Metabolic effects of restoring partial beta-cell function after islet allotransplantation in type 1 diabetic patients

Successful intraportal islet transplantation normalizes glucose metabolism in diabetic humans. To date, full function is not routinely achieved after islet transplantation in humans, with most grafts being characterized by on ly partial function. Moreover, the duration of full function is variable an d cannot be sufficiently predicted with available methods. In contrast, mos t grafts retain partial function for a long time. We hypothesized that part ial function can restore normal protein and lipid metabolism in diabetic in dividuals. We studied 45 diabetic patients after islet transplantation. Lab eled glucose and leucine were infused to assess whole-body glucose and prot ein turnover in 1) 6 type 1 diabetic patients with full function after intr aportal islet transplantation (FF group; C-peptide > 0.6 nmol/l; daily insu lin dosage 0.03 +/- 0.02 U . kg 1 body wt . day(-1); fasting plasma glucose < 7.7 mmol/l; HbA(1c) <less than or equal to> 6.5%), 2) 17 patients with p artial function (PF group; C-peptide > 0.16 nmol/l; insulin dosage < 0.4 U . kg(-1) body wt . day(-1)), 3) 9 patients with no function (NF group; C-pe ptide < 0.16 nmol/l; insulin dosage > 0.4 U . kg(-1) body wt . day(-1)), an d 4) 6 patients with chronic uveitis as control subjects (CU group). Hepati c albumin synthesis was assessed in an additional five PF and five healthy volunteers by means of a primed-continuous infusion of [3,3,3-H-2(3)]leucin e. The insulin requirement was 97% lower than pretransplant levels for the FF group and 57% lower than pretransplant levers for the PF group. In the b asal state, the PF group had a plasma glucose concentration slightly higher than that of the FF (P = 0.249) and CU groups (P = 0.08), but was improved with respect to the NF group (P < 0.01). Plasma leucine (101.1 +/- 5.9 <mu >mol/l) and branched-chain amino acids (337.6 +/- 16.6 mu mol/l) were simil ar in the PF, FF, and CU groups, and significantly lower than in the NF gro up (P < 0.01). During insulin infusion, the metabolic clearance rate of glu cose was defective in the NF group versus in the other groups (P < 0.01). B oth the basal and insulin-stimulated proteolytic and proteosynthetic rates were comparable in the PF, FF, and CU groups, but significantly higher in t he NF group (P = 0.05). In addition, the PF group had a normal hepatic albu min synthesis. Plasma free fatty acid concentrations in the PF and FF group s were similar to those of the CU group, but the NF group showed a reduced insulin-dependent suppression during the clamp. We concluded that the resto ration of similar to 60% of endogenous insulin secretion is capable of norm alizing the alterations of protein and lipid metabolism in type 1 diabetic kidney recipients, notwithstanding chronic immunosuppressive therapy. The r esults of the present study indicate that "success" of islet transplantatio n may be best defined by a number of metabolic criteria, not just glucose c oncentration/metabolism alone.