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P Valensi

Publications and source records attributed to P Valensi.

At least 19 recordsLinked to original sources
PubMed1992

[Pathogenic role of hyperinsulinism in macroangiopathy. Epidemiological data].

The hypothesis of the atherogenic role of endogenous insulin was based on a series of epidemiological studies. Several large-scale prospective studies have demonstrated that diabetes constitutes an independent risk factor for cardiovascular disease. However, neither the duration of diabetes nor the blood glucose level appear to be predictive of the incidence of a cardiovascular accident. More recent prospective studies (Finland, Australia, Paris) in non-diabetic men have shown that hyperinsulinemia, while fasting or after glucose stimulation, constitutes a risk factor for fatal myocardial infarction, but they failed to show whether diabetes or the blood glucose level constituted a risk factor for the disease. Cross-sectional studies have provided similar results. Insulin resistance affects the majority of non-insulin-dependent diabetics and glucose-intolerant patients. It has also been observed in 25 percent of non-obese subjects with a normal glucose tolerance test. Associated hyperinsulinemia prevents the development of diabetes, but diabetes appears when the beta-cell function is altered and can no longer maintain this hyperinsulinemia. However, hyperinsulinemia is not devoid of cardiovascular consequences. Insulin resistance and hyperinsulinemia are also observed in patients with essential hypertension: a correlation between plasma insulin and blood pressure has been reported. These data, together with other experimental arguments, suggest that excessive endogenous insulin may participate in the rise in blood pressure. Furthermore, hypertensive patients have a high risk of coronary heart disease and this risk is not significantly decreased by anti-hypertensive treatments. This is probably related to the presence of other metabolic risk factors associated with insulin resistance: hyperinsulinemia, glucose intolerance, hypertriglyceridemia, decreased HDL cholesterol. These metabolic disorders have been grouped together under the term "syndrome X". All of these risk factors are probably also involved in the development of coronary heart disease in general population. In conclusion, epidemiological studies now suggest that insulin resistance and hyperinsulinemia increase the risk of hypertension and coronary heart disease. A great many experimental studies support this hypothesis. Lastly, it can be proposed that the increased cardiovascular risk in non-insulin-dependent diabetics is related to the fact that they belong to a larger group of insulin-resistant subjects. The management of diabetes, hypertension, and all of the metabolic abnormalities would appear to be the only way of reducing the incidence of cardiovascular disease.

Coronary Disease↗
PubMed1992

[Diabetic neuropathy. Difficulties of diagnosis and choice of tests].

None of the classifications of diabetic neuropathy already published is perfect. "Experts" now recommend an operational classification based on the quantification of signs and neurological deficits, on an electrophysiological investigation and on an easy exploration of autonomic neuropathy. Quantitative evaluation of symptoms can be performed with questionnaires or scales. Quantitative evaluation of deficits can be performed with devices which quantify vibratory and thermic sensations; reproducibility of the results is not yet perfect, but it represents a clear progress over clinical examination. Investigation of the autonomic control of cardiovascular system with standardized tests is the simplest way of exploring the vegetative nervous system; these tests have a fair sensitivity and an excellent reproducibility. Therapeutic trials, particularly with aldose reductase inhibitors or gangliosides, require this wide panel of neurological investigations.

Diabetic Neuropathies↗
PubMed1992

Comparative effects of diabetes mellitus and hypertension on physical properties of human large arteries.

OBJECTIVES: The effects of hypertension and diabetes on the physical properties of large arteries were compared in men. BACKGROUND: Although these two diseases are linked to vascular stiffening, no study has analyzed whether the arterial rigidity in diabetes is as substantial as in hypertension. METHODS: Noninvasive measurements of brachial artery mean pressure, diameter (pulsed Doppler study) and compliance (pulse wave velocity) were obtained in 29 men: 11 control subjects, 9 hypertensive nondiabetic patients and 9 diabetic normotensive patients. Individual diameter- and compliance-pressure curves extrapolated from the measured diameter and mean pressure point with a logarithmic elastic model permitted calculation of isobaric diameter and compliance at the same pressure in each subject. RESULTS: Compared with control subjects, hypertensive patients had a larger brachial artery measured diameter and isobaric diameter (p < 0.01) and lower measured and isobaric compliance (p < 0.001, p < 0.01). Compared with control subjects, diabetic patients had lower measured and isobaric compliance (p < 0.01). Comparison of diabetic and hypertensive patients showed that measured diameter and isobaric diameter were decreased in the former (p < 0.01). In the control and hypertensive groups, mean pressure correlated positively with measured diameter and isobaric diameter (p < 0.01) and negatively with measured and isobaric compliance (p < 0.001 and p < 0.01, respectively). In the control and diabetic groups, fasting glucose correlated negatively with measured and isobaric compliance (p < 0.01, p < 0.05). CONCLUSIONS: Intrinsic alterations of the large artery independent of a stretching pressure effect reduce arterial elasticity similarly in those with hypertension or diabetes. The loss of compliance is related to the chronic elevation of blood pressure in hypertension and to that of glycemia in diabetes and is associated with a relative large artery vasoconstriction in diabetic patients as compared with patients with hypertension.

Adult↗
PubMed1992

Non-beta-adrenergic-mediated peripheral circulatory hyperkinesia in hyperthyroidism.

Systolic time intervals and brachial circulation, evaluated by pulsed Doppler in terms of arterial diameter, blood velocity and flow, and vascular resistance, were studied in 12 hyperthyroid patients and in 12 normal controls. In patients, arterial circulation was studied before and during mechanical exclusion of the hand, and hemodynamic measurements were repeated after beta-blocker treatment and after obtainment of euthyroid state. Compared with controls, patients had higher heart rate (P < 0.001), lower systolic time intervals (P < 0.05, P < 0.01), and higher blood velocity (P < 0.05). Beta blockade decreased heart rate (P < 0.05, P < 0.001) but did not change systolic time intervals and arterial circulation. Euthyroid state decreased heart rate (P < 0.01), preejection period (P < 0.01), and blood velocity (P < 0.01) and flow (P < 0.05). The decreases in velocity and flow before hand exclusion when euthyroid state was obtained were correlated with hyperthyroid values of velocity and flow respectively (r = 0.85, r = 0.90, P < 0.01, P < 0.001). Vascular resistance during hand exclusion was correlated negatively with serum T3 level during hyperthyroid and euthyroid states. Thus, thyroid hormones but not beta-adrenoreceptors participate in the peripheral hyperkinesia of hyperthyroidism.

Adrenergic beta-Antagonists↗
PubMed1992

[Microalbuminuria and hypertension in obese patients].

The present study was designed to evaluate the frequency of an increase in the urinary albumin excretion rate (UAER) and the factors involved in this parameter in non-diabetic obese patients; 122 non-diabetic obese patients were investigated. None had proteinuria or history of nephropathy or uropathy. Fourty of them had moderate hypertension. Compared with a group of 22 lean controls, UAER was significantly higher in the obese patients (19.0 +/- 2.0 (SEM) mg/24 h vs 3.2 +/- 0.6 mg/24 h, p < 0.001). UAER was elevated (> 20 mg/24 h) in 29 patients (23.7%). Prevalence of microalbuminuria was not significantly different in hypertensive than in normotensive patients. However UAER was significantly higher in the 32 patients with a family history of hypertension (29.6 +/- 6.3 mg/24 h vs 15.3 +/- 1.5 mg/24 h, p < 0.002). In patients with microalbuminuria, body weight was significantly higher (100.3 +/- 3.9 kg vs 91.8 +/- 1.9 kg, p < 0.05), plasma albumin was significantly lower (38.3 +/- 0.6 g/l vs 40.3 +/- 0.3 g/l, p < 0.005) and the estimated value of fractional albumin clearance was significantly higher. These results show the high frequency of microalbuminuria in non-diabetic obese patients. They suggest that UAER level may be an index of family hypertension in obese patients and that microalbuminuria is part of a widespread abnormality of the capillary permeability.

Adult↗
PubMed1991

Increased capillary permeability to albumin and diabetic neuropathy.

An increase in the capillary permeability to albumin (CPA) has been reported in diabetic patients. We observed this frequently with a non-invasive isotopic test derived from the Landis method, using 99mTc-albumin and measuring residual radioactivity externally after removal of forearm venous compression. Evidence of the independent effects of hypertension and microangiopathy on CPA has already been found. The present work was designed to investigate CPA using the same test on diabetic patients without retinopathy and clinical proteinuria. Some of these patients had objective clinical distal and symmetrical polyneuropathy. Neuropathy was clearly present in 10 of the 11 patients with an abnormal test unexplained by causes other than diabetes and in only one of the 17 patients with a normal test. The most frequent abnormality affected the late radioactivity disappearance curve, which probably reflects an impaired lymphatic wash-out of interstitial albumin. These results strongly suggest a link between peripheral neuropathy and diabetic functional microangiopathy. An elevated blood flow secondary to sympathetic nerve failure may induce an increase in CPA and a saturation of lymphatic pumping which could also be deficient due to impaired lymphatic innervation.

Adult↗
PubMed1991

Effects of nifedipine and nitrendipine on insulin secretion in obese patients.

Data on the influence of calcium antagonists on glucose tolerance and insulin release in humans are conflicting. The present double-blind, double-dummy, controlled trial was designed to investigate the effect of a short-term (7 days) treatment with nitrendipine, 20 mg b.i.d.; nitrendipine, 20 mg once daily; or placebo on blood glucose and plasma insulin and C-peptide response to an intravenous glucose load in mildly or transiently hypertensive nondiabetic obese patients. No statistically significant differences were found in fasting glucose, insulin, and C-peptide, or in the glucose disappearance rate and in any of the parameters for insulin and C-peptide response after i.v. glucose, between the three groups of patients. However, a slight decrease in early insulin response to glucose was observed in the nifedipine and the nitrendipine groups. This study confirms that calcium antagonists have no clinically relevant effect on glucose homeostasis even if a slight alteration of insulin release after glucose load cannot be ruled out.

Adult↗
PubMed1991

[Comparison of isobaric effects of hypertension and diabetes mellitus on geometric and elastic properties of human arteries].

Hypertensive and diabetic mellitus diseases are known to increase stiffness of the arterial wall. However these alterations probably involve different mechanisms. To this end, we compared the effect of hypertension and diabetes on large artery caliber and elasticity at real pressure conditions and at the same level of pressure. Nine poorly controlled non insulino-dependent diabetic men without hypertension and 9 non-diabetic essential hypertensive men underwent measures of lumen diameter (pulsed Doppler) and segmental compliance (Bramwell and Hill formula; pulse wave velocity) at the brachial artery. Isobaric diameter and compliance were deduced from a non linear model, comparing diameter and pressure on one part, and compliance and pressure on the other. Pulse wave velocity was similarly increased in both diseases (11.5 +/- 1 vs 12.8 +/- 1 m/s; NS; respectively in diabetes and hypertension). Both measured and isobaric diameters were smaller in diabetic patients (4.05 +/- 0.2 vs 5.03 +/- 0.2 mm, p less than 0.1% for the measured diameters respectively in diabetes and hypertension and 4.06 +/- 0.2 vs 5.01 +/- 0.2 mm, p less than 1% for isobaric diameters). The measured and isobaric compliances were not significantly different (2.38 +/- 0.4 vs 2.08 +/- 0.2 cm/mmHg10(-4), NS, for the measured compliance respectively in diabetes and hypertension; 2.28 +/- 0.4 vs 2.4 +/- 0.2, NS for the isobaric compliance). After correction of the effect of mechanical arterial stretch induced by the different blood pressure level of the two groups, significant reduction of diameter in diabetic subjects persisted and isobaric and measured compliances remained unchanged between groups.

Adult↗
PubMed1991

Effect of nifedipine and nitrendipine on insulin release in non-diabetic obese patients: a double-blind, placebo-controlled study.

Calcium antagonists are known to decrease insulin release in vitro. In vivo, their effects on insulin secretion and glucose tolerance are more controversial. We carried out a double-blind, double-dummy, controlled trial to study the effects of nifedipine (40 mg/day; n = 9), nitrendipine (20 mg/day; n = 9) and placebo (n = 10) on insulin release in 3 parallel groups of obese patients with mild or transient hypertension and a normal oral glucose tolerance test. The treatment lasted one week. Patients were asked not to modify their diet throughout the trial, and their body weight did not vary significantly. A 2-hour i.v. glucose tolerance test was performed twice in every patient, just before the first drug intake and one hour after the last one. The following parameters were measured or calculated during each test: basal, peak and early phase levels of blood glucose, insulin and C-peptide; glucose disappearance rate; and glucose, insulin and C-peptide incremental areas under the time-curves. On day 1, the 3 groups of patients were comparable for age, sex, body weight and every biological parameter. One-way analysis of variance did not show any significantly different evolution of those parameters between the 3 treatment groups, but calcium antagonists tended to slightly reduce the early phase of insulin release compared with placebo.

Adolescent↗
PubMed1991

Stimulating effect of forskolin on thyroxine secretion. Influence of calcium.

The aim of this study was to determine, with a rat thyroid fragment perifusion system, the short-term (20 min) effect of forskolin (FK), an adenylate cyclase activator, on T4 secretion, the effect of forskolin on T4 secretion stimulated by theophylline and TSH, and the role played by calcium in the forskolin effect. A dose-dependent effect on T4 secretion was obtained with forskolin, from 10(-8) to 10(-4) mol/l, with a maximal effect between 10(-6) and 10(-5) mol/l. The effect of forskolin was not increased by theophylline. The combined stimulation with forskolin and theophylline induced a T4 release which remained significantly lower than the effect of 22 or 65 mIU/ml TSH. Forskolin slightly increased the stimulating effect of 22 mIU/ml TSH but significantly decreased the effect of 65 mIU/ml TSH. A reduction in the buffer calcium concentration slightly decreased the effect of the forskolin and theophylline stimulations and the effect of the combined stimulation with forskolin and theophylline without suppressing completely the effect of these stimulations. This study demonstrates that 1) low concentrations of forskolin are able to induce a significant T4 release during short-term stimulations; 2) calcium is necessary in order to obtain a maximum effect of adenylate cyclase activation on T4 release; 3) the part of the thyroid hormone response to TSH which is mediated by adenylate cyclase activation is relatively small.

Animals↗
PubMed1990

Effect of beta adrenoceptors and thyroid hormones on velocity and acceleration of peripheral arterial flow in hyperthyroidism.

Brachial artery flow patterns were studied in 10 hyperthyroid and 10 normal subjects. Mean blood velocity and flow were evaluated by pulsed Doppler, and peak systolic acceleration was calculated by computer-assisted digitization of the instantaneous velocity curve. Compared to control subjects, hyperthyroid patients had higher velocity and flow (p less than 0.01, p less than 0.02) and higher peak systolic acceleration (p less than 0.01). In hyperthyroid patients, measurements were repeated after (1) mechanical exclusion of the hand from brachial circulation, (2) short-term beta-blocker treatment and (3) inducement of the euthyroid state. Exclusion of the hand reduced velocity and flow (p less than 0.001) but did not change peak systolic acceleration. Beta blockade induced disparate changes of velocity and flow but reduced peak systolic acceleration (p less than 0.05). In the euthyroid state, decreased blood velocity (p less than 0.01), flow (p less than 0.02) and acceleration (p less than 0.02) were observed. A hyperkinetic arterial circulation consisting of an increase in both velocity and acceleration is thus observable in hyperthyroidism. Hand exclusion showed that velocity seems to be influenced by peripheral factors while beta blockade suggests that acceleration is dependent of beta 1 adrenoceptors. Comparison between euthyroidism and hyperthyroidism indicates that both mean blood velocity and peak systolic acceleration are influenced by thyroid hormones.

Adrenergic beta-Antagonists↗
PubMed1990

Erythrocyte deformability in diabetes and erythrocyte membrane lipid composition.

Erythrocyte deformability was assessed in 40 diabetic patients, 24 insulin-dependent (IDD) and 16 non-insulin-dependent (NIDD), by measuring the initial filtration flow rate of whole blood, isolated red blood cells (RBC), and isolated RBC membranes with the Hanss hemorheometer, and its relationship to the plasma and ghost membrane lipid composition was investigated. RBC deformability was significantly reduced, whereas the deformability of the isolated RBC membranes did not differ significantly from the controls. In the plasma, the triglycerides were high, the high-density lipoprotein (HDL) cholesterol was reduced, and the ratio of total cholesterol over HDL cholesterol was high as compared with the controls. The RBC lipid composition expressed in mumol lipids/10(10) RBC showed significantly lower levels of free cholesterol, sphingomyelines, and phosphatidylcholine, which are the lipids principally located on the outer layer of the RBC membranes. These data suggest that in both IDD and NIDD patients, there may be a relation between these modifications in the RBC lipid composition and rheological impairment of the RBC.

Cholesterol↗
PubMed1990

Transport of thyroid hormones by human erythrocytes: kinetic characterization in adults and newborns.

The uptake of [125I]T3 and [125I]T4 by human erythrocytes was studied. The erythrocytes were obtained from adult subjects (28-41 yr old) and suspended in a protein-free medium. The half-times of equilibration for both T3 and T4 were 6 min. At equilibrium, T3 was concentrated 55-fold inside the cells, while T4 was concentrated 40 times, but these accumulations were not dependent on either cellular ATP or the transmembrane Na+ gradient. The amounts of cell-associated thyroid hormones were 20 times (T3) and 17 times (T4) higher than the amounts of free extracellular hormones at 5 X 10(9) erythrocytes/mL (the blood concentration). Oligomycin and phloretin inhibited T3-saturable transport (but not T4 transport) independently of cellular energy. We suggest that thyroid hormones are concentrated by intracellular trapping. The rates of T3 and T4 efflux from preloaded erythrocytes were similar to the influx rates. The initial velocities of T3 (but not T4) uptake and efflux were 70% saturable. The uptake was specific because the unlabeled analogs T4, triiodothyroacetic acid, rT3, D-T3, and D,L-thyronine inhibited [125I]T3 uptake 60, 125, 160, 190, and 1600 times less, respectively, than did unlabeled T3. The kinetic parameters of T3-saturable uptake, Km, and maximum velocity were determined for three groups of subjects: newborns, 28 to 41-yr-old adults, and 76 to 90-yr-old adults. The Km (67 nmol/L in 28 to 41-yr-old adults) was not age dependent, BUT the maximum velocity was significantly higher in newborns than in adults. We conclude that T3 transport across the human erythrocyte membrane is mediated mainly by facilitated diffusion, whereas T4 transport results from free diffusion. Human erythrocytes might act as a circulating pool of thyroid hormones, especially T3 in newborns.

Adenosine Triphosphate↗
PubMed1989

Effect of nifedipine on thyrotropin, prolactin, and thyroid hormone release in man: a placebo-controlled study.

Nifedipine (10 mg tid) or placebo was administered in a randomized double-blind trial for 1 wk to 2 groups of 10 mildly hypertensive euthyroid patients. Hormonal concentrations (thyrotropin [TSH], prolactin [PRL], thyroxin, triiodothyronine, and reverse triiodothyronine) before and during a TRH test were assessed in the 2 groups before (D0) and after (D7) each treatment. Parameters of the TRH test were determined (peak values, area under the curve [AUC], release [Kr], and elimination [Ke] rate constants) and their D7:D0 ratios were compared in the 2 groups. The TSH (peak values and Kr) and PRL (peak values and AUC) responses to TRH were significantly decreased in the nifedipine group compared to the placebo group. Neither basal nor TRH-stimulated thyroid hormone levels were modified. These results confirm experimental data but seem to be clinically irrelevant.

Adult↗
PubMed1989

Ultradian, circadian and seasonal variations of plasma progesterone and LH concentrations during the luteal phase.

The circadian variations in plasma progesterone (P) and LH concentrations were investigated in six women, aged 23-40 years. All were studied in the mid-luteal phase (7 +/- 2 days after LH mid-cycle surge). Experiments were conducted in autumn and in spring. Blood samples were obtained every 15 min for 24 hr. Plasma P and LH concentrations were measured by RIA. Each subject's time-series was analysed using three methods; visual inspection (chronogram), spectral analysis to estimate component periods of rhythms (tau) and cosinor analysis to quantify the rhythms parameters. Marked temporal variations in plasma P concentration were observed in each subject. The maximal variations over a 24-hr period, ranged between 13-58.5 mmol/l. Differences related to sampling time were statistically validated by ANOVA (p less than 0.00001). Significant harmonic periods were detected by spectral analysis but differed among subjects. In all subjects but one, a circadian rhythm was detected. The acrophase location was similar (about 0700 hr) in the four subjects studied in autumn, but ranged from 1940 to 0320 hr in those studied in spring. An ultradian rhythm with tau = 8 hr was also validated in six time-series with similar acrophases (about 0200, 1000, and 1800 hr). Cosinor analysis of pooled data revealed that the 24-hr, 12-hr, and 8-hr rhythms were statistically significant (p = 0.001) in autumn. algebraic sum of these three cosine functions yielded a circadian waveform with peak-times occurring near 0300 and 1130 hr and a trough-time about 2200 hr. In spring, the circadian pattern appeared quite different, and peak-times were found near 0700 and 2000 hr, and trough-times near 0300 and 1500 hr. Furthermore, the 24-hr mean of P was higher in autumn (28.9 +/- 0.4 nmol/l) than in spring (17.2 +/- 0.4 nmol/l), p from ANOVA less than 0.00001. The evidence for a similar circadian LH pattern is not as strong. Seasonal, circadian and ultradian rhythms characterize the physiologic time structure of plasma P concentration in mid-luteal phase.

Activity Cycles↗
PubMed1989

[Value of endomyocardial biopsy in congestive heart failure in diabetics without coronary disease].

Two cases of congestive heart failure in diabetic females are reported. One patient had moderate hypertension. Echography and angiography revealed a low-output dilated cardiopathy and ruled out the possibility of coronary artery stenosis and thin amyloid deposits were found in one patient. The evolution was favorable with a low-salt diet, associated with diuretic and vasodilator treatments. These case reports confirm the existence of a diabetic myocardiopathy, which may lead to congestive heart failure. They justify a complete hemodynamic analysis and a histopathological evaluation of the myocardium when this complication occurs.

Aged↗