Metabolically healthy obesity is associated with higher risk of both hyperfiltration and mildly reduced estimated glomerular filtration rate: the role of serum uric acid in a cross-sectional study.

BACKGROUND: The impact of metabolically healthy obesity (MHO) on kidney dysfunction remains debatable. Moreover, few studies have focused on the early stages of kidney dysfunction indicated by hyperfiltration and mildly reduced eGFR. Thus, we aimed to investigate the association between the MHO and early kidney dysfunction, which is represented by hyperfiltration and mildly reduced estimated glomerular filtration rate (eGFR), and to further explore whether serum uric acid affects this association. METHODS: This cross-sectional study enrolled 1188 residents aged ≥ 40 years old from Yonghong Communities. Metabolically healthy phenotypes were categorized based on Adult Treatment Panel III criteria. Obesity was defined as body mass index (BMI) ≥ 25 kg/m2. Mildly reduced eGFR was defined as being in the range 60 < eGFR ≤ 90 ml/min/1.73m2. Hyperfiltration was defined as eGFR > 95th percentile after adjusting for sex, age, weight, and height. RESULTS: Overall, MHO accounted for 12.8% of total participants and 24.6% of obese participants. Compared to metabolically healthy non-obesity (MHNO), MHO was significantly associated with an increased risk of mildly reduced eGFR (odds ratio [OR] = 1.85, 95% confidence interval [CI] 1.13-3.01) and hyperfiltration (OR = 2.28, 95% CI 1.03-5.09). However, upon further adjusting for uric acid, the association between the MHO phenotype and mildly reduced eGFR was reduced to null. Compared with MHNO/non-hyperuricemia, MHO/non-hyperuricemia was associated with an increased risk of mildly reduced eGFR (OR = 2.04, 95% CI 1.17-3.58), whereas MHO/hyperuricemia was associated with an observably increased risk (OR = 3.07, 95% CI 1.34-7.01). CONCLUSIONS: MHO was associated with an increased risk of early kidney dysfunction, and the serum uric acid partially mediated this association. Further prospective studies are warranted to clarify the causality.

Association between serum lipoprotein(a) and mildly reduced eGFR: a cross-sectional study.

Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease (CVD) and aortic stenosis. However, the data on the relationship between Lp(a) and mildly reduced estimated glomerular filtration rate (eGFR) has been disputed. This study was conducted to assess the relationship between Lp(a) concentrations and mildly reduced eGFR in healthy subjects.This community-based, cross-sectional study enrolled 1,064 volunteers aged ≥ 40 years who lived in Yonghong Community, Zhonglou District, Changzhou, China, between December 2016 and December 2017. A mildly reduced eGFR was defined as eGFR between 60 and 90 mL/min/1.73m2. A standardized questionnaire and biochemical measurements were used to gather information about participants. The serum concentration of Lp(a) was determined using the latex-enhanced immunoturbidimetric test. Of the total study population, 34.8% (n = 370) were men, and the mean age was 66.8 ± 8.5 years. A significant association existed between Lp(a) levels and the risk of mildly reduced eGFR. Individuals with the highest tertile of Lp(a) had higher odds of mildly reduced eGFR after adjusting for various confounders (adjusted odds ratio [OR]: 1.80, 95% confidence interval [CI]: 1.24-2.60, P = 0.0025) compared to those with the lowest tertile of Lp(a). Multivariable logistic regression of studies in which Lp(a) was presented as continuous variables showed consistent results (adjusted OR: 1.23 for 1-SD increment of Ln-Lp(a), 95% CI: 1.05-1.43). Subgroup analyses showed that study characteristics such as age, sex, obesity, diabetes, and hypertension status did not significantly affect the association (P for all interactions > 0.05). These results suggest that higher serum Lp(a) level was an independent risk factor for mildly reduced eGFR.

Alterations of gut microbiome in patients with type 2 diabetes mellitus who had undergone cholecystectomy.

Patients with type 2 diabetes mellitus (T2DM) have a high risk of developing cholecystic disease. The gut microbiota has been shown to be strongly associated with cholecystectomy and T2DM pathogenesis. However, alterations of the gut microbiome in patients with T2DM who had undergone cholecystectomy remain unexplored. In this study, the gut microbiomes of 14 long-term patients with T2DM who had undergone cholecystectomy (T2DIIC group) and 21 age- and/or sex-matched subjects with new-onset (T2DI group) and long-term (T2DII group) T2DM without cholecystectomy were assessed using 16S rRNA gene sequencing of stool samples. It was found that cholecystectomy could alleviate the decrease in Pielou's evenness and the increase in the relative abundances of the Firmicutes phylum and Lachnospira genus in long-term patients with T2DM compared with T2DII subjects. Moreover, cholecystectomy also significantly increased the relative abundance of the Fusobacteria phylum, as well as that of the Fusobacterium and Bilophila genera. Interestingly, the T2DIIC and T2DI groups showed higher similarities than the T2DII group with respect to patterns of gut microbiota composition and predicted gut metagenomes. In summary, cholecystectomy could partially alleviate long-term diabetes-induced dysbiosis of the gut microbiota composition and function, but alterations in T2DM patient health warrant further study.NEW & NOTEWORTHY The gut microbiome of long-term T2DM patients who had undergone cholecystectomy and age- and/or sex-matched subjects of new-onset and long-term T2DM without cholecystectomy was assessed using 16S rRNA gene sequencing in stool samples. The findings suggest that, cholecystectomy could partially alleviate long-term diabetes-induced dysbiosis of gut microbiome composition and function.

Effects of type 2 diabetes and metformin on salivary microbiota in patients with chronic periodontitis.

Diabetes is closely associated with periodontitis, however, the effects of type 2 diabetes and metformin treatment on the salivary microbiota in chronic periodontitis patients are still insufficiently studied. Saliva was collected from ten patients with moderate to severe chronic periodontitis (CP group) and 20 patients with type 2 diabetes mellitus (T2DM) and moderate to severe chronic periodontitis (ten patients were newly diagnosed with diabetes without drug treatment (DM group), and ten patients were treated with metformin (CP-DM-MET group)). Total DNA was extracted. DNA amplicons of the V3-V4 hypervariable regions of the 16S rRNA gene were generated and subjected to high-throughput sequencing. There was no significant difference in the alpha diversity of the salivary microbiota (Observed_Species, Shannon, Simpson, ACE, Chao1 index) among the three groups. The dominant phyla with relative abundances greater than 1% were Firmicutes, Proteobacteria, Bacteroidota, Actinobacteriota, Fusobacteriota, and Spirochaetota, and no significant difference was found among the three groups. Compared with the CP group, the relative abundance of twelve genera was found changed in CP-DM group, for example, Aggregatibacter, Unclassified_f_Neisseriaceae, Parvimonas, Erysipelotrichace_UCG-006, Atopobium, and Endomicrobium et al. Metformin treatment could partly restore the abundance of several genera in CP-DM, such as Acholeplasma and Comamonas. Compared with the CP group, genus Lactobacillus, Parvimonas, Norank_f_norank_o_Absconditabacteriales_SR1, and Acholeplasma changed significantly in CP-DM-MET group. Plaque index (PLI) was positively correlated with Prevotella and Lactobacillus but negatively correlated with Haemophilus, Lautropia, Unclassified_f_Pasteurellaceae, and TM7x. In conclusion, there was a significant difference in the salivary microbiota of patients with chronic periodontitis complicated by T2DM. Treatment with metformin partially alleviated the alteration in salivary microbiota caused by T2DM.

Relationship of Bone Status with Serum Uric Acid and Bilirubin in Men with Type 2 Diabetes: A Cross-Sectional Study.

BACKGROUND Accumulating evidence has shown that serum uric acid and bilirubin are associated with some chronic diseases, owing to their antioxidant capacity, but the previous research produced discrepant results regarding the relation between uric acid, as well as bilirubin, and bone health. This study was designed to assess the relationship of serum uric acid and total bilirubin with bone mineral density and bone turnover markers in men with type 2 diabetes. MATERIAL AND METHODS In total, 631 male patients with type 2 diabetes were included. Data of patients' medical history, biochemical index, bone mineral density of the lumbar vertebra, femoral neck, and total hip, and bone turnover markers including osteocalcin (OC), amino-terminal propeptide of type I procollagen (PINP), type I collagen carboxy-terminal peptide (CTX), and parathyroid hormone were collected and retrospectively analyzed. RESULTS Both serum uric acid and total bilirubin were positively related to bone mineral density of the lumbar vertebra (b=0.179, p.

Association Between Thyroid Function and Body Composition in Type 2 Diabetes Mellitus (T2DM) Patients: Does Sex Have a Role?

BACKGROUND The relationship between thyroid hormones and body anthropometric measures in type 2 diabetes mellitus (T2DM) patients with normal thyroid function is unclear. The purpose of this study was to evaluate the association between thyroid hormones and body composition in euthyroid T2DM patients in men and women. MATERIAL AND METHODS This was a cross-sectional study that included 561 euthyroid T2DM patients. Fasting venous blood was collected to test laboratory indexes. Bioelectric impedance analysis (BIA) was used to measure body composition. Propensity score matching (PSM) was used to enroll patients with similar baseline characteristics. The least absolute shrinkage and selection operator (LASSO) algorithm was used to establish a linear regression model of thyroid hormone and body composition. PSM was performed to match 159 men and 159 women. RESULTS The LASSO regression analysis suggested that thyroid-stimulating hormone (TSH) level was not correlated with body composition parameters in females. In females, free triiodothyronine (FT3) level was positively correlated with body mass index (BMI), fat-free mass index (FFMI), and skeletal muscle index (SMI), and was negatively correlated with extracellular water fraction (EWF). In males, FT3 level was positively correlated with waist circumference (WC) and SMI and negatively correlated with EWF. Free thyroxine (FT4) level in both women and men was positively correlated with body fat mass (BFM) and left lower-limb muscle mass (LLLMM). Moreover, in males, FT4 level was correlated with more body composition parameters. In euthyroid T2DM patients, FT3 level was positively correlated with SMI and negatively correlated with EWF, while FT4 level was positively correlated with BFM and LLLMM. CONCLUSIONS Thyroid function can affect body composition in euthyroid T2DM patients. Thyroid function is more likely to affect the fat and muscle distribution of males than females.

Effect of Intravenous Glucose Tolerance Test on Bone Turnover Markers in Adults with Normal Glucose Tolerance.

BACKGROUND It is well known that enteral nutrients result in acute suppression of bone turnover markers (BTMs), and incretin hormones are believed to play a significant role in this physiological skeletal response. However, there is limited research exploring the impact of parenteral nutrients on BTMs. Our aim was to assess the influence of intravenous glucose on BTMs in adults with normal glucose tolerance (NGT). MATERIAL AND METHODS We conducted 1-h intravenous glucose tolerance test (IVGTT) in 24 subjects with NGT. Blood samples were collected before and 5, 10, 15, 20, 30, 60 min after administration of glucose, then serum levels of bone formation marker procollagen type I N-terminal propeptide (P1NP) and resorption marker C-terminal cross-linking telopeptides of collagen type I (CTX) were measured. RESULTS During IVGTT, the fasting CTX level fell gradually and reached a nadir of 80.4% of the basal value at 60 min. Conversely, the fasting P1NP level decreased mildly and reached a nadir of 90.6% of the basal value at 15 min, then gradually increased and reached 96.6% at 60 min. The CTX-to-P1NP ratio increased slightly and reached a peak of 104.3% of the basal value at 10 min, then fell gradually and reached a nadir of 83% at 60 min. CONCLUSIONS Our study indicates that intravenous glucose results in an acute suppression of BTMs in the absence of incretin hormones. The mechanism responsible for this needs further investigation.

Association Between the Water Distribution in the Human Body and 25-Hydroxyvitamin D Among the Type 2 Diabetes Mellitus Population: A Possible Pathway Between Vitamin D and Diabetic Nephropathy.

Purpose: To explore the association between the water distribution in the human body and 25-hydroxyvitamin D among patients with type 2 diabetes mellitus (T2DM), and to analyze whether water distribution is a mediator between vitamin D and T2DM complications. Patients and Methods: In total, 533 T2DM inpatients were included from August 1, 2016 to April 1, 2023. Water distribution indicators, whether from the whole body, arms, trunk, or legs, were measured to calculate the association with vitamin D using linear regression analysis. Subgroups based on age, sex, body mass index, and macrovascular complications were established to clarify changes in the association between vitamin D and water distribution in different populations. Mediation analysis was applied to evaluate the correlation between vitamin D, water distribution, and T2DM complications. Results: There was a negative correlation between 25-hydroxyvitamin D and the ratio of extracellular water (ECW)/total body water (TBW) both in the whole body (P=0.045, ß=-0.008) and in certain parts. A U-shaped restricted cubic spline curve further presented an inflection point (approximately 23 ng/mL 25-hydroxyvitamin D) in the relationship between 25-hydroxyvitamin D and the ECW/TBW of the whole body. A negative correlation was observed between ECW/TBW and vitamin D in the obese subgroup (P=0.015, ß=-0.038). In the total effect of vitamin D on diabetic nephropathy (DN), the mediation effect of ECW/TBW accounted for 15.44%. Conclusion: A correlation between vitamin D and water distribution was observed, and a high ECW/TBW was one of the pathways through which low vitamin D levels might affect DN.

1,25-Dihydroxyvitamin D inhibits hepatic diacyglycerol accumulation and ameliorates metabolic dysfunction in polycystic ovary syndrome rat models.

Introduction: We aimed to evaluate the influence of 1,25-dihydroxyvitamin D (1,25(OH)2D) on metabolic dysfunction and elucidate its underlying mechanism using a rat model of polycystic ovary syndrome (PCOS). Methods: Twenty-four Sprague-Dawley rats were randomly divided into four groups: control group (CON, 2 ml/kg of oral 0.5% CMC), 1,25VD group (oral 0.5% CMC and 2.5 ug/kg intraperitoneal 1,25(OH)2D), PCOS group (1 mg/kg oral letrozole), PCOS+1,25VD group (1 mg/kg oral letrozole orally 2.5 ug/kg intraperitoneal 1,25(OH)2D). The treatments were administered for 8 weeks. Body weight, estrus cycle, insulin tolerance, and oral glucose tolerance of the rats in the different groups were assessed. The rats were euthanized at the 8th weeks, and plasma, ovarian, and liver samples were collected and analyzed. The hepatic lipid profile was characterized using HPLC/MRM. Results: Letrozole-induced PCOS rats exhibited increased weight, insulin resistance, postprandial glucose abnormalities, and dyslipidemia. Compared with the PCOS group rats, the PCOS+1,25VD group rats showed reduced body weight, increased sensitivity to insulin, decreased postprandial glucose, and elevated levels of high-density lipoprotein cholesterol. Moreover, abnormally increased liver concentrations of total diacylglycerol (DG) and DG species in the PCOS rats were reversed by treatment with 1,25(OH)2D. Additionally, hepatic DG and insulin sensitivity were correlated. Conclusion: 1,25(OH)2D inhibited hepatic DG accumulation and ameliorated metabolic dysfunction in PCOS rat models.

Using Artificial Intelligence to Diagnose Osteoporotic Vertebral Fractures on Plain Radiographs.

Osteoporotic vertebral fracture (OVF) is a risk factor for morbidity and mortality in elderly population, and accurate diagnosis is important for improving treatment outcomes. OVF diagnosis suffers from high misdiagnosis and underdiagnosis rates, as well as high workload. Deep learning methods applied to plain radiographs, a simple, fast, and inexpensive examination, might solve this problem. We developed and validated a deep-learning-based vertebral fracture diagnostic system using area loss ratio, which assisted a multitasking network to perform skeletal position detection and segmentation and identify and grade vertebral fractures. As the training set and internal validation set, we used 11,397 plain radiographs from six community centers in Shanghai. For the external validation set, 1276 participants were recruited from the outpatient clinic of the Shanghai Sixth People's Hospital (1276 plain radiographs). Radiologists performed all X-ray images and used the Genant semiquantitative tool for fracture diagnosis and grading as the ground truth data. Accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were used to evaluate diagnostic performance. The AI_OVF_SH system demonstrated high accuracy and computational speed in skeletal position detection and segmentation. In the internal validation set, the accuracy, sensitivity, and specificity with the AI_OVF_SH model were 97.41%, 84.08%, and 97.25%, respectively, for all fractures. The sensitivity and specificity for moderate fractures were 88.55% and 99.74%, respectively, and for severe fractures, they were 92.30% and 99.92%. In the external validation set, the accuracy, sensitivity, and specificity for all fractures were 96.85%, 83.35%, and 94.70%, respectively. For moderate fractures, the sensitivity and specificity were 85.61% and 99.85%, respectively, and 93.46% and 99.92% for severe fractures. Therefore, the AI_OVF_SH system is an efficient tool to assist radiologists and clinicians to improve the diagnosing of vertebral fractures. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Case report: Denosumab-associated acute heart failure in patients with cardiorenal insufficiency.

Denosumab is a pivotal treatment for postmenopausal women with osteoporosis. Although its clinical use is generally well tolerated by patients, denosumab in patients with renal insufficiency may increase the risk of hypocalcemia. Thus, we have to consider the population of denosumab in the treatment of osteoporosis and preventive measures for related complications. In a patient with cardiorenal insufficiency, we reported a case of denosumab-induced hypocalcemia complicated by acute left heart failure due to delayed administration of active vitamin D and calcium supplements. The patient's symptoms did not improve after anti-heart failure treatment. However, after adequate calcium and vitamin D supplementation subsequently, the patient's symptoms of heart failure were rapidly relieved, and the serum calcium level returned to normal within three weeks. Therefore, our case showed that the application of denosumab in patients requires assessment of cardiac and renal function, timely calcium and vitamin D supplementation, and enhanced monitoring of serum calcium levels to prevent acute left heart failure induced by denosumab-related hypocalcemia.

Development and validation of a nomogram for predicting the risk of obstructive sleep apnea in patients with type 2 diabetes.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent among patients with type 2 diabetes mellitus (T2DM) in China, but few patients with clinical symptoms of OSA are referred for diagnostic polysomnography (PSG). Thus, this study aimed to develop and validate an easy-to-use nomogram that predicts the severity of OSA in patients with T2DM. METHODS: This retrospective study included consecutive patients with T2DM admitted to the Endocrinology Department, Third Affiliated Hospital of Soochow University between January 1, 2016 and December 31, 2019. OSA was diagnosed with PSG. Participants were randomly assigned to a training cohort (70%) and a validation cohort (30%). Demographic, anthropometric, and biochemical data were collected. A least absolute shrinkage and selection operator (LASSO) regression model was used to reduce data dimensionality and identify factors for inclusion in the nomogram (training cohort). Nomogram validation was performed in the validation cohort. RESULTS: The study included 280 participants in the training group and 118 participants in the validation group. OSA prevalence was 58.5%. LASSO regression identified waist-to-hip ratio (WHR), smoking status, body mass index (BMI), serum uric acid (UA), the homeostasis model assessment insulin resistance index (HOMA-IR), and history of fatty liver disease as predictive factors for inclusion in the nomogram. Discrimination and calibration in the training group (C-index =0.88) and validation group (C-index =0.881) were good. The nomogram identified patients with T2DM at risk for OSA with an area under the curve of 0.851 [95% confidence interval (CI), 0.788-0.900]. CONCLUSIONS: Our nomogram could be used to facilitate individualized prediction of OSA risk in patients with T2DM and help prioritize patients for diagnostic PSG.

Circular RNA hsa_circ_0001445 in plasma as a novel biomarker for osteoporosis in postmenopausal women.

Background: The present study evaluated the potential of hsa_circ_0001445 as a biomarker in plasma for postmenopausal patients with osteoporosis (OPO). Materials & methods: The expression levels of hsa_circ_0001445 in plasma were detected in healthy controls, patients with osteopenia (OPE) and patients with OPO by using quantitative reverse-transcriptase PCR. Results: The expression levels of hsa_circ_0001445 in plasma were much lower in OPO patients compared with OPE patients and healthy controls. Its expression was positively correlated with the T-score and was negatively correlated with ß-isomerized C-terminal telopeptides (ß-CTx). It could distinguish OPE or/and OPO patients from healthy controls. Moreover, its expression was significantly upregulated in the plasma of OPO patients after anti-osteoporotic treatment. Conclusion: Hsa_circ_0001445 in plasma may be a novel potential diagnostic biomarker for OPO.

The effect of an overall healthy lifestyle on early-onset stroke: a cross-sectional study.

BACKGROUND: The impact of an overall healthy lifestyle on early-onset stroke is still unclear. Our study thus aimed to investigate the association of overall healthy lifestyle on early-onset stroke in Chinese hospitalized stroke patients. METHODS: This retrospective study included 821 hospitalized stroke patients from the First People's Hospital of Changzhou. An overall healthy lifestyle was defined as the presence of more than 2 of the following items: healthy diet, no smoking, normal body mass index (BMI <24 kg/m2 ), engaging in moderate to high physical activity (≥3 times/week, and ≥30 minutes each time). Early-onset stroke was defined as a stroke first occurring at 50 years old or younger. RESULTS: Among all participants, there were 98 early-onset stroke patients and 723 late-onset stroke patients. Early-onset patients had a lower prevalence of overall healthy lifestyles than that of late-onset patients (P<0.001). Multivariate logistic regression revealed that an overall healthy lifestyle significantly reduced the risk of early-onset stroke. In reference to those without an overall healthy lifestyle, the multivariate-adjusted odds ratios (ORs) for early-onset stroke among participants with an overall healthy lifestyle was 0.27 [95% confidence interval (CI): 0.07-0.98]. CONCLUSIONS: In Chinese stroke patients, a healthy lifestyle was significantly associated with early-onset stroke. Individuals who were adhering to an overall healthy lifestyle had a lower risk of early-onset stroke compared to those who were not.

Gut microbiota transplantation from db/db mice induces diabetes-like phenotypes and alterations in Hippo signaling in pseudo germ-free mice.

Type 2 diabetes mellitus (T2DM) is an age-related metabolic disease that is of increasing concern. Gut microbiota might have a critical role in the pathogenesis of T2DM. Additionally, Hippo signaling has been associated strongly with the progression of T2DM and the aging process. We adopted db/db male mice as a T2DM model, and the gut microbiota of db/db and m/m mice were transplanted successfully into pseudo germ-free mice. Furthermore, Hippo signaling, including mammalian sterile 20-like protein kinases 1 (MST1), large tumor suppressors 1 (LATS1), Yes-associated protein (YAP), and phosphorylation of YAP (p-YAP) in peripheral tissues were significantly altered and highly correlated with blood glucose in db/db mice. Interestingly, the host after gut microbiota transplantation from db/db mice showed decreased MST1 and LATS1 levels, and p-YAP/YAP ratio in the heart, liver, and kidney compared to those from m/m mice. Negative correlations between fasting blood glucose and Hippo signaling levels in selected peripheral tissues also were identified. These findings suggest that alterations in Hippo signaling in selected peripheral tissues may contribute to the development of T2DM, and that therapeutic interventions improving Hippo signaling by gut microbiota transplantation might be beneficial for the treatment of T2DM and other age-related metabolic diseases.

Differential Levels of Hippo Signaling in Selected Brain and Peripheral Tissues in Streptozotocin-Induced Cognitive Dysfunction in Mice.

Increasing studies have revealed that metabolic disorders, especially diabetes, are high risk factors for the development of Alzheimer's disease (AD) and other neurodegenerative diseases. It has been reported that patients with diabetes are prone to suffer from cognitive dysfunction (CD). Although abnormal glucose metabolism and deposition of amyloid ß (Aß) are proven to have a closely relationship with diabetes-induced CD, its exact mechanism is still undetermined. In this study, a total of 14 mice were intraperitoneally injected with streptozotocin for 5 consecutive days to mimic diabetic models, and then hierarchical cluster analysis was adopted to classify the diabetic mice into CD and Non-CD phenotypes by the results of Morris water maze test (MWMT). Furthermore, we detected Hippo signaling including mammalian sterile 20-like protein kinases1 (MST1), large tumor suppressors 1 (LATS1), Yes-associated protein (YAP) and phosphorylation of YAP (p-YAP) in brain and peripheral tissues. As compared with control mice, the levels of MST1, LATS1 and p-YAP/YAP ratio were increased in medial prefrontal cortex (mPFC), striatum and hippocampus of CD mice, while these proteins were decreased in gut tissue of CD mice. Additionally, there were significant positive correlations between escape latency and p-YAP/YAP ratio in mPFC, anterior cingulate cortex (ACC) and hippocampus, as well as the level of LATS1 in liver, kidney and gut tissues. In conclusion, alterations in Hippo signaling may contribute to CD induced by diabetes. Therefore, therapeutic interventions improving Hippo signaling might be beneficial to the treatment of diabetes-induced CD and other neurodegenerative diseases.

Abnormal gut microbiota composition contributes to cognitive dysfunction in streptozotocin-induced diabetic mice.

Both diabetes and Alzheimer's disease are age-related disorders, and numerous studies have demonstrated that patients with diabetes are at an increased risk of cognitive dysfunction (CD) and Alzheimer's disease, suggesting shared or interacting pathomechanisms. The present study investigated the role of abnormal gut microbiota in diabetes-induced CD and the potential underlying mechanisms. An intraperitoneal injection of streptozotocin administered for 5 consecutive days was used for establishing a diabetic animal model. Hierarchical cluster analysis of Morris water maze (MWM) performance indices (escape latency and target quadrant crossing) was adopted to classify the diabetic model mice into CD and Non-CD phenotypes. Both ß-diversity and relative abundance of several gut bacteria significantly differed between the CD and Non-CD groups. Further, fecal bacteria transplantation from Non-CD mice, but not from CD mice, into the gut of pseudo-germ-free mice significantly improved host MWM performance, an effect associated with alterations in ß-diversity and relative abundance of host gut bacteria. Collectively, these findings suggest that abnormal gut microbiota composition contributes to the onset of diabetes-induced CD and that improving gut microbiota composition is a potential therapeutic strategy for diabetes and related comorbidities.