Table 5:
Glycemic Outcomes for Patients with Type 1 Diabetes Mellitus, from Observational Comparative Studies
| Glycemic Control | |||||||
|---|---|---|---|---|---|---|---|
| Author, Year | Treatment | Immunosuppression Protocol | Graft Loss/Insulin Independence | HbA1c Levels (ng/mL) | Insulin Requirements (U/d) | C-Peptide (ng/mL) | Hypoglycemia |
| Non-uremic patients | |||||||
| Venturini et al, 2006 (47) | 10 ITA or 10 IIT | Induction: daclizumab Maintenance: sirolimus, tacrolimus (Edmonton Protocol) |
ITA: 7.95 ± 0.29 pre-transplantation vs. 7.50 ± 0.46 at 1 y (P = .06) IIT: 8.28 ± 0.36 pre-transplantation vs. 8.15 ± 0.22 at 1 y (NS) |
ITA: 31.1 ± 4.2 pre-transplantation vs. 20.3 ± 5.5 at 1 y (P = .06) IIT: 49.0 ± 3.51 pre-transplantation vs. 48.0 ± 4.05 at 1 y (NS) |
ITA: 0.20 ± 0.06 pre-transplantation vs. 0.84 ± 0.18 at 1 y (P < .01) IIT: 0.21 ± 0.11 pre-transplantation vs. 0.14 ± 0.08 at 1 y (NS) |
||
| Warnock et al, 2008 (49) | 31 ITA or 11 IIT | Induction: ATG Maintenance: sirolimus or MMF, tacrolimus |
16/25 patients (64%) insulin independent at end of follow-up | 6.6 ± 0.7 ITA vs. 7.5 ± 0.9 IIT (P < .01) | 33%–75% of pre-transplantation insulin doses due to partial graft function | ||
| Thompson et al, 2011 (51) | 32 ITA or 13 IIT | Induction: ATG or basiliximab Maintenance: sirolimus or MMF, tacrolimus |
Graft loss: 9/32 (28%) patients Insulin independence: 22/23 (96%) at 3 mo 12/23 (52%) at end of follow-up |
8.1% ± 1.2% pre- vs. 7.0% ± 0.7% post-transplantation (P = NR) 6.7 ± 0.2 ITA vs. 7.8 ± 0.3 IIT (P < .001) |
All 23 ITA patients maintained on immunosuppression had persistently detectable C-peptide | ||
| Maffi et al, 2011 (52) | 33 ITA or 33 PTA | Daclizumab induction, maintenance with sirolimus and tacrolimus (Edmonton Protocol, 22 patients) ATG induction, maintenance with sirolimus and MMF (11 patients) |
Early graft loss: 5/33 (15%) ITA vs. 7/33 (21%) PTA Partial graft function: 9/33 (27%) ITA Insulin independence: 19/33 (57%) ITA vs. 25/33 (76%) PTA |
||||
| D'Addio et al, 2014 (53) | 12 ITA or 12 IIT | Induction: daclizumab Maintenance: tacrolimus, sirolimus (Edmonton Protocol) |
Significant changes in ITA vs. IIT | Significant changes in ITA vs. IIT | |||
| Uremic patients | |||||||
| Gerber et al, 2008 (48) | 13 SIK or 25 SPK | Induction: daclizumab Maintenance: sirolimus, tacrolimus (Edmonton Protocol) |
Primary non-function: 2 SIK vs. 0 SPK Insulin independence at 1 y: 31% SIK vs. 96% SPK |
At baseline: SIK (n = 13) 8.1 ± 1.5 vs. SPK (n = 25) 8.7 ± 1.9 (NS) At 1 y: SIK (n = 13) 6.2 ± 0.8 vs. SPK (n = 25) 6.0 ± 0.6 (NS) At 2 y: SIK (n = 9) 6.3 ± 0.7 vs. SPK (n = 22) 5.7 ± 0.5 (P < .05) At 3 y: SIK (n = 8) 6.7 ± 1.0 vs. SPK (n = 15) 5.8 ± 0.4 (P < .05) At 4 y: SIK (n = 5) 6.2 ± 0.5 vs. SPK (n = 10) 5.5 ± 0.6 (NS) HbA1c at 5 y: SIK (n = 1) 5.7 vs. SPK (n = 3) 5.3 (P = NR) |
50% reduction in SIK group |
At end of follow-up: 1.005 ± 0.735 SIK vs. 2.505 ± 0.762 SPK (P = NR) |
Severe hypoglycemia pre-transplantation: 10/13 patients (77%) in SIK Severe hypoglycemia post-transplantation: 0 in both groups |
| Fiorina et al, 2003 (44) | 37 IAK/SIK or 162 SPK or 42 IIT | Induction: ATG Maintenance: cyclosporine, MMF, prednisone |
Successful vs. unsuccessful IAK/SIK: 24 patients vs. 13 patients |
Successful vs. unsuccessful IAK/SIK vs. SIK vs. SPK: Baseline: 8.3 ± 0.3 vs. 7.7 ± 0.6 vs. 11.2 ± 1.7 vs. 11.1 ± 2.3 At 1 y: 7.35 ± 0.29 vs. 7.96 ± 0.35 vs. 5.8 ± 0.8 vs. 8.9 ± 1.3 (NS) At 4 y: 7.33 ± 0.51 vs. 8.08 ± 0.43 vs. 6.0 ± 0.1 vs. 8.6 ± 0.4 (NS) At 7 y: 7.38 ± 0.35 vs. 8.26 ± 0.61 vs. 6.2 ± 0.2 vs. 8.7 ± 0.5 (NS) |
Successful vs. unsuccessful IAK/SIK: At 1 y: 19.1 ± 4.3 vs. 46.0 ± 6.2 (P < .01) At 4 y: 23.0 ± 5.3 vs. 51.8 ± 8.5 (P = .01) At 7 y: 17.8 ± 4.7 vs. 36.4 ± 9.7 (NS) |
Successful vs. unsuccessful IAK/SIK vs. SIK vs. SPK: Baseline: 0.15 ± 0.02 vs. 0.15 ± 0.03 vs. 0.11 ± 0.02 vs. 0.13 ± 0.03 At 1 y: 1.64 ± 0.25 vs. 0.39 ± 0.25 vs. 1.62 ± 0.15 vs. 0.21 ± 0.09 At 4 y: 1.09 ± 0.16 vs. 0.14 ± 0.02 vs. 1.43 ± 0.21 vs. 0.17 ± 0.05 At 7 y: 1.39 ± 0.49 vs 0.10 ± 0.01 vs. 1.39 ± 0.22 vs. 0.15 ± 0.04 |
|
| Fiorina et al, 2005 (10) | 17 IAK or 25 IIT | Induction ATG Maintenance: cyclosporine, MMF, prednisone |
Insulin independence > 3 mo: 12/17 patients (71%) |
For IAK: 7.7 ± 0.3 pre- vs. 7.7 ± 0.2 at 3 y post-transplantation (NS) For IIT: 8.6 ± 0.6 pre- vs. 8.1 ± 0.5 at 3 y post-transplantation (NS) NS differences between IAK and IIT |
In IAK: 25.2 ± 4.3 pre- vs. 17.3 ± 3.4 at 3 y post-transplantation (P < .05) In IIT: 32.1 ± 7.0 pre- vs. 35.1 ± 4.4 at 3 y post-transplantation (NS) In IAK vs. IIT: pre- and 3 y post-transplantation (P < .05) |
At 3 y: 1.7 ± 0.2 IAK vs. 0.3 ± 0.1 IIT (P < .01) | |
| Fiorina et al, 2005 (46) | 24 IAK/SIK, 166 SPK, 44 IIT | Induction: ATG Maintenance: cyclosporine, MMF, prednisone |
Insulin independence at 6 y: 0% IAK/SIK vs. 100% SPK |
Pre- vs. 6 y post-transplantation: In IAK/SIK: 7.4 ± 0.2 vs. 8.1 ± 0.3 at 6 y (P < .05) In SPK: 5.7 ± 0.1 vs. 5.8 ± 0.2 at 6 y (P < .05) In IIT: 8.0 ± 0.4 vs. 7.8 ± 0.2 at 6 y (NS) |
In successful IAK/SIK: 50% decrease from baseline at 2, 4, and 6 y |
In IAK/SIK: 1.6 ± 0.2 pre-transplantation vs. 1.1 ± 0.4 at 6 y (NS) |
|
| Mixed uremic and non-uremic patients | |||||||
| Frank et al, 2004 (45) | 9 ITA, 4 IAK, 25 SPK, 5 PAK | Induction: daclizumab Maintenance: sirolimus, tacrolimus (Edmonton Protocol) |
Graft loss: 5 patients ITA/IAK, 4 patients SPK/PAK Insulin independence at 2 y: 5 patients (42%) ITA/IAK vs. 25 patients (83%) SPK/PAK |
1 y: 6.3% ITA/IAK vs. 5.0% SPK/PAK (P ≤ .001) Average between insulin-independent patients and those requiring small doses of insulin For ITA/IAK: 5.6% vs. 6.65% (NS) |
During first 600 d post-transplantation: 1.7 ITA/IAK vs. 3.9 SPK/PAK (P < .001) Average between insulin-independent patients and those requiring small doses of insulin: for ITA/IAK: 2.3 vs 1.1 (NS) |
No hypoglycemic episodes in any ITA/IAK patients with graft function | |
| Vantyghem et al, 2009 (72) | 7 ITA, 6 IAK, 17 IIT | Induction: daclizumab Maintenance: sirolimus, tacrolimus (Edmonton Protocol) |
Insulin independence at 1 y ITA/IAK: 10 of 13 patients (77%) |
ITA/IAK vs. IIT: Baseline: 8.2 ± 1.1 vs. 8.4 ± 1.8 (NS) At 1 y: 6.1 ± 0.7 vs. 7.9 ± 1.0 (P < .0001) At 3 y: 6.6 ± 1.1 vs. 8.1 ± 1.3 (P < .01) |
ITA/IAK vs. IIT: Baseline: 46 ± 12 vs. 43 ± 18 (NS) At 1 y: 4.4 ± 8.5 vs. 43 ± 20 (P < .0001) At 3 y: 12 ± 16 vs. 46 ± 19 (P < .0001) |
At 3 mo: 1.5 ± 0.7 At 3 y: 11/13 patients (85%) > 0.2 |
Severe hypoglycemia (no. per week) ITA/IAK vs. IIT: Baseline: 2.6 ± 2.1 vs. 2.9 ± 2.2 (NS) At 1 y: 0.3 ± 0.5 vs. 1.6 ± 1.6 (P < .01) At 3 y: 0.7 ± 1.1 vs. 1.7 ± 1.8 (NS) |
Abbreviations: ATG, antithymocyte globulin; HbA1c, glycosylated hemoglobin; IAK, islet-after-kidney transplantation; IIT, intensive insulin therapy; ITA, islet transplantation alone; MMF, mycophenolate mofetil; NA, not available; NR, not reported; NS, non-significant; PAK, pancreas-after-kidney transplantation; PTA, pancreas transplantation alone; SIK, simultaneous islet-kidney transplantation; SPK, simultaneous pancreas-kidney transplantation.
Source: Adapted from Institute of Health Economics, 2013. (41)