Clinical use of fructosamine in islet transplantation.

Many islet transplant recipients have medical conditions that could interfere with the accuracy of HbA1c measurements (e.g., anemia/dapsone use). Fructosamine is less prone to have clinical interferences and reflects glucose control in a shorter period of time than HbA1c. This study aimed to validate fructosamine use in islet transplant subjects and to evaluate its effectiveness as a predictor for islet graft dysfunction. Thirty-three islet transplant recipients who had concomitant fructosamine and HbA1c data available were retrospectively analyzed. HbA1c, fructosamine, mean capillary blood glucose, and islet graft function (fasting C-peptide/glucose ratio) were assessed. There was a significant and positive association between fructosamine and HbA1c (p < 0.0001). Both variables were also positively associated with mean overall and fasting capillary glucose. Neither fructosamine nor HbA1c was shown by ROC analysis to significantly discriminate between periods with and without subsequent graft dysfunction. HbA1c >6% was predictive of this outcome 1 month in advance (OR 2.95, p = 0.003). However, although significantly associated with graft dysfunction, use of this cutoff as a predictor of dysfunction has poor sensitivity (50%) and specificity (77.6%). Fructosamine above the normal range (>270 mumol/L Quest Diagnostics) was also predictive of ensuing dysfunction (OR 2.47, p = 0.03); however, it had similarly poor sensitivity (62%) and specificity (64%). Fructosamine can be used as an alternative to HbA1c for glycemic assessment in islet transplant recipients in situations with HbA1c assay interference. Neither HbA1c nor fructosamine are good predictors of islet graft dysfunction.

Combined treatment of intrapancreatic autologous bone marrow stem cells and hyperbaric oxygen in type 2 diabetes mellitus.

The objective of this study was to determine whether the combination therapy of intrapancreatic autologous stem cell infusion (ASC) and hyperbaric oxygen treatment (HBO) before and after ASC can improve islet function and metabolic control in patients with type 2 diabetes mellitus (T2DM). This prospective phase 1 study enrolled 25 patients with T2DM who received a combination therapy of intrapancreatic ASC and peri-infusion HBO between March 2004 and October 2006 at Stem Cells Argentina Medical Center Buenos Aires, Argentina. Clinical variables (body mass index, oral hypoglycemic drugs, insulin requirement) and metabolic variables (fasting plasma glucose, C-peptide, HbA1c, and calculation of C-peptide/glucose ratio) were assessed over quartile periods starting at baseline and up to 1 year follow-up after intervention. Means were calculated in each quartile period and compared to baseline. Seventeen male and eight female patients were enrolled. Baseline variables expressed as means +/- SEs were: age 55 +/- 2.14 years, diabetes duration 13.2 +/- 1.62 years, insulin dose 34.8 +/- 2.96 U/day, and BMI 27.11 +/- 0.51. All metabolic variables showed significant improvement when comparing baseline to 12 months follow-up, respectively: fasting glucose 205.6 +/- 5.9 versus 105.2 +/- 14.2 mg/dl, HbAlc 8.8 +/- 0.2 versus 6.0 +/- 0.4%, fasting C-peptide 1.5 +/- 0.2 versus 3.3 +/- 0.3 ng/ml, C-peptide/glucose ratio 0.7 +/- 0.2 versus 3.5 +/- 0.3, and insulin requirements 34.8 +/- 2.9 versus 2.5 +/- 6.7 U/day. BMI remained constant over the 1-year follow-up. Combined therapy of intrapancreatic ASC infusion and HBO can improve metabolic control and reduce insulin requirements in patients with T2DM. Further randomized controlled clinical trials will be required to confirm these findings.

Liver fat accumulation after islet transplantation and graft survival.

Our objective is to evaluate if there is an association between liver fat accumulation after islet transplantation (ITx) and graft survival. A cohort study was conducted in 34 subjects with type 1 diabetes postallogeneic ITx. Liver fat content was evaluated by magnetic resonance imaging (MRI) (change in liver signal intensity on in-phase and opposed-phase images). Kaplan-Meier curves and Cox regression analysis were performed with islet dysfunction duration as the dependent variable and fat liver content as an independent one. Values of p < 0.05 were significant (SSPS(®)18.0 and MedCalc(®)12.5). Patients' mean age was 40 ± 8 years (diabetes duration: 31 ± 12 years; male: 41%). Islet survival did not differ in patients without (51 months, 95% CI 40-62 months) or with steatosis (48 months, 95% CI 38-58 months; p = 0.55) during islet dysfunction period. Nevertheless, survival curves appear to separate late in the follow-up, and after 40 months steatosis was associated with shorter graft survival (p log rank = 0.049). This association remained (RR 23.5, 95% CI 1.1-516.0; p = 0.045) after adjustments for possible confounding factors. In this sample of subjects with type 1 diabetes submitted to ITx, steatosis was not associated with islet failure in the whole cohort. However, in subjects with functional islets after 40 months, a shorter graft survival was observed in those with steatosis during the islet dysfunction period, even after adjustments to variables known to be associated with islet failure.

Lipotoxicity and decreased islet graft survival.

OBJECTIVE To evaluate if baseline serum lipids are associated with islet graft survival in type 1 diabetes islet transplant (ITx) recipients. RESEARCH DESIGN AND METHODS Baseline fasting lipid profile was collected from 44 ITx recipients. Comparisons were performed between subjects below and above the median values of each lipid fraction. Differences in outcomes were compared by Kaplan-Meier curves and Cox regression analysis. RESULTS Subjects with baseline fasting plasma triglycerides and VLDL cholesterol above the median had shorter islet graft survival (triglycerides: 39.7 +/- 6.1 vs. 61.3 +/- 6.6 months, P = 0.029, and VLDL: 41.5 +/- 5.7 vs. 62.8 +/- 7.3 months, P = 0.032). Total, LDL, and HDL cholesterol did not influence islet function. Triglycerides (odds ratio 2.97 [95% CI 1.03-8.52], P = 0.044) maintained its association with graft failure after adjustments for confounders. CONCLUSIONS Higher baseline triglycerides are associated with earlier decline in islet graft function. Prospective clinical trials should address whether it is directly caused by lipotoxicity and if strategies focusing on lowering serum lipids may prolong islet graft survival.

Type 2 diabetes mellitus phenotype and graft survival after islet transplantation.

BACKGROUND: Body fat accumulation decreases insulin sensitivity. It has being associated with earlier onset of type 1 diabetes mellitus (DM) and islet graft failure. The aim of this study was to evaluate whether insulin resistance, characterized by risk factors for type 2 DM, can predict islet graft survival in type 1 DM islet transplant (ITx) recipients. METHODS: Demographic, anthropometrical, and laboratory data, as well as family history of type 2 DM (first degree relatives), were collected from 44 ITx recipients. Risk factors for type 2 DM, such as positive family history of type 2 DM (n=11) and overweight (body mass index >25 kg/m2; n=14), were analyzed separately and in combination, which was designated as "type 2 DM phenotype" (n=5). Differences in outcomes (time-to-graft dysfunction and failure) were compared using Kaplan-Meier curves. Cox regression analysis was performed to control for possible confounding factors. RESULTS: Neither positive family history of type 2 DM nor overweight at baseline could predict islet function outcomes after ITx. However, when both risk factors were grouped, the "type 2 DM phenotype" was associated with earlier islet graft failure (mean estimate graft survival 25.7+/-9.1 vs. 54.1+/-5.2 months, P=0.022). These results were sustained after adjustments for confounding variables (OR 5.20, 95% CI 1.12-24.0). CONCLUSIONS: Predisposition for type 2 DM can coexist with the type 1 DM phenotype and is associated with earlier decline in islet graft function. Prospective clinical trials should address whether it is associated with decreased insulin sensitivity and if insulin sensitizers play a role in prolonging islet graft survival.