肾胰联合移植后1型糖尿病患者血浆胰淀素增加：β细胞功能受损的迹象？

Increased plasma amylin in type 1 diabetic patients after kidney and pancreas transplantation: A sign of impaired beta-cell function?

作者信息

Stadler Marietta, Anderwald Christian, Karer Tina, Tura Andrea, Kästenbauer Thomas, Auinger Martin, Bieglmayer Christian, Wagner Oswald, Kronenberg Florian, Nowotny Peter, Pacini Giovanni, Prager Rudolf

机构信息

Ludwig Boltzmann Institute of Metabolic Diseases and Nutrition, Vienna,

出版信息

Diabetes Care. 2006 May;29(5):1031-8. doi: 10.2337/diacare.2951031.

DOI:10.2337/diacare.2951031

PMID:16644633

Abstract

OBJECTIVE

In response to hyperglycemia, beta-cells release insulin and C-peptide, as well as islet amyloid pancreatic polypeptide, which is involved in glucose homeostasis. After successful pancreas-kidney transplantation (PKT), type 1 diabetic patients may revert to a nondiabetic metabolism without exogenous insulin therapy and re-secrete all beta-cell hormones.

RESEARCH DESIGN AND METHODS

Using mathematical models, we investigated hormone (amylin, insulin, C-peptide) and metabolite (glucose, free fatty acids) kinetics, beta-cell sensitivity to glucose, and oral glucose insulin sensitivity index (OGIS) in 11 nondiabetic type 1 diabetic patients after PKT (BMI 25 +/- 1 kg/m2, 47 +/- 2 years of age, 4 women/7 men, glucocorticoid-free), 6 matching nondiabetic patients after kidney transplantation (25 +/- 1 kg/m2, 50 +/- 5 years, 3 women/3 men, on glucocorticoids), and 9 matching nondiabetic control subjects (24 +/- 1 kg/m2, 47 +/- 2 years, 4 women/5 men) during a 3-h 75-g oral glucose tolerance test (OGTT).

RESULTS

PKT patients had higher fasting amylin (19 +/- 3 vs. control subjects: 7 +/- 1 pmol/l) and insulin (20 +/- 2 vs. control subjects: 10 +/- 1 microU/ml; each P < 0.01) levels. Kidney transplant subjects showed increased OGTT plasma insulin at 90 min and C-peptide levels (each P < 0.05). In PKT patients, plasma glucose from 90 to 150 min was 9-31% higher (P < 0.05 vs. control subjects). Amylin clearance was comparable in all groups. Amylin's plasma concentrations and area under the concentration curve were up to twofold higher in PKT patients during OGTT (P < 0.05). OGIS was not significantly different between groups. beta-Cell sensitivity to glucose was reduced in PKT patients (-64%, P < 0.009). Fasting plasma amylin was inversely associated with beta-cell sensitivity to glucose (r = -0.543, P < 0.004).

CONCLUSIONS

After successful PKT, type 1 diabetic patients with nondiabetic glycemia exhibit increased fasting and post-glucose load plasma amylin, which appears to be linked to impaired beta-cell function. Thus, higher amylin release in proportion to insulin might also reflect impaired beta-cell function in type 1 diabetic patients after PKT.

摘要

目的

为应对高血糖，β细胞会释放胰岛素、C肽以及胰岛淀粉样多肽，后者参与葡萄糖稳态调节。在成功进行胰肾联合移植（PKT）后，1型糖尿病患者无需外源性胰岛素治疗即可恢复至非糖尿病代谢状态，并重新分泌所有β细胞激素。

研究设计与方法

我们运用数学模型，在11例PKT术后的非糖尿病1型糖尿病患者（体重指数25±1kg/m²，年龄47±2岁，4名女性/7名男性，未使用糖皮质激素）、6例匹配的肾移植术后非糖尿病患者（25±1kg/m²，50±5岁，3名女性/3名男性，使用糖皮质激素）以及9例匹配的非糖尿病对照受试者（24±1kg/m²，47±2岁，4名女性/5名男性）进行3小时75克口服葡萄糖耐量试验（OGTT）期间，研究激素（胰淀素、胰岛素、C肽）和代谢物（葡萄糖、游离脂肪酸）的动力学、β细胞对葡萄糖的敏感性以及口服葡萄糖胰岛素敏感性指数（OGIS）。

结果

PKT患者的空腹胰淀素水平（19±3对对照受试者：7±1pmol/l）和胰岛素水平（20±2对对照受试者：10±1μU/ml；P均<0.01）更高。肾移植受试者在OGTT 90分钟时的血浆胰岛素和C肽水平升高（P均<0.05）。在PKT患者中，90至150分钟的血浆葡萄糖水平比对照受试者高9%至31%（P<0.05）。所有组的胰淀素清除率相当。在OGTT期间，PKT患者的胰淀素血浆浓度和浓度曲线下面积比对照受试者高两倍（P<0.05）。各组间OGIS无显著差异，但PKT患者的β细胞对葡萄糖的敏感性降低（-64%，P<0.009）。空腹血浆胰淀素与β细胞对葡萄糖的敏感性呈负相关（r=-0.543，P<0.004）。