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Biomedical subjects

E Ferrannini

Publications and source records attributed to E Ferrannini.

At least 253 records · Page 14Linked to original sources
PubMed1982

Insulin resistance in diabetic ketoacidosis.

The effect of "low-dose" (6--10 U/h) insulin treatment on the rate of decline of plasma glucose concentration was determined in 15 diabetic subjects admitted in ketoacidosis (plasma glucose = 948 79 mg/dl) and in six normal volunteers rendered hyperglycemic by a combined infusion of somatostatin and glucose (plasma glucose = 653 28 mg/dl). The fractional glucose turnover and the half-time of the fall in plasma glucose during insulin treatment were both 10-fold reduced (P less than 0.001) in the diabetics as compared with the controls. In the ketoacidotic subjects, the mean glucose clearance during insulin treatment was only 8% of that in the controls (P less than 0.001). In the normal subjects, tissue glucose clearance during insulin treatment of the hyperglycemia (5.8 0.7 ml/min . kg) was similar to that measured in the same subjects using a standard technique to quantitate insulin sensitivity (euglycemic insulin clamp). In the ketoacidotic patients, a history of prior insulin therapy, but not the degree of hyperglycemia at the time of admission, was associated with a more rapid rate of decline of plasma glucose in response to insulin treatment. We conclude that marked insulin resistance is present in virtually all diabetics in ketoacidosis.

Adult↗
PubMed1981

Synergistic interaction between exercise and insulin on peripheral glucose uptake.

The interaction of exercise and insulin on glucose metabolism was examined in 10 healthy volunteers. Four study protocols were used: study 1: plasma insulin was raised by approximately 100 microunits/ml while plasma glucose was maintained at basal levels for 2 h (insulin clamp). Study 2: subjects performed 30 min of bicycle exercise at 40% of VO2 max. Study 3: an insulin clamp was performed as per study 1. Following 60 min of sustained hyperinsulinemia, however, subjects exercised for 30 min as per study 2. Study 4: subjects were studied as per study 3 except that catheters were inserted into the femoral artery and vein to quantitate leg glucose uptake. During the 60-90 min period of hyperinsulinemia (study 1), glucose uptake averaged 8.73 +/- 0.10 mg/kg per min. With exercise alone (study 2), the increment in peripheral glucose uptake was 1.43 +/- 0.30 mg/kg per min. When hyperinsulinemia and exercise were combined (study 3), glucose uptake averaged 15.06 +/- 0.98 mg/kg per min (P less than 0.01) and this was significantly (P less than 0.001) greater than the sum of glucose uptake when exercise and the insulin clamp were performed separately. The magnitude of rise in glucose uptake correlated closely with the increase in leg blood flow (r = 0.935, P less than 0.001), suggesting that the synergism is the result of increased blood flow and increased capillary surface area to exercising muscle. More than 85% of total body glucose metabolism during studies 1 and 3 was accounted for by skeletal muscle uptake. These results demonstrate that (a) insulin and exercise act synergistically to enhance glucose disposal in man, and (b) muscle is the primary tissue responsible for the increase in glucose metabolism following hyperinsulinemia and exercise.

Adult↗
PubMed1981

Sensitivity of insulin secretion to feedback inhibition by hyperinsulinaemia.

The ability of insulin to inhibit its own secretion was examined in 15 normal subjects given an intravenous infusion of insulin in a dose of 0.25, 0.50, 1.0, 5.0 or 10.0 mU/kg/min for two hours. Arterial plasma insulin concentration achieved during the infusion segregated into three levels of hyperinsulinaemia: 35 +/- 1 (mean +/- SEM), 87 +/- 15 and 828 +/- 210 muU/ml. Plasma glucose concentration was kept constant at the basal level by a variable glucose infusion. Fasting C-peptide (0.29 +/- 0.02 pmol/ml) fell significantly in all subjects during hyperinsulinaemia and reached a concentration of 0.19 +/- 0.03 pmol/ml at 60 min and 0.14 +/- 0.03 at 120 min after the start of the insulin infusion. The C-peptide response was not related to the infusion dose nor to the steady state plasma insulin concentration. It is concluded that (a) basal insulin secretion as evaluated from C-peptide measurements is inhibited by small (24 +/- 3 muU/ml) physiological elevations in plasma insulin concentration independent of changes in plasma glucose, and (b) supraphysiological or even pharmacological elevations in plasma insulin do not result in a further decrease in endogenous insulin secretion above that achieved with mild hyperinsulinaemia.

Adult↗
PubMed1980

[Our experience with over 100 cases of carpal tunnel syndrome].

Reference is made to personal experience with regard to the carpal tunnel syndrome. Attention is drawn to the importance of electromyography in the detection of median nerve deficiency, even in recent forms. The most suitable ways of treating the syndrome are also discussed.

Adrenal Cortex Hormones↗
PubMed1979

The response to intravenous glucose of patients on maintenance hemodialysis: effects of dialysis.

To learn whether a single dialysis can acutely improve the intravenous glucose tolerance (i.v.GTT) of chronically dialyzed patients, a standard i.v.GTT was performed on 10 nonobese uremic subjects on maintenance hemodialysis for 27 +/- 9 (mean +/- SEM) mo, and on a control group of 13 normal subjects. The uremic patients were tested first 0.2-17 (range) hr, and then 65-109 hr, from last dialysis. In the uremic sera, plasma glucose was analyzed by 4 methods; 2 reducing (neocopurine and ferricyanide) and 2 enzymatic (hexokinase and glucose oxidase). The reducing methods markedly overestimated plasma glucose concentration because of the presence of nonglucose reducing substances (notably, creatinine). This inteference was significantly cut down by dialysis. A single dialysis, on the other hand, failed to improve the glucose fractional decay rate (KG) computed from the glucose oxidase data (1.69 +/- 0.2%/min before and 1.35 +/- 0.1 after dialysis, versus 1.47 +/- 0.1 of the normal subjects). The same conclusion was derived from the data measured by the other 3 methods of glucose assay. Fasting plasma insulin concentrations were, on average, above normal (5.5 +/- 0.6 muU/ml) both before (12.3 +/- 2.7, p less than 0.05) and after (17.2 +/- 3.5, p less than 0.01) a single dialysis. Likewise, the area under the glucose-induced plasma insulin curve was significantly greater than normal (1.46 +/- 0.21 mU/ml . min) both before (2.26 +/- 0.34, p less than 0.05), and after (2.86 +/- 0.43, p less than 0.01) dialysis. A single dialysis had little effect on either basal or glucose-stimulated insulin release, and no significant difference in the insulinogenic index (insulin area/glucose area) was found between the control and the uremic group in either test. Insulin response was not correlated with KG, whereas it was significantly associated with higher triglyceride levels. Creatinine, urea or methylguanidine did not appear to have any influence on KG, but lower serum potassium levels were significantly associated with poorer i.v.GTT's. Plasma calcium bore a reciprocal relation to the insulinogenic index. Chronically dialyzed subjects show some degree of tissue insulin resistance, which a single dialysis fails to correct. Electrolyte disturbances may play a role in this metabolic derangement.

Adolescent↗
PubMed1979

Pattern of insulin delivery after intravenous glucose injection in man and its relation to plasma glucose disappearance.

Plasma insulin concentrations after pulse intravenous injection of glucose show an early rise, which declines towards the prestimulation level smoothly. This pattern is the effect of both continuing secretion and hormone disappearance from the plasma. To reconstruct the time-course of the acutal secretory response, we measured insulin disappearance from the plasma of 17 healthy volunteers by means of a bolus intravenous injection of 125I-insulin, and then performed an intravenous glucose tolerance test with frequent blood sampling. The data were analyzed by deconvolution, which made it possible to compute the glucose-induced posthepatic insulin delivery rate minute by minute. Under basal conditions, 2.64 +/- 0.28 (mean +/-SEM) mU/min.m2 reaches the systemic circulation. In the 90 min that follow acute glucose stimulation, 0.86 +/- 0.11 U/m2, a 270% increment over the basal production rate, is made available to the periphery. A wide individual variability was found to exist in both the basal and the glucose-stimulated delivery. They were strongly (P less than 0.001) related to each other in a direct fashion. A first spike of insulin release (107 +/- 12 mU/min) occurred in all the subjects at 2.2 +/- 0.2 min followed, in 16 subjects, by a second spike (38 +/- 6 mU/min), at 11.3 +/- 0.9 min. Two-thirds of the total postglucose insulin output were associated with the initial, oscillatory phase (from 0 to 25 min, on average), and one-third with the "tail" phase (from 25 to 90 min), during which the average delivery rate was 5.0 +/- 0.9 mU/min.m2. The delivery curves were closely (mean squared deviation of 4.5 +/- 0.5 mU/min) reproduced by computer stimulation upon assuming that insulin secretion is a function of both glucose concentration and glucose rate of change. Both the first and the second spike of insulin delivery, but not the total insulin output during the test, showed a significant, positive correlation with the plasma glucose disappearance rate computed between 10 and 60 min. Furthermore, with a time shift of approximately equal to 15 min, a significant relationship between the phases of insulin secretion and the glucose decay rates, computed over corresponding time intervals, was evident throughout the test.

Adolescent↗
PubMed1978

Lack of a gastrointestinal mediator of insulin action in maturity-onset diabetes.

It is suggested that hepatic uptake of orally ingested glucose depends not only on insulin secretion but also on the release of a gastrointestinal factor which mediates insulin action on the liver. In maturity-onset diabetes characterised by hyperinsulinaemia and insulin resistance, deficiency of this gastrointestinal factor may be the primary pathogenetic event leading to postprandial hyperglycaemia. Postprandial hyperglycaemia brings about an increase in insulin secretion; and hyperinsulinaemia, in turn, results in decreased binding of insulin to its receptor and in peripheral (extrahepatic) resistance to insulin.

Administration, Oral↗
PubMed1978

Influence of hyperinsulinemia, hyperglycemia, and the route of glucose administration on splanchnic glucose exchange.

The effects of hyperinsulinemia, hyperglycemia, and the route of glucose administration on total glucose utilization and on net splanchnic glucose exchange were studied in 20 normal volunteers with the hepatic venous catheter technique. Euglycemic hyperinsulinemia [induced by a priming plus continuous infusion of insulin resulting in plasma insulin levels of 400-1200 muunits (international)/ml and a variable glucose infusion] caused a 5- to 6-fold increase above basal in total glucose turnover. However, net splanchnic glucose uptake (0.5 +/- 0.2 mg/kg per min) accounted for only 4-5% of total glucose utilization. When hyperglycemia (223 +/- 1 mg/dl) was induced in addition to hyperinsulinemia by the intravenous infusion of glucose, splanchnic glucose uptake increased 100% to 1.0-1.1 mg/kg per min but was still responsible for only 10-14% of total glucose utilization. In other studies hyperglycemia (223 +/- 2 mg/dl) was maintained constant by a variable intravenous infusion of glucose for 4 hr and oral glucose (1.2 gm/kg) was administered at 1 hr. After the oral glucose, net splanchnic glucose uptake increased to values 6-fold higher than with intravenous glucose despite unchanged plasma glucose levels and plasma insulin concentrations well below those observed in the studies with euglycemic hyperinsulinemia. The results indicate that hyperinsulinemia or hyperglycemia induced by intravenous infusion of glucose or insulin causes minimal net uptake of glucose by the splanchnic bed despite marked stimulation of total glucose turnover. In contrast, administration of glucose by the oral route has a marked stimulatory effect on net splanchnic glucose uptake. These findings suggest that orally consumed glucose causes the release of a gastrointestinal factor that enhances insulin-mediated glucose uptake by the liver.

Administration, Oral↗
PubMed1978

Kinetic analysis of plasma insulin disappearance in nonketotic diabetic patients and in normal subjects. A tracer study with 125I-insulin.

The studies so far reported on the metabolic clearance rate of insulin in human diabetes mellitus have given conflicting results, probably because they have been conducted on few patients and have used a variety of experimental techniques and data treatments. We investigated the kinetics of insulin distribution and degradation in 35 normal subjects and in 42 nonketotic, nonobese, overtly diabetic patients, of whom 26 were above 40 yr old and 16 were 40 yr old or less at diagnosis. The design of the study combined (a) the use of a tracer to perturb minimally the steady state and to avoid glucose infusion; (b) the preparation of purified [(125)I]-monoiodoinsulin, which has a metabolic behavior similar to that of native insulin; and (c) noncompartmental analysis of the plasma immunoprecipitable (125)I-insulin disappearance curves, which were recorded for 2 h after pulse i.v. injection of the tracer.Metabolic clearance rate was found to be similar in diabetics (404+/-18 ml/min.m(2), mean+/-SEM) and in normals (420+/-14), although the latter-onset patients had slightly, if not significantly, lower metabolic clearance rate values than the earlier-onset diabetics (385+/-19 and 443+/-36, respectively). The initial distribution volume of the hormone also did not significantly differ in diabetics and normals and was similar to plasma volume. The reentry rate into the initial distribution volume of the hormone and the total, plasma-equivalent distribution volume of insulin were both significantly raised in diabetics (251+/-12 ml/min.m(2) and 10.3+/-0.5 liters/m(2)) in comparison with normals (195+/-8 and 7.5+/-0.3). The posthepatic delivery rate of insulin was found to be slightly raised in later-onset diabetics (194+/-20 mU/h.m(2)), but somewhat reduced in earlier-onset diabetics (133+/-15) in comparison with normals (172+/-14); these differences reflected the different basal plasma insulin concentrations in these three groups. Chronic treatment with oral hypoglycemic drugs, age, duration of the disease, and degree of metabolic control appeared to have only little effect on the kinetics of insulin.On the basis of these results, we conclude that insulin-independent adult diabetics show, already in the fasting state, a combination of insulin resistance and insulin deficiency and a derangement in insulin distribution, the precise significance of which is uncertain.

Adult↗
PubMed1976

Insulin kinetics after portal and peripheral injection of [125I] insulin. I. Data analysis and modeling.

The kinetics of insulin are commonly investigated by intravenous administration of labeled hormone, whereas native insulin is removed by the liver to some extent before mixing in the systemic circulation. A mathematical model has been developed which makes it possible to interpret the experimental data obtained by peripheral plasma sampling after portal and peripheral injection of the tracer. Equations are given that allow for the computation of metabolic clearance rate, initial distribution volume, production rate, and body mass of insulin. It is demonstrated that hepatic extraction can be calculated from the difference between the clearance rate values obtained after portal and peripheral injection of the tracer; an estimate of total hepatic catabolism is also derived. The assumptions and limitations underlying this mathematical analysis are discussed.

Infusions, Parenteral↗