R. Castoldi

Reduction of insulin resistance by combined kidney-pancreas transplantation in Type 1 (insulin-dependent) diabetic patients

SummaryTo evaluate the effect of combined kidney and pancreas transplantation on insulin action and glucose metabolism, 15 Type 1 (insulin-dependent) diabetic patients who were undergoing combined kidney-pancreas transplantation were studied before transplantation by means of the euglycaemic hyperinsulinaemic clamp technique combined with 3-3H-glucose infusion and indirect calorimetry. Nine of the original 15 patients were studied again after four months and six after 12 months, successful combined kidney-pancreas transplantation with the same experimental protocol. Nine volunteers formed the group of normal subjects. Combined kidney-pancreas transplantation normalised hepatic glucose production and reduced peripheral insulin resistance in Type 1 diabetic uraemic patients, despite chronic immunosuppressive therapy. To further evaluate the hypothesis that residual insulin resistance was due to chronic steroid therapy, 11 additional subjects with chronic uveitis (six of whom were treated with only prednisone, and five treated only with cyclosporin) underwent the same protocol demonstrating a normal hepatic glucose production. The insulin-stimulated peripheral glucose uptake was reduced in the prednisone-treated group, but normal in cyclosporin-treated subjects. Four additional diabetic patients with a kidney transplant were also studied. They showed a peripheral insulin sensitivity intermediate between diabetic uraemic patients and patients after combined transplant. We conclude that short-term (one year) combined kidney-pancreas transplantation improves glucose metabolism by restoring normal rates of hepatic glucose production and reducing peripheral insulin resistance; chronic steroid therapy is the major determinant of residual reduced insulin action. Both kidney and pancreas substitution play a role in reducing peripheral insulin resistance.

Endometriosis of the lung

The first case of a clinically and histologically verified miliary form of endometriosis of the lung is reported here. The cardinal symptom was a menstrually synchronised hemoptysis, which by treatment with high doses of progestins disappeared. After operative castration a complete remittence with normal chest X ray was attained.

Surgical septic complications in diabetic patients

SummaryIn a retrospective study postoperative septic complications were evaluated in 140 insulin-dependent diabetic patients who underwent surgery. The data collected were matched with those of a group of non-diabetic patients, homogeneous for sex, age, and type of surgical procedure. Patients of each group were further divided into 3 subgroups according to the risk of intraoperative contamination (clean-, clean-contaminated, and contaminated procedures). Diabetic patients had a significantly (p<0.01) higher rate of septic complications in clean- and clean-contaminated procedures particularly of wound infections. Our experience suggests that diabetes represents an important risk factor.

Pancreata From Pediatric Donors Restore Insulin Independence in Adult Insulin-Dependent Diabetes Mellitus Recipients

CONTEXTnThe use of pediatric donors can increase the number of donors available for pancreas transplantation.nnnAIMnThe aim of this study was to verify if pancreas transplantation from pediatric donors is as effective as transplantation from adult donors to restore metabolic control in type 1 diabetic patients.nnnMATERIALS AND METHODSnFrom 2000 to April 2009 we performed 17 pancreas transplantations from pediatric donors: 9 simultaneous kidney-pancreas (SPK), 6 pancreas transplantation alone (PTA), and 2 pancreas after kidney (PAK). All subjects received whole organs with enteric diversion of exocrine secretions; 11 underwent systemic and 6 underwent portal venous graft drainage. The immunosuppressive therapy was as follows: prednisone, mycophenolate mofetil, anti-thymocyte globulin (ATG), and cyclosporine or tacrolimus. The pediatric donor population had a mean age of 15.3 years (range, 12-17), a mean weight of 60.1 kg (range, 42-75), and a mean body mass index (BMI) of 21 (range, 17.9-23.4).nnnRESULTSnAfter 9 years the overall patient survival rate was 94.12%, whereas the graft survival rate was 63.35%. Normal glucose and insulin levels were maintained either fasting or during oral glucose tolerance test (OGTT). The group of recipients of pediatric organs was compared with patients receiving organs from adult donors (n = 125); the mean glucose values were lower in the pediatric group, whereas insulin production was higher in the adult patients. Early venous thrombosis was 17.6% in the pediatric group and 20% in adult recipients (Fisher exact test, P = not significant [NS]).nnnCONCLUSIONnPediatric donors restored insulin independence in adult diabetic recipients, representing a valid source of organs for pancreas transplantation.

Octreotide administration in the treatment of pancreatic fistulae after pancreas transplantation

Among the surgical complications of pancreas transplantation are pancreatic fistulae, which arise rather frequently. Suppression of exocrine secretion with polymers has succeeded in reducing the rate of this complication. Nevertheless, in some instances, pancreatic fistulas may occur. Thirty pancreas transplantations were performed in 27 diabetic patients. In 5 cases a pancreatic fistula occurred and was drained after the insertion of a catheter for the collection of secretions. A serous liquid was collected with a high concentration of amylases (61604±19562 IU/24h). Fistula output was 280 ±87 ml/24 h. Patients were treated with octreotide, administered subcutaneously in a dose of 300–750 μg/day. In all patients a progressive reduction in fistula output was observed after a mean of 16+2 days. Fistula flow rate dropped to 24±10 ml/24 h-areduction of 95%±5% and drainage was subsequently stopped. Sonographic followup did not show recurrence of peripancreatic collections in these patients. All patients were insulin-independent up to 12–44 months after surgery.

Mono-oligoclonal immunoglobulin abnormalities in diabetic patients after kidney transplantation: influence of simultaneous pancreas graft

Summary Monoclonal components (MC) are detected in as high as 30 % of renal transplant recipients. Our aim was to evaluate the incidence, relevance and consequence of monoclonal components in patients with Type I (insulin-dependent) diabetes who received kidney (n = 22), kidney and whole pancreas (n = 41), kidney and segmental pancreas (n = 24) and kidney and islets (n = 12) transplants. Immunosuppression was based on prophylactic anti-lymphocyte globulins, corticosteroids, azathioprine and cyclosporin in all patients; acute rejection was treated with steroids or anti-lymphocyte monoclonal immunoglobulin therapy (OKT3) or both. Serum immunofixation was carried out in all patients before transplantation and then after at 6 months and then yearly. Monoclonal components were detected in 81 of 99 patients (82 %); 52 patients (52 %) developed them within 6 months of transplantation, 15 (15 %) between 6 and 12 months, with a peak prevalence at 1 year post-transplant (58 %) and a decrease thereafter (10 % at 9 years). Kidney recipients showed a lower incidence of monoclonal components when compared with those who received kidneys and segmental pancreases and those who received kidneys and whole pancreases. Monoclonal components were more often detected in patients who had previously experienced an acute renal rejection. Cytomegalovirus infection and acute rejection occurring in the same patient further increased the risk of developing monoclonal components, the development of which did not correlate with OKT3 treatment. A Post-transplant lymphoproliferative disorder was developed by two patients (2 %), one with 5 and the other with 6 monoclonal components. In conclusion, diabetic patients receiving kidney and/or Pancreas transplantation, experiencing both cytomegalovirus infection and acute rejection, are at greatest risk of developing monoclonal components but they appear to be benign and transient; multiple band detection is a marker for the subsequent development of post-transplant lymphoprolifertive disorder. [Diabetologia (1998) 41: 1176–1179]

Catabolic response and parenteral nutrition after simultaneous kidney and pancreas transplantation

The aim of the study was to quantify the catabolism rate induced by simultaneous kidney-pancreas transplantation and to evaluate the impact of parenteral nutrition (PN) on recovery of graft function. Twenty-six diabetic uremic patients were studied. The average urea nitrogen production (UNP) was 5.2 +/- 1.7 g during the first 24 h after transplantation, while patients did not receive energy and nitrogen support. Energy (30 kcal.kg-1.day-1) and nitrogen (0.15 g.kg-1.day-1) intake started 24 h after surgery. In 14 patients, a mixed regimen was adopted (70% carbohydrates, 30% lipids), and 12 patients received only hypertonic glycidic solutions. The recovery of kidney function was immediate in all cases, with a prompt decrease in blood urea nitrogen and serum creatinine levels. C-peptide levels rose immediately after the revascularization of the pancreas graft and remained within the normal range during the PN period. No significant difference was observed in UNP or glucose tolerance between the mixed-regimen and glycidic groups. However, on average 6.6, and 1.5 hyperglycemic episodes occurred during the 1st wk of PN in the glycidic and mixed-regimen groups, respectively. The posttransplantation catabolism rate was similar to that induced by an elective major surgical procedure. Eucaloric PN did not affect the recovery of kidney and pancreas graft function. A mixed energy regimen seems to be most suitable for kidney-pancreas transplant patients because it prevents hyperglycemia which might be misdiagnosed as rejection.