Preclinical diabetic cardiomyopathy: relation of left ventricular diastolic dysfunction to cardiac autonomic neuropathy in men with uncomplicated well-controlled type 2 diabetes

Poirier, Paul; Bogaty, Peter; Philippon, F; Garneau, Caroline; Fortin, Claudette; Dumesnil, Jean-G

doi:10.1016/s0026-0495(03)00091-x

Cited by 90 publications

(85 citation statements)

References 44 publications

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“…Abnormal cardiac autonomic function has been associated with poor cardiac output responses to exercise in diabetes (29), probably due to abnormal hemodynamic regulation during exercise. In addition, an indirect link between cardiac autonomic dysfunction and impaired exercise capacity is demonstrated by associations of cardiac autonomic dysfunction with insulin resistance (30) or poor glycemic control (as in the current study) and impaired resting left ventricular diastolic filling (31).…”

Section: Exercise Capacity and Autonomic Cardiac Functionsupporting

confidence: 62%

Determinants of Exercise Capacity in Patients With Type 2 Diabetes

et al. 2005

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OBJECTIVE -Type 2 diabetes is associated with reduced exercise capacity, but the cause of this association is unclear. We sought the associations of impaired exercise capacity in type 2 diabetes. RESEARCH DESIGN AND METHODS -Subclinical left ventricular (LV) dysfunctionwas sought from myocardial strain rate and the basal segmental diastolic velocity (Em) of each wall in 170 patients with type 2 diabetes (aged 56 Ϯ 10 years, 91 men), good quality echocardiographic images, and negative exercise echocardiograms. The same measurements were made in 56 control subjects (aged 53 Ϯ 10 years, 29 men). Exercise capacity was calculated in metabolic equivalents, and heart rate recovery (HRR) was measured as the heart rate difference between peak and 1 min after exercise. In subjects with type 2 diabetes, exercise capacity was correlated with clinical, therapeutic, biochemical, and echocardiographic variables, and significant independent associations were sought using a multiple linear regression model. RESULTS -Exercise capacity, strain rate, Em, and HRR were significantly reduced in type 2 diabetes. Exercise capacity was associated with age (r ϭ Ϫ0.37, P Ͻ 0.001), male sex (r ϭ 0.26, P ϭ 0.001), BMI (r ϭ Ϫ0.19, P ϭ 0.012), HbA 1c (A1C; r ϭ Ϫ0.22, P ϭ 0.009), Em (r ϭ 0.43, P Ͻ 0.001), HRR (r ϭ 0.42, P Ͻ 0.001), diabetes duration (r ϭ Ϫ0.18, P ϭ 0.021), and hypertension history (r ϭ Ϫ0.28, P Ͻ 0.001). Age (P Ͻ 0.001), male sex (P ϭ 0.007), BMI (P ϭ 0.001), Em (P ϭ 0.032), HRR (P ϭ 0.013), and A1C (P ϭ 0.0007) were independent predictors of exercise capacity.CONCLUSIONS -Reduced exercise capacity in patients with type 2 diabetes is associated with diabetes control, subclinical LV dysfunction, and impaired HRR. Diabetes Care 28:1643-1648, 2005C linical and observational studies have shown that exercise capacity is a strong predictor of cardiovascular and overall mortality (1). Patients with type 2 diabetes often complain of fatigue and reduced exercise capacity. Although these symptoms may be related to other disease conditions, such as hypertensive left ventricular (LV) hypertrophy or coronary artery disease, the presence of diabetes may independently contribute to the impaired exercise capacity (2).The causes of reduced exercise capacity in type 2 diabetes are unknown. Overt LV diastolic dysfunction, evidenced by abnormal transmitral flow, has been associated with impaired functional capacity in uncomplicated well-controlled type 2 diabetes (2). However, primary myocardial disease may be present in many patients with type 2 diabetes, without overt systolic or diastolic dysfunction, independent of LV hypertrophy and coronary artery disease (3). Cardiac autonomic dysfunction may play an important role in the development of diabetic heart disease (3). Reduced heart rate recovery (HRR) immediately after exercise is an important indicator of cardiac autonomic dysfunction and contributes to cardiovascular morbidity and mortality in other diseases (4,5). In this study, we sought the extent to which diabetes control, impaired HRR, a...

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Section: Exercise Capacity and Autonomic Cardiac Functionsupporting

confidence: 62%

Determinants of Exercise Capacity in Patients With Type 2 Diabetes

et al. 2005

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“…Another potential limitation was that the average maximal heart rate was lower in youth with type 2 diabetes relative to normoglycemic overweight controls which may explain group-wise differences in the primary outcome measure. Previous studies of cardiorespiratory fitness in youth with type 2 diabetes demonstrated similar reductions in maximal heart rate (35,39) and may be indicative of early central autonomic dysfunction (40). On average, however respiratory exchange ratios exceeded 1.10 in all groups and the rating of perceived exertion was >17/20 in all participants, suggesting that all youth attained volitional exhaustion and peak exercise.…”

Section: Limitationssupporting

confidence: 53%

“…Fasting blood samples were collected before an intravenous bolus of a 25% glucose solution (0.3 g/kg body weight) at time 0, followed by an intravenous bolus of regular human insulin (0.03 U/kg body weight) at 20 min. Blood samples for glucose and insulin were collected at 1,2,3,4,5,6,8,10,14,19,22,25,30,40,50,70, 100, 140, and 180 min. Glucose and insulin kinetics were modeled using the Bergman minimal model using customized software (MINMOD) to quantify insulin sensitivity and β-cell function (15).…”

Section: Insulin Sensitivitymentioning

confidence: 99%

Hepatic Steatosis and Low Cardiorespiratory Fitness in Youth With Type 2 Diabetes

Wittmeier

Wicklow

MacIntosh

et al. 2012

Obesity

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The purpose of this study was to examine the association between cardiorespiratory fitness, ectopic triglyceride accumulation, and insulin sensitivity among youth with and without type 2 diabetes. Subjects included 137 youth ages 13–18 years including 27 with type 2 diabetes, 97 overweight normoglycemic controls, and 13 healthy weight normoglycemic controls. The primary outcome measure was cardiorespiratory fitness defined as peak oxygen uptake indexed to fat free mass. Secondary outcomes included liver and muscle triglyceride content determined by 1H‐magnetic resonance spectroscopy and insulin sensitivity determined by frequently sampled intravenous glucose tolerance test. Despite similar measures of adiposity, peak oxygen uptake was 11% lower (38.9 ± 7.9 vs. 43.9 ± 6.1 ml/kgFFM/min, P = 0.002) and hepatic triglyceride content was nearly threefold higher (14.4 vs. 5.7%, P = 0.001) in youth with type 2 diabetes relative to overweight controls. In all 137 youth, cardiorespiratory fitness was negatively associated with hepatic triglyceride content (r = −0.22, P = 0.02) and positively associated with insulin sensitivity (r = 0.29, P = 0.002) independent of total body and visceral fat mass. Hepatic triglyceride content was also negatively associated with insulin sensitivity (r = −0.35, P < 0.001), independent of adiposity, sex, age, and peak oxygen uptake. This study demonstrated that low cardiorespiratory fitness and elevated hepatic triglyceride content are features of type 2 diabetes in youth. Furthermore, cardiorespiratory fitness and hepatic triglyceride are associated with insulin sensitivity in youth. Taken together, these data suggest that cardiorespiratory fitness and hepatic steatosis are potential clinical biomarkers for type 2 diabetes among youth.

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“…An alternative explanation is that autonomic dysfunction, which appears in diabetic adults [8], occurs in type 2 diabetic adolescents. Autonomic neuropathy has been described early after the diagnosis of type 2 diabetes [4] and reduced maximal heart rate has been reported in type 2 diabetic adults [9].…”

Section: Discussionmentioning

confidence: 99%

Impaired stroke volume and aerobic capacity in female adolescents with type 1 and type 2 diabetes mellitus

et al. 2008

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Aim/hypothesis This study was designed to determine whether type 2 diabetic adolescents have reduced aerobic capacity and to investigate the role of cardiac output and arteriovenous oxygen difference (a−vO 2 ) in their exercise response. Methods Female adolescents (age 12-18 years) with type 2 diabetes mellitus (n=8) and type 1 diabetes mellitus (n=12) and obese (n=10) and non-obese (n=10) non-diabetic controls were recruited for this study. Baseline data included maximal aerobic capacity (cycle ergometer) and body composition. Cardiac output and a−vO 2 were determined at rest and during submaximal exercise. Results Diabetic groups had lower aerobic capacity than nondiabetic groups (p<0.05). Adolescents with type 2 diabetes had lower aerobic capacity than the type 1 diabetic group. Maximal heart rate was lower in the type 2 diabetic group (p <0.05). Exercise stroke volume was 30-40% lower at 100 and 120 beats per min in the diabetic than in the nondiabetic groups (p<0.05). The a−vO 2 value was not different in any condition. Conclusions and interpretation Type 2 diabetic adolescents have reduced aerobic capacity and reduced heart rate response to maximal exercise. Furthermore, type 2 and type 1 diabetic adolescent girls have a blunted exercise stroke volume response compared with non-diabetic controls. Central rather than peripheral mechanisms contribute to the reduced aerobic capacity in diabetic adolescents. Although of short duration, type 2 diabetes in adolescence is already affecting cardiovascular function in adolescents.

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Preclinical diabetic cardiomyopathy: relation of left ventricular diastolic dysfunction to cardiac autonomic neuropathy in men with uncomplicated well-controlled type 2 diabetes

Cited by 90 publications

References 44 publications

Determinants of Exercise Capacity in Patients With Type 2 Diabetes

Determinants of Exercise Capacity in Patients With Type 2 Diabetes

Hepatic Steatosis and Low Cardiorespiratory Fitness in Youth With Type 2 Diabetes

Impaired stroke volume and aerobic capacity in female adolescents with type 1 and type 2 diabetes mellitus

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