Biomedical subjects

P Valensi

Publications and source records attributed to P Valensi.

At least 55 records · Page 3Linked to original sources

PubMed2000

Short-term protein and energy supplementation activates nitrogen kinetics and accretion in poorly nourished elderly subjects.

BACKGROUND: An increase in protein intake exerts a stimulating effect on protein kinetics in children, young adults, and healthy elderly persons. However, there are few data on the response to such dietary changes in malnourished elderly subjects, despite important medical implications in this population. OBJECTIVE: The objective of this study was to determine the metabolic response to short-term nutritional supplementation in moderately malnourished elderly subjects. DESIGN: The influence of 10 d of supplementation (1.67 MJ/d and 30 g protein/d) on body composition, resting energy expenditure, and whole-body protein kinetics was studied in 17 malnourished elderly patients and 12 healthy young adults. A control group of 6 malnourished elderly patients received no supplementation. RESULTS: Supplemented elderly subjects had a significantly greater fat-free mass gain than did unsupplemented elderly subjects (1.3 and 0.1 kg, respectively; age effect, P < 0.05; diet effect, P < 0.02) and a significantly greater increase in fasting rate of protein synthesis than did young supplemented subjects (0.6 and 0.2 g*kg FFM(-1)*11 h(-1); age effect, P < 0.05). The net protein balance in the supplemented elderly subjects in the fed state was positively correlated with protein intake (r(2) = 0.46) and in the fasted state was negatively correlated with protein intake (r(2) = 0.27). The sum of these regressions is a line with increasingly positive net diurnal protein balance produced by increasing protein intake. CONCLUSION: These data provide evidence of a short-term anabolic response of protein metabolism to dietary supplementation in malnourished elderly patients that is likely to improve muscle strength and functional status.

Absorptiometry, Photon↗

PubMed2000

Lamin A/C gene: sex-determined expression of mutations in Dunnigan-type familial partial lipodystrophy and absence of coding mutations in congenital and acquired generalized lipoatrophy.

Missense mutations of the lamin A/C gene, LMNA, have been recently identified in Dunnigan-type familial partial lipodystrophy (FPLD), which belongs to a heterogeneous group of rare disorders affecting adipose tissue distribution and metabolism. In this study, we sequenced the LMNA coding region from patients presenting with FPLD or other forms of lipodystrophy. We identified two heterozygous mutations in exon 8, R482W and R482Q, in FPLD patients (six families and one individual) with various clinical presentations. In addition, we found a novel heterozygous mutation (R584H) in exon 11, encoding specifically the lamin A isoform, in a patient with typical FPLD. Clinical and biochemical investigations in FPLD patients revealed that the expression and the severity of the phenotype were markedly dependent on sex, with female patients being more markedly affected. In subjects with generalized lipoatrophy, either congenital (13 case subjects) or acquired (14 case subjects), or Barraquer-Simon syndrome (2 case subjects), the entire LMNA coding sequence was normal. Although FPLD mutations are predominantly localized in exon 8 of LMNA, the finding of a novel mutation at codon 584, together with the R582H heterozygous substitution recently described, confirms that the C-terminal region specific to the lamin A isoform is a second susceptibility region for mutations in FPLD.

Adipose Tissue↗

PubMed2000

[Dysfunction of the coronary microcirculation in type 2 diabetic patients].

A failure of coronary blood flow to increase during cold pressor test has been shown in patients with coronary atherosclerosis and impaired metabolic coronary vasodilatation in response to atrial pacing has been demonstrated in diabetic patients without significant epicardial artery stenoses. This study was designed to evaluate coronary microvascular adaptation to increased myocardial oxygen demand in response to sympathetic stimulation in diabetic patients with angiographically normal coronary arteries. Microvascular coronary adaptation to increased myocardial oxygen demand due to sympathetic stimulation evoked by the cold pressor test has been examined in 22 type 2 diabetic patients and in 15 control subjects with angiographically normal coronary arteries and no other risk factors. Coronary blood flow was calculated by measuring mean flow velocity in left anterior descending coronary artery by intracoronary Doppler and cross sectional area of the artery by digital angiography. Results show that despite a similar increase in rate-pressure product in the 2 groups (+22.6 +/- 12.4% in diabetic patients and +31.8 +/- 8.2% in control subjects, NS), coronary blood flow increase in left anterior descending artery was significantly lower in diabetic patients than in control subjects (+14.7 +/- 19.8% vs +75.5 +/- 13.5%, respectively, p = 0.0001). In addition, when there was a positive correlation between the 2 parameters in control subjects (R = 0.651, p < 0.01), there was no relationship in diabetic patients (R = 0.054). In conclusion, this study demonstrates that vasodilatation of coronary microcirculation in response to sympathetic stimulation evoked by cold pressor test is impaired in type 2 diabetic patients without epicardial artery lesions. This microvascular impairment during sympathetic stimulation may explain exercise-induced myocardial perfusion abnormalities observed in these patients and may impair microcirculatory coronary vasodilatation during current life stress episodes such as exercise, mental stress or cold exposure.

Adaptation, Physiological↗

PubMed2000

[Hemodynamic consequences of endogenous hyperinsulinism in obese rats with lesions of the ventromedial hypothalamus].

The rat with ventromedian hypothalamus lesions (VMH) is characterized by massive obesity, hyperinsulinemia, increase in parasympathetic tonus and sympathetic depression. The aim of this study was to examine in this model the hemodynamic changes and the baroreflex response and to compare the data with the evaluation of beta adrenergic sensitivity. In VMH rats and Sham operated rats hemodynamic parameters were followed until 8 weeks after operation. Heart rate (HR) and blood pressure (BP) were monitored each week during 24 hours by a telemetric system, a catheter being implanted in aorta. In VMH, HR was significantly lower by the first week (p = 0.02) and until the last measurement. Systolic BP increased progressively in the two groups but was higher in VMH only at 8 weeks (p = 0.03). Compared with Sham rats, 5 days after operation, the percentage of HR acceleration in response to atropine and isoprenaline was significantly higher in VMH, whereas HR response to sodium nitroprussiate was similar in the two groups. Plasma epinephrine and norepinephrine levels were significantly higher in VMH rats. The density of cardiac beta receptors decreased from 15 days to 3 months after operation, similarly in VMH and Sham rats. The affinity of cardiac beta receptors remained stable during the same period and very similar in VMH and Sham rats. This study suggests that in VMH rats 1. bradycardia results mainly from an increase in parasympathetic tone; 2. the increase in reflex tachycardia described in normal rats after insulin infusion needs a normal activity of the sympathetic nervous system; 3. catecholamine levels may be increased despite sympathetic depression, probably as a result of an increase in adrenomedullary secretion possibly due to endogenous hyperinsulinemia; 4. the lack of hypertension in this model including a massive obesity is likely to result from the proper vasodilatory effect of insulin.

Adrenergic Agonists↗

PubMed2000

[Blood pressure and heart rate regulation in diabetics].

Cardiac autonomic neuropathy (CAN) is frequent in subclinical stages. Its prognostic value has been demonstrated. Cardiac autonomic neuropathy induces different functional cardiac changes, especially a reduction in left ventricular contractility and changes in ventricular repolarisation. It is also associated with changes in the daily variations in blood pressure. The association of CAN and silent myocardial ischaemia significantly worsens the prognosis. The investigation of CAN in the greatest number of diabetic patients is therefore justified. The study of heart rate variations during deep respiration, active orthostatism or Valsalva manoeuvre, is still the reference. This method is simple, reproducible and may be carried out in the clinical setting in 10 to 15 minutes. The results must be strictly interpreted with rigour with respect to age. Orthostatic hypotension is a late sign of sympathetic nervous system disease. Spectral analysis of blood pressure variations on orthostatism or the study of cutaneous blood flow during activating the sympathetic system tests of greater sensitivity, should be developed. The demonstration of subclinical CAN should lead to the careful use of drugs which may induce orthostatic hypotension and certain antiarrhythmics, to search for disorders of ventricular repolarisation and for silent myocardial ischaemia in diabetics with several risk factors.

Adolescent↗

PubMed2000

[Electrocardiographic changes and rhythm problems in the diabetic].

Diabetes is a cause of serious myocardial disease related to an increased incidence of coronary artery disease, probably aggravated by cardiac autonomic neuropathy (CAN). In its incipient form, CAN hardly changes the sinus rhythm with an increase in nocturnal heart rate but without an appreciable effect on the indices of variability. In more advanced forms, "CAN+", there are not only changes in the heart rate variability but also in ventricular repolarisation. It is classical to underline the value of the corrected QT interval but this index has little real value. The "QT dispersion", comparing the duration of ventricular repolarisation on the surface leads, is no better a marker from the theoretical point of view. The dynamics of ventricular repolarisation on the other hand seem to be much more indicative of ventricular myocardial disease. They are studied by evaluating the QT-heart rate relationship and its increase distinguishes clearly CAN diabetics from CAN+ diabetics. In addition, in the latter subjects, diurnal physiological increase in the heart rate dependency of the QT interval (QT/RR slope) disappears or even inverse. It is probably this phenomenon which is responsible for the traditionally increased risk of ventricular arrhythmias and particularly sudden death in diabetics with autonomic neuropathy.

Action Potentials↗

PubMed1999

Neanderthal cannibalism at Moula-Guercy, Ardèche, France.

The cave site of Moula-Guercy, 80 meters above the modern Rhone River, was occupied by Neanderthals approximately 100,000 years ago. Excavations since 1991 have yielded rich paleontological, paleobotanical, and archaeological assemblages, including parts of six Neanderthals. The Neanderthals are contemporary with stone tools and faunal remains in the same tightly controlled stratigraphic and spatial contexts. The inference of Neanderthal cannibalism at Moula-Guercy is based on comparative analysis of hominid and ungulate bone spatial distributions, modifications by stone tools, and skeletal part representations.

Animals↗

PubMed1999

Haemodynamic response to an isometric exercise test in obese patients: influence of autonomic dysfunction.

OBJECTIVE: To investigate blood pressure (BP) and heart rate (HR) responses to an isometric exercise test in obese non diabetic patients and to correlate the results with vagal function and plasma insulin concentration. SUBJECTS: 63 obese patients, 36 of whom had abnormal cardiac parasympathetic control (PS+), and 35 healthy control subjects. METHODS: Analysis of HR variations during three standardized tests: deep-breathing, lying-to-standing and Valsalva. Isometric contraction (handgrip) for 5 min. RESULTS: In the PS+ obese patients, resting HR and body mass index (BMI) were significantly higher than in the PS- subjects and there was a trend to higher plasma insulin concentrations. Age-matched comparison showed that during the handgrip test, the increase in HR at the first minute was significantly higher in the PS- obese patients than in the controls. The increase in BP was significantly lower in the PS+ obese patients than in age-and-BMI-matched PS- obese patients. CONCLUSION: These data suggest that 1) there is an increase in cardiac vagal tone in PS- obese patients, since the early increase in HR at 1 min of the handgrip test, results from the withdrawal of vagal tone; 2) BP response to an isometric contraction is impaired in PS+ obese patients due to a lower sympathetic activation; 3) high plasma insulin concentrations may also contribute to limiting the BP response; and 4) autonomic disorders may account for alterations in the haemodynamic changes during exercise.

Adolescent↗

PubMed1999

Soluble L-selectin level is a marker for coronary artery disease in type 2 diabetic patients.

OBJECTIVE: To investigate whether the fall in soluble L-selectin (sL-selectin) level constitutes a marker for myocardial ischemia. RESEARCH DESIGN AND METHODS: The levels of soluble forms of adhesion molecules, i.e., intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), P-selectin (sP-selectin), and L-selectin (sL-selectin), were compared in type 2 diabetic patients without inflammatory syndrome but with symptomatic coronary artery disease (CAD) (group 1, n = 11), with silent ischemic disorders and proven coronary stenoses (group 2, n = 11), with silent myocardial ischemia (SMI) and normal coronary angiography (group 3, n = 10), and without proven SMI (group 4, n = 13). These levels were compared with those of 22 control subjects. RESULTS: The sL-selectin level was significantly lower in groups 1, 2, or 3 with symptomatic CAD or with SMI as compared with the control group (P = 0.0004). Group 4 without myocardial ischemia did not significantly differ from the control subjects (P = 0.6). In type 2 diabetic patients, after controlling for HbA1c, a partial correlation between sL-selectin and the CAD status was significant (P = 0.001). sICAM-1 and sP- or sE-selectin did not differ significantly between type 2 diabetic patients and control subjects or among the different groups of patients. The sVCAM-1 level in type 2 diabetic patients was significantly higher than in the control subjects (P = 0.001), but there were no significant intergroup differences (P = 0.4). CONCLUSIONS: In type 2 diabetic patients, sVCAM-1 is increased with regard to glycemic control, whatever the CAD status. In type 2 diabetic patients with symptomatic CAD or SMI associated with coronary stenoses, sL-selectin is significantly decreased. A marked fall in sL-selectin might constitute a marker for silent CAD in type 2 diabetic patients.

Aged↗

PubMed1999

Determinants of echocardiographically measured left ventricular mass in diabetic patients with or without silent myocardial ischaemia.

Left ventricular hypertrophy (LVH) is a recognized independent risk factor for cardiovascular morbidity and mortality. The purpose of this study was to assess the determinants of left ventricular mass index (LVMI), according to the presence or absence of silent myocardial ischaemia (SMI), in diabetic patients with at least two additional risk factors but with no known coronary artery disease. Eighty diabetic patients (14 Type 1 and 66 Type 2) were studied, and LVMI was measured echocardiographically. Three non-invasive tests (the ECG stress test, thallium-201 myocardial scintigraphy with intravenous dipyridamole infusion, and ambulatory 48-h ECG monitoring) were performed on all patients. Forty-five percent of patients had LVH (LVMI > or = 110 g/m2 in men and > or = 106 g/m2 in women). Twenty-six patients (37%) had SMI assessed on at least one of the non-invasive tests, 7 of whom had significant coronary stenoses on angiography. LVMI was significantly higher in patients with coronary stenoses on angiography than in those with SMI but without coronary stenoses or in those without SMI (p < 0.05), and was correlated with systolic blood pressure. In patients free of SMI, LVMI correlated with creatininemia. In patients with SMI and normal coronary arteries on angiography, LVMI correlated with the waist/hip girth ratio, the log urinary albumin excretion rate and the red blood cell filtration index (a rigidity index). This study suggests that LVH is very frequent in diabetic patients and that the main factor contributing to the increase of LVMI differs according to the presence or absence of SMI and coronary stenoses: volume load in patients free of SMI, microcirculatory disorders in those with SMI but with normal coronary arteries, and blood pressure in those with coronary stenoses.

Analysis of Variance↗

PubMed1999

[Insulin resistance and alteration of cardiac vagal activity in obese patients].

We have previously shown that alterations of vagal control of heart rate variations are found in more than half of non diabetic obese subjects (Int J Obes 1995) and are associated with a more severe insulin resistance in noninsulin dependent diabetic patients (Metabolism 1998). The aim of this study was to examine whether parasympathetic alterations are also associated with a more severe insulin resistance in non diabetic obese subjects. 245 obese subjects (BMI = 34.2 +/- 0.4 kg/m2) aged 38.6 +/- 0.8 years, with a normal oral glucose tolerance test were included. Parasympathetic activity was evaluated by heart rate variations during three standardised tests: Valsalva, deep-breathing and active lying-to-standing, with age being taken into account. The Valsalva maneuver was abnormal in 17.5%, the deep-breathing test in 18% and the lying-to-standing test in 30.3% of the cases. One hundred and thirty subjects (52.1%) had at least one abnormal test. Compared with those with three normal tests, the obese subjects with parasympathetic alterations had very similar BMI and blood pressure, but significantly higher values of heart rate (75.5 +/- 1.4 vs 71.3 +/- 1.1 beats/min, p = 0.02), fasting blood glucose (5.0 +/- 0.1 vs 4.8 +/- 0.1 mmol/L, p = 0.03) and plasma insulin (98 +/- 6 vs 82 +/- 4 pmol/L, p = 0.03). In the whole series of obese subjects, heart rate variations during the deep-breathing and lying-to-standing tests correlated negatively with blood glucose (p = 0.001 and p = 0.03 respectively), and during the deep-breathing test they correlated negatively with the waist/hip ratio (p = 0.004). This data suggests that cardiac parasympathetic alterations should take part in the insulin-resistance syndrome and might account for the poor cardiovascular prognosis linked to this syndrome.

Adult↗

PubMed1999

Bone amyloidoma in a diabetic patient with morbid obesity.

Bone localisations of amyloidosis are rare, usually diffuse and associated with myeloma. We report the case of a patient with massive obesity complicated by diabetes, hypertension, sleep apnea and liver steatosis, who complained of rapidly worsening bilateral polyradiculalgia of the lower limbs. After sufficient weight loss made nuclear magnetic resonance imaging feasible, a spinal tumour was visualised on the 5th lumbar vertebra, extending to soft tissues. Total excision was performed, and pathological studies revealed an amyloid bone tumour with no evidence of myeloma.

Amyloidosis↗

PubMed1998

Coronary artery responses to physiological stimuli are improved by deferoxamine but not by L-arginine in non-insulin-dependent diabetic patients with angiographically normal coronary arteries and no other risk factors.

BACKGROUND: Acetylcholine produces coronary artery (CA) constriction in diabetic patients, suggesting an impairment of endothelium-dependent dilation. In diabetes, multiple metabolic abnormalities may inactivate nitric oxide through oxygen free radical production. METHODS AND RESULTS: To examine the mechanism of this abnormal response, two physiological tests (ie, a cold pressor test [CPT] and coronary flow increase induced by an injection of 10 mg papaverine [PAP] in the distal left anterior descending CA) were performed before and after either intravenous L-arginine (625 mg/min x 10 minutes) or intravenous deferoxamine (50 mg/min x 10 minutes) in 22 normotensive nonsmoking diabetic patients with angiographically normal CAs and normal cholesterol. Coronary surface areas were measured with quantitative angiography. Before the administration of L-arginine or deferoxamine, CPT induced CA constriction in both groups (-14 +/- 10% and -15 +/- 11%, respectively; each P<.001), and PAP injection in distal LAD did not modify significantly proximal LAD dimensions. In the 10 diabetic patients receiving L-arginine, responses to CPT and PAP were not modified. Conversely, in the 12 patients receiving deferoxamine, CA dilated in response to the two tests (+10 +/- 9% after CPT and +22 +/- 7% after PAP, each P<.001). Intracoronary isosorbide dinitrate, an endothelium-independent dilator, produced similar dilation in the two groups (+47 +/- 19% and +41 +/- 15%, respectively; each P<.001). CONCLUSIONS: This study shows that (1) responses of angiographically normal CAs to CPT and to flow increase are impaired in diabetic patients; (2) abnormal responses are not improved by L-arginine, suggesting that a deficit in substrate for nitric oxide synthesis is not involved; and (3) deferoxamine restores a vasodilator response to the two tests, suggesting that inactivation of NO by oxygen species might be partly responsible for the impairment of CA dilation in diabetic patients.

Adult↗

PubMed1998

Increased capillary filtration of albumin in diabetic patients--relation with gender, hypertension, microangiopathy, and neuropathy.

The aim of this study was to investigate the factors associated with an increase in capillary filtration of albumin (CFA) in a large series of diabetic patients and its relationship with gender, hypertension, microangiopathy, and neuropathy. One hundred sixty-three unselected diabetic patients, 74 type I and 89 type II, were included. An isotopic test of CFA was performed with 99m technetium-labeled albumin injected intravenously. Radioactivity was counted externally at the forearm with a gamma camera before, during, and after venous compression. After removal of venous compression, interstitial albumin retention (AR) was calculated and the radioactivity disappearance curve was analyzed by the Fast Fourier transform, which provides an index for lymphatic uptake of interstitial albumin (low-frequency to high-frequency amplitude peak ratio [LF/HF]). An increase in AR and LF/HF was found in 65 (39.9%) and 117 (71.7%) patients, respectively. Increased AR was significantly more frequent in women than in men (P=.018) and in patients without microangiopathic complications than in those with them (P=.028). In men, it was significantly more frequent in type I versus type II diabetic patients (P=.004), and AR was significantly higher in patients with peripheral neuropathy than in those without (P=.004). The LF/HF was also significantly higher in men with peripheral neuropathy (P=.045). In women, the AR level correlated negatively with postprandial glycemia (P=.006) and was significantly higher in patients without microangiopathic complications (P=.003). These data suggest the role of hormonal factors, both sex steroids and insulin, and the major role of peripheral neuropathy in the increase in CFA. The highly prevalent increase in CFA before the onset of microangiopathic complications is consistent with the presence of a functional microcirculatory disorder that might contribute to the occurrence of microangiopathic lesions.

Age Factors↗

PubMed1998

Influence of parasympathetic dysfunction and hyperinsulinemia on the hemodynamic response to an isometric exercise in non-insulin-dependent diabetic patients.

The handgrip test has long been used as a test for investigating cardiac autonomic neuropathy in diabetic patients. However, the factors involved in the hemodynamic response to the handgrip test have not been thoroughly studied. The aim of this study was to investigate blood pressure (BP) and heart rate (HR) responses to an isometric test in non-insulin-dependent diabetics (NIDDs) and to correlate the results with vagal function evaluated by three standardized tests and with plasma insulin levels. Fifty-five NIDDs, 35 of whom had one to three abnormal parasympathetic tests (PS+), were compared with 10 healthy control subjects. Fasting and postprandial plasma insulin levels were significantly higher in the PS+ than in the PS- patients. Resting HR correlated significantly with log fasting and postprandial insulin. In PS+ NIDDs, resting HR was significantly higher than in PS- patients. Age-matched comparisons also showed that resting systolic BP was significantly higher in PS+ patients than in controls. In PS- patients, the mean acceleration of HR was significantly higher than in the control group from the second to the fifth minute, and the BP response was also higher than in controls. These data suggest that (1) sympathetic response to an isometric exercise is increased in PS- NIDDs; (2) cardiac parasympathetic dysfunction is associated with a more severe insulin resistance; and (3) the subsequent higher plasma insulin level may contribute to the increase in resting HR and BP through sympathetic activation while limiting the hemodynamic response to an isometric exercise through its vasodilative effect.

Blood Pressure↗

PubMed1998

Glucose-induced thermogenesis, inhibition of lipid oxidation rate and autonomic dysfunction in non-diabetic obese women.

OBJECTIVE: The aim of this study was to look for a relationship between autonomic dysfunction and alterations in glucose- induced thermogenesis (GIT) and lipid oxidation rate in obese non-diabetic women. SUBJECTS: 37 obese women, 20 with impaired cardiac autonomic function tests (group 1) were matched with 17 women with normal tests (group 2) according to age, weight, body mass index (BMI), waist-to-hip ratio (WHR), fat mass (FM) and fat free mass (FFM). MEASUREMENTS: A series of five standardized tests was carried out, three of which were based mainly on cardiac 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). Energy expenditure (EE), lipid and glucose oxidation rate were determined by indirect calorimetry at fasting and after an oral glucose load (75 g). Blood glucose, insulin and catecholamines responses to glucose were examined. RESULTS: There was no significant difference in plasma glucose, insulin, catecholamines, metabolic rate, glucose and lipid oxidation rate at fasting and plasma glucose, insulin and catecholamine responses to glucose. GIT was slightly but not significantly lower in group 1 (24.7+/-10.4 kJ) than in group 2 (46.8+/-9.0 kJ). The cumulative glucose oxidation rate did not differ significantly in the two groups. The cumulative lipid oxidation rate was significantly lower in group 1 than in group 2 (-49.4+/-4.1 vs -30.8+/-8.0, respectively, P = 0.033). It correlated negatively with the area under the curve of insulin response (r=-0.37, P=0.04). In the multivariate analysis, both autonomic dysfunction and the area under the curve of insulin response correlated significantly with the cumulative lipid oxidation rate. CONCLUSION: This study suggests that 1) the glucose-induced inhibition of the lipid oxidation rate in obese women is greater in the patients with autonomic dysfunction; 2) a decrease in sympathetic activity is likely to be involved in this phenomenon.

Adolescent↗

PubMed1998

Cytochrome P450 2E1 activity in diabetic and obese patients as assessed by chlorzoxazone hydroxylation.

Cytochrome P450 2E1 (CYP2E1) is a phase I detoxification enzyme, which is induced by chronic alcohol consumption. It is involved in the activation of numerous carcinogens and in the production of free radicals. As it has previously been shown to be induced in diabetic and obese rats, the aim of this study was to investigate its induction level in poorly-controlled diabetics and in obese patients (Body Mass Index > 30 kg/m2). CYP2E1 activity was determined in 35 diabetic and 17 obese patients by using the in vivo chlorzoxazone hydroxylation test. Even though the glucidic parameters were highly disturbed (mean fasting glycemia > 7.9 mmol/L, post prandial glycemia > 12.2 mmol/L and fructosamine > 326 mumol/L), CYP2E1 activity was not enhanced either in insulin-dependent diabetics (IDDs, n = 7) nor in non-obese non-insulin-dependent diabetics (NIDDs, n = 15) when compared to controls (n = 42) (0.21 +/- 0.03, 0.33 +/- 0.03 and 0.30 +/- 0.02, respectively, mean +/- SEM). However, this activity was lower in IDDs when compared to NIDDs (P < 0.05). In obese patients, with (n = 13) or without (n = 17) NIDD mellitus, CYP2E1 activity was increased by a mean of 40% when compared to controls. In addition, positive correlations were found in all subjects (controls or patients, n = 74) between CYP2E1 activity and serum cholesterol (r = 0.42, P < 0.0001), triglycerides (r = 0.44, P < 0.0001) and BMI (r = 0.36, P < 0.001). Accordingly, subjects with cholesterol and/or triglyceride serum levels above 6.4 and 1.8 mmol/L, respectively, displayed a mean increase of 40% of their CYP2E1 activity vs subjects within the above values. It is believed that individuals with increased CYP2E1 activity are more susceptible to the adverse effects of CYP2E1-mediated activation of toxins and carcinogens.

Adult↗

PubMed1998

Elevated concentrations of soluble E-selectin and vascular cell adhesion molecule-1 in NIDDM. Effect of intensive insulin treatment.

OBJECTIVE: To evaluate the effects of a 14-day intensive insulin therapy and short-term improvement of glycemic control on serum levels of soluble forms of adhesion molecules, i.e., intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and E-selectin (sE-selectin) in NIDDM patients with poor glycemic control. RESEARCH DESIGN AND METHODS: A total of 16 NIDDM patients were compared with 23 healthy subjects (control group) and investigated before and after intensive insulin treatment. RESULTS: On day 0, sE-selectin and sVCAM-1 levels were significantly higher in NIDDM patients than in nondiabetic control subjects (median 87, range 63-115; median 544, range 408-797 vs. 58, 43-80; 443, 395-573 ng/ml, respectively) (P < 0.008 in both cases). On day 15, the fall in sE-selectin levels was significant (P < 0.0001) and at a lesser extent in sVCAM-1 levels (64, 48-85; 506, 417-678 ng/ml, respectively); these levels reached values that no longer differed from those of control subjects (P = 0.23 and 0.15, respectively). Moreover, the fall in sE-selectin was positively associated with the change in LDL cholesterol and the improvement of glycemia. CONCLUSIONS: In poorly controlled NIDDM patients, sE-selectin levels are increased and significantly fall to normal after short-term improvement of glycemic control. This suggests that assaying sE-selectin makes it possible to detect endothelium activation and to follow its reversal with euglycemia.

Apolipoproteins↗