Siew E D, Pupim L B, Majchrzak K M, Shintani A, Flakoll P J, Ikizler T A
Division of Nephrology and Hypertension, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2372, USA.
Kidney Int. 2007 Jan;71(2):146-52. doi: 10.1038/sj.ki.5001984. Epub 2006 Oct 25.
Deranged protein metabolism is known to complicate uremia. Insulin resistance is evident in chronic hemodialysis (CHD) patients. We hypothesized that the degree of insulin resistance would predict protein catabolism in non-diabetic CHD patients. We examined the relationship between Homeostasis Model Assessment (HOMA) and fasting whole-body and skeletal muscle protein turnover in 18 non-diabetic CHD patients using primed-constant infusions of L-(1-(13)C) leucine and L-(ring-(2)H(5)) phenylalanine. Mean+/-s.d. fasting glucose and body mass index were 80.6+/-9.8 mg/dl and 25.4+/-4.4 kg/m(2), respectively. Median (interquartile range) HOMA was 1.6 (1.4, 3.9). Mean+/-s.e.m. skeletal muscle protein synthesis, breakdown, and net balance were 89.57+/-11.67, 97.02+/-13.3, and -7.44+/-7.14 microg/100 ml/min, respectively. Using linear regression, a positive correlation was observed between HOMA and skeletal muscle protein synthesis (R(2)=0.28; P=0.024), and breakdown (R(2)=0.49; P=0.001). An inverse association between net skeletal muscle protein balance and HOMA was also noted (R(2)=0.20; P=0.066). After adjustment for C-reactive protein, only the relationship between HOMA and skeletal muscle protein breakdown persisted (R(2)=0.49; P=0.006). There were no significant associations between components of whole-body protein turnover and HOMA. This study demonstrates that insulin resistance is evident in non-diabetic dialysis patients, is associated with skeletal muscle protein breakdown, and represents a novel target for intervention in uremic wasting.
已知蛋白质代谢紊乱会使尿毒症病情复杂化。慢性血液透析（CHD）患者存在明显的胰岛素抵抗。我们假设胰岛素抵抗程度可预测非糖尿病CHD患者的蛋白质分解代谢。我们通过对18例非糖尿病CHD患者持续静脉输注L-（1-（13）C）亮氨酸和L-（环-（2）H（5））苯丙氨酸，研究了稳态模型评估（HOMA）与空腹全身及骨骼肌蛋白质周转率之间的关系。空腹血糖和体重指数的平均值±标准差分别为80.6±9.8mg/dl和25.4±4.4kg/m²。HOMA的中位数（四分位间距）为1.6（1.4，3.9）。骨骼肌蛋白质合成、分解及净平衡的平均值±标准误分别为89.57±11.67、97.02±13.3和-7.44±7.14μg/100ml/min。采用线性回归分析，发现HOMA与骨骼肌蛋白质合成（R² = 0.28；P = 0.024）及分解（R² = 0.49；P = 0.001）呈正相关。同时也注意到骨骼肌蛋白质净平衡与HOMA呈负相关（R² = 0.20；P = 0.066）。校正C反应蛋白后，仅HOMA与骨骼肌蛋白质分解之间的关系仍然存在（R² = 0.49；P = 0.006）。全身蛋白质周转率各组分与HOMA之间无显著关联。本研究表明，非糖尿病透析患者存在明显的胰岛素抵抗，与骨骼肌蛋白质分解有关，是尿毒症性消瘦干预的新靶点。
