Lower Glucose Research Articles

Lifestyle and mood correlates of cardiometabolic risk in people with serious mental illness on second-generation antipsychotic medications.

Cardiovascular morbidity and mortality are high in people with serious mental illness (SMI). This problem is mediated, at least in part, by metabolic side effects of second-generation antipsychotics (SGAs) and by unhealthy lifestyle behaviors. We asked whether oral glucose tolerance testing (oGTT) or hemoglobin A1c (HbA1c) is superior in identifying people with SMI at high cardiometabolic risk and whether this risk is shaped by mood, cognition, or lifestyle habits. We evaluated 40 patients with schizophrenia, schizoaffective, or bipolar disorder receiving SGAs by oGTT, HbA1c, comprehensive metabolic and lipid panels, and CRP. Mood was assessed using the Patient Health Questionnaire (PHQ-9), and cognition was assessed using the Saint Louis University Mental Status examination. Diet was assessed using the UK Diabetes and Diet Questionnaire (UKDDQ), and physical activity was assessed using daily step counts. Most patients had prediabetes (preDM) or diabetes mellitus (DM), 72.5% by oGTT, and 52.5% by HbA1c criteria. Pulse rates and insulin resistance indices (Homeostatic Model Assessment of Insulin Resistance, HOMA IR; Matsuda) were significantly different between patients classified as normal or with preDM/DM, using either oGTT or HbA1c criteria. Patients with preDM/DM by HbA1c but not oGTT criteria also had higher waist/hip ratios, triglyceride, and CRP levels (p<0.05). A strong negative correlation was found between average daily step counts and CRP levels (rho = -0.62, p<0.001). Higher UKDDQ scores, or unhealthier diet habits, were associated with higher fasting plasma glucose (rho = 0.28, p = 0.08), triglyceride levels (rho = 0.31, p = 0.05), and insulin resistance (HOMA IR: rho = 0.31, p = 0.06). Higher PHQ-9 scores correlated with lower 2h-oGTT glucose levels (rho = -0.37, p<0.05). OGTT screening is superior to HbA1c screening in detecting preDM and DM early. Patients identified with preDM/DM by oGTT or HbA1c screening are insulin-resistant and have higher pulse rates. Abdominal obesity, unfavorable lipid profiles, and higher CRP levels were noted in patients screened by HbA1c, but not by oGTT. Low physical activity, low depression scores, and unhealthy diet habits were associated with higher CRP and higher glucose and triglyceride levels, respectively. Future studies should assess the impact of specifically tailored individual lifestyle counseling and medical management interventions in this high-risk population.

Postbariatric hypoglycemia, abdominal pain and gastrointestinal symptoms after Roux-en-Y gastric bypass explored by continuous glucose monitoring.

BackgroundAbdominal pain and postbariatric hypoglycemia (PBH) are common after bariatric surgery. ObjectivesThis study aimed to explore the potential relationship between abdominal pain, gastrointestinal symptoms, and PBH more than a decade after Roux-en-Y gastric bypass (RYGB) and whether continuous glucose monitoring (CGM) with dietary intervention has an educational role in reducing symptoms. SubjectsAt two public hospitals in Norway (one University Hospital) 22 of 46 invited patients who reported abdominal pain more than weekly took part. Recruited from a prospective follow-up study of 546 patients 14.5 years after RYGB. MethodsThey used a CGM for two 14-day periods, with a dietary intervention between periods. The Gastrointestinal Symptom Rating Scale (GSRS) and the Dumping Severity Score (DSS) questionnaires were completed at the start and end of the study. ResultsThe 22 women had preoperative age 39.6 ± 7.7 years and body mass index (BMI) 42.0 ± 4.0 kg/m2, present age 54.6 ± 7.7 years and BMI 29.8 ± 4.8 kg/m2. The total GSRS score and DSS of early dumping decreased after the diet intervention. The number of events with Level 1 (<3.9 mmol/L) or Level 2 (<3.0 mmol/L) hypoglycemia did not change in the second period. Half of the patients had fewer, three had unchanged, and eight had more frequent events with Level 1 hypoglycemia after the intervention. Ten patients had Level 2 hypoglycemia. ConclusionThough inconclusive findings, a personalized dietary intervention reduces GSRS. This intervention was accompanied by lower mean absolute glucose in patients with recurrent abdominal pain after bariatric surgery. However, further studies are needed to explore the benefits of CGM in this setting.

Maternal docosahexaenoic acid supplementation during lactation improves exercise performance, enhances intestinal glucose absorption and modulates gut microbiota in weaning offspring mice.

Intestinal dysfunction induced by weaning stress is common during breastfeeding period. Docosahexaenoic acid (DHA) is well known for promoting visual and brain development, but its effects on early intestinal development remain unknown. This study investigated the impact of maternal DHA supplementation during lactation on intestinal glucose absorption and gut microbiota in weaning offspring mice. Dams were supplemented with vehicle (control), 150 mg/(kg body weight · day) DHA (L-DHA), or 450 mg/(kg body weight · day) DHA (H-DHA) throughout lactation by oral administration. After weaning, pups were randomly divided into three groups for athletic analysis, microbial and proteomic analysis, biochemical analysis, 4-deoxy-4-fluoro-D-glucose (4-FDG) absorption test, and gene expression quantitation of glucose transport-associated proteins and mTOR signaling components. The H-DHA group exhibited enhanced grip strength and prolonged swimming duration compared to the control group. Additionally, there were significant increases in jejunal and ileal villus height, and expanded surface area of jejunal villi in the H-DHA group. Microbial analyses revealed that maternal DHA intake increased the abundance of beneficial gut bacteria and promoted metabolic pathways linked to carbohydrate and energy metabolism. Proteomic studies indicated an increased abundance of nutrient transport proteins and enrichment of pathways involved in absorption and digestion in the H-DHA group. This group also showed higher concentrations of glucose in the jejunum and ileum, as well as elevated glycogen levels in the liver and muscles, in contrast to lower glucose levels in the intestinal contents and feces compared to the control group. The 4-FDG absorption test showed more efficient absorption after oral 4-FDG gavage in the H-DHA group. Moreover, the expressions of glucose transport-associated proteins, GLUT2 and SGLT1, and the activation of mTOR pathway were enhanced in the H-DHA group compared to the control group. The L-DHA group also showed similar but less pronounced improvements in these aspects relative to the H-DHA group. Our findings suggested that maternal DHA supplementation during lactation improves the exercise performance, enhances the intestinal glucose absorption by increasing the expressions of glucose transporters, and beneficially alters the structure of gut microbiome in weaning offspring mice.

Association between cystic fibrosis transmembrane regulator genotype and clinical outcomes, glucose homeostasis indices and CF-related diabetes risk in adults with CF.

People living with cystic fibrosis (pwCF) homozygous for F508del present more severe phenotypes. PwCF with compound heterozygous genotypes F508del /A455E and F508del /L206W may have milder cystic fibrosis (CF) phenotypes. We compared F508del homozygotes and common compound heterozygotes (F508del and a second pathogenic variant) in adult patients. Nutritional, pulmonary function and glucose homeostasis indices data were collected from the prospective Montreal CF cohort. Two-hundred and three adults with CF having at least one F508del variant were included. Individuals were divided into subgroups: homozygous F508del/F508del (n=149); F508del/621+1G>T (n=17); F508del/711+1G>T (n=11); F508del/A455E (n=12); and F508del/L206W (n=14). Subgroups with the F508del/L206W and F508del/A455E had a lower proportion with pancreatic exocrine insufficiency (p<0.0001), a higher fat mass (p<0.0001), and lower glucose area under the curve (AUC) (p=0.027). The F508del/L206W subgroup had significantly higher insulin secretion (AUC; p=0.027) and body mass index (p<0.001). Pulmonary function (FEV1) was significantly higher for the F508del/L206W subgroup (p<0.0001). Over a median of 7.37 years, the risk of developing CFRD in 141 patients was similar between groups. PwCF with heterozygous F508del/L206W and F508del/A455E tended to have pancreatic exocrine sufficiency, better nutritional status, improved pulmonary function and better diabetogenic indices, but this does not translate into lower risk of CF-related Diabetes.

Evaluation of Glycosylated Hemoglobin Levels and Effect of Tobacco Smoking in Periodontally Diseased Non-Diabetic Patients.

Chronic diseases have progressively increased worldwide, impacting all areas and socioeconomic groups. Periodontal disease is an increasing global concern and contains risk factors similar to other chronic illnesses. The main risk factor for periodontitis is smoking. Smoking not only hastens periodontal disease but also complicates periodontal therapy. Serum glycosylated hemoglobin levels, which are derived from the average life span of an erythrocyte, are a good indicator of glycemic management during the preceding one to three months. This study was undertaken to assess the association between tobacco smoking and periodontal disease by evaluating plaque score, gingival score, extent and severity index (ESI), and glycemic status by estimating serum HbA1c in cigarette smoker patients compared to non-smokers. The study was conducted with 40 patients in the age range of 20-40 years. Patients were divided into two groups: non-smokers (Group I) and cigarette smokers (Group II). Periodontal clinical parameters such as the plaque index (PI), gingival index (GI), and ESI were recorded during the oral cavity examination. The biochemical marker, serum glycosylated hemoglobin, was measured in both groups. All parameters were measured at baseline and three months after periodontal therapy. The statistical tests used were the paired t-test, and Chi-square test for comparison between both groups. The mean difference of PI of non-smokers was 0.33 ± 0.30, and smokers were 0.52 ± 0.32, which was statistically significant. The mean difference of GI of non-smokers was 0.34 ± 0.19 and smokers 0.36 ± 0.303, which was statistically significant. The mean difference of extent in non-smokers was 5.33 ± 1.59, 5.52 ± 2.43, and smokers were 0.18 ± 0.17. The mean difference in severity in non-smokers was 0.18 ± 0.17, and smokers were 0.31 ± 0.25, which was statistically significant. The mean difference of HbA1c in non-smokers and smokers was 0.43 ± 0.277 and 0.415 ± 0.230, which shows a higher mean difference in non-smokers, which was statistically non-significant. This study concluded that each of Group I and Group II showed substantial improvements in all clinical periodontal variables, which include plaque index (PI), gingival index (GI), extent and severity index (ESI), and biochemical marker serum glycosylated hemoglobin. Controlling inflammation with SRP can improve insulin resistance, lower glucose levels, and prevent non-enzymatic glycation of hemoglobin.

Continuous Glucose Monitoring (CGM) in Healthy Japanese Female University Students Showed Early Morning Lower Sensor Glucose Values.

In this study, Continuous Glucose Monitoring, a 24-h continuous sensor measurement of the glucose level, was performed on 35 female university students in their 20s. The results showed that 51.4% of the subjects had at least one episode of low sensor glucose level <54 mg/dL during the entire measurement period. This severe low glucose level condition was defined as lower sensor glucose values and it tended to occur more frequently during the early morning hours, especially from 3:00 am to 7:00 am. There were no significant differences in the BMI, the average number of steps, the total energy intake, the energy ratio of proteins, fats, or carbohydrates, or the alcohol intake between the lower sensor glucose values occurrence and the non-lower sensor glucose values occurrence groups. In regard to the early morning lower sensor glucose values observed in healthy female university students, we consider that further studies are required.

Sex differences in plasma metabolites in a guinea pig model of allergic asthma.

Sex seems to be a contributing factor in the pathogenesis of bronchial asthma. This study aimed to find sex-related differences in metabolome measured by hydrogen-1 nuclear magnetic resonance ((1)H NMR) spectroscopy in healthy and ovalbumin (OVA)-sensitized guinea pigs. Adult male and female animals were divided into controls and OVA-sensitized groups. OVA-sensitization was performed by OVA systemic and inhalational administration within 14 days; on day 15, animals were killed by anesthetic overdose followed by exsanguination. Blood was taken and differential white blood cell count was measured. Left lung was saline-lavaged and differential cell count in the bronchoalveolar lavage fluid (BALF) was measured. After blood centrifugation, plasma was processed for (1)H NMR analysis. Metabolomic data was evaluated by principal component analysis (PCA). Eosinophil counts elevated in the BALF confirming eosinophil-mediated inflammation in OVA-sensitized animals of both sexes. Sex differences for lactate, glucose, and citrate were found in controls, where these parameters were lower in males than in females. In OVA-sensitized males higher glucose and lower pyruvate were found compared to controls. OVA-sensitized females showed lower lactate, glucose, alanine, 3-hydroxy-butyrate, creatine, pyruvate, and succinate concentrations compared to controls. In OVA-sensitized animals, lactate concentration was lower in males. Data from females (healthy and OVA-sensitized) were generally more heterogeneous. Significant sex differences in plasma concentrations of metabolites were found in both healthy and OVA-sensitized animals suggesting that sex may influence the metabolism and may thereby contribute to different clinical picture of asthma in males and females.

Molecular Approach to Identify Anti-inflammatory Potential of Stevioside in HFD-induced Type 2 Diabetic Rats: Evidence From in Vivo Study

Stevioside is a natural sweetener derived from the leaves of the Stevia rebaudiana plant. It has gained popularity as a sugar substitute due to its intense sweetness without adding calories or affecting blood sugar levels, making it a suitable option for people with diabetes or those looking to reduce their sugar intake. Studies have shown that stevioside has glucose lowering effects. Previous studies have shown that it has significant role in skeletal muscle but its role on expression of inflammatory signaling molecules in adipose tissue against high diet and sucrose-induced type-2 diabetes in experimental rats is yet to be done. The current research was undertaken to investigate if stevioside could also exert its antidiabetic effects by circumventing adipocyte induced inflammation, a key driving factor for insulin resistance in obese individuals. Effective dose of stevioside (20 mg/kg b.wt) was administered orally for 45 days to high fat diet and sucrose induced type-2 diabetic rats. Interestingly, stevioside treatment restores the elevated serum levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α) and sterol regulatory element binding protein-1c (SREBP-1c) and enhances Peroxisome Proliferator–activated receptor-γ (PPAR-γ) in adipocytes of diabetic rats. The gene expression of IR, GLUT4 and PPAR-γ mRNA were also significantly activated in stevioside treated groups but reduced IL-1 beta, IlL-6, IKKB, TNF-alpha and NFkB mRNA expression in diabetic adipose tissue. More importantly, stevioside acts very effectively as metformin to circumvent inflammation and insulin resistance in diabetic rats. Our results clearly show that stevioside inhibits obesity induced insulin resistance by ameliorating the inflammatory events and upregulating insulin signalling molecules. Keywords: Stevioside, HFD-T2DM, pro inflammation, insulin signalling; adipose tissue, obesity; signaling pathways; Therapautics.

Maternal Western diet programs cardiometabolic dysfunction and hypothalamic inflammation via epigenetic mechanisms predominantly in the male offspring

ObjectiveMaternal exposure during pregnancy is a strong determinant of offspring health outcomes. Such exposure induces changes in the offspring epigenome resulting in gene expression and functional changes. In this study, we investigated the effect of maternal Western hypercaloric diet (HCD) programming during the perinatal period on neuronal plasticity and cardiometabolic health in adult offspring. MethodsC57BL/6J dams were fed HCD for 1 month prior to mating with regular diet (RD) sires and kept on the same diet throughout pregnancy and lactation. At weaning, offspring were maintained on either HCD or RD for 3 months resulting in 4 treatment groups that underwent cardiometabolic assessments. DNA and RNA were extracted from the hypothalamus to perform whole genome methylation, mRNA, and miRNA sequencing followed by bioinformatic analyses. ResultsMaternal programming resulted in male-specific hypertension and hyperglycemia, with both males and females showing increased sympathetic tone to the vasculature. Surprisingly, programmed male offspring fed HCD in adulthood exhibited lower glucose levels, less insulin resistance, and leptin levels compared to non-programmed HCD-fed male mice. Hypothalamic genes involved in inflammation and type 2 diabetes were targeted by differentially expressed miRNA, while genes involved in glial and astrocytic differentiation were differentially methylated in programmed male offspring. These data were supported by our findings of astrogliosis, microgliosis and increased microglial activation in programmed males in the paraventricular nucleus (PVN). Programming induced a protective effect in male mice fed HCD in adulthood, resulting in lower protein levels of hypothalamic TGFβ2, NF-κB2, NF-κBp65, Ser-pIRS1, and GLP1R compared to non-programmed HCD-fed males. Although TGFβ2 was upregulated in male mice exposed to HCD pre- or post-natally, only blockade of the brain TGFβ receptor in RD-HCD mice improved glucose tolerance and a trend to weight loss. ConclusionsOur study shows that maternal HCD programs neuronal plasticity in the offspring and results in male-specific hypertension and hyperglycemia associated with hypothalamic inflammation in mechanisms and pathways distinct from post-natal HCD exposure. Together, our data unmask a compensatory role of HCD programming, likely via priming of metabolic pathways to handle excess nutrients in a more efficient way.

The Effect of Acute Hyperglycaemia Induced by Oral Glucose Load on Heart Rate Variability and Skin Microvascular Reactivity in Young Adults.

We aimed to elucidate the effects of acute hyperglycaemia, induced by an oral glucose tolerance test (OGTT), on the autonomic nervous system (ANS) and skin microvascular reactivity at the time point of peak plasma glucose concentration (cglc) in 20 young, healthy participants. We assessed their heart rate variability (HRV) as a measure of the ANS activity and the parameters of post-occlusive reactive hyperaemia (PORH) to estimate skin microvascular reactivity as measured by laser Doppler (LD) fluxmetry. The tests were repeated 30 min after a standard OGTT (75 g glucose dissolved in 250 mL water) and, in a separate control experiment, after drinking the same amount of water. Participants had their cglc and serum insulin measured at three consecutive time-points according to the testing protocol. The low-frequency (LF) spectral power, the LF to high-frequency (LF/HF) ratio, and the diastolic blood pressure increased significantly more after water than after OGTT, and there was a trend of the peak LD flux of PORH decreasing more after OGTT than after water. Significant correlations between some PORH and all the HRV parameters and cglc increase after OGTT were found, implying diminished vascular reactivity evoked by hyperglycaemia in healthy subjects with lower glucose tolerance.

Effects of a Novel Glucokinase Activator, Dorzagliatin, on Glycemic Control and Glucose Fluctuation in Drug-Naïve Patients with Type 2 Diabetes Mellitus.

The prevalence rate of type 2 diabetes mellitus (T2DM) has been increasing and a large proportion of patients still do not achieve adequate or sustainable glycemic control on the basis of previous hypoglycemic treatment. In this present study, we explored whether dorzagliatin, a novel glucokinase activator (GKA), could improve glycemic control and lessen glucose fluctuation in drug-naïve patients with T2DM. A self-comparative observational study of 25 drug-naïve patients with T2DM (aged 18-75 years and HbA1c of 7.5%-11.0%) treated with dorzagliatin 75 mg twice daily for 52 weeks. Before and after dorzagliatin intervention, the serum levels of hemoglobin A1c (HbA1c), insulin, and C-peptide were measured repeatedly during fasting and after a mixed meal. The continuous glucose monitoring (CGM) device was also used to obtain 24-hour glucose profiles and assess the changes in glycemic variability parameters. After 52 weeks of treatment with dorzagliatin, a numerally greater reduction in HbA1c of 1.03% from the baseline was observed in patients with T2DM, accompanied by significant improvement in insulin resistance and insulin secretion. Moreover, the standard deviation of blood glucose (SDBG) and the mean amplitude of glycemic excursion (MAGE) derived from CGM data were significantly decreased after dorzagliatin therapy. The 24-h glucose variation profile showed that study patients had obviously lower mean glucose levels during the postprandial period from the baseline to week 52, an effect also demonstrated by the significant decrease in the incremental area under glucose concentration versus time curve for 2 h (iAUC0-2 h) after meals. This study suggests that dorzagliatin therapy could effectively improve glycemic control and glucose fluctuation in drug-naïve patients with T2DM.

HARNESSING GOLD NANORODS FOR NON-ENZYMATIC GLUCOSE SENSING

This study presents a straightforward and non-enzymatic approach for glucose detection utilizing aggregated gold nanorods (GNRs) based on surface plasmon resonance (SPR). The GNRs exhibited enhanced sensitivity toward glucose concentrations of up to 10 mM. The LSPR-based glucose detection method demonstrated superior sensitivity, stability, ease of use, and a convenient readout. Moreover, the LSPR detection technique can be seamlessly integrated with various sensing platforms, offering the potential to expand the sensor's range and applicability. This study highlights the promising prospects of LSPR-based non-enzymatic glucose detection and its potential for integration into diverse sensing systems. For the 10 mM glucose solution, the addition of 5.85x109 GNRs caused a 136 nm shift. On the other hand, when 50 mM glucose is added, the shift amounted to 82 nm, while adding 100 mM glucose resulted in a shift of 71 nm. This implies that at lower glucose concentrations, the degree of aggregation is greater, suggesting a heightened sensitivity to smaller concentrations. TEM images depicted the formation of the gold nanorod aggregates upon the introduction of 10 mM glucose.

Association Between Hypoglycemia and the Occurrence of Early Onset Sepsis in Premature Infants.

We examined the association between hypoglycemia and the occurrence of early onset sepsis (EOS) in premature infants admitted to the neonatal intensive care unit (NICU). We included infants discharged from 358 NICUs between 1997 and 2020 with gestational age <34 weeks, ≥1 culture collected in the first 3 days of life, and ≥1 serum glucose value recorded on the day of or day prior to culture collection. We used multivariable logistic regression and inverse probability weighting (IPW) and constructed models for three definitions of hypoglycemia: American Academy of Pediatrics (AAP), Pediatric Endocrine Society, and a definition based on neurodevelopmental studies. We performed subgroup analysis in EOS episodes caused by Gram-negative and Gram-positive organisms. Of the 62,178 infants and 64,559 cultures that met study inclusion criteria, 739 (1%) cultures were positive. The median (25th, 75th percentile) glucose value was 75 mg/dL (50, 106) on the day of or day prior to a positive culture versus 70 mg/dL (50, 95) on the day of or day prior to a negative culture. We found that hypoglycemia was not associated with the occurrence of EOS for all organisms and Gram-positive organisms, whereas there was a small but significant association between the lower AAP glucose cutoff value and EOS due to Gram-negative organisms (logistic regression: risk difference [RD] 0.24% [95% CI, 0.01-0.47]; IPW: RD 0.22% [95% CI, 0.00-0.43]). Hypoglycemia may be an early marker of EOS, particularly in episodes caused by Gram-negative organisms and when using a stricter definition of hypoglycemia.

Dietary of different forms of Humulus scandens on growth performance and intestinal bacterial communities in piglets.

The present study was aimed at elucidating the effects of feeding different forms of Humulus scandens (Hu) on performance and bacterial communities in piglets. A total of 160 piglets were divided into four groups: (1) a control (CG, basal diet); (2) a basal diet with Hu pulp (HS), basal diet + Hu pulp; (3) a basal diet with Hu juice (HSJ), basal diet + Hu juice; and (4) a basal diet with Hu residue (HSR), basal diet + Hu residue. Results showed that HS, HSJ, and HSR supplementation led to rich average daily gain (ADG) and poor feed conversion ratio (FCR) during 28 to 70 d of age, increased 120 d body weight (BW), average daily feed intake (ADFI) and ADG and decreased FCR during 71 to 120 d of age. Three experiment groups presented greater (P < 0.05) IgA, IgG, and IgM and lower (P < 0.05) glucose, and blood urea nitrogen. The content of diamine oxidase significantly decreased (P < 0.05) in HS group. The crude protein and crude fiber digestibility were improved (P < 0.05) in HS group and the Ca digestibility was increased (P < 0.05) in HS and HSJ groups. HSR supplementation improved the abundance of Firmicutes and decreased the abundance of Bacteroidetes. Hu supplementation with different forms increased the proportion of Lactobacillus in cecum content. These results indicated that supplemental feeding of Hu with different forms improved serum immunity, nutrient digestibility, and bacterial communities in piglets, promoting growth and development, which may be regarded as a reference for developing novel feed resources for piglets.

Effects of methotrexate, &lt;em&gt;Moringa oleifera&lt;/em&gt;, and &lt;em&gt;Andrographis paniculata&lt;/em&gt; extracts on the myocardial and aortic tissue of streptozotocin-nicotinamide-induced hyperglycemic rats

BACKGROUND Methotrexate (MTX) could lower glucose levels in type 1 diabetes mellitus, while Moringa oleifera and Andrographis paniculata supplementations have similar effects on hyperglycemia. This study aimed to analyze the effects of MTX, M. oleifera, and A. paniculata leaf extracts on the myocardial interleukin (IL)-6 and the histopathology of the left ventricle and aorta.&#x0D; METHODS 49 rats were divided equally into 7 groups: negative control and diabetic induced by streptozotocin-nicotinamide (STZ-NA) injection consisting of positive control (STZ-NA only), M. oleifera (500 mg/kgBW/day), A. paniculata (500 mg/kgBW/day), MTX (7 mg/kgBW/week), MTX (7 mg/kgBW/week)+M. oleifera (500 mg/kgBW/day), and MTX (7 mg/kgBW/week)+A. paniculata (500 mg/kgBW/day). We analyzed oral MTX, M. oleifera, and A. paniculata leaf extracts’ effects on random blood glucose, myocardial IL-6, and cardiac histopathology of STZ-NA-induced hyperglycemic male rats. Data were analyzed using Wilcoxon and Kruskal–Wallis tests.&#x0D; RESULTS Myocardial IL-6 in the M. oleifera group was significantly lower compared to the positive control group (p = 0.041). Compared to the positive control group, the myocardial necrosis and aortic intima–media thickness in the MTX+A. paniculata group were significantly reduced (p = 0.005 and 0.001, respectively).&#x0D; CONCLUSIONS MTX, M. oleifera, and A. paniculata showed antihyperglycemic effect, both individually and in combination. A. paniculata leaf extract had a significant cardioprotective effect in STZ-NA-induced hyperglycemia.

Fluorinated thiazole–thiosemicarbazones hybrids as potential PPAR-γ agonist and α-amylase, α-glucosidase antagonists: Design, synthesis, in silico ADMET and docking studies and hypoglycemic evaluation

In addition to Peroxisome Proliferator-Activated Receptor-gamma (PPAR-γ), which is essential for controlling type-2 diabetes mellitus, α-amylase and α-glucosidase inhibition is a key strategy in managing postprandial hyperglycemia. In this work a series of 2-(1-(2-((4-fluorophenyl)amino)-4-methylthiazol-5-yl)ethylidene)hydrazine-1-carbothioamide derivatives (3–6) was designed and synthesized through theiosemicarbazide derivatives, the structural elucidation of the new synthesized compounds was established using elemental and spectroscopic analyses. The antidiabetic activities of the new thiazole-thiosemicarbazone hybrids were screened in vivo for blood glucose lowering activity in normal rats and compared with pioglitazone as antidiabetic standard. Male Sprague-Dawley rats had reduced blood sugar levels after exposure to compounds 5 and 6 compared to pioglitazone. Additionally, the PPAR-γ agonist activity of compounds 5 and 6 as well as their ability to inhibit α-amylase and α-glucosidase were assessed. When compared to standard acarbose, which had an IC50 value of 0.74 ± 0.15 mM/mL, compound 5 showed the highest α-glucosidase inhibitory activity with IC50 value of 0.446 ± 0.01 mM/mL, while compound 6 showed good activity with an IC50 value of 1. 914 ± 0.04 mM/mL. However, compound 5 and compound 6 had weak α-amylase inhibitory activity, with IC50 values of 11.78 ± 0.58 and 24.18 ± 1.2 µg/mL respectively. Furthermore, Peroxisome proliferator activated receptor γ [PPAR-γ] agonist activity for compound 5 and compound 6 was assessed and gave promising result as [PPAR-γ] agonist with IC50 value of 0.938 ± 0.023 and 0.947 ± 0.024 ng/mL respectively superior to that of pioglitazone with IC50 value of 1.912 ± 0.11 ng/mL. All the results supported compound 5 as promising candidates for construction of new antidiabetic agents. Also, in silico ADMET and docking studies for the most promising derivatives 5, 6, Acarbose, and Pioglitazone were done.

Post-Coronary Artery Bypass Grafting Outcomes of Patients with/without Type-2 Diabetes Mellitus and Chronic Kidney Disease Treated with SGLT2 Inhibitor Dapagliflozin: A Single-Center Experience Analysis.

Increasingly, SGLT2 inhibitors save patients with heart failure and comorbidities such as type-2 diabetes mellitus (T2DM) and chronic kidney disease (CKD); the inhibition of sodium-glucose cotransporter 2 (SGLT2) was first studied in patients with diabetes as a solution to lower glucose levels by preventing glucose reabsorption and facilitating its elimination; in the process, researchers took notice of how SGLT2 inhibitors also seemed to have beneficial cardiovascular effects in patients with both diabetes and cardiovascular disease. Our single-center prospective study assesses outcomes of post-coronary artery bypass grafting (CABG) rehabilitation and SLGT2 inhibition in CABG patients with/without T2DM and with/without CKD. One hundred twenty consecutive patients undergoing CABG were included in the analysis. Patients were divided into four subgroups: diabetes patients with chronic kidney disease (T2DM + CKD), diabetes patients without chronic kidney disease (T2DM-CKD), prediabetes patients with chronic kidney disease (PreD+CKD), and prediabetes patients without chronic kidney disease (PreD-CKD). Echocardiographic and laboratory investigations post-surgery (phase I) and 6 months later (phase II) included markers for cardiac ischemia, glycemic status, and renal function, and metabolic equivalents were investigated. One hundred twenty patients participated, mostly men, overweight/obese, hypertensive, smokers; 65 had T2DM (18 with CKD), and 55 were prediabetic (17 with CKD). The mean ejection fraction increased by 8.43% overall but significantly more in the prediabetes group compared to the T2DM group (10.14% vs. 6.98%, p < 0.05). Overall, mean heart-type fatty-acid-binding protein (H-FABP) levels returned to normal levels, dropping from 68.40 ng/mL to 4.82 ng/mL (p = 0.000), and troponin data were more nuanced relative to an overall, strongly significant decrease of 44,458 ng/L (p = 0.000). Troponin levels in patients with CKD dropped more, both in the presence of T2DM (by 82,500 ng/L, p = 0.000) and in patients without T2DM (by 73,294 ng/L, p = 0.047). As expected, the overall glycated hemoglobin (HbA1c) levels improved significantly in those with prediabetes (from 6.54% to 5.55%, p = 0.000); on the other hand, the mean HbA1c changed from 7.06% to 6.06% (p = 0.000) in T2DM, and the presence or absence of CKD did not seem to make any difference: T2DM+CKD 7.01-6.08% (p = 0.000), T2DM-CKD 7.08-6.04% (p = 0.000), PreD+CKD 5.66-4.98% (p = 0.014), and PreD-CKD 6.03-4.94% (p = 0.00). Compared to an overall gain of 11.51, the GFRs of patients with CKD improved by 18.93 (68.15-87.07%, p = 0.000) in the presence of established diabetes and 14.89 (64.75-79.64%, p = 0.000) in the prediabetes group. Regarding the patients' cardiac statuses, the results from our single-center analysis revealed a significant decrease in ischemic risk (H-FABP and hs-cTnI levels) with improvements in mean ejection fraction, glycemic status, and renal function in patients post-CABG with/without T2DM, with/without CKD, and with SGLT2 inhibitor dapagliflozin treatment while undergoing cardiac rehabilitation.

Impact of Protease Inhibitor-Based Highly Active Antiretroviral Therapy on Fetal Subcutaneous Fat Tissue in HIV-Pregnant Women in a Middle-Income Country.

HIV infection continues to be a global public health challenge, affecting approximately 1.7 million reproductive-aged women. Protease inhibitor-based highly active antiretroviral therapy (PI-HAART) has significantly reduced the risk of vertical transmission of HIV from mother to child. Nevertheless, concerns linger regarding the long-term effects, particularly on body composition, notably subcutaneous fat tissue (SFT). Although HIV-associated lipodystrophy syndrome (LS) has been well documented in adults and older children, its impact on fetuses exposed to PI-HAART remains underexplored. This study aims to evaluate SFT in the fetuses of HIV-pregnant women exposed to PI-HAART, assessing the potential clinical implications. We conducted a comparative study between HIV-pregnant women receiving PI-HAART and an HIV-negative control group. Fetometry measurements were obtained via 3D ultrasound. SFT in the fetal arm and thigh segments was assessed. Data were analyzed using lineal multivariate regression and receiver-operating characteristics (ROC)-curve analysis. Fetuses exposed to PI-HAART exhibited a significant reduction in subcutaneous fat, particularly in the proximal third-middle union of the femur (coefficient: -2.588, p = 0.042). This reduction was correlated with lower newborn serum glucose levels (65.7 vs. 56.1, p = 0.007; coefficient: -1.277, p = 0.045). Our study sheds light on the connection between PI-HAART, fetal subcutaneous fat, and neonatal health. These findings might reveal the long-lasting effects of PI-HAART on newborns and children's well-being. Our results emphasize the need for a more balanced approach to managing pregnant women with HIV in developing countries and open new venues for research on the impact of intrauterine PI-HAART exposure on energy metabolism and fetal programming.

The citrate transporter SLC13A5 as a therapeutic target for kidney disease: evidence from Mendelian randomization to inform drug development

BackgroundSolute carrier family 13 member 5 (SLC13A5) is a Na+-coupled citrate co-transporter that mediates entry of extracellular citrate into the cytosol. SLC13A5 inhibition has been proposed as a target for reducing progression of kidney disease. The aim of this study was to leverage the Mendelian randomization paradigm to gain insight into the effects of SLC13A5 inhibition in humans, towards prioritizing and informing clinical development efforts.MethodsThe primary Mendelian randomization analyses investigated the effect of SLC13A5 inhibition on measures of kidney function, including creatinine and cystatin C-based measures of estimated glomerular filtration rate (creatinine-eGFR and cystatin C-eGFR), blood urea nitrogen (BUN), urine albumin-creatinine ratio (uACR), and risk of chronic kidney disease and microalbuminuria. Secondary analyses included a paired plasma and urine metabolome-wide association study, investigation of secondary traits related to SLC13A5 biology, a phenome-wide association study (PheWAS), and a proteome-wide association study. All analyses were compared to the effect of genetically predicted plasma citrate levels using variants selected from across the genome, and statistical sensitivity analyses robust to the inclusion of pleiotropic variants were also performed. Data were obtained from large-scale genetic consortia and biobanks, with sample sizes ranging from 5023 to 1,320,016 individuals.ResultsWe found evidence of associations between genetically proxied SLC13A5 inhibition and higher creatinine-eGFR (p = 0.002), cystatin C-eGFR (p = 0.005), and lower BUN (p = 3 × 10−4). Statistical sensitivity analyses robust to the inclusion of pleiotropic variants suggested that these effects may be a consequence of higher plasma citrate levels. There was no strong evidence of associations of genetically proxied SLC13A5 inhibition with uACR or risk of CKD or microalbuminuria. Secondary analyses identified evidence of associations with higher plasma calcium levels (p = 6 × 10−13) and lower fasting glucose (p = 0.02). PheWAS did not identify any safety concerns.ConclusionsThis Mendelian randomization analysis provides human-centric insight to guide clinical development of an SLC13A5 inhibitor. We identify plasma calcium and citrate as biologically plausible biomarkers of target engagement, and plasma citrate as a potential biomarker of mechanism of action. Our human genetic evidence corroborates evidence from various animal models to support effects of SLC13A5 inhibition on improving kidney function.

Pharmacological screening of antidiabetic activity of ethanolic extracts of justicia tranquebarensis on streptozocin induced rats.

Non-communicable diseases like diabetes mellitus are becoming major health problem these days. There is an increasing demand by patients to use the natural products (plants) with anti-diabetic activity due to the severe side effects associated with the use of insulin and oral anti-diabetic drugs. One such plant is Justicia tranquebareinsis which has been traditionally used for the treatment of diabetes mellitus. The aim of this study was, therefore, to evaluate hypoglycemic activity of ethanol extract of Justicia tranquebareinsis in streptozotocin-induced diabetic rats, respectively and to carry out acute toxicity test. Two doses (200 mg/kg and 400 mg/kg) of the ethanol extract of Justicia tranquebareinsis were administered to normal glucose loaded and diabetic rat to study blood glucose lowering effect. Ethanol extract of Justicia tranquebareinsis (200mg/kg and 400mg/kg, p.o.) showed significant tolerance (P &lt; 0.05) to oral glucose load at 1 and 2 hrs after glucose load. The extract also produced significant (P &lt; 0.05) blood glucose reduction at 4 hours after its administration in normoglycemic mice. The extract at 400mg/kg dose level produced significant (P &lt; 0.05) reduction in blood glucose level at 2, 3 and 4 hours of treatment in streptozotocin (45 mg/kg) induced diabetic mice. Acute oral toxicity studies of ethanol extract of Justicia tranquebareinsis in rats showed no death or signs of toxicity at the dose of 2000 mg/kg indicating the safety nature of the extract. The results of the experiments showed that ethanol extract of Justicia tranquebareinsis has significant antihyperglycemic activity in streptozotocin induced diabetic rat and improvement in glucose tolerance and slight hypoglycemic activity in normal rat justifying the traditional claim for its use in diabetes.