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  • American Diabetes Association  (2)
  • 1
    In: Diabetes Care, American Diabetes Association, Vol. 19, No. 3 ( 1996-03-01), p. 236-240
    Abstract: The majority of islet transplant recipients remain insulin-requiring, although many have near-normal connecting peptide (CP) levels. Insulin resistance may be one possible cause of the continuing need for exogenous insulin in islet transplant recipients. To assess this, we have studied the insulin sensitivity index (S1) in one patient with near-normal CP levels after islet transplant who remained insulin-requiring. RESEARCH DESIGN AND METHODS The islet transplant recipient is a 36-year-old woman with no residual CP who received a kidney transplant, followed 7 days later by an islet transplant. The islets were infused into the liver via the umbilical vein. Induction immunosuppression consisted of OKT3, prednisone, cyclosporin A, and azathioprine, with maintenance on the latter three. RESULTS Maximum CP levels after a standardized Sustacal meal were 2.09, 1.18, 0.85, and 0.81 nmol/l at 1,6,18, and 24 months posttransplant, respectively. Insulin requirements at the same times were 0.27, 0.45, 0.49, and 0.62 U·kg−1·d−1, while S1 was 36.3, 53.3, and 13.2 min −1·nmol−1·ml at 6,18, and 24 months, respectively. This compares with S1 values of 43.3 ± 10.0 min−1·nmol−1·ml for normal subjects. CONCLUSIONS This patient had near-normal S1 and CP levels, but she was unable to discontinue insulin therapy, suggesting that other factors are critical. Despite this, she maintained normal or near-normal glycated hemoglobins, indicating metabolic benefit from the islet transplant.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1996
    detail.hit.zdb_id: 1490520-6
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  • 2
    Online Resource
    Online Resource
    American Diabetes Association ; 1997
    In:  Diabetes Vol. 46, No. 3 ( 1997-03-01), p. 372-378
    In: Diabetes, American Diabetes Association, Vol. 46, No. 3 ( 1997-03-01), p. 372-378
    Abstract: We determined the metabolic effects of insulin derived from renal subcapsular islet grafts, either with systemic delivery of insulin through renal venous drainage (REN) or with portal delivery of insulin after renal vein–to–superior mesenteric vein anastomosis (RMA), in streptozotocin-induced diabetic Lewis rats, in comparison with normal rats. After gavage glucose, the plasma glucose responses were similar to normal in REN and RMA rats; however, hyperinsulinemia occurred in REN rats (area under the concentration curves [AUCs] of insulin, 27 ± 3 nmol · l−1 · min) in comparison with RMA (14 ± 2) and normal rats (19 ± 2), P & lt; 0.003, with no difference in C-peptide responses. The ratio of AUC C-peptide to AUC insulin was lower in REN (2.0 ± 0.2) than in RMA (3.4 ± 0.3) and normal animals (3.2 ± 0.3), P & lt; 0.0005. In euglycemic-hyperinsulinemic clamp studies using the same insulin infusion rate (10 pmol · kg−1 · min−1), insulin resistance was found in REN animals (mean glucose infusion rate [GIR], REN: 7.5 ± 1.2; RMA: 12.0 ± 1.2; normal: 12.7 ± 1.0 mg · kg−1 · min−1; P & lt; 0.008), with higher steady-state insulin levels in REN (554 ± 63 pmol/l) than in RMA (291 ± 26) and normal rats (269 ± 60), P & lt; 0.0001. With matching steady-state insulin levels in RMA and REN rats during infusion of insulin at 20 pmol · kg−1 · min−1 in RMA rats (steady-state insulin 623 ± 64 pmol/l), GIR was 15.7 ± 0.7 mg · kg−1 · min−1. Thus, systemic delivery of insulin from islet grafts is associated with hyperinsulinemia, insulin resistance, and decreased metabolic clearance of insulin. These abnormalities are prevented by portal delivery of insulin from islet grafts in the same site. The findings are consistent with the hypothesis that portal delivery of insulin is important in maintenance of normal whole-body insulin sensitivity.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 1997
    detail.hit.zdb_id: 1501252-9
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