Objectives The purpose of this study was to compare myocardial triglyceride content and function between patients with uncomplicated type 2 diabetes mellitus (T2DM) and healthy subjects within the ...same range of age and body mass index (BMI), and to study the associations between myocardial triglyceride content and function. Background T2DM is a major risk factor for cardiovascular disease. Increasing evidence is emerging that lipid oversupply to cardiomyocytes plays a role in the development of diabetic cardiomyopathy, by causing lipotoxic injury and myocardial steatosis. Methods Myocardial triglyceride content and myocardial function were measured in 38 T2DM patients and 28 healthy volunteers in the same range of age and BMI by proton magnetic resonance (MR) spectroscopy and MR imaging, respectively. Myocardial triglyceride content was calculated as a percentage relative to the signal of myocardial water. Results Myocardial triglyceride content was significantly higher in T2DM patients compared with healthy volunteers (0.96 ± 0.07% vs. 0.65 ± 0.05%, p < 0.05). Systolic function did not significantly differ between both groups. Indexes of diastolic function, including the ratio of maximal left ventricular early peak filling rate and the maximal left ventricular atrial peak filling rate (E/A) and E peak deceleration, were significantly impaired in T2DM compared with those in healthy subjects (1.08 ± 0.04 ml/s2 × 10−3 vs. 1.24 ± 0.06 ml/s2 × 10−3 and 3.6 ± 0.2 ml/s2 × 10−3 vs. 4.4 ± 0.3 ml/s2 × 10−3 , respectively, p < 0.05). Multivariable analysis indicated that myocardial triglyceride content was associated with E/A and E peak deceleration, independently of diabetic state, age, BMI, heart rate, visceral fat, and diastolic blood pressure. Conclusions Myocardial triglyceride content is increased in uncomplicated T2DM and is associated with impaired left ventricular diastolic function, independently of age, BMI, heart rate, visceral fat, and diastolic blood pressure.
Regional left ventricular (LV) myocardial functional changes in early diabetic cardiomyopathy have not been well documented. LV multidirectional strain and strain rate analyses by 2-dimensional ...speckle tracking were used to detect subtle myocardial dysfunction in 47 asymptomatic, male patients (age 57 ± 6 years) with type 2 diabetes mellitus. The results were compared to those from 53 male controls matched by age, body mass index, and body surface area. No differences were found in the LV end-diastolic volume index (40.7 ± 8.9 vs 44.1 ± 7.8 ml/m2 , p = NS), end-systolic volume index (16.0 ± 4.8 vs 17.8 ± 4.3 ml/m2 , p = NS), ejection fraction (61.0 ± 5.5% vs 59.8 ± 5.3%, p = NS). The transmitral E/A (0.95 ± 0.21 vs 1.12 ± 0.32, p = 0.007) and pulmonary S/D (1.45 ± 0.28 vs 1.25 ± 0.27, p = 0.001) ratios were more impaired in the patients with diabetes mellitus. Importantly, the diabetic patients had impaired longitudinal, but preserved circumferential and radial systolic and diastolic, function. Diabetes mellitus was an independent predictor for longitudinal strain, systolic strain rate and early diastolic strain rate on multiple linear regression analysis (all p <0.001). In conclusion, the LV longitudinal systolic and diastolic function were impaired, but the circumferential and radial functions were preserved in patients with uncomplicated type 2 diabetes mellitus.
Prolonged Caloric Restriction in Obese Patients With Type 2 Diabetes Mellitus Decreases Myocardial Triglyceride Content and Improves Myocardial Function Sebastiaan Hammer, Marieke Snel, Hildo J. ...Lamb, Ingrid M. Jazet, Rutger W. van der Meer, Hanno Pijl, Edo A. Meinders, Johannes A. Romijn, Albert de Roos, Johannes W. A. Smit In type 2 diabetes mellitus (T2DM), myocardial triglyceride (TG) stores are increased. We studied the effects of prolonged caloric restriction on myocardial TG content, myocardial function, and glucoregulation in obese patients with T2DM. Caloric restriction decreased body weight associated with improved glucoregulation, a decrease in myocardial TG content, and improvements in diastolic function. We conclude that myocardial TG stores in obese patients with T2DM are flexible and amendable to therapeutic intervention by caloric restriction. Therefore, the data emphasize the potential relevance of measuring myocardial TG content as a surrogate marker to assess the effects of metabolic interventions on the heart.
Objectives The purpose of this study was to investigate the relationship between hepatic triglyceride content and both myocardial function and metabolism in type 2 diabetes mellitus (T2DM). ...Background Heart disease is the leading cause of mortality in T2DM. Central obesity and hepatic steatosis, both hallmark abnormalities in T2DM, have been related to increased risk of heart disease. Methods Sixty-one T2DM patients underwent myocardial perfusion and substrate metabolism measurements by positron emission tomography, using 15 Owater, 11 Cpalmitate, and 18 F-2-fluoro-2-deoxy- d -glucose. In addition, whole-body insulin sensitivity (M/I) was determined. Myocardial left ventricular function and high-energy phosphate metabolism were measured using magnetic resonance imaging and 31 P-magnetic resonance spectroscopy, respectively. Hepatic triglyceride content was measured by proton magnetic resonance spectroscopy. Patients were divided according to hepatic triglyceride content (T2DM-low ≤5.56% vs. T2DM-high >5.56%). Results In addition to decreased M/I (p = 0.002), T2DM-high patients had reduced myocardial perfusion (p = 0.001), glucose uptake (p = 0.005), and phosphocreatine/adenosine triphosphate (PCr/ATP) ratio (p = 0.003), compared with T2DM-low patients, whereas cardiac fatty acid metabolism and left ventricular function were not different. Hepatic triglyceride content correlated inversely with M/I (Pearson's r = −0.620, p < 0.001), myocardial glucose uptake (r = −0.413, p = 0.001), and PCr/ATP (r = −0.442, p = 0.027). Insulin sensitivity correlated positively with myocardial glucose uptake (r = 0.528, p < 0.001) and borderline with myocardial PCr/ATP (r = 0.367, p = 0.072), whereas a positive association was found between cardiac glucose uptake and PCr/ATP (r = 0.481, p = 0.015). Conclusions High liver triglyceride content in T2DM was associated with decreased myocardial perfusion, glucose uptake, and high-energy phosphate metabolism in conjunction with impaired M/I. The long-term clinical implications of hepatic steatosis with respect to cardiac metabolism and function in the course of T2DM require further study.
Identification of asymptomatic patients with diabetes mellitus (DM) at increased risk for coronary artery disease (CAD) remains a challenge. Carotid intima-media thickness (CIMT) has been proposed as ...a surrogate marker for CAD but only limited data are available. The purpose of the study was to evaluate the potential of CIMT for prediction of CAD in asymptomatic patients with DM. Prospectively, CIMT of the left and right common carotid arteries was assessed by B-mode ultrasound in 150 asymptomatic diabetic patients (50 ± 13 years old, 83 men). In addition, noninvasive multislice computed tomographic coronary angiography was performed to relate CIMT to the presence and severity of CAD. For this purpose, patients were classified as having (1) no atherosclerosis, (2) nonobstructive atherosclerosis, or (3) obstructive stenosis with ≥50% luminal diameter narrowing. Mean CIMT increased significantly from 0.58 ± 0.08 mm in patients with normal coronary arteries (n = 59, 39%) to 0.67 ± 0.12 mm in patients with nonobstructive atherosclerosis (n = 54, 36%). Highest mean CIMT (0.75 ± 0.12 mm) was observed in patients with obstructive stenosis (n = 36, 25%, p <0.01). Receiver operating characteristics curve analysis yielded a sensitivity and specificity of 85% and 72%, respectively, with a CIMT cut-off value of 0.67 mm, for predicting obstructive coronary atherosclerosis. Multivariate analysis of baseline risk factors showed CIMT to be an independent predictor of any and obstructive atherosclerosis (p <0.01). In conclusion, a significant relation was shown between CIMT and the presence and severity of CAD in asymptomatic patients with DM. Assessment of CIMT may be useful to identify diabetic patients at higher risk for CAD.
Objectives This study was designed to evaluate myocardial substrate and high-energy phosphate (HEP) metabolism in asymptomatic men with well-controlled, uncomplicated type 2 diabetes with verified ...absence of cardiac ischemia, and age-matched control subjects, and to assess the association with myocardial function. Background Metabolic abnormalities, particularly an excessive exposure of the heart to circulating nonesterified fatty acids and myocardial insulin resistance are considered important contributors to diabetic cardiomyopathy in animal models of diabetes. The existence of myocardial metabolic derangements in uncomplicated human type 2 diabetes and their possible contribution to myocardial dysfunction still remain undetermined. Methods In 78 insulin-naive type 2 diabetes men (age 56.5 ± 5.6 years, body mass index 28.7 ± 3.5 kg/m2 , glycosylated hemoglobin A1c 7.1 ± 1.0%; expressed as mean ± SD) without cardiac ischemia and 24 normoglycemic control subjects (age 54.5 ± 7.1 years, body mass index 27.0 ± 2.5 kg/m2 , glycosylated hemoglobin A1c 5.3 ± 0.2%), we assessed myocardial left ventricular (LV) function by magnetic resonance imaging, and myocardial perfusion and substrate metabolism by positron emission tomography using H215 O, carbon11 C-palmitate, and 18-fluorodeoxyglucose 2-fluoro-2-deoxy-D-glucose. Cardiac HEP metabolism was assessed by phosphorous P 31 magnetic resonance spectroscopy. Results In patients, compared with control subjects, LV diastolic function (E/A ratio: 1.04 ± 0.25 vs. 1.26 ± 0.36, p = 0.003) and myocardial glucose uptake (260 ± 128 nmol/ml/min vs. 348 ± 154 nmol/ml/min, p = 0.015) were decreased, whereas myocardial nonesterified fatty acid uptake (88 ± 31 nmol/ml/min vs. 68 ± 18 nmol/ml/min, p = 0.021) and oxidation (85 ± 30 nmol/ml/min vs. 63 ± 19 nmol/ml/min, p = 0.007) were increased. There were no differences in myocardial HEP metabolism or perfusion. No association was found between LV diastolic function and cardiac substrate or HEP metabolism. Conclusions Patients versus control subjects showed impaired LV diastolic function and altered myocardial substrate metabolism, but unchanged HEP metabolism. We found no direct relation between cardiac diastolic function and parameters of myocardial metabolism.
Objectives Dilutional coagulopathy as a consequence of cardiopulmonary bypass (CPB) system priming may also be affected by the composition of the priming solution. The direct effects of distinct ...priming solutions on fibrinogen, one of the foremost limiting factors during dilutional coagulopathy, have been minimally evaluated. Therefore, the authors investigated whether hemodilution with different priming solutions distinctly affects the fibrinogen-mediated step in whole blood clot formation. Design Prospective observational laboratory study. Setting University hospital laboratory. Participants Eight male healthy volunteers. Interventions Blood samples diluted with gelatin-, albumin-, or hydroxyethyl starch (HES)-based priming solutions were ex-vivo evaluated for clot formation by rotational thromboelastometry. Measurements and Main Results The intrinsic pathway (INTEM) coagulation time increased from 186 ± 19 seconds to 205 ± 16, 220 ± 17, and 223 ± 18 seconds after dilution with gelatin-, albumin-, or HES-containing prime solutions (all p < 0.05 v baseline). The extrinsic pathway (EXTEM) coagulation time was only minimally affected by hemodilution. Moreover, all 3 priming solutions significantly reduced the INTEM and EXTEM maximum clot firmness. The HES-containing priming solution induced the largest decrease in the maximum clot firmness attributed to fibrinogen, from 13 ± 1 mm (baseline) to 6 ± 1 mm ( p < 0.01 v baseline). Conclusions All studied priming solutions prolonged coagulation time and decreased clot formation, but the fibrinogen-limiting effect was the most profound for the HES-containing priming solution. These results suggest that the composition of priming solutions may distinctly affect blood clot formation, in particular with respect to the fibrinogen component in hemostasis.
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