[Nutrition and atherosclerosis].
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Biomedical subjects
Publications and source records attributed to P Drouin.
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The euglycemic hyperinsulinaemic clamp is a means for the study of insulin sensitivity. Several techniques have been described: some are manual, others are automatic and use hypertonic glucose (50%). A semi-automatic technique is described using an artificial B cell (Biostator Miles) and a pump (Vial). The method and its reproductibility in ten healthy subjects were studied. The choice of appropriate algorithms ensure a constant and stable insulin level of 93,3 +/- 5 uU/ml and good glycemic feedback through graduated glucose perfusion. The use of a supplementary pump in series with an artificial pancreas insures basic glucose input without recourse to strong concentrations (20%); glycemic feedback of the artificial pancreas is thereby dynamically controlled. The glucose requirement is 8,08 +/- 0,73 mg/kg/min. The same values are found in the same patients three weeks later and resemble those obtained using other techniques. Automatic feedback makes the technique objective; low concentration glucose solution avoids damage to veins.
Oral tests using 50 g of sucrose and 100 g of white bread were carried out in ten insulin-dependent diabetics (four with signs of residual B-cell function and in six without). Plasma glucose and C-peptide (CPR) were estimated during the 180 minutes after ingestion. After bread intake, plasma glucose increase was significantly delayed (30 min.). Hyperglycemia (greater than 2.5 g/l) lasted significantly longer after bread then after sucrose ingestion. Blood glucose decreased more quickly in subjects with residual B-cell function than in subjects without. CPR was not significantly modified by either of the carbohydrate loads. In the controlled insulin-dependent diabetic the hyperglycemia observed results from the ease of carbohydrates hydrolysis and from the amount of available glucose. The role of fructose seems weak in the case of sucrose because its conversion to glucose would be minimized in the presence of metabolic normalization as indicated by a well controlled blood glucose.
In rodents fenofibrate shares with other triglyceride-lowering agents the potential to increase the liver peroxisome population. It was therefore of interest to look for this effect in hyperlipoproteinemic patients receiving this drug. Light and electron microscopy of liver biopsies from a group of 10 patients treated with fenofibrate and from another group of 13 receiving diet only, show no morphological difference between both groups. In contrast with the rodent data the morphometric study reveals no significant changes in the number (fenofibrate group: 7.96 10(10) cm-3; group receiving diet alone: 8.41 10(10) peroxisomes per cm3 of liver tissue) or in the size (fenofibrate group: diameter = 0.53 +/- 0.07 micron; group receiving diet alone: 0.50 +/- 0.06) of peroxisomes. The difference between our results and those obtained consistently in rodents may be due to the relatively low dose in man and/or a species-dependant difference in enzyme content of liver peroxisomes, itself related to an apparent difference in the way in which lipids are handled.
The authors mention the previous conditions to the prescription of a diet for primary hyperlipoproteinemia : definition of the metabolic disease and of its nutritional dependence, precise knowledge of earlier nutritional uses, demonstration of vascular risk factor linked to the hyperlipoproteinemia, i.e. obesity which always requires a hypocaloric diet. A low cholesterol and saturated fatty acid diet reduces by 10% the cholesterolemia, and sometimes exempts from use of medical drugs in moderate hypercholesterolemia. The exceptional hyperchylomicronemia are reduced by drastic reduction of the lipid fraction of the diet, which is compensated by use of MCT. The dietetic treatment of endogenous hypertriglyceridemia depends on their nutritional dependence : an alcohol dependence implies a complete suppression of alcoholic drinks. A glucid dependence implies the suppression of simple carbohydrates and a reduction of the glucidic fraction of the diet.
Plasma beta-Thromboglobulin levels (beta-TG) were measured by radioimmunoassay in two groups of diabetic patients: first group of 152 diabetics classified according to their vascular complications and anti-diabetic therapy, a second group of 21 poorly controlled insulin-dependent diabetics before and after 24 and 48 hours of strict blood glucose control using an artificial pancreas. beta-TG levels were on average higher in diabetic patients than in 47 healthy subjects. There was no difference between beta-TG levels in non-insulin-dependent patients with one or two microangiopathic lesions were not different from patients without complications. Only diabetics with severe degenerative lesions reveal plasma beta-TG levels significantly increased. Blood Glucose control during 48 hours is accompanied by a significant reduction of beta-TG levels, although the values remained higher than those of the control group. These results suggest that platelet hyperfunction shown in diabetes by beta-TG can precede the appearance of clinically detectable lesions, but the influence of lesions on platelet behaviour is still obscure. It appears however that strict metabolic control of diabetes could have some part in platelet hyperactivity.
In rodents fenofibrate shares with other triglyceride-lowering agents the potential to increase the liver peroxisome population. It was therefore of interest to look for this effect in hyperlipoproteinemic patients receiving this drug. Light and electron microscopy of liver biopsies from a group of 10 patients treated with fenofibrate and from another group of 15 receiving diet only, show no morphological difference between both groups. In contrast with the rodent data the morphometric study reveals no significant changes in the number (fenofibrate group: 7.96 10(10) cm-3; group receiving diet alone: 8.41 10(10) peroxisomes/cm3 of liver tissue) or in the size (fenofibrate group: Diameter = 0.53 +/- 0.07 micrometer--group receiving diet alone: 0.50 +/- 0.06) of peroxisomes. The difference between our results and those obtained consistently in rodents may be due to the relatively low dose in man and/or a species-dependent difference in enzyme content of liver peroxisomes, itself related to an apparent difference in the way in which lipids are handled.
Plasma glucose and insulin responses to a 50-gm oral glucose challenge were determined in 396 nonobese subjects: 220 patients with endogenous hypertriglyceridemia and 176 normal persons. These groups were further subdivided on the basis of relative body weight: 1.0-1.1 and 1.1-1.2. Patients with endogenous hypertriglyceridemia whose obesity index was between 1.0 and 1.1 had significantly increased plasma glucose (more than 25%, P less than 0.001) and insulin (more than 18%, P less than 0.01) responses. Similar findings were also observed in patients with endogenous hypertriglyceridemia whose index of obesity was between 1.1 and 1.2, ie, there was a 25% increase in the plasma glucose response (P less than 0.001) and a 37% increase in the plasma insulin response (P less than 0.001). Thus, endogenous hypertriglyceridemia can occur in nonobese individuals, and these patients have an increase in their plasma glucose and insulin responses when weight-matched with nonobese normal subjects.
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Total plasma cholesterol and lipoprotein fractions were studied before and after 4 months fenofibrate (Lipanthyl) treatment of 34 hypercholesterolemic adults (16 IIa and 18 IIb), using a concanavalin A precipitation technique. The total plasma cholesterol levels decreased significantly for both IIa and IIb (24 and 18%, respectively, p less than 0.001). Fenofibrate reduced the apoprotein B bound cholesterol in IIa and IIb (29 and 27%, respectively, p less than 0.001). Apoprotein A bound cholesterol increased significantly in IIb (29%, p less than 0.001), but there was no significant increase in IIa (11%). Triglycerides were significantly reduced in both groups. In the light of concanavalin A specificity for apoprotein B and the utility of this technique, it is suggested that the concanavalin A precipitation technique may be applied to hyperlipidemic subjects undergoing treatment with lipid-lowering agents.
Two techniques for the separation of high density lipoproteins are compared: ultracentrifugation and concanavalin A precipitation. There is a significant correlation for the high density lipoproteins cholesterol levels found by the two techniques (r = 0.66, p less than 0.001). Nonetheless ultracentrifugation gives higher values than precipitation. When the ultracentrifuged high density lipoproteins fraction was precipitated with concanavalin A, a highly significant correlation was found between the amounts of apoprotein B and cholesterol present in the precipitate (r = 0.90, p less than 0.001). These results indicate the presence of a subfraction of the ultracentrifuged high density lipoproteins fraction which is precipitated by concanavalin A and which contains apoprotein B. This fraction is present in varying proportions according to the type of hyperlipoproteinemia, types iib and IV having the greatest amounts. In conclusion, only the concanavalin A precipitation technique results in a separation of apoprotein B-containing and non-apoprotein B-containing lipoproteins. This renders it preferable to ultracentrifugation for determining atherogenicity risks.
The authors mention the previous conditions to the prescription of a diet for primary hyperlipoproteinemia: definition of the metabolic disease and of its nutritional dependance, precise knowledge of earlier nutritional uses, demonstration of vascular risk factor linked to the hyperlipoproteinemia, i.e. obesity which always requires a hypocaloric diet. A low cholesterol and saturated fatty acid diet reduces by 10% the cholesterolemia, and sometimes exempts from use of medical drugs in moderate hypercholesterolemia. The exceptional hyperchylomicronemia are reduced by drastic reduction of the lipid fraction of the diet, which is compensated by use of MCT. The dietetic treatment of endogenous hypertriglyceridemia depends on their nutritional dependance: an alcohol dependance implies a complete suppression of alcoholic drinks. A glucid dependance implies the suppression of simple carbohydrates and a reduction of the glucidic fraction of the diet.
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Variations in peptide composition of apoprotein C from very low density lipoproteins were studied in 10 type IV hyperlipoproteinemics, before and after triglyceridemia normalization through appropriate diet. The subjects were sensitive to carbohydrates or alcohol : a reduction or elimination of the inducing nutrient led to a decrease in serum triacylglycerol levels, correlated with an increase in the proportion of apo CII and a decrease in the proportion of apo CIII1. Apo CIII2 was not affected. This led to an increased ratio, apo CII/apo CIII1. The percentage of variation of different lipid (triacylglycerols and cholesterol) and protein (apoproteins CII, CIII2) parameters were also studied.
The fatty acid incorporation into adipose tissue (FIAT) and glucose incorporation into adipose tissue (GLIAT) have been measured in 11 patients suffering from Type IV hyperlipoproteinaemia during the hypertriglyceridaemic phase (HTG) and after normalization of triacylglycerol (TG) levels as a result of a diet which was adapted to the nutritional response of subjects. Results have been compared with those obtained in 10 reference subjects. During the HTG phase FIAT and GLIAT activities were significantly lower than in the case of reference subjects: FIAT (76.5 vs 185 nmol divided by 3/g adipose tissue/h, GLIAT (92.5 vs 208 nmol x2/g adipose tissue/h). After reduction of HTG, these activities increased in a significant way, FIAT (137.7 vs 76.5 nmol divided by 3/g/h) and GLIAT (160 vs 92.5 nmol X 2/g/h). These results agree with the hypothesis that the reduced incorporation of fatty acids and glucose into adipose tissue, measured in vitro, is partly due to the modification of the profile of lipoproteins and apoproteins related to hypertriglyceridaemia.
Radiological evidence of progression of diabetic foot lesions was studied in 31 patients. Three types of progression could be distinguished: lesions became worse (16 cases), improved (8 cases), or fluctuated in extent (6 cases). Mechanisms of production of the lesions and their prognostic significance are analyzed. Progression of the lesion is usually the result of infection. Reconstructive therapy requires evidence of a satisfactory vascular integrity in patients with associated arterial and neurological disorders. A fluctuating course is a typical finding in diabetic osteoarthropathy.
The measurement of the venous distensibility by straingauge plethysmography during a semi-continuous variation (3 mm Hg every 20 seconds) of the cuff pressure during its inflation from 0 to 100 mm Hg and its deflation allow to record the venous hysteresis and to determine accurately the venous pressure. The standardized and automatic (Periflow J.S.I.) new method is highly discriminative between controls and varicose patients.
Manufacturing quality, accuracy and users opinion (i.e. medical and nurses staff and patients) were compared among five Destrostix reading reflectance-meters for home-blood-glucose-monitoring. Two machines (dextrometer and glucometer) equipped with microprocessors, integrated circuits and good quality wiring are best made. Reflectance-meter capillary blood glucose measurements were found to be accurate enough for home-blood-glucose-monitoring, compared to a reference method. However, two machines from the same brand were different in blood glucose accuracy. Glucocheck had poorest results. Users prefer small sized, battery powered machines. Glucometer appears to be best suited to home-blood-glucose-monitoring.