Diabetic Cardiomyopathy: Insights into Pathogenesis, Diagnostic Challenges, and Therapeutic Options

Aneja, Ashish; Tang, W.H. Wilson; Bansilal, Sameer; García, Mario J.; Farkouh, Michael E.

doi:10.1016/j.amjmed.2008.03.046

Cited by 423 publications

(385 citation statements)

References 72 publications

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“…Streptozotocin-induced diabetic rats develop cardiomyopathy, with initial impairment of diastolic function followed by left ventricular contractile dysfunction, symptoms that are very similar to the events in type 1 diabetic patients [4].…”

Section: Introductionmentioning

confidence: 89%

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Regression of diabetic complications by islet transplantation in the rat

et al. 2009

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Aims/hypothesis Type 1 diabetes is a chronic disease leading to complications such as peripheral neuropathies, nephropathy and cardiovascular disease. Pancreatic islet transplantation is being extensively investigated for blood glucose control in animals and in human type 1 diabetic patients, but the question of whether it can reverse long-term diabetic complications has not been fully explored. We investigated the effects of islet transplantation on diabetic complications in a rat model of streptozotocin-induced diabetes.Methods Three groups of rats were used: healthy controls, diabetic and diabetic rats transplanted with microencapsulated islets at 2 months after diabetes induction, when neuropathy was detectable by a decrease in tail nerve conduction velocity (NCV) and impaired nociceptive thresholds. Blood glucose levels and body weight were measured weekly. The variables considered were: thermal (hot plate test) and mechanical sensitivity (Randal-Selitto paw withdrawal test), NCV and Na+, K+-ATPase activity in the sciatic nerve. At the end of the experiments hearts were removed for morphometric determination and myocyte number, and kidneys removed for histological examination. Results Islet transplantation in diabetic rats induced normoglycaemia in a few days, accompanied by a rapid rise in body weight and amelioration of impaired nociceptive thresholds, as well as normalisation of NCV and Na + , K + -ATPase, which were both about 25% below normal in diabetic rats. Myocyte loss was reduced (−34%) by islet transplantation and the observed mild kidney damage of diabetic rats was prevented. Conclusions/interpretation Besides controlling glycaemia, transplantation of microencapsulated pancreatic islets induced almost complete regression of neuropathy and prevented cardiovascular alterations.

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Section: Introductionmentioning

confidence: 89%

“…It causes multiple organ damage (peripheral nerves, heart, kidney, eyes), leading to an increasing prevalence and severity of several complications [2], among the most frequent of which are peripheral neuropathies [3] and cardiovascular diseases [4].…”

Section: Introductionmentioning

confidence: 99%

Regression of diabetic complications by islet transplantation in the rat

et al. 2009

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“…Coronary artery disease is a major factor, but heart failure in the absence of other contributing factors is also prevalent 1, 2. This condition, termed diabetic cardiomyopathy, is particularly problematic because it can exacerbate comorbidities and increase the occurrence and progression of heart failure 3. It is, thus, critical to identify the mechanisms that promote heart failure in diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

Cardiac Insulin Signaling Regulates Glycolysis Through Phosphofructokinase 2 Content and Activity

Humphries

Matsuzaki

Vadvalkar

et al. 2017

JAHA

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BackgroundThe healthy heart has a dynamic capacity to respond and adapt to changes in nutrient availability. Diabetes mellitus disrupts this metabolic flexibility and promotes cardiomyopathy through mechanisms that are not completely understood. Phosphofructokinase 2 (PFK‐2) is a primary regulator of cardiac glycolysis and substrate selection, yet its regulation under normal and pathological conditions is unknown. This study was undertaken to determine how changes in insulin signaling affect PFK‐2 content, activity, and cardiac metabolism.Methods and ResultsStreptozotocin‐induced diabetes mellitus, high‐fat diet feeding, and fasted mice were used to identify how decreased insulin signaling affects PFK‐2 and cardiac metabolism. Primary adult cardiomyocytes were used to define the mechanisms that regulate PFK‐2 degradation. Both type 1 diabetes mellitus and a high‐fat diet induced a significant decrease in cardiac PFK‐2 protein content without affecting its transcript levels. Overnight fasting also induced a decrease in PFK‐2, suggesting it is rapidly degraded in the absence of insulin signaling. An unbiased metabolomic study demonstrated that decreased PFK‐2 in fasted animals is accompanied by an increase in glycolytic intermediates upstream of phosphofructokianse‐1, whereas those downstream are diminished. Mechanistic studies using cardiomyocytes showed that, in the absence of insulin signaling, PFK‐2 is rapidly degraded via both proteasomal‐ and chaperone‐mediated autophagy.ConclusionsThe loss of PFK‐2 content as a result of reduced insulin signaling impairs the capacity to dynamically regulate glycolysis and elevates the levels of early glycolytic intermediates. Although this may be beneficial in the fasted state to conserve systemic glucose, it represents a pathological impairment in diabetes mellitus.

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“…2 Hyperglycemia activates the local myocardial renin-angiotensin and endothelial systems, and consequently myocyte necrosis and fibrosis increase. 8,20 In previous studies, the degree of diastolic dysfunction 562 Clin. Cardiol.…”

Section: Discussionmentioning

confidence: 98%

“…10 In the early phase of DCMP, the pathologic changes can be reversible with strict metabolic control, but in the continuous process the myocardial changes become irreversible and the risk of developing heart failure increases. 8,11,12 Although it is common, diagnosis of DCMP is very difficult. Of the many methods under evaluation, the most frequently used methods are magnetic resonance imaging and echocardiography.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Value of Poor R‐Wave Progression in Electrocardiograms for Diabetic Cardiomyopathy in Type 2 Diabetic Patients

Bildirici

Ural

Acar

et al. 2010

Clinical Cardiology

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Background: Diabetic cardiomyopathy (DCMP) is a common complication of diabetes and is associated with increased mortality. It has been suggested that a poor R-wave progression in a resting electrocardiogram (ECG) could be a sign of cardiomyopathy. Hypothesis: The aim of this study was primarily to analyze the relationship between poor R-wave progression and DCMP, and the effect of poor R-wave progression on cardiac functions in long-term follow-up. Methods: Seventy type 2 normotensive diabetics (33 female, 37 male; mean age, 52.9 ± 10.4 years) were included in the study. Poor R-wave progression in an ECG was defined as an R wave <3 mm in V1-3 derivations. The patients were randomized in 2 groups, which were those without (group I, n = 34) and those with poor R-wave progression (group II, n = 36). All patients underwent conventional and tissue Doppler echocardiography and were followed in an outpatient clinic setting for 4 years. Results: Demographic variables were similar between the 2 groups. In group II, left ventricular (LV) relaxation abnormality was more prevalent, the Tei index was higher, and in tissue Doppler mitral annulus Em velocities were significantly lower and Am velocities were higher than those with normal R-wave progression. At the end of the 4-year follow-up period, LV ejection fraction was decreased in group II, whereas LV mass index and Tei index were significantly increased. Conclusions: LV diastolic dysfunction is more frequently observed in diabetic patients with poor R-wave progression in ECG, which may be an early sign of LV dysfunction and DCMP in diabetics. IntroductionThe prevalence of diabetes is steadily increasing, and the number of diabetic people is expected to reach 300 million globally by 2025. 1 Cardiovascular disease is a serious of complication of diabetes and is responsible for 80% of the deaths among diabetics. 2 Although coronary artery disease is very common, heart failure is also a major cause of mortality and morbidity in patients with diabetes mellitus. 3 Up to 75% of patients with unexplained idiopathic dilated cardiomyopathy were found to be diabetic. 4 The Framingham Heart Study showed that the frequency of heart failure in diabetic men is twice that of nondiabetics, and it is 5 times higher in diabetic women compared to nondiabetic women. 1,5 Diabetic cardiomyopathy (DCMP) was first reported in 1972 by Rubler. 6 It is characterized by the development of diastolic dysfunction at the early stage followed by systolic dysfunction in the absence of coronary artery disease, hypertension, or significant valvular heart disease. 7 -9 In the Strong Heart Study, diabetes was significantly related to higher left ventricular (LV) mass and wall

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Diabetic Cardiomyopathy: Insights into Pathogenesis, Diagnostic Challenges, and Therapeutic Options

Cited by 423 publications

References 72 publications

Regression of diabetic complications by islet transplantation in the rat

Regression of diabetic complications by islet transplantation in the rat

Cardiac Insulin Signaling Regulates Glycolysis Through Phosphofructokinase 2 Content and Activity

Diagnostic Value of Poor R‐Wave Progression in Electrocardiograms for Diabetic Cardiomyopathy in Type 2 Diabetic Patients

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