Biosynthetic human C-peptide or NaCl (154 mmol.l-1) was given intravenously to 13 Type 1 (insulin-dependent) diabetic patients to determine the renal and splanchnic exchange of C-peptide. Catheters were inserted percutaneously into an artery and a renal and hepatic vein. Infusions of C-peptide were given for 60 min at two dose levels (5 and 30 pmol.kg-1.min-1). Insulin was infused throughout the study (0.5 mU.kg-1.min-1) and plasma glucose was kept constant by a variable glucose infusion. The regional blood flows were measured by indicator dilution techniques. In 11 of the 13 patients basal C-peptide levels were not detectable. The arterial steady-state C-peptide concentration was 0.81 +/- 0.10 nmol.l-1 and 2.33 +/- 0.30 nmol.l-1 at the low and high rate infusions, respectively. Renal uptake was 124 +/- 18 pmol.min-1 at the low infusion corresponding to 39% of the infused amount. At the higher dose C-peptide infusion renal uptake increased to 155 +/- 21 pmol.min-1 (p less than 0.05). Urinary excretion of C-peptide was 7 +/- 2 pmol.min-1 at the low dose infusion and increased to 34 +/- 6 pmol.min-1 at the high dose infusion (p less than 0.01). The proportions of infused amount excreted were fairly constant and between 2% and 3%. No net exchange of C-peptide was found across the splanchnic vascular bed. The rate of glucose infusion had to be increased by 35% during the low dose C-peptide, but not during NaCl infusion in order to maintain a constant plasma glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Normalization of hepatic glucose regulation despite systemic insulin delivery. Studies in patients with pancreatic transplantation for type 1 (insulin-dependent) diabetes mellitus.

With current surgical techniques for pancreatic transplantation, the graft is anastomosed to the iliac vessels, resulting in delivery of insulin to the systemic circulation rather than to the portal vein as in healthy man. The possible influence of the altered route of insulin delivery on the regulation of splanchnic glucose metabolism was studied in four patients with Type 1 (insulin-dependent) diabetes mellitus at 6-19 months after combined pancreatic and kidney transplantation. Four non-diabetic, age-matched renal transplant recipients and two groups of age-matched healthy subjects served as controls. The studies were carried out in the basal state and during two rates of intravenous glucose infusion (2 and 4 mg.kg-1.min-1). Fasting arterial glucose and splanchnic glucose output was similar in all groups. Basal hyperinsulinaemia was present in pancreatic graft recipients compared to healthy subjects. During low rate intravenous glucose infusion splanchnic glucose output decreased to a similar extent in all groups. With the higher glucose infusion rate (4 mg.kg-1.min-1) a net glucose uptake was observed which was similar in all three groups. Peripheral glucose uptake was unchanged at the lower glucose infusion rate but increased by 45-55% at the higher rate. It is concluded that despite systemic insulin delivery from a heterotopic pancreatic graft, hepatic glucose metabolism appears normal both in the post-absorptive state and in response to glucose-stimulated endogenous insulin secretion. Portal insulin delivery is thus not necessary for normal hepatic glucose metabolism in the Type 1 diabetic patient.

Adult↗

PubMed1991

The Stockholm experience with pancreatic transplantation using enteric exocrine diversion.

Between April 1974 and June 1990, 128 pancreatic transplantations were performed. Of these 117 were with pancreatico-enterostomy. In four consecutive series of combined transplantations in uraemic diabetic patients the 1-year graft survival rate have successively improved (27%, 65%, 68% and 73%). In three similar series of single pancreatic transplantations the results also improved but still remained inferior (0%, 33% and 33%). In a series of combined transplantations performed in preuraemic diabetic patients the 1-year actuarial graft survival rate was only 25%. The results with pancreatic transplantation with pancreatico-enterostomy are now satisfactory. However, immunological loss graft function still constitute a major problem in the non- or pre-uraemic recipients. The metabolic control in patients with functioning grafts is normal or near-normal in the majority of patients followed for at least 1 year.

Diabetes Mellitus, Type 1↗

PubMed1991

Long-term metabolic control after pancreas transplantation with enteric exocrine diversion.

Long-term metabolic control after pancreatic transplantation with enteric exocrine diversion was evaluated in 42 Type I (insulin-dependent) diabetic pancreas recipients with functioning grafts for 1 to 7 years. Glycaemic control (fasting blood glucose, glycosylated haemoglobin A1c, oral and intravenous glucose tolerance tests) was normal or near-normal in most patients, and showed no deterioration with time. In ten patients with functioning grafts for 5 years there was a small, but significant, improvement in the glucose control at 3 to 5 years as compared with that at 6 months post-operatively. In the latter recipients the number of acute rejection episodes correlated negatively with the intravenous glucose tolerance at 6 months (r = -0.64, p less than 0.01) and at 5 years (r = -0.60, p less than 0.01) after transplantation, respectively. The glycaemic control at 6 and 12 months after transplantation was similar whether segmental (n = 35) or whole-organ (n = 7) pancreatic grafts had been used. In six non-uraemic recipients who had received a pancreas transplant alone the serum cholesterol increased in all but one patient (0.05 less than p less than 0.1), and the LDL/HDL-cholesterol ratio was significantly higher (p less than 0.005) one year after transplantation than before. Conversely, in six diabetic patients who had lost the function of their single pancreatic grafts the lipid and lipoprotein profiles remained unaltered. It is concluded that the long-term glycaemic control after segmental or whole-organ pancreatic transplantation with enteric exocrine diversion remains essentially normal in most recipients, and it may even improve with time.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Effect of pancreas transplantation on glucose counterregulation in insulin-dependent diabetic patients prone to severe hypoglycaemia.

Pancreatic transplantation was performed in three patients with insulin-dependent diabetes mellitus in whom recurrent and severe episodes of hypoglycaemia had been found to be due to defective glucose counterregulation. Thus in these patients the spontaneous blood glucose recovery after insulin-induced hypoglycaemia (0.1 U kg-1 h-1 i.v. insulin until blood glucose levels fell below 2.8 mmol l-1) was delayed, and the responses of glucagon, epinephrine and growth hormone (GH) were absent or diminished. After pancreas transplantation the patients exhibited essentially normal blood glucose control. When the insulin infusion test was repeated 3 months after the transplantation, the blood glucose level recovered rapidly after insulin withdrawal. The glucagon response was restored, and the responses of epinephrine and GH were improved. Plasma C-peptide was suppressed by approximately 50%, which is less than is observed in normal subjects. It is concluded that glucose counterregulation improves after pancreas transplantation. This appears to be mainly due to an improvement in the hypoglycaemia-induced glucagon response, but an amelioration of sympatho-adrenal and hypothalamic-pituitary regulatory mechanisms may also be involved. The apparent failure to suppress completely the insulin release from the denervated pancreas transplant indicates that inhibition of beta-cell secretion during insulin-induced hypoglycaemia may be partly under neural control.

Adult↗

PubMed1991

Improved glucose counterregulation after pancreas transplantation in diabetic patients with unawareness of hypoglycemia.

Explore the source record for details and available documents.

Adult↗

PubMed1990

Lack of relationship between glibenclamide metabolism and debrisoquine or mephenytoin hydroxylation phenotypes.

The pharmacokinetics of a single oral dose of 1.75 mg glibenclamide were studied in 15 healthy Caucasians including five poor metabolisers of debrisoquine and five poor metabolisers of S-mephenytoin. Plasma glibenclamide concentrations and the urinary concentrations of trans-4- and cis-3-hydroxyglibenclamide were analyzed by h.p.l.c. Thirty-six +/- 6% (mean +/- s.d., n = 15) of the given dose of glibenclamide was excreted in 48 h urine as hydroxylated metabolites, 27 +/- 4% as trans-4-hydroxyglibenclamide and 8 +/- 2% as cis-3-hydroxyglibenclamide. There were no differences in the plasma pharmacokinetics of glibenclamide or in the urinary excretion of the metabolites between poor and extensive metabolisers of debrisoquine, neither between the two mephenytoin hydroxylator phenotypes. The study thus indicates that the disposition of glibenclamide is not influenced by these two independent polymorphisms of drug oxidation.

Adult↗

PubMed1990

Increased lipolytic sensitivity to catecholamines in diabetic patients with severe autonomic neuropathy.

Lipolytic sensitivity to catecholamines was studied in gluteal adipocytes from diabetic subjects with severe (n = 3), mild (n = 6) or no autonomic neuropathy (n = 8). Two of the three patients with severe autonomic neuropathy had a completely abolished plasma epinephrine response to insulin-induced hypoglycaemia, whereas the third patient showed a reduced and delayed plasma epinephrine response. Lipolytic sensitivity to isoprenaline (P less than 0.05), and to epinephrine in the presence of yohimbine (P less than 0.0001), was significantly increased in the diabetic subjects with severe autonomic neuropathy, compared to the other study groups. Moreover, the specific binding of the beta-adrenoceptor antagonist (+-)-4-(3-butylamino-2-hydroxypropoxyl)-(5.7-3H)-benzimidazole- -2-one-hydrochloride (3H-CGP) was markedly exaggerated (P less than 0.05) in the patients with severe autonomic neuropathy. These findings demonstrate that the lipolytic sensitivity to catecholamines in adipose tissue was increased only in patients with severe autonomic neuropathy and impaired epinephrine response to insulin-induced hypoglycaemia. This increased beta-adrenergic sensitivity could, at least in part, be attributed to an increased density of beta-adrenergic receptors in the adipocytes.

3-Hydroxybutyric Acid↗

PubMed1990

Hypoglycemia risk during exercise after intramuscular injection of insulin in thigh in IDDM.

The influence of bicycle exercise (60% of W170 [working capacity at a pulse rate of 170 beats/min]; 40 min) on the absorption of 125I-labeled fast-acting insulin (10 U; Actrapid human insulin) after intramuscular compared with subcutaneous injection in the thigh was studied on 2 consecutive days in 10 insulin-dependent diabetes mellitus (IDDM) patients. Insulin absorption was measured as disappearance of radioactivity (1st-order elimination rate constants) by continuous external monitoring and as appearance of plasma free immunoreactive insulin (IRI). Subcutaneous adipose tissue blood flow (ATBF) and skeletal muscle blood flow (MF) were measured concomitantly in the contralateral thigh with the 133Xe wash-out technique. Plasma glucose was determined intermittently. The rate constant for 125I-insulin increased during exercise from 0.46 +/- 0.08 to 1.17 +/- 0.14%/min after intramuscular injection (P less than 0.001) and from 0.31 +/- 0.05 to 0.45 +/- 0.09%/min (NS) after subcutaneous injection. The rate constant of 125I-insulin from muscle remained elevated during the 80-min recovery period. The peak plasma free-IRI value was 39 mU/L higher, the area under the IRI curve was approximately 80% greater, and the decrease in plasma glucose was approximately 2 mM greater after intramuscular injection. Whereas MF increased fivefold, ATBF did not rise significantly during exercise. The results demonstrate that intramuscular compared with subcutaneous thigh injection of insulin followed by bicycle exercise induces a marked increase in insulin absorption and a substantial fall in plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1990

Pancreatic transplantation using enteric exocrine diversion: the Stockholm experience with 117 cases.

One-hundred twenty-eight pancreatic transplantations were performed between 1974 and 1990; 117 of which were with pancreatico-enterostomy. Combined renal and pancreatic transplantations were performed in 68 uremic patients and in 8 preuremic recipients. Single pancreatic transplantations were performed in 31 recipients and in 6 instances, the pancreatic transplantation was performed in a patient who already had a renal graft. In 4 consecutive series (n = 15, 20, 21, 11) of combined transplantations in uremic diabetic patients, the 1-year graft survival rate has excessively improved markedly (27%, 65%, 68%, and 73%). In 3 similar series of single pancreatic transplantations (n = 7, 13, 6) the results also improved, but still remained inferior (0%, 33%, and 33%). In 42 patients followed for more than 1 year after transplantation, the mean blood glucose tolerance test 4.2 +/- 0.5, HbA1c 5.1 +/- 0.8, 2-hour blood glucose level of the oral glucose tolerance test 6.9 +/- 2.1 and the K-value of the intravenous glucose tolerance test 1.2 +/- 0.6%. The results with pancreatic transplantation with pancreatico-enterostomy are now satisfactory. However, immunological graft losses still constitute a major problem in the non- or preuremic recipients.

Diabetes Mellitus, Type 1↗