The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Comparison of clinical characteristics and treatment outcomes between initially diagnosed type 1 and type 2 diabetes mellitus patients presenting with diabetic ketoacidosis.

OBJECTIVE: Patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) can present with diabetic ketoacidosis (DKA) as the first manifestation. Differentiating types of newly diagnosed diabetes could provide appropriate long-term management. Therefore, we conducted this study to compare clinical characteristics and outcomes between initially diagnosed type 1 and type 2 diabetes mellitus patients presenting with DKA. MATERIALS AND METHODS: A retrospective study was conducted on adult patients who presented with DKA as the first diagnosis of diabetes in our tertiary hospital between January 2005 and December 2019. Demographic data, precipitating causes, laboratory investigations, treatment, and outcomes were obtained by chart review. The primary outcome was to compare the clinical characteristics of initially diagnosed patients with T1DM and T2DM who presented with DKA. RESULTS: A total of 100 initially diagnosed diabetic patients who presented with DKA were analyzed (85 T2DM patients and 15 T1DM patients). Patients with T1DM were younger than patients with T2DM (mean age 33 ± 16.2 vs. 51 ± 14.5 years, p value < 0.001). Patients with T2DM had a higher body mass index, family history of diabetes, precipitating factors, plasma glucose, and lower renal function than those with T1DM. There was no difference in resolution time or DKA management between T1DM and T2DM patients. The overall mortality rate of DKA was 4%. CONCLUSION: In this population, most adult patients who presented with DKA had T2DM. Older age, obesity, a family history of diabetes, and the presence of precipitating factors were strong predictors of T2DM. We can implement the same clinical management for DKA in both T1DM and T2DM patients. However, T2DM patients had longer hospitalization than T1DM patients. After DKA resolution for 12 months, more than half of patients with T2DM could discontinue insulin. Therefore, the accurate classification of the type of diabetes leads to appropriate treatment.

Using the illness-death model to estimate age- and sex-standardized incidence rates of diabetes in Mexico from 2003 to 2015.

BACKGROUND: We aimed to estimate the age-specific and age-standardized incidence rate of diabetes for men and women in Mexico between 2003 and 2015, and to assess the relative change in incidence of diabetes between 2003 and 2015. METHODS: We use a partial differential equation describing the illness-death model to estimate the incidence rate (IR) of diabetes for the years 2003, 2009 and 2015 based on prevalence data from National Health Surveys conducted in Mexico, the mortality rate of the Mexican general population and plausible input values for age-specific mortality rate ratios associated with diabetes. RESULTS: The age-standardized IR of diabetes per 1000 person years (pryr) was similar among men (IRm) and women (IRw) in the year 2003 (IRm 6.1 vs. IRw 6.5 1000/pryr), 2009 (IRm: 7.0 vs. IRw: 8.4 1000/pryr), and in 2015 (IRm 8.0 vs. IRw 10.6 1000/pryr). The highest incident rates were observed among men and women in the 60-69 age group. CONCLUSIONS: Overall, the incidence rate of diabetes in Mexico between the years 2003 and 2015 remained stable. However, rates were markedly higher among women in the age group 40-49 and 50-59 in the year 2015 compared with rates in 2003.

The association between waist-to-hip ratio (WHR) with diabetes in the PERSIAN Guilan cohort study population.

BACKGROUND: Waist circumference (WC), or waist-to-hip ratio (WHR), potentially offers a more accurate reflection of intra-abdominal fat accumulation and could serve as a superior predictor of type 2 diabetes mellitus (T2DM) risk compared to BMI. The current study investigated the relationship between WHR and its influencing factors among diabetes patients enrolled in the Prospective Epidemiological Research Studies in Iran (PERSIAN) Guilan Cohort study (PGCS). METHOD: In this cross-sectional study of 10,520 participants, 2,531 had T2DM. Waist and hip circumference, body mass index (BMI), underlying diseases, and demographical data of participants were recorded. Also, fasting blood sugar (FBS), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides (TG) were assessed. All data was analyzed using SPSS version 16; the significant level was < 0.05. RESULTS: The mean age of participants was 51.52 ± 8.90 years, and 39.9% had a BMI between 25 and 30 kg/m2. The prevalence of diabetes was 24.1% (n = 2531). About 7628 (72.5%) individuals had abnormal WHR, and 2072 (19.7%) were diabetics. Among patients with diabetes, abnormal WHR was significantly associated with age over 50, female gender, higher BMI, and lower LDL (P < 0.05). CONCLUSION: The study showed a higher prevalence of abnormal WHR in diabetic patients. Abnormal WHR in patients with diabetes was significantly associated with age, gender, and BMI.

Therapeutic Potential of Brassica oleracea and Raphanus sativus Aqueous Extracts on a Prediabetic Rat Model.

Type 2 diabetes (T2D) is a serious health problem, and its prevalence is expected to increase worldwide in the years ahead. Cruciferous vegetables such as Brassica oleracea var. capitata L. (green cabbage) and Raphanus sativus L. (radish) have therapeutic properties that can be used to support the treatment of T2D. This study evaluated the effect of B. oleracea (BAE) and R. sativus (RAE) aqueous extracts on zoometric parameters, glycemic profiles, and pancreas and liver in prediabetic rats induced by a high-sucrose diet (HSD). BAE and RAE were administered to male HSD-induced Wistar rats (n = 35) at 5 and 10 mg/kg doses for 5 weeks. Zoometric and biochemical changes were measured, and then the pancreas and liver histological preparations were analyzed to observe the protective effect. BAE decreased feed intake and weight gain. Both extracts decreased fasting glucose and insulin levels compared with control (not treated), although not significantly (P > .05). The extracts significantly (P < .05) reduced homeostatic model assessment for insulin resistance, homeostasis model assessment of ß-cell function, and glucose intolerance, similar to metformin control. In addition, minor damage occurred in the pancreas and liver. The results indicated that BAE and RAE decreased weight gain, improved glucose regulation, and protected the pancreas and liver in HSD rats. Therefore, they have multiple therapeutical properties and may be helpful in the prevention of T2D.

Timing of gestational diabetes diagnosis and progression to type 2 Diabetes: A comparative analysis.

AIM: To evaluate and compare the risk of progressing to type 2 diabetes (T2DM) based on the timing of gestational diabetes (GDM) diagnosis during pregnancy. METHODS: Retrospective analysis of pregnant individuals with gestational diabetes and post-pregnancy follow up. Data sourced from Meuhedet HMO's computerized laboratory system, cross-tabulated with the Israeli National Diabetes Registry. The cohort was divided into normoglycemic, early GDM (diagnosed by fasting plasma glucose 92-125 mg/dL (5.1-6.9 mM) at < 15 weeks), 2nd trimester GDM (diagnosed at 24-28 weeks), and late GDM (diagnosed after 29 weeks). Statistics included univariate analysis followed by survival analysis. Risk was further analyzed for individuals by obesity status. RESULTS: 75,459 entered the analysis: 90 % normoglycemic, 7.9 % early GDM, 1.4 % 2nd trimester GDM, and 0.7 % late GDM. Median post-pregnancy follow-up time was 4.3 (IQR 3.3-5.1). 2nd trimester GDM showed the highest T2DM risk annually after pregnancy. Cox regression analysis, adjusted for confounders, revealed a significantly higher T2DM risk for 2nd-trimester GDM compared to early and late GDM. Late GDM did not confer additional significant T2DM risk. Stratification by obesity status highlighted that early GDM increased the risk of T2DM only in individuals without obesity. CONCLUSIONS: GDM diagnosis timing significantly impacts T2DM risk. 2nd trimester GDM carries the highest T2DM risk.

Iron chelation mitigates mitochondrial dysfunction and oxidative stress by enhancing nrf2-mediated antioxidant responses in the renal cortex of a murine model of type 2 diabetes.

Renal iron overload is a common complication of diabetes that leads to oxidative stress and mitochondrial dysfunction in the kidneys. This study investigated the effects of iron chelation using deferiprone on mitochondrial dysfunction and oxidative stress in the renal cortex of a murine model of type 2 diabetes. Diabetic rats were treated with deferiprone (50 mg/kg BW) for 16 weeks. Our results show that iron chelation with deferiprone significantly increased the nuclear accumulation of Nrf2, a transcription factor that regulates the expression of antioxidant enzymes. This led to enhanced antioxidant capacity, reduced production of reactive oxygen species, and improved mitochondrial bioenergetic function in diabetic rats. However, chronic iron chelation led to altered mitochondrial respiration and increased oxidative stress in non-diabetic rats. In conclusion, our findings suggest that iron chelation with deferiprone protects mitochondrial bioenergetics and mitigates oxidative stress in the renal cortex, involving the NRF2 pathway in type 2 diabetes.

Serum melatonin levels in type 2 diabetic patients with depressive symptoms compared to non-depressed individuals.

Background: Melatonin, mainly regulating the body's circadian rhythm, may have protective effects against type 2 diabetes mellitus (DM2)-induced depression due to its antioxidant and regulatory impact in the pathogenesis of both DM2 and depression. This study aimed to find the association of serum melatonin levels with depression in DM2 patients. Methods: A total of 50 DM2 patients were recruited in this retrospective cross-sectional study and divided into 25 patients with depression (DM2-DP) and 25 without depression symptoms (DM2-NDP). Depression was diagnosed using the Hospital Anxiety and Depression Scale (HADS) assessment. Fasting blood samples were collected and examined for the level of serum melatonin and other biomarkers. All statistical analysis was performed by SPSS software Version 22, and a p-value less than 0.05 was considered statistically significant for all tests. Results: The depression score was significantly lower in DM2-NDP than DM2-DP (p< 0.001). The mean weight was significantly lower in the DM2-DP group (P= 0.021). Total cholesterol, triglyceride, and anxiety scores were higher, and the melatonin level was lower in DM2-DP. The correlation of melatonin levels was positive with age, DBP, HbA1C, FBS, and TG. In contrast, it was negative with male gender, BMI, diabetes duration, SBP, TC, family history of DM, depression score, and anxiety score. However, no significant differences were seen. Conclusion: Lower melatonin may be associated with depression and anxiety in patients with DM2. The serum melatonin level might be a strong predictor of depression in DM2 patients.

Effect of fixed-ratio insulin combinations on adherence in type 2 diabetes: Systematic review.

AIMS: To systematically review evidence on the effect of fixed-ratio combinations on adherence in people with type 2 diabetes. METHODS: Systematic searches were conducted using MEDLINE and EMBASE in March 2023. Standardised screening, data extraction and risk of bias assessment were conducted. All review procedures were conducted independently by two reviewers. Eligible studies assessed the effect of fixed-ratio combinations on adherence in people with type 2 diabetes. Narrative synthesis was conducted to analyse findings. RESULTS: A total of 488 records were identified, of which 37 proceeded to full-text screening and 7 - each representing a unique study - were included in the systematic review. Among the included studies, 3 were randomised controlled trials and 4 were cohort studies. Following narrative synthesis, it was shown that fixed-ratio combinations improved patient satisfaction and treatment adherence. CONCLUSIONS: Available evidence supports a benefit for fixed-ratio combinations on patient satisfaction and treatment adherence in people with type 2 diabetes.

Overactive bladder symptoms experiences of diabetic women in Türkiye: A qualitative study.

In diabetic patients, poor management of hyperglycemia and prolonged disease duration may lead to neuropathy-related overactive bladder (OAB) symptoms. To effectively manage OAB symptoms in women with type 2 diabetes, it is essential to know how patients perceive these problems, their lives, and strategies. This study aimed to understand the experience of OAB symptoms in Turkish women with type 2 diabetes from their point of view. A qualitative descriptive design was adopted with individual, semi-structured interviews. Participants were selected by purposive sampling. The data were evaluated by using Van Manen's thematic analysis method. The symptom management theory formed the conceptual framework of this study. The Consolidated Criteria for Reporting Qualitative Research checklist was used. A total of 18 patients were recruited and individually interviewed. Semi-structured interviews were conducted from May to August 2023. The three main themes emerged: (i) the meaning of OAB symptoms; (ii) difficulties caused by OAB symptoms; and (iii) coping with OAB symptoms. The subthemes included the negative effects of OAB symptoms on daily life, difficulties in physical, psychological, and sexual life, and positive and negative behavior in coping with OAB symptoms. OAB symptoms affect the physical, psychosocial, and sexual lives of women with type 2 diabetes. Women with type 2 diabetes try to cope in different ways but often do not receive the support they need from families. Therefore, nurses should integrate the urinary problems of women with type 2 diabetes into routine clinical assessments and provide counseling to women.

Pathological concordance rate and outcomes by subtype in advanced papillary renal cell carcinoma.

OBJECTIVE: To evaluate the clinical significance of subtyping (type 1 vs 2) of papillary renal cell carcinoma (PRCC) in patients treated with targeted therapy, as well as the concordance, sensitivity and positive predictive value (PPV) of local review pathology review. METHODS: Patients with advanced refractory PRCC were randomised to receive sunitinib or cabozantinib, crizotinib or savolitinib, stratified by PRCC subtype (type 1, type 2, or not otherwise specified [NOS]/mixed) by local review. Central review was retrospectively conducted by three expert genitourinary pathologists who independently reviewed cases. The sensitivity and PPV of local review were estimated and outcomes [objective response rate (ORR), progression-free survival (PFS)] were summarised for treatment groups stratified by subtypes by central review. RESULTS: Amongst the 147 patients reviewed, the prevalence of individual subtypes varied by local or central review (type 1: 17.7% vs 29.3%; type 2: 53.1% vs 45.6%; NOS/mixed: 29.3% vs 25.2%), respectively. Individual cases were frequently reclassified and local pathology review demonstrated low sensitivity (type 1: 48%, 95% confidence interval [CI] 33, 65; type 2: 67%, 95% CI 55, 78; NOS/mixed: 43%, 95% CI 27, 61). The PPVs of local review were 80%, 57.7% and 37% for type 1, 2 and NOS/mixed, respectively. Compared to sunitinib, cabozantinib demonstrated improved PFS for both type 1 and type 2 PRCC subgroups (7.4 vs 9.0 and 2.9 vs 5.6 months, respectfully) as well as higher ORR. CONCLUSIONS: The PRCC subtype assignment did not identify a subset of patients with greater clinical benefit from cabozantinib, with significant discordance between local and central review. Our findings confirm the limited clinical value of pathological subtyping of metastatic PRCC, in line with the recent World Health Organisation 2022 guidelines. PATIENT SUMMARY: In this study, categorising papillary renal cell carcinoma into type 1 or 2 subtypes showed limited concordance between central and local pathological review and did not enrich for patients more likely to benefit from cabozantinib in the S1500 PAPMET trial.

JWH133 attenuates behavior deficits and iron accumulation in the 6-OHDA-induced Parkinson's disease model rats.

Growing evidence indicated that activation of cannabinoid type 2 (CB2) receptors protect dopamine neurons in the pathogenesis of Parkinson's disease (PD). However, the mechanisms underlying neuroprotection mediated by CB2 receptors are still elusive. In this study, we investigated the effects of CB2 receptor activation on 6-OHDA-induced dopamine neuron degeneration and iron accumulation in the substantia nigra (SN) of rats. We found that treatment with JWH133, a selective CB2 receptor agonist, significantly improved the apomorphine (APO)-induced rotational behavior in 6-OHDA-treated rats. The decreased numbers of tyrosine hydroxylase (TH)-positive neurons, reduced TH protein expression in the lesioned SN of rats were effectively restored by JWH133. Moreover, we found that JWH133 inhibited the increase of iron staining cells in the lesioned SN of rats. To explore the protective mechanisms of activation of CB2 receptors on dopamine neurons, we further observed the effect of JWH133 on 1-methyl-4-phenylpyridinium (MPP+) treated primary cultured ventral mesencephalon (VM) neurons from rats. We found that JWH133 significantly inhibited the increase of intracellular reactive oxygen species (ROS), the activation of Caspase-3, the decrease of mitochondrial transmembrane potential (ΔΨm), and the decrease of Bcl-2/Bax protein expression caused by MPP+ treatment. JWH133 also inhibited the MPP+-induced up-regulation of divalent metal transporter-1 (DMT1) and down-regulation of ferroportin-1 (FPN1). Furthermore, JWH133 also suppressed the MPP+-accelerated iron influx in the VM neurons. These results suggest that activation of CB2 receptor suppresses MPP+-inducedcellular iron accumulation and prevents neurodegeneration.

Metabolic dysfunction-associated steatotic liver disease has become the most common cause of hepatocellular carcinoma in Sweden: A nationwide cohort study.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease globally, and can lead to hepatocellular carcinoma (HCC), a leading cause of cancer-related death. We aimed to determine the extent to which MASLD is an increasing cause of HCC in Sweden and to determine clinical characteristics associated with underlying MASLD. Using the Swedish quality registry for liver cancer (SweLiv), we identified all adults with a diagnosis of HCC in Sweden between 2012 and 2018. Baseline data were retrieved from SweLiv and other nationwide registers. Totally, 3494 patients with HCC were identified. Of them, 757 patients (22%) had MASLD-HCC. The proportion with MASLD-HCC increased from 19% in 2012 to 25% in 2018 (ptrend = 0.012), and MASLD was since 2017 the leading cause of HCC, surpassing hepatitis C. MASLD was the fastest growing cause of HCC with a 33% increment during the study period. Compared to other patients with HCC, those with MASLD-HCC were older (75 vs. 67 years, p < .001), less commonly had cirrhosis (61% vs. 82%, p < .001), had larger tumours (median 5.5 vs. 4.3 cm, p < .001), and more often extrahepatic metastasis (22% vs. 16%, p < .001). Patients with HCC caused by MASLD or by other causes were equally likely to be diagnosed in an early stage (Barcelona Clinic Liver Cancer 0-A, 27% vs. 30%, p = .129). MASLD is now the leading cause of HCC in Sweden.

Exercise Training and Spexin Ameliorate Thyroid Changes in Obese Type 2-Diabetic Rats: The Possible Interlaying Mechanisms.

Thyroid dysfunction and diabetes mellitus are prevalent endocrine disorders that often coexist and influence each other. The role of spexin (SPX) in diabetes and obesity is well-documented, but its connection to thyroid function is less understood. This study investigates the influence of exercise (EX) and SPX on thyroid hypofunction in obese type 2 diabetic rats. Rats were divided into normal control, obese diabetic sedentary, obese diabetic EX, and obese diabetic SPX groups, with subdivisions for M871, and HT-2157 treatment in the later 2 groups. High-fat diet together with streptozotocin injection induced obesity and diabetes. The EX-group underwent swimming, while the SPX-group received SPX injections for eight weeks. Results showed significant improvements in thyroid function, metabolic, oxidative, and inflammatory states with EX and SPX-treatment. The study also explored the involvement of galanin receptor isoforms (GALR) 2/3 in SPX effects on thyroid function. Blocking GALR2/3 receptors partially attenuated the beneficial effects, indicating their interaction. These findings underscore the importance of EX and SPX in modulating thyroid function in obesity and diabetes. Comprehending this interplay could enable the development of new treatment approaches for thyroid disorders associated with obese type 2 diabetes. Additional research is necessary to clarify the exact mechanisms connecting SPX, EX activity, and thyroid function.

Assessment of potential genetic markers for diabetic foot ulcer among Moscow residents.

PURPOSE: Diabetic foot ulcer (DFU) is one of the most severe complications of type 2 diabetes, which is manifested in chronic skin ulcers of lower extremities. DFU treatment remains complex and expensive despite the availability of well-established protocols. Early prediction of potential DFU development at the onset of type 2 diabetes can greatly improve the aftermath of this complication. METHODS: To assess potential genetic markers for DFU, a group of diabetic patients from Moscow region with and without DFU was genotyped for a number of SNPs previously reported to be associated with the DFU. RESULTS: Obtained results did not confirm previously claimed association of rs1024611, rs3918242, rs2073618, rs1800629, rs4986790, rs179998, rs1963645 and rs11549465 (respectively, in MCP1, MMP9, TNFRSF11B, TNFα, TLR4, eNOS, NOS1AP and HIF1α genes) with the DFU. Surprisingly, the t allele of rs7903146 in the TCF7l2 gene known as one of the most prominent risk factors for type 2 diabetes has shown a protective effect on DFU with OR(95%) = 0.68(0.48-0.96). CONCLUSION: Non-replication of previously published SNP associations with DFU suggests that the role of genetic factors in the DFU onset is either highly variable in different populations or is not as significant as the role of non-genetic factors.

Role of NQO1 Gene Involvement and Susceptibility of T2DM Among Saudi Arabia Population.

NQO1 disruption enhances susceptibility to oxidative stress during hyperglycemia and is a significant contributor to the development and progression of diabetes. Oxidative stress has been linked to several symptoms, including hyperglycemia, reactive oxygen species buildup, high blood pressure, and the expression of inflammatory markers. Therefore, the present research aimed to evaluate the genetic abnormality of NQO1 (rs1800566, C609T) gene polymorphism, expression, and vitamin-D level assessment among Type 2 diabetes mellitus (T2DM) patients. The study included 100 newly diagnosed T2DM cases and 100 healthy individuals as healthy controls. Total RNA was extracted from the whole blood using the TRIzol method, and further cDNA was synthesized, and expression was evaluated. There is a significant difference in NQO1 (rs1800566, C609T) genotype distribution among the T2DM patients and healthy controls (p = 0.04). Compared with the NQO1 CC wild-type genotype, the NQO1 CT heterozygous genotype had an odds ratio of 1.96 (1.08-3.55), and the NQO1 TT mutant type genotype had an odds ratio of 3.31 (0.61-17.77). Significantly decreased expression of NQO1 mRNA was observed with heterozygous CT (p < 0.0001) and homozygous mutant TT genotype (p = 0.0004), compared with homozygous wild-type CC genotype. NQO1 mRNA expression level was also compared with vitamin D levels among the T2DM patients. T2DM patients with vitamin D deficiency had 1.83-fold NQO1 mRNA expression, while vitamin D insufficient and sufficient T2DM cases had 3.31-fold (p < 0.0001) and 3.70-fold (p < 0.0001) NQO1 mRNA expression. It was concluded that NQO1 (rs1800566, C609T) CT and TT genotypes played a significant role in the worseness of type II diabetes mellitus, and decreased expression of NQO1 mRNA expression could be an essential factor for disease worseness as well as hypermethylation could be a factor for reduced expression leading to disease severity. The decreased NQO1 mRNA expression with heterozygous CT and mutant TT genotype associated with vitamin D deficiency may contribute to disease progression.

Preemptive embolization of abdominal aortic aneurysm sac side branch arteries promotes early sac shrinkage after endovascular aneurysm repair1.

OBJECTIVES: The association between the occlusion rate of the side branch arteries branching from the abdominal aortic aneurysm sac and aneurysm sac shrinkage is unclear. We aimed to evaluate the efficacy of preemptive embolization of multiple side branch arteries branching from the abdominal aortic aneurysm sac in early aneurysm sac shrinkage after endovascular aneurysm repair. METHODS: Patients undergoing endovascular aneurysm repair of abdominal aortic aneurysms, with or without preemptive embolization of multiple side branch arteries, including the inferior mesenteric artery and lumbar arteries, between January 2016 and August 2021, were retrospectively evaluated. Preemptive embolization was introduced at our institution in January 2018 and has been performed in all patients who undergo endovascular aneurysm repair since then. We compared occlusion rates of the side branch arteries, frequency of type 2 endoleaks, changes in aneurysm sac size, percentage of aneurysm sac size decrease, and frequency of reduction in the aneurysm sac diameter by >5 mm. RESULTS: The study included 43 patients in the embolization group and 20 in the non-embolization group. Preemptive embolization was successfully performed without any ischemic complications. The total occlusion rate of side branch arteries was significantly higher in the embolization group than in the non-embolization group (70.2% vs. 29.3%, P<0.05). At 24 months of follow-up, the type 2 endoleak frequency was significantly lower in the embolization group than in the non-embolization group (6.9% vs. 31.6%, P<0.05). The frequency of reduction in the aneurysm sac diameter by >5 mm was significantly higher in the embolization group than in the non-embolization group at 24 months (62.1% vs. 31.6% P<0.05). The optimal cutoff value for the total occlusion rate of the side branch arteries to achieve reduction in the aneurysm sac diameter by >5 mm at 24 months, after endovascular aneurysm repair, was 66.7% in all patients (area under the curve=0.634; sensitivity=62.5%; specificity=70.8%). These findings suggest that occluding 66.7% or more of the side branch arteries may result in early aneurysmal shrinkage. CONCLUSION: Preemptive embolization of multiple side branch arteries, branching from the abdominal aortic aneurysm sac, may contribute to early aneurysm sac shrinkage; this may serve as a marker for fewer late complications after endovascular aneurysm repair.

Effects of insonification on repairing the renal injury of diabetic nephropathy rats.

INTRODUCTION: Prolonged hyperglycemia in diabetes mellitus can result in the development of diabetic nephropathy (DN) and increase the susceptibility to kidney failure. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive modality that has demonstrated effective tissue repair capabilities. The objective of this study was to showcase the reparative potential of LIPUS on renal injury at both animal and cellular levels, while also determining the optimal pulse length (PL). RESEARCH DESIGN AND METHODS: We established a rat model of DN, and subsequently subjected the rats' kidneys to ultrasound irradiation (PL=0.2 ms, 10 ms, 20 ms). Subsequently, we assessed the structural and functional changes in the kidneys. Additionally, we induced podocyte apoptosis and evaluated its occurrence following ultrasound irradiation. RESULTS: Following irradiation, DN rats exhibited improved mesangial expansion and basement membrane thickening. Uric acid expression increased while urinary microalbumin, podocalyxin in urine, blood urea nitrogen, and serum creatinine levels decreased (p<0.05). These results suggest that the optimal PL was 0.2 ms. Using the optimal PL further demonstrated the reparative effect of LIPUS on DN, it was found that LIPUS could reduce podococyte apoptosis and alleviate kidney injury. Metabolomics revealed differences in metabolites including octanoic acid and seven others and western blot results showed a significant decrease in key enzymes related to lipolysis (p<0.05). Additionally, after irradiating podocytes with different PLs, we observed suppressed apoptosis (p<0.05), confirming the optimal PL as 0.2 ms. CONCLUSIONS: LIPUS has been demonstrated to effectively restore renal structure and function in DN rats, with an optimal PL of 0.2 ms. The mechanism underlying the alleviation of DN by LIPUS is attributed to its ability to improve lipid metabolism disorder. These findings suggest that LIPUS may provide a novel perspective for future research in this field.

Plasma sphingolipids mediate the association between gut microbiome composition and type 2 diabetes risk in the HELIUS cohort: a case-cohort study.

INTRODUCTION: The association between the gut microbiome and incident type 2 diabetes (T2D) is potentially partly mediated through sphingolipids, however these possible mediating mechanisms have not been investigated. We examined whether sphingolipids mediate the association between gut microbiome and T2D, using data from the Healthy Life in an Urban Setting study. RESEARCH DESIGN AND METHODS: Participants were of Dutch or South-Asian Surinamese ethnicity, aged 18-70 years, and without T2D at baseline. A case-cohort design (subcohort n=176, cases incident T2D n=36) was used. The exposure was measured by 16S rRNA sequencing (gut microbiome) and mediator by targeted metabolomics (sphingolipids). Dimensionality reduction was achieved by principle component analysis and Shannon diversity. Cox regression and procrustes analyses were used to assess the association between gut microbiome and T2D and sphingolipids and T2D, and between gut microbiome and sphingolipids, respectively. Mediation was tested familywise using mediation analysis with permutation testing and Bonferroni correction. RESULTS: Our study confirmed associations between gut microbiome and T2D and sphingolipids and T2D. Additionally, we showed that the gut microbiome was associated with sphingolipids. The association between gut microbiome and T2D was partly mediated by a sphingolipid principal component, which represents a dominance of ceramide species over more complex sphingolipids (HR 1.17; 95% CI 1.08 to 1.28; proportional explained 48%), and by Shannon diversity (HR 0.97; 95% CI 0.95 to 0.99; proportional explained 24.8%). CONCLUSIONS: These data suggest that sphingolipids mediate the association between microbiome and T2D risk. Future research is needed to confirm observed findings and elucidate causality on a molecular level.