Functional study of insulin secretion pattern following segmental neoprene-injected pancreatic allograft in insulin-dependent (type 1) diabetic recipients.
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Biomedical subjects
Publications and source records attributed to A Secchi.
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We performed 39 neoprene-injected pancreatic transplants (38 segmental and 1 total) in 37 insulin-dependent diabetic recipients from October 1976 to May 1983. The best results were obtained when the pancreas was transplanted simultaneously with the kidney (25 cases). The use of Cyclosporin A (CyA) for immunosuppression did not reduce the early pancreatic failures, but it seems to have slightly improved the long-term survival. The glycaemic control was better in patients treated by CyA alone than in those receiving steroids. The main side effects of CyA were nephrotoxicity and some immunoglobulin abnormalities with or without lymphoproliferative disorders occurring after treatment with CyA and ALG.
Regular or crystalline insulin with sodium glycocholate as surfactant administered intranasally to normal volunteers induced hypoglycaemia and an increase in serum immunoreactive insulin concentrations. Serum C-peptide concentrations decreased or remained unchanged. Insulin administered intravenously to three of these subjects yielded a potency ratio of 1:8 for intranasal and intravenous insulin. In four insulin-dependent diabetics a cross-over study was performed on different days, insulin being administered once intranasally and once subcutaneously in a ratio of 1:9. In these patients the intranasal insulin was more effective than the subcutaneous insulin in preventing hyperglycaemia after breakfast. In four other insulin-dependent diabetics 11-hours monitoring was performed twice on two different days, insulin being administered in divided dosage sufficient to achieve a reasonable glycaemic profile. The administration during the morning, whereas subcutaneous insulin was more effective than intranasal during the afternoon.
No statistically significant correlations were detected between plasma CEA levels, DNCB skin test responses, peripheral lymphocytes and plasma immunoglobulins in 90 patients with G.I. advanced adenocarcinomas, treated with BCG aspecific immunotherapy and chemoterapy.
Ninety-seven pancreatic grafts in 92 insulin-dependent diabetic patients were performed during the last 11 years. Eighty-three of these grafts were carried out after neoprene duct injection, the other patients underwent pancreato-duodenal transplantation. In 80 cases, a double pancreas and kidney graft was performed. Five different immunosuppressive protocols were subsequently applied. Actuarial survival of patients and pancreata was 75.1% and 47%, after one year and 54.6% and 22.1%, respectively, 4 years after transplantation. Slightly better results were observed in double pancreas and kidney transplantation. The survival of both patients and pancreas improved when the most recent immunosuppressive protocols including cyclosporin A and only small doses of steroids were applied. The main causes of loss of the pancreatic graft were rejection, vascular thrombosis and death of the patient with functioning organ. Metabolic studies showed good insulin secretion with normal or impaired glucose tolerance as well as good short and half-term glycemic control. Whole pancreas grafts with enteric diversion yielded prompter and higher insulin secretion but the incidence of surgical complications was increased. In comparison to the data recorded at 6 months after pancreas transplantation, 5 patients of our series with still functioning organ showed an equally satisfactory and unchanged glycemic control after more than 4 years from surgery. In these patients, the previously high insulinemic values decreased to normal levels. However, 3 of these patients showed a decrease in post-prandial peaks as confirmed also by OGTT. However, mean blood glucose level was not altered. In our series the suppression of exocrine pancreatic secretion by neoprene duct injection did not appear to represent a relevant cause of decrease in endocrine function. The results obtained do not yet allow us to draw definite conclusions as to the efficacy of pancreas transplantation in the treatment of degenerative complications in diabetic patients.
In a previous study, we observed an impairment of the theophylline-induced suppressive system in recent onset IDDM patients, and demonstrated also a correlation with metabolic derangement. The aim of this study was to better investigate the relationship between theophylline sensitivity (ThS) and blood glucose/plasma insulin levels in recent onset IDDM patients subjected to preprogrammed variations by an insulin/glucose clamp with artificial pancreas. Eight patients were studied within 8 weeks from the onset of IDDM. ThS was evaluated as the ability of theophylline to inhibit blastogenic response of peripheral blood lymphocytes (PBL) to Concanavalin A (ConA), after 120 min preincubation of the cells. All patients were connected to an artificial pancreas. Through i.v. continuous insulin infusion (0.02 U/kg/h) and/or i.v. continuous glucose and saline infusion, the following experimental conditions, lasting at least 1h, were obtained: T1: relative euglycemia and normal insulinemia; T2: relative euglycemia and hyperinsulinemia; T3: hyperglycemia and normal insulinemia; T4: hyperglycemia and hyperinsulinemia. ThS was maintained in 6/8 patients at T1 and in 8/8 patients at T4. ThS was lost in 4/8 patients at T2 and T3. These data suggest that the loss of ThS induced by hyperglycemia can be corrected by hyperinsulinemia, and that it is maintained when euglycemia is accompanied by hypoinsulinemia. It is lost when these two parameters lose their interrelationship.
In diabetic patients cardiovascular morbidity and mortality is still a major problem. Our aim was to study the effect of kidney-pancreas transplantation on survival, cardiovascular events, and causes of death in diabetic type 1 uremic patients. Three hundred and thirty-three uremic IDDM patients were enrolled in our waiting list for kidney-pancreas transplantation: 107 underwent kidney-pancreas transplantation (KP), 34 underwent kidney transplantation alone (KA), whereas 192 patients remained on dialysis (WL). Actuarial survival and causes of death were recorded over a period of 7 years. Seven-year survival rate was 75% for the KP group, 63% for the KA group, and 37% for the WL group (p = 0.001). Cardiovascular death rate was 9.8% in the KP group, 17.6% in the KA group, and 18.1% in the WL group (KP vs. WL, p = 0.05). Rate of acute myocardial infarction in the KP group was lower than in the KA group (2.4% vs. 17.6%, p = 0.005) as well as rate of acute pulmonary edema (0.8% vs. 23.5%, p = 0.0001) and rate of hypertensive patients at 1 (40.9% vs. 85.0%, p = 0.0001) and at 2 years (57.6% vs. 80%, p = 0.03). Kidney-pancreas transplant helped to obtain euglycemia with positive effects on survival and cardiovascular events.
The aim of this study was to evaluate the insulin (IRI) response to different stimuli and insulin sensitivity in Type 2 diabetic patients responsive to oral hypoglycaemic agents (OHA) and in Type 2 diabetic patients with secondary failure of OHA (SF), all patients being of normal body weight (relative body weight less than 120%), and the possible role of cyclic AMP in the reduced IRI release. SF patients, without islet cell antibodies (ICA), with hyperglycaemia lasting more than 3 months, underwent tests with i.v. tolbutamide (n = 21), i.v. glucose (n = 14), i.v. glucagon (n = 19), i.v. arginine infusion (n = 18); the arginine infusion was repeated in 12 patients during administration of aminophylline, an inhibitor of phosphodiesterase. The same tests were performed in groups of 8 to 15 OHA patients and in groups of 6 to 17 healthy subjects. During all the tests, blood glucose levels were higher in SF patients, than in OHA patients and in healthy subjects. Both SF patients and OHA patients had no IRI response to glucose; SF patients, in contrast to OHA patients, had a reduced IRI response to tolbutamide and to glucagon. The IRI response to arginine was not different in OHA, in SF patients and in healthy controls, but was significantly enhanced by aminophylline only in healthy controls. Insulin infusions (1.66 mU/Kg/min for 90 min) were performed in OHA patients and in SF patients at blood glucose levels of 150 and of 250 mg/dl: during the last 60 min, the amount of glucose metabolized (M), and the insulin sensitivity (M/I) index were greater in OHA than in SF patients.(ABSTRACT TRUNCATED AT 250 WORDS)
The incidence of diabetes in kidney transplant recipients is between 4 and 20% in patients previously not affected by this pathology. This difference is partially due to the immunosuppressive therapy administered. The incidence of diabetes is very high during the first quarter after the transplant, and it becomes stable during the following quarters. The presence of diabetes - evaluated by postprandial glycemia and glycated hemoglobin - should be checked quarterly during the first year after the transplant, every six months during the second year, and yearly starting from the third year. The immunosuppressive therapy (calcineurin inhibitors and steroids), familial history, age, race, and weight (BMI) are among the risk factors of diabetes post-transplant. An increased risk of rejection seems to be among the principal consequences of diabetes in transplant recipients. Moreover, these patients are more prone to infections, cardiovascular disease, and the degenerative complications of diabetes. These facts increase the risk of organ insufficiency, morbidity, and mortality. To manage diabetes in transplant recipients it is necessary to identify at-risk patients before the transplantation, thus avoiding complicated and hazardous examinations after the transplant. After the transplantation, the modifiable risk factors, such as the immunosuppressant drugs used and the control of body weight, must be checked. The control of hypertension is important as well.
The present study was aimed at evaluating the role of the Autonomic Nervous System (ANS) in the insulin (IRI) response to arginine in humans. Nine patients who were recipients of simultaneous segmental pancreatic and renal grafts (6 receiving steroids and azathioprine as immuno suppression therapy, 3 treated with Cyclosporine A), 3 non-diabetic patients with kidney grafts (receiving steroid and azathioprine) and 10 normal subjects were studied. Arginine induced a clear IRI release in all subjects with no significant difference among the groups. Somatostatin (SRIF) inhibited IRI release to a similar degree in all subjects. Since the transplanted pancreas is completely denervated, these data suggest that the integrity of the ANS is not essential to the IRI response to arginine, nor for the inhibitory effect of SRIF on IRI release.
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