Nutrition & Diabetes最新文献

Objective: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common complication of type 2 diabetes mellitus (DM). The transcription factor zinc fingers and homeoboxes 2 (ZHX2) has been implicated in the pathogenesis of chronic liver diseases, yet its precise role and underlying mechanism in DM-induced hepatic injury remain poorly elucidated.

Methods: To investigate this, we used a high-fat diet (HFD) and streptozotocin (STZ) administration to create a DM model in mice, while high glucose (HG) exposure was used to simulate DM in vitro. Through various experiments such as luciferase reporter assay, chromatin immunoprecipitation, RNA immunoprecipitation, and rescue experiments, we aimed to uncover the mechanisms involving ZHX2.

Results: Our findings revealed that ZHX2 was lower and YTHDF2 was higher in the livers of DM mice and HG-induced Huh7 cells. ZHX2 overexpression rescued DM-induced liver injury. ZHX2 overexpression also reversed DM-induced hepatic ferroptosis in vivo and in vitro. Mechanistically, YTHDF2 recognized m6A-modified ZHX2 mRNA and promoted its degradation. In turn, ZHX2 inhibited the transcription of YTHDF2 by binding to its promoter region. Knockdown of ZHX2 led to increased ferroptosis in Huh7 cells through activating YTHDF2-induced GPX4 and SLC7A11 degradation.

Conclusion: These findings highlight the involvement of the ZHX2-YTHDF2-ferroptosis pathway in DM-induced liver injury and suggest that targeting this pathway may hold therapeutic potential for improving such injuries.

Several studies have illustrated the association of the triglyceride glucose (TyG) index with in-hospital and intensive care unit (ICU) mortality. However, no studies have compiled this evidence and reached a conclusion. This study aimed to quantify the association of the TYG index with the risk of in-hospital and ICU mortality. An extensive search of databases including PubMed, Scopus, and Web of Science, was performed up to 21 Jan 2024. Nineteen studies were included in the meta-analysis. The outcomes were in-hospital mortality in 18 studies and ICU mortality in 8 studies. Among the 42,525 participants, 5233 in-hospital and 1754 ICU mortality cases were reported. The pooled analysis revealed that each unit increase in the TYG index was associated with a 33% and 45% increase in the risk of in-hospital (RR = 1.33; 95% CI: 1.23, 1.43; I squared = 90.3%) and ICU (RR: 1.45; 95% CI: 1.25, 1.67; I squared = 44.8%) mortality, respectively. Subgroup analysis revealed a stronger association between the TYG index and the risk of in-hospital mortality in patients with cardiovascular diseases than in those with cerebrovascular diseases (P_{heterogeneity between Groups} = 0.014). The findings of this study showed a positive association between the TyG index and the risk of in-hospital and ICU mortality. (PROSPERO registration ID: CRD420245414390).

Background: Type 2 diabetes mellitus (T2DM) is currently a major global public health problem. Although disease remission is possible, few biomarkers have been identified which can help us select the diet that best promotes remission. Our aim was to study the potential of miRNAs as a tool to apply the Mediterranean diet or the low-fat diet in order to achieve T2DM remission in patients with coronary heart disease.

Methods: From the CORDIOPREV study (n = 1002), a prospective, randomized, single-blind, controlled dietary intervention trial, all patients newly diagnosed with T2DM (n = 190) at baseline were included in the present study. Of these, after adhering to a low fat or Mediterranean diet for 60 months, 73 patients showed T2DM remission (Responders) and 110 continued with the disease (Non-responders). Plasma levels of 56 miRNAs were determined by RT-PCR. Generalized linear model, ROC curves and COX regression analyses were performed.

Results: We observed that patients with low baseline plasma levels of miR-let7b-3p showed a high probability of T2DM remission after the consumption of a low-fat diet. In addition, patients with high levels of miR-141-5p, miR-182, and miR-192 at baseline showed a high probability of T2DM remission after following the Mediterranean diet. Scores built using miRNAs and clinical variables showed that high levels of a low-fat diet score and a high Mediterranean diet score were associated with a high probability of T2DM remission.

Conclusion: MiRNAs could be used as a tool for selecting the most efficient nutritional therapy (mediterranean or low-fat diet) to achieve T2DM remission in patients with coronary heart disease.

Objective: To assess whether the role of selenium on pre-diabetes is differential by age, given comorbidities and decreased β-cell function in older adults.

Research design and methods: We evaluated the cross-sectional association of blood selenium with the homeostatic model assessment for insulin resistance (HOMA-IR) and β-cell function (HOMA-β) in middle-aged (Aragon Workers Health Study [AWHS], N = 1186), and older (Seniors ENRICA [Study on Nutrition and Cardiovascular Risk in Spain]-2 [SEN-2], N = 915) diabetes-free adults. A subsample of participants from AWHS (N = 571) and SEN-2 (N = 603) had glucose and insulin repeated measurements for longitudinal analysis. We validated the cross-sectional dose-response associations in the 2011-2018 National Health and Nutrition Examination Survey (NHANES, N = 1317 middle age and N = 960 older) participants. Selenium was measured in whole blood with ICP-MS in AWHS, SEN-2 and NHANES.

Results: The cross-sectional geometric mean ratios (95% confidence intervals) per two-fold selenium increase were 1.09 (1.01, 1.19) for HOMA-IR and 1.15 (1.06, 1.24) for HOMA-β in AWHS; and 1.13 (0.98, 1.31) and 1.03 (0.90, 1.18), in SEN-2. The cross-sectional dose-response associations were consistent in NHANES, with mostly increasingly positive trends for both HOMA endpoints in younger adults and a plateau at levels >~150 μg/L in older adults. The longitudinal dose-response consistently showed positive associations at high selenium dose for both HOMA endpoints in the younger, but not the older, study population.

Conclusions: Increased blood selenium was associated with increased insulin resistance and β-cell function in middle-aged, but not in older individuals, especially for β-cell function. The results suggest that selenium-associated insulin resistance might induce compensatory increased β-cell function at younger ages, being this compensatory capacity decreased with aging.

Background: Our mechanistic understanding on metabolic beneficial effects of dietary polyphenols has been hampered for decades due to the lack of functional receptors for those compounds and their extremely low plasma concentrations. Recent studies by our team and others suggest that those dietary polyphenols target gut microbiome, and gut-liver axis and that hepatic fibroblast factor 21 (FGF21) serves as a common target for various dietary interventions.

Methods: Utilizing liver-specific FGF21 null mice (lFgf21^-/-), we are asking a straightforward question: Is hepatic FGF21 required for curcumin or resveratrol, two typical dietary polyphenols, in exerting their metabolic beneficial effect in obesogenic diet-induced obesity mouse models.

Results: On low-fat diet feeding, no appreciable defect on glucose disposal was observed in male or female lFgf21^-/- mice, while fat tolerance was moderately impaired in male but not in female lFgf21^-/- mice, associated with elevated random and fasting serum triglyceride (TG) levels, and reduced hepatic expression of Ehhadh and Ppargc1a, which encodes the two downstream effectors of FGF21. On high-fat-high-fructose (HFHF) diet challenge, Fgf21^fl/fl but not lFgf21^-/- mice exhibited response to curcumin intervention on reducing fasting serum TG, and on improving fat tolerance. Resveratrol intervention also affected FGF21 expression or its downstream effectors. Metabolic beneficial effects of resveratrol intervention observed in HFHF diet-challenged Fgf21^fl/fl mice were either absent or attenuated in lFgf21^-/- mice.

Conclusion and significance: We conclude that hepatic FGF21 is required for curcumin or resveratrol in exerting their major metabolic beneficial effect. The recognition that FGF21 as the common target of dietary intervention, demonstrated in current as well as previous investigations, brings us a novel angle in understanding metabolic disease treatment and prevention. It remains to be further explored how various dietary interventions regulate FGF21 expression and function, via certain common or unique gut-liver or gut-brain-liver axis.

Background: It is important to detect the predictors of prediabetes progressing to diabetes. Although polyols affect glycometabolism, little is known about the association between fasting serum polyol levels of participants with habitual diet and the risk of prediabetes progressing to type 2 diabetes.

Methods: In this nested case-control study, 180 participants who developed from prediabetes to type 2 diabetes (progressors), and 180 matched controls (non-progressors) with prediabetes during a 3.5-year follow-up were enrolled. The baseline levels of serum polyols in the fasting state were quantified using time-of-flight mass spectrometry. Multivariate conditional logistic regression was performed to assess the effects of the differential polyol levels on the risk of incident diabetes from prediabetes.

Results: The baseline fasting xylitol levels, but not sorbitol or erythritol levels, were higher in non-progressors than in progressors (P < 0.001). Non-progressors, in comparison with progressors, had significantly higher proportions within the third tertile of xylitol levels (71/180 non-progressors [39.4%] vs. 49/180 progressors [27.2%]). After adjusting for potential confounders, the odds ratio of risk for incident diabetes in the highest tertile of xylitol levels was 0.338 (95% confidence interval 0.182-0.628), when compared with those in the lowest tertile. In addition, the association between xylitol levels and incident diabetes was persistent in those with fasting hyperglycemia and both fasting and 2h-post-glucose-load hyperglycemia, but not in the isolated 2h-post-glucose-load hyperglycemia.

Conclusions: Elevated baseline fasting serum xylitol levels are associated with a lower risk of prediabetes progressing to diabetes. This association was particularly evident in those with fasting hyperglycemia. These findings suggest that fasting serum xylitol levels may serve as an important predictor and protective factor against the development of diabetes.

Background: As all kown, both hypovitaminosis D and insulin resistance (IR) have been linked to adiposity. However, the extent of adiposity's mediating influence on the hypovitaminosis D-IR relationship among adolescents remains to be elucidated. Additionally, the intricate effects of obesity and blood lipid profiles on IR are not yet fully understood.

Methods: We conducted a comprehensive analysis of NHANES data from 2011 to 2018, examining the correlation between adiposity indices such as Body Mass Index (BMI), Fat Mass Index (FMI, defined as the ratio of fat mass to height squared), hypovitaminosis D, and IR. We employed the XGBoost algorithm to identify key factors significantly influencing IR, thereby deepening our insight into the link between adiposity and insulin resistance. Furthermore, we applied mediation analysis to precisely assess the mediating role of adiposity indices in the relationship between hypovitaminosis D and IR.

Results: Our study revealing significant correlations between adiposity indices, hypovitaminosis D, and IR after variable adjustment. Notably, subgroup analysis indicated a pronounced hypovitaminosis D -adiposity association in female adolescents, which was not observed in males. The XGBoost algorithm pinpointed obesity and blood lipid indicators significantly affecting IR, with total fat mass, triglyceride, cholesterol, BMI, and FMI ranked by descending importance. Mediation analysis disclosed that adiposity indices mediate a substantial portion of the hypovitaminosis D -IR relationship, with FMI (43.84%, p < 0.001) and BMI (40.87%, p < 0.001) showing significant mediating effects.

Conclusion: The study confirmed significant correlations between adiposity indices, hypovitaminosis D, and IR in adolescents, with gender-specific differences in the hypovitaminosis D -adiposity link. Cholesterol was found to have a more substantial influence on IR than BMI and FMI. Furthermore, FMI was identified as a more potent mediator of the hypovitaminosis D-IR relationship compared to BMI, highlighting its importance in the pathophysiology of insulin resistance in adolescents.

Background: Episodic memory decline is a common complication of type 2 diabetes (T2D). To comprehensively explore the neural mechanisms underlying it, we aimed to explore the sequence that episodic memory-related behavioral and brain-imaging biomarkers appear abnormal in the progression of T2D.

Methods: We enrolled 62 healthy controls and 110 patients with T2D. The California Verbal Learning Test, Montreal cognitive assessment, and Stroop color word test was used to assess the episodic memory, general cognitive function, and executive function. Principal component analysis was applied to extract behavioral biomarkers. Imaging biomarkers included structural and functional MRI features of the entorhinal cortex-hippocampus and hippocampus-anterior cingulate cortex pathways. We used a novel discriminative event-based model to determine the sequence that memory-related biomarkers appear abnormal and estimate the stage of memory decline.

Results: T2D patients exhibited poorer memory, general cognitive function, and executive function compared to healthy controls after controlling age, sex, and education level. In the progression of T2D, functional interaction between brain regions showed abnormalities first, followed by memory tests, the cerebral spontaneous neural activity, and finally the gray matter volume. Besides, abnormalities appeared earlier in the entorhinal cortex than in the anterior cingulate cortex. Later stage of memory decline was distributed in older patients with T2D and was associated with higher systolic blood pressure, postprandial blood glucose, and low-density lipoprotein.

Conclusions: In T2D, behavioral and brain imaging biomarkers of episodic memory appear abnormal in a specific sequence, and the stage of memory decline was closely associated with old age and vascular risk factors.

Clinical trial registration: NCT02420470, ClinicalTrials.gov ( https://www.

Clinicaltrials: gov/ ).

Background: Diabetes mellitus (DM) and arthritis are prevalent conditions worldwide. The intricate relationship between these two conditions, especially in the context of various subtypes of arthritis, remains a topic of interest.

Objective: To investigate the relationship between diabetes and arthritis, with a focus on Rheumatoid Arthritis (RA), using data from the National Health and Nutrition Examination Survey (NHANES) and Mendelian Randomization (MR) analysis.

Methods: Data from six consecutive NHANES cycles from 2007 to 2018 were analyzed, involving 30,062 participants after applying exclusion criteria. The association between diabetes and arthritis was assessed using logistic regression. MR was employed to determine the causal relationship between the two conditions using Genome-Wide Association Study (GWAS) data.

Results: The prevalence of arthritis in diabetic patients was almost twice that of non-diabetic patients. Logistic regression showed a significant gross association between arthritis and diabetes with an OR of 2.90 (95% CI: 2.66-3.16). After adjusting for age, gender, race, and other factors, the association yielded an OR of 1.14 (95% CI: 1.00-1.29, p < 0.05). MR analyses indicated a significant association between Type 1 Diabetes and RA (OR = 1.407, p = 0.002), but no significant correlation was observed for Type 2 Diabetes.

Conclusion: There is an association between diabetes and arthritis, with potential genetic links between Type 1 Diabetes and RA.

Background: Studies have proposed that probiotic intake may ameliorate some of the clinical components of metabolic syndrome (MetS). This study aimed to determine the effects of a new developed synbiotic yogurt containing Lactobacillus plantarum, Lactobacillus pentosus, and Chloromyces marcosianos yeast on the components of MetS in adults with MetS.

Methods: In this randomized, placebo-controlled, clinical trial, 44 participants were divided into two groups to receive 300 grams of synbiotic yogurt or regular yogurt daily for 12 weeks. Anthropometric measurements, blood pressure, and biochemical parameters evaluated before and after the intervention.

Results: Daily consumption of synbiotic yogurt containing L. plantarum, L. pentosus, and C. marcosianos yeast in adults with MetS caused a significant decrease in the levels of fasting blood glucose (FBG) (p = 0.005), fasting insulin (p = 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) index (p < 0.001), waist to hip ratio (WHR) (p = 0.02) and systolic blood pressure (p = 0.008) in the intervention group compared to the control group.

Conclusions: According to the findings of this study, daily consumption of the synbiotic yogurt was associated with improvements in insulin resistance, systolic blood pressure and WHR, which could be beneficial in patients with MetS.