Empagliflozin Treatment is Associated With Improvements in Cardiac Energetics and Function and Reductions in Myocardial Cellular Volume in Patients With Type 2 Diabetes

Cardiovascular disease (CVD) is a common cause of morbidity/mortality in patients with type 2 diabetes mellitus (T2DM). Echocardiography can detect changes in cardiac geometry/function before overt CVD symptoms. This study aimed to evaluate left ventricular (LV) geometry and function in normotensive/hypertensive patients with T2DM without overt cardiac symptoms. A cross-sectional study in which fifty normotensives and fifty hypertensive adults with DM without overt cardiac symptoms were enrolled from the cardiology/diabetes clinics of Jos University Teaching Hospital (JUTH) in a simple random manner. Relevant history, physical examination and biochemical investigations were performed. 12-lead electrocardiography and echocardiograph assessment of LV geometry and function were also performed. Data was analyzed using Epi-info 7 statistical software; p value < 0.05 was considered significant. There were 27 females and 29 females in both groups. The prevalence of abnormal LV geometry was 36.0%, 95% CI 33.2-38.8% and 58.0%, 95% CI 55.2-60.8% in the normotensive and hypertensive groups respectively, P=0.028. Similarly, the prevalence of LV dysfunction was 38.0%, 95%CI 35.2-40.8% and 62.0%, 95%CI 59.2-64.8% respectively, P=0.017. The independent predictors of LV dysfunction were found to be duration of diabetes (OR 7.74, 95%CI 4.46-10.46), duration of hypertension ≥5years (OR 4.15, 95%CI 4.01-9.27), smoking (OR 4.34, 95%CI 1.32-6.23), body mass index ≥25 (OR 5.53, 95%CI 1.38-2.09) and glycosylated haemoglobin ≥7 (OR 7.11, 95%CI 2.15-0.81). There is high prevalence of LV dysfunction/abnormal LV geometry in T2DM patients without overt cardiac symptoms; co-morbid hypertension worsens these abnormalities. Early and periodic echocardiography is recommended with appropriate intervention in these patients.

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Expression and function of P2X7 receptor and CD39/Entpd1 in patients with type 2 diabetes and their association with biochemical parameters

Cellular Immunology ◽

10.1016/j.cellimm.2011.03.022 ◽

2011 ◽

Vol 269 (2) ◽

pp. 135-143 ◽

Cited By ~ 27

Author(s):

Mariana H. García-Hernández ◽

Liliana Portales-Cervantes ◽

Nancy Cortez-Espinosa ◽

Juan M. Vargas-Morales ◽

Juan F. Fritche Salazar ◽

...

Keyword(s):

Type 2 Diabetes ◽

Biochemical Parameters ◽

P2x7 Receptor ◽

And Function

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THE EMERGENCE OF FRAILTY MAY LEAD TO A STATE OF BURNT OUT TYPE 2 DIABETES

Journal of Frailty & Aging ◽

10.14283/jfa.2016.98 ◽

2016 ◽

pp. 1-6

Author(s):

A.H. ABDELHAFIZ ◽

L. KOAY ◽

A.J. SINCLAIR

Keyword(s):

Type 2 Diabetes ◽

Β Cells ◽

Risk Of Mortality ◽

Vulnerable Patients ◽

Increased Risk ◽

History Of ◽

The One ◽

And Function ◽

Glucose Dynamics

Ageing is associated with hyperglycaemic tendency due to the change in body composition leading to accumulation of visceral fat and increased insulin resistance on the one hand and reduced insulin secretion due to decreased number and function of the β-cells of the pancreas on the other. However, with the emergence of frailty there may be a tendency towards normoglycaemia or even hypoglycaemia due to malnutrition, weight loss and reduced physiologic reserve. This shift in glucose metabolism induced by frailty may change the natural history of type 2 diabetes from a progressive to a regressive course. Studies which showed increased risk of mortality with low HbA1c included frail patients in the lower HbA1c categories and healthier patients in the higher HbA1c categories suggesting that frailty is a possible confounding factor. Therefore, hypoglycemia may be a prognostic tool to identify vulnerable patients who may be at increased risk of mortality. The metabolic changes of insulin/glucose dynamics associated with frailty need further research.

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Insulin and Insulin Receptors in Adipose Tissue Development

International Journal of Molecular Sciences ◽

10.3390/ijms20030759 ◽

2019 ◽

Vol 20 (3) ◽

pp. 759 ◽

Cited By ~ 20

Author(s):

Angelo Cignarelli ◽

Valentina Genchi ◽

Sebastio Perrini ◽

Annalisa Natalicchio ◽

Luigi Laviola ◽

...

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Insulin Receptor ◽

Intracellular Signaling ◽

Insulin Receptors ◽

Metabolic Effects ◽

Endocrine Activity ◽

Differentiated Cells ◽

And Function

Insulin is a major endocrine hormone also involved in the regulation of energy and lipid metabolism via the activation of an intracellular signaling cascade involving the insulin receptor (INSR), insulin receptor substrate (IRS) proteins, phosphoinositol 3-kinase (PI3K) and protein kinase B (AKT). Specifically, insulin regulates several aspects of the development and function of adipose tissue and stimulates the differentiation program of adipose cells. Insulin can activate its responses in adipose tissue through two INSR splicing variants: INSR-A, which is predominantly expressed in mesenchymal and less-differentiated cells and mainly linked to cell proliferation, and INSR-B, which is more expressed in terminally differentiated cells and coupled to metabolic effects. Recent findings have revealed that different distributions of INSR and an altered INSR-A:INSR-B ratio may contribute to metabolic abnormalities during the onset of insulin resistance and the progression to type 2 diabetes. In this review, we discuss the role of insulin and the INSR in the development and endocrine activity of adipose tissue and the pharmacological implications for the management of obesity and type 2 diabetes.

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DBC1, p300, HDAC3, and Siah1 coordinately regulate ELL stability and function for expression of its target genes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1912375117 ◽

2020 ◽

Vol 117 (12) ◽

pp. 6509-6520 ◽

Cited By ~ 1

Author(s):

Subham Basu ◽

Mahesh Barad ◽

Dipika Yadav ◽

Arijit Nandy ◽

Bidisha Mukherjee ◽

...

Keyword(s):

Type 2 Diabetes ◽

Rna Polymerase Ii ◽

Target Genes ◽

Mononuclear Cells ◽

Elongation Factor ◽

Diabetes Patient ◽

Elongation Complex ◽

Peripheral Blood Mononuclear ◽

And Function

Among all of the Super Elongation Complex (SEC) components, ELL1 (also known as ELL) is the only bona fide elongation factor that directly stimulates transcription elongation by RNA polymerase II. However, the mechanism(s) of functional regulation of ELL1 (referred to as ELL hereafter), through its stabilization, is completely unknown. Here, we report a function of human DBC1 in regulating ELL stability involving HDAC3, p300, and Siah1. Mechanistically, we show that p300-mediated site-specific acetylation increases, whereas HDAC3-mediated deacetylation decreases, ELL stability through polyubiquitylation by the E3 ubiquitin ligase Siah1. DBC1 competes with HDAC3 for the same binding sites on ELL and thus increases its acetylation and stability. Knockdown of DBC1 reduces ELL levels and expression of a significant number of genes, including those involved in glucose metabolism. Consistently, Type 2 diabetes patient-derived peripheral blood mononuclear cells show reduced expression of DBC1 and ELL and associated key target genes required for glucose homeostasis. Thus, we describe a pathway of regulating stability and functions of key elongation factor ELL for expression of diverse sets of genes, including ones that are linked to Type 2 diabetes pathogenesis.

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