Dysfunction In Diabetic Patients Research Articles

Oxidative Stress, Endothelial Dysfunction, and N-Acetylcysteine in Type 2 Diabetes Mellitus.

Significance: Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality globally. Endothelial dysfunction is closely associated with the development and progression of CVDs. Patients with diabetes mellitus (DM) especially type 2 DM (T2DM) exhibit a significant endothelial cell (EC) dysfunction with substantially increased risk for CVDs. Recent Advances: Excessive reactive oxygen species (ROS) and oxidative stress are important contributing factors to EC dysfunction and subsequent CVDs. ROS production is significantly increased in DM and is critically involved in the development of endothelial dysfunction in diabetic patients. In this review, efforts are made to discuss the role of excessive ROS and oxidative stress in the pathogenesis of endothelial dysfunction and the mechanisms for excessive ROS production and oxidative stress in T2DM. Critical Issues: Although studies with diabetic animal models have shown that targeting ROS with traditional antioxidant vitamins C and E or other antioxidant supplements provides promising beneficial effects on endothelial function, the cardiovascular outcomes of clinical studies with these antioxidant supplements have been inconsistent in diabetic patients. Future Directions: Preclinical and limited clinical data suggest that N-acetylcysteine (NAC) treatment may improve endothelial function in diabetic patients. However, well-designed clinical studies are needed to determine if NAC supplementation would effectively preserve endothelial function and improve the clinical outcomes of diabetic patients with reduced cardiovascular morbidity and mortality. With better understanding on the mechanisms of ROS generation and ROS-mediated endothelial damages/dysfunction, it is anticipated that new selective ROS-modulating agents and effective personalized strategies will be developed for the management of endothelial dysfunction in DM.

Associations of Cognitive Impairment with All-Cause and Cardiovascular Mortality Among Individuals with Diabetes: A Prospective Cohort Study.

This study explored the association between diabetes, cognitive imFpairment (CI), and mortality in a cohort of 2931 individuals aged 60 and above from the 2011 to 2014 NHANES. Mortality data was gathered through 2019, and multivariable Cox proportional hazards models were used to determine the association between diabetes, CI, and mortality adjusting for sociodemographic characteristics, lifestyle factors, and comorbidity conditions. The study spanned up to 9.17years, observing 579 deaths, with individuals having both diabetes and CI showing the highest all-cause mortality (23.6 events per 100 patient-years). Adjusted analysis revealed a 2.34-fold higher risk of all-cause mortality for this group, surpassing those with diabetes or CI alone. These results held after a series of stratified and sensitivity analyses. In conclusion, CI was linked to higher all-cause mortality in individuals with diabetes, emphasizing the need to address cognitive dysfunction in diabetic patients.

Effect of SGLT2 Inhibitors on Post-PCI Outcomes after Acute Myocardial Infarction in Diabetic Patients: A Systematic Review and Meta-Analysis

Background: Acute myocardial infarction (AMI) is related with poor outcomes in patients with diabetes mellitus (DM). Whether diabetic patients with AMI undergoing percutaneous coronary intervention (PCI) benefit from sodium–glucose cotransporter 2 inhibitors (SGLT2i) in terms of cardiovascular mortality, myocardial damage, and left ventricular function is unclear. Methods: Through a comprehensive search in PubMed, EMBASE, and Web of science databases from January 2018 to September 2023, randomized controlled trials were performed to compare SGLT2i with other oral antidiabetic medications in diabetic patients with AMI undergoing PCI. Cardiovascular mortality constituted the primary outcome. Secondary outcomes were high-sensitivity troponin I (hs-TnI) levels, left ventricular ejection fraction (LVEF), and contrast-induced acute kidney injury (CI-AKI). Results: SGLT2i significantly reduced cardiovascular mortality risk versus other antidiabetic agents (hazard ratio (HR): 0.35, 95% confidence interval (CI): 0.21–0.58, p < 0.0001). SGLT2i also lowered hs-TnI levels across all time points (mean difference: –2931 ng/L, p < 0.001). After adjustment for publication bias, this difference was no longer significant. However, peak hs-TnI levels remained significantly lower with SGLT2i (mean difference: –3836 ng/L, p < 0.001). Finally, SGLT2i improved LVEF versus comparators, with a mean difference of –5.00% (95% CI: –6.69 to –3.31, p < 0.001) at hospital discharge. SGLT2i was also associated with 60% lower odds of CI-AKI (odds ratio (OR): 0.40, 95% CI: 0.22–0.75, p = 0.004). Conclusions: Compared with other antidiabetic medications, SGLT2i may lower cardiovascular mortality, infarct size, and prevent left ventricle (LV) systolic dysfunction in diabetic patients with AMI undergoing PCI. The use of SGLT2i in this high-risk group is supported by these findings.

Evaluation of Brain Stem Function in Diabetics with and Without Distal Symmetrical Polyneuropathy Using the Blink Reflex

Background: Diabetic peripheral neuropathy (DPN) is the commonest complication of T2DM. Neuropathy is a descriptor for a spectrum of clinical and subclinical symptoms with varying anatomical distributions, clinical histories, and perhaps underlying pathogenetic mechanisms. The distal Symmetrical sensory polyneuropathy is chronic, symmetrical, length-dependent sensorimotor. Studies of the blink reflex have shown potential as a method of assessing brainstem activity. Objective: The primary purpose of this research was to assess the function of the blink reflex in the early detection of cranial nerves and brain stem dysfunction in diabetes patients with and without polyneuropathy. We also aimed to see whether there were differences in blink reflex abnormalities between diabetes individuals with and without polyneuropathy. Patients and Methods: The study included a group of sixty-60 diabetic patients. Clinician and electrophysiologist evaluations were used to determine the severity of neuropathy. Patients with diabetes were separated into two groups: those with and without neuropathy. Results: A statistically significant difference between the two groups was for C.R.2 latency, and I.R.2 latency with a P-value <0.001. Except for blink reflex’s R1 latency (P-value >0.2), all other Blink reflex parameters were statistically different between patients who experience diabetic neuropathy and those who didn’t. Regarding HbA1c, a significant positive association with IR2 latency and C.R.2 latency was noted (Pvalue <0.001) and also, a statistically significant negative association was found with I.R.2 duration and C.R.2 duration (P-value <0.001). Amplitudes of sural, tibial and peroneal nerves were negatively associated with Blink reflex Latencies and positively associated with blink reflex duration. Conclusion: In conclusion, blink-reflex parameters (including ipsi-lateral R.2 latency, contra-lateral R.2 latency) are significantly associated with HBA1C level and degree of peripheral diabetic neuropathy. Received Sept. 2022 Accepted Nov. 2023 Published Jan. 2024

Protein PDK4 Interacts with HMGCS2 to Facilitate High Glucoseinduced Myocardial Injuries.

As a distinct type of cardiomyopathy, diabetic cardiomyopathy (DCM) is featured as diastolic or systolic cardiac dysfunction in diabetic patients. In order to broaden the understanding of molecular mechanisms in DCM, we intended to explore the mechanism of the interaction between PDK4 protein and Hmgcs2 in high glucose (HG)-induced myocardial damage. PDK4 and Hmgcs2 expression in the myocardium of diabetes mellitus (DM) model rats and HG-incubated cardiomyocyte line H9C2 was analyzed by western blot analysis. Echocardiography and TUNEL assay were utilized for respective assessment of cardiac structure and function and cardiomyocyte apoptosis in DM rats after silencing PDK4 or/and Hmgcs2. In vitro, the impact of PDK4 and Hmgcs2 on HG-induced cardiomyocyte injuries was identified with cell counting kit-8 and flow cytometry assays, along with detection of LDH release, caspase-3/7 activities, and reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Moreover, a coimmunoprecipitation assay was utilized to test the interaction between PDK4 and Hmgcs2. Both PDK4 and Hmgcs2 were highly expressed in the myocardial tissues of DM rats. Mechanistically, PDK4 interacted with Hmgcs2 to upregulate Hmgcs2 expression in HG-induced H9C2 cells. Silencing PDK4 improved cardiac function and reduced cardiomyocyte apoptosis in DM rats. In HG-induced H9C2 cells, PDK4 or Hmgcs2 silencing enhanced cell viability and reduced LDH release, caspase-3/7 activities, cell apoptosis, and ROS and MDA levels, and these trends were further promoted by the simultaneous silencing of PDK4 and Hmgcs2. In summary, the silencing of PDK4 and Hmgcs2 alleviated HG-induced myocardial injuries through their interaction.

Metformin reverses impaired osteogenesis due to hyperglycemia-induced neutrophil extracellular traps formation.

Diabetic patients suffer from delayed fracture healing and impaired osteogenic function, but the underlying pathophysiological mechanisms are not fully understood. Neutrophil extracellular traps (NETs) formed by neutrophils in high glucose microenvironments affect the healing of wounds and other tissues. Some evidence supports that NETs may inhibit osteogenic processes in the microenvironment through sustained inflammatory activation. In this study, we observed that high glucose-induced NETs led to sustained inflammatory activation of macrophages. Pro-inflammatory NETs inhibited the osteogenic function of osteoblasts in vitro. A bone defect healing model based on diabetic rat animal models confirmed that bone healing was impaired in a high glucose environment, but this process could be reversed by DNase I, a NETs clearance agent. More importantly, the classic hypoglycemic drug metformin had a similar antagonistic effect as DNase I and could reverse the inhibitory effect of NETs on osteogenesis in a high-glucose environment. In summary, we found that NETs formation induced by high glucose microenvironment is a potential cause of osteogenic dysfunction in diabetic patients, and metformin can reverse this osteogenic disadvantage.

Subclinical right ventricular dysfunction in patients with asymptomatic type 2 diabetes mellitus: A cross-sectional study

BackgroundDiabetic cardiomyopathy, which involves both the right and left ventricles, progresses from a preclinical stage to overt heart failure. Detection of this entity at a preclinical stage could be crucial in intervening to halt its progression to overt heart failure. There is a paucity of literature on subclinical RV dysfunction in diabetic patients, and it is even rarer in the Indian literature. Our study intended to study this clinical entity through an echocardiographic assessment of asymptomatic patients. ObjectivesThis was a cross-sectional observational analytic study, comparing subclinical RV dysfunction in diabetic and non-diabetic subjects by using echocardiography as a primary objective, while the secondary objective of the study was to find out the correlation between RV dysfunction and the duration of diabetes mellitus and HbA1C levels. MethodsConventional echocardiography with tissue Doppler imaging (TDI) was used to measure nine different echocardiographic parameters in the diabetic and non-diabetic groups. All probable causes of RV dysfunction were excluded before enrolling the patients in the study. Unpaired t-test was used to compare the parameters between the two groups, and multivariate regression analysis was done taking into consideration age, duration of diabetes, and HbA1C levels as the independent variables, and echocardiographic parameters as the dependent variables. ResultsOut of the nine different echocardiographic parameters, Tricuspid annular plane systolic excursion (TAPSE), RV end diastolic diameter (RVEDD), Tricuspid peak late diastolic velocity (A), E/A ratio, RV basal segment peak myocardial systolic velocity (Sm), RV basal segment peak early diastolic velocity (Em), RV basal segment peak late diastolic velocity (Am), and E/Em ratio showed statistically significant differences between the two groups. These results show the presence of subclinical RV dysfunction in diabetic patients. TAPSE and E/A ratio showed a significant correlation with the duration of diabetes, while Em showed a significant correlation with HbA1C. ConclusionDiabetes mellitus is associated with subclinical systolic as well as diastolic RV dysfunction. In addition to helping identify people at high risk, the early recognition of RV dysfunction gives us a window of opportunity to take action and slow down the disease's course. This study emphasizes that the early identification of RV diastolic as well as systolic dysfunction in asymptomatic Type 2 diabetic patients can be a helpful tool in halting the progression of disease from subclinical to frank clinical cases, thereby preventing the morbidity and mortality associated with heart failure. Hence, it adds value to the pre-existing literature.

Mollugin activates GLP-1R to improve cognitive dysfunction in type 2 diabetic mice

AimsThe incidence of diabetic cognitive dysfunction is increasing year by year, and it has gradually become a research hot spot. Studies have shown that glucagon-like peptide-1 receptor (GLP-1R) agonists can improve cognitive dysfunction in diabetic patients. This study focuses on whether small molecule GLP-1R agonists from traditional Chinese medicine (TCM) can improve the diabetic cognitive dysfunction. Materials and methodsThe small molecules from TCM were screened by cell membrane chromatography (CMC) with GLP-1R-HEK293 cell membrane column. MTT assay, flow cytometry, immunofluorescence cytochemistry and other methods were used to determine the effects of mollugin on the apoptosis rate and reactive oxygen species (ROS) level of high glucose (HG)/hydrogen peroxide (H2O2) induced PC12 cells. Real-Time PCR was used to detect mRNA expression in mouse cerebral cortex. Water maze test was further used to confirm the effect of mollugin on cognitive dysfunction in T2DM mice. Key findingsMollugin bound to GLP-1R, promoted Ca2+ influx, increased insulin secretion and cAMP content in β-TC-6 cells. Mollugin enhanced the cell viability, ameliorated apoptosis, reduced intracellular ROS levels in HG/H2O2-injured PC12 cells. Mollugin reduced the T2DM mice's escape latency, improved neuronal cell damage, decreased the expression of Pik3ca, Akt1 and Mapk1 mRNA in the cerebral cortex tissue. SignificanceThe results suggest that mollugin could improve cognitive dysfunction in T2DM mice through activating GLP-1R/cAMP/PKA signal pathway.

Study of correlation of hypothyroidism with diabetic microvascular complications in type 2 diabetic adult Indian females

Background: Patients with type 2 diabetes mellitus are more prone to thyroid disorders. Hypothyroidism in them leads to an aggravation of microvascular complications. Screening for thyroid dysfunction in diabetic patients will allow early treatment of hypothyroidism. The aim of this study is to assess the correlation of hypothyroidism with diabetic microvascular complications. Methods: This is a cross‑sectional study that was conducted at department of medicine GSVM Medical College, Kanpur. 200 female patients with type 2 diabetes mellitus attending the out‑patient department were included. Subjects with any prior history of thyroid disease, chronic liver disease, or acute illness were excluded from the study. Results: Our study describes 14% prevalence of hypothyroidism (subclinical hypothyroidism 13.5%) among 200 diabetic subjects. Among hypothyroid patients 64.29% patients had nephropathy, 60.71% patients had neuropathy, 64.29% patients had retinopathy whereas euthyroid patients had 26.74%, 25% and 29.07% nephropathy, neuropathy, and retinopathy respectively. Conclusions: The prevalence of hypothyroidism was 14% among female patients with type 2 diabetes mellitus in this study. Overt hypothyroidism was 0.5 % and subclinical hypothyroidism was more common (13.5%) among the study subjects. Patients having hypothyroidism were more likely to be having diabetic nephropathy, neuropathy, and retinopathy.

568-P: Study of the Effect of PPARß/δ Activation on Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DC), the leading cause of death among people with diabetes, is definedas the occurrence of myocardial dysfunction in diabetic patients that is not directly attributableto coronary artery disease, hypertension, or valve disease. No specific drugs have yet beenapproved for treating DC and the use of Peroxisome Proliferator-Activated Receptor (PPAR)β/δagonists for the treatment of this disease show promise. Here, we examined as to whethertreatment with a PPARβ/δ agonist can prevent or ameliorate this pathology and as to whetherstreptozotozin (STZ)-induced DC is exacerbated in PPARβ/δ-deficient mice. In the STZ-induced mouse model of DC, an increase in cardiac fibrosis and an impairment inglucose and fatty acid metabolism was observed. Treatment with the PPARβ/δ agonist GW0742partially reduced the STZ-induced fibrosis, inflammation and metabolic disturbances, suggestingthat PPARβ/δ activation might be a potential target to prevent this disease suggesting a closerelation between inflammation and fibrosis in cardiac dysfunction of DC. In addition, we showthat PPARβ/δ suppression exacerbated hyperglycemia-induced DC and that PPARβ/δ activationthrough administration of agonists like GW501516 prevented the induction of some of themolecular mechanisms involved in the development of DC in these cells. Overall, these findingsdemonstrate the implication of PPARβ/δ in DC and suggest that its activation might be aneffective therapeutic tool for preventing or treating DC. Disclosure A.Rostami: None.

Frequency of Thyroid Dysfunction in Diabetic Patients

Thyroid hormones are involved in the control of insulin secretion, beta-cell function/multiplication, liver glucose synthesis, output and peripheral utilization. Thyroid dysfunction identification and correction help in glycemic control. Objective: To know the frequency of thyroid dysfunction in diabetic patients. Methods: This descriptive cross-sectional study was done in the Medical-C Department, Ayub Teaching Hospital Abbottabad from July 2018 to August 2019. Total 150 diabetic patients were enrolled by using non-probability consective sampling. Patients were labelled as diabetics on the basis of diabetes history, anti-diabetic medications use, high blood glucose (>200mg/dl) on presentation or on previous high blood sugar reading or a high HbA1c value. Fresh venous blood sample was sent for thyroid function tests (T3, T4 and TSH). Thyroid dysfunction in our study was defined as patient having Thyroid Stimulating Hormone (TSH) value above or below the normal range. Data of patients were collected on study pro forma and was analyzed using statistical program SPSS version-20.0 Results: There were 67 (44.66%) male and 83 (55.33%) female patients. The mean age was 51.83 ± 14.52 years. Thyroid dysfunction was detected in 37 (24.66%) study participants. Out of 67 male patients, 11 (16.41%) had thyroid dysfunction and out of 83 female patients, 26 (31.32%) had thyroid dysfunction. Subclinical hypothyroidism was present in 4 (2.7%), 5 (3.3%) had hypothyroidism, 20 (13.3%) had subclinical hyperthyroidism and 8 (5.3%) had hyperthyroidism. Conclusion: This study suggests that a significant portion of diabetic patients suffer from thyroid dysfunction.

Evaluating Diagnostic Ultrasound of the Vagus Nerve as a Surrogate Marker for Autonomic Neuropathy in Diabetic Patients.

Background and Objectives: Diagnostic ultrasound of the vagus nerve has been used to examine different polyneuropathies, and it has been suggested to be useful as a marker of autonomic dysfunction in diabetic patients. Materials and Methods: We analyzed the cross-sectional area (CSA) of the right vagus nerve of 111 patients with type 2 diabetes in comparison to 104 healthy adults and 41 patients with CIDP (chronic inflammatory demyelinating polyneuropathy). In the diabetes group, sympathetic skin response (SSR) was measured as an indicator for autonomic neuropathy. Carotid intima-media thickness (CIMT) was measured as a surrogate for atherosclerosis. Clinical symptoms of polyneuropathy were assessed using the Neuropathy Symptom Score and the Neuropathy Disability Score. Results: In total, 61.3% of the diabetes patients had clinical signs of polyneuropathy; 23.4% had no SSR at the feet as an indicator of autonomic neuropathy. Mean vagus nerve CSA did not differ in patients with and without diabetic polyneuropathy or in diabetic patients with and without SSR at the feet. No significant correlation was found between vagus nerve CSA and CIMT or SSR parameters in diabetic patients. Mean CSA of the right vagus nerve was slightly larger in diabetic patients (p = 0.028) and in patients with CIDP (p = 0.015) than in healthy controls. Conclusions: Effect sizes and mean differences were rather small so that a reliable diagnosis cannot be performed based on the vagus nerve measurement of a single person alone. Vagus nerve CSA seems not suitable as an indicator of autonomic dysfunction or cardiovascular risk in diabetic patients.

Astragalin ameliorates renal injury in diabetic mice by modulating mitochondrial quality control via AMPK-dependent PGC1α pathway.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes mellitus, and oxidative stress and mitochondrial dysfunction play an important role in this process. It has been shown that aldose reductase (ALR2) catalyzes NADPH-dependent reduction of glucose to sorbitol, resulting in oxidative stress and mitochondrial dysfunction in diabetic patients. Astragalin (AG), a flavonoid extracted from Thesium chinense Turcz., shows an inhibitory activity on ALR2. In this study, we investigated the therapeutic effects of AG against renal injury in streptozocin (STZ)-induced diabetic mouse model. Diabetic mice were orally administered AG (5, 10 mg·kg-1·d-1) for 4 weeks. We showed that AG treatment greatly improved the proteinuria and ameliorated renal pathological damage without affecting the elevated blood glucose in diabetic mice. Furthermore, AG treatment significantly suppressed highly activated ALR2, and reduced oxidative stress in the kidney of diabetic mice and in high glucose and lipids-stimulated HK2 cells in vitro. We demonstrated that AG treatment modulated mitochondrial quality control and ameliorated apoptosis, boosting mitochondrial biogenesis, maintaining mitochondrial dynamic homeostasis, and improving energy metabolism disorder in vivo and in vitro. In high glucose and lipids-stimulated HK2 cells, we found that AG (20 μM) restored the phosphorylation level of AMPK, and upregulated the expression and transcriptional activity of PGC1α, whereas treatment with H2O2, blockade of AMPK with Compound C or knockdown of AMPKα with siRNA abolished the protective effect of AG on mitochondrial function, suggesting that antioxidant effects and activation of AMPK-dependent PGC1α pathway might be the molecular mechanisms underlying the protective effects of AG on mitochondrial quality control. We conclude that AG could be a promising drug candidate for the treatment of diabetic renal injury through activating AMPK.

Motor skills training-induced activation of descending pathways mediating cortical command to hindlimb motoneurons in experimental diabetic rats

Diabetes disrupts the corticospinal tract (CST) system components that control hindlimb and trunk movement, resulting in weakness of the lower extremities. However, there is no information about a method to improve these disorders. This study aimed to investigate the rehabilitative effects of 2 weeks of aerobic training (AT) and complex motor skills training (ST) on motor disorders in streptozotocin-induced type 1 diabetic rats. In this study, electrophysiological mapping of the motor cortex showed that the diabetes mellitus (DM)-ST group had a larger motor cortical area compared to the DM-AT group and sedentary diabetic animals. Moreover, hand grip strength and rotarod latency increased in the DM-ST group; however, these two parameters did not change in the DM-AT group, as well as in control and sedentary diabetic rats. Furthermore, in the DM-ST group, cortical stimulation-induced and motor-evoked potentials were preserved after the interception of the CST; however, this potential disappeared after additional lesions were made on lateral funiculus, suggesting that their function extends to activating motor descending pathways other than the CST locating lateral funiculus. According to immunohistochemical analysis, the larger fibers present on the dorsal part of the lateral funiculus, which corresponds to the rubrospinal tract of the DM-ST group, expressed the phosphorylated growth-associated protein, 43 kD, which is a specific marker of axons with plastic changes. Additionally, electrical stimulation of the red nucleus revealed expansion of the hindlimb-responsible area and increased motor-evoked potentials of the hindlimb in the DM-ST group, suggesting a strengthening of synaptic connections between the red nucleus and spinal interneurons driving motoneurons. These results reveal that ST induces plastic changes in the rubrospinal tract in a diabetic model, which can compensate for diabetes by disrupting the CST system components that control the hindlimb. This finding suggests that ST can be a novel rehabilitation strategy to improve motor dysfunctions in diabetic patients.

A Cross-Sectional Study of p66Shc Gene Expression in Liquid Biopsy of Diabetic Patients. Is it Possible to Predict the Onset of Renal Disease?

Background: Diabetic nephropathy (DN) is a disorder affecting glomerular function that, histologically, is due to the presence of glomerulosclerosis accompanied with endothelial dysfunction of the afferent and efferent renal arterioles. Insulin resistance in diabetic patients is known to be one of the causes of endothelial dysfunction because it increases oxidative stress, and one of the main genes regulating the production pathways of reactive oxygen species is p66Shc. The aim of this study was to evaluate the p66Shc gene expression as a precocious biomarker of renal dysfunction in diabetic patients, using liquids samples of urine sediment and peripheral blood. Methods: 29 diabetic patients and 37 healthy donors were recruited from the Centro Universitário FMABC outpatient clinic. The RT-gPCR technique was applied to evaluate p66Shc gene expression in urine and peripheral blood samples from diabetic patients, which were compared with healthy donors. Results: There was no significant expression of p66Shc gene in samples from diabetic patients compared with healthy donors. However, p66Shc expression in the blood samples of diabetics (0.02417±0.078652-ΔCT, n=29) was 3.6 times higher than in healthy participants (0.00689±0.01758, n=37) while in the urine samples, it was 1.48 times higher in diabetics group (0.02761±0.05412-ΔCT) than in CTL group (0.0186±0.02199). Conclusion: There was no significant p66Shc gene expression in peripheral blood and urine samples of diabetic patients without kidney injury compared with healthy donors, although there is a tendency for this gene to participate in the oxidative imbalance present in diabetes.

Evaluation of Left Ventricular Diastolic Dysfunction in diabetic patients with preserved Ejection fraction and its association with myocardial performance index

Background: Diastolic dysfunction causes impairment of ventricular filling when the ventricle becomes stiff, relaxes slowly or incompletely. Diabetes mellitus increases the risk of diastolic dysfunction which can develop heart failure even in the absence of other co-morbidities. Tei index is an echocardiographic tool to evaluate global function of ventricle. Objective: To determine the prevalence of Left Ventricular diastolic dysfunction (LVDD) in patients with type 2 diabetes mellitus; and its association with LV myocardial performance index (Tei Index). Method: 100 patients with type 2 diabetes mellitus with normal left ventricular ejection fraction without overt cardiac disease were included. LVDD was determined as per using 2016 American Society of Echocardiology (ASE) guideline. LV Tei index was calculated by tissue doppler imaging method. Results: Mean age of the patients was 58.1 ± 12.6 years with 54 percent male. Mean HbA1C was 7.45± 0.99. 23 (23%) patients met the criteria of LVDD and 46 (46%) patients did not have LVDD. Whereas 31 (31%) of patients were categorized as indeterminate. Tei index was significantly higher in patients with LVDD (0.56±0.05 and 0.43±0.06 (p <0.05). Conclusion: Prevalence of LV diastolic dysfunction in type 2 diabetes mellitus was 23% in our study. There was a significant association between LVDD and Tei index. Rising trend of prevalence of diastolic dysfunction with increasing age of patients was observed. J Inv Clin Cardiol 2023; 5(1): 14-18

Targeting APLN/APJ restores blood-testis barrier and improves spermatogenesis in murine and human diabetic models

Type 2 diabetes mellitus is one of the most prevalent metabolic diseases presenting with systemic pathologies, including reproductive disorders in male diabetic patients. However, the molecular mechanisms that contributing to spermatogenesis dysfunction in diabetic patients have not yet been fully elucidated. Here, we perform STRT-seq to examine the transcriptome of diabetic patients’ testes at single-cell resolution including all major cell types of the testis. Intriguingly, whereas spermatogenesis appears largely preserved, the gene expression profiles of Sertoli cells and the blood-testis barrier (BTB) structure are dramatically impaired. Among these deregulate pathways, the Apelin (APLN) peptide/Apelin-receptor (APJ) axis is hyper-activated in diabetic patients’ testes. Mechanistically, APLN is produced locally by Sertoli cells upon high glucose treatment, which subsequently suppress the production of carnitine and repress the expression of cell adhesion genes in Sertoli cells. Together, these effects culminate in BTB structural dysfunction. Finally, using the small molecule APLN receptor antagonist, ML221, we show that blocking APLN/APJ significantly ameliorate the BTB damage and, importantly, improve functional spermatogenesis in diabetic db/db mice. We also translate and validate these findings in cultured human testes. Our findings identify the APLN/APJ axis as a promising therapeutic target to improve reproduction capacity in male diabetic patients.

Treatment of Erectile Dysfunction in Patients with Diabetes

Diabetes and erectile dysfunction often go hand in hand. Different types of medications and therapies are required for the effective management of erectile dysfunction. Treatment options for erectile dysfunction in diabetes patients are discussed in this article. Effectiveness and limitation of the medications have been clarified here and, finally, side effects and contraindication of different medications for erectile dysfunction management have also been reflected. Erectile dysfunction treatment in diabetes patients not only depends on selecting proper medication, but glycaemic control also; therefore, both diabetes and ED are required to treat simultaneously.

Thyroid dysfunction in type 2 diabetes mellitus patients attending diabetic clinic in a tertiary care centre: a cross-sectional study

Background: Thyroid disease and type 2 diabetes mellitus are two common co-existing endocrinopathies found in the general population. Since thyroid dysfunction complicates the metabolic derangement observed in diabetes, its treatment is necessary in order to achieve stability of metabolic control. Therefore, the aim of the present investigation was to estimate the functional thyroid disorders and the associated factors in type 2 diabetes patients.Methods: In 230 diabetic patients, the blood sugar level and thyroid function tests were performed and compared. Most of the patients were in the age group of 51-60 years (36.08%).Results: The prevalence of thyroid dysfunction in diabetic patients was 15.21% with a higher rate in female patients. Subclinical hypothyroidism (12.17%) was the commonest thyroid dysfunction.Conclusions: The data suggest that subclinical hypothyroidism was more prevalent in type 2 diabetes mellitus, and may confer a greater risk of diabetic complications. It is therefore important to diagnose thyroid dysfunction in diabetic patients and the practice should be inculcated in diabetic care.

Roles of Reactive Oxygen Species in Vascular Complications of Diabetes: Therapeutic Properties of Medicinal Plants and Food

The rising prevalence of chronic metabolic disorders, such as obesity and type 2 diabetes, most notably associated with cardiovascular diseases, has emerged as a major global health concern. Reactive oxygen species (ROS) play physiological functions by maintaining normal cellular redox signaling. By contrast, a disturbed balance occurring between ROS production and detoxification of reactive intermediates results in excessive oxidative stress. Oxidative stress is a critical mediator of endothelial dysfunction in obesity and diabetes. Under a hyperglycemic condition, the antioxidant enzymes are downregulated, resulting in an increased generation of ROS. Increases in ROS lead to impairment of endothelium-dependent vasodilatations by reducing NO bioavailability. Chronic treatments with antioxidants were reported to prevent the development of endothelial dysfunction in diabetic patients and animals; however, the beneficial effects of antioxidant treatment in combating vascular complications in diabetes remain controversial as antioxidants do not always reverse endothelial dysfunction in clinical settings. In this review, we summarize the latest progress in research focused on the role of ROS in vascular complications of diabetes and the antioxidant properties of bioactive compounds from medicinal plants and food in animal experiments and clinical studies to provide insights for the development of therapeutic strategies.