circulating but unchanged cerebrospinal fluid adiponectin levels in APNtg mice. Thus, increased adiponectin levels in the brain are likely needed to stimulate anxiolytic effects.

Perceived stress and progression of cardiometabolic risk factors among South Asians with prediabetes in a lifestyle intervention trial

AimsTo examine associations between perceived stress and cardiometabolic risk factors in South Asians with prediabetes and assess whether a diabetes prevention program mitigates the impact of stress on cardiometabolic health. MethodsWe conducted a secondary analysis of the Diabetes Community Lifestyle Improvement Program, a lifestyle modification trial for diabetes prevention in India (n = 564). Indicators for cardiometabolic health (weight, waist circumference, blood pressure, glucose, HbA1c, and lipids) were measured at each visit while perceived stress was assessed via questionnaire at baseline. Multivariable linear regression assessed associations between stress and cardiometabolic parameters at baseline and 3-year follow up. ResultsAt baseline, perceived stress was associated with higher weight (b=0.16; 95% CI: 0.04, 0.29) and waist circumference (b=0.11; 95% CI: 0.01, 0.21) but lower 30-minute postload glucose (b=−0.44; 95% CI: −0.76, −0.14) and LDL cholesterol (b=−0.40; 95% CI: −0.76, −0.03). Over the study period, perceived stress was associated with weight gain (b=0.20; 95% CI: 0.07, 0.33) and increased waist circumference (b=0.14; 95% CI: 0.04, 0.24). Additionally, higher perceived stress was associated with lower HDL cholesterol among the control arm (pinteraction = 0.02). ConclusionsBaseline stress was associated with negative cardiometabolic risk factor outcomes over time in those with prediabetes.