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Biomedical subjects

L Monnier

Publications and source records attributed to L Monnier.

At least 55 records · Page 3Linked to original sources

Nonfasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes.

OBJECTIVE: To evaluate the relative value of plasma glucose (PG) at different time points in assessing glucose control of type 2 diabetic patients. RESEARCH DESIGN AND METHODS: Glycemic profiles, i.e., PG at prebreakfast (8:00 A.M.), prelunch (11:00 A.M.), postlunch (2:00 P.M.), and extended postlunch (5:00 P.M.) times over the same day, were obtained in 66 type 2 diabetic patients on an ambulatory basis. The different time points of PG were compared with a measurement of HbA1c made in a reference laboratory. RESULTS: Extended postlunch PG was lower than prebreakfast PG (104 +/- 21 vs. 133 +/- 35 mg/dl, P < 0.02) in patients demonstrating good diabetic control (HbA1c < or = 7.0%), was not different from prebreakfast PG (149 +/- 47 vs. 166 +/- 26 mg/dl, NS) in patients demonstrating fair diabetic control (7.0% < HbA1c < or = 8.5%), and was higher than prebreakfast PG (221 +/- 62 vs. 199 +/- 49 mg/dl, P < or = 0.01) in those demonstrating poor diabetic control (HbA1c < or = 8.5%). Prebreakfast, prelunch, postlunch, and extended postlunch PG values were all significantly correlated with HbA1c. Multiple linear regression analysis demonstrated that postlunch PG and extended postlunch PG correlated significantly and independently with HbA1c, but that prebreakfast PG and prelunch PG did not. Moreover, postlunch PG and extended postlunch PG demonstrated better sensitivity, specificity, and positive predictive value in predicting poor glycemic control than did prebreakfast PG or prelunch PG. CONCLUSIONS: In type 2 diabetes, postlunch PG and extended postlunch PG are better predictors of glycemic control than fasting plasma glucose (FPG). We therefore suggest that they be more widely used to supplement, or substitute for, FPG in evaluating the metabolic control of type 2 diabetic patients.

Adult↗

Multicentre evaluation of the DCA 2000 system for measuring glycated haemoglobin. DCA 2000 Study Group.

The recommended method for assessing long-term blood glucose control in diabetic patients is the measurement of glycated haemoglobin (Hb). The Ames DCA 2000 system for assaying glycated Hb uses an immunoassay with a monoclonal antibody specific for an aminoacid sequence within the HblAc molecule. This study compared the performance of the DCA 2000 system for HblAc measurement with that of high-performance liquid chromatography (HPLC). A total of 1.016 insulin-dependent and non-insulin-dependent diabetic patients from 5 outpatient clinics took part. The correlation coefficients between DCA 2000 and HPLC data ranged between 0.94 and 0.98, depending on site. The mean variations and 95% confidence intervals for the differences between the results for each sample were: site A 0.172 (-1.186 to 1.53), site B -0.275 (-1.317 to 0.767), site C -0.146 (-0.868 to 0.576), site D -0.088 (-0.864 to 0.688), and site E -0.251 (-1.099 to 0.597). The sensitivity of the DCA 2000 assay ranged between 80 and 94%, and the specificity between 88 and 100%, depending on site. For pooled results, the correlation coefficient assayed by the two methods was 0.95. The mean variation was -0.116 and the 95% confidence interval -1.23 to 0.998. The sensitivity of DCA 2000 was 91%, and the specificity 94%. DCA tended to underestimate HbAlc slightly as compared to HPLC. This study confirms the reliability of DCA 2000 for measuring glycated Hb. The system is easy to use and provides valuable information for the care of the diabetic patients.

Antibodies, Monoclonal↗

[Determinants of the left ventricular mass in obese patients. Influence of lean body mass].

Systolic blood pressure and body mass index (BMI) are the main determinants of the left ventricular mass (LVM). The mechanism of this cardiac hypertrophy in the obese individual is multifactorial and involves hemodynamic as well as metabolic factors. The association of LVM with the morphologic features of the individual are well known. The aim of this study was to assess the influence of the morphologic and metabolic features of obese women on LVM. 2D echocardiography evaluation of LVM was done in 24 normotensive, normoglycemic obese women (BMI [27.5-52.2 Kg/m2). Lean and fat body mass were determined by bio-impedancemetry, insulin sensitivity (Si) by the minimal model (Bergman), and basal metabolism by using indirect calorimetry. There was a positive correlation between LVM and BMI (r = 0.61; p = 0.001), waist to hip ratio (r = 0.45; p = 0.03), basal metabolism (r = 0.61, p = 0.001), lean (r = 0.74, p = 0.0002) and fat (r = 0.49; p = 0.01) body mass. Fasting glycemia was positively correlated with LVM (r = 0.62; p = 0.001), but not Si. LVM was also positively correlated to the triglyceride level. No relations were found with systolic or diastolic blood pressure. Multivariate regression analysis was performed to determine the relative contribution of lean body mass (the morphologic variable with the best association to LVM in univariate analysis), blood glucose, waist to hip ratio, age and triglycerides. The multiple r for the model was 0.87 (p < 0.001). Lean body mass and blood glucose were found to be the only significant and independent predictors of LVM (p = 0.001 and p = 0.03 respectively). We conclude that: 1) lean body mass is an important determinant of LVM in obese normotensive individuals. Hence, in obese women, correcting LVM for lean body mass might be more accurate than correcting it for body surface area or height. 2) There is no relationship between LVM and insulin sensitivity. The link between blood glucose and LVM needs to be studied further.

Adult↗

Regulation of growth of cultured smooth muscle cells from diabetic rats by interleukin-1 beta: role of nitric oxide.

We examined the influence of streptozotocin-induced diabetes on the growth of cultured rat aortic smooth muscle cells in the presence of interleukin-1 beta. Interleukin-1 beta induced a dose-dependent biphasic effect on proliferation of diabetic and control smooth muscle cells, consistent with the data on [3H]thymidine incorporation and cell counts. However, the major effect of interleukin-1 beta was to stimulate growth of diabetic cells and inhibit growth of control cells. Furthermore, interleukin-1 beta induced a dose-dependent increase in nitric oxide (NO) release and in intracellular cyclic GMP accumulation: nitrite release was similar in both smooth muscle cell models but cyclic GMP accumulation was greater in diabetic cells than in controls. These results suggest that the inhibitory loop involving NO is not effective enough to completely counterbalance the stimulatory effects of interleukin-1 beta on diabetic cells. Therefore, experimental diabetes may modify the interleukin-1 beta-regulated smooth muscle cell growth.

Animals↗

Enhanced antiproliferative effect of nitric oxide in cultured smooth muscle cells from diabetic rats.

We examined the influence of experimental diabetes on the proliferation of cultured vascular smooth muscle cells (VSMCs) in presence of a nitric oxide (NO)-generating agent, sodium nitroprusside (SNP), and 8-bromo-cGMP. VSMC cultures were prepared from aortas of control and streptozotocin-diabetic rats. SNP induced a time- and dose-dependent inhibition of control and diabetic VSMC proliferation, consistent with the data on [3H]thymidine incorporation, cell counts, and index of culture mass. However, the responses to SNP were significantly enhanced in VSMCs from diabetic rats. SNP induced an increased dose-dependent accumulation of intracellular cGMP in diabetic VSMCs. In contrast, growth-inhibitory responses to 8-bromo-cGMP were not significantly different between the two VSMC models. Moreover, basal cGMP content in VSMCs was lower in diabetic rats than in controls, a result that can explain the enhanced proliferation observed in VSMCs from diabetic rats. These results suggest an enhanced antiproliferative effect of NO in VSMCs from diabetic rats through increased cGMP production. Therefore, experimental diabetes may impair and up-regulate soluble guanylate cyclase activity in VSMCs.

Animals↗

Adenosine inhibitory effect on enhanced growth of aortic smooth muscle cells from streptozotocin-induced diabetic rats.

1. There is evidence to suggest that adenosine may regulate arterial smooth muscle cell (SMC) growth and proliferation, which is a key event in atherogenesis. This regulation may be mediated via adenylate cyclase. As diabetes is a known risk factor for atherosclerosis, we investigated the growth of aortic SMC from diabetic rats in primary culture and their sensitivity to adenosine and to adenylate cyclase activity. 2. Diabetes was induced with streptozotocin (STZ, 66 mg kg-1, i.p.) Aortic SMC primary cultures were prepared from STZ-diabetic and age-matched rats 5 weeks after the STZ injection. 3. SMC from STZ-diabetic rats grew faster and reached greater densities at confluence than those from non-diabetic animals. 4. Adenosine inhibited growth in both control and diabetic SMC. However, cells from STZ-diabetic rats were apparently more sensitive to adenosine. 5. Direct activation of adenylate cyclase by forskolin induced a dose-dependent growth inhibition, similar in both groups of cells. 6. Cholera toxin, an activator of stimulatory GTP-binding protein (Gs), induced a similar growth inhibitory response in non-diabetic and diabetic SMC. Pertussis toxin (PTX), an inactivator of inhibitory GTP-binding protein (Gi), did not itself affect SMC growth. However, PTX increased dose-dependently the growth inhibition induced by adenosine in SMC from non-diabetic rats but not in SMC from diabetic rats. 7. These findings suggest a functional abnormality in Gi activity in SMC from diabetic rats, that would explain the increased sensitivity to the nucleoside. This impaired inhibitory pathway may reflect changes in the growth regulation of SMC in experimental diabetic states.

Adenosine↗

Evaluation of the risk of stone formation: study on crystalluria in patients with recurrent calcium oxalate urolithiasis.

OBJECTIVE: The aim of this study was to determine the usefulness of the morning calcium oxalate crystalluria in detecting stone formers particularly prone to recurrence. METHODS: Over a 24-hour period of urine collection, the morning calcium oxalate crystalluria was evaluated as well as the risk of stone formation, established with Tiselius and Parks indices, for 25 recurrent stone formers (group 1) and 25 normal controls (group 2). RESULTS: Morning crystalluria (type, size, number/ml and state of aggregate) and the Tiselius index were comparable in the two groups. Conversely, calciuria as well as the citrate/ calcium ratio and the Parks index varied significantly for stone formers and normal controls. No particular correlation appeared between crystalluria and indices of Tiselius and Parks, calciuria, calcium-oxalate product or calcium/ oxalate and citrate/calcium ratios. CONCLUSIONS: Morning calcium oxalate crystalluria does not enable an efficient characterization of recurrent stone formers. Its discordance with others potential indicators of the risk of stone formation poses the problem of their respective validity and evokes the prevalence of still unknown inhibiting agents in the phenomenon of crystallization.

Calcium Oxalate↗

[Indicators of the risk of calcium oxalate urinary calculi: comparative study of the Parks' and Tiselius' indices, urinary citrate/calciuria ratio, and morning crystalluria].

Despite the progress in basic research, the precise assessment of the risk of calcium oxalate urinary stones and the detection of patients at particular risk of recurrent stones are often problematical. A population of 55 renal stone patients and 50 controls served as a basis for various comparative studies of Parks' index, Tiselius' index, the urinary citrate/urinary calcium ratio and the morning calcium oxalate crystalluria. Parks' index and the urinary citrate/urinary calcium ratio were highly discriminant, in contrast with Tiselius' index and crystalluria, which were statistically comparable in the 2 groups. A close correlation was observed for the 3 versions of Tiselius' index, which estimates diuresis, but no particular correlation was detected between crystalluria and the other parameters studied. Parks' index and the urinary citrate/urinary calcium ratio are potentially adapted to the detection and monitoring of renal stone patients at risk of recurrence. On the other hand, the various Tiselius' indices can be essentially used to evaluate urinary calcium oxalate oversaturation and possibly to control treatments interfering with this parameter. The formula simply based on diuresis, and the 24-hour urinary calcium and oxalate excretion (CaO.71.Ox.V-1.2) appears to be sufficient for this purpose. The absence of correlation between crystalluria and the other potential indicators of lithogenic risk raises the problem of their respective validity as well as the possible prevalence in the crystallization process of the powerful inhibitors which are currently unidentified, but probably macromolecular.

Calcium↗

Effects of insulin therapy upon plasma lipid fatty acids and platelet aggregation in NIDDM with secondary failure to oral antidiabetic agents.

The effects of intensive insulin therapy on metabolic control, fatty acid metabolism and platelet function were studied in 18 non-obese non-insulin-dependent diabetics (NIDDs) with secondary failure to oral antidiabetic drugs (OAD). Patients were randomly allocated either to continue maximal OAD (Group I, n = 9) or to receive a multiple injection regimen of insulin therapy (Group II, n = 9) for a 6-month period. At baseline both groups were identical for clinical and biological parameters. At study day 180, fasting blood glucose (P < 0.01) and mean capillary blood glucose (P < 0.05) were reduced in group II but the difference between HbA1 percentages remained non-significant. At study day 60, in total plasma lipids, oleic acid was lower (P < 0.05), linoleic acid (P < 0.05) and the sum of polunsaturated fatty acids (PUFA) (P < 0.05) were higher in group II than I. In triglycerides, palmitic acid was lower in group II at study days 60 (P < 0.01) and 180 (P < 0.05), whereas gamma-linolenic acid was decreased (P < 0.05) at study day 180 only. A similar change was noted in cholesterol esters for gamma-linolenic acid at study day 60 (P < 0.05). No difference was noted between both groups for platelet agregation, insulin sensitivity and clinical parameters despite a significant increase in body weight in group II at study day 180. Positive correlations were obtained between the content of different lipid fractions in some PUFA and the glucose clearance. We conclude that optimized insulin therapy in NIDDs with secondary failure to OAD leads to a transient improvement in glucidic and lipidic metabolism but has no significant effect upon platelet aggregation and insulin sensitivity.

Adenosine Diphosphate↗

Differential incorporation of fish-oil eicosapentaenoate and docosahexaenoate into lipids of lipoprotein fractions as related to their glyceryl esterification: a short-term (postprandial) and long-term study in healthy humans.

We investigated how the distribution of eicosapentaenoate (EPA, 20:5n-3) and docosahexaenoate (DHA, 22:6n-3) in the sn-2 and sn-1(3) positions of fish-oil triacylglycerols influenced their respective incorporation into triacylglycerol, cholesterol esters, and phospholipids of two lipoprotein fractions: low- and very-low-density lipoprotein (VL/LDL) and high-density lipoprotein (HDL). Nine healthy volunteers were studied over both a short-term (0-8 h) and a long-term (30 d) postprandial period of daily supplementation with 2 g EPA and 1.3 g DHA given as 11 g fish-oil triacylglycerol in which DHA was predominantly situated in the sn-2 position. Our results strongly suggest that the higher triacylglycerol incorporation of DHA and the higher metabolic availability of EPA compared with DHA for phospholipid accumulation (particularly in the short-term study) depend on their respective preferential sn-2/sn-1(3) positions in fish-oil triacylglycerol, emphasizing the important role of the triacylglycerol structure and its potential manipulation for modulating availability of either or both fatty acids.

Adult↗

Idiopathic calcium oxalate urinary lithiasis: usefulness of Parks' and Tiselius' indices in the evaluation of the risk of stone formation.

Different indices of the risk of urinary calcium oxalate crystallization were compared to determine their usefulness in detecting the stone-formers particularly prone to recurrence. Urine volume and calcium, oxalate, citrate, magnesium or creatinine were determined in 55 patients presenting with an idiopathic calcium oxalate urolithiasis, as well as in 50 control subjects. On 24-hour urine samples, these elements allowed for the calculation and comparison of different indices of lithogenous risk as proposed by Parks and Tiselius. Both Parks' indices and the urinary citrate-calcium ratio varied significantly between the two groups, but conversely Tiselius' indices were statistically comparable. The three Tiselius' indices taking the 24-hour urine volume into account were also strongly correlated. Parks' index and the urinary citrate-calcium ratio are highly discriminating and potentially relevant to select the stone-formers with a high risk of relapse. Tiselius' indices basically reflect urinary calcium oxalate saturation, and can only be used clinically to control the treatment interfering with this. In this respect, the formula based simply on urine volume, calcium and oxalate over 24 h (Ca0.71.Ox.V-1.2) appears to be sufficient.

Adolescent↗

[Insulin, diabetes and cholesterol metabolism].

Cholesterol metabolism is altered in diabetic states. Three main mechanisms seem to be involved in these alterations: a) an increased glycation of cholesterol-rich lipoproteins, b) an insulin-resistant state which is mainly present in overweight type 2 diabetic patients, and c) changes in insulin secretion which depends on the clinical type of diabetes. Insulin per se exerts beneficial effects on the metabolism of cholesterol binding lipoproteins. Despite insulin has a stimulatory influence on the endogenous cholesterol synthesis from Acetyl-CoA, this hormone tends to decrease the LDL cholesterol concentrations through two additional effects: a diminution in the ApoB VLDL synthesis and an increase in the LDL catabolism. In well controlled diabetic patients, plasma concentrations of cholesterol binding lipoproteins are generally found within the normal range. These patients exhibit usually a normal sensitivity to insulin in the liver and peripheral tissues. In this case, the VLDL production is generally decreased, the LDL catabolism is either increased or normal, and therefore the endogenous cholesterol synthesis from Acetyl-CoA remains setted at a normal level. In poorly controlled and/or in insulin resistant diabetic patients, both VLDL cholesterol production and cholesterogenesis are increased, mainly as a consequence of the insulin-resistant state. The excessive glycation of LDL results in a diminution of their catabolism and therefore in an increase of their plasma concentrations. The reverse cholesterol transport pathway is also altered, the modifications being characterized by a diminution in HDL cholesterol concentrations, especially in the HDL2 subfraction. All these changes are certainly involved in the accelerated development of cardio-vascular complications encountered in diabetic patients.

Animals↗

Urinary calcium oxalate saturation in 'stone formers' and normal subjects: an application of the EQUIL2 program.

OBJECTIVE: To produce an index of lithogenic risk which identifies patients at risk of stone recurrence and facilitates the monitoring of prophylactic treatments. PATIENTS AND METHODS: The EQUIL2 program provides an evaluation of the state of urinary saturation, particularly of calcium oxalate, based on the pH and total concentrations (mmol/l) of sodium, potassium, calcium, magnesium, uric acid, chloride, ammonium, citrate, phosphate, sulphate, oxalate, pyrophosphate and carbon dioxide. The morning urinary calcium oxalate saturation coefficient was thus calculated for 30 stone-formers (Group 1) and 30 normal control subjects (Group 2). RESULTS: Urine from the majority of individuals was saturated, with no significant difference between the two groups. There appeared to be a correlation between the state of saturation and the urinary calcium oxalate molar product in both stone-formers (r = 0.931) and controls (r = 0.914). CONCLUSION: In future studies on urinary calcium oxalate saturation, it should be possible to supplement the sophisticated coefficient determined by the EQUIL2 program with the molar product, except in cases where monitoring therapies have little or no effect on urinary oxalate or urinary calcium levels.

Adult↗

Circadian variations in the risk of urinary calcium oxalate stone formation.

OBJECTIVE: To evaluate the circadian fluctuations in the risk of urinary calcium oxalate stone formation with regard to critical periods of crystallization. PATIENTS AND METHODS: Over a given time period, the Tiselius index depends on urine volume and urinary excretion of oxalate, calcium, citrate and magnesium. This crystallization potential was evaluated during three successive periods spread over 24 h for 25 recurrent stone-formers aged 16-76 years (mean 50) and 25 control subjects aged 27-71 years (mean 44). RESULTS: There was no significant difference in the value of the Tiselius index for all equivalent time periods in both groups of patients. The minimum value was recorded in the afternoon and the circadian pattern of the index illustrated the predominant importance of urinary output in its determination. Morning urinary concentrations and excretions of citrate, and nocturnal levels of magnesium were significantly higher in the stone-formers when compared with the control subjects. CONCLUSION: The lithogenic risk for calcium oxalate stones was maximal at the end of the night or during the early morning, when urinary output was minimal. This circadian study revealed abnormalities that are not apparent from non-fractionated 24 h urine samples, and which were potentially relevant to therapy.

Adolescent↗