Restoration of Glucose Counterregulation by Islet Transplantation in Long-standing Type 1 Diabetes
Article Figures & Tables
Figures
- Figure 1
Islet cell hormonal responses during the hyperinsulinemic-hypoglycemic clamp in T1D subjects before (○) and 6 months after (▲) islet transplantation (n = 12) and in nondiabetic control subjects (■) (n = 8). For C-peptide (A), data are not shown before transplantation when undetectable (<0.1 ng/mL), and the response during the euglycemic clamps is shown for the T1D subjects 6 months after transplantation (△) (n = 12) and in the control group (□) (n = 8). For glucagon (B) and pancreatic polypeptide (C), the shaded area represents the 95% CI for data derived from all the hyperinsulinemic-euglycemic control experiments (n = 32).
- Figure 2
Sympathoadrenal (epinephrine [A] and autonomic symptoms [B]) and EGP (C) responses during the hyperinsulinemic-hypoglycemic clamp in T1D subjects before (○) and 6 months after (▲) islet transplantation (n = 12) and in nondiabetic control subjects (■) (n = 8, except for epinephrine, where n = 6). The shaded area represents the 95% CI for data derived from the hyperinsulinemic-euglycemic control experiments (n = 32, except for epinephrine, where n = 30).
Tables
- Table 1
Subject characteristics
T1D subjects Before islet transplantation After islet transplantation Nondiabetic control subjects Male/female sex (n) 5/7 5/7 4/4 Age (years) 45 ± 3 47 ± 3** 44 ± 3 Weight (kg) 71 ± 3 65 ± 3** 77 ± 5 BMI (kg/m2) 25 ± 1 23 ± 1** 25 ± 1 HbA1c (%)a 7.1 ± 0.2 5.6 ± 0.1** 5.5 ± 0.1** T1D duration (years) 29 ± 4 31 ± 4** — Insulin use (units ⋅ kg−1 ⋅ day−1) 0.48 ± 0.05 0.06 ± 0.05** — IE/kg transplanted — 9,648 ± 666 — Tacrolimus (μg/L) — 4.3 ± 0.4 — Sirolimus (μg/L)b — 8.4 ± 0.5 — Clarke scorec 6.3 ± 0.2 0.4 ± 0.3** — HYPO scored 2,564 ± 715 ND — Lability indexe 719 ± 67 93 ± 56** — Data are mean ± SE. IE/kg, islet equivalent (whereby an islet equivalent approximates a standard islet diameter of 150 μm) transplanted per kilogram of recipient body weight; ND, not done.
aTo convert to mmol/mol, multiply by 10.93 and subtract 23.50.
bOne subject was converted from sirolimus to mycophenolate mofetil as a result of the development of interstitial pneumonia 4 weeks after transplant that subsequently resolved (9).
cClarke score of hypoglycemia unawareness (7 = most, 0 = none) (12).
dHYPO score of hypoglycemia severity developed by Ryan et al. (13).
eLability index measure of glycemic lability developed by Ryan et al. (13).
**P < 0.01 for comparison with T1D subjects before transplantation.
- Table 2
Magnitudea of C-peptide suppression and counterregulatory responses
T1D subjects Before islet transplantation After islet transplantation Nondiabetic control subjects n 12 12 8b C-peptide (ng/mL) ― 0.16 ± 0.02 0.13 ± 0.01 Glucagon (pg/mL) 33 ± 3 60 ± 7** 95 ± 13**† PP (pmol/L) 32 ± 8 76 ± 23* 160 ± 16**† Epinephrine (pg/mL) 130 ± 16 253 ± 21** 419 ± 46**‡ Autonomic symptoms (∆) 2.2 ± 0.9 5.3 ± 1.0§ 6.9 ± 2.4* EGP (mg ⋅ kg−1 ⋅ min−1) 0.59 ± 0.12 1.18 ± 0.13* 1.42 ± 0.14** Free fatty acids (μmol/L) 50 ± 7 161 ± 37* 114 ± 18** Data are mean ± SE. PP, pancreatic polypeptide.
aThe magnitude of each hormonal, EGP, free fatty acid, and incremental symptom response to the hypoglycemic clamps was assessed as the mean of values obtained during the last 60 min of each clamp.
bn = 6 for epinephrine.
*P < 0.05 for comparison with T1D subjects before transplantation.
**P < 0.01 for comparison with T1D subjects before transplantation.
§P = 0.06 for comparison with T1D subjects before transplantation.
†P < 0.05 for comparison with T1D subjects after islet transplantation.
‡P < 0.01 for comparison with T1D subjects after islet transplantation.
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