Mechanisms and therapeutic implications of diabetic heart disease

Fang, Zhi You. (2004). Mechanisms and therapeutic implications of diabetic heart disease PhD Thesis, School of Medicine, The University of Queensland.

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Author Fang, Zhi You.
Thesis Title Mechanisms and therapeutic implications of diabetic heart disease
School, Centre or Institute School of Medicine
Institution The University of Queensland
Publication date 2004
Thesis type PhD Thesis
Supervisor Thomas H. Marwick
Total pages 311
Language eng
Subjects 11 Medical and Health Sciences
Formatted abstract

Diabetes is associated with increased risk for cardiovascular disease, particularly congestive heart failure, contributing to higher morbidity and mortality in these patients. The degree to which diabetes itself - rather than associated comorbid diseases - is associated with this is unclear. Certainly, some evidence points towards diabetes as being independently associated with abnormal left ventricular (LV) systolic and diastolic function and changes in myocardial structure. However, the exact causes of diabetic cardiomyopathy are still incompletely understood and many patients with early stage diabetic heart disease remain undiagnosed and untreated due to the asymptomatic nature of the disease. It is not known how frequently subclinical LV abnormalities are present in diabetic patients before they clinically manifest heart failure and what treatments (if any) might be effective to reverse or treat the problem at an early stage. 

This thesis initially reviews the evidence for a diabetic cardiomyopathy. This is followed by discussion of possible mechanisms and potential treatments for the disease. The third chapter describes the methodologies used in this thesis. Recent new noninvasive tissue Doppler techniques have made it possible to identify subtle changes in diabetic heart disease, and the advantages and disadvantages of these - as well as conventional parameters for evaluation of cardiac function and structure - are explored. 

Chapter 5 applies tissue Doppler imaging (TDI) for detection of early diabetic heart disease. In this study, 186 patients with normal ejection fraction and no evidence of coronary artery disease (CAD) were divided into four groups and diabetic patients, with or without LV hypertrophy (LVH), were compared with controls or LVH patients without diabetes. The results show diabetic patients without overt heart disease demonstrate evidence of longitudinal systolic dysfunction and increased myocardial reflectivity. Although these changes are similar to those caused by LVH, they are independent and incremental to the effects of LVH. 

Chapter 6 assesses the relationship between longitudinal and radial contractility in subclinical diabetic heart disease. In this study, radial and longitudinal function in 53 diabetic patients with no LVH, normal ejection fraction and no ischaemia were compared with those in age-matched controls. The results show radial contractility appears to compensate for reduced longitudinal contractility in subclinical LV dysfunction occurring in the absence of ischaemia or LVH. 

Chapter 7 examines the role of small vessel disease in the development of diabetic cardiomyopathy. In this study, 41 diabetic patients with normal resting LV function and a normal dobutamine echo were compared with 41 control subjects with a low probability of CAD. The results demonstrate the absolute and relative increases in myocardial systolic or diastolic function from rest to peak stress were similar in diabetic and control groups despite a significantly lower baseline in the diabetic group. Thus, subtle LV dysfunction is present in diabetic patients without overt cardiac disease. The normal response to stress suggests that ischemia due to small-vessel disease may not be important in early diabetic heart muscle disease. 

Chapter 8 investigates the prevalence of subclinical cardiomyopathy in diabetic patients without known cardiac disease and the role of plasma brain natriuretic peptide (BNP) for screening tool. A group of 101 asymptomatic diabetic patients without known cardiac disease underwent clinical evaluation, measurement of BNP, exercise stress testing and detailed echocardiographic assessment. The results show subclinical systolic and diastolic dysfunction occurs in a significant proportion of patients with type II diabetes, but BNP does not appear to be sufficiently sensitive to identify these abnormalities. 

Chapter 9 assesses the determinants of subclinical diabetic heart disease. Myocardial systolic and diastolic function in a group of 120 diabetic patients without CAD or LVH were correlated with clinical, therapeutic, and echocardiographic and biochemical variables and significant independent associations were sought using a multiple linear regression model. The results indicate subclinical LV dysfunction is associated with poor diabetic control, advancing age and hypertension; ACE inhibitor and insulin therapy appear to be protective.

Chapter 10 determines whether myocardial changes contribute to the reduced exercise capacity that is often observed in apparently well diabetics. In 79 diabetic patients without evidence of CAD, the association of exercise capacity was sought with clinical, biochemical, echocardiographic variables. The results demonstrate age (p = 0.018), body mass index (p = 0.008) and myocardial early diastolic velocity (p = 0.019) were independent predictors of exercise capacity in diabetic patients, suggesting that independent of age, hypertension and obesity, diastolic dysfunction due to diabetes may play an important role in reduced exercise capacity. 

Finally Chapter 11 investigates whether exercise training can attenuate LV dysfunction seen in type 2 diabetic patients without CAD. A total of 46 diabetic patients were randomly assigned to an intervention group with a minimum of 150 min per week of moderate-intensity aerobic exercise and resistance training or a control group for 8 weeks. After intervention, myocardial diastolic function in the training group was significantly increased compared with that in the control group but no significant changes were found in myocardial systolic function.

Keyword Diabetic angiopathies
Congestive heart failure
Cardiovascular system -- Diseases -- Etiology
Diabetes -- Complications

Document type: Thesis
Collection: UQ Theses (RHD) - UQ staff and students only
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Created: Fri, 27 Apr 2012, 10:47:47 EST by Erica Wei on behalf of Scholarly Communication and Digitisation Service