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Biomedical subjects

B Tronier

Publications and source records attributed to B Tronier.

At least 37 records · Page 2Linked to original sources

Metabolic and cardiovascular responses to epinephrine in diabetic autonomic neuropathy.

Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients. To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 micrograms per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients with autonomic neuropathy (P less than 0.01) but was unchanged in the other groups. Since cardiac output increased to a similar extent in the three groups, the decrease in blood pressure was due to a significantly larger decrease (P less than 0.01) in total peripheral vascular resistance in the patients with autonomic neuropathy. The heart rate increased significantly more during the infusions in the patients with neuropathy than in those without neuropathy. Epinephrine produced a greater increase in blood glucose, the glucose-appearance rate, lactate, glycerol, and free fatty acids in the patients with autonomic neuropathy than in the other groups (P less than 0.05). These findings indicate that several beta-receptor-mediated responses to epinephrine are enhanced in patients with diabetic autonomic neuropathy. The underlying mechanism remains to be elucidated.

Adult↗

Kinetics of circulating endogenous insulin, C-peptide, and proinsulin in fasting nondiabetic man.

Plasma concentrations of insulin, C-peptide, and proinsulin were measured in different vascular beds in order to determine renal, hepatic, and systemic kinetics of the endogenous peptides in the fasting condition. Nineteen nondiabetic subjects were studied, two were normal, nine had minor vascular disorders, four had cirrhosis without organic kidney disease, and four had organic kidney disease with moderately decreased glomerular filtration rate. In subjects without organic kidney disease the arteriorenal venous extraction ratios of insulin, C-peptide, and proinsulin were mean 0.27, 0.20, and 0.21, respectively (n = 14). These values were significantly reduced in kidneys with organic disease. Renal plasma clearance values of insulin, C-peptide, and proinsulin were mean 113, 87, and 90 mL/min, respectively (n = 6). Urinary clearances were substantially lower (0.8, 13, 3.5 mL/min, respectively), indicating that a significant degradation of these peptides also takes place in the normal kidney. In subjects without liver disease the estimated hepatic extraction ratio of insulin was mean 0.48, under the assumption that no C-peptide is removed by the liver. Endogenously released insulin was removed from plasma in kidney, liver, and elsewhere in the approximate proportion 10%:65%:25%, whereas, C-peptide was removed by one half in kidney and the other half elsewhere. The overall metabolic clearance rates of insulin and C-peptide were estimated to be 15 and 4.5 mL/min/kg, respectively. The results indicate that the kidney contributes substantially to removal of insulin, C-peptide, an proinsulin, mainly by degradation, less by urinary excretion.

Adult↗

Metabolic control and B cell function in patients with insulin-dependent diabetes mellitus secondary to chronic pancreatitis.

Among 88 unselected patients with chronic pancreatitis 35% (95% confidence limits 25 to 46) had insulin-dependent diabetes, 31% (21% to 41%) had non-insulin-dependent diabetes or impaired glucose tolerance (by intravenous glucose tolerance test), and 34% (24% to 45%) had normal glucose tolerance. B cell function measured by C-peptide concentration after 1 mg glucagon IV correlated with the pancreatic enzyme secretion (meal stimulated duodenal lipase content). B cell function was preserved to a greater extent (P less than .01), and glycosylated hemoglobin and fasting level of glucose were lower (P less than .01 to .05) in the 31 patients with pancreatogenic diabetes than than in 35 otherwise comparable patients with type I (insulin-dependent) diabetes, yet daily insulin dose was similar in the two groups. Glucagon stimulated C-peptide was inversely correlated to glycosylated hemoglobin in insulin-dependent patients with pancreatogenic diabetes and in type I diabetes. Since body mass indices were identical in the two groups, better glucoregulation was not due to reduced food intake or malabsorption in pancreatogenic diabetes. Rather residual B cell function and/or different secretion of other pancreatic hormones in pancreatogenic diabetes may account for different metabolic control in type I IDDM compared with insulin-dependent pancreatogenic diabetes.

Adult↗

Effect of sham-feeding on glucose tolerance and insulin secretion.

Glucose, 25 g, was infused iv with or without sham-feeding in seven normal males. Sham-feeding improved glucose tolerance, incremental area of blood glucose being 63% (P less than 0.05) of that during iv glucose without sham-feeding. The actual insulin secretion evaluated from the total area under the C-peptide and insulin curves did not differ during iv glucose with or without sham-feeding. These results suggest that the cephalic-vagal reflex improves glucose tolerance during iv glucose, independent of changes in beta-cell function.

Adult↗

C-peptide and insulin secretion in diabetes mellitus treated with oral hypoglycaemic agents or diet alone. A 3 years epidemiological cohort study on the Island of Falster, Denmark.

In a 3 yr epidemiological cohort study of 273 diabetics treated with oral hypoglycaemic agents (OHA) and 60 diet-treated diabetics the predictive value of fasting plasma C-peptide levels was assessed with the attempt to discriminate between insulin dependence and non-insulin dependence. Serum insulin, blood glucose, haemoglobin AI, bicarbonate, urine for ketone bodies, height and weight were measured too. All but 8 OHA-treated patients (97%) had fasting C-peptide greater than 0.40 pmol/ml at both investigations. Six had C-peptide in the interval 0.21-0.40 pmol/ml at both investigations and 2 a C-peptide less than or equal to 0.20 pmol/ml all of which became insulin dependent during the 3 yr period. The highest fasting C-peptide concentrations were found in overweight diabetics with a blood glucose level greater than 8.5 mmol/l. Overweight diabetics had significantly elevated fasting insulin compared to the normal weights but when the IRI concentrations were corrected by the body mass index hyperinsulinaemia was positively correlated with high levels of blood glucose and haemoglobin AI, i.e. poor glycaemic control and not with overweight. The results suggest that determination of fasting plasma C-peptide can be an additional clinical help in discriminating between insulin dependence and non-dependence.

Adult↗

Effects of short-term hyperglycemia on insulin secretion in normal humans.

Stepwise glucose clamps were used to study beta-cell insulin response to glucose in normal and noninsulin-dependent diabetic subjects and to study changes in response after hyperglycemia. In normal subjects, insulin increment, delta I, correlated with glucose increment above basal, delta G, during the first 6 min of hyperglycemia, r = 0.748, P less than 0.0001. After 1 h of hyperglycemia, mean delta I/ delta G was reduced from 50 to 23 (mean difference 23 +/- 5) pmol/mmol, P = 0.0002; but delta I/% change in glucose (delta G') was unaltered (2.3 vs. 1.7, mean difference 0.4 +/- 0.3 pmol/%). Second-phase response correlated with mean glucose elevation (r = 0.835, P less than 0.0001), and no plateau was reached after 3 h at 3 mmol/l above basal glucose (rate of change of insulin concentration = 0.5; range, 0.3-0.8 pmol . l-1 . min-1). In diabetic subjects, delta I/ delta G was 20% of normal, while delta I/ delta G' was 63% of normal and second-phase response 30% of normal. We conclude that hyperglycemia per se reduces delta I/ delta G and must be considered when assessing insulin responses. Noninsulin-dependent diabetic subjects have defective first- and second-phase responses.

Blood Glucose↗

C-peptide in diabetes mellitus treated with insulin. A 3-year epidemiological study on the island of Falster, Denmark.

In a 3 yr prospective epidemiological study of 227 insulin-treated diabetics the clinical value of fasting C-peptide measurements for discriminating between insulin dependence and non-insulin dependence was assessed. A significant difference (p less than 0.01) in fasting C-peptide secretion was found between diabetics with an early onset age (less than 30 yr) and a late onset age (greater than or equal to 30 yr). Among diabetics with a late onset age (n = 124) 45% were classified as non-insulin dependent according to fasting C-peptide levels (greater than 0.40 pmol/ml) and characterized by overweight. Diabetics with C-peptide concentrations less than 20 pmol/ml were characterized by an early onset of diabetes mellitus (less than 30 yr), the duration of diabetes mellitus (greater than 5 yr), slight deviation from ideal weight, development of insulin antibodies and high daily insulin dosage. Among the 57 diabetics with a C-peptide level greater than 0.40 pmol/ml 31 accepted and could maintain good metabolic control in a period of 3 yr after change from treatment with insulin to treatment with oral hypoglycaemic agent and diet or diet regime alone. It is concluded that measurement of fasting C-peptide is of additional clinical importance for the choice of treatment of diabetics.

Adult↗

The importance of plasma free insulin and counterregulatory hormones for the recovery of blood glucose following hypoglycaemia in type 1 diabetics.

After induction of hypoglycaemia in 31 Type 1 (insulin-dependent) patients, the 10 patients with the slowest recovery of blood glucose from hypoglycaemia were arbitrarily compared with the 10 patients with the fastest recovery of blood glucose. No differences were found between the two groups regarding response of glucagon to hypoglycaemia, whereas the epinephrine (2-fold), norepinephrine (2.4-fold) and cortisol responses were significantly greater in the group with the slow recovery. The plasma free insulin concentrations were higher (2-fold) in the group with slow recovery from 30 min after stop of insulin and throughout the study. This may be explained by a 3-fold greater amount of insulin binding antibodies in this group compared to the group with fast recovery from hypoglycaemia. An inverse significant correlation was demonstrated between the rates of recovery and the amounts of insulin binding antibodies in all the patients (P less than 0.02). This implicates that enhanced counterregulatory hormone responses in the group with the slow recovery from hypoglycaemia could not compensate for the hypoglycaemic effect of a concomitant higher plasma free insulin concentration. Insulin binding antibodies, acting as a depot of circulating insulin, may be a risk factor of prolonged hypoglycaemia in Type 1 diabetics.

Adolescent↗

The effect of gastric bypass operation on glucose tolerance in obesity.

A series of variables involved in glucose handling were monitored before and after gastric bypass operation for morbid obesity. Blood glucose, insulin, C-peptide, gastric inhibitory polypeptide (GIP), pancreatic polypeptide (PP), and gastrin were measured basally and after an oral glucose load. Blood glucose, insulin, C-peptide, and PP were also measured after an intravenous glucose load. Adrenocortical function was evaluated by measuring plasma cortisol and urinary excretion of 17-hydroxy-corticosteroids and 17-ketosteroids. Nine subjects were examined before and 3 and 12 months after operation. Glucose tolerance improved postoperatively concomitant with decreased basal levels of C-peptide and insulin, increased hepatic insulin extraction, and evidence of reduced adrenocortical function. Parallel with reduced insulin resistance, support for an increase in both insulin secretion and removal was obtained postoperatively. It is concluded that the considerable endocrine abnormalities seen in morbid obesity can be normalized after gastric bypass operation and weight reduction.

Adult↗

Human proinsulin standards.

Two new batches of pancreatic human proinsulin have been compared with biosynthetic human proinsulin. Standards of these three proinsulin preparations were made on the basis of quantitative amino-acid analyses and compared in two proinsulin radioimmunoassays with a proinsulin standard prepared 14 years ago. The curves of the new standards were superimposable. However, they differed considerably from the curve of the old standard which proved to be only one-third of the strength of the new standards, thereby leading to a threefold over-estimation of proinsulin concentrations when the old standard is used. We conclude that the new standards should replace previously used standards.

Amino Acids↗

Plasma proinsulin and C-peptide concentrations in children with hyperinsulinaemic hypoglycaemia.

Plasma concentrations of proinsulin and C-peptide were measured in five children presenting with severe hypoglycaemia associated with elevated plasma levels of immunoreactive insulin (IRI) in order to determine whether the profile of circulating B-cell products related to the underlying pathophysiology of the pancreas. Results were compared with data from 13 normal infants. Four children, three neonates and a nine year old girl, were subjected to partial or total pancreatectomy. The neonates had nesidioblastosis, nesidioblastosis with a microadenoma, and a functional abnormality without histological derangement respectively; the older child had a localised adenoma. The remaining child, a neonate, had transient hypoglycaemia and elevated IRI levels associated with hyperlactataemia and hyperalaninaemia. All the children had markedly elevated plasma proinsulin concentrations; the highest levels were seen in the child with an isolated adenoma and in the neonate with nesidioblastosis and a microadenoma. Both of these children also had substantially elevated plasma C-peptide concentrations. The remaining three neonates had plasma C-peptide levels, which although in the normal range for normoglycaemia were inappropriately elevated during hypoglycaemia. It is concluded that elevated proinsulin and C-peptide concentrations are seen in children with hypoglycaemia associated with increased plasma IRI levels and that the profile of the concentrations does not provide a reliable marker for the nature of the underlying pancreatic abnormality.

Alanine↗

Glucose turnover and hormonal changes during insulin-induced hypoglycemia in trained humans.

Eight athletes (T), studied the third morning after the last exercise session, and seven sedentary males (C) (maximal O2 consumption 65 +/- 4 vs. 49 +/- 4 (SE) ml X kg-1 X min-1, for T and C men, respectively) had insulin infused until plasma glucose, at an insulin level of 1,600 pmol X l-1, was 1.9 mmol X l-1. Glucose turnover was determined by primed constant rate infusion of 3-[3H]glucose. Basal C-peptide (0.46 +/- 0.04 vs. 0.73 +/- 0.06 pmol X ml-1) and glucagon (4 +/- 0.4 vs. 10 +/- 2 pmol X l-1) were lower (P less than 0.05) and epinephrine higher (0.30 +/- 0.06 vs. 0.09 +/- 0.03 nmol X l-1) in T than in C subjects. During and after insulin infusion production, disappearance and clearance of glucose changed identically in T and C subjects. However, in spite of identical plasma glucose concentrations, epinephrine (7.88 +/- 0.99 vs. 3.97 +/- 0.40 nmol X l-1), growth hormone (97 +/- 17 vs. 64 +/- 6 mU X l-1), and pancreatic polypeptide (361 +/- 84 vs. 180 +/- 29 pmol X l-1) reached higher levels (P less than 0.05) and glucagon (28 +/- 3 vs. 47 +/- 10 pmol X l-1) lower levels in T than in C subjects. Blood pressures changed earlier in athletes during insulin infusion, and early recovery of heart rate, free fatty acid, and glycerol was faster. Responses of norepinephrine, cortisol, C-peptide, and lactate were similar in the two groups. Training radically changes hormonal responses but not glucose kinetics in insulin hypoglycemia.

Adult↗