Carlo Vigorito

Liver Fat Is Reduced by an Isoenergetic MUFA Diet in a Controlled Randomized Study in Type 2 Diabetic Patients

OBJECTIVE To evaluate the effects of qualitative dietary changes and the interaction with aerobic exercise training on liver fat content independent of weight loss in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS With use of a factorial 2 × 2 randomized parallel-group design, 37 men and 8 women, aged 35–70 years, with type 2 diabetes in satisfactory blood glucose control on diet or diet plus metformin treatment were assigned to one of the following groups for an 8-week period: 1) high-carbohydrate/high-fiber/low–glycemic index diet (CHO/fiber group), 2) high-MUFA diet (MUFA group), 3) high-carbohydrate/high-fiber/low–glycemic index diet plus physical activity program (CHO/fiber+Ex group), and 4) high-MUFA diet plus physical activity program (MUFA+Ex group). Before and after intervention, hepatic fat content was measured by 1H NMR. RESULTS Dietary compliance was optimal and body weight remained stable in all groups. Liver fat content decreased more in MUFA (−29%) and MUFA+Ex (−25%) groups than in CHO/fiber (−4%) and CHO/fiber+Ex groups (−6%). Two-way repeated-measures ANOVA, including baseline values as covariate, showed a significant effect on liver fat content for diet (P = 0.006), with no effects for exercise training (P = 0.789) or diet-exercise interaction (P = 0.712). CONCLUSIONS An isocaloric diet enriched in MUFA compared with a diet higher in carbohydrate and fiber was associated with a clinically relevant reduction of hepatic fat content in type 2 diabetic patients independent of an aerobic training program and should be considered for the nutritional management of hepatic steatosis in people with type 2 diabetes.

Effect of activation of the H1 receptor on coronary hemodynamics in man.

We evaluated the effects of selective activation of H1 receptors on coronary hemodynamics in 16 patients divided into two groups: group A, 11 patients with atypical angina or valvular heart disease and normal coronary arteries, and group B, five patients with spontaneous angina, four of whom had significant (greater than 70% stenosis) coronary artery disease and one with normal coronaries. Selective H1 receptor stimulation was achieved by infusing 0.5 microgram/kg/min of histamine intravenously for 5 min after pretreatment with cimetidine (25 mg/kg). Heart rate was maintained constant (100 beats/min) by coronary sinus pacing and coronary blood flow (CBF) was measured by thermodilution. In group A, during histamine infusion mean aortic pressure fell from 99 +/- 5 to 77 +/- 4 mm Hg (mean +/- SEM, p less than .001), coronary vascular resistance (CVR) decreased from 1.07 +/- 0.17 to 0.82 +/- 0.14 mm Hg/ml/min (p less than .02), and CBF and myocardial oxygen consumption remained unchanged. None of the patients in this subgroup developed angina during histamine infusion. In group B, while no significant average changes in mean arterial pressure, CVR, or CBF were observed, two of the five patients (40%) developed angina during histamine infusion, accompanied by ST-T elevation, a decrease in CBF, and an increase in CVR. In one of these two patients circumflex coronary arterial spasm was angiographically demonstrated during histamine-induced angina. Our results suggest that stimulation of the H1 receptor induces a reduction of CVR, probably resulting from vasodilation of small coronary resistance vessels.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise intolerance in chronic heart failure: mechanisms and therapies. Part II

Muscular fatigue and dyspnoea on exertion are among the most common symptoms in chronic heart failure; however their origin is still poorly understood. Several studies have shown that cardiac dysfunction alone cannot fully explain their origin, but the contribution of the multiorgan failure present in this syndrome must be highlighted. We aimed to summarize the existing evidence and the most controversial aspects of the complex interplay of different factors involved in the symptom generation. In the first part of the review, six key factors were revised (the heart, the lung, the skeletal muscle, the hormonal changes, the O2 delivery to the periphery, the endothelium). In this second part, the role of the excitatory reflexes and the cardiac cachexia are presented. Finally, potential therapeutic implications are discussed here. We believe that a better knowledge of the pathophysiology of this syndrome may contribute to the management of the patients and to the improvement in their stress tolerance and quality of life.

Hemodynamic effects of magnesium sulfate on the normal human heart

Abstract Because of its antiarrhythmic properties,1 parenteral magnesium sulfate has been widely used in the last decades in treating several supraventricular or ventricular arrhythmias2,3 even in patients with cardiovascular diseases. Recently, intravenous magnesium sulfate has proved effective in treating arrhythmias associated with acute myocardial infarction4 and long QT syndrome.5 However, a systematic evaluation of its effects on cardiovascular hemodynamics has not been reported. Recent experimental6 and clinical7 observations have suggested that magnesium sulfate may exert a vasodilator effect on human coronary arteries. The present study investigates the effects of magnesium sulfate infusion on coronary and systemic hemodynamics in humans.

Arterial stiffness and vitamin D levels: the Baltimore longitudinal study of aging.

CONTEXT The importance of vitamin D for bone health has long been acknowledged. Recent evidence suggests that vitamin D can also play a role in reducing the risk of several other diseases, including cardiovascular disease. OBJECTIVE The aim of this study is to test the hypothesis that 25-hydroxyvitamin D (25-OH D) is an independent cross-sectional correlate of central arterial stiffness in a normative aging study population. DESIGN AND SETTINGS We conducted a cross-sectional analysis. SUBJECTS We studied 1228 healthy volunteers (50% males; age, 70±12 yr) of the Baltimore Longitudinal Study of Aging. MAIN OUTCOME MEASURES We measured carotid-femoral pulse wave velocity (PWV) and 25-OH D levels. RESULTS We found a significant inverse association between PWV and 25-OH D levels (adjusted r2=0.27; β=-0.43; P=0.001). After adjusting for age, gender, ethnicity, season of blood draw, estimated glomerular filtration rate, physical activity level, cardiovascular risk factors score (smoking, visceral obesity, hypercholesterolemia, hypertension, and diabetes), calcium/vitamin D supplementation, serum calcium, and PTH levels, the association between PWV and 25-OH D levels was only slightly reduced and remained statistically significant (adjusted r2=0.34; β=-0.34; P=0.04). CONCLUSIONS Vitamin D levels are inversely associated with increased arterial stiffness in a normative aging population, irrespective of traditional risk factor burden. Further research is needed to understand the mechanism of this association and to test the hypothesis that vitamin D supplementation can reduce arterial stiffness.

Differential effects of insulin on splanchnic and peripheral glucose disposal after an intravenous glucose load in man.

The present study was designed to investigate the mechanisms by which insulin regulates the disposal of an intravenous glucose load in man. A combined tracer-hepatic vein catheter technique was used to quantitate directly the components of net splanchnic glucose balance (NSGB), i.e., splanchnic glucose uptake and hepatic glucose output, and peripheral (extrasplanchnic) glucose uptake. Four different protocols were performed: (a) intravenous infusion of glucose alone (6.5 mg kg(-1) min(-1)) for 90 min (control group); (b) glucose plus somatostatin (0.6 mg/h) and glucagon (0.8 ng kg(-1) min(-1); (c) glucose plus somatostatin, glucagon, and insulin (0.15 mU kg(-1) min(-1)); and (d) glucose plus somatostatin, glucagon, and insulin (0.4 m U kg(-1) min(-1)). In groups 2-4, arterial blood glucose was raised to comparable levels to those of controls ( approximately 170 mg/dl) by a variable glucose infusion. In the control group, plasma insulin levels reached 40 muU/ml at 90 min. NSGB switched from a net output of 1.71+/-0.13 to a net uptake of 1.5-1.6 mg kg(-1) min(-1) due to a 90-95% suppression of hepatic glucose output (P < 0.01) and a 105-130% elevation of splanchnic glucose uptake (from 0.78+/-0.13 to 1.6-1.8 mg kg(-1) min(-1); P < 0.01). Peripheral glucose uptake rose by 150-160% (P < 0.01). In group 2, plasma insulin fell to <5 muU/ml. Net splanchnic glucose output initially rose twofold but later returned to basal values. This response was entirely accounted for by similar changes in hepatic glucose output since splanchnic glucose uptake remained totally unchanged in spite of hyperglycemia. In contrast, peripheral glucose uptake rose consistently by 100% (P < 0.01) despite insulin deficiency. In an additional group of experiments, glucose metabolism by the forearm muscle tissue was quantitated during identical conditions to those of group 2 (hyperglycemia plus insulin deficiency). Both the arterial-deep venous blood glucose difference and forearm glucose uptake increased markedly by 300-400% (P < 0.05 - <0.01). In group 3, plasma insulin was maintained at near-basal, peripheral levels (12-14 muU/ml). Hepatic glucose output decreased slightly by 35-40% (P < 0.05) while splanchnic glucose uptake remained unchanged. Consequently, the net glucose overproduction seen in group 2 was totally prevented although NSGB still remained as a net output. In group 4, peripheral insulin levels were similar to those of the control group (35-40 muU/ml). The suppression of hepatic glucose output was more pronounced (60-65%) and splanchnic glucose uptake rose consistently by 65% (P < 0.01). Consequently, NSGB did not remain as a net output but eventually switched to a small uptake (0.3 mg kg(-1) min(-1)). Peripheral glucose uptake rose to the same extent as in controls. IT IS CONCLUDED THAT: (a) the suppressive effect of hyperglycemia on hepatic glucose output is strictly dependent on the degree of hepatic insulinization; (b) insulin plays an essential role in promoting splanchnic glucose uptake after an intravenous glucose load whereas hyperglycemia per se is totally unable to activate this process; (c) peripheral glucose uptake is markedly stimulated by hyperglycemia even in the face of insulin deficiency. Direct evidence also demonstrates that the skeletal muscle is involved in this response. Our data, thus, indicate that insulin rather than hyperglycemia regulates splanchnic glucose disposal in man. On the other hand, hyperglycemia per se appears to be an important regulator of glucose disposal by peripheral tissues.

Long-term effects of cardiac rehabilitation on end-exercise heart rate recovery after myocardial infarction.

Background Heart rate recovery (HRR) is a marker of vagal tone that is a powerful predictor of mortality in patients with coronary artery disease. Design This study aims at evaluating the effects of long-term exercise training on HRR after acute myocardial infarction (AMI), in order to clarify whether prolonged exercise training could maintain a long-term improvement of HRR. Methods Forty-four patients after AMI were enrolled in a 3-month hospital-based exercise training programme. At the end, patients were subdivided into two groups: group A (n = 22), patients discharged with a specific home-based exercise training programme and instructions for improving leisure-time physical activity; group B (n = 22), patients discharged with generic instructions to maintain physical activity. All patients underwent a cardiopulmonary exercise test before, at the end of 3 months exercise training and at 6 months follow-up. Results At the end of the hospital-based exercise training programme we observed an increase in peak oxygen consumption [VO2peak; from 13.9 ± 3.6 to 18 ± 2.7 ml/kg per min (A) and from 14.1 ± 3.9 to 17.9 ± 2.1 ml/kg per min (B), P<0.001] and in HRR [from 17.1 ± 1.8 to 23.4 ± 1.4 beats/min (A), and from 18.8 ± 2.1 to 24.3 ± 1.9 beats/min (B), P<0.001]. At 6 months’ follow-up we observed a further improvement in VO2peak (from 18.0 ± 2.7 to 20.3 ± 2.7 ml/kg per min, P<0.001) and in HRR (from 23.4 ± 1.4 to 27.8 ± 2.1 beats/min, P<0.001) in group A, but a significant decrease in VO2peak and in HRR in group B (P<0.001). Conclusion Long-term exercise training is useful for maintaining or improving the beneficial results of the standard 3-month exercise training programme on cardiovascular capacity and HRR. This observation may bear beneficial prognostic effects on patients after AMI.

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide.

Aims To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. Methods Sixty-one postinfarction patients were randomized into two groups: group T [n = 30, LV ejection fraction (EF) 41.6 ± 11.3%, mean ± SD] entered a 6-month ET programme, whereas group C (n = 31, EF 42.0 ± 7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. Results At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; −9%, P<0.001), a reduction in NT-proBNP (−71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (−40%, P<0.001; T vs. C group, P<0.001). Conclusions Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.

Mechanisms of epinephrine-induced glucose intolerance in normal humans.

To evaluate the role of the splanchnic bed in epinephrine-induced glucose intolerance, we selectively assessed the components of net splanchnic glucose balance, i.e., splanchnic glucose uptake and hepatic glucose production, and peripheral glucose uptake by combining infusion of [3-(3)H]glucose with hepatic vein catheterization. Normal humans received a 90-min infusion of either glucose alone (6.5 mg/kg(-1) per min(-1)) or epinephrine plus glucose at two dose levels: (a) in amounts that simulated the hyperglycemia seen with glucose alone (3.0 mg/kg(-1) per min(-1)); and (b) in amounts identical to the control study. During infusion of glucose alone, blood glucose rose twofold, insulin levels and net posthepatic insulin release increased three- to fourfold, and net splanchnic glucose output switched from a net output (1.65+/-0.12 mg/kg(-1) per min(-1)) to a net uptake (1.56+/-0.18). This was due to a 90-95% fall (P < 0.001) in hepatic glucose production and a 100% rise (P < 0.001) in splanchnic glucose uptake (from 0.86+/-0.14 to 1.71+/-0.12 mg/kg(-1) per min(-1)), which in the basal state amounted to 30-35% of total glucose uptake. Peripheral glucose uptake rose by 170-185% (P < 0.001). When epinephrine was combined with the lower glucose dose, blood glucose, insulin release, and hepatic blood flow were no different from values observed with glucose alone. However, hepatic glucose production fell only 40-45% (P < 0.05 vs. glucose alone) and, most importantly, the rise in splanchnic glucose uptake was totally blocked. As a result, splanchnic glucose clearance fell by 50% (P < 0.05), and net splanchnic glucose uptake did not occur. The rise in peripheral glucose uptake was also reduced by 50-60% (P < 0.001). When epinephrine was added to the same dose of glucose used in the control study, blood glucose rose twofold higher (P < 0.001). The initial rise in splanchnic glucose uptake was totally prevented; however, beyond 30 min, splanchnic glucose uptake increased, reaching levels seen in the control study when severe hyperglycemia occurred. Splanchnic glucose clearance, nevertheless, remained suppressed throughout the entire study (40%-50%, P < 0.01). It is concluded that (a) the splanchnic bed accounts for one-third of total body glucose uptake in the basal state in normal humans; (b) epinephrine markedly inhibits the rise in splanchnic glucose uptake induced by infusion of glucose; and (c) this effect does not require a fall in insulin and is modulated by the level of hyperglycemia. Our data indicate that the splanchnic bed is an important site of glucose uptake in post-absorptive humans and that epinephrine impairs glucose tolerance by suppressing glucose uptake by both splanchnic and peripheral tissues, as well as by its well known stimulatory effect on endogenous glucose production.

Cardiovascular effects of histamine infusion in man.

Summary Histamine (H) is stored in man in the cardiovascular as well as in other systems, from where it can be released under exposure to immunologic and nonimmunologic stimuli. To understand better the hemodynamic changes produced in man by endogenous H release, we infused H for 3.5–7 min at the rate of 0.4 μg/kg/min i.v. in four patients with normal left ventricular (LV) function undergoing diagnostic cardiac catheterization. We observed a significant fall in systolic, diastolic, and mean aortic pressure, systemic vascular resistance, LV end-diastolic pressure, and stroke index, and a significant rise in heart rate, cardiac output, and LV dP/dtmax, with small changes in mean pulmonary arterial pressure and pulmonary vascular resistance. During infusion there was also a significant rise in plasma H, epinephrine, and norepinephrine. All hemodynamic changes started 1–2 min after the beginning of H infusion and reverted to normal within 5 min from the end of the infusion. Subjective complaints were mild and transient in all patients. One patient progressed from first- to third-degree atrioventricular block, with prompt recovery of 1:1 atrioventricular conduction at the end of infusion. Thus, exogenous H administration in man at the rate of 0.4 μg/kg/min produces significant and transient hemodynamic changes, mainly represented by systemic hypotension, tachycardia, and increased LV performance. These latter can be attributed to the associated increase in sympathoadrenergic activity, although a direct cardiac effect of H cannot be excluded.