Transforming growth factor-beta (TGF-β), a cytokine with near omnipresence, is an integral part of many vital cellular processes across the human body. The family includes three isoforms: Transforming growth factor-beta 1, 2, and 3. These cytokines play a significant role in the fibrosis cascade. Diabetic kidney disease (DKD), a major complication of diabetes, is increasing in prevalence daily, and the classical diagnosis of diabetes is based on the presence of albuminuria. The occurrence of nonalbuminuric DKD has provided new insight into the pathogenesis of this disease. The emphasis on multifactorial pathways involved in developing DKD has highlighted some markers associated with tissue fibrosis. In diabetic nephropathy, TGF-β is significantly involved in its pathology. Its presence in serum and urine means that it could be a diagnostic tool while its regulation provides potential therapeutic targets. Completely blocking TGF-β signaling could reach untargeted regions and cause unanticipated effects. This paper reviews the basic details of TGF-β as a cytokine, its role in DKD, and updates on research carried out to validate its candidacy.

The global prevalence of diabetes is on an upward trajectory. The management of complications related to the condition has seen limited progress in recent years. Klotho, characterized as an anti-aging protein that mitigates oxidative stress and inflammation, has previously been correlated with all-cause mortality in the broader United States population. The objective of this research was to investigate the persistence of this relationship among diabetic patients.

This study meticulously analyzed data (2007-2016) sourced from the National Health and Nutrition Examination Survey, encompassing a cohort of 3,560 individuals. To elucidate the links of Klotho with all-cause mortality in diabetic patients, a multivariate Cox proportional hazards regression model was employed. The relationship was further explored using the restricted cubic spline model, threshold analysis, and subgroup analysis. Additionally, a mediation analysis was conducted to unravel the influence of age on the observed correlations.

Throughout the observation period, which had a median duration of 84 months, the incidence of all-cause mortality reached 18.511%. The Cox model analysis revealed a statistically significant association between Klotho levels and all-cause mortality. Further, the application of restricted cubic splines revealed a nuanced, nonlinear relationship between exposure factors and outcome across the entire study population (nonlinear P < 0.001), pinpointing a critical threshold at 829.138 pg/mL. Subgroup analyses showed consistent correlation between Klotho levels and mortality across various groups. Intriguingly, mediation analysis indicated that age was a significant mediator, accounting for 76.1% of the observed correlation of Klotho levels with all-cause mortality among diabetic patients.

Low levels of Klotho were found to be strongly associated with an increased risk of all-cause mortality in individuals with diabetes (Klotho levels < 829.138 pg/ml), and a nonlinear relationship was observed between these two variables. These associations were largely mediated by age.

Diabetes is a chronic metabolic disease that is endemic worldwide and is characterized by persistent hyperglycemia accompanied by multiple severe complications, including cardiovascular disease, kidney dysfunction, neuropathy, and retinopathy. The pathogenesis of diabetes mellitus and its complications is multifactorial, involving various molecular and cellular pathways. In recent years, research has indicated that mechanisms of cell death play a significant role in the advancement of diabetes and its complications. PANoptosis is a complex phenomenon caused by three cell death pathways: programmed apoptosis, necroptosis and pyroptosis. The contribution of PANoptosis to diabetes and its complications remains incompletely understood. Non-coding RNA, an important molecule in gene expression regulation, has shown significant regulatory functions in a variety of diseases. This paper reviews the underlying mechanisms of diverse types of non-coding RNAs (including lncRNA, miRNA and circRNA) in regulating PANoptosis and their specific contributions in diabetes, aiming to explore how non-coding RNAs influence PANoptosis and their effects in diabetes.

Background: Metabolic syndrome is a complex disorder characterized by the coexistence of multiple risk factors, including dysglycemia, hypertension, dyslipidemia, and visceral obesity. Both metabolic syndrome and diabetes mellitus are closely associated with the onset of microvascular complications such as retinopathy, polyneuropathy, and nephropathy. Methods: This narrative review analyzed 137 studies published up to 2025, retrieved from PubMed and Crossref databases. The objective was to identify and evaluate potential biomarkers that could facilitate the early detection of microvascular complications in patients with metabolic syndrome. Results: Several biomarkers demonstrated a strong correlation with microvascular complications in individuals with metabolic syndrome. These findings suggest their potential role in early diagnosis and risk assessment. Conclusions: The identification of reliable biomarkers may enhance early detection and targeted interventions for microvascular complications in metabolic syndrome. Further research is essential to validate these markers and establish their clinical applicability in routine medical practice.

Diabetic retinopathy (DR) is associated with abnormal lipid metabolism and inflammation. However, a single lipid or inflammatory parameter cannot accurately predict the prognosis of DR independently, because it is prone to be affected by various confounding factors. This study aimed to explore the relationship between the inflammation-lipid indicator C-reactive protein (CRP)/high-density lipoprotein cholesterol (HDL-C) and DR occurrence in subjects with type 2 diabetes mellitus (T2DM).

This hospital-based retrospective study included 784 T2DM patients. Diabetic retinopathy was diagnosed by nonmydriatic fundus photography and/or fundus examination apparatus. T2DM patients were divided into non-DR and DR groups. Demographics variables, clinical history and serum biochemical indicators of the subjects were collected. We also calculated the CRP/HDL-C ratio. The association between the CRP/HDL-C and DR was assessed using multivariate logistic regression analyses.

A total of 784 participants, 612 without DR and 172 with DR, were included in the final sample analysis. Compared with non-DR participants, the DR diagnostic group had significantly higher CRP/HDL-C (4.03 ± 1.67 vs. 2.66 ± 0.97; p < 0.001). Then, the patients were grouped based on the quartiles of CRP/HDL-C, there was a gradual increase in the prevalence of DR was noted in T2DM patients along with the increased quartile of the CRP/HDL-C ratio (Q1: 7.65%; Q2: 15.31%; Q3: 19.90%; Q4: 44.90%; p = 0.028). After adjustment for the impact of various covariates, the odds ratio (OR) of the third and fourth vs. the first quartile of CRP/HDL-C were 2.905 (95% confidence interval [CI]: 1.372 ~ 6.152, p = 0.005) and 9.938 (95% CI: 4.987 ~ 19.804, p < 0.001), respectively. Further, multivariate logistic regression model showed that the CRP/HDL-C ratio (OR 3.176, 95% CI: 1.280 ~ 7.877, p = 0.013) was identified as risk factor for DR. Moreover, the area under the curve (AUC) to evaluate the predictive value of CRP/HDL-C for the risk of DR occurrence was 0.752 (95% CI: 0.711 ~ 0.794).

The ratio of C-reactive protein (CRP) to high-density lipoprotein cholesterol (HDL-C) is associated with DR in patients with T2DM, and CRP/HDL-C may be an effective marker to help identify the risk of DR in patients with T2DM.

Coenzyme Q10 (CoQ10) is a naturally occurring antioxidant that has been suggested to have beneficial effects on lipid profiles and blood pressure. This systematic review and meta-analysis aim to evaluate the effects of CoQ10 supplementation on these parameters in patients with Type 2 Diabetes (T2D).

To assess the impact of CoQ10 supplementation on lipid profiles and blood pressure in individuals diagnosed with Type 2 Diabetes.

A systematic literature search was conducted in databases such as PubMed, Cochrane Library, and Scopus for randomized controlled trials (RCTs) published up to July 2024. Studies included were those that examined the effects of CoQ10 supplementation on lipid profiles (total cholesterol, LDL, HDL, triglycerides) and blood pressure (systolic and diastolic) in T2D patients.

16 studies were included. CoQ10supplementation reduced SBP (WMD: -3.86 mmHg, 95% CI: -6.01 to -1.71, P = 0.014, I2 = 83.7%; P < 0.001) and DBP (WMD: -2.70 mmHg, 95% CI: -4.50 to -0.91, P = 0.024, I2 = 92.1%; P < 0.001), but did not change lipid profile. Additionally, subgroup analysis indicated that the effects of CoQ10 on lipid profiles levels were more pronounced in studies where the daily dosage of CoQ10 was 100 mg or less, and the duration of the study was under 12 weeks.

Coenzyme Q10 supplementation appears to have a beneficial effect on lipid profiles and may contribute to lowering blood pressure in patients with Type 2 Diabetes. These findings suggest that CoQ10 could be a valuable adjunctive therapy for managing cardiovascular risk in this population. Additional in-depth research is needed to validate these findings and understand the underlying mechanisms in more detail.

Type 2 diabetes mellitus (T2DM) is associated with chronic hyperglycemia, leading to severe complications, including increased risk of cancer. Protein tyrosine phosphatase non-receptor type 3 (PTPN3) is implicated in both T2DM and cancer progression. The aim of the present study was to investigate the role of PTPN3 genetic polymorphisms and expression in patients with T2DM, as well as to examine changes in body weight, blood glucose levels, and hepatic PTPN3 expression in db/db obese mice in comparison with control mice at 4, 16 and 32 weeks. A total of 469 patients with T2DM and 1,699 healthy control subjects were analyzed for PTPN3 genetic polymorphisms using blood samples. Additionally, the body weight of genetically diabetic obese db/db mice and genotype control mice, and their fasting blood glucose and PTPN3 mRNA and protein expression levels were assessed in the respective liver tissues at different stages of T2DM progression (4, 16 and 32 weeks) using reverse transcription-quantitative PCR, western blot and immunohistochemistry staining analyses. The allele C frequency of rs75235286 (82.1 vs. 79.1%, P=0.044) and allele G frequency of rs17202063 (82.8% vs. 79.5%, P=0.027) in PTPN3 SNPs differed significantly between T2DM patients and healthy controls. Additionally, the body weight of db/db mice and blood glucose levels were significantly increased from the 4th to 32nd week compared with control mice. Furthermore, db/db mice exhibited significantly elevated hepatic mRNA and protein expression levels of PTPN3 compared with control mice, especially at the 32nd week. Taken together, these findings suggested that an increased level of PTPN3 expression may serve a role in the progression of diabetic complications in patients with T2DM, highlighting the importance of further investigation into PTPN3 as a potential therapeutic target to decrease cancer risk and enhance treatment outcomes in T2DM.

Diabetes mellitus (DM) is a significant global health issue, associated with various microvascular and macrovascular complications that significantly impair patients' quality of life as well as healthspan and lifespan. Despite the availability of several anti-diabetic medications with different mechanisms of action, there remains no definite curative treatment. Hence, discovering new efficient complementary therapies is essential. Natural products have received significant attention due to their advantages in various pathological conditions. Resveratrol is a natural polyphenol that possesses antioxidant and anti-inflammatory properties, and its efficacy has been previously investigated in several diseases, including DM. Herein, we aimed to provide a holistic view of the signaling pathways and mechanisms of action through which resveratrol exerts its effects against DM and its complications.

The aim of this study is to explore the impact of blood lipids and statins on renal function and all-cause mortality in patients with diabetic nephropathy (DN). PubMed, Embase, Web of Science, and Cochrane Library were systematically searched until April 9, 2024, for relevant studies of blood lipids and statins on renal function and all-cause mortality in patients with DN. After the selection, total cholesterol levels (TC), total triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), estimated glomerular filtration rate (eGFR), urinary albumin excretion (UAE), serum creati-nine (SCR), end-stage renal disease (ESRD), and all-cause mortality indexes were extracted for finally meta-analysis. In total, 25 papers containing 21,411 patients with DN were finally included in this study. Levels of TC and LDL-C, which are continuous variables, were higher in DN patients who developed ESRD [TC/weighted mean difference (WMD) = 0.517, 95 % confidence interval (CI): (0.223, 0.812), p = 0.001; LDL-C/WMD = 0.449, 95%CI: (0.200, 0.698), p < 0.001]. In addition, this study also observed that statins may reduce UAE levels [WMD = -46.814, 95% CI: (-71.767, -21.861), p < 0.001]. Finally, the survey indicated that statins may be associated with an ESRD reduction [HR = 0.884, 95% CI: (0.784, 0.998), p = 0.045]. Blood lipids, particularly TC and LDL-C, may slow the progression of DN to ESRD. Besides, statins may protect the kidneys by lowering the excretion of UAE levels and reducing the risk of ESRD. Based on the above outcomes, the findings of this study provided robust evidence-based medical support for the future prevention, surveillance, and management of DN.

A potassium voltage-gated channel subfamily J member 11 (KCNJ11) is a candidate gene for diabetes and cardiovascular disease. We investigated the relationship of KCNJ11 E23K gene polymorphism with type 2 diabetes (T2DM) and diabetes-related cardiovascular disease (CVD).

In this case-control study, the KCNJ11 E23K (rs5219) single nucleotide polymorphism was evaluated using the PCR-RFLP method in 780 patients with T2DM and 425 healthy controls. The genotype distribution was compared between subgroups of patients with CVD (524) and without CVD (256).

The genotyping results showed that the T allele and TT genotype were associated with the risk of T2DM (OR 1.26, p = 0.008 and OR 1.55, p = 0.0019, respectively). The T2DM group was analyzed according to the presence or absence of CVD. The T allele frequency was significantly higher in CVD+ than CVD- patients (49% vs 28%, p = 0.0001). The frequency of TT genotype in CVD+ subgroup was 20% compared to 8.5% in CVD-. This shows the significant correlation of the T allele with CVD in T2DM patients in all genetic association models. The OR for T allele was 2.44, p < 0.0001 representing 2.5-fold higher odds of CVD. For TT genotype, the OR 5.61, p < 0.0001 represents almost 6-fold higher risk of CVD development. The multiple logistic regression analysis showed that KCNJ11 E23K polymorphism was a significant risk predictor for CVD development (p < 0.0001).

This is the first study of the relationship between KCNJ11 gene polymorphism and cardiovascular risk in T2DM patients in Polish population. The E23K (rs5219) polymorphism is associated with T2DM. It also increases the risk of cardiovascular disease in T2DM patients. If confirmed in other studies, it can be considered a potential marker for predicting the risk of CVD in T2DM patients.

Diabetic nephropathy (DN) is a microvascular complication of type 2 diabetes mellitus (T2DM) that develops after years of T2DM and affects approximately one in four diabetic patients. Thioredoxin (TXN), thioredoxin reductase (TXNRD), and thioredoxin-interacting protein (TXNIP) are part of the thioredoxin antioxidant system, which is involved in DN. We included 897 Slovenian patients with T2DM lasting more than 10 years in our preliminary study. In total, 344 patients with DN were included in our case group, while 553 without DN comprised our control group. The genotypes of TXN2 rs8140110, TXNRD2 rs1548357, and TXNIP rs7212 were determined for all participants using real-time PCR. We found a statistically significant association between the T allele of the TXN2 rs8140110 polymorphism and DN (p < 0.001; OR: 0.52; 95% CI: 0.36-0.74). The TT and TC genotypes were also significantly less likely to develop DN in comparison to the CC genotype according to the dominant model of inheritance (p < 0.001; OR: 0.51; 95 CI: 0.34-0.75). We did not find a statistically significant association between rs1548357 or rs7212 and DN. To conclude, the rs8140110 polymorphism in the TXN2 gene is associated with DN in Slovenian patients with T2DM.

Erectile dysfunction (ED) is considered one of the complications of diabetes mellitus (DM), affecting about 35-75% of diabetic patients. Studies suggest that anti-diabetic drugs could potentially alleviate ED in diabetics, yet the effects of different drug classes remain unknown.

Our study aims to investigate the influence of various anti-diabetic drugs on ED.

Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review and meta-analysis were carried out, focusing on clinical research linking anti-diabetic drugs and ED. Relevant studies were sought from PubMed, Embase, and Cochrane Library databases. Review Manager 5.4.1 facilitated meta-analysis and subgroup analysis, while Stata 15.1 was employed for sensitivity analysis to ensure result robustness.

An initial search yielded 3,906 articles across databases. After screening the titles and abstracts of 3,906 articles and performing a full-text review of 30 selected articles, we selected three studies for analysis ultimately. Our most significant finding is that glucagon-like peptide-1 receptor agonists (GLP-1RAs) show an advantage over metformin in improving erectile dysfunction in diabetic patients (Z = 2.41, P = 0.02), with a particularly notable effect observed in patients with higher BMI or obesity (Z = 2.26, P = 0.02). This suggests that GLP-1RAs may offer a promising therapeutic option for this patient population. Additionally, thiazolidinediones may enhance sexual function, although their safety and efficacy require further confirmation. Acarbose, insulin, and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) also show potential for positively impacting ED, but more research is needed to establish their efficacy. Finally, the impact of metformin and sulfonylureas on ED remains uncertain, with mixed evidence from existing studies.

In conclusion, GLP-1RAs demonstrate an advantage over metformin in improving erectile dysfunction in diabetic patients. Other antidiabetic drugs also show potential for enhancing erectile function in this population, but further extensive clinical trials are needed to address knowledge gaps and safety concerns.

Background: The lack of availability of test results in vascular surgery outpatient clinics impedes the medical management of vascular risk factors, such as dyslipidaemia and diabetes mellitus. This study sought to evaluate the feasibility of using computer-assisted processes to promote the ordering of routine investigations to promote this management. Method: After consultation with specialist clinicians, clinician-programmers developed a rule-based system to facilitate the ordering of lipid studies and HbA1c prior to vascular clinic appointments. A four-week historical control period prior to the initiation of the intervention was compared to a four-week period following the intervention. Results: There were 1165 patients in the study. In the pre-intervention period, 38.0% of patients had HbA1c and 17.9% had lipid studies in the preceding 6 months. In the post-intervention period, HbA1c and lipid studies were ordered for 100% of vascular outpatients (p < 0.001). Conclusions: The use of computer-assisted processes to facilitate the requesting of routine outpatient investigations is feasible and shows early signs of being effective. Follow-up studies examining clinical endpoints are required.

Diabetic erectile dysfunction (DED) is a prevalent but often overlooked microvascular complication of type 2 diabetes mellitus (T2DM), with strong associations to cardiovascular disease. The pathophysiology of erectile dysfunction (ED) in T2DM patients is more intricate than in non-diabetic individuals, likely involving multiple pathogenic mechanisms such as endothelial dysfunction, vascular alterations, neuropathy, and oxidative stress. Traditional Chinese Medicine (TCM) has long been utilized in the management of DED, drawing on an extensive body of clinical experience. In TCM, DED is typically attributed to imbalances such as renal yang deficiency or insufficiencies in qi and blood. Herbal therapies within the TCM framework offer a multifaceted approach to treatment, targeting not only the replenishment of kidney yang and the regulation of qi and blood but also incorporating strategies for glycemic control and renal protection. This holistic approach has demonstrated effectiveness in alleviating erectile dysfunction in diabetic patients, thereby improving quality of life. However, the complexity of Chinese herbal formulations, with their diverse bioactive constituents, complicates the identification of specific active compounds and the mechanistic understanding of their therapeutic actions. This complexity has contributed to ongoing skepticism regarding the clinical utility of TCM and herbal remedies in the treatment of DED.

This study aimed to investigate the pathological mechanisms underlying the therapeutic effects of TCM in the treatment of DED, with a specific focus on the associated signaling pathways. By elucidating these mechanisms, the study seeks to provide a scientific basis for novel therapeutic strategies and enhance the viability of TCM-based approaches for DED management. Future research should prioritize the development of efficacious Chinese patent medicines tailored for the treatment of DED.

This study utilizes keywords such as "diabetic erectile dysfunction", "signaling pathways", "traditional Chinese Medicine", "bioactive compounds", "herbal", "herbal monomers", and "herbal extracts" to conduct a comprehensive literature search in databases including Embase, PubMed, Web of Science, CNKI, Wanfang, and VIP, spanning all relevant publications up to February 2024.

It has been demonstrated that TCM extract can treat the DED by influencing the signaling pathways involved.

A comprehensive literature review was conducted across multiple databases, followed by rigorous screening, exclusion, summarization, synthesis, and analysis of relevant studies. The results indicate that TCM for DED primarily targets key pathological features, including endothelial dysfunction, vascular and neural abnormalities, and oxidative stress. The underlying mechanisms involve the NO/cGMP, eNOS, and PI3K/Akt/mTOR signaling pathways, contributing to significant improvements in erectile function. These findings provide a scientific basis for the use of TCM in DED, offering viable therapeutic options and innovative strategies to advance TCM-based treatment approaches. Furthermore, TCM exhibits notable potential in mitigating the pathological progression of DED. The pharmacological mechanisms and molecular signaling pathways of TCM extracts have been extensively investigated, underscoring their high value for clinical research and therapeutic development.

Type-2 diabetes mellitus (T2DM) is a major metabolic disorder needing insulin-independent treatments; this study developed Schiff base 1,3,4-thiadiazole as Sodium Glucose Co-transporters 2 (SGLT2) inhibitors.

The target compounds were synthesized followed by docking studies, in vitro and in vivo analysis.

In vitro assay revealed SSS 6 and SSS 2 exhibited high SGLT2 inhibition activity i.e. 78.57% ± 2.8 and 74.60% ± 1.12 compared to dapagliflozin (93.65% ± 4.48) at same dosage in enzyme inhibition assays. In vivo results reveals that SSS 2 significantly improved excretion of urinary glucose (854 ± 46.51 mg/body weight) as compared to dapagliflozin (775 ± 32.68 mg/body weight. SSS 6 and SSS 2 significantly decreased blood glucose levels (137 ± 4.89 mg/dL and 183 ± 15.07 mg/dL) relative to dapagliflozin (158 ± 15.9 mg/dL).

Compounds SSS 6 and SSS 2 emerge as a potential candidates for further investigation as SGLT2 inhibitors for treating T2DM.

Sexual dysfunction (SD) is a common problem among males with type-2 diabetes mellitus (T2DM) but often goes underdiagnosed and underreported. This study aimed to measure the prevalence and risk factors of SD among males with T2DM attending diabetes clinics in Bahrain.

A cross-sectional study was conducted in ten primary health centers in Bahrain using a self-administered questionnaire. The questionnaire consisted of three parts: sociodemographic characteristics and the Sexual Assessment and Dysfunction in Diabetic Men (SAD-M) questionnaire. Descriptive and inferential analyses, including logistic regression, were performed.

A total of 313 patients with an average age of 54.3 ± 10.0 years were included. More than half of the patients had dyslipidemia (n = 220, 70.3%) and hypertension (n = 178, 56.9%). Approximately half of the participants had no morning erections (n = 161, 51.4%), and about a third had less than three sexual intercourse attempts in the last six months (n = 90, 28.8%). Of the participants, 32.6% had moderate SD, 42.5% had mild SD, and 25% had no SD. Univariate analysis showed that male patients with SD were older (P < 0.001) and had a higher body mass index (P = 0.036) compared to those without SD. In addition, unemployed patients (P < 0.001), Bahraini (P < 0.001), had diabetes for 10 years or more (P < 0.001) and had prostate and spinal diseases (P = 0.004 and P = 0.010, respectively) had higher rates of SD. Logistic regression analysis showed that older patients (P = 0.007) and patients with a diabetes duration of more than 10 years were more likely to have SD than their counterparts (OR = 14.908, P < 0.001).

SD is a common problem among males with T2DM in Bahrain, especially among older patients and those with a prolonged history of diabetes. Therefore, primary care providers should consider screening for SD in male patients with T2DM.

Genetic factors play a significant role in the occurrence and clinical course of diabetic peripheral neuropathy (DPN). This research aimed to search the influence of adiponectin single nucleotide polymorphisms (SNPs) on the risk of developing and the severity of DPN in Egyptian patients. Adiponectin SNPs were genotype in 360 participants comprising diabetic sufferers with and without peripheral neuropathy and healthy volunteers via the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. Regarding the + 45 T/G SNP, the TG/ and GG genotypes and the G allele were linked to an rised risk of DPN by comparing the DPN group with both the control and diabetic patients without peripheral neuropathy (DWPN) groups, and when comparing the DWPN group with the control group. Concerning + 276 G/T SNP, the GT genotype and T allele were linked to a declined risk of occuring DPN when comparing the DPN group with both other groups. Patients with DPN had greater frequencies of the GA genotype of the - 11,391 G/A SNP than individuals in the control group, while patients with DPN had greater frequencies of the AA genotype than patients in the DWPN group. Regarding clinic-pathological features, a meaningful rise in the mean values of fasting blood glucose (FBG), duration of the disease, and Toronto Clinical Neuropathy Severity Score (TCSS) were noted in the + 45 GG genotype and G allele carriers. Contrariwise, the + 276 TT genotype carriers had lower mean values for the same clinic-pathological features. For the T allele carriers, the same results were observed in case of duration of the disease and TCSS value. Our results concluded that adiponectin + 45 T/G SNP could be a risk factor considering DPN and the severity of the disease. The - 11391G/A SNP might be associated with DPN. In addition, + 276 G/T SNP could be a protective factor regarding DPN and the severity of the disease.

Hemorrhoidal disease is a common anorectal condition characterized by the enlargement and distal displacement of the typical vascular structures in the anal canal. The relationship between DM, lipid metabolism, and hemorrhoidal disease remains underexplored. This study aims to investigate the prevalence of hemorrhoids and the association between glycemic control and lipid profile in diabetic patients.

This retrospective cross-sectional study included 752 patients who underwent colonoscopy at Erzurum Regional Training and Research Hospital between June 2021 and August 2024. The study population comprised 452 patients with type 2 diabetes mellitus (mean age 63.4 ± 11.0) and 300 nondiabetic patients (mean age 62.8 ± 10.8). The presence of hemorrhoids was confirmed through colonoscopy. Glycemic control parameters, lipid profile, and other biochemical parameters were analyzed.

Hemorrhoids were found in 47.3% (n = 214) of diabetic patients and 17.3% (n = 52) of nondiabetic patients, indicating a significantly higher prevalence in the diabetic group (OR = 4.3, CI = 3.0-6.2, p < 0.001). Diabetic patients with hemorrhoids had significantly higher mean HbA1C (8.1 ± 2.1 vs. 7.5 ± 1.8, p < 0.001), low-density lipoprotein (p < 0.001), and triglyceride levels (p = 0.005) compared to those without hemorrhoids. Additionally, a longer duration of diabetes and higher hypertension prevalence were observed in the hemorrhoid group.

The findings suggest that poor glycemic control and dyslipidemia are significantly associated with an increased prevalence of hemorrhoids in diabetic patients. These results highlight the importance of comprehensive management of diabetes, including lipid control, to potentially reduce the risk of hemorrhoidal disease.

Age is the principal risk factor for neurodegeneration in both the retina and brain. The retina and brain share many biological properties; thus, insights into retinal aging and degeneration may shed light onto similar processes in the brain. Genetic makeup strongly influences susceptibility to age-related retinal disease. However, studies investigating retinal aging have not sufficiently accounted for genetic diversity. Therefore, examining molecular aging in the retina across different genetic backgrounds will enhance our understanding of human-relevant aging and degeneration in both the retina and brain-potentially improving therapeutic approaches to these debilitating conditions.

Transcriptomics and proteomics were employed to elucidate retinal aging signatures in nine genetically diverse mouse strains (C57BL/6J, 129S1/SvlmJ, NZO/HlLtJ, WSB/EiJ, CAST/EiJ, PWK/PhK, NOD/ShiLtJ, A/J, and BALB/cJ) across lifespan. These data predicted human disease-relevant changes in WSB and NZO strains. Accordingly, B6, WSB, and NZO mice were subjected to human-relevant in vivo examinations at 4, 8, 12, and/or 18M, including: slit lamp, fundus imaging, optical coherence tomography, fluorescein angiography, and pattern/full-field electroretinography. Retinal morphology, vascular structure, and cell counts were assessed ex vivo.

We identified common molecular aging signatures across the nine mouse strains, which included genes associated with photoreceptor function and immune activation. Genetic background strongly modulated these aging signatures. Analysis of cell type-specific marker genes predicted age-related loss of photoreceptors and retinal ganglion cells (RGCs) in WSB and NZO, respectively. Fundus exams revealed retinitis pigmentosa-relevant pigmentary abnormalities in WSB retinas and diabetic retinopathy (DR)-relevant cotton wool spots and exudates in NZO retinas. Profound photoreceptor dysfunction and loss were confirmed in WSB. Molecular analyses indicated changes in photoreceptor-specific proteins prior to loss, suggesting photoreceptor-intrinsic dysfunction in WSB. In addition, age-associated RGC dysfunction, loss, and concomitant microvascular dysfunction were observed in NZO mice. Proteomic analyses revealed an early reduction in protective antioxidant processes, which may underlie increased susceptibility to DR-relevant pathology in NZO.

Genetic context is a strong determinant of retinal aging, and our multi-omics resource can aid in understanding age-related diseases of the eye and brain. Our investigations identified and validated WSB and NZO mice as improved preclinical models relevant to common retinal neurodegenerative diseases.

Type 2 Diabetes Mellitus (T2DM) can lead to long-term vascular complications such as diabetic peripheral neuropathy (DPN). This study aimed to investigate the role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) and angiotensin II type 1 receptor (AT1R) A1166C variants in the predisposition to T2DM in the Turkish population and their association with DPN.

The study included 90 T2DM patients (42 with DPN) and 50 healthy individuals. ACE I/D and ATIR A1166C gene regions were analyzed for the variant. Both the general genotype distribution of these variants and the observed genotype ratios were examined separately.

In the T2DM group, the proportion of individuals with the AA genotype of the AT1R A1166C variant was lower than in the control group, and the proportion of individuals with the AC genotype was higher. There was no significant difference in the genotype distribution between the groups for the ACE I/D variant. There was no significant difference in the genotype distribution of the ACE I/D and ATIR A1166C variants in patients with and without DPN.

In the Turkish population, no significant difference was observed in the overall genotype distribution of ACE I/D and AT1R A1166C variants between T2DM patients and healthy individuals, whereas the AC genotype of the AT1R A1166C variant was more frequent in T2DM patients, and the AA genotype was less frequent. For both variants, no significant difference was observed in the genotype distribution between T2DM patients with and without DPN.

The effects of resveratrol supplementation on inflammation and oxidative stress in patients with type 2 diabetes mellitus (T2DM) were controversial. A meta-analysis was performed to assess the changes in levels of inflammation and oxidative stress in patients with T2DM.

Relevant literatures before November 6, 2024 were screened through Web of Science,Embase,the Cochrane Library and other sources (ClinicalTrials, ProQuest Dissertations and Theses). The quality of the literature was evaluated according to the Cochrane Handbook of Systematic Reviews. The study quality was assessed using the risk-of-bias 2 tool and the Grading of Recommendations Assessment,Development and Evaluation (GRADE) system. Review Manager 5.3 conducted meta-analysis of the data included in the literature.

This meta-analysis was conducted in six randomized controlled trials involving 533 participants. Our results showed that supplementation with resveratrol significantly reduced C-reactive protein levels(SMD = -1.40, 95%CI(-2.60, -0.21), P = 0.02; Level of evidence: low), lipid peroxide levels (SMD = -0.99, 95%CI(-1.36, -0.61), P < 0.00001; Level of evidence: low), 8-isoprostanes(SMD = -0.79, 95%CI(-1.16, -0.42), P < 0.0001; Level of evidence: low) and oxidative stress score (SMD = -1.62, 95%CI(-2.49, -0.75), P = 0.0003; Level of evidence: very low). In addition, compared to placebo, Supplementation with resveratrol significantly increased glutathione peroxidase levels (SMD = 0.38, 95%CI(0.03, 0.74), P = 0.04; Level of evidence:low) and catalase levels (SMD = 0.33, 95%CI(0.03, 0.63), P = 0.03; Level of evidence: low). However, no significant difference was observed in improving interleukin-6 levels (SMD = -1.35, 95%CI(-2.75, -0.05), P = 0.06; Level of evidence: very low), tumor necrosis factor α levels (SMD = -3.30, 95%CI(-7.47, 0.87), P = 0.12; Level of evidence: very low), superoxide dismutase levels (SMD = 0.39, 95%CI(-0.26, 1.04), P = 0.24; Level of evidence: very low), total antioxidant capacity levels (SMD = 0.39, 95%CI(-0.23, 1.00), P = 0.21; Level of evidence: very low) and malondialdehyde levels (SMD = -3.36, 95%CI(-10.30, 3.09), P = 0.29; Level of evidence: very low).

Resveratrol improved inflammation and oxidative stress in T2DM patients to some extent. This provides a new idea and method for clinical treatment. However, due to the limitations of the study, more large-sample, multi-center clinical studies are needed to verify this conclusion.

Type 2 Diabetes Mellitus (T2DM) is closely associated with the development of vascular damage in the heart. In this study, the researchers aimed to determine whether Aerobic Training (AT) and Vitamin D supplementation (Vit D) could alleviate heart complications and vascular damage caused by diabetes. The effects of an eight-week AT program and Vit D on the expression of miR-1, IGF-1 genes, and VEGF-B in the cardiomyocytes of rats with T2DM.

This study was an experimental investigation. Fifty male Wistar rats were divided into 2 groups Non-Diabetic Obese Control (NC; n = 10), and diabetic (n = 40). The rats were then randomly divided into four groups: AT plus Vit D (AT + Vit D; n-=10), AT (n = 10), Vit D (Vit D; n = 10), and Control Diabetic (C; n = 10). The exercise groups underwent treadmill training for 8 weeks at an aerobic intensity equal to 50-60% of their maximal oxygen uptake (VO2max), which corresponded to a speed of 15-25 m/min at a 0% incline, for 30-60 min per day, 5 days per week. The Vit D and AT + Vit D groups received 5,000 international units (IU) of Vitamin D (combined with sesame oil) per week via a single-dose injection. Data were analyzed using one-way analysis of variance (ANOVA) followed by Tukey's post-hoc test for multiple comparisons among the groups. Paired data were analyzed using paired t-tests.

The results showed that BW, BMI, and FI significantly decreased in the AT + Vit D (p = 0.001 for all variables), AT (p = 0.001 for all variables), and Vit D (p = 0.001 for all variables) groups compared to baseline. In contrast, BW, BMI, and FI increased in the C (p = 0.001, p = 0.006, p = 0.020, respectively) and NC (p = 0.001 for all variables) groups. Significant differences were observed between the groups in terms of visceral fat, insulin, glucose, and HOMA-IR (p = 0.001 for all variables). Serum 25-hydroxyvitamin D levels varied significantly among the groups (p = 0.002). The AT + Vit D group showed significantly increased VEGF-B (p = 0.001 for both comparisons), upregulated IGF-1 (p = 0.001 for both comparisons), and downregulated miR-1 (p = 0.001 for both comparisons) compared to the AT and Vit D groups, respectively.

AT and Vit D increased the expression of IGF-1 and VEGF-B in the heart of T2DM rats while decreasing the expression of miR-1. These effects were more pronounced when AT and Vit D were combined. The study concludes that the combination of AT and Vit D has cardio-protective effects in T2DM rats, counteracting abnormal angiogenesis induced by diabetes. These effects are mediated, at least in part, by the upregulation of IGF-1 and VEGF-B, and the downregulation of miR-1.

Diabetic peripheral neuropathy (DPN) is length-dependent peripheral nerve damage arising as a complication of type 1 or type 2 diabetes in up to 50% of patients. DPN poses a substantial burden on patients, who can experience impaired gait and loss of balance, predisposing them to falls and fractures, and neuropathic pain, which is frequently difficult to treat and reduces quality of life. Advanced DPN can lead to diabetic foot ulcers and non-healing wounds that often necessitate lower-limb amputation. From a socioeconomic perspective, DPN increases both direct health-care costs and indirect costs from loss of productivity owing to neuropathy-related disability. In this Review, we highlight the importance of understanding country-specific and region-specific variations in DPN prevalence to inform public health policy and allocate resources appropriately. We also explore how identification of DPN risk factors can guide treatment and prevention strategies and aid the development of health-care infrastructure for populations at risk. We review evidence that metabolic factors beyond hyperglycaemia contribute to DPN development, necessitating a shift from pure glycaemic control to multi-targeted metabolic control, including weight loss and improvements in lipid profiles.

Patients with diabetes mellitus (DM) often exhibit refractory erectile dysfunction (ED). Red-light-controllable nitric oxide donor (NORD-1) and red-light irradiation have successfully enhanced erectile function in intact rats. In this study, we investigated whether the combination of NORD-1 and red-light irradiation effectively treated ED in streptozotocin (STZ)-treated rats with DM.

Seven-week-old male Sprague-Dawley rats were used in this study. Rats in the DM and sham groups received intravenous STZ (50 mg/kg) and saline, respectively. One week after treatment, the blood glucose level of rats in the DM group was >250 mg/dL. Five weeks after the treatment, we performed a functional study by measuring intracavernous pressure (ICP) under cavernous nerve stimulation before and after NORD-1 treatment with and without light irradiation. Additionally, we performed an isometric tension study using the corpus cavernosum of rats treated with NORD-1 or the control compound, SiR650.

The ICP/mean arterial pressure (MAP) ratio was significantly lower in the DM group than in the sham group before and after NORD-1 treatment without light irradiation (both p<0.05). After NORD-1 treatment with light irradiation, the ICP/MAP ratio in the sham and DM groups was significantly enhanced than before and after NORD-1 treatment without light irradiation (all p<0.05). The ICP/MAP ratio in the DM group after NORD-1 with light irradiation was similar to that in the sham group under normal conditions before NORD-1 treatment. Moreover, the systemic blood pressure was not affected by NORD-1 or light irradiation. In the tension study, the corpus cavernosum of rats treated with SiR650 was not changed by red light in the sham or DM groups. However, the rats treated with NORD-1 were strongly relaxed by red light in both groups.

NORD-1 and red-light irradiation could improve ED in the presence of DM without lowering blood pressure.

The correlation between thyroid hormone (TH) sensitivity and microvascular complications of type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to explore the association between TH sensitivity and the risk of diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic neuropathy (DNP) in euthyroid T2DM patients. This study included a total of 946 hospitalized T2DM patients and calculated their sensitivity to the TH index, and each patient completed screenings for DKD, DR, and DNP. Multivariate logistic regression, generalized additive modeling, and subgroup analysis were used to assess the association between TH index sensitivity and the risks of DKD, DR, and DNP. After adjusting for confounding factors, a significant linear correlation was observed between the sensitivity of the thyroid feedback quartile index 3 (TFQI3) and DKD risk. However, the sensitivities of thyroid-stimulating hormone index (TSHI), thyrotropin thyroxine resistance index (TT4RI) and partial thyroid feedback quartile index (PTFQI) exhibited nonlinear correlations with the risk of developing DKD. The effect sizes to the left of the inflection point for TSHI, TT4RI and PTFQI were (odd ratio [OR] = 0.53, 95% confidence interval [CI]: 0.288-0.977), (OR = 0.863, 95%Cl: 0.751-0.992) and (OR = 0.007, 95%Cl: 0-0.724), respectively. However, there was no significant correlation between TH index sensitivity and DR/DNP risk. This study provides valuable insights into the relationship between TH sensitivity and the risks of DKD, DR, and DNP, with substantial clinical implications for individual prediction among T2DM patients.

Probiotics are gaining recognition as a viable strategy for mitigating cardiovascular risk factors. Specifically, recent studies highlight their potential benefits in managing cholesterol levels, blood pressure, and inflammation, which are critical components in the prevention of cardiovascular diseases (CVD). This comprehensive review aims to elucidate the impact of probiotic consumption on major cardiovascular risk factors, including individuals with hypertension, type II diabetes mellitus, metabolic syndrome, hypercholesterolemia, and in secondary prevention in coronary artery disease. Scientific evidence based on human studies suggests that probiotic consumption is associated with positive effects on anthropometric measures, inflammation markers, blood pressure, glucose metabolism markers, lipid profiles, and endothelial function. However, these findings should be interpreted pragmatically and acknowledge the significant variability in results. This variability may be attributed to factors such as probiotic composition (single strain or multiple strains), the characteristics of the delivery matrix (food, capsules, and sachets), the duration of the intervention, the dosage regimen, and baseline health profiles of the participants. Incorporating probiotics as part of a comprehensive and healthy lifestyle approach can be considered a feasible strategy for both the prevention and management of CVD. However, further research is needed on factors influencing the effect of probiotics, such as: (i) optimal probiotic strain(s), (ii) appropriate dosage, (iii) duration of treatment, (iv) optimal delivery vehicle, and (v) sex-specific differences.

Diabetes is one of the most catastrophic diseases ruling every corner of the world, and this has led to elevated incidents of end-stage kidney disease (ESKD). The standard treatment for ESKD is kidney transplantation/replacement, which is limited due to a deficiency of donors. Hence, dialysis has become the second-best option for treating patients with ESKD. Patients with ESKD with underlying diabetes have an additional risk of complications and infections over non-diabetic ESKD patients. Furthermore, these patients also experience variations in blood glucose levels and are more liable to develop malnutrition. This article elaborates on the different dialysis methods for ESKD patients. This editorial highlights the evidence-based studies that include randomized clinical trials, cohort studies, retrospective studies and case-control studies and suggests the most suitable type of dialysis under the following components.

Purpose: To identify baseline characteristics that predict visual outcomes after a lapse in treatment among patients with diabetic macular edema (DME) who received intravitreal antivascular endothelial growth factor injections. Methods: In this retrospective study, patients with DME who had lapses in treatment of 3 months or longer were separated into 2 groups (stable vision, n = 201; vision loss, n = 61) based on an Early Treatment Diabetic Retinopathy Study vision loss threshold of 10 letters. Stepwise backward logistic regression was used to analyze baseline factors associated with vision loss and to create a predictive algorithm. Results: In the final regression model, the length of lapse in treatment (odds ratio [OR]; 1.15, 95% CI, 1.07-1.25), diabetic foot disease (OR, 3.02; 95% CI, 1.09-8.2), and Medicaid insurance (OR, 4.60; 95% CI, 1.20-18.7) were positively associated with vision loss (P < .05). Time since diagnosis of diabetic retinopathy (OR, 0.95; 95% CI, 0.91-0.99) was negatively associated with vision loss (P < .05). The final prediction model had a sensitivity of 20% and a specificity of 84%, with an area under the curve of 65%. Conclusions: For patients with DME at high risk for a lapse in treatment, baseline characteristics can help predict vision loss and guide management.

China has the largest population of individuals with diabetes, and the prevalence of various complications among patients with type 2 diabetes remains high. Diabetic nephropathy affects approximately 20% to 40% of diabetic patients, becoming a major cause of chronic kidney disease and end-stage renal disease. Furthermore, around 50% of patients develop diabetic peripheral neuropathy (DPN), which is closely associated with physical disability, increased healthcare costs, and reduced work productivity. There is an urgent need for novel strategies in prevention, diagnosis, and treatment to improve patient outcomes.

In this study, 163 patients with type 2 diabetes were selected as the observation group and further divided into three subgroups based on homocysteine (HCY) levels. The study measured several clinical parameters, including homocysteine, blood glucose, blood lipids, glycated hemoglobin, urinary microalbumin, urinary albumin-to-creatinine ratio (ACR), electromyography, and highly-sensitive C-reactive protein (CRP), among others. The levels of these indicators were analyzed and compared across the subgroups.

The results revealed significant differences in uric acid, creatinine, urinary microalbumin, urinary ACR, and nerve conduction velocity (right tibial nerve sensory conduction) among different HCY levels in patients with type 2 diabetes (P < 0.05). Linear regression analysis indicated that homocysteine levels were associated with systolic blood pressure, glycated hemoglobin, fasting C-peptide, uric acid, creatinine, urinary microalbumin, and nerve conduction velocity (including motor conduction velocity of the ulnar nerve and sensory conduction velocity of the sural nerve).

The clinical assessment of homocysteine in diabetic patients holds significant importance in the prevention of microvascular complications. Lowering HCY levels may offer a promising therapeutic approach for managing microvascular disease in diabetes.

Diabetic peripheral neuropathy (DPN) results in an enormous burden and reduces the quality of life for patients. Considering there is no specific drug for the management of DPN, traditional Chinese medicine (TCM) has increasingly drawn attention of clinicians and researchers around the world due to its characteristics of multiple targets, active components, and exemplary safety.

To summarize the current status of TCM in the treatment of DPN and provide directions for novel drug development, the clinical effects and potential mechanisms of TCM used in treating DPN were comprehensively reviewed.

Existing evidence on TCM interventions for DPN was screened from databases such as PubMed, the Cochrane Neuromuscular Disease Group Specialized Register (CENTRAL), and the Chinese National Knowledge Infrastructure Database (CNKI). The focus was on summarizing and analyzing representative preclinical and clinical TCM studies published before 2023.

This review identified the ameliorative effects of about 22 single herbal extracts, more than 30 herbal compound prescriptions, and four Chinese patent medicines on DPN in preclinical and clinical research. The latest advances in the mechanism highlight that TCM exerts its beneficial effects on DPN by inhibiting inflammation, oxidative stress and apoptosis, endoplasmic reticulum stress and improving mitochondrial function.

TCM has shown the power latent capacity in treating DPN. It is proposed that more large-scale and multi-center randomized controlled clinical trials and fundamental experiments should be conducted to further verify these findings.

Diabetic nephropathy (DN) is one of the most common and serious complications of diabetes. The purpose of this study was to explore the relationship between serum microRNA-338-3p (miR-338-3p) and miR-105-3p and bone metabolic markers in patients with DN at different stages.

A total of 153 patients diagnosed and treated in the Department of Nephrology from July 2020 to October 2021 were selected as the study objects. According to the staging criteria of diabetic nephropathy and 24-h urinary albumin quantitative level, the patients were divided into control group (35 cases), microalbuminuria group (37 cases), clinical stage albuminuria group (27 cases) and renal failure group (54 cases). Gene expressions were measured by real-time fluorescence quantitative PCR. The correlation was analyzed by Spearman. Serum miR-338-3p and miR-150-5p in the prediction of renal failure in DN was analyzed by ROC curve.

The levels of urinary albumin and serum creatinine were markedly increased with the increase of DN stage (p < 0.05). Compared with the microalbuminuria group, the expression levels of serum miR-383-3p, serum miR-105-3p, 25(OH)-D, BGP and PINP were obviously decreased, but the expression of parathyroid hormone (PTH) and type I collagen (β-CTX) was largely increased in clinical proteinuria group (p < 0.05). Compared with the clinical proteinuria group, the expression levels of serum miR-383-3p, serum miR-105-3p, 25(OH)-D, BGP and PINP were largely decreased, but the expression of PTH and β-CTX was obviously increased in the renal failure group (p < 0.05). Spearman correlation results showed that serum expressions of miR-383-3p and miR-105-3p were negatively correlated with PTH and β-CTX, and positively correlated with 25(OH)-D, BGP and PINP (p < 0.05). ROC curve analysis showed that the AUC of serum miR-338-3p and miR-150-5p was 0.896 with the specificity and sensitivity of 96.66% and 73.47%, which had certain predictive value for the occurrence of renal failure in DN.

The expression levels of serum miR-383-3p and miR-105-3p were significantly correlated with bone metabolism markers. The combined test can provide new ideas and insights for the clinical treatment of osteoporosis in DN.

Diabetic kidney disease (DKD) is a prominent complication arising from diabetic microangiopathy, and its prevalence and renal impact have placed it as the primary cause of end-stage renal disease. Traditional Chinese Medicine (TCM) has the distinct advantage of multifaceted and multilevel therapeutic attributes that show efficacy in improving clinical symptoms, reducing proteinuria, protecting renal function, and slowing DKD progression. Over recent decades, extensive research has explored the mechanisms of TCM for preventing and managing DKD, with substantial studies that endorse the therapeutic benefits of TCM compounds and single agents in the medical intervention of DKD.

This review lays the foundation for future evidence-based research efforts and provide a reference point for DKD investigation.

The relevant literature published in Chinese and English up to 30 June 2023, was sourced from PubMed, Cochrane Library, VIP Database for Chinese Technical Periodicals (VIP), Wanfang Data, CNKI, and China Biology Medicine disc (CBM). The process involved examining and summarizing research on TCM laboratory tests and clinical randomized controlled trials for DKD treatment.

The TCM intervention has shown the potential to inhibit the expression of inflammatory cytokines and various growth factors, lower blood glucose levels, and significantly affect insulin resistance, lipid metabolism, and improved renal function. Furthermore, the efficacy of TCM can be optimized by tailoring personalized treatment regimens based on the unique profiles of individual patients. We anticipate further rigorous and comprehensive clinical and foundational investigations into the mechanisms underlying the role of TCM in treating DKD.

Imaging techniques that quantitatively and automatically measure changes in the myocardial microcirculation in patients with diabetes are lacking.

To detect diabetic myocardial microvascular complications using a novel automatic quantitative perfusion MRI technique, and to explore the relationship between myocardial microcirculation dysfunction and fibrosis.

Prospective.

101 patients with type 2 diabetes mellitus (T2DM) (53 without and 48 with complications), 20 healthy volunteers.

3.0T; modified Look-Locker inversion-recovery sequence; saturation recovery sequence and dual-bolus technique; segmented fast low-angle shot sequence.

All participants underwent MRI to determine the rest myocardial blood flow (MBF), stress MBF, myocardial perfusion reserve (MPR), and extracellular volume (ECV), which represents the extent of myocardial fibrosis.

Kolmogorov-Smirnov test, Shapiro-Wilk test, Kruskal-Wallis H test, Mann-Whitney U test, chi-square test, Spearman correlation coefficient, multivariable linear regression analysis. P < 0.05 was considered statistically significant.

The rest MBF was not significantly different between the T2DM without complications group (1.1, IQR: 0.9-1.3) and the control group (1.1, 1.0-1.3) (P = 1.000), but it was significantly lower in the T2DM with complications group (0.8, 0.6-1.0) than in both other groups. The stress MBF and MPR were significantly lower in the T2DM without complications group (1.9, 1.5-2.3, and 1.7, 1.4-2.1, respectively) than in the control group (3.0, 2.6-3.5, and 2.7, 2.4-3.1, respectively), and were also significantly lower in the T2DM with complications group (1.1, 0.9-1.4, and 1.4, 1.2-1.8, respectively) than in the T2DM without complications group. A decrease in MBF and MPR were significantly associated with an increase in the ECV.

Quantitative perfusion MRI can evaluate myocardial microcirculation dysfunction. In T2DM, there was a significant decrease in both MBF and MPR compared to healthy controls, with the decrease being significantly different between T2DM with and without complications groups. The decrease of MBF was significantly associated with the development of myocardial fibrosis, as determined by ECV.

2 TECHNICAL EFFICACY: Stage 3.

The global burden of type 2 diabetes (T2D) and colorectal cancer (CRC) continues to rise. Observational studies have suggested a link between T2D and an elevated risk of CRC. However, these studies are often susceptible to confounding factors and reverse causation, leading to inconsistent findings. There is a specific gap in knowledge regarding the causal nature of the relationship between T2D and CRC, which this study aims to address using a more robust approach. To fill this gap, we employed Mendelian randomization (MR), a method that uses genetic variants as instrumental variables (IVs) to infer causality, providing clearer insight into the genetic links between T2D and CRC.

A bidirectional MR study was conducted to investigate the causal links between T2D and CRC. Genetic instruments for T2D were derived from two large genome-wide association studies (GWAS) with a total sample size of X individuals, and CRC genetic instruments were obtained from a GWAS with Y individuals. The MR analysis utilized the inverse-variance weighted (IVW) method as the primary analysis, alongside sensitivity analyses such as heterogeneity and pleiotropy analysis to account for potential pleiotropy and bias. Additionally, to enhance the robustness of the findings and minimize the influence of data from different GWAS sources, we performed a meta-analysis of the IVW results.

The MR analysis and meta-analysis revealed that genetically predicted T2D is associated with an increased risk of CRC (Pooled ORIVW = 1.07, 95% CI 1.02-1.12, P = 0.003). However, the reverse analysis did not indicate a causal effect of genetically predicted CRC on T2D risk (Pooled ORIVW = 1.02, 95% CI 0.96-1.09, P = 0.469). Sensitivity analyses supported the robustness of these findings, indicating no evidence of heterogeneity or pleiotropic effects that could bias the results (all P > 0.05).

Our bidirectional MR study and meta-analysis provide evidence that T2D increases the risk of colorectal cancer. However, there is no evidence to support a reverse causal relationship. These findings highlight the importance of monitoring and managing T2D as part of CRC prevention strategies.

The oral cavity may suffer from diseases and lesions of different natures that can result in changes to the underlying microvasculature. These changes are typically observed during the examination of biopsy samples, but there is still a need to investigate methods for characterizing them in live tissues. Capillaroscopy, a medical imaging technique using polarized light and magnification, has shown promise in providing enhanced imaging of the oral mucosa microvasculature in preliminary studies. The present work proposed to review the literature on what capillaroscopy is, its applications in the imaging of oral mucosa microvasculature, and its diagnostic and prognostic significance in various diseases and conditions. While there is the limited literature available, further research in oral capillaroscopy, particularly in the field of oral oncology, is needed to determine its potential benefits in diagnosing and predicting outcomes for potentially malignant oral disorders and cancers.

The number of people suffering from type 2 diabetes has rapidly increased. Taking into account, that elevated intracellular lipid concentrations, as well as their metabolism, are correlated with diminished insulin sensitivity, in this study we would like to show lipids spectroscopy markers of diabetes. For this purpose, serum collected from rats (animal model of diabetes) was analyzed using Fourier Transformed Infrared-Attenuated Total Reflection (FTIR-ATR) spectroscopy. Analyzed spectra showed that rats with diabetes presented higher concentration of phospholipids and cholesterol in comparison with non-diabetic rats. Moreover, the analysis of second (IInd) derivative spectra showed no structural changes in lipids. Machine learning methods showed higher accuracy for IInd derivative spectra (from 65 % to 89 %) than for absorbance FTIR spectra (53-65 %). Moreover, it was possible to identify significant wavelength intervals from IInd derivative spectra using random forest-based feature selection algorithm, which further increased the accuracy of the classification (up to 92 % for phospholipid region). Moreover decision tree based on the selected features showed, that peaks at 1016 cm-1 and 2936 cm-1 can be good candidates of lipids marker of diabetes.

Recent studies have linked sarcopenia development to the hallmarks of diabetes, oxidative stress, and insulin resistance. The anti-oxidant and insulin sensitivityenhancing effects of incretin-based therapies may provide a promising option for the treatment of sarcopenia. This review aimed to unveil the role of oxidative stress and insulin resistance in the pathogenesis of sarcopenia and explore the potential benefits of incretin-based therapies in individuals with sarcopenia.

PubMed, the Cochrane Library, and Google Scholar databases were searched by applying keywords relevant to the main topic, to identify articles that met our selection criteria.

Incretin-based therapies manifested anti-oxidant effects by increasing the anti-oxidant defense system and decreasing free radical generation or by indirectly minimizing glucotoxicity, which was mainly achieved by improving insulin signaling and glucose homeostasis. Likewise, these drugs exhibit insulin-sensitizing activities by increasing insulin secretion, transduction, and β-cell function or by reducing inflammation and lipotoxicity.

Incretin-based therapies, as modulators of oxidation and insulin resistance, may target the main pathophysiological factors of sarcopenia, thus providing a promising strategy for the treatment of this disease.

Previous observational studies about the link between dietary factors and diabetic microvascular complications (DMCs) is controversial. Thus, we systemically assessed the potential causal relationship between diet and DMCs risk using Mendelian randomization (MR) methods.

We used genome-wide association studies (GWAS) statistics to estimate the causal effects of 17 dietary patterns on three common DMCs in European. Summary statistics on dietary intakes were obtained from the UK biobank, and data on DMCs [diabetic retinopathy (DR), diabetic nephropathy (DN), and diabetic neuropathy (DNP)] were obtained from the FinnGen Consortium. A two-sample MR (TSMR) was conducted to explore the causal relationships of dietary habits with DMCs. In addition, multivariable MR analysis (MVMR) was performed to adjust for traditional risk factors for eating habits, and evaluated the direct or indirect effects of diet on DMCs.

TSMR analysis revealed that salad/raw vegetable intake (odd ratio [OR]: 2.830; 95% confidence interval [CI]: 1.102-7.267; p = 0.0306) and fresh fruit intake (OR: 2.735; 95% CI: 1.622-4.611; p = 0.0002; false discovery rate [FDR] = 0.0082) increased the risk of DR, whereas cheese intake (OR: 0.742; 95% CI: 0.563-0.978; p = 0.0339) and cereal intake (OR: 0.658; 95% CI: 0.444-0.976; p = 0.0374) decreased the risk of DR. Salad/raw vegetable (OR: 6.540; 95% CI: 1.061-40.300; p = 0.0430) and fresh fruit consumption (OR: 3.573; 95% CI: 1.263-10.107; p = 0.0164) are risk factors for DN, while cereal consumption (OR: 0.380; 95% CI: 0.174-0.833; p = 0.0156) is the opposite. And genetically predicted higher pork intake increased the risk of DNP (OR: 160.971; 95% CI: 8.832-2933.974; p = 0.0006; FDR = 0.0153). The MVMR analysis revealed that cheese intake may act as an independent protective factor for DR development. Moreover, fresh fruit intake, salad/raw vegetable intake and pork intake may be independent risk factors for DR, DN and DNP, respectively. Other causal associations between dietary habits and DMCs risk may be mediated by intermediate factors.

This causal relationship study supports that specific dietary interventions may reduce the risk of DMCs.

Globally, diabetes mellitus is a major public health concern affecting 10.5% of the population. Nearly 90% of these people have Type 2 diabetes mellitus (T2DM). In Bhutan, T2DM is prevalent in 5.6% of the population, and around 60% are unaware of their diagnosis of diabetes. There is no baseline information on the rate and the risk factors for complications of diabetes in Bhutan. The study assessed the clinical profile and the risk factors for complications of T2DM at the Jigme Dorji Wangchuk (JDW) National Referral Hospital, Bhutan.

A descriptive cross-sectional study was conducted at the JDW National Referral Hospital, Bhutan, from January to December 2019. Patients with T2DM attending diabetic clinics were included in the study. Demographic variables and metabolic profiles were recorded using a standard pro forma. Descriptive statistics were used to express the results. The association of clinical profiles with the microvascular complication was assessed using multivariate logistic analysis with statistical significance at p < 0.05.

There were 292 patients with T2DM during the study period. The rate of microvascular complication is around 25% in T2DM. Among the complications, diabetic retinopathy occurred in over 51%, followed by neuropathy (29.7%) and nephropathy (18.9%). Over 1/3rd of patients had a duration of diabetes over 10 years with a mean duration of 6.3 (5.4) years, and around 44% (127/292) of them had poor glycemic control (HbA1C ≥ 7%). The age ≥ 60 years and the duration of diabetes ≥ 10 years were independent risk factors for microvascular complications in T2DM patients. Regular exercise prevents retinopathy (OR 0.4, 95%CI 0.2-0.9, p = 0.026).

There is a microvascular complication in 1 in 4 of type 2 diabetic patients. Age over 60 years and a duration of diabetes of more than 10 years are independent risk factors for microvascular complications, and regular exercise is preventive for microvascular complications.

Renal interstitial fibrosis (RIF) is a significant pathological change in diabetic kidney disease (DKD) that can be induced by endothelial-to-mesenchymal transition (EndMT). Lymphangiogenesis, mediated by the vascular endothelial growth factor-C (VEGF-C)/vascular endothelial growth factor receptor-3 (VEGFR-3) pathway, plays a crucial role in the development of RIF in DKD. Although numerous studies have demonstrated the efficacy of empagliflozin in treating renal injury, its effects on lymphangiogenesis in DKD-related RIF and the underlying mechanisms remain unclear. In the present study, significant lymphangiogenesis was assessed in the renal interstitium of patients with DKD. We subsequently explored the relationship between DKD-related RIF and lymphangiogenesis in mouse models, high-glucose (HG)-stimulated renal HK-2 cell lines, and human lymphatic endothelial cells (hLECs). Additionally, we evaluated the effects of empagliflozin on these processes. The results revealed that HG induces lymphangiogenesis, which exacerbates RIF by promoting inflammatory responses. Furthermore, hLECs directly contributed to the progression of DKD-related RIF through EndMT. Further analysis revealed that tubular epithelial cells (TECs) act as effector cells for VEGF-C, with the epithelial-to-mesenchymal transition (EMT) of TECs occurring concurrently with the EndMT of lymphatic vessels. Empagliflozin inhibited RIF in DKD by suppressing the VEGF-C/VEGFR3 pathway and reducing lymphangiogenesis. In conclusion, this study elucidates the interplay between lymphangiogenesis, EndMT, and RIF in DKD and provides new insights into the mechanism by which empagliflozin treats DKD.

Type 2 diabetes mellitus (T2DM) is a globally prevalent chronic condition. Individuals with T2DM are at increased risk of developing complications associated with both macrovascular and microvascular pathologies. These comorbidities reduce patient quality of life and increase mortality. Dietary restriction is a principal therapeutic approach for managing T2DM. This study assessed the effects of various dietary regimens on body weight and metabolic profiles in T2DM patients, aiming to determine the most beneficial interventions for enhancing clinical outcomes and overall well-being.

We conducted a literature search in PubMed, Embase, and Web of Science from 2003 to April 15, 2024. The risk of bias was assessed via the Revised Cochrane risk-of-bias tool for randomized trials (RoB2). The certainty of the evidence was appraised via the confidence in network meta-analysis (CINeMA) framework. Intermittent fasting (IF) was directly compared with continuous energy restriction (CER) via Review Manager 5.4. Network meta-analysis was statistically assessed via R Studio 4.3.3 and STATA 14.0.

Eighteen studies involving 1,658 participants were included. The network meta-analysis indicated that intermittent energy restriction, the twice-per-week fasting, time-restricted eating, fasting-mimicking diets (FMD), and CER interventions were more effective than conventional diets. Direct comparisons revealed that IF was as effective as CER for reducing glycated haemoglobin A1c, body weight, and body mass index. The results of the cumulative ranking analysis demonstrated that FMD had the greatest combined intervention effect, followed by TRE in terms of overall effectiveness.

Both IF and CER exert positive influences on weight control and metabolic profile enhancement in individuals with T2DM, with FMD as part of IF demonstrating the greatest impact. To substantiate these findings, more rigorous randomized controlled trials that directly compare the effects of the different IF regimens with one another and with the CER regimen are needed.