Uncomplicated type 1 diabetes and preclinical left ventricular myocardial dysfunction: Insights from echocardiography and exercise cardiac performance evaluation

Palmieri, Vittorio; Capaldo, Brunella; Russo, Cesare; Iaccarino, Michele; Pezzullo, Salvatore; Quintavalle, Gabriele; Minno, G. Di; Riccardi, Gabriele; Celentano, Aldo

doi:10.1016/j.diabres.2007.09.014

Cited by 48 publications

(48 citation statements)

References 41 publications

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“…In addition to hyperglycemia, diabetic patients also commonly suffer from hyperlipidemia, which can lead to increased atherosclerosis and incidence of heart disease [30]. DM is associated with a specific cardiomyopathy, in which left ventricular dysfunctions present as the earliest manifestation of diabetic cardiomyopathy [31]. Moreover, heart dysfunctions observed in diabetic patients are believed to be caused by a progression of diabetic nephropathy [32].…”

Section: Discussionmentioning

confidence: 98%

The anti‐diabetic effect of anthocyanins in streptozotocin‐induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis

Nizamutdinova

Jin

Chung

et al. 2009

Molecular Nutrition Food Res

155

103

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Hyperglycemia, abnormal lipid and antioxidant profiles are the most usual complications in diabetes mellitus. Thus, in this study, we investigated the anti-diabetic and anti-oxidative effects of anthocyanins (ANT) from black soybean seed coats in streptozotocin (STZ)-induced diabetic rats. The administration of ANT markedly decreased glucose levels and improved heart hemodynamic function (left ventricular end diastolic pressure, +/-dp/dt parameters). ANT not only enhanced STZ-mediated insulin level decreases, but also decreased the triglyceride levels induced by STZ injection in serum. Diabetic rats exhibited a lower expression of glucose transporter 4 proteins in the membrane fractions of heart and skeletal muscle tissues, which was enhanced by ANT. In addition, ANT activated insulin receptor phosphorylation, suggesting an increased utilization of glucose by tissues. Moreover, ANT protected pancreatic tissue from STZ-induced apoptosis through regulation of caspase-3, Bax, and Bcl-2 proteins. Furthermore, ANT significantly suppressed malondialdehyde levels and restored superoxide dismutase and catalase activities in diabetic rats. Interestingly, the observed effects of ANT were superior to those of glibenclamide. Taken together, ANT from black soybean seed coat have anti-diabetic effects that are due, in part, to the regulation of glucose transporter 4 and prevention of insulin resistance and pancreatic apoptosis, suggesting a possible use as a drug to regulate diabetes.

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Section: Discussionmentioning

confidence: 98%

The anti‐diabetic effect of anthocyanins in streptozotocin‐induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis

Nizamutdinova

Jin

Chung

et al. 2009

Molecular Nutrition Food Res

155

103

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“…As one of the earliest characteristic of DCM, left ventricle diastolic dysfunction occurred followed by systolic dysfunction [34,35]. Left ventricular dysfunction is a common feature of the diabetic heart.…”

Section: Discussionmentioning

confidence: 99%

Advanced Interfere Treatment of Diabetic Cardiomyopathy Rats by aFGF-Loaded Heparin-Modified Microbubbles and UTMD Technique

Zhang

Shen³

et al. 2016

Cardiovasc Drugs Ther

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This study aims to investigate the preclinical performance and mechanism of a novel strategy of aFGF-loaded heparin-modified microbubbles (aFGF-HMB) combined with ultrasound-targeted microbubble destruction (UTMD) technique for diabetic cardiomyopathy (DCM) prevention. Type 1 diabetic rats were induced by streptozotocin. Twelve weeks after intervention, indexes from transthoracic echocardiography and cardiac catheterization showed that the left ventricular function in the aFGF-HMB/UTMD group was significantly improved compared with diabetes control (DM). From Picrosirius Red staining and TUNEL staining, the aFGF-HMB/UTMD group showed significant difference from the other groups. The cardiac collagen volume fraction (CVF) and myocardial cell apoptosis index (AI) in aFGF-HMB/UTMD group decreased to 7.2 % and 7.11 % respectively, compared with the DM group (CVF = 24.5 % and AI =20.3 % respectively). The results of myocardial microvascular density (MCD) also proved the strongest inhibition of aFGF-HMB/UTMD group on DCM progress. CD31 staining of aFGF-HMB/UTMD group reached 22 n/hrp, much higher than that of DM group (9 n/hrp). These results confirmed that the abnormalities including left ventricular dysfunction, myocardial fibrosis, cardiomyocytes apoptosis and microvascular rarefaction could be suppressed by twice weekly aFGF treatments for 12 consecutive weeks (free aFGF or aFGF-HMB+/-UTMD), with the strongest improvements observed in the aFGF-HMB/UTMD group (P < 0.05 vs free aFGF or aFGF-HMB). Western blot analyses of heart tissue further revealed the highest aFGF, anti-apoptosis protein (Bcl-2), VEGF-C, pAkt, pFoxo-3a levels and strongest reduction in pro-apoptosis proteins (Bax) level in aFGF-HMB/UTMD group. Overall, aFGF-HMB combined with UTMD technique might be developed as an effective strategy to prevent DCM in future clinical therapy.

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“…First found in diabetic patients [79], impaired exercise augmentation correlates with sympathetic denervations already in the very early phase of diabetic dysfunction, sometimes before any manifestation of heart failure by imaging methods at rest can be detected [32,65]. This impaired cardiac performance after exercise without coronary heart disease is referred to as disturbed contractile reserve, which can be attributed to mitochondrial dysfunction and/or altered calcium homeostasis [18,19].…”

Section: Tab 1 Composite View Of Clinical Symptoms Morphology Hemomentioning

confidence: 99%

Diabetic cardiomyopathy—fact or fiction?

Maisch

Alter

Pankuweit

2011

Herz

141

139

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Epidemiologic as well as clinical studies confirm the close link between diabetes mellitus and heart failure. Diabetic cardiomyopathy (DCM) is still a poorly understood "entity", however, with several contributing pathogenetic factors which lead in different stages of diabetes to characteristic clinical phenotypes. Hyperglycemia with a shift from glucose metabolism to increased beta-oxidation and consecutive free fatty acid damage (lipotoxicity) to the myocardium, insulin resistance, renin-angiotensin-aldosterone system (RAAS) activation, altered calcium homeostasis and structural changes from the natural collagen network to a stiffer matrix due to advanced glycation endproduct (AGE) formation, hypertrophy and fibrosis contribute to the respective clinical phenotypes of DCM. We propose the following classification of cardiomyopathy in diabetic patients: a) Diastolic heart failure with normal ejection fraction (HFNEF) in diabetic patients often associated with hypertrophy without relevant hypertension. Relevant coronary artery disease (CAD), valvular disease and uncontrolled hypertension are not present. This is referred to as stage 1 DCM. b) Systolic and diastolic heart failure with dilatation and reduced ejection (HFREF) in diabetic patients excluding relevant CAD, valvular disease and uncontrolled hypertension as stage 2 DCM. c) Systolic and/or diastolic heart failure in diabetic patients with small vessel disease (microvascular disease) and/or microbial infection and/or inflammation and/or hypertension but without CAD as stage 3 DCM. d) If heart failure may also be attributed to infarction or ischemia and remodeling in addition to stage 3 DCM the term should be heart failure in diabetes or stage 4 DCM. These clinical phenotypes of diabetic cardiomyopathy can be separated by biomarkers, non-invasive (echocardiography, cardiac magnetic resonance imaging) and invasive imaging methods (levocardiography, coronary angiography) and further analysed by endomyocardial biopsy for concomitant viral infection. The role of specific diabetic drivers to the clinical phenotypes, to macro- and microangiopathy as well as accompanying risk factors or confounders, e.g. hypertension, autoimmune factors or inflammation with or without viral persistence, need to be identified in each individual patient separately. Thus hyperglycemia, hyperinsulinemia and insulin resistance as well as lipotoxicity by free fatty acids (FFAs) are the factors responsible for diabetic cardiomyopathy. In stage 1 and 2 DCM diabetic cardiomyopathy is clearly a fact. However, precise determination of to what degree the various underlying pathogenetic processes are responsible for the overall heart failure phenotype remains a fiction.

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Uncomplicated type 1 diabetes and preclinical left ventricular myocardial dysfunction: Insights from echocardiography and exercise cardiac performance evaluation

Cited by 48 publications

References 41 publications

The anti‐diabetic effect of anthocyanins in streptozotocin‐induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis

The anti‐diabetic effect of anthocyanins in streptozotocin‐induced diabetic rats through glucose transporter 4 regulation and prevention of insulin resistance and pancreatic apoptosis

Advanced Interfere Treatment of Diabetic Cardiomyopathy Rats by aFGF-Loaded Heparin-Modified Microbubbles and UTMD Technique

Diabetic cardiomyopathy—fact or fiction?

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