[Plasma insulin responses to oral and venous glucose in various forms of diabetes mellitus].
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Biomedical subjects
Publications and source records attributed to A Orsetti.
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In a 46-year old Caucasian woman, the authors report a B-cell adenoma with plasma immunoreactive insulin (IRI) ranging from 10 to 32 microunits/ml, despite severe spontaneous hypoglycemia. In a peroperative sample withdrawn from the portal vein, normal IRI (40 micromicron/ml) in the presence of high insulin-like activity (290 microunits/ml) was observed by using a biological assay performed on rat epididymal fat tissue. Furthermore, this material did not cross-react with insulin antibodies and was undetectable in systemic venous samples. Although further identification by chromatographic extraction was not performed, the substance secreted by the tumor is probably identical to the non-suppressible insulin-like activity (NSILA) isolated by Froesch and responsible for hypoglycemia in a few cases of extrapancreatic tumors. The absence of this material in systemic samples indicates an immediate removal by a single passage through the liver.
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We investigated whether zincuria is associated with microalbuminuria in type I (insulin-dependent) diabetics (IDDM). In 169 IDDM, 215 overnight urine samples were collected for simultaneous assay of zinc and albumin. In 76 samples with excessive microalbuminuria (greater than 15 mg/L), zincuria was higher than in the 139 other samples (0.83 +/- 0.06 vs 0.58 +/- 0.03 mg/L p less than 0.001), though zincuria and microalbuminuria were not significantly correlated. An exercise provocation test was performed in 78 IDDM. Although microalbuminuria increased, zincuria did not change during the test. Another group of 83 IDDM underwent urinary zinc determination over a period of 1 h of recumbency. The 48 patients who had a zincuria higher than the mean + 2 SD of control values had higher microalbuminuria at rest (48 +/- 16 micrograms/min vs 12 +/- 2 p less than 0.01) and after exercise (111 +/- 33 vs 42 +/- 14 p less than 0.02) than the remaining 35 subjects. Both subgroups did not differ for zinc intake and zincemia. Thus, incipient nephropathy as detected by the measurement of microalbuminuria is associated with a highly significant increase in zinc excretion, which is not proportional to albumin leakage, nor is it amplified during exercise. Hyperzincuria is not explained by an increase in zinc intake and does not result in hypozincemia.
A possible role for zinc deficiency in some cases of growth retardation in southern France was investigated. Control values for zinc for 160 children (age = 12.5 +/- 2.4 yr) are 0.85 +/- 0.22 mg/L (mean +/- 2 SD). Twenty-five children with low serum zinc values (less than 0.63 mg/L) and 25 matched short children with normal serum zinc values (greater than 0.63 mg/L) were studied. Children in the two groups did not differ significantly in age, pubertal development, stature, and weight. For the 25 children whose serum values were low, we found significantly lower values for bone age delay, growth velocity in mm/month, as well as the ratio between calculated growth velocity and theoretical growth velocity for the bone age (so that zincemia was correlated to these parameters in the whole sample of 50 subjects). Nevertheless, no significant difference could be found between the two groups for serum somatomedin C, serum osteocalcin values, and GH responses to the GH stimulatory tests (exercise test, overnight sampling, insulin-induced hypoglycemia, arginine test). Therefore, low serum zinc is associated with a retardation in both somatic growth and pubertal maturation.
Trace elements have been shown to improve red blood cell (RBC) deformability: zinc in sickle cell disease and magnesium in an in vitro model of chemically rigidified erythrocytes. In this study, we investigated the effect and the influence of incubation time of zinc or magnesium on an in vitro model of rigidified RBCs by heating. Erythrocyte rigidity was determined by viscosimetry at high shear rate by a falling ball viscosimeter MT 90. In the first part of the study, six normal volunteers participated. Viscosimetry was performed on native blood before and after heating the sample for 10 min at 50 degrees C. Therefore, increasing concentrations of zinc gluconate (final concentration: 0.5-4 g/L) or isotonic NaCl as control medium were added to the sample. Heating induced a twofold increase in all indices of RBC rigidity (p < 0.05). At all these concentrations of zinc, a highly significant, dose-related fluidifying effect was observed (40-70%): this effect was immediately obtained and did not change over 60 min. Even at the highest concentration, recovery was not complete. In the second part of the study, we studied magnesium's effects on blood. In a first protocol, whole blood was rigidified by heating at 56 degrees C for 10 min, and the correcting effect of 5 min of incubation at 37 degrees C of RBCs in 150 mmol/L NaCl, MgSO4, magnesium acetate, and magnesium gluconate was investigated. In a second protocol, the same incubation with NaCl and magnesium salts was made on blood that had not been previously heated.(ABSTRACT TRUNCATED AT 250 WORDS)
Serum zinc was measured in 20 adolescent gymnasts (9 boys, 11 girls, age 12-15 yr) explored for detecting possible adverse effects of intense training on pubertal maturation and growth. They had low serum zinc (0.599 +/- 0.026 mg/L) when compared to matched control sedentary children (n = 118 mean 0.81 +/- 0.014 p < 0.001). Girls had lower zinc than boys (0.557 +/- 0.023 vs 0.651 +/- 0.044 p < 0.001). Zinc was correlated to isometric adductor strength (r = 0.468 p < 0.05). Children with serum zinc < 0.6 mg/L had lower insulin-like growth factor binding protein 3 than others (2.326 +/- 0.264 vs 2.699 +/- 0.12 p < 0.01). Thus, zinc is lowered in trained adolescent gymnasts and even lower in females. This reduction could play some role in abnormalities of puberty, growth, or muscular performance.
Zinc improves both insulin secretion and insulin sensitivity, and exerts insulin-like effects. We investigated its acute effects on the parameters of glucose assimilation determined with the minimal model technique from frequent sampling intravenous glucose tolerance test (FSIVGTT) in seven healthy volunteers. FSIVGTTs (0.5 g/kg of glucose, followed by 2 U insulin i.v. injection at 19 min) were performed after the subjects had taken 20 mg zinc gluconate twice (the evening before and 30 min before the beginning of the test) or placebo pills (simple blind randomized protocol). Glucose assimilation was analyzed by calculating Kg (slope of the exponential decrease in glycemia), glucose effectiveness Sg (i.e., ability of glucose itself to increase its own disposal independent of insulin response), and SI (insulin sensitivity, i.e. the effect of increases in insulinemia on glucose disposal). The two latter parameters were calculated by fitting the experimental data with the two equations of Bergman's "minimal model." Zinc increased Kg (p < 0.05) and Sg (p < 0.05), whereas SI and insulin first-phase secretion did not significantly increase. This study suggests that zinc improves glucose assimilation, as evidenced by the increase in Kg, and that this improvement results mainly from an increase in glucose effectiveness (insulin-like effect), rather than an action on insulin response or insulin sensitivity.
In eight patients exhibiting chemical diabetes mellitus with a poststimulative hypoglycemia, we observed that the pattern of the oral glucose tolerance test (OGTT) was improved when indigestible fiber was added to the oral glucose load. As compared with a standard OGTT, the peak blood glucose, expressed as per cent change from baseline, was particularly blunted by pectin or by cellulose phosphate but remained unchanged with cellulose supplementation. The time interval required to reach the blood glucose peak was significantly prolonged with pectin. The rate of blood glucose rise was reduced to a greater extent by pectin than by cellulose phosphate, which in turn was more efficient than cellulose. The blood glucose nadir expressed as per cent change from baseline was blunted by pectin, while the results were not significantly different after addition of either cellulose phosphate or cellulose. On the other hand, the plasma immunoreactive insulin did not show any significant change whether the glucose was given with or without one of the aforementioned types of fiber. From these results, it is concluded that an additional fiber intake may be of interest in the management of chemical diabetes. The use of pectin may diminish the poststimulative hypoglycemia.
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Sixteen patients suffering from symptoms suggestive of idiopathic reactive hypoglycaemia and reproducible during an oral glucose tolerance test when plasma glucose was less than or equal to 2.8 mM, were included in an acute, double-blind and cross-over study to test the efficacy of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor versus placebo. Patients were randomized to ingest 100 mg Miglitol or placebo together with a sucrose solution (45 g/m2 body surface), one week apart. During four hours, plasma glucose levels were continuously monitored and plasma insulin and gastric inhibitory polypeptide (GIP) levels were measured at 30-minute intervals; serum C-peptide concentration was determined at 0, 30, 60 minutes and then every hour. The post-load rise in plasma glucose was significantly blunted by Miglitol, as shown by the reduced plasma glucose peak, the diminished early (0-120 min) area under the glycaemic curve and the decreased rate of plasma glucose rise. Thereafter, plasma glucose nadir was significantly raised and rate of plasma glucose fall was slowed by Miglitol with a concomitant improvement in the hypoglycaemic index. Insulin secretion was dampened as indicated by parallel reduction of plasma insulin and serum C-peptide peaks; morever, early area under the insulin curve and total (0-240 min) area under the C-peptide curve were significantly reduced. Decrease of plasma GIP peak and total area under the GIP curve were also significant. During sucrose tolerance test with Miglitol, hypoglycaemic symptoms were significantly alleviated but intestinal side-effects were common. Blunting the insulin response to glucose directly by delaying glucose absorption and indirectly through reducing GIP secretion, may be a valuable therapeutic approach in reactive hypoglycemia; nevertheless, long-term study with Miglitol are needed, due to the poor intestinal tolerance of this drug in the present acute study.
Disclosure of microalbuminuria gives a hope to improve renal and perhaps cardiovascular outcome of diabetes mellitus by the mean of an early treatment. We studied in 30 diabetic patients for each sex, consecutively admitted to hospital the efficacy of a colorimetric tablet-test for quick screening of microalbuminuria. The results obtained from a 24 hours-urine collection are compared to those observed with a reference radio-immunologic method. In this population whose prevalence for microalbuminuria over 15 micrograms/mn is 30%, the test shows a sensibility and a negative predictive value of 100%, but a specificity and a positive predictive value of about 40%. Else, intensity of positivity follows systolic blood pressure and creatininemia increase. If the good and cheap screening value of the test can be acknowledged, its positivity needs however a precise evaluation by a reference assay before therapeutic decision.
The aim of the present study was to evaluate the acute effect of acarbose, an alpha-glycosidase inhibitor, on glycemic and insulin response to an oral sucrose load in sixteen patients suffering from idiopathic reactive hypoglycemia. In each subject, two oral sucrose tolerance tests (45 g/m2 body surface) were performed with either placebo or acarbose in a double-blind random order. Compared with placebo, acarbose dramatically flattened the blood glucose curve with values significantly lower from 30 to 90 min and higher from 150 to 240 min. Moreover the magnitude of both glucose peak and nadir, and rate of blood glucose rise and fall were significantly reduced by acarbose as was the hypoglycemic index. Plasma insulin levels from 30 to 120 min, insulin peak and area under the insulin curve were significantly lower after ingestion of acarbose. Thus, in reducing the early rise in blood glucose and insulin after sucrose ingestion, acarbose prevents the occurrence of reactive hypoglycemia; the present study confirms that this drug may be of value in the treatment of reactive hypoglycemia.
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