Correlation Between Retinopathy and Coronary Microcirculation Dysfunction in Patients with Type 2 Diabetes Mellitus.

PURPOSE: The aim of this study is to evaluate the correlation between retinopathy and coronary microcirculation dysfunction (CMD) in type 2 diabetes mellitus (T2DM) patients. METHODS: 198 T2DM patients with left ventricular ejection fraction (LVEF)>50%, no epicardial coronary artery stenosis diagnosis by coronary angiography (CAG) and successfully completed coronary blood flow reserve (CFR) test and laboratory examination were enrolled, and fundus examination was performed on all participants. Two groups were divided according to CFR value, including 86 patients with CMD (CFR≤2.5) in study group and 112 patients without CMD (CFR>2.5) in control group. The composition of various retinopathy in two groups was observed, and the correlation between retinopathy and CMD was analyzed using ordered logistic regression. RESULTS: There were 13 cases with arteriovenous (A/V) nicking, 4 cases with proliferative diabetic retinopathy (PDR), 14 cases with non-proliferative diabetic retinopathy (NPDR), 17 cases with diabetic retinopathy (DR) with A/V nicking, 38 cases without retinopathy in study group, and 18 cases, 7 cases, 20 cases, 4 cases and 63 cases for each in control group. After adjustment for age, gender, hypertension, diabetes duration, dyslipidemia, glycosylated hemoglobin (HbA1c), body mass index (BMI), A/V nicking, PDR and NPDR, the diference of DR with A/V nicking between study and control group remained statistically signifcant (OR 2.0, 95% CI 0.79 to 3.21, p = 0.001). CONCLUSION: DR with A/V nicking could be used as an independent predictor of T2DM patients with CMD. CFR testing should be performed on patients with this kind of eye sign, even if they do not have any symptoms of heart disease. Meanwhile, DR with A/V nicking might be served as a reference indicator of CMD in T2DM patients with chest pain who were unable to be tested for CFR.

COVID-19 and Diabetes: A Comprehensive Review of Angiotensin Converting Enzyme 2, Mutual Effects and Pharmacotherapy.

The potential relationship between diabetes and COVID-19 has been evaluated. However, new knowledge is rapidly emerging. In this study, we systematically reviewed the relationship between viral cell surface receptors (ACE2, AXL, CD147, DC-SIGN, L-SIGN and DPP4) and SARS-CoV-2 infection risk, and emphasized the implications of ACE2 on SARS-CoV-2 infection and COVID-19 pathogenesis. Besides, we updated on the two-way interactions between diabetes and COVID-19, as well as the treatment options for COVID-19 comorbid patients from the perspective of ACE2. The efficacies of various clinical chemotherapeutic options, including anti-diabetic drugs, renin-angiotensin-aldosterone system inhibitors, lipid-lowering drugs, anticoagulants, and glucocorticoids for COVID-19 positive diabetic patients were discussed. Moreover, we reviewed the significance of two different forms of ACE2 (mACE2 and sACE2) and gender on COVID-19 susceptibility and severity. This review summarizes COVID-19 pathophysiology and the best strategies for clinical management of diabetes patients with COVID-19.

Neutrophil-to-lymphocyte ratio is associated with coronary microvascular dysfunction in type 2 diabetes mellitus patients.

AIMS: Our study is aimed to investigate the relationship between neutrophil-to-lymphocyte ratio (NLR) and coronary microvascular dysfunction (CMD) in type 2 diabetes mellitus (T2DM) patients. METHODS: We retrospect the consecutive medical files of 160 T2DM patients and recorded their clinical information and laboratory findings. Patients were divided into CMD group (n = 87) and non-CMD group (n = 73). We compared the NLR values of the two groups. Meanwhile we also observed the prevalence of CMD at different NLR levels. Then, logistic regression and ROC analysis were performed. RESULTS: NLR value of CMD group was significantly lower than non-CMD group (2.01 ± 0.74 vs 2.53 ± 0.69, P＜0.001). Prevalence of CMD in low (NLR ≤ 1.53, n = 30), medium (1.53 < NLR ≤ 2.20, n = 53) and high (NLR > 2.20, n = 77) group were 90%, 61.1%, and 39.2% respectively. The prevalence of CMD significantly increased as NLR level decreased. After adjusting potential related factors, NLR was still significantly correlated with CMD (OR = 0.295, 95 %CI:0.162-0.539, P < 0.001). The area under ROC curve (AUC) was 0.707 (95 %CI:0.627-0.786, P < 0.001). CONCLUSIONS: Our results showed that NLR is associated with CMD in T2DM patients, and the prevalence of CMD may increase as NLR level decrease.

Intermittent high glucose induces pyroptosis of rat H9C2 cardiomyocytes via sodium-glucose cotransporter 1.

Cardiomyocyte death is an important pathogenic process in cardiac complications of diabetes. Diabetic patients often suffer glycemic variability. Pyroptosis is a form of programmed cell death triggered by inflammasomes and related with caspase-1 and gasdermin D activation. The present study was designed to examine the effects of intermittent high glucose simulating glycemic variability on the pyroptosis of cardiomyocytes in vitro. Rat H9C2 cardiomyocytes were incubated with normal glucose (NG), constant high glucose (CHG) and intermittent high glucose (IHG). Results showed that compared to CHG treatment, IHG further inhibited cell proliferation and promoted cell death of H9C2 cardiomyocytes. In addition, IHG upregulated higher levels of the expressions of inflammasome NLR family pyrin domain containing 3 (NLRP3) and adaptor protein apoptosis-associated speck-like protein containing CARD domain (ASC) and increased higher levels of activated caspase-1 and gasdermin D than CHG treatment. Moreover, the production of reactive oxygen species (ROS) and activation of NF-κB that is induced by IHG were significantly higher than that induced by CHG. Knockdown of sodium-glucose cotransporters 1 (SGLT1) in H9C2 cardiomyocytes was performed and the effects of SGLT1 on IHG-induced pyroptosis was evaluated. The results demonstrated that knockdown of SGLT1 partially reduced IHG-induced pyroptosis, ROS generation and NF-κB activation. Our results indicated that IHG is harmful to cardiomyocytes and it might be partially because of the SGLT1-depedent pyroptosis in cardiomyocytes.

Inhibition of SGLT1 protects against glycemic variability-induced cardiac damage and pyroptosis of cardiomyocytes in diabetic mice.

AIMS: Glycemic variability has been shown to be more harmful in the development of diabetic complication than sustained chronic hyperglycemia. In this present study, we tried to reveal the effects of glycemic variability on cardiac damage in diabetic mice and investigate whether sodium-glucose cotransporter 1 (SGLT1), an important cardiac glucose transporter, functions as an important mediator in the process. MATERIALS AND METHODS: Type 2 diabetes mellitus (DM) mice were induced by a high-fat diet and intraperitoneal injection of streptozotocin (STZ), and then glycemic variability in type 2 diabetes mellitus (GVDM) was induced by alternately injecting insulin and glucose to DM mice. In order to determine the roles of SGLT1 in GVDM mice, SGLT1 inhibition was performed using shRNA against SGLT1. The blood glucose level, the cardiac function and myocardial injury were assessed. And the expressions of SGLT1 and the activations of NLRP3/caspase-1 pathway and NF-κB in left ventricular tissues were measured. KEY FINDINGS: The results showed that SGLT1 was highly expressed in heart of GVDM mice compared to control and DM groups, and knockdown of SGLT1 reduced glycemic variability in GVDM mice. Moreover, glycemic variability impaired cardiac function, aggravated cardiac injury and induced NLRP3/caspase-1-mediated inflammatory response and pyroptosis. And knockdown of SGLT1 significantly attenuated the cardiac damages that induced by glycemic variability. SIGNIFICANCE: The results indicated that glycemic variability could cause cardiac damage and induce inflammatory response and pyroptosis of cardiomyocytes in diabetic mice, which could be partially blocked by SGLT1 silence.