The relationship of cardiac diastolic dysfunction to concurrent hormonal and metabolic status in type I diabetes mellitus.
ABSTRACT The presence of diabetic cardiomyopathy and its relationship to concurrent hormonal and metabolic status have not been defined in patients with uncomplicated type I diabetes mellitus. Accordingly, radionuclide left ventricular angiograms and simultaneous metabolic profiles were obtained in 8 type I diabetic patients who had no major diabetic complications and in 11 normal subjects. Occult coronary artery disease was excluded by electrocardiogram exercise testing. Hemodynamics and systolic function did not differ between the groups. However, the peak filling rate (PFR; end-diastolic volumes per s) was less in the diabetic patients at rest [mean, 4.1 +/- 0.2 (+/- SE) vs. 4.8 +/- 0.2; P less than 0.05] and during aerobic (6.8 +/- 0.2 vs. 8.30 +/- 0.3; P less than 0.01) and anaerobic exercise (8.8 +/- 0.3 vs. 9.8 +/- 0.4; P less than 0.05). The time to PFR was prolonged in the diabetic patients at rest (174 +/- 10 vs. 133 +/- 7 ms; P less than 0.01) and during anaerobic exercise (126 +/- 5 vs. 103 +/- 6 ms; P less than 0.01). Plasma glucose and insulin levels were elevated in the diabetic patients at rest and during exercise. Otherwise, the metabolic and hormonal levels did not differ between the groups. In the diabetic patients, no single metabolic or hormonal parameter correlated with PFR or time to PFR. Impairment of diastolic filling also did not correlate with level of glycosylated hemoglobin or duration of diabetes. The alteration in diastolic filling present in type I diabetic patients who have no other diabetic complications may represent the earliest functional effect of diabetic cardiomyopathy.
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ABSTRACT: An abnormal left ventricular (LV) diastolic function is an early sign of diabetic cardiomyopathy, which is characterized by an impaired diastolic and/or systolic function of the left ventricle in the absence of ischemic, valvular, or hypertensive heart disease, and serves as a marker of cardiovascular risk. However, it is unclear whether LV diastolic abnormalities can be detected in patients with impaired glucose tolerance (IGT) or mild diabetes without LV hypertrophy (LVH). We examined echocardiographic data from 92 consecutive Japanese patients aged 45-79 years with or without IGT or mild diabetes in the absence of LVH. Impaired glucose tolerance or mild diabetes was defined as the presence of one or more of the following criteria: fasting plasma glucose >110 mg/dl, hemoglobin A1c >5.6%, homeostasis model assessment ratio >1.73, or the taking of oral antihyperglycemic drugs. Left ventricular hypertrophy was defined as an LV mass index (LVMI) >116 g/m(2) in men and >104 g/m(2) in women. Patients with ischemic, valvular, or hypertensive heart disease were excluded. The age, blood pressure, heart rate, and LVMI were similar between patients with (IGT/DM group, n = 43) and without IGT or mild diabetes (non-IGT/DM group, n = 49), whereas the body mass index and waist circumference (WC) were greater in the IGT/DM compared to the non-IGT/DM group (P < 0.05 and P < 0.001, respectively). The transmitral E/A ratio was lower and the deceleration time longer in the IGT/DM than in the non-IGT/DM group (both P < 0.05). Stepwise regression analysis revealed that age and WC were independent determinants of the E/A ratio. In conclusion, diastolic abnormalities without LVH can be detected in Japanese patients with IGT or mild diabetes. The E/A ratio decreases in association with abdominal fat accumulation.Heart and Vessels 01/2010; 25(1):45-50. · 2.13 Impact Factor
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ABSTRACT: The spectrum of diabetic heart disease involves a progression from normal heart to preclinical left ventricular diastolic and systolic dysfunction followed by overt echocardiographic evidence of left ventricular (LV) dysfunction and finally symptomatic heart failure. To compare the value of tissue Doppler imaging (TDI) over the conventional echocardiography in the assessment of early myocardial dysfunction in type 1 diabetics in correlation with serum N-terminal pro-brain natriuretic peptide (NT-pro-BNP), state of metabolic control, and diabetes duration. Sixty subjects were included; 40 type 1 diabetics (aged 12-18 years). Twenty matched subjects served as controls. They were subjected to clinical examination with assessment of cardiovascular reflexes for autonomic neuropathy. Laboratory investigations included mean random blood sugar (MRBS), hemoglobin A1c (HbA1c), urinary microalbumin, and serum determination of NT-pro-BNP. Echocardiography for chamber dimensions, systolic and diastolic function, Tie index, and longitudinal myocardial global biventricular function by pulsed TDI of 6 LV walls and right ventricle (RV) free wall. All diabetics and controls had normal LV dimensions, LV mass index and systolic functions except for higher left ventricular posterior wall (LVPW) in diabetics (P < 0.05). LV and RV diastolic dysfunction diagnosed in 25% of diabetics by conventional Doppler with higher peak A (P < 0.05, P < 0.05) and lower E/A (P < 0.05, P < 0.05) compared to controls. Diabetics had larger Tie index (P < 0.05). TDI showed delayed myocardial relaxation in 52.5% of diabetics with lower LV and RV peak Em (P < 0.05, P < 0.01) and Em/Am (P < 0.01, P < 0.001) compared to controls. NT-pro-BNP was elevated in diabetics (P < 0.01) with best cut-off value = 62.5 Fmol/mL, sensitivity (82%), and specificity (95%) for detection of isolated diastolic dysfunction in diabetics. It was correlated negatively with LV Em (P < 0.05), Em/Am (P < 0.01) and positively with Am (P < 0.01), impaired diastolic velocities were associated with higher HbA1c. Asymptomatic diabetics had evidence of subtle right and LV dysfunction with delayed myocardial relaxation which was related to metabolic control. Tissue Doppler (TD) has an additional value in evaluating ventricular filling. NT-pro-BNP is considered a sensitive, specific, and predictive marker for diastolic dysfunction.Pediatric Diabetes 09/2009; 10(8):513-21. · 2.08 Impact Factor
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ABSTRACT: Approximately 25% of children and adolescents with type 1 diabetes will develop diastolic dysfunction. This defect, which is characterized by an increase in time to cardiac relaxation, results in part from a reduction in the activity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2a), the ATP-driven pump that translocates Ca(2+) from the cytoplasm to the lumen of the sarcoplasmic reticulum. To date, mechanisms responsible for SERCA2a activity loss remain incompletely characterized. The streptozotocin (STZ)-induced murine model of type 1 diabetes, in combination with echocardiography, high-speed video detection, confocal microscopy, ATPase and Ca(2+) uptake assays, Western blots, mass spectrometry, and site-directed mutagenesis, were used to assess whether modification by reactive carbonyl species (RCS) contributes to SERCA2a activity loss. After 6-7 weeks of diabetes, cardiac and myocyte relaxation times were prolonged. Total ventricular SERCA2a protein remained unchanged, but its ability to hydrolyze ATP and transport Ca(2+) was significantly reduced. Western blots and mass spectroscopic analyses revealed carbonyl adducts on select basic residues of SERCA2a. Mutating affected residues to mimic physio-chemical changes induced on them by RCS reduced SERCA2a activity. Preincubating with the RCS, methylglyoxal (MGO) likewise reduced SERCA2a activity. Mutating an impacted residue to chemically inert glutamine did not alter SERCA2a activity, but it blunted MGO's effect. Treating STZ-induced diabetic animals with the RCS scavenger, pyridoxamine, blunted SERCA2a activity loss and minimized diastolic dysfunction. These data identify carbonylation as a novel mechanism that contributes to SERCA2a activity loss and diastolic dysfunction during type 1 diabetes.Diabetes 02/2011; 60(3):947-59. · 7.90 Impact Factor