Department of Surgery, Division of Transplantation, University of Wisconsin, Madison, WI 53792-7375, USA.
Diabetes Obes Metab. 2010 Nov;12(11):994-1003. doi: 10.1111/j.1463-1326.2010.01290.x.
Pancreatic islet transplantation (PIT) represents a potential curative treatment for patients with type 1 diabetes, but only 10-15% of patients remain insulin independent 5 years post-transplant. It is not known whether intrinsic insulin resistance exacerbated by immunosuppression plays a pivotal role in low graft survival. The study objective was to understand the changes in insulin resistance, glucose effectiveness (S(g)) and free fatty acid dynamics (FFAd) before and after PIT.
Insulin sensitivity index (S(i)), S(g) and FFAd were measured before and after PIT in 10 lean patients, 8 of whom reached insulin independence. Modified Bergman minimal model of frequently sampled intravenous glucose tolerance tests were performed pretransplant and at 12 months post-transplant. Nine non-diabetic control (NDC) subjects matched by age, gender and BMI were used.
Pretransplant S(i) and S(g) were 3.5 ± 0.8 × 10(-5)/min/(pmol/l) and 0.74 ± 0.24 × 10(-2)/min, respectively. S(i) was significantly lower than matched NDCs [10.8 ± 0.6 × 10(-5)/min/(pmol/l), p < 0.004]; S(g) did not reach statistical significance (1.27 ± 0.22 × 10(-2)/min, p = 0.25). Compared to pretransplant values, mean post-transplant S(i) and S(g) were 9.6 ± 1.3 × 10(-5)/min/(pmol/l)and 1.28 ± 0.22 ×10(-2)/min, respectively, indicating significant improvement for S(i) but not S(g) (p = 0.008 and p = 0.06). Twelve-month post-PIT compared to NDC values were not significantly different (p = 0.58 and 0.97, respectively). In addition, fractional disposal rate for FFA which directly depends on the endogenous insulin release (10-20 min) nearly normalized after PIT (p = 0.06).
These preliminary findings demonstrate that PIT can restore glucose disposal and insulin sensitivity and partially correct glucose effectiveness and FFAd.
胰岛移植（PIT）为 1 型糖尿病患者提供了一种潜在的治愈方法，但只有 10-15%的患者在移植后 5 年内保持胰岛素独立性。目前尚不清楚免疫抑制引起的内在胰岛素抵抗是否在移植物存活率低中发挥关键作用。本研究的目的是了解 PIT 前后胰岛素抵抗、葡萄糖效应（S(g)）和游离脂肪酸动力学（FFAd）的变化。
10 例瘦型患者在 PIT 前后测量胰岛素敏感性指数（S(i)）、S(g)和 FFAd，其中 8 例达到胰岛素独立性。在移植前和移植后 12 个月进行改良 Bergman 静脉内葡萄糖耐量试验频繁采样的最小模型。使用 9 名年龄、性别和 BMI 匹配的非糖尿病对照（NDC）受试者。
移植前 S(i)和 S(g)分别为 3.5±0.8×10(-5)/min/(pmol/l)和 0.74±0.24×10(-2)/min。S(i)明显低于匹配的 NDC[10.8±0.6×10(-5)/min/(pmol/l)，p<0.004]；S(g)未达到统计学意义（1.27±0.22×10(-2)/min，p=0.25）。与移植前相比，平均移植后 S(i)和 S(g)分别为 9.6±1.3×10(-5)/min/(pmol/l)和 1.28±0.22×10(-2)/min，表明 S(i)显著改善，但 S(g)没有改善（p=0.008 和 p=0.06）。与 NDC 值相比，PIT 后 12 个月差异无统计学意义（p=0.58 和 0.97）。此外，直接依赖内源性胰岛素释放的 FFA 分数清除率（10-20 分钟）在 PIT 后几乎正常化（p=0.06）。
这些初步发现表明，PIT 可以恢复葡萄糖处置和胰岛素敏感性，并部分纠正葡萄糖效应和 FFAd。
