Search Results (299)

Background/Objectives: In all types of diabetes, elevated blood glucose levels cause pathological changes in skeletal muscle, primarily due to oxidative stress, mitochondrial dysfunction, and excessive production of reactive oxygen species (ROS). Regular exercise can help mitigate these effects; however, the underlying mechanisms, particularly those involving the mitochondrial permeability transition pore (mPTP), remain incompletely understood. This study aimed to explore the effects of aerobic exercise training (AET) on oxidative stress and the expression of mPTP components in the skeletal muscle of streptozotocin-induced diabetic rats. Methods: Male Wistar rats were randomly divided into three groups: Healthy Sedentary (H-SED), Diabetic Sedentary (D-SED), and Diabetic Exercise-trained (D-EXER); n = 6 per group. The D-EXER group performed AET (0° slope) 5 days/week for 8 weeks. After the intervention period, body weight and fasting blood glucose (FBG) levels were measured, and soleus muscles were collected and analyzed for oxidative stress biomarkers, Western blotting, and gene expression using qRT-PCR. Results: Following an 8-week intervention, AET reduced FBG concentrations. Accordingly, in the soleus muscles of the D-EXER group, ROS levels decreased, and redox balance was improved compared to the D-SED group. Exercise training reduced CypD and Casp9 mRNA expression and increased Bcl-2 mRNA expression, whereas Ant1 mRNA expression was only slightly altered. CypD protein expression was decreased in exercised diabetic rats, while VDAC1 protein and mRNA levels remained unchanged. In the D-EXER group, there were significant inverse correlations between CypD and Casp9 mRNA expression levels and glutathione redox state. Conclusions: The current study suggests that 8 weeks of AET, in addition to reducing hyperglycemia, may favorably influence oxidative balance and the expression of mPTP-related molecular components in diabetic skeletal muscle. Full article

Type 2 diabetes mellitus (T2DM) is an endocrine–metabolic disorder characterized by pancreatic islet dysfunction-induced hyperglycemia, which triggers hepatic injury, intestinal microbiota dysbiosis, and systemic complications. Fagopyrum tararicum seeds exhibit various biological activities, including antioxidant, hypolipidemic, and antihypertensive effects. However, there is limited research exploring how supernatants derived from the water extraction–ethanol precipitation of Fagopyrum tararicum seeds (SWEPFT) modulate the intestinal microbiota and their potential link to T2DM. This study evaluates SWEPFT’s effects on hyperglycemia and intestinal microbiota in T2DM mice. After a 4-week therapeutic period, SWEPFT markedly ameliorated hyperglycemia, as evidenced by reduced body weight (BW), fasting blood glucose (FBG), and glycated serum protein (GSP) and improved insulin sensitivity/resistance indicators (HOMA-IS/IR) and β-cell function (HOMA-β). Furthermore, the levels of both Akt1 and Slc2a2 transcription displayed notable enhancement. SWEPFT-H (high-dose SWEPFT) exhibited superior effects to SWEPFT-L (low-dose SWEPFT) in improving BW, FBG, and HOMA-IS. Moreover, SWEPFT modulated the intestinal microbiota by decreasing the Firmicutes/Bacteroidetes ratio, augmenting the proportion of Intestinimonas and Ruminiclostridium, and increasing the short-chain fatty acid content. A correlation analysis identified Candidatus_Arthromitus, Anaeroplasma, Candidatus_Stoquefichus, and Harryflintia as potential T2DM biomarkers linked to glycemic regulation. These findings elucidate SWEPFT’s critical role in microbiota modulation and hyperglycemia alleviation, providing a novel perspective for T2DM pathogenesis research and therapeutic development. Full article

Background: Early prediction of gestational diabetes mellitus (GDM) remains a major clinical challenge, and the current oral glucose tolerance test (OGTT) is time-consuming and inconvenient for clinical routine. This study aimed to develop a novel predictive model for postprandial hyperglycemia GDM (pp-GDM) and postprandial glucose elevation using fasting serological and metabolic profiles. Method: We used High-Performance Liquid Chromatography-Mass Spectrometry (HPLC-MS) to analyze fasting plasma amino acid profiles at 24–28 weeks of gestation for 60 pp-GDM patients and 120 controls. Binary logistic regression model was constructed to identify potential biomarkers for pp-GDM prediction. Results: By incorporating amino acid indicators such as isoleucine, phenylalanine, threonine, and aspartate into the predictive model alongside traditional predictors (including BMI at sampling, fasting insulin, glycated hemoglobin, and uric acid), the overall predictive performance was significantly improved from 78.2% to 91.1%. A clinically practical nomogram for risk assessment was subsequently developed. Conclusions: This fasting metabolite-based model provides a reliable tool for early prediction of pp-GDM and postprandial hyperglycemia, which may reduce the need for OGTT and facilitate timely clinical decision making. Full article

Precision medicine starts with a precision diagnosis. Yet up to 80% of cases of monogenic diabetes, a form of diabetes characterized by mutations in a single gene, are either overlooked or misdiagnosed. A genetic test for monogenic diabetes does not always lead to a precise diagnosis, as novel variants are often classified as variants of unknown significance. Variant interpretation requires collation of a framework of evidence, including population, computational, and segregation data, and can be assisted by functional analysis. The inclusion of functional data can be challenging, depending on the number of benign and pathogenic variants available for benchmarking assays. Glucokinase is the rate-limiting step for glucose metabolism in the pancreatic beta-cell and governs the threshold for glucose-stimulated insulin release. Loss-of-function alleles in the glucokinase (GCK) gene are a cause of stable fasting hyperglycemia from birth and/or diabetes. In this study, we functionally characterized 25 variants identified during diagnostic testing or in exome sequencing studies. We assessed their kinetic characteristics, stability, and interaction with pharmacological and physiological regulators. We integrated our functional data with existing data from the ClinGen Monogenic Diabetes Variant Curation Expert Review panel using a gene-specific framework to assist variant classification. We show how functional evidence can aid variant classification, thus enabling diagnostic certainty. Full article

Background: Iodine deficiency remains a significant public health concern worldwide and may contribute to metabolic disorders beyond thyroid dysfunction. Emerging evidence suggests that nutritional factors, such as vitamin A, may influence the health effects of iodine deficiency, yet population-based evidence remains limited. This study aimed to investigate the associations between iodine deficiency and cardiometabolic risk factors (blood pressure, glucose, and lipids) and to explore whether these associations are different between adults with different vitamin A levels. Methods: A total of 4723 adults (1895 males and 2828 females) were included in this cross-sectional study. Participants were categorized based on iodine status and serum vitamin A levels. Demographic, anthropometric, and biochemical indicators were assessed through standardized examinations. Multivariable linear and logistic regression models were used to evaluate the associations between iodine deficiency and continuous (systolic blood pressure [SBP], diastolic blood pressure [DBP], fasting blood glucose [FBG], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], triglycerides [TGs]) and binary outcomes (hypertension, hyperglycemia, and dyslipidemia), with stratified analyses by gender, age, and vitamin A status. Results: Iodine deficiency was significantly associated with higher SBP (β = 2.89, 95% confidence interval [CI]: 2.00–3.77), DBP (β = 1.08, 0.55–1.60), FBG (β = 0.06, 0.01–0.12) and TC (β = 0.05, 0.00–0.10). The odds of hypertension (odds ratio [OR] = 1.41, 1.23–1.63) and hyperglycemia (OR = 1.39, 1.17–1.65) were also increased. Stratified analyses indicated that these associations were more pronounced among participants with vitamin A deficiency than those with sufficient vitamin A. In this subgroup, iodine deficiency was positively associated with FBG (β = 0.14, 0.03–0.25), TC (β = 0.08, 0.00–0.15), and hyperglycemia (OR = 1.35, 1.04–1.76). Conclusions: The findings suggest that the association of iodine deficiency with adverse cardiometabolic risk factors may be stronger in individuals with concurrent vitamin A deficiency. This highlights the potential value of integrated nutritional assessments and supports the need for longitudinal studies to confirm these interactions and assess the effects of combined micronutrient supplementation. Full article

To better understand the molecular mechanisms by which a Western diet (WD) promotes the development of type 2 diabetes (T2D), we analyzed changes in the expression profiles of multiple glucose-regulatory tissues of male C57BL/6 mice. We fed the mice with either a regular control diet (CD) or a WD. Standard glucose and insulin tolerance tests were performed, and body weight, plasma glucose, and triglyceride levels were measured to assess the glucose homeostasis in vivo. The WD induced obesity, glucose intolerance, and insulin resistance, with a fasting hyperglycemia. Further, we identified several changes in the gene expression of the analyzed candidate genes in all the examined target tissues, including the downregulation of Tcf7l2 in the liver, pancreas, white and brown adipose tissue (0.72, 0.56, 0.36, and 0.22-fold, respectively), in contrast to a marked upregulation in the intestine (2.57-fold). We also found downregulation of PPARγ in the white and brown adipose tissue (0.55, 0.41-fold, respectively) and upregulation in the pancreas, liver, intestine, and skeletal muscle (1.25, 1.46, 1.97, and 2.59-fold, respectively). Our findings provide important insight into the characteristic pattern of changes in expression of candidate genes during the early stages of insulin resistance and glucose intolerance in this diet-induced mouse model of T2D. Full article

Background and Objectives: Cardiometabolic diseases are rising in Latin America, yet rural Amazonian populations remain understudied. We aimed to characterize the prevalence and factors associated with a simple composite cardiometabolic risk in rural Amazonian adults. Materials and Methods: We conducted an analytical cross-sectional study during community screenings in San Martín, Peru, in 2025, enrolling adults aged ≥ 18 years. The outcome was present when ≥2 biological/anthropometric alterations were identified at the same visit (hypertension, dyslipidemia, hyperglycemia, hyperuricemia, general obesity, abdominal obesity, or elevated waist-to-hip ratio). Behaviors included current tobacco use, alcohol risk (AUDIT), and physical activity (IPAQ). We summarized variables (univariate), compared groups (bivariate: chi-square; Fisher for alcohol), and fitted modified Poisson regression with robust errors to estimate prevalence ratios (PRs); variables with p ≤ 0.20 in bivariate analysis entered multivariable models. Results: We enrolled 205 adults; 70.2% met the composite outcome. In multivariable models, abdominal obesity (adjusted PR [aPR] 1.70; 95% CI 1.40–2.10), hyperglycemia (1.65; 1.25–2.17), hyperuricemia (1.38; 1.19–1.61), dyslipidemia (1.25; 1.07–1.46), and general obesity (1.21; 1.04–1.40) were independently associated with cardiometabolic risk. Hypertension (1.06; 0.88–1.29) and elevated waist-to-hip ratio (1.20; 0.88–1.63) were not. Physical activity differed crudely but showed no independent association; tobacco and alcohol were not associated. Conclusions: In this rural Amazonian population, we observed a high prevalence of composite cardiometabolic risk and found that central adiposity and metabolic derangements, not blood pressure or self-reported behaviors, were the main correlates. Simple measures such as waist circumference, fasting glucose or HbA1c, a basic lipid panel, and serum urate may help flag adults at higher cardiometabolic risk in similar low-resource primary-care settings, but prospective studies are needed to evaluate their predictive value and screening performance. Full article

Background: Glucocorticoid-induced hyperglycemia (GCIH) is a common adverse effect of glucocorticoid (GC) therapy. Although evidence on oral antidiabetic medications (OADMs) for GCIH is emerging, direct comparisons with insulin therapy remain limited. This study aimed to compare the efficacy and safety of OADMs and sliding scale insulin (SSI) in patients with autoimmune diseases who developed GCIH. Methods: We retrospectively analyzed 97 patients who developed GCIH during GC therapy equivalent to ≥20 mg/day of prednisolone. Patients were classified into SSI-only (n = 41), OADM (n = 31), and basal–bolus/basal or bolus insulin (BBI/BI) (n = 25) groups. The primary endpoint was mean preprandial blood glucose (BG), adjusted for patient characteristics. Secondary outcomes included hospital stay, hypoglycemia, insulin use, and glycated hemoglobin. Results: In univariate analysis, the mean preprandial BG levels during the treatment period were significantly associated with the mean initial preprandial BG levels. Adjusted mean preprandial BG during treatment did not differ significantly between the OADM and SSI-only groups, whereas the BBI/BI group had higher pre-breakfast BG (p = 0.016). Among first-time GC users, those in the OADM group using cyclophosphamide had significantly lower fasting BG than non-users (p = 0.011). Conclusions: In patients with autoimmune diseases receiving ≥20 mg/day GC, OADM provided glycemic control comparable to SSI with similar hypoglycemia risk. Early preprandial BG levels during the first 3 days of GC therapy may help predict glycemic outcomes. Prospective studies with standardized regimens are needed to optimize GCIH management. Full article

This study investigated the anti-obesogenic effects of 3D-printed snacks—developed from indigenous composite inks of cowpea, sorghum, and orange-fleshed sweet potato—in male and female Wistar rats fed a high-fat diet (HFD). Four experimental diets (TD1–TD4) were formulated from snacks using two blend ratios (33.33%:33.33%:33.33%) and 50%:10%:40%) and two processing states (raw and bioprocessed). Following a five-week HFD-induction period, the rats were supplemented for an additional five weeks with diets containing 20% of these snacks, Orlistat, or HFD alone. Physiological assessments included body weight, fasting glucose, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), serum lipids, sex hormones, angiotensin-converting enzyme (ACE) activity, and histological evaluation of cardiac tissue. HFD feeding induced hyperglycemia, dyslipidemia, and insulin resistance. Supplementation with the 3D-printed snacks improved glycemic control, with the TD4 (bioprocessed blend; 50:10:40%) restoring glucose levels close to baseline. TD1 and TD2 (raw blends) improved lipid and hormonal profiles in females, whereas TD3 (bioprocessed blend; 33.33%:33.33%:33.33%) significantly reduced triglycerides and elevated HDL in males. Importantly, only TD1 (raw blend; 33.33%:33.33%:33.33%) significantly reduced ACE activity in males, providing a unique cardioprotective mechanism not observed with other snack formulations. Histological analyses revealed inflammatory infiltration and fibroplasia in HFD and Orlistat groups, whereas all 3D-printed snacks preserved normal myocardial architecture without necrosis or fibrosis. Collectively, these findings demonstrate that 3D-printed snacks derived from indigenous composite inks improved metabolic dysfunctions associated with diet-induced obesity. The optimal formulation appears application-specific: TD4 for glycemic control, TD3 for lipid management in males, and TD1/TD2 for metabolic improvements in females. Full article

Background: Resistant starch, and specially retrograded starches (RS), have been suggested as useful biological molecules to improve the glucose management in diabetic conditions. However, the influence of the botanical origin in the RS biological capacities make necessary its evaluation, where RS from legumes have been paid less attention compared to other sources as cereals. Objectives: A RS product obtained from creole Faba beans (Vicia faba L. creole), was evaluated for the first time as a material capable of improving glucose homeostasis in diabetic conditions. Methods: The RS ingredient investigated (with a reduced digestibility of 50%) was tested in a Wistar rat model with induced diabetes, fed with a 15 or 30% replacement of RS ingredient in the diet. Diverse nutritional and biomarkers were analysed. Results: As a result of the reduced digestibility of the RS ingredient, diabetic animals fed with RS replacement (15% or 30%) showed attenuated postprandial hyperglycemia responses, reducing the hyperglycemic condition close to 29% compared to non-treated diabetic animals (24.56 ± 7.50 and 25.02 ± 3.54 vs. 34.65 ± 1.89 mmol/L, respectively). In addition, fasting serum glucose levels were significantly reduced (22%). Other biochemical parameters associated with glucose metabolism, such as glycosylated hemoglobin and AGEs levels, also improved. Furthermore, significant improvements in nutritional parameters (such as weight gain) and a lower insulin resistance index were determined. In contrast, no clear effects were observed in lipid metabolism and oxidative stress biomarkers in the treated group. Conclusions: The results of this research suggest that the retrograded starch from creole beans evaluated could be a potential functional food ingredient capable of enhancing glucose homeostasis in diabetic conditions. Full article

Objectives: The purpose of this study is to evaluate the trend of anthropometric and cardiometabolic risk (CMRs) changes among health professionals over a three-year period at a medical center in Taiwan. Study Design: A 3-year follow-up cohort study design. Methods: This cohort study was conducted from 2019 to 2022 in a single healthcare center. The participants underwent annual physical check-ups for three consecutive years. CMRs were measured using standard methods and weight status change was measured using BMI. We used McNemar test and Wilcoxon Sign Rank test to evaluate the differences within and between subgroups. We used logistic regression to examine the risk of increased CMRs among subgroups of different weight status changes. Results: A total of 2217 participants (1641 females and 576 males) were included in this study, with a mean age of 40.2 ± 10.2 years. During this period, 72 (4.4%) female participants’ weight status changed from normal weight to overweight or obese and 530 (32.3%) remained overweight or obese. Among males, the proportion was 6.8% and 61.1%, respectively (p < 0.01). Participants who remained overweight or obese have more adverse CMRs. Compared to remained normal weight male subjects, the mean systolic blood pressure (131.0 ± 18.1 mmHg) and fasting blood glucose (94.4 ± 13.5 mg/dL) were higher in remained overweight or obese subjects (p < 0.001). Among females, those who remained overweight or obese have 4.01 (95% CI 2.92–5.51) times higher risk for abnormal diastolic blood pressure and 2.98 (95% CI 2.05–4.32) times higher risk for abnormal blood glucose compared to those with remained normal weight. Conclusions: Participants who remained overweight or became obese had more adverse CMRs such as high blood pressure, hyperglycemia, and dyslipidemia during the 3-year follow-up period. Full article

Recently, a growing interest has been focused to the role of vitamin C in chronic diseases. Type 2 Diabetes Mellitus and the Metabolic Syndrome are complex, chronic disorders intrinsically linked by a common underlying element, such as chronic low-grade inflammation and excessive oxidative stress. Vitamin C, or ascorbic acid, is an essential water-soluble micronutrient and a highly potent non-enzymatic antioxidant that is critical for scavenging reactive oxygen species and maintaining cellular redox balance. It represents a cofactor for many enzymes, being involved in many biological functions, such as normal immune system functioning, catecholamine metabolism, dietary iron absorption, and collagen biosynthesis. Individuals with type 2 diabetes mellitus and metabolic syndrome frequently exhibit lower circulating and dietary vitamin C levels compared to healthy controls, a deficiency that may be associated with disease-related inflammation and higher body weight. In this sense, it has been shown that vitamin C improves skeletal muscle insulin sensitivity in experimental settings and modulates critical functions like vascular endothelial health. However, this potential is challenged by the fact that chronic hyperglycemia can interfere with the active cellular uptake and transport of vitamin C, potentially leading to relative intracellular deficiency in diabetic patients regardless of intake. It is interesting to note that different studies have demonstrated an inverse relationship between vitamin C concentrations and the prevalence of metabolic syndrome and type 2 diabetes. Vitamin C supplementation in people with diabetes and metabolic syndrome has controversial effects. While several studies indicate a significant reduction in fasting blood glucose or HbA1c, others revealed no significant effect on insulin resistance. This review aims to explore the pathophysiological role and therapeutic potential of vitamin C in type 2 diabetes and metabolic syndrome. Full article

Background: Acute and chronic hyperglycemia in patients with type 2 diabetes mellitus (T2DM) causes endothelial dysfunction and arterial stiffness, contributing to early mortality from cardiovascular disease (CVD). Although L-citrulline (CIT) supplementation improves endothelial function in older women and decreases fasting glucose in those with T2DM, whether it improves vascular function and blood glucose during acute hyperglycemic states in T2DM is unknown. Methods: We randomized 16 patients with T2DM (age 62 ± 6 years) to consume either CIT (6 g/day) or placebo for 4 weeks. Brachial artery flow-mediated dilation (FMD), brachial and aortic blood pressure, aortic and leg arterial stiffness (pulse wave velocity, PWV), and blood glucose concentration were assessed in the fasted state and 60 min following glucose ingestion (during acute hyperglycemia). Results: Four weeks of L-citrulline supplementation improved FMD, femoral-ankle PWV, aortic systolic blood pressure, and blood glucose concentration in the fasted state compared to placebo (all p < 0.05). During acute hyperglycemia, CIT supplementation increased FMD and reduced femoral-ankle PWV, aortic systolic BP, and glucose levels compared to placebo (all p < 0.05). Conclusions: CIT supplementation is beneficial to improve vascular function and glucose levels during chronic and acute hyperglycemia in middle-aged and older adults with T2DM. Full article

Type 2 diabetes mellitus (T2DM) is a global health challenge characterized by insulin resistance and pancreatic β-cell dysfunction. While human umbilical cord mesenchymal stem cells (HUCMSCs) show therapeutic potential, their efficacy can be limited by the harsh in vivo microenvironment. 20(R)-Rg3, a ginsenoside with anti-inflammatory and antioxidant properties, may enhance HUCMSCs’ function, but the combined effect and mechanism of this “cell-molecule” strategy remain unclear. This study aimed to investigate the therapeutic effects and underlying mechanisms of a combination therapy using 20(R)-Rg3 and HUCMSCs in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2DM mouse model. Diabetic mice were treated with PBS, HUCMSCs alone, or HUCMSCs pre-treated with 20(R)-Rg3. Fasting blood glucose and body weight were monitored. Insulin resistance was assessed via oral glucose tolerance tests (OGTTs) and intraperitoneal insulin tolerance tests (IPITTs). Serum biochemical parameters (lipids, liver and kidney function, insulin, C-peptide) were analyzed. Histopathological examination (H&E, PAS) of the liver, kidney, and pancreas was performed, alongside immunofluorescence for islet hormones. Transcriptomic analysis (RNA-seq) was conducted on HUCMSCs with or without 20(R)-Rg3 pretreatment to elucidate potential signaling pathways. Results demonstrated that the combination significantly reduced hyperglycemia and improved insulin sensitivity more effectively than HUCMSCs alone. It also ameliorated dyslipidemia, enhanced liver and kidney function, promoted glycogen synthesis, and facilitated pancreatic islet “regeneration”. Transcriptomic analysis indicated that the synergistic effect is primarily mediated through activation of the PI3K/Akt signaling pathway. These findings suggest that 20(R)-Rg3 potentiates the therapeutic efficacy of HUCMSCs, providing a promising combinatorial strategy for T2DM treatment. Full article

Poultry have higher blood glucose concentrations, which are 1.5–2 times those of their mammalian counterparts with equivalent body mass, yet do not show any adverse effects. However, the underlying mediators that inhibit systemic inflammation under hyperglycemia are unclear. In this study, chickens and rats were chosen as representatives of poultry and mammals, and the physiological differences in blood glucose regulation between them were investigated under control conditions and streptozotocin (STZ)-induced hyperglycemia, respectively, to explore the internal causes of hyperglycemia without symptoms in poultry. Firstly, the fasting blood glucose (FBG) and glucagon concentrations increased significantly (p < 0.01) and the insulin concentrations decreased when chickens and rats were treated with STZ (p < 0.001). STZ injections in rats resulted in higher oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) levels (p < 0.001), but there was no significant difference in chickens. In addition, the body weight development of STZ-inducted rats was retarded, while it was not the case for chickens receiving STZ. Secondly, high glucose metabolism products, including advanced glycation end products (AGEs) were detected in STZ-inducted rats and chickens. The AGEs concentration in the rats receiving STZ was significantly higher than that in control group rats (p < 0.001); however, there was no significant difference in chickens. Also, the concentrations of free amino acids inhibiting AGEs were further explored, and higher concentrations of taurine, leucine, and lysine were observed in chickens than those observed in rats (p < 0.05). Moreover, the concentrations were decreased significantly in STZ-treated chickens (p < 0.05). Finally, the inflammation in tissues vulnerable to high blood glucose was examined, and it was found that there were significantly increased mRNA and protein expression levels of inflammatory factors such as nuclear factor-κB (NF-κB) and interleukin-1β (IL-1β) in STZ-injected rats (p < 0.001), while there was no obvious effect in STZ-induced chickens. The results revealed the damage and inflammation resulting from STZ-induced hyperglycemia in chickens were significantly lower compared to rats. This may be attributed to the high concentrations of free amino acids in chickens, which inhibit AGE formation by functioning as carbonyl scavengers. This study elucidates the underlying causes of the absence of inflammation in chickens compared to rats under hyperglycemic conditions, offering new insights for controlling diabetic complications. Full article