Search Results (5,410)

Background/Objectives: Predicting post-COVID-19 diabetes is crucial for enhancing patient care and public health. This study investigates the role of metabolic factors in predicting the glycemic outcomes in patients recovering from moderate to severe COVID-19. Methods: We conducted a retrospective analysis of 135 patients without pre-existing diabetes, selected from a cohort of 1980 individuals hospitalized between January 2020 and December 2022. Metabolic parameters, including blood glucose, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), Triglyceride/Glucose (TyG) index, and high-sensitivity C-reactive protein (hs-CRP), were assessed at discharge and followed up after 4 months (T4) and 12 months (T12). Results: Statistical analysis revealed significant correlations of initial glycemia, HOMA-IR, and hs-CRP with the subsequent glycemic levels at T4 and T12. Multiple regression analysis confirmed that initial glycemia, HOMA-IR, and hs-CRP were strong predictors of elevated glycemia, while the TyG index did not show a significant predictive value. Conventional diabetes risk factors, including body mass index (BMI) and lipid profiles, showed low predictive power for post-COVID-19 glycemia. Conclusions: This research highlights the critical role of metabolic and inflammatory pathways in managing glycemic control in COVID-19 patients. Markers like blood glucose, HOMA-IR, and hs-CRP are significant predictors of blood glucose levels, while the TyG index appears less helpful in this context. Early, targeted interventions based on these markers can improve patient outcomes and reduce the risk of post-COVID-19 complications like diabetes. Full article

Exercise is a recognized non-pharmacological treatment for improving glucose homeostasis in type 2 diabetes (T2DM), with resistance exercise (RE) showing promising results. However, the mechanism of RE improving T2DM has not been clarified. This study aims to investigate the effects of RE on glucose and lipid metabolism, insulin signaling, and mitochondrial function in T2DM mice, with a focus on the regulatory role of miR-30d-5p. Our results confirmed that RE significantly improved fasting blood glucose, IPGTT, and ITT in T2DM mice. Enhanced expression of IRS-1, p-PI3K, and p-Akt indicated improved insulin signaling. RE improved glycolipid metabolism, as well as mitochondrial biogenesis and dynamics in skeletal muscle of T2DM mice. We also found that miR-30d-5p was upregulated in T2DM, and was downregulated after RE. Additionally, in vitro, over-expression of miR-30d-5p significantly increased lipid deposition, and reduced glucose uptake and mitochondrial biogenesis. These observations were reversed after transfection with the miR-30d-5p inhibitor. Mechanistically, miR-30d-5p regulates glycolipid metabolism in skeletal muscle by directly targeting SIRT1, which affects the expression of PGC-1α, thereby influencing mitochondrial function and glycolipid metabolism. Taken together, RE effectively improves glucose and lipid metabolism and mitochondrial function in T2DM mice, partly through regulating the miR-30d-5p/SIRT1/PGC-1α axis. miR-30d-5p could serve as a potential therapeutic target for T2DM management. Full article

Parkinson’s disease (PD) is a prevalent neurodegenerative condition for which there are symptomatic treatments but no disease-modifying therapies (DMTs). Extensive research over the years has highlighted the need for a multi-target DMT approach in PD that recognizes the various risk factors and their intricate interplay in contributing to PD-related neurodegeneration. Widespread risk factors, such as emotional stress and metabolic factors, have increasingly become focal points of exploration. Our review aims to summarize interactions between emotional stress and selected key players in metabolism, such as insulin, as potential mechanisms underlying neurodegeneration in PD. Full article

Background: Type 2 diabetes mellitus is a metabolic disorder characterized by insulin resistance (IR), which is prevalent worldwide and has significant adverse health effects. Metformin is commonly prescribed as a pharmacological treatment. Physical exercise is also recognized as an effective regulator of glycemia, independent of metformin. However, the effects of inter-day concurrent training (CT)—which includes both endurance and resistance exercises—combined with metformin treatment on metabolic markers and cardiorespiratory fitness in individuals with IR remain controversial. Objective: This study aimed to analyze the effects of a 12-week inter-day CT program on metabolic markers and cardiorespiratory fitness in overweight/obese individuals with IR, both with and without metformin treatment. Additionally, inter-individual responses to CT were examined. Materials and Methods: Data from the 2022–2023 Obesity Center database were retrospectively analyzed. According to the eligibility criteria, 20 overweight/obese individuals diagnosed with IR participated in a 12-week CT program (three weekly sessions: two endurance and one resistance exercise session). Participants were divided into three groups: the exercise group (E-G: n = 7, 32.86 ± 8.32 years, 85.2 ± 19.67 kg), the exercise–metformin group (E-MG: n = 6, 34.83 ± 12.91 years, 88.13 ± 12.66 kg), and the metformin-only control group (M-G: n = 7, 34.43 ± 13.96 years, 94.23 ± 13.93 kg). The M-G did not perform physical exercise during the 12 weeks but continued pharmacological treatment. Body composition, metabolic markers, and cardiorespiratory fitness were assessed before and after the 12-week CT program. Results: A group-by-time interaction was observed for fasting insulin (F_2,17 = 34.059, p < 0.001, η²_p = 0.88), the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) (F_2,17 = 35.597, p < 0.001, η²_p = 0.80), and maximal fat oxidation (MFO) (F_2,17 = 4.541, p = 0.026, η²_p = 0.348) following the CT program. The maximal oxygen uptake (VO2_max) showed significant improvements in the E-G (F = 4.888, p = 0.041, ∆+13.3%). Additionally, the percentage of fat mass (%FM) and body mass (BM) were significantly reduced across all groups (F = 125.244, p < 0.001 and F = 91.130, p < 0.001, respectively). The BM decreased by ∆−9.43% in the E-G (five responders, Rs), ∆+9.21% in the EM-G (5 Rs), and ∆+5.15% in the M-G (3 Rs). The %FM was reduced in the E-G by ∆−22.52% (seven Rs). Fasting insulin and the HOMA-IR significantly improved in both the E-G and EM-G, with fasting insulin showing a ∆−82.1% reduction in the E-G (five Rs) and a ∆−85% reduction in the EM-G (six Rs). Similarly, the HOMA-IR improved by ∆+82.6% in the E-G (three Rs) and by ∆+84.6% in the EM-G (six Rs). Conclusions: The 12-week inter-day concurrent training program, whether combined with metformin or not, was similarly effective in improving metabolic markers in patients with insulin resistance as metformin treatment alone. Both exercise groups demonstrated a significant reduction in insulin sensitivity and an increase in maximal fat oxidation. Meanwhile, exclusive pharmacological treatment with metformin markedly decreased cardiorespiratory fitness, and consequently, fat oxidation. Full article

Background: In this study, we aimed to investigate the relationship between diabetic nephropathy (DN) and triglyceride/glucose (TyG) index and triglyceride/high-density lipoprotein cholesterol ratio (Tg/HDL-C) as surrogate markers of insulin resistance. Method: Medical records of 15,378 individuals between February 2019 and May 2024 were examined. Serum glucose, Tg, HDL-C, HbA1c, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio (UACR) were evaluated and the TyG index and TG/HDL-C ratios were calculated for each individual. DN was defined as a UACR ≥ 30 mg/g and/or eGFR <60 mL/min/1.73 m². Results: Of 10,714 patients, DN was detected in 3763 (35.1%). Females had 10% higher odds of developing DN compared to males. A TyG index at or above the determined cutoff point (9.58) indicated a risk of DN and the sensitivity and specificity values were 44.01% and 71.28%, respectively. The risk of DN was 1.95 times higher in individuals with a TyG index value of ≥9.58 compared to those with a TyG index <9.58. While the Tg/HDL ratio was significant in detecting DN in the univariate analysis (odds ratio (OR) 1.59; 95% confidence interval 1.46–1.73), this significance was not found in the multivariate analysis (OR 1.15; 95% confidence interval 0.94–1.40). Conclusions: A high TyG index is associated with DN in patients with type 2 diabetes and it might be a potential marker in predicting DN. Full article

Background: Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder characterized by insulin resistance and inadequate insulin production. Given the increased frequency of T2DM and the health issues it can cause, there is an increasing need to develop alternative T2DM management strategies. One such approach is Chinese Medicine (CM), a complementary therapy widely used in T2DM treatment. Given the emphasis on gut microbiota in current research, studying CM in the treatment of T2DM via gut microbiota modulation could be beneficial. Scope and approach: The use of various CM methods for managing T2DM via gut microbiota modulation is highlighted in this review. Following an introduction of the gut microbiota and its role in T2DM pathogenesis, we will review the potential interactions between gut microbiota and T2DM. Thereafter, we will review various CM treatment modalities that modulate gut microbiota and provide perspectives for future research. Key findings and discussion: In T2DM, Akkermansia, Bifidobacterium, and Firmicutes are examples of gut microbiota commonly imbalanced. Studies have shown that CM therapies can modulate gut microbiota, leading to beneficial effects such as reduced inflammation, improved metabolism, and improved immunity. Among these treatment modalities, Chinese Herbal Medicine and acupuncture are the most well-studied, and several in vivo studies have demonstrated their potential in managing T2DM by modulating gut microbiota. However, the underlying biomolecular mechanisms of actions are not well elucidated, which is a key area for future research. Future studies could also investigate alternate CM therapies such as moxibustion and CM exercises and conduct large-scale clinical trials to validate their effectiveness in treatment. Full article

Background and Objectives: Adjuvant treatment with aromatase inhibitors (AIs) in breast cancer (BC) survivors can cause adverse effects such as metabolic syndrome (MS) (insulin resistance, central obesity, atherogenic dyslipidemia, and hypertension) associated with morbidity and premature mortality. We evaluate the effect of a multimodal program based on physical exercise and health education on MS and health-related quality of life (QoL) in postmenopausal women with BC under AIs. Methods: A total of 56 postmenopausal women, diagnosed with BC, aged 60 years or older (mean age 67.2 years) and on hormonal treatment with AIs, were included in the multimodal physical exercise and health education program, and evaluated before and after their participation. The assessment of the five criteria of the MS included the following: waist circumference, high blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Two main instruments were used to evaluate the impact of the intervention on QoL: the EORTC QLQ C30 (questionnaire for cancers in general) and the EORTC QLQ BR23 (specifically for breast cancer patients). The EuroQol 5D (EQ-5D) was also used to compare these results. Results: The percentage of women meeting the MS criteria was 37.7% at baseline and fell to 15.1% at 3 months after the intervention (p = 0.02). The intervention significantly reduced hypertension (p < 0.001), central obesity (p < 0.001), and the concentration of triglycerides (p = 0.016). No significant changes were observed in fasting glucose and HDL concentration. A statistically significant improvement was found in QoL (on both the QLQ30 and BR23 scales). A multivariate regression model analysis identified marital status (being married) (95% CI: 1.728–131.615, p = 0.014), and percentage of attendance at health education sessions (95% CI: 1.010–1.211, p = 0.029) as positive predictive variables of improvement in MS. Conclusions: The implementation of multimodal, community-based programs of physical exercise and health education improve the prevalence of MS and specific criteria of MS and QoL in postmenopausal women with breast cancer receiving AI treatment. Full article

Oxidized low-density lipoproteins (ox-LDLs) are involved in atherosclerotic plaque formation and progression and have been linked to insulin resistance (IR). Myeloperoxidase is a potent oxidant of lipoproteins related to atherogenic risk. High-density lipoproteins (HDLs) are considered antioxidants due to their association with paraoxonase 1 (PON1). However, HDL can also be oxidized (ox-HDL), and its relationship with IR has not been described. This study evaluated the relationship between circulating levels of myeloperoxidase and paraoxonase 1, diet, and serum levels of ox-LDL and ox-HDL in young people with IR. This cross-sectional study examined 136 young subjects (67 and 69 with and without insulin resistance, respectively). Serum levels of ox-LDL, ox-HDL, myeloperoxidase, and PON1 were quantified using an enzyme-linked immunosorbent assay. The nutritional dietary content of the foods was determined with a food frequency questionnaire, which was analyzed with Nutrimind 2013 software. Serum ox-HDL levels were higher in young subjects without IR than those with IR (p = 0.031). Women with IR presented increased ox-LDL levels compared with women without IR (p = 0.012) and men with IR (p < 0.001). In the IR group, serum ox-LDL levels were negatively correlated with total cholesterol, triglycerides, and LDL-C, whereas the correlation was positive in the insulin-sensitive group. Consumption of vitamins B1 and B2 was related to increased HDL-C levels, while higher ox-LDL levels were related to vitamin K intake. In addition, low energy consumption and phosphorus increased PON1 levels. The results suggest that insulin resistance in young women may promote lipoprotein oxidation, and the intake of B complex vitamins may have an antiatherogenic effect. Full article

Insulin resistance, stem cell dysfunction, and muscle fiber dystrophy are all age-related events in skeletal muscle (SKM). However, age-related changes in insulin isoforms and insulin receptors in myogenic progenitor satellite cells have not been studied. Since SKM is an extra-pancreatic tissue that does not express mature insulin, we investigated the levels of insulin receptors (INSRs) and a novel human insulin upstream open reading frame (INSU) at the mRNA, protein, and anatomical levels in Baltimore Longitudinal Study of Aging (BLSA) biopsied SKM samples of 27–89-year-old (yrs) participants. Using RT-qPCR and the MS-based selected reaction monitoring (SRM) assay, we found that the levels of INSR and INSU mRNAs and the proteins were positively correlated with the age of human SKM biopsies. We applied RNAscope fluorescence in situ hybridization (FISH) and immunofluorescence (IF) to SKM cryosections and found that INSR and INSU were co-localized with PAX7-labeled satellite cells, with enhanced expression in SKM sections from an 89 yrs old compared to a 27 yrs old. We hypothesized that the SKM aging process might induce compensatory upregulation of INSR and re-expression of INSU, which might be beneficial in early embryogenesis and have deleterious effects on proliferative and myogenic satellite cells with advanced age. Full article

Obesity is characterized by low-grade inflammation that originates predominantly from the expanding visceral adipose tissue, in which adipocytes respond to lipid overload with hypertrophy, and consequently die by apoptosis. Recruited adipose tissue macrophages (ATMs) take up the excess lipids and remove the dead cells; however, long-term exposure to high concentrations of lipids alters their phenotype to M1-like ATMs that produce pro-inflammatory cytokines and resistin leading to insulin resistance and other obesity-related pathologies. Mer tyrosine kinase is expressed by macrophages and by being an efferocytosis receptor, and by suppressing inflammation, we hypothesized that it might play a protective role against obesity. To our surprise, however, the loss of Mer protected mice against high-fat diet (HFD)-induced obesity. We report in this paper that Mer is also expressed by adipocytes of both white and brown adipose tissues, and while its activity facilitates adipocyte lipid storage both in vitro and in vivo in mice exposed to HFD, it simultaneously attenuates thermogenesis in the brown adipose tissue contributing to its ‘whitening’. Our data indicate that Mer is one of the adipocyte tyrosine kinase receptors, the activity of which contributes to the metabolic decision about the fate of excess lipids favoring their storage within the body. Full article

Background and Objectives: Obesity-related chronic inflammation may lead to neuroinflammation and neurodegeneration. This study aimed to evaluate the neurometabolic profile of obese patients using cerebral multivoxel magnetic resonance spectroscopy (mvMRS) and assess correlations between brain metabolites and obesity markers, including body mass index (BMI), waist circumference, waist-hip ratio, body fat percentage, and indicators of metabolic syndrome (e.g., triglycerides, HDL cholesterol, fasting blood glucose, insulin, and insulin resistance index (HOMA-IR)). Materials and Methods: This prospective study involved 100 participants, stratified into two groups: 50 obese individuals (BMI ≥ 30 kg/m²) and 50 controls (18.5 ≤ BMI < 25 kg/m²). Anthropometric measurements, body fat percentage, and biochemical markers were evaluated. All subjects underwent long- and short-echo mvMRS analysis of the frontal and parietal supracallosal subcortical and deep white matter, as well as the cingulate gyrus, analyzing NAA/Cr, Cho/Cr, and mI/Cr ratios, along with absolute concentrations of NAA and Cho. Results: Obese participants exhibited significantly decreased NAA/Cr and Cho/Cr ratios in the deep white matter of the right cerebral hemisphere (p < 0.001), while absolute concentrations of NAA and Cho did not differ significantly between groups (p > 0.05). NAA levels showed negative correlations with more reliable obesity parameters (waist circumference and waist-to-hip ratio) but not with BMI, particularly in the deep frontal white matter and dorsal anterior cingulate gyrus of the left cerebral hemisphere. Notably, insulin demonstrated a significant negative impact on NAA (ρ = −0.409 and ρ = −0.410; p < 0.01) and Cho levels (ρ = −0.403 and ρ = −0.392; p < 0.01) at these locations in obese individuals. Conclusions: Central obesity and hyperinsulinemia negatively affect specific brain regions associated with cognitive and emotional processing, while BMI is not a reliable parameter for assessing brain metabolism. Full article

Background: Metabolic dysfunction-associated liver disease (MASLD) and alcohol-associated liver disease (ALD) are among the leading causes of liver disease worldwide. The exact roles of epigenetic factors in both diseases remains largely unknown. In this context, liver DNA methylation remains a field that requires further exploration and understanding. Methods: We performed a systematic review of liver DNA methylation in humans with MASLD or ALD using Ovid MEDLINE, Ovid Embase, and Cochrane Library. We included human studies where liver DNA methylation was assessed in patients with MASLD and/or ALD. The Rayyan platform was used to select studies. Risk of bias was assessed with the “risk of bias in non-randomized studies of interventions” tool, ROBINS-I. We performed pathway analysis using the most important differentially methylated genes selected in each article. Results: Fifteen articles were included in this systematic review. The risk of bias was moderate to serious in all articles and bias due to confounding and patient selection was high. Sixteen common pathways, containing differentially methylated genes, including cancer pathways, were identified in both diseases. Conclusions: There are common pathways, containing differentially methylated genes, in ALD and MASLD, such as pathways in cancer and peroxisome proliferator-activated receptor (PPAR) signaling pathways. In MASLD, the insulin signaling pathway is one of the most important, and in ALD, the MAPK signaling pathway is the most important. Our study adds one more piece to the puzzle of the mechanisms involved in steatotic liver disease. Full article

Colchicine is an alkaloid traditionally used to treat inflammatory conditions such as gout and familial Mediterranean fever. Currently, there are proposals for the use of this drug in several other situations, such as cardiovascular and liver diseases and diabetes. In this study, the current literature on the potential of colchicine in the treatment of obesity and metabolic syndrome (MS) was evaluated. The inhibitory action of the NLRP3 inflammasome and other processes, such as reductions in the migration and activation of immune system cells, are effects observed in both in vitro studies and animal models related to colchicine, as well as the promotion of mechanisms of the intensification of lipid metabolism, the reduction of tissue fibrosis, and the reduction of serum glucose and triglycerides. These factors are associated with changes in the prognoses of patients with MS, which, together with obesity, has a high association with inflammatory mechanisms for its maintenance and secondary impairments to homeostasis. In humans, clinical research has rarely addressed the use of colchicine in obesity and MS, with only one pilot randomized clinical trial having been conducted, which identified a beneficial anti-inflammatory effect on endothelial function and the process of insulin resistance in this population. However, it is not yet possible to extrapolate its findings and apply its results to a broader context. Given the potential of this “ancient drug” in various pathological contexts and its good tolerability, it is important that its properties continue to be investigated and that more clinical studies be conducted to expand the therapeutic applications of this low-cost substance in patients with obesity and MS. Full article

Background/Objectives: Polycystic ovary syndrome is a common endocrine disorder in women of reproductive age characterized by insulin resistance and hormonal imbalances. Recent research suggests that probiotics and synbiotics may improve these parameters by modulating the gut microbiota. This study systematically reviewed randomized clinical trials evaluating the impact of probiotic, prebiotic, and synbiotic supplementation on insulin resistance and hormonal parameters in women with PCOS. Methods: Exhaustive searches were conducted in PubMed, Cochrane CENTRAL, Scopus, Web of Science, and Embase, following PRISMA guidelines. Randomized trials assessing supplementation with probiotics, prebiotics, or synbiotics for at least 8 weeks in women diagnosed with PCOS according to the Rotterdam criteria were included. Data on participants, interventions, and outcomes related to insulin resistance and hormones were extracted. Results: Eleven studies from Iran involving overweight or obese women aged 15 to 48 were included. Probiotic and synbiotic supplementation showed significant improvements in insulin resistance (reductions in HOMA-IR, fasting glucose, and insulin), lipid profiles (decreased LDL and triglycerides; increased HDL), and hormonal balance (increased SHBG, decreased total testosterone). Synbiotics had more pronounced effects than probiotics or prebiotics alone. Adherence was high, and side effects were minimal. Conclusions: Despite promising results, limitations such as small sample sizes, homogeneous populations, and short intervention durations limit the generalization of the findings. Larger, longer, multicenter trials with diverse populations and standardized methodologies are needed to confirm the efficacy and safety of synbiotics in managing PCOS. Integrating these interventions could improve clinical management and quality of life for affected women, but additional evidence is required to support widespread use. Full article