Fluoxetine Attenuated Anxiety-Like Behaviors in Streptozotocin-Induced Diabetic Mice by Mitigating the Inflammation

Patients with diabetes mellitus (DM) showed an increased risk of anxiety. High anxiety levels are also shown to increase stress of diabetic patients, which may contribute to poor clinical outcomes. The mechanisms underlying the development of anxiety disorders in diabetic patients remain unknown. As a result, there are no available treatments yet. Here, we tested the hypothesis that glial cells in the hippocampal area of DM mice might be responsible for their anxiety-like behaviors. Furthermore, we postulated that treatment with antidepressant, fluoxetine, could reduce anxiety behaviors and prevent the dysregulation of glial cells (oligodendrocyte and astrocyte) in DM mice. Diabetic mice were administered a single injection of streptozotocin (STZ), followed by treatment with fluoxetine. Mice were then tested on Y maze, open field, dark and light transition, and elevated plus maze tests to measure the status of anxiety and cognition. After completing these behavioral tests, mice were sacrificed and western blot was used to detect the oligodendrocyte and astrocyte maker proteins in hippocampal tissues. Emphasis was directed towards adult oligodendrocyte precursor cells (OPCs) and their marker protein to measure their proliferation and differentiation. We found that fluoxetine could effectively mitigate the level of anxiety and attenuate the cognitive dysfunction in diabetic mice. Meanwhile, fluoxetine inhibited astrocyte activation in mice exposed to STZ, prevented the loss of myelin basic protein (MBP), and affected the function of OPCs in these diabetic mice. The results suggested that the changes of these glial cells in the brains of diabetic mice might be related to the high anxiety levels and cognitive deficit in DM mice. Fluoxetine could ameliorate the high anxiety level and prevent cognitive deficit via inhibiting astrocyte activation and repairing the oligodendrocyte damage.

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Quetiapine Attenuates the Neuroinflammation and Executive Function Deficit in Streptozotocin-Induced Diabetic Mice

Mediators of Inflammation ◽

10.1155/2019/1236082 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Kexin Wang ◽

Feng Song ◽

Hongxing Wang ◽

Jun-hui Wang ◽

Yu Sun

Keyword(s):

Cognitive Deficit ◽

Neuroprotective Effect ◽

Underlying Mechanism ◽

Diabetic Mouse ◽

Diabetic Patients ◽

Diabetic Mice ◽

Protein Loss ◽

Monocyte Chemoattractant Protein 1 ◽

Beneficial Effects ◽

Increased Risk

Diabetic patients are at increased risk for developing memory and cognitive deficit. Prior studies indicate that neuroinflammation might be one important underlying mechanism responsible for this deficit. Quetiapine (QTP) reportedly exerts a significant neuroprotective effect in animal and human studies. Here, we investigated whether QTP could prevent memory deterioration and cognitive impairment in a streptozotocin- (STZ-) induced diabetic mouse model. In this study, we found that STZ significantly compromised the behavioral performance of mice in a puzzle box test, but administering QTP effectively attenuated this behavioral deficit. Moreover, our results showed that QTP could significantly inhibit the activation of astrocytes and microglia in these diabetic mice and reduce the generation and release of two cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCP-1). Meanwhile, QTP also prevented the protein loss of the synaptic protein synaptophysin (SYP) and myelin basic protein (MBP). Here, our results indicate that QTP could inhibit neuroinflammatory response from glial cells and block the injury of released cytokines to neurons and oligodendrocytes in diabetic mice (DM). These beneficial effects could protect diabetic mice from the memory and cognitive deficit. QTP may be a potential treatment compound to handle the memory and cognitive dysfunction in diabetic patients.

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The Capacity of a Specific Anti-Streptococcus Mutans Monoclonal Antibodies Test to Identify the Diabetic Patients with Increased Risk of Periodontal Disease

Revista de Chimie ◽

10.37358/rc.17.11.5927 ◽

2017 ◽

Vol 68 (11) ◽

pp. 2556-2559

Author(s):

Mona Ionas ◽

Sebastian Ioan Cernusca Mitariu ◽

Adela Dancila ◽

Tiberiu Horatiu Ionas ◽

Raluca Monica Comaneanu ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Periodontal Disease ◽

Streptococcus Mutans ◽

Mutans Streptococci ◽

Diabetic Patients ◽

A Value ◽

Salivary Level ◽

Increased Risk ◽

The Status

By means of a specific anti-Streptococcus mutans monoclonal antibodies test we want to identify the diabetic patients which have an increased risk to develop the periodontal disease. The highest percentage, of 88.1% of all patients included in this study represents the subjects with a level greater than 500,000 cfu / mL of streptococcus mutans. The Kruskal-Wallis test reveals a value of p = 0.283 resulted from the status of diabetes in patients and the level of streptococcus mutans in saliva. In conclusion, the status of diabetes in patients seems not to influence the salivary level of mutans streptococci determined with the method used in our study.

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Current state-of-the-art antiplatelet and anticoagulation therapy in diabetic patients with coronary artery disease

Future Cardiology ◽

10.2217/fca-2021-0014 ◽

2021 ◽

Author(s):

Johny Nicolas ◽

Victor Razuk ◽

Gennaro Giustino ◽

Roxana Mehran

Keyword(s):

Diabetes Mellitus ◽

Complex Disease ◽

Anticoagulation Therapy ◽

Treatment Strategies ◽

Diabetic Patients ◽

Current State ◽

Organ Systems ◽

Patients With Diabetes ◽

The Status ◽

Artery Disease

Diabetes mellitus is a complex disease that leads to long-term damage to various organ systems. Among the numerous cardiovascular disease-related complications, thrombotic events frequently occur in patients with diabetes. Although guidelines exist for treating and preventing most diabetes-related co-morbidities, the evidence on antithrombotic therapy in primary and secondary prevention is limited due to the scarcity of randomized trials dedicated to patients with diabetes mellitus. Most of the available data are derived from studies that only included a small proportion of patients with diabetes. The present review provides an overview of the status of knowledge on antiplatelet and anticoagulation therapy in patients with diabetes, focusing on the risk–benefit balance of these therapies and future treatment strategies.

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New Fast Acting Glucagon for Recovery from Hypoglycemia, a Life-Threatening Situation: Nasal Powder and Injected Stable Solutions

International Journal of Molecular Sciences ◽

10.3390/ijms221910643 ◽

2021 ◽

Vol 22 (19) ◽

pp. 10643

Author(s):

Lucia La Sala ◽

Antonio E. Pontiroli

Keyword(s):

Severe Hypoglycemia ◽

Well Being ◽

Nasal Administration ◽

Diabetic Patients ◽

Good Glycemic Control ◽

Increased Risk ◽

The Us ◽

Patients With Diabetes ◽

Adults And Children ◽

Fast Acting

The goal of diabetes care is to achieve and maintain good glycemic control over time, so as to prevent or delay the development of micro- and macrovascular complications in type 1 (T1D) and type 2 diabetes (T2D). However, numerous barriers hinder the achievement of this goal, first of all the frequent episodes of hypoglycemia typical in patients treated with insulin as T1D patients, or sulphonylureas as T2D patients. The prevention strategy and treatment of hypoglycemia are important for the well-being of patients with diabetes. Hypoglycemia is strongly associated with an increased risk of cardiovascular disease in diabetic patients, due probably to the release of inflammatory markers and prothrombotic effects triggered by hypoglycemia. Treatment of hypoglycemia is traditionally based on administration of carbohydrates or of glucagon via intramuscular (IM) or subcutaneous injection (SC). The injection of traditional glucagon is cumbersome, such that glucagon is an under-utilized drug. In 1983, it was shown for the first time that intranasal (IN) glucagon increases blood glucose levels in healthy volunteers, and in 1989–1992 that IN glucagon is similar to IM glucagon in resolving hypoglycemia in normal volunteers and in patients with diabetes, both adults and children. IN glucagon was developed in 2010 and continued in 2015; in 2019 IN glucagon obtained approval in the US, Canada, and Europe for severe hypoglycemia in children and adults. In the 2010s, two ready-to-use injectable formulations, a stable non-aqueous glucagon solution and the glucagon analog dasiglucagon, were developed, showing an efficacy similar to traditional glucagon, and approved in the US in 2020 and in 2021, respectively, for severe hypoglycemia in adults and in children. Fast-acting glucagon (nasal administration and injected solutions) appears to represent a major breakthrough in the treatment of severe hypoglycemia in insulin-treated patients with diabetes, both adults and children. It is anticipated that the availability of fast-acting glucagon will expand the use of glucagon, improve overall metabolic control, and prevent hypoglycemia-related complications, in particular cardiovascular complications and cognitive impairment.

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Abstract 6238: Clarifying the Opportunities to Improve Survival After MI in Diabetic Patients

Circulation ◽

10.1161/circ.118.suppl_18.s_1164-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Lance S Longmore ◽

Kimberly J Reid ◽

Mikhail Kosiborod ◽

Frederick A Masoudi ◽

Verna Welch ◽

...

Keyword(s):

Cardiovascular Disease ◽

Patient Characteristics ◽

Psychosocial Health ◽

Diabetic Patients ◽

Biological Factors ◽

Increased Risk ◽

Wide Range ◽

Patients With Diabetes ◽

Multivariable Models ◽

Adjusted Model

While diabetes is known to be associated with increased mortality after MI, whether these differences in outcome are due to patient characteristics, treatment, or other biological factors is unknown. We analyzed a contemporary cohort of MI survivors to comprehensively adjust for demographics, comorbidities, psychosocial, health status, clinical and treatment factors to determine if residual disparities in outcomes exist. We studied 2481 hospital survivors of MI in the prospective, 19-center PREMIER study (29% with diabetes). Multivariable models with sequential adjustment were employed to identify the extent to which variation in a wide range of patient characteristics (Figure ) accounted for differences in 3-year mortality in patients with and without diabetes. Unadjusted mortality was more than 2.5-fold greater for patients with diabetes (HR 2.55, 95% CI 2.08–3.14). Mortality was most attenuated by diabetes-related comorbidities (Figure ). The fully-adjusted model identified a significant, albeit attenuated, excess 3-year mortality among patients with diabetes (HR 1.57, 95% CI 1.22–1.99). Patients with diabetes experience a substantially increased risk for 3-year mortality after MI, even after accounting for a wide range of patient and treatment characteristics. This suggests that unmeasured, biologic variables associated with diabetes may mediate this difference. Further inquiry into the pathogenesis of diabetic cardiovascular disease is needed to identify new opportunities to improve the prognosis of patients with diabetes.

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The Challenge of Lipid Management in Patients with Diabetes or Other Endocrine Disorders

European Endocrinology ◽

10.17925/ee.2011.07.02.92 ◽

2010 ◽

Vol 7 (2) ◽

pp. 92

Author(s):

Alberico L Catapano ◽

Liliana Grigore ◽

Angela Pirillo ◽

◽

...

Keyword(s):

Statin Therapy ◽

Meta Analysis ◽

Diabetic Patients ◽

Endocrine Disorders ◽

Lipid Management ◽

Increased Risk ◽

Patients With Diabetes ◽

Associated Risk Factors

Diabetes increases the risk of developing cardiovascular disease (CVD), and several guidelines suggest that subjects with diabetes are at high risk of developing CVD. The increased risk can be attributed, at least in part, to associated risk factors, including hypertension and dyslipidaemia. The role of statins in primary and secondary prevention of CVD is well established, and the positive effect has been clearly demonstrated also in patients with type 2 diabetes. A number of studies have evaluated the effect of statin therapy on incident CVD and shown that statin therapy produces a great reduction in cardiovascular risk, but a recent meta-analysis revealed a slight increase in the risk of developing diabetes. Such risk is, however, low, especially when compared with the reduction in cardiovascular events and should not interfere with the choice of treating diabetic patients with a cholesterol-lowering therapy.

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Implication of Current ASE/EACVI Left Ventricular Diastolic Function Classification in Predicting 2-Year MACE in Asymptomatic Patients with Diabetes and Hypertension

European Heart Journal ◽

10.1093/eurheartj/ehab724.0105 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

D Foo ◽

K H Lam ◽

M Igo ◽

M N A Sulaiman ◽

M Y Ku ◽

...

Keyword(s):

Left Atrial Volume ◽

Left Ventricular ◽

Volume Index ◽

Diabetic Patients ◽

Prognostic Impact ◽

Left Atrial Volume Index ◽

Asymptomatic Patients ◽

Number Of Patients ◽

Increased Risk ◽

Patients With Diabetes

Abstract Background Left ventricular diastolic dysfunction (LVDD) has been shown to be more prevalent in patients with diabetes, and once progress to overt heart failure, carry worse clinical outcomes. Substantial number of patients were classified as indeterminate DF based on the current ASE/EACVI guidelines. The implication of current DF classification in predicting MACE among diabetic patients is not well established. Purpose To assess prognostic impact of current guidelines-based DF classification, and determine predictors of 2-year MACE based on individual LVDD parameters. Methods A total of 111 patients with diabetes and hypertension who attended diabetic clinic follow-up at the primary healthcare settings were enrolled. All patients had no prior cardiovascular events, had preserved left ventricular (LV) ejection fraction on echocardiography and sinus rhythm on ECG at screening. Echocardiography was performed to obtain parameters of LV dimensions, LV volumes and LVDD. The 2016 ASE/EACVI guidelines were applied to classify DF. All patients were followed up until 2 years to assess MACE. Results There were 65 (58.6%) female patients. Mean age was 59.86 (7.45); mean duration of DM was 10.5 (5.41). 80 (72.1%) patients were classified as having normal DF (nDF); 24 (21.6%) patients were classified as indeterminate DF (iDF); 7 patients (6.3%) were classified as LVDD. Patients with LVDD had significantly higher LV mass index (LVMI) (mean 121.72±23.28g/m2 vs 116.62±24.66g/m2 in iDF vs 102.50±22.89g/m2 in nDF); higher left atrial volume index (LAVI) (mean 41.24±10.28ml/m2 vs 30.55±10.07ml/m2 in iDF vs 25.75±6.30ml/m2 in nDF); lower lateral e' velocity (mean 6.35±2.05cm/s vs 7.37±1.73cm/s in iDF vs 8.59±2.13cm/s in nDF); higher septal E/e' ratio (mean 14.89±3.29 vs 12.16±3.99 in iDF vs 9.99±2.35 in nDF); higher average septal-lateral E/e' ratio (mean 14.22±3.77 vs 11.34±3.74 in iDF vs 9.04±2.10 in nDF). Among these 111 patients, 10 patients (9%) reported MACE at 2 years. The risk of 2-year MACE is elevated in both iDF [odds ratio (OR) 3.80, 95% CI 0.87–16.54, p=0.075] and LVDD [OR 7.60, 95% CI 1.11–52.02, p=0.039]. LVMI (OR 1.027, 95% CI 1.004– 1.051, p=0.023), LAVI (OR 1.092, 95% CI 1.017–1.172), and average septal-lateral E/e' ratio (OR 1.276, 95% CI 1.047–1.557, p=0.016) significantly correlated with 2-year MACE. Conclusions LVDD is correlated with increased MACE at 2 years. LVMI, LAVI and average septal-lateral E/e' ratio were predictors of increased risk of MACE at 2 years. Further investigation with larger sample size is warranted. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health Malaysia

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Proteomic mechanistic profile of patients with diabetes at risk of developing heart failure: insights from the HOMAGE trial

Cardiovascular Diabetology ◽

10.1186/s12933-021-01357-9 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Job A. J. Verdonschot ◽

João Pedro Ferreira ◽

Pierpaolo Pellicori ◽

Hans-Peter Brunner-La Rocca ◽

Andrew L. Clark ◽

...

Keyword(s):

Heart Failure ◽

At Risk ◽

Plasma Concentrations ◽

Diabetic Patients ◽

Proteomic Profile ◽

Developing Heart ◽

Diabetes Status ◽

Increased Risk ◽

Patients With Diabetes ◽

Patients At Risk

Abstract Background Patients with diabetes mellitus (DM) are at increased risk of developing heart failure (HF). The “Heart OMics in AGEing” (HOMAGE) trial suggested that spironolactone had beneficial effect on fibrosis and cardiac remodelling in an at risk population, potentially slowing the progression towards HF. We compared the proteomic profile of patients with and without diabetes among patients at risk for HF in the HOMAGE trial. Methods Protein biomarkers (n = 276) from the Olink®Proseek-Multiplex cardiovascular and inflammation panels were measured in plasma collected at baseline and 9 months (or last visit) from HOMAGE trial participants including 217 patients with, and 310 without, diabetes. Results Twenty-one biomarkers were increased and five decreased in patients with diabetes compared to non-diabetics at baseline. The markers clustered mainly within inflammatory and proteolytic pathways, with granulin as the key-hub, as revealed by knowledge-induced network and subsequent gene enrichment analysis. Treatment with spironolactone in diabetic patients did not lead to large changes in biomarkers. The effects of spironolactone on NTproBNP, fibrosis biomarkers and echocardiographic measures of diastolic function were similar in patients with and without diabetes (all interaction analyses p > 0.05). Conclusions Amongst patients at risk for HF, those with diabetes have higher plasma concentrations of proteins involved in inflammation and proteolysis. Diabetes does not influence the effects of spironolactone on the proteomic profile, and spironolactone produced anti-fibrotic, anti-remodelling, blood pressure and natriuretic peptide lowering effects regardless of diabetes status. Trial registration NCT02556450.

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Association of Myocardial Fibrosis Detected by Late Gadolinium-Enhanced MRI with Clinical Outcomes of Patients with Diabetes: A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-30053/v1 ◽

2020 ◽

Author(s):

Zhi Yang ◽

Rong Xu ◽

Jia-rong Wang ◽

Hua-yan Xu ◽

Hang Fu ◽

...

Keyword(s):

Myocardial Fibrosis ◽

Random Effects ◽

Data Extraction ◽

Meta Analysis ◽

Imaging Biomarker ◽

Diabetic Patients ◽

Significant Heterogeneity ◽

Cardiac Events ◽

Increased Risk ◽

Patients With Diabetes

Abstract Background Prior studies demonstrated that myocardial fibrosis assessed by late gadolinium-enhanced (LGE) MRI is associated with an increased risk for major adverse cardiac and cerebrovascular events (MACCE) or major adverse cardiac events (MACE) in patients with diabetes. However, the results of these studies were controversial and limited. Therefore, we performed this meta-analysis assessing the associations of myocardial fibrosis detected by LGE with the risk of MACCE and MACE in patients with diabetes. Methods We selected studies using MEDLINE, EMBASE and Cochrane by Ovid on December 2019. Prospective and retrospective studies that assessed the associations of myocardial fibrosis detected by LGE with the risk of MACCE or MACE in patients with diabetes with a disease duration of at least 12 months. Two independent reviewers performed the data extraction using a standardized form. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated by a random-effects model. Results Eight studies with 1121 patients were included in this meta-analysis, and follow-up of patients ranged from 17 to 70 months. The prevalence of LGE in the total sample was high, occurring in 38.09%. The annualized event rates (AERs) for MACCE was 11.94% in patients with diabetes and LGE. The presence of myocardial fibrosis detected by LGE was associated with an increased risk for MACCE (HR: 2.58; 95%CI 1.42-4.71; P=0.002) and MACE (HR: 5.28; 95%CI 3.20-8.70; P=0.000) in patients with diabetes. In a subgroup meta-analysis, ischemic fibrosis detected by LGE was associated with MACCE/MACE (HR 3.75, 95%CI 2.11-6.69; P=0.000) in patients with diabetes. In diabetic patients with preserved ejection fraction, the association between myocardial fibrosis detected by LGE and MACCE/MACE remained significant (HR: 4.02; 95%CI 2.22-7.25; P=0.000). All of the meta-analyses showed no significant heterogeneity from random effects. Conclusion This study demonstrated that myocardial fibrosis detected by LGE conferred an increase in the risk of MACCE/MACE in patients with diabetes and may be an imaging biomarker for risk stratification.

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Long-term glycemic variability and risk of stroke in patients with diabetes: a meta-analysis

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-021-00770-0 ◽

2022 ◽

Vol 14 (1) ◽

Author(s):

Xiaoli Ren ◽

Zhiyun Wang ◽

Congfang Guo

Keyword(s):

Standard Deviation ◽

Coefficient Of Variation ◽

Meta Analysis ◽

Glycemic Variability ◽

Diabetic Patients ◽

Increased Risk ◽

Follow Up Studies ◽

Patients With Diabetes

Abstract Objectives Long-term glycemic variability has been related to increased risk of vascular complication in patients with diabetes. However, the association between parameters of long-term glycemic variability and risk of stroke remains not fully determined. We performed a meta-analysis to systematically evaluate the above association. Methods Medline, Embase, and Web of Science databases were searched for longitudinal follow-up studies comparing the incidence of stroke in diabetic patients with higher or lower long-term glycemic variability. A random-effect model incorporating the potential heterogeneity among the included studies were used to pool the results. Results Seven follow-up studies with 725,784 diabetic patients were included, and 98% of them were with type 2 diabetes mellitus (T2DM). The mean follow-up duration was 7.7 years. Pooled results showed that compared to those with lowest category of glycemic variability, diabetic patients with the highest patients had significantly increased risk of stroke, as evidenced by glycemic variability analyzed by fasting plasma glucose coefficient of variation (FPG-CV: risk ratio [RR] = 1.24, 95% confidence interval [CI] 1.11 to 1.39, P < 0.001; I2 = 53%), standard deviation of FPG (FPG-SD: RR = 1.16, 95% CI 1.02 to 1.31, P = 0.02; I2 = 74%), HbA1c coefficient of variation (HbA1c-CV: RR = 1.88, 95% CI 1.61 to 2.19 P < 0.001; I2 = 0%), and standard deviation of HbA1c (HbA1c-SD: RR = 1.73, 95% CI 1.49 to 2.00, P < 0.001; I2 = 0%). Conclusions Long-term glycemic variability is associated with higher risk of stroke in T2DM patients.

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