Juha Mustonen

Aerobic exercise and the lipid profile in type 1 diabetic men: a randomized controlled trial

PURPOSE Despite the potential importance of favorable changes in the lipid profile produced by aerobic exercise, training-induced lipid profile changes in atherosclerosis-prone type 1 diabetes mellitus (DM) have not heretofore been adequately addressed. METHODS We assessed the effect of a 12- to 16-wk aerobic exercise program on cardiorespiratory fitness and the lipid profile in young men with type 1 DM. Generally active men aged 20-40 yr with type 1 DM (N = 56) were randomized into training (N = 28) and control (untrained, N = 28) groups after baseline measurements. Training consisted of 30-60 min moderate-intensity running 3-5 times a week for 12-16 wk. RESULTS For the 42 men finishing the study, peak oxygen consumption (VO2 peak) increased significantly only in the trained group. Total and low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B decreased and the high-density lipoprotein (HDL)/apo A-I ratio increased in the trained group. HDL and apo A-I increased in both groups. The exercise program brought about improvements in the HDL/LDL and apo A-I/apo B ratios and apo B and triglyceride levels when comparing the relative (%) changes in the trained versus control group. In the trained group, men with HDL/LDL ratios below the group median at baseline showed even more favorable changes in their lipid profile than those with higher initial HDL/LDL ratios. Body mass index, percent body fat and hemoglobin A1c did not change during the training period in either group. CONCLUSIONS Endurance training improved the lipid profile in already physically active type 1 diabetic men, independently of effects on body composition or glycemic control. The most favorable changes were in patients with low baseline HDL/LDL ratios, likely the group with the greatest benefit to be gained by such changes.

Noninvasive Detection of Cardiac Sympathetic Nervous Dysfunction in Diabetic Patients Using [123I]Metaiodobenzylguanidine

The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP- group), and 6 male nondiabetic control subjects. The mean age was comparable in all groups, and the subjects had no evidence of coronary heart disease. Reduced heart-rate variation in a deep-breathing test was used as a criterion for autonomic neuropathy. Immediately after injection, the peak net influx rate of MIBG to myocardium was significantly (P < 0.05) reduced in both diabetic groups. At 6 hr after MIBG injection, the MIBG uptake of the myocardium was significantly (P < 0.05) smaller in the ANP+ group than in the control group. In the ANP- group, the MIBG uptake of the myocardium was between that of the ANP+ group and that of the control group. Our data show that reduced myocardial MIBG accumulation is associated with autonomic dysfunction in diabetic patients, but it can occur to a lesser extent also in diabetic patients without apparent autonomic neuropathy. The measurement of the myocardial MIBG accumulation is a promising new method to detect cardiac sympathetic nervous dysfunction in diabetic patients.

Impairment of diastolic function in middle-aged Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetic patients free of cardiovascular disease

SummaryLeft ventricular systolic and diastolic function was studied using systolic time intervals and echocardiography in 19 male and 17 female patients with Type 1 (insulin-dependent) diabetes, 24 male and 15 female patients with Type 2 (non-insulin-dependent) diabetes and 24 male and 24 female control subjects. The subjects for the present study were selected from a population based study in which 117 Type 1 and 510 Type 2 diabetic patients and 649 non-diabetic subjects were originally examined. After exclusions, none of the subjects had any evidence of coronary heart disease, hypertension or other diseases known to affect left ventricular function. There were no consistent differences in systolic time intervals or echocardiographic variables of systolic function between patients with Type 1 diabetes and non-diabetic control subjects; but patients with Type 2 diabetes showed an increased fractional shortening. Female patients with Type 2 diabetes showed an increased left ventricular mass not explicable by hypertension. Isovolumic relaxation period was longer in male (86±3 ms; mean±SEM) and female patients (84±6 ms) with Type 2 diabetes than in male (76±3 ms; p<0.05) and female (71±3 ms; p<0.05) control subjects. Peak diastolic filling rate was lower in female patients with Type 1 diabetes (12.8±0.8 cm/s, p<0.05) and in male (11.5±0.8 cm/s; p<0.01) and female patients (11.5±0.6 cm/s; p<0.001) with Type 2 diabetes as compared to male (14.4±0.7 cm/s) and female (14.9±0.5 cm/s) control subjects. In male patients with Type 1 diabetes the respective value (12.7±0.6 cm/s) did not differ significantly from that in male control subjects. Altogether 14 diabetic patients (26%) showed an abnormal low peak diastolic filling rate. The impaired diastolic filling among diabetic patients did not show any relationship to the duration and metabolic control of diabetes or the presence of microangiopathy, but a weak correlation was found between the peak diastolic filling rate and the diminution of heart rate variation suggestive of the presence of diabetic autonomic neuropathy.

Left ventricular function and dimensions in newly diagnosed non-insulin-dependent diabetes mellitus

Left ventricular (LV) function and dimensions were assessed with Doppler and M-mode echocardiography in 26 men and 17 women with newly diagnosed non-insulin-dependent diabetes mellitus, and in 13 healthy control men and 13 women. The diabetic men had lower peak filling rate normalized to mitral stroke volume than the control men (mean +/- standard error of the mean, 4.2 +/- 0.1 vs 4.9 +/- 0.3 stroke volume/s, p less than 0.01). The diabetic women had increased LV mass (102 +/- 12 vs 86 +/- 8 g/m2, p less than 0.01) and decreased fractional shortening (34 +/- 1 vs 38 +/- 1%, p less than 0.05) when compared with control women. At 3 and 15 months, 23 diabetic men and 15 women were reexamined. Concomitantly with decreasing blood glucose levels, fractional shortening improved mainly during the first 3 months and was significantly higher in both diabetic men (36 +/- 2 vs 30 +/- 2%, p less than 0.05) and women (38 +/- 1 vs 34 +/- 1%, p less than 0.05) at 15 months than at baseline. In the diabetic men, peak filling rate increased from 4.3 +/- 0.1 stroke volume/s at baseline to 4.8 +/- 0.2 stroke volume/s at 15 months (p less than 0.05). At 15 months, peak filling rate was correlated (r = 0.61, p less than or equal to 0.001) with autonomic nervous function assessed as heart rate variability during deep breathing test in diabetic men who also showed an inverse correlation between LV hypertrophy and heart rate variability throughout the follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired left ventricular systolic function during exercise in middle-aged insulin-dependent and noninsulin-dependent diabetic subjects without clinically evident cardiovascular disease

Equilibrium radionuclide angiocardiography was performed on 19 men and 17 women with insulin-dependent diabetes mellitus (IDDM) and on 24 men and 15 women with noninsulin-dependent diabetes mellitus (NIDDM) and on 24 male and 24 female control subjects aged 46 to 67 years. All were without clinically evident cardiovascular disease. No significant differences were found in left ventricular (LV) ejection fraction at rest between men with IDDM (56 +/- 1%; mean +/- standard error of the mean) or NIDDM (58 +/- 1%) and control men (58 +/- 1%), whereas LV ejection fraction was higher in women with IDDM (63 +/- 1%; p less than 0.01) and NIDDM (64 +/- 2%; p less than 0.01) than in control women (58 +/- 1%). An abnormal LV ejection fraction response to dynamic exercise (an increase of less than 5% units or a decrease) was observed in 1 control man (4%), in 8 men with IDDM (42%, p less than 0.01) and in 10 men with NIDDM (42%, p less than 0.01). The respective figures were 4 (17%) for control women, 7 (44%, difference not significant) for women with IDDM and 10 (71%, p less than 0.01) for women with NIDDM. Abnormal LV ejection fraction response to exercise in diabetic patients was not related to the metabolic control of diabetes, presence of microangiopathy or abnormalities in the autonomic nervous function. Myocardial perfusion scintigraphy performed in 18 diabetic patients in whom LV ejection fraction decreased during exercise showed a reversible perfusion defect in only 5 (28%).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular systolic function in middle-aged patients with diabetes mellitus

In cross-sectional studies of asymptomatic diabetic patients, multiple abnormalities in left ventricular (LV) function have been found. Long-term significance of these abnormalities is unknown because follow-up studies have not been previously performed. LV ejection fraction (EF) by radionuclide angiocardiography was examined in middle-aged control subjects (n = 44), in patients with insulin-dependent (IDDM) (n = 32) and non-insulin-dependent (NIDDM) (n = 32) diabetes mellitus at baseline and after 4-year follow-up. At baseline, all study subjects were free from cardiovascular disease. LVEF at rest did not differ between the groups at baseline. The decrease in LVEF at rest during follow-up was 1.1 +/- 1.1% (mean +/- SEM) in control subjects, 3.1 +/- 1.3% (p = NS, compared with control subjects) in patients with IDDM, and 7.2 +/- 1.4% (p < 0.01) in patients with NIDDM. At follow-up examination, abnormally low LVEF at rest (< 50%) was found in 7% of control subjects, 13% of patients with IDDM (p = NS), and in 31% of patients with NIDDM (p < 0.05). Compared with control subjects, the prevalence of an abnormal LVEF response to exercise (an increase by < 5%, or a decrease) was higher in diabetic groups at both examinations. This prevalence increased in control subjects from 10% at baseline to 26% at follow-up examination.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Sympathetic Denervation in Patients With Coronary Artery Disease Without Previous Myocardial Infarction

Myocardial infarction damages sympathetic nerve fibers coursing through the infarct zone. In this study we investigated whether coronary artery disease without myocardial infarction results in sympathetic denervation. We examined 12 patients without a history of previous myocardial infarction and 19 postinfarction patients. 1-123 metaiodobenzylguanidine (MIBG) and technetium-99m sestamibi (MIBI) single-photon emission tomography were conducted at rest to determine the extent of denervated myocardium and the extent of myocardium with reduced perfusion, respectively. In addition, myocardial perfusion during exercise was assessed with MIBI. A MIBG or MIBI defect was determined as being regional uptake of < or =30% of the maximal myocardial activity. All but 1 patient without previous infarction had MIBG defects. MIBG defects (10.3 +/- 8.5% of left ventricular mass) were significantly larger than MIBI defects at rest (2.4 +/- 3.2%, p <0.001) and during exercise (4.8 +/- 6.1%, p <0.05). In multiregression analysis, the size of an MIBG defect was associated with severity of coronary stenoses (> or =90% of lumen diameter; p <0.05), but not with age, number of significant stenoses (> or =50% of lumen diameter), left main disease, functional class, left ventricular ejection fraction, angina pectoris, maximal ST depression, or mean workload during exercise test. MIBG and MIBI defects were significantly larger in patients with severe coronary stenoses than in patients with moderate stenoses (50% to 89% of lumen diameter) (16.4 +/- 8.9% vs 6.0 +/- 5.2% [p <0.05] and 5.0 +/- 3.1% vs 0.6 +/- 1.3% [p <0.001], respectively). The size of MIBG (16.1 +/- 8.9%) and MIBI defects (7.3 +/- 6.5%) at rest in postinfarction patients did not differ from patients with severe stenoses. Our study demonstrates that cardiac adrenergic tissue is very sensitive to ischemia and that regional cardiac sympathetic denervation can occur in patients with stable coronary artery disease without previous myocardial infarction.

Myocardial infarction in diabetic and non-diabetic persons with and without prior myocardial infarction: the FINAMI Study

Aims/hypothesisWe compared the risk of acute coronary events in diabetic and non-diabetic persons with and without prior myocardial infarction (MI), stratified by age and sex.MethodsA Finnish MI-register study known as FINAMI recorded incident MIs and coronary deaths (n=6988) among people aged 45 to 74 years in four areas of Finland between 1993 and 2002. The population-based FINRISK surveys were used to estimate the numbers of persons with prior diabetes and prior MI in the population.ResultsPersons with diabetes but no prior MI and persons with prior MI but no diabetes had a markedly greater risk of a coronary event than persons without diabetes and without prior MI. The rate of recurrent MI among non-diabetic men with prior MI was higher than the incidence of first MI among diabetic men aged 45 to 54 years. The rate ratio was 2.14 (95% CI 1.40–3.27) among men aged 50. Among elderly men, diabetes conferred a higher risk than prior MI. Diabetic women had a similar risk of suffering a first MI as non-diabetic women with a prior MI had for suffering a recurrent MI.Conclusions/interpretationBoth persons with diabetes but no prior MI, and persons with a prior MI but no diabetes are high-risk individuals. Among men, a prior MI conferred a higher risk of a coronary event than diabetes in the 45–54 year age group, but the situation was reversed in the elderly. Among diabetic women, the risk of suffering a first MI was similar to the risk that non-diabetic women with prior MI had of suffering a recurrent MI.

Decreased myocardial 123I-metaiodobenzylguanidine uptake is associated with disturbed left ventricular diastolic filling in diabetes

Metaiodobenzylguanidine (MIBG) is a guanethidine analog that participates in the norepinephrine uptake in postganglionic sympathetic neurons. Labeling MIBG with radiotracer allows the noninvasive visualization of sympathetic innervation of the heart.l In diabetic heart, abnormalities in left ventricular systolic and diastolic function have been described,2-4 and cardiac diabetic autonomic neuropathy has been suggested to contribute to

Aging of the population may not lead to an increase in the numbers of acute coronary events: a community surveillance study and modelled forecast of the future

Objective To examine the incidence, mortality and case fatality of acute coronary syndrome (ACS) in Finland during 1993–2007 and to create forecasts of the absolute numbers of ACS cases in the future, taking into account the aging of the population. Design Community surveillance study and modelled forecasts of the future. Setting and methods Two sets of population-based coronary event register data from Finland (FINAMI and the National Cardiovascular Disease Register (CVDR)). Bayesian age–period–cohort (APC) modelling. Participants 24 905 observed ACS events in the FINAMI register and 364 137 in CVDR. Main outcome measures Observed trends of ACS events during 1993–2007, forecasted numbers of ACS cases, and the prevalence of ACS survivors until the year 2050. Results In the FINAMI register, the average annual declines in age-standardised incidence of ACS were 1.6% (p<0.001) in men and 1.8% (p<0.001) in women. For 28-day case fatality of incident ACS, the average annual declines were 4.1% (p<0.001) in men and 6.7% (p<0.001) in women. Findings in the country-wide CVDR data were consistent with the FINAMI register. The APC model, based on the CVDR data, suggested that both the absolute numbers of ACS events and the prevalence of ACS survivors reached their peak in Finland around 1990, have declined since then, and very likely will continue to decline until 2050. Conclusions The ACS event rates and absolute numbers of cases have declined steeply in Finland. The declining trends are likely to continue in the future despite the aging of the population.