Diabetes Mellitus Function Research Articles

Kidney hemodynamic effects of sodium-glucose cotransporter 2 inhibitors in diabetes: physiology and clinical implications

Abstract The progressive loss of kidney function in diabetes mellitus is partly attributable to the occurrence of glomerular hyperfiltration. Consequently, therapeutic interventions that lower intra-glomerular pressure are a cornerstone of treatment in diabetic kidney disease. Sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently reduce glomerular filtration rate (GFR) and calculated intraglomerular pressures across studies. However, the net effect on arteriolar tone that leads to acute GFR declines may differ between cohorts. While pre-glomerular vasoconstriction appears to be the dominant mechanism responsible for GFR dipping in patients with type 1 diabetes (T1D) and glomerular hyperfiltration, other factors, including postglomerular vasodilation, may contribute to the acute GFR decline in normofilterering individuals with T1D and type 2 diabetes. Regardless of the responsible mechanisms, acute changes in GFR are associated with long-term kidney function preservation—a relationship that may reflect an underlying protective decline in glomerular hypertension.

Identification of circRNAs expression profiles and functional networks in parotid gland of type 2 diabetes mouse

BackgroundCircular RNAs (circRNAs) are a novel kind of non-coding RNAs proved to play crucial roles in the development of multiple diabetic complications. However, their expression and function in diabetes mellitus (DM)-impaired salivary glands are unknown.ResultsBy using microarray technology, 663 upregulated and 999 downregulated circRNAs companied with 813 upregulated and 525 downregulated mRNAs were identified in the parotid glands (PGs) of type2 DM mice under a 2-fold change and P < 0.05 cutoff criteria. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis of upregulated mRNAs showed enrichments in immune system process and peroxisome proliferator-activated receptor (PPAR) signaling pathway. Infiltration of inflammatory cells and increased inflammatory cytokines were observed in diabetic PGs. Seven differently expressed circRNAs validated by qRT-PCR were selected for coding-non-coding gene co-expression (CNC) and competing endogenous RNA (ceRNA) networks analysis. PPAR signaling pathway was primarily enriched through analysis of circRNA-mRNA networks. Moreover, the circRNA-miRNA-mRNA networks highlighted an enrichment in the regulation of actin cytoskeleton.ConclusionThe inflammatory response is elevated in diabetic PGs. The selected seven distinct circRNAs may attribute to the injury of diabetic PG by modulating inflammatory response through PPAR signaling pathway and actin cytoskeleton in diabetic PGs.

Assessment of Serum Urea and Creatinine Levels in Diabetic Patients

Diabetic nephropathy is the leading cause of renal morbidity which occurs when chronic diabetes destroys the filtering system of the kidneys. Serum urea and creatinine are widely used as renal function test parameters. This study aims to assess the level of serum urea and creatinine in diabetic patients and their relationship with each other. The study was conducted in Ayub Teaching Hospital from September 15 to December 20, 2019. A total of 176 samples from confirmed diabetic patients were analyzed including 85 female and 91 male patients. Also, 83 control samples were taken for this study. Serum urea and creatinine levels were assessed to evaluate diabetic nephropathy in diabetic patients. SPSS (version 23) was used for statistical analysis. Pearson correlation analysis was used to check the relationship of blood sugar level, creatinine, and urea. Descriptive statistics (mean ± SD) were measured for the continuous variable. Scatter plot diagrams were added for the easy visualization and interpretation of the data. The significant level was set at p &lt; 0.05. Out of the 176 diabetic samples, 32 had abnormally high serum creatinine and 66 had abnormal serum urea. In controls, one individual had high creatinine and three individuals had high serum urea. A significant increase in both urea and creatinine levels was observed in diabetic samples. Both serum urea and creatinine showed a strong positive correlation with the level of glucose and remained statistically significant (p &lt; 0.01). Similarly, blood glucose level showed a strong correlation with the renal function test parameters. Hence, it was concluded that serum urea and creatinine are important parameters to assess kidney function in diabetes mellitus.&#x0D;

The Impact of Punica granatum Linn and Its Derivatives on Oxidative Stress, Inflammation, and Endothelial Function in Diabetes Mellitus: Evidence from Preclinical and Clinical Studies.

Diabetes mellitus is recognized as the leading contributor to cardiovascular disease and associated mortality rates worldwide. Despite the use of pharmaceutical drugs to treat diabetes, its prevalence continues to rise alarmingly. Therefore, exploring remedies with a lower toxicity profile is crucial while remaining safe and effective in addressing this global public health crisis. Punica granatum Linn (pomegranate), known for its properties and safety profile, has been investigated in applied research and preclinical and clinical trials. However, conflicting reports still exist regarding its effects in diabetes. According to our knowledge, no systematic review has been conducted to critically analyze evidence from preclinical and clinical trials simultaneously, explicitly focusing on oxidative stress, inflammation, and endothelial function in diabetes. Therefore, in this systematic review, we searched for evidence on the impact of pomegranate in diabetes using databases such as PubMed, Scopus, and Google Scholar. Our inclusion criteria were limited to studies published in English. Of the 170 retrieved studies, 46 were deemed relevant and underwent critical analysis. The analyzed evidence suggests that pomegranate has the potential to alleviate oxidative stress, inflammation, and endothelial dysfunction in diabetes. Although a beneficial impact was noted in these markers, the endothelial function evidence still requires validation through further clinical trials with a powered sample size.

Plantar Pain, Balance and Foot Functions in Individuals with Diabetes Mellitus

Aim: The aim of this study was to investigate the relationship between plantar pain, balance and foot function in Diabetes Mellitus (DM) patients with obese and non-obese. Material and Methods: Fifty-four patients were diagnosed as DM were included. Participants were seperated as non-obese (n=27) and obese (n=27). The balance abilities (dynamic and static balance) of participants were examined with the Portable Computerized Kinesthetic Ability Trainer (SportKAT-550). Pain, disability and function status of foot were assessed according to Foot Function Index (FFI) and Manchester Foot Pain and Disability Index (MFPDI). Results: FFI-Disability and MFPDI scores of the Non-Obese.Group were significantly better than Obese Group. While there were no significant correlation between BMI and MFPDI, FFI-Activity.Limitation and FFI-Disability scores in both groups (p&gt;0.05), there was medium and positive significant correlation just between BMI and FFI-Pain.in.Non-Obese Group (p

The co-existence of peripheral and vestibular neuropathy in diabetes: a cross-sectional study

PurposeDiabetic neuropathy can lead to decreased peripheral sensation and motor neuron dysfunction associated with impaired postural control and risk of falling. However, the relationship between decreased peripheral sensation and impaired vestibular function in diabetes mellitus is poorly investigated. Therefore, the aim of this study was to investigate the relationship between peripheral and autonomic measurements of diabetic neuropathy and measurements of vestibular function.MethodsA total of 114 participants with type 1 diabetes (n = 52), type 2 diabetes (n = 51) and controls (n = 11) were included. Vestibular function was evaluated by video head impulse testing. Peripheral neuropathy was assessed by quantitative sensory testing and nerve conduction. Autonomic neuropathy using the COMPASS 31 questionnaire. Data were analyzed according to data type and distribution.ResultsMeasurements of vestibular function did not differ between participants with type 1 diabetes, type 2 diabetes or controls (all p-values above 0.05). Subgrouping of participants according to the involvement of large-, small- or autonomic nerves did not change this outcome. Correlation analyses showed a significant difference between COMPASS 31 and right lateral gain value (ρ = 0.23, p = 0.02,), while no other significant correlations were found.ConclusionDiabetic neuropathy does not appear to impair vestibular function in diabetes, by means of the VOR.Clinical trialsNCT05389566, May 25th, 2022.

EFFECT OF L-ARGININE SUPPLEMENTATION WITH ENDOTHELIAL FUNCTION IN DIABETES MELLITUS AND CARDIOVASCULAR DISEASE

&#x0D; Abstract&#x0D; Background: Cardiovascular disease is the main complication that induces morbidity in diabetes mellitus patients. Endothelial function plays a role in these complications. Nitric oxide is a nitrogen-free radical produced from L-arginine, involved in several mechanisms for maintaining endothelial function to prevent cardiovascular disease and diabetes mellitus.&#x0D; Methods: A search for relevant literature in PubMed, Cochrane, and ProQuest was conducted. After assessing the relevancy and eligibility of the literature, two pieces of literature were selected and critically appraised.&#x0D; Results: There are two works of literature from systematic review and meta-analysis were found. The studies suggest pro and contra L-arginine supplementation with endothelial function in diabetes mellitus and cardiovascular disease. &#x0D; Conclusions: L-arginine might be the alternative supplement for cardiovascular disease and diabetes mellitus, but further analysis in improved studies is needed to confirm.&#x0D; Keywords: l-arginine, diabetes mellitus, cardiovascular disease, endothelial&#x0D;

CCL4 Deletion Accelerates Wound Healing by Improving Endothelial Cell Functions in Diabetes Mellitus.

Chronic inflammation in diabetes mellitus (DM) is the leading cause of non-healing wounds. Chemokine CC motif ligand 4 (CCL4) is enhanced in the circulation and in the wounds of DM patients. This study aimed to investigate the effect of endogenous CCL4 inhibition on diabetic wound healing. Endothelial progenitor cells (EPCs) and human dermal microvascular endothelial cells (HDMECs) were used. Mice were injected with streptozotocin to generate hyperglycemia. An enhanced CCL4 level as well as decreased tube formation and migration abilities were observed in high-glucose-treated HDMECs and in EPCs from type 2 DM patients. CCL4 inhibition by siRNA restored the damaged cell function by upregulating the Akt/endothelial nitric oxide synthase/vascular endothelial growth factor/stromal cell-derived factor-1α pathways. Wild-type diabetic mice had delayed wound repair, whereas the CCL4-knockout diabetic mice showed an accelerated rate of wound closure. In a Matrigel plug assay, CCL4-knockout diabetic mice showed higher blood vessel and hemoglobin levels. Higher CD31 and Ki67 expression in the wound area and Matrigel plugs was detected in the CCL4-knockout diabetic mice. CCL4-knockout mice had upregulated angiogenic factors and downregulated inflammatory factors. This study might provide the theoretical basis for CCL4 inhibition as a therapeutic option for clinical diabetic wound treatment.

A CROSS-SECTIONAL STUDY OF THYROID DISORDER IN PATIENTS WITH TYPE 2 DIABETES MELLITUS IN A TERTIARY CARE HOSPITAL

Objectives: The objectives of the study were to assess thyroid function in diabetes mellitus by estimating free T3, free T4, and TSH in type 2 diabetic subjects, and the correlation between TSH and HbA1c. Methods: It was a cross-sectional study. The study was conducted at the Sapthagiri Institute of Medical Science in Bengaluru, Karnataka, and a total of 75 newly diagnosed type 2 diabetes mellitus patients were enrolled for this study from January 2020 to January 2021. Results: The prevalence of thyroid disorder among type 2 diabetes mellitus patients was 14.7% (11). Out of 11 cases, 4 (5.4%) cases belonged to hypothyroidism, 1 (1.3%) case was hyperthyroidism, 6 (8.0%) cases were subclinical hypothyroidism, and subclinical hyperthyroidism cases were not found in this study. Normal thyroid function was found in 64 (85.3%) cases. Conclusion: Thyroid disorders are more prevalent in people with type 2 diabetes. Female diabetics are more likely to have this finding. Subclinical hypothyroidism is the most frequent thyroid disorder. Thyroid disorders are more commonly associated with diabetes among people with diabetes who have poor metabolic control.

Role of Vitamin D in Cardiovascular Autonomic Function in Diabetes Mellitus

In India, the most encountered metabolic disorder is Type 2 Diabetes Mellitus (T2DM). T2DM is one of the chronic diseases, and there would be 80 million diabetic individuals in India by 2030.[1] Even though it is usually of adult type, nowadays it is observed frequently in the younger age group. Almost all systems in our body are affected by this disorder. Vitamin D is a fat-soluble vitamin present in sunlight and in certain foods. Vitamin D supports the immune system, cardiovascular system, and it also regulates insulin levels. Vitamin D is a neuroactive substance which stimulates central nervous system to keep the sympathetic and parasympathetic nervous system in balance with each other.[2] Vitamin D Receptors (VDRs) are widely distributed in nerve fibres of the brain and spinal cord to which activated Vitamin D (1,25-dihydroxy vitamin D) binds to build up vagal activity, and this physiological function of Vitamin D is implemented by its potential to traverse the blood-brain barrier to reach the brain. Also, the biogenesis of neurotransmitters regulating cardiovascular autonomic function occurs proportionately with the help of Vitamin D. The basal heart rate and blood pressure regulation by the sympathetic and parasympathetic nervous system are suppressed in case of low serum Vitamin D levels, and thus, Vitamin D deficiency has an adverse effect over cardiac autonomic functions.[2] The onset and severity of cardiac autonomic neuropathy in T2DM is linked to Vitamin D.[3] Autonomic dysfunctions like postural orthostatic tachycardia syndrome and orthostatic hypotension are associated with low Vitamin D levels.[4]&nbsp;Read more . . .&nbsp;

Serum-Derived Small Extracellular Vesicles From Diabetic Mice Impair Angiogenic Property of Microvascular Endothelial Cells: Role of EZH2.

BackgroundImpaired angiogenic abilities of the microvascular endothelial cell (MVEC) play a crucial role in diabetes mellitus–impaired ischemic tissue repair. However, the underlying mechanisms of diabetes mellitus–impaired MVEC function remain unclear. We studied the role of serum‐derived small extracellular vesicles (ssEVs) in diabetes mellitus–impaired MVEC function.Methods and ResultsssEVs were isolated from 8‐week‐old male db/db and db/+ mice by ultracentrifugation and size/number were determined by the Nano‐sight tracking system. Diabetic ssEVs significantly impaired tube formation and migration abilities of human MVECs. Furthermore, local transplantation of diabetic ssEVs strikingly reduced blood perfusion and capillary/arteriole density in ischemic hind limb of wildtype C57BL/6J mice. Diabetic ssEVs decreased secretion/expression of several pro‐angiogenic factors in human MVECs. Mechanistically, expression of enhancer of zest homolog 2 (EZH2), the major methyltransferase responsible for catalyzing H3K27me3 (a transcription repressive maker), and H3K27me3 was increased in MVECs from db/db mice. Diabetic ssEVs increased EZH2 and H3K27me3 expression/activity in human MVECs. Expression of EZH2 mRNA was increased in diabetic ssEVs. EZH2‐specific inhibitor significantly reversed diabetic ssEVs‐enhanced expression of EZH2 and H3K27me3, impaired expression of angiogenic factors, and improved blood perfusion and vessel density in ischemic hind limb of C57BL/6J mice. Finally, EZH2 inactivation repressed diabetic ssEVs‐induced H3K27me3 expression at promoter of pro‐angiogenic genes.ConclusionsDiabetic ssEVs impair the angiogenic property of MVECs via, at least partially, transferring EZH2 mRNA to MVECs, thus inducing the epigenetic mechanism involving EZH2‐enhanced expression of H3K27me3 and consequent silencing of pro‐angiogenic genes. Our findings unravel the cellular mechanism and expand the scope of bloodborne substances that impair MVEC function in diabetes mellitus.

Description of Cognitive Function in Diabetes Mellitus: A Literature Review

Cognitive decline in diabetes mellitus is not fully understood, though is generally ascribed to blood sugar levels exceeding normal (hyperglycemia), hypoglycemia conditions and insulin resistance. Cognitive function consists of aspects of memory, attention, executive function, perception, language, and psychomotor functions which affect the decline in cognitive function, especially in people with Diabetes Mellitus. This study aims to summarize the results of research on cognitive function in people with Diabetes Mellitus. The research method used was a literature review with an assessment using JBI critical appraisal tools. Articles were sourced via the PubMed database and Google Scholar using the search term ‘Cognitive Function AND Diabetes Mellitus’. The inclusion criteria were studies with quantitative design, full text, a population comprised of patients with Diabetes Mellitus, written in Indonesian or English. Six articles were reviewed, all the results state that patients with Diabetes Mellitus experienced a decrease in cognitive function, especially in the Executive Function, Visuospatial, and the Memory Domains.&#x0D; &#x0D; Keywords: Cognitive function, Diabetes mellitus, Literature review

Evaluation of thyroid function in diabetes mellitus at a tertiary care hospital in central Karnataka

Background: The thyroid hormone abnormalities are closely associated with diabetes. Undetected, untreated thyroid dysfunction may impair diabetes control, its early detection. Hence, prompt treatment among diabetics would be beneficial in achieving glycemic control, minimizing cardiovascular risk and improving general well‑being. In this central Karnataka As the data on thyroid disorders in diabetics is limited region, the present study was taken up to estimate the thyroid dysfunction in diabetic patients. Aim: To estimate the thyroid dysfunction in diabetic patients. Material and Methods: Hospital-based cross-sectional study was conducted after obtaining institutional ethics committee clearance, at a tertiary care teaching hospital in Chitradurga, Karnataka, among 100 diagnosed cases of diabetes mellitus. Patients’ lipid, thyroid and diabetic profiles were estimated and were then divided as hypothyroid, hyperthyroid, and euthyroid depending on the thyroid profiles. Results: Out of 100 diabetic patients, 71% were euthyroid, 23% hypothyroid and 6% were hyperthyroid. BMI, waist: hip ratio, TSH were significantly lower (22.3±1.8 Kg/mt2; 0.79±0.18), whereas T3 and T4 were significantly elevated among hyperthyroid patients compared to hypothyroid and euthyroid group. Levels of FBS, total cholesterol, triglycerides, LDL cholesterol and HbA1c were significantly elevated in hypothyroid patients. The mean levels of FBS, total cholesterol, triglycerides, LDL cholesterol and HbA1c were significantly elevated in hypothyroid patients compared to euthyroid group. Conclusion: Unidentified thyroid dysfunction could negatively impact diabetes and its complications and may be one of the prime causes of poor management of type 2 DM. Therefore, there is a need for routine assay of thyroid hormones in type 2 diabetic patients to improve the medical management as well as to reduce the morbidity in them.

Interplay of the adenosine system and NO in control of renal haemodynamics and excretion: Comparison of normoglycaemic and streptozotocin diabetic rats

The adenosine (Ado) system may participate in regulation of kidney function in diabetes mellitus (DM), therefore we explored its role and interrelation with NO in the control of renal circulation and excretion in normoglycemic (NG) and streptozotocin-diabetic (DM) rats. Effects of theophylline (Theo), a non-selective Ado receptor antagonist, were examined in anaesthetized NG or in streptozotocin induced diabetic (DM) rats, untreated or after blockade of NO synthesis with l-NAME. We measured arterial blood pressure (MABP), whole kidney blood flow and renal regional flows: cortical and outer- and inner-medullary (IMBF), determined as laser-Doppler fluxes. Renal excretion of water, total solutes and sodium and in situ renal tissue NO signal (selective electrodes) were also determined. Theo experiments disclosed minor baseline vasoconstrictor and vasodilator tone in the kidney of NG and DM rats, respectively. NO blockade increased baseline MABP and decreased renal haemodynamics, similarly in NG and DM rats, indicating comparable vasodilator influence of NO in the two groups. Unexpectedly, in all rats with intact NO synthesis, Ado receptor blockade increased kidney tissue NO. In NO-deficient NG and DM rats, Ado receptor blockade induced comparable renal vasodilatation, suggesting similar vasoconstrictor influence of the Ado system. However, DM rats showed an unexplained association of decreased MABP and IMBF and increased NO signal. Higher baseline renal excretion in DM rats indicated inhibition of renal tubular reabsorption due to the prevalence of natriuretic A2 over antinatriuretic A1 receptors. In conclusion, the experiments provided new insights in functional interrelation of adenosine and NO in normoglycaemia and streptozotocin-diabetes.

Assessment of thyroid Function in Diabetes Mellitus (middle &amp; old population) at Western UP

Diabetes mellitus (DM) and thyroid dysfunctions are the two most common endocrine disorders to come across in any clinical practice. Both thyroid hormones and insulin act antagonistically in metabolic pathways or cycles of cells. The aim of our study is to look for thyroid dysfunction in patients with type 2 DM and its correlation with insulin resistance (IR).A cross-sectional study was carried out among 325 diagnosed type 2 diabetic patients. Thyroid stimulating hormone (TSH), free triiodothyronine, free thyroxine, and insulin were measured in fasting serum sample. 325 study subjects majority 50.8% (165) belongs to age group 41-50 years followed by 28.3%(92) belongs to age group 51 -60 years while least subjects 0.9%(3) belongs to age group more than 80 years. 325 study subjects majority 58.5 %( 190) were female while rest 41.5% (153) were male. Subjects maximum 165(50.8%) have TSH level &amp;#60;4.60 micro IU/ml followed by 154 (47.9%) study subjects who have TSH level between 4.66-10microIU/ml and only 6 participants have TSH level more then 10microIU/The relationship between diabetes mellitus and thyroid disorders is characterized by a complex interdependent interaction. Unidentified thyroid dysfunction could negatively impact diabetes and its complications and may be one of the prime causes of poor management of type 2 DM. Therefore, there is a need for routine assay of thyroid hormones in type 2 diabetic patients to improve the medical management as well as to reduce the morbidity in them.

Coriolus versicolor alleviates diabetic cardiomyopathy by inhibiting cardiac fibrosis and NLRP3 inflammasome activation.

Coriolus versicolor (CV) is a traditional medicine and food mushroom. Our previous study demonstrated that CV extract exhibited anti-hyperglycemia and anti-insulin resistance effects. However, the effect of CV on cardiac function in diabetic cardiomyopathy (DCM) remains unclear. Therefore, we aimed to investigate the effect of CV on cardiac function in diabetes mellitus (DM) rats. We found that the cardiac dysfunction of DM rats was markedly improved by CV extract treatment. CV extract administration significantly attenuated cardiac fibrosis in DM rats, which was accompanied by suppressed transforming growth factor beta 1 (TGF-β1)/Smad signaling as indicated by decreased levels of TGF-β1, p-Smad2, and p-Smad3 and increased Smad7 expression. Moreover, CV extract treatment significantly alleviated cardiac inflammation as shown by decreased levels of NLRP3 receptor, cleaved caspase-1, IL-1β, and IL-18 in DM rats at least partly due to the inhibition of the NF-κB. In addition, high-glucose treatment induced cardiac fibrosis and increased cardiac inflammation in cardiac fibroblast cells, but these effects were ameliorated by CV extract treatment. Therefore, we conclude that the protective effect of CV on DCM is associated with the suppression of TGF-β1/Smad signaling and attenuation of NLRP3 inflammasome activation, suggesting that CV extract may be a potential therapeutic agent for DCM.

Tissue Doppler Imaging versus Conventional Echocardiography in Evaluation of Cardiac Functions in Diabetes Mellitus

Background: Conventional echocardiography and tissue Doppler imaging have been highlighted to diagnose diastolic and systolic heart dysfunction. We aimed to compare tissue Doppler imaging with conventional echocardiography to diagnose heart dysfunctions in diabetes mellitus type 1 (DMT1) patients. Materials and Methods: This case-control study was conducted in the Ali Asghar Clinic, Zahedan, Iran. The study lasted from 2017 to 2018 on 140 participants aged from 4-18 years, and consisted of 70 patients with DMT1, and 70 children who referred to hospital for checkup as control group. The participants went under tissue Doppler imaging andconventional echocardiography (M mode and 2D) by an invariable cardiologist. The 5 ml blood samples were taken to test blood leptin and ferritin. The data were analyzed using SPSS software (version 18.0). Results: Conventional findings such as left and right deceleration time, left, and right peak E velocity, left ejection time, left Myocardial performance index and TDI findings such as left, and right ET’, right S’, right E’, left MPI’, right MPI’, and left E/E’ were different in patients and the control group (p<0.05). Left and right deceleration time, and LV Mass index in conventional and left ET’, right ET’ in TDI were different in age groups of patients (p<0.05). In sex groups, left deceleration time, left peak A velocity, right acceleration time, right deceleration time and right E/A in conventional and left ET’, left ICT’, left IRT’, right ICT’, right IRT’, right S’ and right MPI’ in TDI were different (p<0.05). Conclusion: This study concluded that both conventional and TDI were different between DMT1 patients and the control group, but TDI was stronger in discrimination.

Metformin Prevents High Glucose Induced Disruption of Coronary Artery Endothelial Barrier Function and Accelerates Wound Healing Via Regulating Junctional Protein, VE‐Cadherin

Despite the great strides have been made in treating diabetes induced vascular endothelial barrier dysfunction, current treatments have shown limited success in reversing vascular pathologies. Increase in endothelial permeability via modification of endothelial junctional proteins, such as vascular endothelial cadherin (VE‐Cadherin), leads to the formation of minute inter‐endothelial gaps, and the infiltration of protein‐rich fluid in the interstitial space. If remained unchecked, the persistent buildup of edema underlying the endothelial lining sets the stage for the serious life‐threatening complications. Hyperglycemia‐induced endothelial dysfunction contributes vascular complications of diabetes. Moreover, wound healing impairment is also increasingly recognized to be a consequence of hyperglycemia‐induced dysfunction of endothelial in type 2 diabetes mellitus (T2DM). Metformin, an oral anti‐hyperglycemic agent, is the first‐line drug in the clinic for patients with T2DM. Clinical studies suggested that the beneficial effect of metformin on the incidence of diabetes complications was not only related to its action on blood glucose normalization. We hypothesized that the metformin prevents high glucose‐induced endothelial barrier dysfunction and accelerates wound healing process in human coronary endothelial cells (HCAE) via preventing the destabilization of VE‐cadherin. Endothelial permeability was evaluated by using Electric Cell‐substrate Impedance Sensing (ECIS) mechanism, a measure of trans‐endothelial electrical resistance (TEER) across the endothelial monolayers using TEER electrodes. Wound healing assay was performed by employing electric signals to both wound and monitor the healing process in endothelial monolayer. Our data show that 25mM glucose concentration increased endothelial permeability and abrogated the wound healing process. Metformin at the dose of 10mM significantly prevented alteration of endothelial barrier function and enhances wound healing process in the presence of high glucose concentration. To investigate the signaling mechanism involved in the protection offered by metformin, we found that metformin prevented myosin light chain kinase (MYLK) phosphorylation and increased in VE‐cadherin expression, suggesting abrogation of increase endothelial contractility and dismantling the junctional proteins in presence of high glucose concentration. In conclusion, our study shows that metformin maintained endothelial barrier function and improved the process of wound healing in endothelial cells exposed to high glucose. Thus, metformin is emerging as a potential therapeutics in improving coronary endothelial barrier function in diabetes mellitus.Support or Funding InformationThis work was supported by funding from CTRE SEED Grant Award to Mohammad Tauseef.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Alterations in postural control, gait pattern, and muscle function in diabetes mellitus: does it matter in children and adolescents with type 1 diabetes?

Diabetes mellitus (DM) is associated with chronic microvascular complications such as neuropathy. The most frequent is diabetic pe-ripheral neuropathy (DPN) which is related to chronic disability and decrease in quality of life. Alterations in postural control, gait per-formance, and muscle function are widely described in the literature. However, the role of other non-neuropathic factors in these altera-tions remains unclear. Although neuropathy is rather rare in children and adolescents with type 1 DM, there is evidence that early chang-es and symptoms might have their onset in the early stages of the disease. On the other hand, there is no evidence on functional changes related to neuromuscular status in the paediatric population with type 1 DM.

Relation between sexual dysfunction and metabolic syndrome

The prevalence of the metabolic syndrome, type 2 diabetes mellitus, cardiovascular diseases, obesity and depression have increased during the recent years. As the sexual dysfunction is also frequent, we aimed to search for the associations between sexual dysfunction and the metabolic syndrome and its components, respectively, by reviewing the literature. The clinical and biochemical components of the metabolic syndrome included cardiovascular disease, type 2 diabetes mellitus, visceral obesity and depression, furthermore, insulin resistance, atherogenic lipid profile, hypogonadism, chronic systemic inflammation and endothelial dysfunction were all demonstrated to affect adversely the sexual function. The dysfunction of the sexual arousal response shows a strong association in men and a milder one in women with the cardiovascular diseases and depression. Sexual function in diabetes mellitus is mostly impaired by microvascular injury, polyneuropathy and autonomic neuropathy. Erectile dysfunction and disorder of the female sexual arousal response and the orgasm, respectively, are associated with insulin resistance, atherogenic lipid profile and systemic inflammatory condition in overweight or obese patients. Sexual dysfunction particularly in men can be an early sign of the severe complications of metabolic syndrome. The pathogenetic link between the metabolic syndrome and the sexual dysfunction seems to be the insulin resistance. Both metabolic syndrome and sexual dysfunction can be restored by altering the lifestyle. Orv Hetil. 2019; 160(3): 98-103.