Secondary failure of oral hypoglycaemic agents in lean patients with type 2 diabetes mellitus: insulin sensitivity, insulin response to different stimuli, and the role of cyclic-AMP.

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)     

Thy 1.2 antigen inducing capacity of a calf thymus acid hydrolysate and its fractions

Splenic null cells of normal mice have been shown to undergo phenotypic induction of Thy 1.2 antigen by various thymic extracts. This experimental model has been employed in characterizing the Thy 1.2 inducing ability of an acid lysate from calf thymus and its various fractions. Incubation of splenocytes from C3H/He mice with unfractionated Thymomodulin induces a dose-response percent increase in the Thy 1.2 antigen bearing cells (9.28 +/- 2.6%, p less than 0.05). Comparable increase appears in fractions 5B (9.46 +/- 0.55%, p less than 0.001) and 5C (8.09 +/- 3%, p less than 0.005), obtained by ultrafiltration and containing peptides of m.w. 600-10,000 d and less than 600 d, respectively. The activity is confined to the acid fraction (6.61 +/- 0.54%, p less than 0.001) isolated by isoelectrofocusing. Control lysate from pig duodenal mucosa was devoid of Thy 1.2 inducing activity. The present findings indicate that Thymomodulin possesses Thy 1.2 inducing capacity on murine null cells and that such activity is maintained and enhanced after various fractionation procedures.     

Persistence of anomalies in the growth hormone-releasing hormone-stimulated growth hormone response in diabetic-uremic patients after combined kidney-pancreas transplantation

Increased circulating growth hormone (GH) levels and aberrant response to different stimuli characterize both type 1 diabetes mellitus and chronic uremia and are associated with severe retinal, kidney and heart complications. Combined kidney and pancreas transplantation is a therapy that restores the endogenous, closed-loop, insulin secretion in diabetes and cure uremia. To evaluate if combined transplantation can restore a normal secretion and response of GH to growth hormone releasing hormone (GH-RH), we studied four groups of subjects: (1) seven type 1 diabetic patients with end-stage renal failure who had received pancreas and kidney transplantation (KPTx); (2) six diabetic uremic subjects, candidates for combined transplantation (IDDUP); (3) nine patients with chronic uveitis on immunosuppressive therapy comparable to pancreas recipients, six of whom treated only with prednisone (UVEST), while three (4) were treated with both prednisone and cyclosporin (UVESTCY). All subjects underwent a GH-RH test (50 microg intravenously, i.v., at 13:00 h). Serum insulin levels were significantly higher in IDDUP compared to UVEST (P=0.05) both at baseline and post GH-RH stimulus, while were similar to KPTx (P=0.2) and UVESTCY (P=0.7). In contrast, plasma free fatty acids were similar in all groups. In IDDUP baseline plasma glycerol was higher than in KPTx (P=0.04) and UVEST (P=0.02) and similar to UVESTCY (P=0.36); glycerol concentration did not change after GH-RH (P=0.08). Before and after GH-RH, serum GH levels tended to be higher in IDDUP (P=0.5) and KPTx (P=0.2) compared to UVEST and UVESTCY. Our results indicate that: 1) kidney-pancreas transplantation does not normalize the GH response to GH-RH; 2) GH abnormalities are not due either to the chronic immunosuppressive therapy or to the insulin effect on GH release; 3) GH abnormalities are probably secondary to functional and/or organic complications of the hypothalamus and/or pituitary as a sequela of diabetes mellitus.     

A psychosomatic approach to idiopathic recurrences of anterior uveitis

We examined 60 patients affected by idiopathic recurrent anterior uveitis and studied the relevance of stressful life events and psychological distress in relation to relapses of the disease. The results were statistically insignificant when compared to the control groups. We found that neither life events nor psychological distress played a contributory role in this disease.     

Impact of recipient and donor ages on patient and graft survival after kidney transplantation

BACKGROUND: The purpose of the study was to evaluate the impact of donor and recipient ages on patient and graft survival after kidney transplant. METHODS: Patients in a hospital database undergoing kidney transplant for end-stage renal disease (ESRD) during the period 1985 to May 2006 (n = 410; mean age 42 +/- 10 years; 61% men and 39% women) were divided into two groups: group A, patients of 60 years or older (6%, n = 24), and group B, those younger than 60 years (94, n = 386). In 204 patients (49.8%) the pancreas was transplanted simultaneously with the kidney. RESULTS: Overall 1-, 3-, 5-year patient survivals were 92%, 90%, 88% in group A and 95%, 90%, 87% in group B (P = .6, NS). Overall 1-, 3-, 5-year kidney graft was 92%, 75%, 65% in group A and 92%, 84%, 79% in group B (P = .7, NS). Donors were divided into two groups: group 1, 55 years or older (15%, n = 62), versus group 2, those younger than 55 years (85%, n = 348). Overall 1-, 3-, 5-year patient survivals were 91%, 86%, 76% in group 1 and 97%, 94%, 90% in group 2 (P = .0009). Overall 1-, 3-, 5-year kidney graft survivals were 87%, 82%, 76% in group 1 and 94%, 86%, 82% in group 2 (P = .02). CONCLUSIONS: Renal transplantation is an effective option for the treatment of ESRD in elderly patients. The overall rates of patient and kidney graft survival are comparable to those of younger patients. Donor age > or =55 years had a negative effect on patient and kidney graft survival.     

Effect of pancreas transplantation on life expectancy, kidney function and quality of life in uraemic Type 1 (insulin-dependent) diabetic patients

The aim of our study was to evaluate the effects of haemodialysis, kidney transplantation and simultaneous kidney and pancreas transplantation on survival of diabetic subjects and on kidney function. 40 Type 1 (insulin-dependent) diabetic patients received a kidney transplantation: in 31 cases the kidney was transplanted simultaneously to a pancreas graft from the same donor (KP group), while in 9 cases the pancreas was not available (K group). 44 uraemic Type 1(insulin-dependent) diabetic patients on dialysis and in waiting list for kidney transplantation, constituted the control group (HD group). Patient survival rate 1, 3 and 5 years following transplantation was better in KP group (93%, 89%, 89%, respectively) than in K group (88%, 88%, 73%, respectively) and in HD group (88%, 62%, 51%, respectively). Kidney graft survival at 1, 3 and 5 years post-transplant was better in KP group (93%, 72%, 72%, respectively) than in K group (76%, 61%, 31%, respectively). 1 year after transplantation, patients of the KP group who had lost the pancreas for technical reasons (thrombosis) were included in the K group so as to evaluate the effect of the transplanted pancreas on long-term patient and kidney survival. Patient survival rate in the KP group (17 patients) at 2 and 4 years was 100%, while at the same intervals it was 78% in the K group (13 patients). Kidney graft function rate at 2 and 4 years was 93% in the KP group (17 grafts) and 54% and 27% respectively in the K group (14 grafts). Evaluation of quality of life in patients receiving a kidney and pancreas transplantation showed an improvement in psychological well-being, when compared to patients receiving a kidney transplantation alone. Physical well-being was similar in patients transplanted with kidney and pancreas or with kidney alone.     

Liver Perfusion Changes Occurring During Pancreatic Islet Engraftment: A Dynamic Contrast‐Enhanced Magnetic Resonance Study

The aim of this study was to investigate liver microvascular adaptation following the intraportal infusion of pancreatic islets (pancreatic islet transplantation [islet‐tx]) in diabetic patients using dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). DCE‐MRI was performed before and 7 days after islet‐tx in six diabetic patients. Initial area under curve (AUC60) and volume transfer coefficient (Ktrans) were assessed as markers of liver perfusion. Clinical and metabolic monthly follow‐up was performed in all patients, considering fasting C‐peptide and β‐score as main indices of graft function. High variability in the response of liver microvasculature to islet infusion was observed: two patients showed a significant reduction in liver perfusion after transplantation (pt.2: AUC60 = ?23.4%, Ktrans = ?31.7%; pt.4: AUC60 = ?23.7%, Ktrans = ?27.9%); three patients did not show any significant variation of liver perfusion and one patient showed a significant increase (pt.3: AUC60 = +31%, Ktrans = +42.8%). Interestingly, a correlation between DCE‐MRI parameters and indices of graft function was observed and, in particular, both patients with DCE‐MRI evidence of posttransplantation liver perfusion reduction experienced premature graft failure. Our preliminary study demonstrated that DCE‐MRI may identify different adaptive responses of liver microvasculature in patients submitted to islet‐tx. These different responses could have an impact on islet engraftment, although reported findings need confirmation from larger studies.