Catastrophic antiphospholipid syndrome as a complication of systemic sclerosis.

A 62-year-old man with a history of systemic sclerosis was admitted with diffuse alveolar hemorrhage and acute kidney injury without clinical data suggestive of glomerulonephritis. Laboratory tests showed anemia, leukocytosis with neutrophilia, thrombocytopenia, elevated serum creatinine and metabolic acidosis. Antinuclear antibodies were positive at a titer of 1/640 (speckled, 1/160; nucleolar, 1/320) while rheumatoid factor, anti Scl-70, anti-centromere, anti-neutrophil cytoplasmic antibody and anti-glomerular basement membrane antibodies were negative and serum complement levels were within normal range. During the following days, the patient developed multiple organ failure and, eventually, died. Lupus anticoagulant was revealed positive after the patient's death, suggesting a catastrophic antiphospholipid syndrome. Clinical data and autopsy were consistent with this diagnosis.

Circulating free nitrotyrosine and cognitive decline.

OBJECTIVE: To determine if the circulating nitrotyrosine level significantly correlates with parameters measuring cognitive abilities. MATERIALS AND METHODS: One-hundred and twelve community-living subjects (ranging in age from 27 to 98 years) were evaluated for cognitive abilities [Mini Mental State Examination (MMSE) score] and circulating free nitrotyrosine plasma level, as well as for several variables that might influence cognitive abilities (age, education) and nitrotyrosine level (body mass index, haematological parameters, cardiovascular and inflammatory indices). RESULTS: In the sub-group of cognitively impaired subjects (score at MMSE < 23.9), but not in that of cognitively not impaired subjects, a significant inverse correlation exists between nitrotyrosine level and MMSE score (r = -0.378; P < 0.02). CONCLUSIONS: The finding, if confirmed by longitudinal studies, could play a role in the management of the subjects with Mild Cognitive Impairment, the clinical condition considered as a transitional state between the changes of cognitive ability in normal aging and dementia.

Plasma leptin concentrations and cardiac autonomic nervous system in healthy subjects with different body weights.

Previous studies have shown that leptin stimulates sympathetic nervous system; heart rate variability (HRV) is a widely used technique for assessing the sympathovagal balance at the cardiac level. The aim of our study was to investigate a possible relationship between plasma leptin levels and the autonomic regulation using spectral analysis of HRV. In 120 healthy nonobese subjects the plasma leptin concentration was determined, and HRV was recorded at baseline and during tilt. All subjects were categorized in quartiles of plasma leptin concentration. Analysis of data showed a significant increase in body mass index, body fat, fasting plasma insulin, triglyceride concentration, and homeostatic model assessment values throughout the different quartiles of plasma leptin concentration. Concerning cardiovascular parameters, heart rate, arterial blood pressures, and RR intervals were not significantly different among the quartiles. Total power and high frequency (HF) in normalized units were significantly decreased, whereas low frequency (LF) normalized units was progressively increased from the first to the fourth quartile. Thus, the LF/HF ratio rose gradually and significantly from the lowest to the highest quartile. Such results were independent of the body fat estimate (P < 0.03 for the trend). The change in the LF/HF ratio was significantly enhanced during tilt (P < 0.001 vs. rest values for all quartiles); the effect was stronger in subjects in the fourth quartile of plasma leptin concentration (P < 0.005 for the trend). The latter parameter was also independent of body fat content and distribution (P < 0.01). Our study shows that increasing fasting plasma leptin concentrations are associated with a shift of the sympathovagal balance toward a progressive increase in sympathetic activation and an increased response to orthostatic stimulus in nonobese subjects with different body fat contents.

The BB-paraoxonase genotype is associated with impaired brachial reactivity after acute hypertriglyceridemia in healthy subjects.

The possible relationship between paraoxonase (PON) gene polymorphism and brachial reactivity in healthy adult subjects in the presence of acute hypertriglyceridemia (HT), as a prooxidant factor, was investigated. In 101 healthy subjects the response to flow- induced vasodilatation was measured before and after Intralipid infusion. In the same subjects the A/B PON polymorphism was detected. The frequency was 0.545 for AA genotype, 0.356 for the AB genotype, and 0.099 for the BB genotype. At baseline all genotype groups had a similar increase in brachial artery diameter and flow. After Intralipid infusion, subjects sharing the BB genotype had a significant decrease vs. baseline values in changes in brachial artery diameter (P for trend < 0.001 vs. the other genotypes), but not in flow. In a subgroup of 55 subjects distributed among the 3 PON genotypes the same study protocol was repeated by buccal nitroglycerine administration to study the endothelium-independent vasodilatation. Again, subjects with the BB genotype had the worse vasodilation (P for trend < 0.001). Furthermore, subjects sharing the BB genotype had the lowest endothelium-independent and -dependent changes in diameter (P for trend < 0.001 vs. the other genotypes) independently of gender ratio, basal plasma triglycerides concentrations, and changes in plasma triglycerides concentrations. In conclusion, our study demonstrates that transient HT decreases vascular reactivity more in subjects with the PON BB genotype than in those with the other PON genotypes.

Role of free fatty acids on cardiac autonomic nervous system in noninsulin-dependent diabetic patients: effects of metabolic control.

Decreased heart rate variability (HRV) is a risk factor for cardiovascular mortality. Elevated plasma free fatty acid (FFA) levels decrease HRV in healthy subjects. Thus, we investigated the effect of changes in plasma FFA levels on HRV, in non-insulin-dependent diabetes (NIDDM) patients. Thirty NIDDM patients free from diabetic neuropathy volunteered for a study made by two phases. In study A, changes in HRV along a 10% lipid emulsion infusion + heparin (n = 15) or saline infusion (control study; n = 15) were investigated. In study B, all patients (n = 30) underwent further determination of HRV after 3 months of improved metabolic control achieved by intensified insulin treatment. In study A, lipid emulsion infusion increased plasma FFA (P < 0.001) and catecholamine concentrations (P < 0.005), mean arterial blood pressure (P < 0.005), low frequency/high frequency (LF/HF) ratio (P < 0.001). Delta plasma FFA levels correlated with delta LF/HF ratio (r = 0.57; P < 0.02). Along with saline infusion, metabolic and cardiovascular parameters remained unchanged throughout the test. In study B, improved metabolic control lowered fasting plasma glucose (P < 0.005), FFA (P < 0.001), norepinephrine (P < 0.02), epinephrine (P < 0.04), and glycosylated hemoglobin levels (P < 0.001), mean arterial blood pressure(P < 0.05), and LF/HF ratio (P < 0.001). Again percent decline in plasma FFA correlated with the percent change in LF/HF ratio (r = 0.72; P < 0.001). In a multivariate analysis, percent changes in LF/HF ratio were associated with percent changes in plasma FFA independently of gender and percent changes in body mass index, waist/hip ratio, plasma norepinephrine, epinephrine, glycosylated hemoglobin, and daily insulin therapy. Our study demonstrates that changes in plasma FFA levels may have a parallel effect on cardiac sympathetic/parasympathetic nervous system balance in NIDDM patients.

Chronic administration of pharmacologic doses of vitamin E improves the cardiac autonomic nervous system in patients with type 2 diabetes.

BACKGROUND: Type 2 diabetes is associated with elevated oxidative stress and declines in antioxidant defense. The disease is also characterized by an imbalance in the ratio of cardiac sympathetic to parasympathetic tone. Antioxidants, vitamin E in particular, may have beneficial effects on the cardiac autonomic nervous system through a decline in oxidative stress. OBJECTIVE: We investigated the possible effects of vitamin E on the cardiac autonomic nervous system, as assessed by analysis of heart rate variability, in patients with type 2 diabetes and cardiac autonomic neuropathy. DESIGN: In a double-blind randomized controlled trial, 50 patients with type 2 diabetes were assigned to treatment with vitamin E (600 mg/d) or placebo for 4 mo. RESULTS: The anthropometric characteristics of the patients remained unchanged throughout the study. Chronic vitamin E administration was associated with decreases in concentrations of glycated hemoglobin (P < 0.05), plasma insulin (P < 0.05), norepinephrine (P < 0.03), and epinephrine (P < 0.02); a lower homeostasis model assessment index (P < 0.05); and improved indexes of oxidative stress. Furthermore, vitamin E administration was associated with increases in the R-R interval (P < 0.05), total power (P < 0.05), and the high-frequency component of heart rate variability (HF; P < 0.05) and decreases in the low-frequency component (LF; P < 0.05) and the ratio of LF to HF (P < 0.05). Finally, change in the plasma vitamin E concentration was correlated with change in the LF-HF ratio (r = -0.43, P < 0.04) independently of changes in the homeostasis model assessment index and plasma catecholamines concentrations. CONCLUSIONS: Chronic vitamin E administration improves the ratio of cardiac sympathetic to parasympathetic tone in patients with type 2 diabetes. Such an effect might be mediated by a decline in oxidative stress.

Elevated plasma fatty acid concentrations prolong cardiac repolarization in healthy subjects.

BACKGROUND: High fatty acid concentrations have been shown to stimulate sympathetic nervous system activity, which may modify ventricular repolarization and thus the Q-T interval on electrocardiogram recordings. OBJECTIVE: The aim of this study was to investigate whether acute elevations of plasma fatty acid concentrations influence the corrected Q-T interval (Q-Tc), Q-Tc dispersion, and sympathetic nervous system activity in healthy nonobese subjects. DESIGN: Thirty-two healthy subjects (x +/- SD: 48+/-7 y of age) received an infusion of 10% triacylglycerol emulsion plus heparin (a bolus of 200 U followed by 0.2 U min(-1) * kg body wt(-1) for 180 min); on another occasion and in random order, the same subjects received a saline infusion. RESULTS: Compared with the saline infusion, infusion of 10% triacylglycerol emulsion increased plasma fatty acids (P<0.001) and was associated with an increase in mean blood pressure (P<0.05), heart rate (P<0.05), Q-Tc (P<0.01), Q-Tc dispersion (P<0.01), and plasma epinephrine (P<0.005). Furthermore, individual changes in plasma epinephrine correlated with changes in Q-Tc (r = 0.60, P<0.001) and Q-Tc dispersion (r = 0.53, P< 0.02) even after adjustment for age, sex, and body mass index (P<0.03 for all correlations). Only changes in plasma fatty acids (P = 0.04) and plasma epinephrine (P = 0.006) concentrations were significantly and independently associated with the lengthening of the Q-T interval. CONCLUSION: Our study showed that elevated plasma fatty acid concentrations might affect cardiac repolarization, at least in part because of an increase in plasma catecholamines.

Elevated plasma fatty acid concentrations stimulate the cardiac autonomic nervous system in healthy subjects.

BACKGROUND: Fatty acids have been shown to stimulate the sympathetic nervous system in rats. Power spectral analysis of heart rate variability (HRV) is a safe and useful tool with which to evaluate cardiac autonomic nervous system (ANS) activity. Whether changes in plasma fatty acid concentrations affect the sympathetic nervous system or HRV in humans is unknown. OBJECTIVE: We investigated the possible changes in HRV after a significant increase in plasma fatty acid concentration. DESIGN: Subjects were randomly assigned to receive an infusion of lipid emulsion (10% triacylglycerol emulsion for 180 min) + heparin (a bolus of 200 U followed by 0.2 U*min(-)(1)*kg body wt(-)(1); n = 20) or 0.9% NaCl (for 180 min; n = 10). RESULTS: Lipid emulsion + heparin infusion was associated with a rise in plasma epinephrine and norepinephrine concentrations. The rise in plasma fatty acid concentration was associated with a significant decline in the RR interval (P: < 0.03) and in total power (P: < 0.03). Analysis of the different components of HRV showed that lipid emulsion + heparin infusion stimulated low- frequency (LF) components (P: < 0.03 at the second hour and P: < 0. 01 at the third hour) and inhibited high-frequency (HF) components (P: < 0.03 at the second and third hours). Consequently, the LF-HF ratio was significantly stimulated (P: < 0.03 at the second hour and P: < 0.01 at the third hour). Such results persisted, although attenuated, when the study was repeated in association with a propranolol infusion (n = 8). CONCLUSION: Elevated plasma fatty acid concentrations may stimulate cardiac autonomic nervous system activity.

Association of fasting plasma free fatty acid concentration and frequency of ventricular premature complexes in nonischemic non-insulin-dependent diabetic patients.

We investigated the association between free fatty acid (FFA) concentration and ventricular premature complexes (VPCs) in nonischemic patients with non-insulin-dependent diabetes mellitus using 3 approaches: cross-sectional analysis (n = 142), intervention including induction of elevated FFA levels with Intralipid heparin (n = 15), and reduction in FFA levels with Acipimox (n = 34) and a longitudinal follow-up study (n = 59). Patients at the third tertile of fasting plasma FFA concentration had the strongest increase in VPCs. Independently of age, sex, body mass index (BMI), waist/hip ratio, left ventricular mass index, glycated hemoglobin, fasting plasma insulin and triglyceride concentration, and daily physical activity, FFA concentration and VPCs were significantly correlated (r = 0.21 p <0.01). At multiple logistic regression analysis independently of age, sex, BMI, waist/hip ratio, left ventricular mass index, mean arterial blood pressure, glycated hemoglobin, fasting plasma insulin, triglycerides and potassium concentration, fasting plasma low-density lipoprotein/high-density lipoprotein cholesterol ratio, and daily physical activity, plasma FFA concentration was a significant determinant of VPCs (odds ratio 1.2, 95% confidence interval 1.0 to 2.3). Intralipid infusion (10% in 24 hours) (n = 15) and acipimox administration (250 mg, 4 times/day) (n = 34) increased, and decreased fasting plasma FFA concentration, respectively. In those studies, change in VPCs paralleled the effects on plasma FFA. In the longitudinal study (n = 59), plasma FFA concentration predicted the development of VPCs (RR 1.4 95% confidence interval 1.0 to 1.9) independently of age, sex, BMI, waist/hip ratio, left ventricular mass index, mean arterial blood pressure, fasting plasma triglyceride concentration, fasting plasma low-density lipoprotein/high-density lipoprotein cholesterol ratio, and daily physical activity. In conclusion, in nonischemic patients with non-insulin-dependent diabetes mellitus, plasma FFA concentration is associated with the frequency of ventricular premature complexes.

Oxidative stress and advancing age: results in healthy centenarians.

OBJECTIVE: Our study aims at investigating the degree of oxidative stress in centenarians DESIGN: Indices of oxidative stress (reaction products of malondialdehyde with thiobarbituric acid (TBARS) and lipid hydroperoxides (LPO)), and plasma concentrations of antioxidant defenses (plasma vitamin E and C concentrations and reduced/oxidized glutathione ratio (GSH/GSSG)) were determined. SUBJECTS: Eighty-two subjects volunteered for the study. They were divided into three groups: (1) adults (<50 years of age, n=30); (2) aged subjects (70-99 years, n=30); (3) centenarians (age > or=100 years, n=22). MEASUREMENTS: TBARS and LPO, plasma vitamin E and C concentrations, and plasma GSH/GSSG ratio were determined. Insulin action was assessed by euglycemic hyperinsulinemic glucose clamp. MAIN RESULTS: TBARS (0.44+/-0.07 vs 0.31+/-.05 nmol malondialdehyde/mL plasma, P=.020) and LPO (0.36+/-0.05 vs 0.31+/-.04 micromol/L, P=.050) were lower in centenarians than in aged subjects. In contrast, plasma GSH/GSSG ratio (0.82+/-0.09 vs 1.17+/-.06, P=.010), vitamin C (72.3+/-4.6 vs 59.4+/-3.8 micromol/L P=.010), and vitamin E (29.1+/-2.2 vs 24.4+/-2.3 micromol/L P=.050) concentrations were more elevated in centenarians than in aged subjects. Differences in daily vegetable intake, in fasting plasma glucose and free fatty acid (FFA) concentrations, and in insulin action are significant determinants of degree of oxidative stress. A specific genetic background in centenarians might also provide a possible explanation. CONCLUSIONS: The degree of oxidative stress is lower in healthy centenarians than in aged subjects.

ACE gene polymorphism and insulin action in older subjects and healthy centenarians.

OBJECTIVES: To evaluate the possible relationship between angiotensin-converting enzyme (ACE) insertion-deletion (ID) genotype and insulin resistance in a population of healthy older Italian subjects. DESIGN: Prospective recruitment of a convenience sample. PARTICIPANTS: One hundred twenty-five subjects age 62 to 105 in good health and not taking any drug known to interfere with glucose metabolism. RESULTS: In the sample population, the relative frequencies of the ACE genotypes deletion-deletion (DD) (0.424), ID (0.400), and insertion-insertion (II) (0.176) were not significantly different from values predicted by Hardy-Weinberg equilibrium. The genotype distribution was similar in men and women. Subjects carrying the II genotype had a higher FPG (P <.001) and FPI (P <.001) than did subjects with DD or ID genotype. Subjects with II genotype also had a significantly higher HOMA index than did subjects with DD or ID genotype (P for trend <.002). In a multivariate stepwise regression analysis, the ACE ID polymorphism was significantly and independently associated with the HOMA index (P <.001). The same result was confirmed performing multivariate analysis in the younger group and centenarians separately. CONCLUSIONS: In an older population, the presence of II ACE genotype is associated with a high degree of insulin resistance independent of other anthropometric variables known to interfere with insulin action; this association is significant in both the younger subjects and the centenarians.

Hyperinsulinemia is associated with ventricular premature complexes.

The study investigated a possible association between fasting plasma insulin (FPI) levels and ventricular premature complexes (VPCs). One hundred eighty-six subjects without coronary artery disease (CAD), diabetes, hypertension, and left ventricular hypertrophy were recruited. All subjects underwent 24-hour electrocardiographic monitoring and oral glucose tolerance testing. The subjects were slightly overweight, normotensive, and nondiabetic. Subjects at the third tertile of FPI concentrations were the oldest and heaviest, with prevalent upper-body fat distribution, and had enhanced fasting plasma triglyceride and potassium concentrations, lower fasting plasma high-density lipoprotein (HDL) cholesterol concentration, and a greater number of VPCs versus subjects at the first and second tertiles. Independently of age, sex, body mass index (BMI), and waist to hip ratio (WHR), VPCs were correlated with FPI concentration (r = .19, P < .01). Multiple logistic regression analyses in which the presence or absence of VPCs was the dependent variable demonstrated that FPI concentrations were associated with VPCs independently of age, sex, BMI, WHR, daily physical activity (DPA), left ventricular mass index (LVMI), plasma low-density lipoprotein (LDL)/HDL cholesterol ratio, and triglyceride concentration (odds ratio [OR], 1.2; 95% confidence interval [CI], 1.0 to 1.6). After addition to the model of fasting plasma free fatty acids ([FFA] OR, 0.7; 95% CI, 0.6 to 1.3) or potassium (OR, 0.7; 95% CI, 0.6 to 1.1) concentrations, the association between FPI concentrations and VPCs is no longer significant. In conclusion, FPI concentrations are associated with VPCs in nondiabetic, normotensive, nonischemic subjects.

Effects of different insulin infusion rates on heart rate variability in lean and obese subjects.

The low-frequency to high-frequency ratio (LF/HF ratio) is an index of cardiac sympathovagal balance. We hypothesized that insulin might also stimulate the LF/HF ratio. Thus, 15 lean and 15 obese subjects were studied. Each subject underwent sequential hyperinsulinemic clamps (insulin infusion rate 0.50, 1, and 2 mU/kg x min) while the heart rate was recorded by the Holter technique continuously. Indirect calorimetry allowed determination of the respiratory quotient (Rq) and substrate oxidation. The leg blood flow (LBF), leg vascular resistance (LVR), and plasma norepinephrine concentration were also measured. In seven lean subjects, hyperinsulinemic clamps were repeated along with propranolol infusion (0.1 mg x kg(-1) as an intravenous bolus dose followed by continuous intravenous infusion of 0.5 mg x kg(-1) x min(-1) throughout the study). Lean subjects had better insulin action than obese subjects. Insulin infusion was associated with an increase of the deltaLF/HF ratio in both lean (P < .001 for time-dependent changes) and obese (P < .02 for time-dependent changes) subjects; however, the extent of insulin-mediated stimulation of the LF/HF ratio was greater in lean versus obese subjects. Insulin infusion did not significantly affect HF values in both groups. Independently of gender, body fat, changes in the plasma norepinephrine concentration, LBF, and LVR, the deltaLF/HF ratio at the end of the fastest insulin infusion (0.8 +/- 0.2 v 0.3 +/- 0.2, P < .04) was still greater in lean versus obese subjects. The deltaLF/HF ratio was also more stimulated during insulin versus insulin + propranolol infusion in lean subjects. In conclusion, insulin stimulates the LF/HF ratio in both lean and obese subjects and thus produces a shift in the cardiac autonomic nervous system activity toward sympathetic predominance.

Cardiovascular risk in type 2 diabetics and pharmacological regulation of mealtime glucose excursions.

In type 2 diabetic patients mealtime glucose fluctuations are important determinants of overall glucose control and overall risk of diabetes cardiovascular complications. In fact, acute elevation of plasma glucose concentrations trigger an array of tissue response that may contribute to development of such vascular complications since it may result in a thrombophilic condition, causes endothelial dysfunction (possibly through a reduction of nitric oxide availability) and is responsible for non-enzymatic glycation and production of free- radicals with ensuing oxidative stress. To keep post-prandial glucose with narrow range, metiglinide analogues drugs have been developed. In particular, repaglinide and nateglinide seem the most useful ones. In fact, both drugs improve 1(st) phase insulin release but they do not affect the total daily amount of insulin released by the pancreas. Due to the mechanism of action and to pharmacokinetic properties, repaglinide and nateglinide allow diabetic patients to get a more tight metabolic glucose control with a contemporary reduction in the cases of severe hypoglycaemia. In conclusions, repaglinide and nateglinide are new and powerful pharmacological tools not only for achieving a better metabolic glucose control but also for preventing the development of diabetes-related cardiovascular complications.

Losartan mediated improvement in insulin action is mainly due to an increase in non-oxidative glucose metabolism and blood flow in insulin-resistant hypertensive patients.

We investigated the possible role of losartan on insulin-mediated glucose uptake, substrate oxidation and blood flow in insulin-resistant hypertensive patients. Sixteen newly diagnosed patients with mild-to-moderate hypertension were studied. The study design was a single-blind, randomised, placebo-controlled trial. After a 1 week run-in period, each patient was randomly assigned to placebo (n = 7) and losartan (n = 9). Both treatment periods lasted 4 weeks. At baseline, and at the end of the placebo and losartan treatment periods, euglycaemic hyperinsulinaemic glucose clamp and indirect calorimetry were performed. Before and along each glucose clamp, blood flow was also determined in the femoral artery by image-directed duplex ultrasonography combining B-mode imaging and pulse Doppler beams. Losartan vs placebo lowered systolic blood pressure by 163 +/- 3.5 and 147 +/- 4.1 mm Hg (P < 0.001), and diastolic blood pressure by 95 +/- 3.2 and 85 +/- 3.2 mm Hg (P < 0.001). Losartan enhanced glucose metabolic clearance rate by 5.1 +/- 0.3 and 6.3 +/- 0.4 mg/kg x min (P < 0.05), and whole body glucose disposal (WBGD) by 29.2 +/- 0.5 and 38.1 +/- 0.4 mumol/kg free fatty mass (FFM) x min (P < 0.01) but did not affect heart rate. Insulin-mediated change in blood flow was greater after losartan than placebo administration (111 +/- 4 vs 84 +/- 3%, P < 0.01). Per cent change in insulin-mediated stimulation of blood flow and WBGD were also correlated (r = 0.76, P < 0.01). Analysis of substrate oxidation revealed that losartan administration improved insulin action and non-oxidative glucose metabolism (NOGM) (30.8 +/- 2.2 vs 22.8 +/- 2.8 mumol/kg FFM x min, P < 0.05). In conclusion losartan improves insulin-mediated glucose uptake through an increase in NOGM and blood flow in hypertensive patients.

Effect of low dose Amiodarone on the incidence of sudden death in elderly patients with congestive heart failure: a double-bind, placebo-controlled study.

To determine if low-dose Amiodarone could reduce sudden death (SD) among patients with congestive heart failure, a prospective, double-blind, placebo-controlled study was conducted. The study group consisted of 46 patients (36 men and 10 women, mean age 71 +/- 5 years) with complex ventricular ectopy documented by 48-hour Holter monitoring. Randomization divided the patients into two treatment groups: the first group received Amiodarone (400 mg/day for 1 week and then 100 mg/day), while the second group received placebo. The drug significantly reduced ventricular arrhythmias, but then was no decrease in incidence of SD. This study demonstrates not only that low-dose Amiodarone can be safely administered to elderly patients with congestive heart failure and it will significantly suppress ventricular arrhythmias, but also that reduction in ventricular arrhythmias and the risk of SD are not linearly related.

Should we recommend the therapeutical use of vitamin E in diabetic patients?

The therapeutic application of vitamin E was initially restricted to thrombocytopenic purpura and later extended to coronary artery diseases and peripheral vascular arteriosclerosis due to the potency of its effects. Several recent studies have pointed out that vitamin E supplementation is useful for reducing low-density lipoprotein oxidation and thus might be protective towards coronary heart disease. Such data has been confirmed in many in vitro data, while in vivo results of reports from epidemiological studies are much more controversial. More consistent is the evidence showing vitamin E to improve endothelial function especially in diabetic patients. Finally, chronic vitamin E has been demonstrated to improve the metabolic control in diabetic patients. Whether chronic vitamin E administration at pharmacological doses and for long time, is safe is still debated. A sure response to such a query will open the possibility for recommending vitamin E as a therapeutic agent in diabetic patients.

Age-related insulin resistance: is it an obligatory finding? The lesson from healthy centenarians.

It is widely known that advancing age is associated with impaired glucose handling. A unifying hypothesis explaining the relationship between aging and insulin resistance might encompass four main pathways, namely: (a) anthropometric changes (relative and absolute increase in body fat combined with a decline in fat free mass) which could be the anatomic substrate for explaining the reduction in active metabolic tissue; (b) environmental causes, mainly diet style and physical activity; (c) neuro-hormonal variations [decline in plasma dehydroepandrosterone sulphate (DHEAS) and IGF-1]; and finally (d) the rise in oxidative stress. Indeed previous studies have also investigated the occurrence and the degree of insulin resistance in healthy centenarians. Such data demonstrated that age-related insulin resistance is not an obligatory finding in the elderly and that healthy centenarians have a preserved insulin action compared to aged subjects. Why insulin action is preserved in centenarians is still not known. Nevertheless, a possible approach to the question is to outline the centenarians' anthropometric, endocrine and metabolic characteristics in order to design a clinical picture of such metabolic "successful aging". According to the remodeling theory of age, the preserved insulin action in centenarians might be the net result of the continuous adaptation of the body to the deleterious changes that occur over time. Nevertheless, only future longitudinal studies specifically designed to investigate the relationship between extreme old age and degree of insulin sensitivity will provide a conclusive answer with regard to the pathophysiology of adaptive metabolic changes occurring in the elderly.

Differences in heart rate variability parameters during the post-dialytic period in type II diabetic and non-diabetic ESRD patients.

BACKGROUND: Heart rate variability parameters were evaluated in 10 healthy subjects, 10 type II diabetic patients and 20 end-stage renal disease (ESRD) patients (11 non-diabetic and nine type II diabetic) undergoing chronic haemodialysis. The study was divided in two phases. METHODS: In the first phase all subjects underwent electrocardiograph (ECG) recording under baseline conditions. In the second phase only ESRD patients underwent haemodialysis and ECG recording. On the day of dialysis and ECG recording the ECG recording was started 1 h before the haemodialysis session (pre-dialytic period), and continued throughout the dialysis (dialytic period), until the morning after (post-dialytic period). RESULTS: Compared with ESRD patients, non-ESRD patients showed the lowest cardiac sympathetic activity. Diabetic patients compared to non-diabetic patients showed a prevalence of cardiac sympathetic activity in the pre-dialytic period (P < 0.01). During the dialytic period in comparison with the pre-dialytic one, a further increase in cardiac sympathetic activity was observed in both diabetic and non-diabetic ESRD patients (P < 0.001). However, in the post-dialysis period the cardiac autonomic nervous system activity remained at the pre-dialytic condition in the diabetic group. In contrast, in the non-diabetic group the cardiac autonomic balance shifted towards a parasympathetic prevalence in the post-dialytic period (P < 0.01). In addition, a significant correlation was found between changes in heart rate variability and changes in plasma urea concentration in the non-diabetic group only (r = 0.65; P < 0.03). CONCLUSIONS: Non-insulin-dependent diabetic uraemic patients undergoing a chronic haemodialysis programme have a severe impairment of heart rate variability. This is probably due to autonomic neuropathy related to the effects of both diabetes and chronic uraemic conditions. In non-diabetic haemodialysis patients uraemia causes similar but reversible changes in heart rate variability compared with the changes caused by diabetes.

Effects of glucose ingestion on cardiac autonomic nervous system in healthy centenarians: differences with aged subjects.

BACKGROUND: Spectral analysis of heart rate variability (HRV) investigates the cardiac autonomic nervous system (ANS) activity. In particular, low frequency/high frequency (LF/HF) is considered an index of cardiac sympatho-vagal balance and is stimulated by glucose ingestion in healthy subjects. No studies have evaluated the effect of glucose ingestion on cardiac ANS in centenarians. MATERIALS AND METHODS: In 30 healthy centenarians (HC) and 25 aged subjects (AS) power spectral analysis of HRV was investigated during an oral glucose ingestion. RESULTS: Glucose ingestion rose LF/HF ratio in both groups studied. Such stimulatory effects were restrained to the first 60 min of the study. Independent of age, gender, body mass index (BMI) and fasting plasma norepinephrine and FT3 concentrations, HC had basal total power (1318 +/- 546 vs. 1918 +/- 818 msec2, P < 0.01), lower low frequency (LF) (33 +/- 21 vs. 50 +/- 11 n.u., P < 0. 03), and higher high frequency (HF) (74 +/- 18 vs. 43 +/- 15 n.u., P < 0.05) than AS. Consequently, LF/HF ratio (0.43 +/- 0.07 vs. 0.91 +/- 0.05, P < 0.02) was also lower in HC than in AS. In AS, but not in HC, the baseline LF/HF ratio correlated significantly with BMI (r = 0.48, P < 0.01), waist-hip-ratio (WHR) (r = 0.45, P < 0.02), fasting plasma insulin (r = 0.49, P < 0.01) and norepinephrine (r = 0.57, P < 0.02) concentration. Glucose ingestion was associated with a significant rise in LF/HF ratio in both groups studied but per cent changes in glucose mediated stimulation of LF/HF was lower in HC than in AS. In a control study, water administration did not affect power spectral parameters of HRV. CONCLUSION: Our study demonstrates that basal- and glucose-stimulated LF/HF, an indirect index of cardiac sympatho-vagal balance, are lower in HC than in AS.