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Biomedical subjects

P Valensi

Publications and source records attributed to P Valensi.

At least 91 records · Page 5Linked to original sources
PubMed1996

Diabetic neuropathy in elderly patients. What can be done?

The prevalence of diabetes mellitus increases markedly with age. Furthermore, advancing age is a strong risk factor for diabetic neuropathy, independent of the duration of diabetes mellitus and glycaemic control. Several biological changes occurring during the aging process may account for the facilitating effect of age on diabetic neuropathy. These include an increase in the production of advanced glycosylation end-products (AGEs), a defect in the polyol pathway, nerve vascular alterations and impaired resistance to oxidative stress. The clinical diagnosis of diabetic neuropathy is often difficult in elderly patients. The relationship between symptoms and neuropathy and that between neuropathy and diabetes mellitus are more difficult to ascertain in elderly patients due to age-related changes in the peripheral and autonomic nervous system and associated diseases frequently encountered in this population. Diagnosis of diabetic neuropathy is based on nerve conduction studies, vibratory perception threshold determination and assessment of autonomic function. For most of these tests, reference values are markedly influenced by age and their interpretation should use carefully age-adjusted reference intervals. Identification of peripheral diabetic neuropathy indicates a high risk of foot complications, such as ulcers and gangrene, often resulting in amputation, whereas cardiovascular autonomic neuropathy is associated with an increased risk of postural hypotension and coronary events. All these risks increase markedly with aging. Therapeutic trials in elderly patients with diabetic neuropathy are lacking. Treatment of diabetic neuropathy consists of achievement of better glycaemic control and treatment of symptoms related to neuropathy. Specific treatments capable of preventing or curing neuropathy are under investigation. The interesting results obtained with aldose reductase inhibitors in animal studies contrast with disappointing results in patients with diabetes mellitus. Other metabolic approaches, like antioxidants and gamma-linolenic acid, seem promising. Clinical complications of diabetic neuropathy in the elderly are often severe. Early detection is required, since at the present time a preventive approach is the most effective way to avoid or postpone debilitating complications. More research is needed to make effective curative treatments of diabetic neuropathy available.

Age Factors↗
PubMed1996

Effect of ramipril on insulin sensitivity in obese patients. Time-course study of glucose infusion rate during euglycaemic hyperinsulinaemic clamp.

To assess the effects of angiotensin converting enzyme (ACE) inhibitor on insulin action in obesity, five normotensive non-diabetic obese women were examined on two occasions as part of a double-blind, randomized, cross-over study involving ten days of treatment with either 1.25 mg ramipril or placebo. The study consisted of a euglycaemic hyperinsulinaemic clamp (two periods of insulin infusion at rates of 0.4 and 1 mU/kg/min, 2 h for each step) combined with indirect calorimetry. The most notable results involved a significantly faster time-course of glucose infusion rates during the first 30 min of each insulin infusion period [analysed by calculating slopes (S1 and S2)] after ramipril than placebo administration. The mean glucose infusion rates reached during the last 30 min of each insulin infusion period (G1 and G2), as well as the increases in carbohydrate oxidation rates during the clamp (C1-C0 and C2-C0) and the decreases in plasma nonesterified fatty acids (A0-A1 and A0-A2), were not significantly different after ramipril and placebo. According to robust principal component analysis of S1, S2, G1, G2, C1, C2, A1 and A2 (orthogonally to C0 and A0), insulin sensitivity was improved with ramipril as compared to placebo (p = 0.013). This study strongly suggests that a low dose of an ACE inhibitor increases the activation phase of insulin action in normotensive nondiabetic obese patients and may accelerate insulin action.

Adult↗
PubMed1996

Effect of insulin concentration on bioavailability during nasal spray administration.

The bioavailability of rapid-acting insulin administered as a nasal spray was studied in 6 type 1 (insulin-dependent) diabetic patients. They received long-acting bovine insulin (Ultratardum 40 U/ml, Organon) as basal treatment at 8 a.m. Rapid-acting insulin was also administered at 8 a.m., then at noon and 6 p.m, subcutaneously on day 1 as a 100 U/ml solution and intranasally by aerosol spray as a 100 U/ml and 500 U/ml with 1% (w/v) 9 lauryl ether solution on day 2 and day 3 respectively. On days 2 and 3, the dose of insulin was at least nine times higher than the subcutaneous dose on day 1. Free and total plasma insulin concentrations were assayed after the noon insulin administration. The peaks of the free and total plasma insulin levels were reached earlier and the return to basal levels was obtained earlier after nasal insulin administration than after insulin injected subcutaneously. The bioavailability of nasal spray insulin versus subcutaneous insulin with a 100 U/ml insulin solution was similar to that with a 500 U/ml insulin solution: 5.14 +/- 0.38% (m +/- SEM) and 4.64 +/- 0.46% according to the total plasma insulin level. This study suggests that the bioavailability of nasal spray insulin is not increased by increasing insulin concentration in our experimental conditions.

Administration, Intranasal↗
PubMed1996

Microalbuminuria in obese patients with or without hypertension.

OBJECTIVE: To evaluate the prevalence in obese patients of an increased urinary albumin excretion rate (UAER) and the factors involved in this parameter. SUBJECTS: Two hundred and seven nondiabetic obese patients with BMI = 34.7 +/- 5.7 (SD) kg/m2. None had proteinuria or a history of nephropathy or uropathy. Fifty-two had moderate hypertension. A control group of 22 lean healthy subjects was also studied. MEASUREMENTS: The UAER was determined from 24-h urine samples by means of immunonephelemetry laser method. Creatinine clearance was calculated. Glycemia and plasma C peptide at fasting and 120 mine after glucose oral administration, HbA1c, serum fructosamine, plasma total cholesterol and triglycerides, HDL and LDL cholesterol were measured. Food intakes were determined by dietary history. RESULTS: Compared with the control group, the UAER was significantly higher in the obese patients (18.0 +/- 20.1 mg/24 h vs 3.2 +/- 2.8 mg/24 h, P < 0.0001). It was elevated (> 30 mg/24 h) in 25 obese patients (12.1%) and in particular, in 19.2% of the obese patients with hypertension. It was significantly higher in the patients with android or mixed (both android and gynoid) obesity than in those with gynoid obesity (p = 0.050). Log UAER correlated negatively with the duration of hypertension (p = 0.038) and was higher in the patients with familial hypertension than in those without (p = 0.002). Log UAER correlated strongly with log creatinine clearance (p < 0.0001) and fractional albumin clearance (p < 0.0001). It correlated significantly with fasting and 120 min after glucose plasma C peptide concentrations (p = 0.018 and p = 0.046, respectively). Creatinine clearance was significantly higher in the patients with android or mixed obesity than in those with gynoid obesity (p = 0.001). Log creatinine clearance correlated negatively with age (p = 0.046), and log LDL cholesterol (p = 0.025) and positively with log lipid caloric intake (p = 0.014). CONCLUSION: These results show the high prevalence of microalbuminuria in nondiabetic obese patients and suggest the involvement of renal hyperfiltration. Microalbuminuria may be an indicator of familial hypertension in obese subjects. Insulin resistance may be involved in the increase in the UAER. Nutritional factors, particularly lipid intake, may contribute to this increase in the UAER via an increase in glomerular hyperfiltration.

Adult↗
PubMed1996

Erythrocyte rheological changes in obese patients: influence of hyperinsulinism.

OBJECTIVE: To investigate the rheological properties of RBC in obese subjects and the factors associated with their changes. SUBJECTS: Two consecutive studies of non diabetic obese subjects. MEASUREMENTS: Filtration index of RBC using the Hanss hemorheometer, RBC filterability using a cell transit time analyser and RBC aggregation measured on the Myrenne aggregometer. RESULTS: In both studies an increase in the filtration index of RBC, namely a reduction in their deformability, was found. In the first study the filtration index correlated negatively with hematocrit and positively with plasma C peptide levels. In the second study RBC filterability was also studied by the cell transit time analyzer in which there is no aggregate formation. The RBC transit time was not found to be different in the obese patients and in the controls, but RBC aggregation was increased and correlated significantly with body weight and BMI. RBC aggregation worsened after four days of hypocaloric diet. CONCLUSION: (1) obesity, independently of the other cardiovascular risk factors, is associated with significant changes in RBC rheology; (2) these changes are probably related for the most part to plasma factors, possibly via hyperinsulinemia, even if changes in the chemical composition of the RBC membrane are not excluded, (3) RBC aggregation worsens during the first days of a hypocaloric diet; (4) rheological changes in RBC seem to be another component of the insulin resistance syndrome.

Adult↗
PubMed1996

High prevalence of diabetes mellitus in patients with chronic hepatitis C. A case-control study.

OBJECTIVES AND METHODS: Extrahepatic manifestations have been reported in hepatitis C virus infection. To assess the relationship between diabetes mellitus and hepatitis C virus, we studied 152 patients with chronic hepatitis C and 152 controls hospitalized during the same period with hepatitis B virus (n = 51) or alcohol-induced (n = 101) liver diseases matched for age, sex, and the presence of cirrhosis (prevalence: 58%). Patients with jaundice, ascites, encephalopathy, prothrombin activity < 65%, or serum albumin < 35 g/L were excluded. RESULTS: Diabetes, defined by fasting serum glycemia > 1.4 g/L on at least two separate occasions or previously treated overt diabetes, was present in 38 patients with chronic hepatitis C (24%) and in 13 patients in the control group (9%, P < 0.002). In the 51 diabetic patients, irrespective of serum anti-hepatitis C virus status, 41 (81%) had non insulin dependent diabetes and 45 (88%) had cirrhosis. Family history of diabetes or obesity was observed in 2 (5%) of the diabetic patients with chronic hepatitis C and in 6 (46%) of the diabetic controls (P = 0.002). Plasma C-peptide (855 +/- 448 pmol/L versus 1,152 +/- 491 pmol/L, NS) and insulin levels (83 +/- 40 pmol/L versus 184 +/- 86 pmol/L, NS), assayed in 17 diabetic patients with chronic hepatitis C and in 9 diabetic controls, were lower in the former. The prevalence of HLA B8, DR3 or DR4 antigens, which was searched for in 77 patients with chronic hepatitis C, was not different in diabetic and non diabetic patients, and, was similar to the reference population. Serum islet-cell antibodies were found in 5 patients with chronic hepatitis C (3 with diabetes) and in 2 controls. CONCLUSION: Diabetes mellitus is more prevalent in patients with chronic hepatitis C than in patients with other liver diseases, and usually occurs in the absence of predisposing factors. These results suggest a role of hepatitis C virus infection in the pathogenesis of diabetes.

Adult↗
PubMed1996

[Erythrocyte rheology and heart hypertrophy in diabetes mellitus].

Reduced red cell filtration and increased aggregation have been reported in diabetic patients. Heart enlargement is a classical complication of high blood pressure but is also frequently encountered in diabetics. The aim of this work was to explore the relationship between rheological disorders and heart enlargement in diabetics and in an animal model of genetically diabetic rats. 1. Among a series of 92 patients with insulin-dependent or non-insulin-dependent diabetes mellitus, silent myocardial ischemia was evidenced in 28. Coronarography in 24 of these patients was strictly normal in 15. In the patients with angiographically normal coronary arteries, the coronary reserve was perturbed by intracoronary injection of papaverine. The left ventricular mass was normal in 79 patients. In patients with silent myocardial ischemia and angiographically normal coronary arteries, there was a positive correlation between left ventricular mass and red cell filtration index using the Hanss hemorheometer (n = 8, r = 0.954, p = 0.001). 2. Red cell stiffness was studied sequentially from 3 to 18 months in diabetic rats Goto Kakisaki (GK). In these rats, cardiac index (heart weight/body weight) was significantly higher than that in Wistors control rats (0.27 +/- 0.02% vs. 0.17 +/- 0.01%, p < 0.001) and was significantly correlated with erythrocyte magnesium (r = 0.920, p 0.026). Overall, the cardiac index in the rats was significantly correlated with red cell filtration (r = 0.370, p = 0.044). In GK rats, heart rate was significantly slower and systolic blood pressure was slightly higher than in control rats (telemetric measures). These findings show that in diabetes mellitus, heart enlargement may be determined by factors other than hypertension or sensitivity to sympathetic stimulation and might be favored by rheological changes and/or excessive intracellular magnesium. In patients with diabetes, the reduced coronary reserve could result in left ventricular hypertrophy but also rheological changes.

Animals↗
PubMed1996

[The Laser-Doppler microcirculation technique in the study of the orthosympathetic system in obese and non-insulin-dependent diabetic patients].

Parasympathetic as well as cardiovascular sympathetic activity is perturbed in the heart of diabetic and obese subjects. The aim of this work was to assess the effect of sympathetic control on variations in skin blood flow in 14 controls, 42 subjects with non-insulin-dependent diabetes and 57 obese subjects without diabetes. All subjects had normal blood pressure and had no other disease state which might modify skin blood flow. Laser-Doppler measurement of skin blood flow on the palmar aspect of the right first finger was performed at rest and during three tests which activate sympathetic tone: deep respiration (R), active orthostatism (O) and Valsalva's manoeuvre (V). In all 113 subjects, there was a negative correlation between age and the standard deviation of blood skin flow at rest (p = 0.001) and rate of blood skin flow decline during R (p = 0.002), O (p < 0.0001) and V (p = 0.005). The standard deviation and slope of decline in blood skin flow during R was lower than the initial levels in controls in 11 diabetes patients and 6 obese subjects and in 15 diabetic patients and 12 obese subjects respectively. The slope of decline in skin blood flow during O was positively correlated with plasma cholesterol (p = 0.002), red cell aggregation index (p = 0.013) and negatively with hematocrit, glucose control and creatininemia. The respective effects of these factors were analyzed in each of the three groups of subjects. These preliminary results suggest that 1) the variation in skin blood flow at rest is regulated by the sympathetic system and the drop in skin blood flow during the three tests activating the sympathetic system decreases with age, 2) sympathetic control of peripheral vasoconstriction is reduced in many diabetic and obese subjects, 3) red cell aggregability and different metabolic parameters and renal function have an effect.

Diabetes Mellitus, Type 2↗
PubMed1995

The effects of metformin on the capillary permeability to albumin in women patients with cyclic edema.

An experimental work has suggested the efficacy of metformin, an oral antidiabetic agent, on capillary permeability. This agent has been tested in 10 women patients with cyclic edema, 7 of them being obese. The capillary permeability to albumin studied by an isotope test derived from Landis's method was initially increased. After a mean of six-weeks of treatment the albumin retention and an index demonstrating the interstitial protein elimination through the lymph route were significantly improved. Concomitantly, the swelling feelings were reduced in 8 cases and the lower limb edema had decreased or disappeared in 8 of 9 patients who initially presented these symptoms. The effects of metformin are beneficial and have been observed to be independent of glycemic change. The results suggest a special effect of this agent on the microcirculation. Nevertheless, a controlled study is required.

Adult↗
PubMed1995

Cardiac autonomic function in obese patients.

OBJECTIVE: The aim of this work was to determine the presence and prevalence of alterations in cardiac autonomic function in obese, non-diabetic subjects. SUBJECTS: These were 121 obese people, 15 with glucose intolerance and none with diabetes, and a group of 40 healthy people. MEASUREMENTS: A series of five standardized tests was carried out, three of which were based mainly on parasympathetic control (heart rate response to Valsalva, deep breathing and lying-to-standing) and two on cardiovascular sympathetic function (blood pressure response to standing and to handgrip). RESULTS: The response to the deep breathing test correlated negatively with age, as it did in control subjects. At least one parasympathetic test, age-adjusted, was abnormal in 49 patients (40.5%). Five other patients had an abnormal handgrip test, and no patient had orthostatic hypotension. No correlation was found between the parasympathetic test results and sex or body mass index. Prevalence of cardiac autonomic dysfunction, considered to be present when at least one parasympathetic test was abnormal, did not differ according to a gynoid or android type of obesity. A significant negative correlation was found between heart rate response to deep breathing and fasting glycemia. CONCLUSION: It was concluded that cardiac autonomic dysfunction evidenced by means of simple, reliable, reproducible tests is frequent in the non-diabetic obese subject. This disorder could explain the poor cardiovascular prognosis associated with obesity. Whether it is a complication of obesity or a marker associated with certain kinds of obesity (of hypothalamic origin) remains to be clarified.

Adolescent↗
PubMed1995

[Multicenter evaluation of the Nutri-Expert Telematic System in diabetic patients].

Nutri-Expert is a system for self-monitoring and dietetic education, accessible through Minitel. A preliminary randomised evaluation of one hundred diabetic patients in the Midi-Pyrénées region showed that Nutri-Expert improved dietetic knowledge, dietary habits and metabolic balance. The aim of the present study was to show that the system can be successfully prescribed to patients by physicians outside the center which originated it, indicating the benefit of a wider use of Nutri-Expert, among the diabetic population. One hundred and fifty-five patients, recruited by six French centres of diabetology, used Nutri-Expert from their homes for six months. Clinical examination, tests of dietetic knowledge and biological tests, including lipid fractions, were carried out before and after six months of use. After six months, there was a significant improvement in the patients' dietetic knowledge and in some biological parameters. Nutri-Expert is thus useful even when prescribed by a centre other than the hospital which devised the system. It is an additional beneficial tool in the ambulatory management of diabetic patients.

Adolescent↗
PubMed1995

Clinical implications of impaired microcirculation.

Various types of microcirculation disturbances have been described in the course of systemic diseases, hypertension, diabetes, obesity, and the so-called "idiopathic oedema" syndrome. This article summarizes the relevant microcirculatory disorders associated with diabetes and their pathophysiology. These functional disorders occur before or in association with anatomical lesions of diabetic microangiopathy. Increased capillary permeability to albumin is frequently observed in diabetes. In a placebo-controlled trial, Daflon 500 mg, a purified, micronized, flavonoidic fraction, significantly improved this disorder. Patients complaining of an oedematous syndrome almost always have an increased extracellular fluid volume, probably largely due to increased capillary permeability. Diabetes and "idiopathic oedema" therefore constitute two examples of the major clinical implications of impaired microcirculation.

Capillary Permeability↗
PubMed1994

Gonadal and adrenal catheterization during adrenal suppression and gonadal stimulation in a patient with bilateral testicular tumors and congenital adrenal hyperplasia.

We report the case of a patient with bilateral testicular tumors and congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Catheterization of the left testicular and adrenal veins was performed. The presence of 11 beta-hydroxylated steroids in the spermatic veins confirmed the presence of testicular tumor secondary to adrenal rest cells. After adrenal suppression by dexamethasone combined with gonadal stimulation with hCG, a dramatic decrease in androgens and adrenal steroids was observed in the peripheral blood. Compared to the periphery, 21-deoxycortisol and 11 beta-hydroxy-delta 4-androstenedione levels remained higher than that of 21-deoxycorticosterone in the gonadal vein, but not in the adrenal vein, which seems to indicate that the nature of this ectopic tissue is unusual and that its sensitivity to dexamethasone depends on the adrenocortical zones. No rise in estradiol or testosterone was obtained after hCG stimulation, suggesting that all of the testicular tissue was inactive or destroyed. This finding was confirmed by histological examination.

Adrenal Glands↗
PubMed1994

Reduction of anti-thyroid hormone autoantibodies through plasma exchange and corticosteroid therapy.

Anti-thyroid hormone autoantibodies are occasionally found in Hashimoto's disease. They can interfere with thyroid hormone assays. The authors report the case of a 35-year-old hypothyroid (TSH between 29 and 46 microIU/ml) female patient with Hashimoto's disease and surprisingly high free and total levels of plasma T4 and T3 assayed with different solid phase radio-immunologic kits. Two immunoenzymologic assay kits gave a T4 level close to the one expected. The presence of circulating anti-T4, T3 and reverse T3 autoantibodies was demonstrated by precipitating the corresponding tracers with the patient's serum in the presence of polyethylene glycol without heterologous antibodies. The replacement treatment of 150 micrograms l-thyroxine allowed normalization of TSH at 3.4 microIU/ml, but the patient remained tired and anxious, with headaches and tachycardia. After discontinuing treatment for one month a series of four plasma exchanges was carried out in six days. After the first exchange the binding percentages were already much lower and went even lower after the other exchanges. After the fourth one, the free T4 and T3 levels were closer to the expected levels:7.3 pmol/l (N:10-30 pmol/l) and 4.3 pmol/l (N:3-9 pmol/l). Treatment by prednisone made it possible to maintain the percentages of binding to the three tracers for two weeks at the levels reached after the fourth plasma exchange. Two months after discontinuing corticosteroid treatment they returned to the initial levels and were again interfering with the free T4 and T3 assays. This finding suggests that usefulness of the thyroid hormone immuno-enzymologic assay, which apparently is not affected by the anti-thyroid hormone autoantibody interference.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗