Freehand three-dimensional echocardiographic evaluation of the effect of telmisartan compared with hydrochlorothiazide on left ventricular mass in hypertensive patients with mild-to-moderate hypertension: a multicentre study.

Antihypertensive efficacy, effects on left ventricular mass index (LVMI) and tolerability of telmisartan, an angiotensin II receptor blocker, were compared with those of hydrochlorothiazide (HCTZ). Adult patients with mild-to-moderate hypertension and an optimal acoustic window by two-dimensional echocardiography were randomised at baseline to 12 months' double-blind, once-daily treatment with telmisartan 80 mg or HCTZ 25 mg. Two-dimensional echocardiography and freehand precordial three-dimensional echocardiography and 24-h ambulatory blood pressure monitoring were performed at baseline and after treatment. Of the 41 telmisartan group patients and 28 HCTZ group patients, 40 and 25, respectively, completed the study. Following treatment, 24-h mean SBP (telmisartan 157 +/- 11 vs 133 +/- 7 mmHg, P<0.001; HCTZ 154 +/- 10 vs 144 +/- 11 mmHg, P<0.003) and DBP (telmisartan 96 +/- 6 vs 83 +/- 5 mmHg, P<0.001; HCTZ 95 +/- 7 vs 87 +/- 8 mmHg, P<0.003) were significantly reduced. Telmisartan produced significantly greater 24-h mean SBP and DBP reductions than HCTZ (P<0.001). LVMI was significantly reduced by telmisartan (141 +/- 16 vs 125 +/- 19 g/m2, P<0.001), but not by HCTZ (139 +/- 20 vs 135 +/- 22 g/m(2)). Incidences of adverse events in both the treatment groups were low; two cases of hypokalaemia occurred with HCTZ. In conclusion, telmisartan 80 mg was well tolerated and significantly reduced SBP, DBP and LVMI after 12 months' treatment compared with HCTZ.

Effects of losartan on hypertension and left ventricular mass: a long-term study.

This study evaluated the anti-hypertensive efficacy, tolerability and effects on left ventricular mass of losartan, a selective angiotensin II receptor antagonist, after 22 months in patients with essential hypertension. The study included 77 hypertensive patients who were randomised at baseline to 22 months double-blind once-daily treatment with losartan 50 mg (L group n = 44 patients, mean age 54+/-9 years) or hydrochlorothiazide 25 mg (HCTZ group, n = 33 patients, mean age 56+/-7 years). Routine haematology, blood chemistry, standard electrocardiography, echocardiography and ambulatory non-invasive 24-h blood pressure (BP) monitoring were performed at baseline and after 10 and 22 months. The results showed good tolerability and a significant mean systolic and diastolic BP reduction in all groups (L group: 22 mm Hg and 11 mm Hg; HCTZ group: 11 mm Hg and 7 mm Hg, respectively for systolic and diastolic mean BP). Moreover, a remarkable reduction in left ventricular mass index was reached after 10 and 22 months only in the L group (L group: delta = -11 g/m2, P<0.02; HCTZ group: delta = -5 g/m2, P= 0.38). In conclusion, losartan was well tolerated and produced a significant reduction in BP and left ventricular mass in hypertensive patients

Myocardial wall thickness and left ventricular geometry in hypertensives. Relationship with insulin.

In hypertensive patients the presence of left ventricular (LV) hypertrophy has been associated with a more severe degree of insulin resistance. Whether myocardial wall thickness or LV geometry are associated with a different degree of insulin resistance is still unknown in essential hypertensives. For this reason 26 men with new diagnosed essential hypertension were enrolled. All patients underwent echocardiographic examination and euglycemic hyperinsulinemic glucose clamp combined with indirect calorimetry. According to LV mass and relative wall thickness data, all patients were categorized in four groups: 1) patients with a normal geometric LV pattern (n = 8) (PAT = 0); 2) patients with concentric remodeling LV mass (n = 8) (PAT = 1); 3) patients with eccentric LV hypertrophy (n = 3) (PAT = 2); and 4) patients with concentric LV hypertrophy (n = 7) (PAT = 3). All groups were similar for anthropometric characteristics. Patients with normal echocardiographic LV pattern (PAT = 0) had higher whole body glucose disposal (WBGD), oxidative and nonoxidative glucose metabolism, and lower lipid oxidation than patients with abnormal echocardiographic LV patterns (PAT = 1 to 3). Nevertheless, no significant differences among the groups with abnormal echocardiographic patterns were found. After controlling for age, body mass index (BMI), waist/hip ratio (WHR), and mean arterial blood pressure, only sum of the wall thickness was significantly correlated with fasting plasma insulin (r = -0.38, P < .05), WBGD (r = - 0.50, P < .009), and NOGM (r = - 0.48, P < .02). In multivariate analysis, a model made by age, BMI, WHR, systolic and diastolic blood pressure, and WBGD explained 38% of the echocardiographic pattern variability. In this model, WBGD (P < .02) was significantly and independently associated with echocardiographic patterns explaining 19% of the echocardiographic pattern variability. In conclusion, our data demonstrate that in arterial hypertension hyperinsulinemia/insulin resistance mainly affects myocardial wall thickness, whereas only a trivial association with LV geometry occurs.

[Prognostic value of the exertion test in patients treated with thrombolytic therapy for acute myocardial infarct]. / Il valore prognostico del test da sforzo in pazienti trombolisati per infarto acuto del miocardio.

Prognostic value of exercise testing after thrombolytic therapy in patients with acute myocardial infarction. Few studies have evaluated the prognostic value of exercise testing in patients suffering from acute myocardial infarction (AMI) and thrombolysis. For this reason the authors studies 398 patients divided into two groups: 189 thrombolysed patients (T) and 209 non-thrombolysed patients (NT), matched for age, sex, AMI site and treatment received. Thrombolysis was performed within 6 hours of the onset of symptoms using rt-PA in an accelerated regime (90 degrees) preceded by sodium heparin infusion 5000 UI i.v. in bolus, and followed by sodium heparin for 5 days, maintaining a PTT value 2-3 times the basal level. The efficacy of thrombolytic treatment was confirmed by the presence pf at least two of the following markers: CK peak time, rapid reduction of ST overunlevelling, reperfusion arrhythmia. All patients underwent exercise testing using the cycloergometer after suspending treatment at 3 weeks and 6 months after AMI, and a echocardiographic examination on the first day and after 6 months. These data show that thrombolytic treatment reduces the myocardial damage during the course of AMI, enabling the patient to exercise longer and causes improved myocardial contractility with a lower asynergic index compared to non-reperfused patients. Moreover, significantly fewer ergometric tests that were positive for residual ischemia were observed in T compared to NT. The incidence of mortality one year after AMI was low in both groups, albeit lower in T. This confirms the important prognostic role of ergometric tests also in this population.

[Clinical value of multiplane transesophageal echocardiography in the diagnosis of lipomatous hypertrophy of the interatrial septum. Report of two clinical cases]. / Utilità clinica dell'ecocardiografia transesofagea multiplanare nella diagnosi di ipertrofia lipomatosa del setto interatriale. Descrizione di due casi clinici.

Lipomatous hypertrophy of interatrial septum is a very rare condition associated with supraventricular arrhythmias and sudden death. The authors describe two clinical cases of lipomatous hypertrophy and underline usefulness of multiplane transesophageal echocardiography in the diagnosis of this affection.

Morpho-functional assessment of interatrial septum: a transesophageal echocardiographic study.

BACKGROUND: Despite the increasing number of reports on lipomatous hypertrophy of interatrial septum, a standardization of measurement of the dimensions of the interatrial septum (IAS) in the different phases of cardiac cycle has not been reported. Moreover, no data on modification of thickness with age and in specific cardiac diseases are available. OBJECTIVE: Our purpose was to study whether the changes of thickness and thinning of IAS may be related to age, left atrial dimension, cardiac cycle and different cardiac diseases. METHODS: 248 patients (mean age 52.7 +/- 19.9 years) underwent transthoracic (TTE) and transesophageal (TEE) echocardiography. IAS was measured at the constant regions anterior and posterior to the fossa ovalis. IAS thickness (tk), thinning (th) and % thinning (% th) were measured. RESULTS: IAS thickness ranged from 4 to 13 mm at the time of ventricular end-systolic phase (mean 6.7 +/- 1.9 mm) and from 6 to 16 mm at the time of atrial systole (mean 9.9 +/- 1.8 mm); significant statistical difference between these values was found (P < 0.01). IAS thinning ranged from 1 to 7 mm (mean 3.42 +/- 1.8) while % IAS thinning from 18 to 76% (mean 36.53 +/- 16.36%). Statistical analysis showed a significant positive correlation between age and ventricular end-systolic thickness and atrial systolic thickness and thinning. An insignificant correlation was found between age and % IAS thinning and between left atrial dimension and IAS tk and th. CONCLUSIONS: Our results demonstrate that IAS thickness increases by age; no correlation exists between IAS thinning and age. There is no difference between IAS thickness and thinning in patients with or without cardiac disease. We believe that the thickness of IAS can be considered hypertrophic only if it exceeds the value of 15 mm during both ventricular end-systolic and atrial systolic phases of the cardiac cycle. IAS thickness and thinning might be an additional parameter to evaluate systolic atrial function particularly with regard to maintenance of synus rhythm after conversion from atrial fibrillation as well as to better understand its role in determining the filling of ventricles in different clinical conditions.

Left ventricular hypertrophy is associated with a stronger impairment of non-oxidative glucose metabolism in hypertensive patients.

Hypertensive patients with left ventricular hypertrophy (LVH) have a higher degree of hyperinsulinaemia than hypertensive patients without LVH. Obese patients with LVH have also been demonstrated to have a very low glucose disappearance rate after an intravenous glucose bolus. No studies have investigated the difference in insulin action and substrate oxidation in hypertensive patients with and without LVH. For this reason 36 subjects were enrolled for our study: (1) healthy control subjects (n = 10); (2) hypertensive patients without LVH (n = 12); and (3) hypertensive patients with LVH (n = 14). All subjects underwent an oral glucose tolerance test (OGTT, 75 g of glucose) and a euglycaemic hyperinsulinaemic glucose clamp (insulin infusion rate, 7.1 pmol (kg min)-1 for 120 min). In this latter test indirect calorimetry allowed substrate oxidation determination. Echocardiographic methods allowed LVH assessment. Hypertensive patients with LVH had the lowest insulin-mediated nonoxidative glucose metabolism compared to hypertensive patients without LVH (P < 0.01) and to healthy subjects (P < 0.001). In the whole group of hypertensive patients (n = 26), partial correlations showed left ventricular mass index (LVMI) associated with fasting plasma insulin levels (r = 0.44 P < 0.005), insulin-mediated whole body glucose disposal (r = -0.41 P < 0.01) and nonoxidative glucose metabolism (r = -0.33 P < 0.04) independently of age, body weight, systolic blood pressure and plasma catecholamines levels. In conclusion, our data provide evidence that LVH in hypertensive patients is associated with a worsening in nonoxidative glucose metabolism.

Chronic intake of pharmacological doses of vitamin E might be useful in the therapy of elderly patients with coronary heart disease.

Thirty elderly (mean +/- SEM: 73.8 +/- 2.1 y) nondiabetic, moderately obese (body mass index = 28.3 +/- 0.6 kg/m2) patients with stable effort angina underwent an oral-glucose-tolerance test and a euglycemic hyperinsulinemic glucose clamp before and after vitamin E supplementation (900 mg/d for 4 mo). The study was of a randomized, placebo-controlled, double-blind, and crossover design. Anthropometric indexes were stable throughout the study. Despite similar fasting and 2-h plasma glucose concentrations, vitamin E administration (compared with placebo) lowered fasting (88 +/- 14 and 68 +/- 9 pmol/L, P < 0.02) and 2-h (348 +/- 43 and 263 +/- 28 pmol/L, P < 0.05) plasma insulin concentrations, plasma triglyceride concentrations (1.34 +/- 0.06 and 1.07 +/- 0.03 mmol/L, P < 0.05), and the ratio of plasma LDL to HDL cholesterol (7.64 +/- 0.31 and 5.52 +/- 0.38, P < 0.02). Vitamin E administration was associated with higher nonoxidative glucose metabolism (18.1 +/- 0.5 and 10.6 +/- 0.7 mumol.kg lean body mass-1.min-1, P < 0.03) than was placebo administration during the euglycemic glucose clamp. We conclude that chronic intake of pharmacological doses of vitamin E might be useful in the therapy of elderly insulin-resistant patients with coronary heart disease.

Low fasting and insulin-mediated intracellular magnesium accumulation in hypertensive patients with left ventricular hypertrophy: role of insulin resistance.

Twenty-five hypertensive patients (13 males/12 females) with left ventricular hypertrophy (LVH) and 12 hypertensive patients (6 males/6 females) without LVH were studied. Both groups were matched for age, sex, body mass index, percentage body fat, arterial BP and known duration of hypertension. After a seven day wash-out period from antihypertensive treatment each subject underwent: (1) an oral glucose tolerance test, (2) an euglycemic hyperinsulinaemic glucose clamp (insulin infusion rate 7.1 pM/kg per min), (3) an echocardiographic determination of left ventricular mass index, and (4) 24h ECG Holter monitoring. All tests were performed in random order and on different days. All investigators were unaware of the patient groups. Hypertensive patients with LVH had lower fasting intracellular (erythrocyte) magnesium concentrations (1.85 +/- 0.06 vs. 2.07 +/- 0.04 mM; P < 0.001) but higher fasting plasma insulin concentrations (86 +/- 4 vs. 59 +/- 5 pM; P < 0.001) Glucose clamp study demonstrated a lower insulin-mediated glucose disposal (24.8 +/- 0.4 vs. 30.1 +/- 0.3 microM/kg of lean body mass per min; P < 0.05) and a net change in intracellular magnesium accumulation (17.9 +/- 1.3 vs. 27.3 +/- 1.8%, P < 0.01) in response to insulin infusion in hypertensive patients with LVH than in those without LVH. After adjustment for fasting plasma insulin levels and insulin-mediated glucose uptake, fasting and insulin-mediated erythrocyte magnesium accumulation were no longer different between the two groups. In conclusion, hypertensive patients with LVH compared with those without LVH have a lower intracellular magnesium content due a higher degree of insulin resistance.

Evidence for a relationship between oxidative stress and insulin action in non-insulin-dependent (type II) diabetic patients.

Ten healthy subjects and 30 non-insulin-dependent (type II) diabetic patients matched for age, gender ratio, body mass index, lean body mass (LBM), waist to hip ratio, and arterial blood pressure volunteered for the study. In all subjects, fasting plasma free radical (O2-) levels and basal membrane lipid fluidity (MLF) and protein mobility (MPM) were determined. The whole group of subjects underwent a euglycemic hyperinsulinemic glucose clamp with simultaneous indirect calorimetry for substrate oxidation determination. Diabetic patients versus controls displayed higher fasting plasma glucose (8.3 +/- 0.4 v 5.1 +/- 0.4 mmol/L, P +/- .001), O2- (0.48 +/- 0.02 v 0.16 +/- 0.02 mumol/L x min), and hemoglobin A1c ([HbA1C] 7.9% +/- 0.4% v 5.7% +/- 0.3%, P < .03) levels and a stronger reduction in basal MLF (0.243 +/- 0.006 v 0.318 +/- 0.009, P < .003) and basal MPM (0.348 +/- 0.003 v 0.518 +/- 0.010, P < .002). Whole-body glucose disposal (WBGD) and oxidative and nonoxidative glucose metabolism were also significantly lower in diabetics than in controls. In diabetic patients (n = 30), plasma O2- levels correlated with basal MLF (r = -.59, P < .005), basal MPM (r = -.84, P < .001), fasting plasma insulin level (r = .51, P < .004), WBGD (r = -.53, P < .002), and nonoxidative (r = -.45, P < .01) glucose metabolism. In conclusion, our results demonstrate that a relationship between plasma O2- levels and insulin action occurs in non-insulin-dependent diabetics.

Pharmacological doses of vitamin E and insulin action in elderly subjects.

Twenty elderly (77 +/- 0.4 y), nonobese [body mass index (in kg/m2) 26.4 +/- 0.5] subjects with normal glucose tolerance were submitted to a euglycemic hyperinsulinemic (3.5 pmol.min/kg) glucose clamp in a double-blind, crossover, randomized procedure after 4 mo treatment with either vitamin E (900 mg d-alpha-tocopherol/d, Ephynal; Roche, Milan, Italy) or placebo. Body mass index was practically unchanged throughout the study. After the glucose clamp, insulin-mediated stimulation 2 of whole-body glucose disposal (18.4 +/- 0.5 vs 26.1 +/- 0.6 mumol.min/kg lean body mass P < 0.02) was significantly potentiated by vitamin E rather than placebo administration. Furthermore, net changes in plasma vitamin E concentrations correlated with net changes in insulin-stimulated whole-body glucose disposal (r = 0.60 P < 0.003). Plasma vitamin E concentrations seem to play an important role in the modulation of insulin action in elderly people.

Insulin resistance and hypertension in the elderly. Optimal drug therapy.

Numerous trials have demonstrated the negative effects of some antihypertensive drugs upon glucose handling. Such findings seem particularly interesting in aged hypertensive patients who are also insulin resistant and affected by physiological changes in the renal and cardiovascular systems. It appears that calcium channel blockers and angiotensin converting enzyme (ACE) inhibitors are the most appropriate drugs to lower blood pressure in aged insulin-resistant hypertensive patients. All calcium channel blockers studied have displayed similar metabolic effects, while among the ACE inhibitors studied, lisinopril was associated with the best metabolic responses. beta-Blockers and thiazide diuretics have strong negative effects on glucose handling. Further studies are needed in order to investigate the metabolic effects of alpha 1-antagonists in aged patients with insulin resistance and hypertension.

[Bacterial endocarditis due to Erysipelothrix rhusiopathiae. A clinical case report]. / Endocardite batterica da Erysipelotrix rhusiopathiae. Descrizione di un caso clinico.

The authors describe an unusual case of bacterial endocarditis. A very rare etiologic agent, Erysipelothrix rhusiopathiae, was isolated. The patient was not fisherman or butcher and he did ot other risky job. Moreover the disease had an atypical course.

Total-body and myocardial substrate oxidation in congestive heart failure.

Congestive heart failure is a condition associated with increased plasma norepinephrine levels, which have been demonstrated to impair glucose handling. In the present study, 10 patients suffering from congestive heart failure and 10 healthy age- and body mass index-matched subjects were submitted to a hyperinsulinemic (insulin infusion rate, 0.5 mU/kg.min-1) glucose clamp, while simultaneous D-3H-glucose infusion and indirect calorimetry allowed for determination of glucose turnover parameters and substrate oxidation, respectively. On a separate day, basal local (myocardial) indirect calorimetry was also performed. Our data demonstrate that in congestive heart failure, fasting myocardial glucose oxidation (Gox) was inhibited with a simultaneous increase in lipid oxidation (Lox). In our patients, a significant decrease in total-body insulin-stimulated glucose metabolism (31.0 +/- 0.5 v 20.3 +/- 0.4 mumol/kg.min-1, P < .01) and nonoxidative glucose metabolism (18.9 +/- 1.1 v 11.0 +/- 0.5 mumol/kg.min-1, P < .05) was also found. Such latter changes were also associated with a simultaneous overdrive of Lox (0.4 +/- 0.2 v 1.9 +/- 0.2 mumol/kg.min-1, P < .02) that was correlated with an enhanced availability of plasma free fatty acids (FFAs).

Plasma vitamin C affects glucose homeostasis in healthy subjects and in non-insulin-dependent diabetics.

In aged healthy (n = 10) and non-insulin-dependent (type II) diabetic (n = 10) subjects matched for age [67.3 +/- 0.5 vs. 68.0 +/- 0.4 yr, P = not significant (NS)], body mass index (25.7 +/- 0.7 vs. 26.0 +/- 0.2 kg/m2, P = NS), gender ratio [6 males (M)/4 females (F) vs. 5 M/5 F], and mean arterial blood pressure (104 +/- 6 vs. 105 +/- 9 mmHg, P = NS), we determined the changes in insulin secretion and action after vitamin C infusion and the relative increase in plasma vitamin C levels. At the highest vitamin C infusion rate (0.9 mmol/min) the increase in plasma vitamin C levels did not affect B cell response to glucose, but it improved Conard's K values and whole body glucose disposal in healthy subjects and in diabetic patients. In both groups of subjects vitamin C-mediated increase in insulin action was mainly due to an improvement in nonoxidative glucose metabolism. After fasting, plasma vitamin C levels correlated with basal whole body glucose disposal (r = -0.44, P < 0.05; n = 20). After vitamin C infusion, percent change in plasma vitamin C level correlated with the percent decline in membrane microviscosity (r = 0.53, P < 0.01; n = 20) and increase in whole body glucose disposal (r = 0.63, P < 0.003; n = 20). In conclusion, plasma vitamin C levels seem to play a role in the modulation of insulin action in aged healthy and diabetic subjects.

Metabolic features of patients with and without coronary heart disease but with a superimposable cluster of cardiovascular risk factors.

BACKGROUND: Many studies have shown a significant association between the magnitude of insulin resistance and the plasma insulin levels in non-diabetic patients. It has also been shown that all major cardiovascular risk factors are associated with the presence of hyperinsulinemia or insulin resistance. However, studies have not addressed the possible metabolic differences in insulin action that can occur in patients with and without coronary heart disease (CHD) but with a superimposable cluster of risk factors. METHODS: Three groups of patients matched for age, sex, and lean body mass, but different in their absence of risk factors (group A; n = 8), presence of risk factors but no clinical and electrocardiographic signs of CHD (group B; n = 12), and the presence of risk factors, family history of CHD, and clinical and electrocardiographic signs of CHD (group C; n = 14) volunteered for the study. Patients in groups B and C were also matched for main risk factors. All patients were submitted to a euglycemic hyperinsulinemic glucose clamp during which a an infusion of 3H-glucose and indirect calorimetry facilitated the determination of glucose turnover parameters and substrate oxidation. RESULTS: Patients with CHD (group C) had the highest fasting plasma insulin levels (98 +/- 13 pmol/l) compared with patients in group B (86 +/- 4 pmol/l; P < 0.05) and in group A (63 +/- 4 pmol/l; P < 0.05) and the lowest insulin-mediated stimulation in non-oxidative glucose metabolism. Fasting lipid oxidation was similar in the three groups, but a stronger insulin-mediated inhibition in the control patients (group A) was found. Multiple regression analysis of the pooled data from the patients in groups B and C (n = 26) demonstrated that all risk factors considered correlated (t = 1.58, P < 0.04) with total body glucose disposal (TBGD) and accounted for 77% of the variability in TBGD. Furthermore, a separate analysis for groups B and C demonstrated a different contribution of all risk factors (89% and 65% for groups B and C, respectively) to the variability in TBGD. In group C patients, a multiple logistic regression analysis encompassing all risk factors studied, but also the family history of CHD, explained 92% of the variability in TBGD. CONCLUSION: In patients with and without CHD but with similar risk factors, a significant reduction in non-oxidative glucose metabolism occurs; nevertheless, such impaired glucose handling seems to be worsened in the presence of CHD. Further studies will be needed to determine the cause of such differences.

Slowing of mitral valve annular calcium in systemic hypertension by nifedipine and comparisons with enalapril and atenolol.

Mitral annular calcium (MAC) is a condition that often occurs in patients with systemic hypertension. To evaluate the effectiveness of nifedipine in preventing MAC, 223 patients with systemic hypertension of recent onset and without MAC were selected and randomly enrolled in 3 groups: group 1 (76 patients) received nifedipine; group 2 (72 patients) received enalapril; and group 3 (75 patients) received atenolol. After 5 years, these treatments significantly reduced systolic (p < 0.001) and diastolic (p < 0.05) blood pressure (BP) in 3 treated groups. M-mode echocardiography revealed MAC only in 2 patients in the nifedipine group (2.6%), in 13 in the enalapril group (18%) and in 15 in the atenolol group (20%). The degree of MAC was mild (< 5 mm) in the 2 patients in group 1, in 5 of the 13 in group 2, and in 6 of the 15 in the group 3, whereas it was severe (> 5 mm) in the remaining 8 in the enalapril group and in the other 9 in the atenolol group. There was also a significant correlation in the degree of MAC, left atrial enlargement and mitral regurgitation. In addition, atrial fibrillation and atrioventricular conduction defects were associated with severe MAC. These results indicate that nifedipine is an effective drug both in the long-term management of systemic hypertension and in preventing or delaying MAC.

Daily vitamin E supplements improve metabolic control but not insulin secretion in elderly type II diabetic patients.

OBJECTIVE: To investigate the potential metabolic benefits deriving from daily vitamin E administration in type II diabetic patients. RESEARCH DESIGN AND METHODS: Twenty-five type II diabetic patients were invited to randomly take placebo or vitamin E (d-alpha-tocopherol; 900 mg/day) along a similar 3-mo period in a double-blind, crossover procedure. A wash-out period of 30 days separated the two treatment periods. At the end of each treatment period blood samples were drawn for plasma metabolites determination, and an intravenous glucose tolerance test (25 g of glucose as bolus in 3 min) was performed. During this study oral hypoglycemic agents were not discontinued or changed in their dosage. RESULTS: Chronic vitamin E administration reduced plasma glucose (8.3 +/- 0.3 vs. 7.5 +/- 0.2 mM, P > 0.05), triglycerides (2.27 +/- 0.08 vs. 1.67 +/- 0.09 mM, P < 0.02), free fatty acids (786 +/- 116 vs. 483 +/- 64 mM), total cholesterol (6.74 +/- 0.09 vs. 5.50 +/- 0.10 mM, P < 0.05), low-density lipoprotein cholesterol (4.73 +/- 0.11 vs. 3.67 +/- 0.07 mM, P < 0.04), and apoprotein B (1.7 +/- 0.3 vs. 1.0 +/- 0.1 g/L) levels but did not affect beta-cell response to glucose. HbA1 levels (7.8 +/- 0.3 vs. 7.1 +/- 0.5%, P < 0.05) were also significantly lowered after chronic vitamin E administration. CONCLUSIONS: Daily vitamin E supplements seem to produce a minimal but significant improvement in the metabolic control in type II diabetic patients. More studies are necessary before conclusions can be drawn about the safety of vitamin E during long-term administration.