Diastolic dysfunction is associatedwith altered myocardial metabolism inasymptomatic normotensive patientswith well-controlled type 2 diabetes mellitus

Diamant, Michaëla; Lamb, Hildo J.; Groeneveld, Ymte; Endert, Edwin L.; Smit, Johannes W. A.; Bax, Jeroen J.; Romijn, Johannes A.; Roos, Albert de; Radder, J.K.

doi:10.1016/s0735-1097(03)00625-9

Cited by 348 publications

(258 citation statements)

References 35 publications

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“…A question that remains not properly addressed, however, is what factor(s) determine(s) patient susceptibility to develop cardiac dysfunction considering that not all diabetic patients will develop cardiac dysfunction and some patients develop dysfunction even with their diabetes being well controlled (27,28).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Variant for Complex I Reveals a Role in Diabetic Cardiac Remodeling

Savitha

Vásquez‐Vivar

Migrino

et al. 2012

Journal of Biological Chemistry

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Background: Mitochondrial dysfunction may influence myocardial remodeling in diabetes.Results: Impaired respiratory complex activity and energy depletion without mitochondrial uncoupling was identified in a new conplastic rat model of diabetes. Conclusion: mtDNA mutations are a risk factor for developing myocardial dysfunction in diabetes. Significance: Identifying mtDNA background is important for recognizing patients at risk for heart diseases.Myocardial remodeling and dysfunction are serious complications of type 2 diabetes mellitus (T2DM). Factors controlling their development are not well established. To specifically address the role of the mitochondrial genome, we developed novel conplastic rat strains, i.e. strains with the same nuclear genome but a different mitochondrial genome. The new animals were named T2DN mtFHH and T2DN mtWistar , where the acronym T2DN denotes their common nuclear genome (type 2 diabetic nephropathy (T2DN) rats) and mtFHH or mtWistar the origin of their mitochondria, Fawn Hooded Hypertensive (FHH) or Wistar rats, respectively. The T2DN mtFHH and T2DN mtWistar showed a similar progression of diabetes as determined by HbA1c, cholesterol, and triglycerides with normal blood pressure, thus enabling investigation of the specific role of the mitochondrial genome in cardiac function without the confounding effects of obesity or hypertension found in other models of diabetes. Echocardiographic analysis of 12-week-old animals showed no abnormalities, but at 12 months of age the T2DN mtFHH showed left ventricular remodeling that was verified by histology. Decreased complex I and complex IV but not complex II activity within the electron transport chain was found only in T2DN mtFHH , which was not explained by differences in protein content. Decreased cardiac ATP levels in T2DN mtFHH were in agreement with a lower ATP synthetic capacity by isolated mitochondria. Together, our data provide experimental evidence that mtDNA sequence variations have an additional role in energetic heart deficiency. The mitochondrial DNA background may explain the increased susceptibility of certain T2DM patients to develop myocardial dysfunction. Type 2 diabetes mellitus (T2DM)2 is a complex and heterogeneous disorder with a prevalence nearing epidemic proportions worldwide. Myocardial dysfunction and heart failure are serious complications developing in many cases independently of coronary artery disease and hypertension. It is considered that molecular alterations at the myocyte level may be a key factor in the development of myocardial dysfunction. The pathogenesis of ventricular dysfunction has been examined previously in genetic animal models of T2DM (1-3). Because these models present with a variety of metabolic disorders, it has been impossible to isolate the influence of intrinsic mitochondrial impairments in disease mechanisms.A new rat model of type 2 diabetes mellitus was developed by crossing diabetic male Goto-Kakizaki (GK) rats with female Fawn Hooded Hypertensive (FHH) rats (4). This new T2DM rat ...

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Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA Variant for Complex I Reveals a Role in Diabetic Cardiac Remodeling

Savitha

Vásquez‐Vivar

Migrino

et al. 2012

Journal of Biological Chemistry

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“…The beneficial effect of insulin treatment on diastolic function is possibly related to maintaining a more normal metabolic milieu and prevention of further myocardial structural change or fibrosis. Altered myocardial energy metabolism has been shown to contribute to LV diastolic functional changes in patients with type 2 diabetes [20]. Both islet transplantation and insulin therapy lead to a complete reversal of the haemodynamic and metabolic alterations in diabetes [21], and insulin improves energy metabolism in diabetic hearts during hypoperfusion and significantly reduced the elevated diastolic tension [22].…”

Section: Discussionmentioning

confidence: 99%

Determinants of subclinical diabetic heart disease

et al. 2005

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Aims/hypothesis: Subclinical left ventricular (LV) dysfunction has been shown by tissue Doppler and strain imaging in diabetic patients in the absence of coronary disease or LV hypertrophy, but the prevalence and aetiology of this finding remain unclear. This study sought to identify the prevalence and the determinants of subclinical diabetic heart disease. Methods: A group of 219 unselected patients with type 2 diabetes without known cardiac disease underwent resting and stress echocardiography. After exclusion of coronary artery disease or LV hypertrophy, the remaining 120 patients (age 57±10 years, 73 male) were studied with tissue Doppler imaging. Peak systolic strain of each wall and systolic (Sm) and diastolic (Em) velocity of each basal segment were measured from the three apical views and averaged for each patient. Significant subclinical LV dysfunction was identified according to Sm and Em normal ranges adjusted by age and sex. Strain and Em were correlated with clinical, therapeutic, echocardiographic and biochemical variables, and significant independent associations were sought using a multiple linear regression model. Results: Significant subclinical LV dysfunction was present in 27% diabetic patients. Myocardial systolic dysfunction by peak strain was independently associated with glycosylated haemoglobin level (p<0.001) and lack of angiotensin-converting enzyme inhibitor treatment (p=0.003). Myocardial diastolic function (Em) was independently predicted by age (p=0.013), hypertension (p=0.001), insulin (p=0.008) and metformin (p=0.01) treatment. Conclusions/interpretation: In patients with diabetes mellitus, subclinical LV dysfunction is common and associated with poor diabetic control, advancing age, hypertension and metformin treatment; ACE inhibitor and insulin therapies appear to be protective.

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“…Firstly, diastolic dysfunction has been shown to be associated with aortic stiffness in patients with diabetes mellitus with no coronary artery disease [47]. Secondly, altered diastolic function in type 2 diabetes is associated with reduced myocardial metabolism, assessed using magnetic resonance imaging [48]. It is possible that the degree of hyperglycaemia may also play a role, as a higher fasting glucose and glycated haemoglobin are associated with abnormal left ventricular relaxation in diabetic patients [46].…”

Section: Discussionmentioning

confidence: 99%

The epidemiology of left ventricular hypertrophy in type 2 diabetes mellitus

2005

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Aims/hypothesis: Patients with type 2 diabetes mellitus are at greater cardiovascular risk than the general population. Although it is widely acknowledged that diabetes is a risk factor for coronary artery disease, the increased prevalence of potentially lethal left ventricular abnormalities in this population is less well appreciated. Methods: We carried out an echocardiographic study of 500 subjects with type 2 diabetes mellitus to assess the prevalence of left ventricular hypertrophy (LVH) and left ventricular systolic dysfunction (LVSD). We also assessed whether abnormalities in diastolic filling parameters were present. Results: Of the 371 patients in whom left ventricular mass could be successfully assessed, 264 had LVH (71%). Left ventricular systolic dysfunction was much less common, being present in 16/385 patients (4.2%). Long axis contraction was abnormal in 29/429 patients (6.8%). Diastolic filling abnormalities were present in 178/435 (41%) of patients who could be classified using the selected criteria. Conclusions: We conclude that left ventricular abnormalities are common in type 2 diabetic patients. As medical therapy is available for both LVH and LVSD and has been demonstrated to reduce cardiovascular death, these left ventricular abnormalities could be ideal targets for screening, followed by selective therapeutic intervention.

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Diastolic dysfunction is associatedwith altered myocardial metabolism inasymptomatic normotensive patientswith well-controlled type 2 diabetes mellitus

Abstract: These results indicate that altered myocardial energy metabolism may contribute to LV diastolic functional changes in patients with recently diagnosed, well-controlled and uncomplicated type 2 diabetes.

Cited by 348 publications

References 35 publications

Mitochondrial DNA Variant for Complex I Reveals a Role in Diabetic Cardiac Remodeling

Mitochondrial DNA Variant for Complex I Reveals a Role in Diabetic Cardiac Remodeling

Determinants of subclinical diabetic heart disease

The epidemiology of left ventricular hypertrophy in type 2 diabetes mellitus

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