leptin and Diabetic-Cardiomyopathies

Sodium-glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of serious heart failure events in patients with type 2 diabetes, but little is known about mechanisms that might mediate this benefit. The most common heart failure phenotype in type 2 diabetes is obesity-related heart failure with a preserved ejection fraction (HFpEF). It has been hypothesized that the synthesis of leptin in this disorder leads to sodium retention and plasma volume expansion as well as to cardiac and renal inflammation and fibrosis. Interestingly, leptin-mediated neurohormonal activation appears to enhance the expression of SGLT2 in the renal tubules, and SGLT2 inhibitors exert natriuretic actions at multiple renal tubular sites in a manner that can oppose the sodium retention produced by leptin. In addition, SGLT2 inhibitors reduce the accumulation and inflammation of perivisceral adipose tissue, thus minimizing the secretion of leptin and its paracrine actions on the heart and kidneys to promote fibrosis. Such fibrosis probably contributes to the impairment of cardiac distensibility and glomerular function that characterizes obesity-related HFpEF. Ongoing clinical trials with SGLT2 inhibitors in heart failure are positioned to confirm or refute the hypothesis that these drugs may favourably influence the course of obesity-related HFpEF by their ability to attenuate the secretion and actions of leptin.

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diabetic Nephropathies; Heart; Heart Failure; Humans; Hypoglycemic Agents; Intra-Abdominal Fat; Kidney Tubules; Leptin; Models, Biological; Myocardium; Obesity; Renal Insufficiency; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume

Topics: Animals; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Evidence-Based Medicine; Heart; Heart Failure; Humans; Hypoglycemic Agents; Leptin; Myocardium; Obesity; Sodium-Glucose Transporter 2; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume

Diabetic cardiomyopathy (DCM) is an established complication of diabetes mellitus. In West Virginia, the especially high incidence of diabetes and heart failure validate the necessity of developing new strategies for earlier detection of DCM. Since most DCM patients remain asymptomatic until the later stages of the disease when the fibrotic complications become irreversible, we aimed to explore biomarkers that can identify early-stage DCM.. The patients were grouped into 4 categories based on clinical diabetic and cardiac parameters: Control, Diabetes (DM), Diastolic dysfunction (DD), and Diabetes with diastolic dysfunction (DM+DD), the last group being the preclinical DCM group.. Echocardiography images indicated severe diastolic dysfunction in patients with DD+DM and DD compared to DM or control patients. In the DM and DM+DD groups, TNFα, isoprostane, and leptin were elevated compared to control (p<0.05), as were clinical markers HDL, glucose and hemoglobin A1C. Fibrotic markers IGFBP7 and TGF-β followed the same trend. The Control group showed higher beneficial levels of adiponectin and bilirubin, which were reduced in the DM and DM+DD groups (p<0.05).. The results from our study support the clinical application of biomarkers in diagnosing early stage DCM, which will enable attenuation of disease progression prior to the onset of irreversible complications.

Topics: Adiponectin; Bilirubin; Biomarkers; Case-Control Studies; Diabetic Cardiomyopathies; Electrocardiography; Humans; Insulin-Like Growth Factor Binding Proteins; Interleukin-6; Isoprostanes; Leptin; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; West Virginia

Diabetic cardiomyopathy (DCM) is one of the most severe complications of diabetes without a clear pathogenesis. Th is study investigated the adiponectin (APN) and leptin levels in type II DCM, as well as their correlation with advanced glycation end-products (AGEs). From 2011-2013, 78 type II diabetes mellitus (T2DM) cases (40-65 years old) in the Taian region were randomly selected. Based on the results of colour Doppler ultrasonography and coronary angiography, the cases were divided into a simple T2DM group (40 cases) and a DCM group (38 cases). Forty healthy subjects were used as normal control (NC). An enzyme-linked immunosorbent assay was performed to determine the levels of fa tty inflammatory factors such as APN, leptin and AGEs, and a correlation analysis was conducted. In the T2DM group, the APN levels were decreased but the leptin and AGE levels were significantly increased compared to the NC group. In the DCM group, the APN levels were decreased but the leptin and AGE levels were significantly increased (P<0.01) compared to the T2DM group. Th e AGE levels were positively correlated with disease progression and with fasting plasma glucose levels, glycated haemoglobin, insulin resistance and leptin, but were negatively correlated with APN levels. Additionally, the APN and leptin levels were independently related to the AGE levels. Fatty inflammatory factors play a significant role in the progression of both simple T2DM and DCM. Th e results of this study revealed the pathogenesis of DCM and indicated the potential significance of AGEs in DCM prevention and treatment.

Topics: Adiponectin; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Disease Progression; Female; Glycated Hemoglobin; Glycation End Products, Advanced; Humans; Inflammation Mediators; Insulin Resistance; Leptin; Male; Middle Aged

Diabetics die from cardiovascular disease at a much greater rate than nondiabetics. Cardiac autonomic imbalance predicts increased cardiovascular risk and mortality. We studied the relationship between cardiac autonomic imbalance and adipose tissue-derived inflammation in newly diagnosed and established type 2 diabetes.. Non-diabetics, newly diagnosed diabetics, and established diabetics were included. Anthropomorphic and biochemical measurements were obtained, and insulin resistance was approximated. Cardiac autonomic function was assessed using conventional measures and with power spectral analysis of heart rate.. Heart rate variability was reduced in all diabetics. Interleukin-6 was higher in diabetics, as was the high molecular weight adiponectin-to-leptin ratio. Interleukin-6 correlated negatively with measures of autonomic balance. Ratios of adiponectin to leptin correlated positively with measures of autonomic balance. Cardiac autonomic imbalance and inflammation occur early in diabetes and are interrelated.. Cardiac autonomic imbalance correlates with the adipose tissue-derived inflammation seen early in type 2 diabetes.

Topics: Adiponectin; Adipose Tissue; Autonomic Nervous System Diseases; Biomarkers; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Heart; Heart Rate; Humans; Inflammation; Insulin Resistance; Interleukin-6; Leptin