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Biomedical subjects

L Monnier

Publications and source records attributed to L Monnier.

At least 37 records · Page 2Linked to original sources
PubMed2000

Energy metabolism and substrates oxidative patterns in type 2 diabetic patients treated with sulphonylurea alone or in combination with metformin.

OBJECTIVE: To compare substrates oxidative patterns in type 2 diabetic patients treated with sulphonylurea alone or in combination with metformin. METHODS: Plasma glucose (PG), plasma insulin (PI) and substrates oxidation rates measured by indirect calorimetry were compared during a test day at 8.00 a.m. (before breakfast), 11.00 a.m. (before the lunch), 2.00 p.m. (2 h after the lunch) and at 5.00 p.m. in 56 diabetic patients treated with diet (group C, n = 14), sulphonylurea (group S, n = 14) or with a sulphonylurea-metformin combination (group SM, n = 28). RESULTS: The three groups were comparable for age, body mass index (b.m.i.), body composition and PG levels. Mean glucose oxidation (Gox) was increased since mean lipid oxidation (Lox) was decreased in group S in comparison both with group C (3.02+/-0.08 vs. 2.62+/-0.08 g/min/kg/10(3), p < 0.05; 0.53+/-0.04 vs. 0.88+/-0.09 g/min/kg/10(3), p < 0.01). Mean Lox was also decreased in group S in comparison with group SM (0.88+/-0.06 vs. 0.53+/-0.04 g/min1/kg1/10(3), p < 0.0001) whereas the difference in Gox between these latter two groups was only significant in the basal state (1.94+/-0.17 vs. 2.47+/-0.17 g/min1/kg1/10(3), p < 0.05). Mean respiratory quotient (RQ) was increased in group S (0.90+/-0.01) in comparison both with group C (0.86+/-0.01, p < 0.001) and with group SM (0.86+/-0.01, p < 0.001). Mean energy expenditure was lower in group S than in group SM (21.4+/-0.6 vs. 23.6+/-0.6 kcal/min/kg/10(3), p < 0.05). Substrates oxidative patterns, RQ values and energy expenditure were similar in group C and in group SM. CONCLUSIONS: When compared to patients treated with a sulphonylurea-metformin bitherapy, patients treated with a sulphonylurea monotherapy have a shift in their ratio of fat to carbohydrate oxidation that could make body weight loss more difficult in this latter group.

Blood Glucose↗
PubMed2000

[Very-low-calorie-diets: is there a place for them in the management of the obese diabetic?].

It is well-recognized that standard caloric restrictions (1500 kcal/day) are usually poorly effective in achieving weight losses in overweight type 2 diabetic patients. For that reason very-low-calorie-diets (VLCDs) were developed as a mean for initiating or accelerating weight reduction. Short-term studies indicate that VLCDs result generally in weight losses that are three times greater than those obtained with standard low-calorie-diets. Fasting blood glucose values are improving in parallel to weight losses and in many patients the improvement in glycemic control is better than that expected from the magnitude of weight losses. However the results are rather disappointing after several months or years of follow-up. For example it has been demonstrated that weight regain can be observed as soon as the patient is shifted to a refeeding or maintenance dietary program at the end of the VLCD period. Long-term results on glycemic control and body weight reduction are generally similar with standard low-calorie-diets and with VLCDs, the final results depending on the magnitude of weight loss whatever the prescribed diet. At short-term the VLCDs can be helpful first for initiating weight losses and second for sensitizing the patient to the potential benefits of complying to dietary measures.

Blood Glucose↗
PubMed2000

[Specific effect of postprandial glycemic peaks on HBA1c and angiopathy].

Most studies argue for a strong relation between postprandial blood glucose and cardiovascular risk. Thus the DIS study establishes a significant link between postprandial glucose and the incidence of myocardial infarction as well as the occurrence of death. The DECODE study shows that identifying individuals at risk for death can be done through OGTT 2 h blood glucose, whatever fasting glycemia is. Kumamoto study shows a reduction in microangiopathic complications when postprandial blood glucose is corrected by a multiinjection protocol. Finally, a study conducted in Montpellier shows that postprandial blood glucose better reflects the overall diabetes control than fasting glycemia. Altogether, these data suggest that managing postprandial blood glucose is essential for the prevention of vascular outcome in diabetic patients.

Blood Glucose↗
PubMed1999

[Diet and fitness in type 2 diabetes].

Fitness and dietary measures remain the corner stone of the treatment of type 2 diabetic patients. The two objectives of these measures are: (i) to improve the glycemic control and to normalize the biological abnormalities which are frequently associated with the diabetic state; (ii) to prevent the micro and macrovascular complications. All these measures should be simplified, and sufficiently attractive to be acceptable and accepted by the patient. Weight-loss objectives in overweight diabetic patients should remain within reasonable limits: a few kilogram- loss is sufficient in many cases. In order to maintain the palatability of the diet, the dietary fat intake must be set at sufficient high levels, just by adjusting the carbohydrates/monounsaturates fat balance. When physical training is recommended, this activity must appear as a leisure and not as a constraint. More generally the management plan should be multifactorial and avoid contradictory measures.

Diabetes Mellitus, Type 2↗
PubMed1999

Involvement of Nitric Oxide in the Inhibition of Aortic Smooth Muscle Cell Proliferation by Calcium Dobesilate.

Vascular smooth muscle cell (SMC) proliferation is a key process in the pathogenesis of atherosclerosis. Numerous factors are involved in the regulation of SMC growth. Nitric oxide (NO) induces the inhibition of SMC proliferation whereas oxidized low-density lipoproteins (LDL) have a mitogenic effect. Calcium dobesilate (Doxium) is an angioprotective agent for treating vascular diseases. It has been shown to increase NO production and to have antioxidant properties but its mechanism of action is not yet fully understood. This study investigated the effect of calcium dobesilate on proliferation of rat aortic SMC in culture. Proliferation was evaluated by cell number and DNA synthesis. Orally administered calcium dobesilate (30, 100, or 200 mg/kg/day for 7 days) induced a dose-dependent decrease of proliferation of SMC in primary culture compared with controls. In vitro treatment with calcium dobesilate (0.05-5 mM) inhibited both DNA synthesis and proliferation in a time- and concentration-dependent manner. In both ex vivo and in vitro models, the inhibition was reversible upon removal of the drug. Calcium dobesilate also stimulated NO production and NO synthase activity. Inhibitors of NO synthesis attenuated the inhibitory effect of calcium dobesilate (300 µM) on DNA synthesis. In addition, calcium dobesilate (2.5-40 µM) induced a dose-dependent protection of cooper-induced LDL oxidation. These results showed that calcium dobesilate inhibits SMC proliferation, partly by a NO-dependent mechanism, and suggest that it could be effective in the treatment of pathological disorders associated with vascular SMC proliferation.

Journal Article↗
PubMed1999

[Primary nutritional and drug prevention of atherosclerosis].

Atherosclerosis results from a multifactorial process. For that reason, primary prevention of cardiovascular diseases requires several measures that should exhibit antiatherogenic, antithrombotic, antioxidative and antihypertensive properties. Two types of therapeutic strategies can be individualized. Nutritional interventions are the first line measures for population wide primary prevention in subjects at low risk of developing atheroscleric diseases. In high risk individuals who have either one major risk factor (LDL cholesterol above 190 mg/dL) or several additional risk factors, dietary measures must be frequently combined with drug treatments. However, the cost-effectiveness ratio should be weighed prior to any treatment especially with statins. Dietary measures consist to reduce caloric intakes in overweight subjects, or more generally to adopt eating patterns which correspond to the following recommendations: (i) proteins = 15% of total calories; (ii) saturated and polyunsatured fats = 10% each; (iii) carbohydrates plus monounsaturated fats = 65%. Such dietary instructions permit individual dietary changes, just by adjusting the carbohydrates/monounsaturates balance, the sum of both nutrients remaining in all cases equal to two-thirds to total calories. Drug treatments are only indicated after secondary dietary failure. They are generally based on the use of statins since the efficacy of these treatments has been clearly established by such preventive trials as the WOSCOP Study, provided that the therapeutic interventions result in significant reduction of LDL cholesterol levels over several years. Antiplatelet agents (aspirin), antihypertensive therapies, antioxidant supplementations with vitamins E or C are also recommended in some individuals for completing the beneficial effects of the above mentioned measures.

Anticholesteremic Agents↗
PubMed1999

Assessment of insulin sensitivity from plasma insulin and glucose in the fasting or post oral glucose-load state.

OBJECTIVE: To compare insulin sensitivity indexes derived from plasma insulin (I) and glucose (G) in the basal state (Sib) and at the second hour (I2h and G2h) of an oral glucose tolerance test (OGTT, Si2h) (i) with measurements of insulin sensitivity using the insulin modified frequently sampled intravenous glucose tolerance test (FSIVGTT) [Si(IVGTT)] and (ii) with modelling of fasting glucose and insulin by the homeostasis model assessment (HOMA). SUBJECTS: 47 subjects entered the study. 31 subjects were classified as having normal glucose tolerance (NGT), 10 as having impaired tolerance to glucose (IGT) and six as type 2 diabetes mellitus according to the World Health Organisation (WHO) criteria. MEASUREMENTS: Sib and Si2h were calculated as follows. Sib = 10(8)/(I x G x VD), Si2h = 10(8)/(I2hr x G2hr x VD) where VD is an estimate of the apparent glucose distribution volume. A third insulin sensitivity index (SiM) was calculated by averaging Sib and Si2h. HOMA was calculated as follows: I/(22.5 x e(-lnG)) RESULTS: Si(IVGTT), Sib, SI2h and SiM were all significantly higher in subjects with NGT than in those with IGT or type 2 diabetes. Si(IVGTT) was highly correlated (P < or = 0.0001) with the three insulin sensitivity indexes found in the total population, in subjects with NGT and in those with IGT. In type 2 diabetic patients, a significant correlation was only noted when SiM was tested against Si(IVGTT) (P < or = 0.05). In most circumstances, the associations of Si(IVGTT) with Sib, SI2h and SiM were stronger than the corresponding associations with Ib, I2h or HOMA. SiM was the index that correlated best with Si(IVGTT) in the whole group (r = 0.92, P < 0.0001) as well as in NGT (r = 0.86, P < 0.0001), IGT (r = 0.96; P < 0.0001) and type 2 diabetes (r = 0.83, P < or = 0.05) subgroups. CONCLUSIONS: Calculations of sensitivity indexes from G and I concentrations in the basal state and during a conventional 2 h OGTT appear to be useful for coupling in the same simple and single test both a determination of glucose tolerance and an estimate of insulin sensitivity.

Administration, Oral↗
PubMed1998

Use of a prostacyclin analogue in cholesterol crystal embolism.

The prognosis of cholesterol embolism is often poor, and no treatment is presently available. We report the use of a stable prostacyclin analogue in treating cholesterol embolism in a diabetic patient with arteriopathy. As a sole therapy, it improved cutaneous manifestations and pain, in parallel with an increased transcutaneous oxymetry. We think that prostacyclin analogues are novel candidates for the treatment of cholesterol embolism.

Aged↗
PubMed1998

Relationship between insulin sensitivity, obesity, body fat distribution and beta-endorphinaemia in obese women.

OBJECTIVE: To study the associations of obesity (as body mass index (BMI)), of body fat distribution (as waist to hip ratio (WHR)) and of beta-endorphinaemia (beta-EP-aemia) with fasting insulin and glucose concentrations, with insulin secretion (as first phase insulin response (FPIR)) and with insulin sensitivity (SI) in obese women. DESIGN: a cross-sectional study of insulin sensitivity in obese women. SUBJECTS: 45 obese women (age: 20-70 y, BMI: 27-50). MEASUREMENTS: Frequently sampled intravenous glucose tolerance test (FSIGTT), FPIR, fasting glucose, fasting insulin, BMI, body fat topography (WHR), beta-EP-aemia, plasma ACTH. RESULTS: In univariate analysis the following positive associations were observed: fasting glucose with age and WHR, fasting insulin with BMI and WHR, beta-EP plasma concentration with WHR; SI was negatively associated with BMI, WHR and beta-EP plasma concentrations. This pattern of associations remained unaltered in multivariate analysis including age, BMI and WHR as independent variables. The contribution of beta-EP plasma concentrations to SI variability was corroborated by a stepwise multiple regression analysis: 53.8% of SI variation could be explained by BMI (30.7%), by beta-EP plasma concentrations (17.2%) and by WHR (5.9%). Finally, women were divided into two groups according to whether they had a peripheral (P-BFD, WHR < or = 0.80, n = 24) or an abdominal (A-BFD, WHR > or = 0.85, n = 16) body fat distribution. After adjustment for age and BMI, SI values were lower while beta-EP and ACTH plasma concentrations were higher in the A-BFD compared to the P-BFD group. In this latter group, 54.8% of SI variation was explained by the same variables as in the whole group. In the A-BFD group, higher WHR was associated with lower FPIR. CONCLUSIONS: 1) The major finding of this study is that, in non-diabetic obese women (especially those with a P-BFD), higher beta-EP plasma concentrations are associated with lower insulin sensitivity. This association is independent of both the magnitude of obesity and the pattern of fat distribution, although these two parameters are strong predictors of SI. 2) The major reduction in SI observed in women with A-BFD probably results from the additive effects of obesity, of elevated beta-EP plasma concentrations and of metabolic and endocrine alterations in relation with the central pattern of fat distribution.

Adult↗
PubMed1998

Phenotype modulation in primary cultures of aortic smooth muscle cells from streptozotocin-diabetic rats.

Diabetes mellitus is a major risk factor for atherosclerosis. In atherosclerotic lesions, arterial smooth muscle cells (SMC) change from a contractile to a synthetic phenotype characterized by active proliferation. A similar phenotype modulation occurs in vitro when isolated arterial SMC are grown in culture and is characterized by both changes in cell morphology and a typical switch in actin isoform expression. In this study, we examined the influence of streptozotocin (STZ)-induced diabetes on the differentiation state and the phenotype modulation of cultured rat aortic SMC. We used transmission electron microscopy to study the fine structure of STZ-diabetic and non-diabetic SMC in primary culture and immunological methods for the determination of the proportions of alpha-smooth muscle actin (alpha-SM) and nonmuscle beta-actin (beta-NM) isoforms. Cultured STZ-diabetic SMC exhibited a large cytoplasmic volume, rich in rough endoplasmic reticulum, when compared with cultured non-diabetic SMC. alpha-SM, organized in stress fibers, was less homogeneously and abundantly distributed and by contrast, beta-NM was more abundant in STZ-diabetic than in non-diabetic SMC. Cytofluorimetric analyses demonstrated that the alpha-SM content was reduced in freshly STZ-diabetic SMC. Furthermore, during logarithmic growth of cultured SMC, the decrease of alpha-SM was more important in STZ-diabetic than in non-diabetic SMC. Immunoblotting of actin isoforms confirmed that expression of beta-NM was more important in STZ-diabetic than in non-diabetic SMC even in freshly isolated cells. The results suggest that SMC from STZ-diabetic rats express a more dedifferentiated state and undergo a more rapid phenotypic modulation in primary cultures than SMC from non-diabetic rats. Therefore, diabetes could induce changes in the phenotype of arterial SMC which might be associated with the onset or progression of the atherogenic process.

Actins↗
PubMed1998

[Changes in dietary management of diabetic patients].

In the late 1990s, diet remains the cornerstone of diabetes therapy. Dietary and nutritional recommendations should seek to reduce the hyperglycaemic state which is the main risk factor for microangiopathy. Furthermore, the prevention of macrovascular complications should lead to dietary prescriptions that combine such properties as antiatherosclerotic, antithrombotic, and antihypertensive measures and such advantages as reducing oxidative stress. The means for achieving such objectives are, first, weight-loss interventions in obese patients and, secondly, the choice of a judicious balance between carbohydrates and monounsaturated fats in all individuals. Dietary measures must achieve a compromise between their acceptability by the patient and medical requirements. For that reason, caloric restriction should be moderate, leading to progressive weight loss (-3 kg monthly), with reasonable weight targets at the end of the weight-reduction period. Compliance with dietary advice usually results in significant savings in medical costs. However, long-term maintenance of dietary measures is difficult to achieve in most individuals, except those enrolled in well-structured training programmes.

Body Weight↗
PubMed1997

Cholesterol biosynthesis in normocholesterolemic patients after cholesterol removal by plasmapheresis.

Plasmapheresis and low-density lipoprotein (LDL)-apheresis are recognized procedures for the treatment of hyperlipidemia resistant to diet and lipid-lowering drugs and provide information on cholesterol synthesis in hypercholesterolemic patients. However, cholesterol synthesis after acute cholesterol removal from plasma has never been investigated in normocholesterolemic patients. In this study, cholesterol synthesis was evaluated in three normocholesterolemic patients by determination of plasma lathosterol, lathosterol-to-cholesterol ratio, and plasma mevalonic acid. In a short-term kinetic study, samples were collected before and after plasmapheresis and every 6 hours during 24 hours. In the second part of the study, cholesterol synthesis was evaluated daily for 3 days. In normocholesterolemic patients, cholesterol returns to basal levels in 3 days. However, cholesterol removal did not result in a significant increase in lathosterol-to-cholesterol ratio or in plasma mevalonic acid, despite a slight increase in lathosterol. In contrast, when repeated plasma exchanges induced a dramatic hypocholesterolemia (< 1 mmol/liter), an acute but transient stimulation of cholesterol synthesis was observed (lathosterol/cholesterol ratio and MVA, respectively, increase from 8.2 to 22.3 and from 28 nmol/liter to 98 nmol/liter). This study shows that cholesterol synthesis is not stimulated by plasmapheresis in normocholesterolemic patients but is enhanced in dramatic hypocholesterolemic patients (< 1 mmol/liter).

Cholesterol↗
PubMed1997

Supplementation with wine phenolic compounds increases the antioxidant capacity of plasma and vitamin E of low-density lipoprotein without changing the lipoprotein Cu(2+)-oxidizability: possible explanation by phenolic location.

OBJECTIVES: To evaluate the effect of the red wine phenolic compound (RWPC) dietary supplementation without alcohol interference on: (1) some of the biochemical characteristics of LDL, (2) the oxidative susceptibility of LDL and (3) the antioxidant capacity of total plasma (Pl-AOC). In order to account for discrepancies between the three series of data, the in vitro stability of the association of phenolic compounds and LDL was tested. DESIGN: An intervention study with 20 volunteers. Each served as his own control. Cu(2+)-oxidizability of LDL and Pl-AOC were tested on blood samples before and after dietary supplementation. Cu(2+)-oxidizability of LDL was also tested by co-incubation in the presence of RWPC or phenolic acids with or without extensive dialysis. SETTING: The Laboratory of Lipid Biochemistry and Biology, School of Medicine, and the Laboratory of Metabolic Diseases, Lapeyronie Hospital, University of Montpellier, France. SUBJECTS: Healthy males, nonsmokers and moderate drinkers, submitted to a dietary regimen deprived of vitamin E and C for a period of 10 d before supplementation. They also abstained from alcohol, wine, fruit juices, coffee, tea and cola beverages during this period. INTERVENTION: Six 0.33 g capsules/d (namely two capsules at each meal) of a preparation of red wine phenolic compounds in a dry powder form were given to the volunteers over a period of two weeks. Blood samples were drawn in fasting conditions at day 0 and day 14 of the supplementation period. RESULTS: Supplementation led to: (1) in LDL, a significant increase in vitamin E content (n = 20, P = 0.01) or vitamin E/total fatty acid bis-allylic carbon number ratio (n = 20, P = 0.006) without modification in the other biochemical characteristics or Cu(2+)-oxidizability; (2) in plasma, a significant increase in the antioxidant capacity (n = 11, P = 0.01). In vitro studies showed that RWPC or sinapic, caffeic or ferulic acids incubated in the presence of LDL increased the protection of the lipoparticle against oxidation (caffeic > sinapic > ferulic). This effect, however, was totally lost after extensive dialysis. CONCLUSIONS: The enhancing effect of the RWPC supplementation on Pl-AOC may be due to a phenolic-compound action both in the aqueous phase of plasma and at the surface of lipoprotein particles. Surface location possibly explains the enhancing-sparing effect of supplementation on LDL vitamin E and the absence of effect on dialysed-LDL oxidizability.

Adult↗