The n-3 to n-6 fatty acid ratio determined the immunoregulatory potential of intravenous fat emulsions in vivo. Both n-3 and n-6 fatty acids were immunosuppressive when applied as the main polyunsaturated fatty acid sources. PBMC cytokine release was significantly reduced in these groups. The more balanced the n-3 to n-6 ratios, the less immunosuppressive the fat emulsion. There was no immunosuppressive effect at an n-3 to n-6 ratio of 1:2.1.
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)
Insulin resistance and increased demand for insulin secretion occur after successful pancreas transplantation. To investigate the potential effects of immunosuppression and pancreas transplantation on fasting -cell function, we studied fasting proinsulin and 32,33 split proinsulin secretion cross-sectionally and longitudinally in segmental pancreatic graft recipients (SPx, n = 18); in whole-pancreas graft recipients (WPx, n = 13); in nondiabetic kidney transplant recipients (Kx, n = 14) and in normal subjects (Ns, n = 14). Basal insulin secretion rates were significantly increased in SPx 15.8 (1.7), WPx 24.4 (4.5) and Kx 22.1 (2.1) vs Ns 9.7 (1.6) pmol min ؊1 l
؊1, p Ͻ 0.05, mean (SEM). Total proinsulin, intact proinsulin and 32,33 split proinsulin concentrations were significantly higher in all the transplanted groups than in normal subjects (p Ͻ 0.05), whereas the total proinsulin to C-peptide ratio and the 32,33 split proinsulin ratio were higher in SPx than in WPx, Kx and Ns ( Ͻ 0.05). In the longitudinal study, -cell function in terms of proinsulin secretion remained stable for 1 year. In conclusion, fasting glucose homeostasis in pancreas-kidney transplant recipients is obtained at the expense of increased proinsulin secretion and increased insulin secretion rates, primarily induced by immunosuppression. In segmental pancreas graft recipients, increased fasting proinsulin and 32,33 split proinsulin relative to the number of -cells transplanted indicate more stress on the residual -cell and therefore higher secretory demand than in whole pancreas transplant recipients.
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