Effect Of Type 2 Diabetes Mellitus Research Articles

Basement membrane proteins in various arterial beds from individuals with and without type 2 diabetes mellitus: a proteome study

BackgroundBasement membrane (BM) accumulation is a hallmark of micro-vessel disease in diabetes mellitus (DM). We previously reported marked upregulation of BM components in internal thoracic arteries (ITAs) from type 2 DM (T2DM) patients by mass spectrometry. Here, we first sought to determine if BM accumulation is a common feature of different arteries in T2DM, and second, to identify other effects of T2DM on the arterial proteome.MethodsHuman arterial samples collected during heart and vascular surgery from well-characterized patients and stored in the Odense Artery Biobank were analysed by liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS). We included ascending thoracic aortas (ATA) (n = 10 (type 2 DM, T2DM) and n = 10 (non-DM)); laser capture micro-dissected plaque- and media compartments from carotid plaques (n = 10 (T2DM) and n = 9 (non-DM)); and media- and adventitia compartments from ITAs (n = 9 (T2DM) and n = 7 (non-DM)).ResultsWe first extended our previous finding of BM accumulation in arteries from T2DM patients, as 7 of 12 pre-defined BM proteins were significantly upregulated in bulk ATAs consisting of > 90% media. Although less pronounced, BM components tended to be upregulated in the media of ITAs from T2DM patients, but not in the neighbouring adventitia. Overall, we did not detect effects on BM proteins in carotid plaques or in the plaque-associated media. Instead, complement factors, an RNA-binding protein and fibrinogens appeared to be regulated in these tissues from T2DM patients.ConclusionOur results suggest that accumulation of BM proteins is a general phenomenon in the medial layer of non-atherosclerotic arteries in patients with T2DM. Moreover, we identify additional T2DM-associated effects on the arterial proteome, which requires validation in future studies.

Type 2 Diabetes Mellitus Intersects With Pancreatic Cancer Diagnosis and Development.

The relationship between type 2 diabetes mellitus (T2DM) and pancreatic cancer (PC) is complex. Diabetes is a known risk factor for PC, and new-onset diabetes (NOD) could be an early manifestation of PC that may be facilitate the early diagnosis of PC. Metformin offers a clear benefit of inhibiting PC, whereas insulin therapy may increase the risk of PC development. No evidence has shown that novel hypoglycemic drugs help or prevent PC. In this review, the effects of T2DM on PC development are summarized, and novel strategies for the prevention and treatment of T2DM and PC are discussed.

Auditory and Vestibular Functioning in Individuals with Type-2 Diabetes Mellitus: A Systematic Review.

Introduction Diabetes mellitus is a metabolic disease associated with a rise in the level of blood glucose. Individuals with diabetes mellitus are more likely to develop hearing loss, tinnitus, and dizziness due to macro- and microvascular complications. The extent to which auditory and vestibular functions are impaired in individuals with type-2 diabetes mellitus is still under debate. Objective To systematically review studies focusing on auditory and vestibular functions in individuals with type-2 diabetes mellitus. Data Synthesis A search was conducted in the PubMed, MedlinePlus, Ingenta Connect and Google Scholar databases for articles published until June 2019. A total of 15,980 articles were primarily retrieved, 33 of which were shortlisted based on the inclusion criteria set by the investigators for the systematic review. Out of 33 full-length articles, 26 evaluated the functioning of the auditory system, while 7 evaluated the functioning of the vestibular system. Most studies related to auditory functioning reported a significant effect of type-2 diabetes mellitus on the peripheral auditory system, whereas studies on vestibular functioning reported no significant effect of diabetes mellitus on the functioning of the peripheral vestibular end-organ. Conclusion Overall, the results of various audiological and peripheral vestibular tests reveal distinctive peripheral and/or central auditory and vestibular end-organ impairments in individuals with type-2 diabetes mellitus.

Type 2 diabetes mellitus in older adults: clinical considerations and management.

The past 50 years have seen a growing ageing population with an increasing prevalence of type 2 diabetes mellitus (T2DM); now, nearly half of all individuals with diabetes mellitus are older adults (aged ≥65 years). Older adults with T2DM present particularly difficult challenges. For example, the accentuated heterogeneity of these patients, the potential presence of multiple comorbidities, the increased susceptibility to hypoglycaemia, the increased dependence on care and the effect of frailty all add to the complexity of managing diabetes mellitus in this age group. In this Review, we offer an update on the key pathophysiological mechanisms associated with T2DM in older people. We then evaluate new evidence relating particularly to the effects of frailty and sarcopenia, the clinical difficulties of age-associated comorbidities, and the implications for existing guidelines and therapeutic options. Our conclusions will focus on the effect of T2DM on an ageing society.

Combined influence of diabetes mellitus and obesity on left ventricle remodeling in hypertensive patients

The aim of the study was to evaluate the effect of type 2 diabetes mellitus (T2DM) and obesity influence on the left ventricular (LV) remodeling peculiarities in hypertensive patients. Materials and methods. In total, 327 patients, aged 38–74 years, were comprehensively examined. The enrolled patients were divided into 4 groups in dependence of the presence of associated disease: the 1st group – n = 87 hypertensive patients with T2DM combined with obesity, the 2nd group – n = 71 hypertensive patient with T2DM and the 3rd group – n = 65 hypertensive patients with obesity; the comparison group consisted of 74 patients with essential hypertension (EH) but without obesity or diabetes. Echocardiography was performed according to the standard method of H. Feigenbaum to estimate the LV parameters. HbA1c was determined by turbidimetric method. Serum glucose levels were determined by ELISA. Results. When comparing the three patient groups with those who had only EH, the most significant influence was found in combined influence of T2DM and obesity on the development of unfavorable type of LV remodeling with values of χ2 = 29.371 and Pearson's contingency coefficient (C) ‒ 0.393 (P < 0.05). The presence of concomitant T2DM without obesity had a significant moderate relationship with the development of unfavorable LV geometry, χ2 = 11.029 and C ‒ 0.266 (P < 0.05), which indicates a much smaller impact on the process compared to the polymorbid effect of T2DM with obesity. Comparison of patients with a combination of EH and obesity with those who had only EH did not show a significant effect of concomitant obesity on the development of unfavorable types of LV geometry with values of χ2 and C: 0.529 and 0.062, respectively (P > 0.05). Conclusions. Essential hypertension with type 2 diabetes mellitus and obesity polymorbidity, but not in combination with type 2 diabetes mellitus or obesity alone, has the most significant association with hypertrophic types of LV remodeling. The co-existence of type 2 diabetes mellitus and obesity in hypertensive patients leads to the development of predominantly LV concentric hypertrophy.

Impact of type 2 diabetes mellitus on left ventricular diastolic function in patients with essential hypertension: evaluation by volume-time curve of cardiac magnetic resonance

BackgroundEssential hypertension and type 2 diabetes mellitus (T2DM) are two common chronic diseases that often coexist, and both of these diseases can cause heart damage. However, the additive effects of essential hypertension complicated with T2DM on left ventricle (LV) diastolic function have not been fully illustrated. This study aims to investigate whether T2DM affects the diastolic function of the LV in patients with essential hypertension using the volume-time curve from cardiac magnetic resonance (CMR).MethodsA total of 124 essential hypertension patients, including 48 with T2DM [HTN(T2DM +) group] and 76 without T2DM [HTN(T2DM-) group], and 52 normal controls who underwent CMR scans were included in this study. LV volume-time curve parameters, including the peak ejection rate (PER), time to peak ejection rate (PET), peak filling rate (PFR), time to peak filling rate from end-systole (PFT), PER normalized to end-diastolic volume (PER/EDV), and PFR normalized to EDV (PFR/EDV), were measured and compared among the three groups. Multivariate linear regression analyses were performed to determine the effects of T2DM on LV diastolic dysfunction in patients with hypertension. Pearson correlation was used to analyse the correlation between the volume-time curve and myocardial strain parameters.ResultsPFR and PFR/EDV decreased from the control group, through HTN(T2DM −), to HTN(T2DM +) group. PFT in the HTN(T2DM-) group and HTN(T2DM +) group was significantly longer than that in the control group. The LV remodelling index in the HTN(T2DM −) and HTN(T2DM +) groups was higher than that in the normal control group, but there was no significant difference between the HTN(T2DM −) and HTN(T2DM +) groups. Multiple regression analyses controlling for covariates of systolic blood pressure, age, sex, and heart rate demonstrated that T2DM was independently associated with PFR/EDV (β = 0.252, p < 0.05). The volume-time curve method has good repeatability, and there is a significant correlation between volume-time curve parameters (PER/EDV and PFR/EDV) and myocardial peak strain rate, especially circumferential peak strain rate, which exhibited the highest correlation (r = − 0.756 ~ 0.795).ConclusionsT2DM exacerbates LV diastolic dysfunction in patients with essential hypertension. The LV filling model changes reflected by the CMR volume-time curve could provide more information for early clinical intervention.

Effect of Type 2 Diabetes Mellitus and Diabetic Medication on Pulmonary Function

Background: Type 2 diabetes mellitus (T2DM) is a chronic condition with an impairing effect on multiple organs. Numerous respiratory disorders have been observed in patients with T2DM. However, the effect of T2DM on pulmonary function is inconclusive. Aims: In this study, we investigated the effect of T2DM on respiratory function and the correlation of glycemic control, diabetes duration and insulin intake. Methods: 1500 patients were recruited for this study; 560 having T2DM for at least a year were included in the final data, in addition to 540 healthy volunteers. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow at 25-75% (FEF 25-75%), as well as FEV1/FVC ratio values were measured. Results: A two-sample t-test showed that z-scores produced by Al-Qerem et al.’s equations for FEV1, FVC, and FEF 25-75% were significantly lower for the T2DM group than the control group (p &lt; 0.01). FEV1/FVC ratio in the T2DM group was significantly higher (p &lt; 0.01). Multiple linear regression analysis found that glycemic control represented by HbA1c as well as disease duration were negatively associated with the pulmonary function (p &lt; 0.01). However, insulin intake was found to have no significant correlation with pulmonary function. Conclusion: T2DM was linked to reduced pulmonary function and was consistent with a restrictive ventilation pattern. HbA1c, as well as disease duration, were found to be independent risk factors for reduced pulmonary function.

Effect of Type-2 Diabetes Mellitus in Retinopathy Patients on MDA, SOD Activity and its Correlation with HbA1c

Effect of Type-2 Diabetes Mellitus in Retinopathy Patients on MDA, SOD Activity and its Correlation with HbA1c

Increased Risk of Nasal Septal Abscess After Septoplasty in Patients with Type 2 Diabetes Mellitus.

To investigate the risk of nasal septal abscess (NSA) in patients with type 2 diabetes mellitus (T2DM) after septoplasty. Retrospective cohort study through Taiwan National Health Insurance database. The Taiwan National Health Insurance Research Database was used to conduct this retrospective cohort study. A total of 382 patients with T2DM (DM group) diagnosed between 2000 and 2010 and 382 matched patients without a DM diagnosis (non-DM group) were enrolled. Patients were followed up until death or December 31, 2013. NSA incidence was the main outcome. After septoplasty, the cumulative incidence of NSA in the DM group was significantly higher than that in the non-DM group (P< .001). Cox proportional hazards regression indicated a significant association between T2DM and higher NSA incidence (adjusted hazard ratio, 2.62; 95% CI, 1.44-3.61; P< .001). However, subgroup analysis and sensitivity testing demonstrated that the effect of T2DM on NSA risk was stable. In addition, the subgroup with a Diabetes Complications Severity Index (DCSI) of ≥1 had higher NSA risk than that with DCSI=0 (adjusted hazard ratio, 3.58; 95% CI, 2.10-6.09; P< .001). The treatment type for NSA did not differ between the groups. T2DM is an independent risk factor for NSA in patients undergoing nasal septoplasty, and the NSA risk is greater among patients with high DM severity. IV Laryngoscope, 131:E2420-E2425, 2021.

Alteration of salivary microbiome in periodontitis with or without type-2 diabetes mellitus and metformin treatment

We aimed to explore the effects of type-2 diabetes mellitus (T2DM) and hypoglycemic therapy on the salivary microbiome in periodontitis patients and identify the potential salivary micro-biomarker for the early warning of T2DM. Saliva samples were collected from healthy individuals (Health), periodontitis patients (P), T2DM patients, periodontitis patients with T2DM (DAP), and DAP patients treated with Metformin (Met). Samples were determined by16S rRNA gene sequencing. 29 phyla, 322 genera, and 333 species of salivary microbiome were annotated. Compared to the Health group, the P and DAP group showed a significantly higher diversity of saliva microbiota, while the T2DM and Met group had no significant difference in microbial abundance but showed a trend of increasing diversity. Other than well-known periodontitis-inducing pathogens, the proportion of Prevotella copri, Alloprevotella rava, and Ralstonia pickettii, etc. were also significantly increased in periodontitis patients with or without T2DM. After effective glycemic control, the abundance of Prevotella copri, Alloprevotella rava, Ralstonia pickettii, etc. decreased in periodontitis patients with companion T2DM. The accuracies of the classification models in differentiating Health-vs.-P, DAP-vs.-P, and T2DM-vs.-P were 100%, 96.3%, and 98.1%, respectively. Hypoglycemic therapy could reconstruct the saliva microbiota and hence improve the localized conditions of diabetes patients with periodontitis.

Type 2 diabetes is an independent predictor of lowered peak aerobic capacity in heart failure patients with non-reduced or reduced left ventricular ejection fraction

BackgroundAlthough type 2 diabetes mellitus (T2DM) is one of the most frequent comorbidities in patients with chronic heart failure (CHF), the effects of T2DM on the exercise capacity of CHF patients are fully unknown. Here, we tested the hypothesis that the coexistence of T2DM lowers CHF patients’ peak aerobic capacity.MethodsWe retrospectively analyzed the cases of 275 Japanese CHF patients with non-reduced ejection fraction (left ventricular ejection fraction [LVEF] ≥ 40%) or reduced EF (LVEF < 40%) who underwent cardiopulmonary exercise testing. We divided them into diabetic and nondiabetic groups in each CHF cohort.ResultsThe mean peak oxygen uptake (VO2) value was 16.87 mL/kg/min in the non-reduced LVEF cohort and 15.52 mL/kg/min in the reduced LVEF cohort. The peak VO2 was lower in the diabetics versus the nondiabetics in the non-reduced LVEF cohort with the mean difference (95% confidence interval [95% CI]) of − 0.93 (− 1.82 to − 0.04) mL/kg/min and in the reduced LVEF cohort with the mean difference of − 1.05 (− 1.96 to − 0.15) mL/kg/min, after adjustment for age-squared, gender, anemia, renal function, LVEF, and log B-type natriuretic peptide (BNP). The adjusted VO2 at anaerobic threshold (AT), a submaximal aerobic capacity, was also decreased in the diabetic patients with both non-reduced and reduced LVEFs. Intriguingly, the diabetic patients had a lower adjusted peak O2 pulse than the nondiabetic patients in the reduced LVEF cohort, but not in the non-reduced LVEF cohort. A multivariate analysis showed that the presence of T2DM was an independent predictor of lowered peak VO2 in CHF patients with non-reduced LVEF and those with reduced LVEF.ConclusionsT2DM was associated with lowered peak VO2 in CHF patients with non-reduced or reduced LVEF. The presence of T2DM has a negative impact on CHF patients’ exercise capacity, and the degree of impact is partly dependent on their LV systolic function.

Alteration of the Condylar Oral Bone in Obese and Gastric Bypass Mice

Obesity is the main cause of type 2 diabetes mellitus (T2DM). Roux-en-Y gastric bypass (RYGB) surgery is an effective treatment for this obesity-related health problem. However, the adverse effects of T2DM on bone tissue persist or even aggravate after this surgical procedure. As studies on the mandibular condyle bone are scarce, the aim of the present study was to assess its compositional characteristics in T2DM and RYGB conditions. Thirty-two male C57BL/6 mice at 8 weeks of age were randomly assigned to receive either a high-fat or low-fat diet. After 14 weeks of high-fat diet intake, seven obese mice were subjected to RYGB surgery. All animals were euthanized at the age of 30 weeks. Mandibular bones were removed and the trabecular condyle region was assessed using Raman spectroscopy. A decreased mineralization was observed for both T2DM and RYGB condyle bones when compared to controls, with elevated carbonate substitutions for the RYGB group. No compositional differences in crystallinity and presence of advanced glycation end products were found between the groups, with the exception of an increased presence of N-carboxymethyl-lysine in RYGB bone compared to their T2DM counterpart. Site-specific measurements revealed a non-uniform bone composition, with increasing mineralization and carbonate substitutions towards the centre of the mandibular condyle. T2DM and RYGB surgery affect the mandibular condyle bone quality, as investigated at compositional level. Assessment of bone structural properties and remodelling should be carried out to further explore the effects of T2DM and RYGB surgery on this skeleton area.

Pulmonary Pathology Among Patients with Type 2 Diabetes Mellitus: An Updated Systematic Review and Meta-analysis.

Restrictive lung pathology was reported in the previous meta-analysis among patients with Type 2 Diabetes mellitus (T2DM) which is date back to 2010. To see the effect of T2DM on pulmonary functions through updated systematic review and meta-analysis. PubMed. English language case-control or cross-sectional studies, published between 1 January 2010 to 31 August 2018. T2DM and non-diabetic subjects were compared for at least one of the pulmonary function variables i.e. Forced expiratory volume in 1st second (FEV1), % FEV1, Forced vital capacity (FVC), % FVC and % FEV1/FVC. Methodological quality of the study was assessed using Newcastle-Ottawa Quality Assessment Scale. Meta-analysis was done using Review Manager 5.3 (RevMan 5.3) and meta-regression was conducted using R statistical software. We selected 22 articles that met our inclusion and exclusion criteria. Results reveal that among patients with T2DM all variables were reduced except %FEV1/FVC which shows statistically nonsignificant results with P=0.46. This confirms that T2DM patients have a restrictive type of lung pathology. Only articles from the PubMed database were included. Conclusion and Implications of Key Findings: This review affirms the existing evidence of restrictive pathology among patients with T2DM. The future study could be conducted to see the effect of various rehabilitation protocols on pulmonary function among patients with T2DM.

0613 The Effects of Diabetes on Obstructive Sleep Apnea Severity and Progression: A Propensity Score Analysis

Abstract Introduction Obstructive sleep apnea (OSA) is associated with increased glucose intolerance and insulin resistance, and commonly coexists with type 2 diabetes mellitus (T2DM). Research suggests an independent association between these two conditions. However, more research into the role of T2DM in the development of OSA, or vice versa, is needed. Methods Leveraging data from 139 participants with T2DM from the Sleep AHEAD cohort and 5,085 participants without T2DM from the Sleep Heart Health Study (SHHS), we conducted two complementary propensity score (PS) subclassification analyses to estimate the effect of T2DM on the oxygen desaturation index (ODI), both at baseline and over 4-5 years of follow-up. PS models included age, sex, race, body mass index, neck circumference, waist circumference, total cholesterol, HDL cholesterol, triglycerides, Epworth Sleepiness Scale, and comorbid hypertension or cardiovascular disease. Models evaluating ODI progression also included baseline ODI. Results The PS subclassification analysis identified 109 participants with T2DM and 480 without T2DM, balanced with respect to baseline covariates, for evaluation of the effect of T2DM on baseline ODI. On average, those with T2DM had a 9 events/hour greater ODI compared to those without (24.3 [20.8, 27.9] vs. 15.3 [13.6, 16.9] events/hour; p&amp;lt;0.0001). Among patients with baseline ODI≥5, a second PS subclassification identified 99 with T2DM and 227 without for evaluating the effect of T2DM on ODI progression. No difference in change in ODI was observed between those with and without T2DM (mean [95% CI] difference -0.25 [-10.7, 10.2] events/hour; p=0.963). Conclusion Using two robust PS subclassification designs to minimize selection bias, we evaluated the effect of T2DM on baseline ODI and ODI progression in adults with OSA after 4-5 years. Those with T2DM had more severe baseline ODI, but there were no meaningful differences in ODI progression. Results further our understanding of the association between these coexisting conditions. Support NIH grant HL070301

Zengye Decoction Ameliorates Insulin Resistance by Promoting Glucose Uptake.

The incidence of type 2 diabetes mellitus (T2DM) has been increasing in recent years and has become a serious threat to human health. Zengye Decoction (ZYD), a well-known traditional Chinese medicinal formula, has been used in the treatment of T2DM with yin asthenia and extreme heat since Qing Dynasty. However, the characteristics of antidiabetic activities of ZYD have not been fully elucidated. In our study, high-fat diet and streptozotocin were used to establish the T2DM rat model. After 3 weeks of treatment with ZYD, the fasting blood glucose (FBG), oral glucose tolerance, the fasting serum insulin concentration, insulin sensitivity index (ISI), serum lipid profiles, and pancreas histopathology were measured. Then, under circumstance of insulin-resistant glucose consumption, 2-(N-(7-nitrobenz-2-oxa-l,3-diazol-4-yl) amino)-2-deoxyglucose (2-NBDG) uptake and glycogen content in C2C12 myotubes, 3T3-L1 adipocytes, and HepG2 cells were determined, respectively. Finally, the expressions of key targets in the insulin signaling pathway were measured to explain the potential mechanism underlying these activities. After administration with ZYD, a notable reduction in FBG levels, oral glucose tolerance test-area under the curve, blood lipid metabolism, and ISI values were observed compared with the diabetic control group. Moreover, ZYD restored the damaged islet cells in T2DM rats. Significant increases in glucose consumption, glucose uptake, glycogen content, expression of glucose transporter type 4, and the ratio of p-Akt/Akt were observed in the ZYD groups. According to the above results, ZYD exhibited glucose disposal, including glucose consumption, glucose uptake, and glycogen content and promoted the Akt signal pathway, which indicates that ZYD exerts significant hypoglycemic effect in T2DM.

Circulatory miRNAs as Novel Non-Invasive Biomarkers for the Diagnosis of Coronary Artery Disease in Patients with and Without Diabetes Mellitus

MicroRNAs are short non-coding RNAs implicated in the negative regulation of candidate genes of various disease complications including coronary artery disease (CAD). Our study aims to identify the diagnostic potential of circulatory miR-133b and miR-21 in the pathophysiology of CAD and the effect of type-2 diabetes mellitus (T2DM) per se on their expression. A total of 132 subjects were recruited from Delhi and surrounding regions including 78 subjects with angiographically proven CAD with and without T2DM. Quantitative real-time PCR assays were carried out to measure the relative expression profiles of miRNAs. In this study, miR-133b was found to be significantly downregulated by 4.63 fold whereas, miR-21 was upregulated by 2.0 fold in plasma samples of CAD patients. Moreover, we found that the presence of T2DM in CAD patients substantially affected and deviated the expression of both the miRNAs in an opposing manner. miR-133b deviated from 4.94 to 3.91 fold whereas, miR-21 deviated from 2.04 to 1.82 fold. Furthermore, both the miRNAs exhibited significant diagnostic potential at optimum cut-off values with area under curve (AUC) of >79% as assessed by receiver operating characteristics (ROC) curve analysis. To the best of our knowledge, this is the first report from Indian population describing the significant differential expression profile of miR-133b and miR-21 in CAD patients suggesting their crucial role in the pathophysiology and individual’s susceptibility in developing CAD. We conclude that miR-133b and miR-21 can be considered as novel, non-invasive biomarkers in the diagnosis of CAD in the presence or absence of T2DM.

Identification of Potential Therapeutic Targets and Pathways of Liraglutide Against Type 2 Diabetes Mellitus (T2DM) Based on Long Non-Coding RNA (lncRNA) Sequencing.

BackgroundThe aim of this study was to explore the potential therapeutic targets and pathways of liraglutide against type 2 diabetes mellitus (T2DM) in streptozotocin-induced diabetic rats based on lncRNA sequencing.Material/MethodsMale Wistar rats were randomly divided into 3 groups: the control group (n=10), the T2DM model group (high-sugar and high-fat diet, and streptozotocin-induced, n=11), and the liraglutide group (model plus liraglutide, n=10). After 8 weeks of drug treatment, lncRNA sequencing was used to identify the lncRNA therapeutic targets and their related protein-coding genes of liraglutide against T2DM, which were further studied by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to determine the major biological processes and pathways involved in the action of liraglutide treatment. Lastly, several lncRNA targets were randomly detected based on quantitative real-time polymerase chain reaction (QRT-PCR) to verify the accuracy of sequencing results.ResultsA total of 104 lncRNA targets of liraglutide against T2DM were screened, with 27 upregulated and 77 downregulated, including NONRATT030354.2, MSTRG.1456.6, and NONRATT011758.2. The major biological processes involved were glucose and lipid metabolism and amino acid metabolism. Liraglutide had a therapeutic effect in T2DM, mainly through the Wnt, PPAR, amino acid metabolism signaling, mTOR, and lipid metabolism-related pathways.ConclusionsIn this study, we screened 104 lncRNA therapeutic targets and several signaling pathways (Wnt, PPAR, amino acid metabolism signaling pathway, mTOR, and lipid metabolism-related pathways) of liraglutide against T2DM based on lncRNA sequencing.

Abstract TMP32: Transcriptome Changes of Brain Myeloid Cells After Ischemic Stroke in Type 2 Diabetic Mice

Introduction: Type 2 diabetes mellitus (T2DM) is associated with poor outcome after stroke. Brain myeloid cells are considered to play a pivotal role in modulating brain damage and recovery after stroke, but how myeloid response to stroke under diabetic condition is largely unclear. We used single-cell RNA sequencing (scRNA seq) to determine the transcriptome profiles of brain myeloid cells under diabetic and ischemic conditions using T2DM mouse model. Hypothesis: The altered gene expression in the brain myeloid cells under diabetic condition leads to the aggravation of ischemic brain injury. Methods: We performed scRNA seq in Percoll gradient-isolated brain mononuclear cells from middle-aged db/db and db/+ mice three days after direct middle cerebral artery occlusion (MCAO) or sham-operation. Clusters of brain myeloid cells were predominantly annotated as macrophages (mp) or microglia (mg) according to the expression of marker genes in each cell type. We identified DM-unique differentially expressed genes (DEGs) and stroke-unique DEGs, and assessed the biological role of these DEGs by enrichment analysis. Results: Myeloid cell population was increased in DM ( db/db without MCAO; mp 37.3% mg 10.6%) and stroke ( db/+ with MCAO; mp 26.2% mg 33.2%) group compared to control ( db/+ without MCAO; mp 3.4% mg 0.8%) group. In macrophages, 91 DM-unique (64 up- and 27 down-regulated) and 464 stroke-unique (458 up- and 6 down-regulated) DEGs were identified, whereas 258 stroke-unique (254 up- and 4 down-regulated) DEGs were identified in microglia. Enrichment analysis revealed that DM-unique down-regulated DEGs in macrophages were related to MHC class II antigen processing involved in Staphylococcus aureus infection pathway, indicating a possible relationship between immunosuppression and stroke aggravation in diabetes. DM-unique and stroke-unique up-regulated DEGs were related to oxidative phosphorylation, phagocytosis, and protein metabolism. Conclusions: The present study demonstrated altered gene expression profile and molecular network of brain myeloid cells in response to diabetic and ischemic conditions by scRNA seq, providing a clue to the underlying mechanism of the adverse effect of T2DM on stroke.

Association between body mass index and hand grip strength on bone mineral density in type 2 diabetes mellitus - A cross-sectional study

Background: Diabetes mellitus (DM) affects most of the organs with high rate of morbidity and mortality. Osteoporosis is also one of the common metabolic bone diseases. Osteoporosis and muscle weakness have been linked with type 2 DM (T2DM). However, there are limited studies and inconsistent results regarding type 2 diabetes and its effect on bone mineral density (BMD) and handgrip strength (HGS). Aims and Objectives: This study aims to find the effect of T2DM on BMD, body mass index (BMI), and HGS. Materials and Methods: A total of 328 participants of age group 30–70 years were included in the study. BMI was calculated using Quetelet index. Measurement of HGS was done using a handgrip dynamometer following standard methods. HGS max in kg and endurance time (ET) in seconds were recorded. BMD was recorded using bone sonometer, in the distal end of tibia. The results were analyzed on the basis of the WHO – compliant T-score and Z-score. Results: Among diabetic patients, BMI had a weak negative correlation with BMD and HGS max (P = 0.035). BMD had a weak positive correlation with HGS max and ET. HGS was significantly higher in non-diabetic males, whereas in non-diabetic females, both HGS and ET were significantly higher (P < 0.001). There was no significant difference in the BMD between T2DM and non-diabetics. Conclusion: In our study, we noted better muscle strength among non-diabetics and no significant difference in BMD between diabetics and non-diabetics, whereas incidence of osteoporosis was more among diabetics though statistically not significant.

P6309Impaired secretion of clusterin in pericardial fluid of diabetics, a deleterious outcome for the cardiac micro-vasculature

Abstract Background Extracellular vesicles are vital mediators of cell-to-cell communications. We previously demonstrated that in the adult heart, exosomes released in the pericardial fluid (PF) have the functional capability to induce cell survival and angiogenesis in recipient endothelial cells. It has previously been shown that PF exosomes from patients with an existing myocardial infarction (MI) contain clusterin (CLU). Remarkably, secreted CLU is cardio-protective as evidenced by enhanced arteriogenesis and reduced apoptosis in animal models of MI. We hypothesize that type 2 Diabetes Mellitus (T2DM) along with ischemic heart disease (IHD) alters PF EV content impairing its reparative angiogenic potential. Aim To investigate the role of T2DM in modulating human PF exosomal content and its vascular action. Methods and results PF samples were collected from 3 different groups of patients (N=3): 1) Ischemic heart disease (IHD) with or 2) without T2DM, and 3) non-ischaemic, non-diabetic controls operated for mitral valve repair. The impact of PF exosomes on human coronary microvascular ECs (HCMECs) was evaluated by cell based functional assays for measuring apoptosis, proliferation and angiogenesis. Interestingly, unlike PF exosomes from control patients, PF exosomes from DM patients with IHD promoted EC apoptosis and impaired angiogenesis. To investigate the effect of T2DM on PF content, we performed high throughput proteomic and metabolomic analysis of whole PF and PF EVs. We identified proteins and metabolites that were differentially expressed under T2DM condition by using the R package Limma. Employing a network approach, protein and metabolic data were integrated by using our newly developed inhouse R package Metabosignal. This networks approach revealed an interesting interaction circuit involving protein CLU. The T2DM-associated reduction of CLU level in the PF, identified from the “omics” analyses was confirmed by ELISA (n=8 patients per group). To examine the effects of DM and ischemia on CLU intracellular expression and secretion, HCMECs were exposed to high D-glucose (HG, 25 mM) and hypoxia (1%O2). In line with our PF data, HCMECs exposed to HG and hypoxia showed lower levels of both CLU mRNA and secreted CLU (ELISA). Importantly, recombinant CLU (rCLU) treatment on HCMECs rescued their angiogenic potential, induced cell proliferation and protected them from apoptosis under both HG and hypoxia conditions. In addition, silencing of endogenous levels of CLU in HCMECs impaired angiogenesis, suggesting that CLU might be an inherent component of the angiogenesis machinery in ECs. Conclusions This study suggests that DM reduces the level of secreted CLU in the PF, depriving myocardial micro-vessels of this protective and regenerative mediator. Restoring diminished CLU levels in the diabetic heart could be a possible therapeutic approach for contrasting diabetic micro-angiopathy. Acknowledgement/Funding British Heart Foundation Program Grant