Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus
Plasma total homocysteine and cysteine in relation to glomerular filtration rate in diabetes mellitus
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DOI：
10.1046/j.1523-1755.1999.0550031028.x
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发表时间：
1999-03-01
影响因子：
19.6
通讯作者：
Berne, C
中科院分区：
文献类型：
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作者：
Wollesen, F;Brattström, L;Berne, C
背景。血浆总同型半胱氨酸（tHcy）和总半胱氨酸（tCys）浓度由细胞内代谢和肾血浆清除率决定，我们假设肾小球滤过是血浆tHcy和tCys的主要决定因素。我们研究了肾小球滤过率（GFR）与血浆tHcy和tcy之间的关系。我们测定了50例胰岛素依赖型糖尿病（IDDM）和30例非胰岛素依赖型糖尿病（NIDDM）患者的GFR、尿白蛋白排泄率（UAER）、血浆tHcy、tcy、蛋氨酸、维生素B-12、叶酸、c肽和常规指标。所有患者均接受胰岛素强化治疗，血清肌酐浓度低于115 μ mol/l。糖尿病患者血浆tHcy平均值（0.1 mu mol/l）低于正常人（11.1 mu mol/l, P = 0.0014）。糖尿病患者血浆tCys平均值（266.1 mu mol/l）也低于正常人（281.9 mu mol/l, P = 0.0005）。73%的糖尿病患者有相对高滤过。血浆tHcy和tcy与GFR、血清叶酸和血清B12密切且独立相关。然而，血浆tHcy与其他22个测试变量（包括年龄、血清肌酐浓度、UAER、每日胰岛素总剂量和血糖控制）中的任何一个都没有独立的相关性。肾小球滤过率是血浆tHcy和tCys浓度的独立决定因素，而GFR对于无明显肾病的糖尿病患者的同型半胱氨酸和半胱氨酸的肾脏清除率有限制。GFR的下降解释了血浆tHcy与年龄相关的增加，而高滤过解释了糖尿病患者血浆tHcy和tCys浓度低于正常水平。
Background. The plasma concentrations of total homocysteine (tHcy) and total cysteine (tCys) are determined by intracellular metabolism and by renal plasma clearance, and we hypothesized that glomerular filtration is a major determinant of plasma tHcy and tCys. We studied the relationships between the glomerular filtration rate (GFR) and plasma tHcy and tCys in populations of diabetic patients with particularly wide ranges of GFR.Methods. We measured GFR, urine albumin excretion rate (UAER), plasma tHcy, tCys, methionine, vitamin B-12, folate, C-peptide, and routine parameters in 50 insulin-dependent diabetes mellitus (IDDM) and 30 non-insulin-dependent diabetes mellitus (NIDDM) patients. All patients underwent intensive insulin treatment and had a serum creatinine concentration below 115 mu mol/liter.Results. Mean plasma tHcy in diabetic patients (0.1 mu mol/liter) was lower than in normal persons (11.1 mu mol/liter, P = 0.0014). Mean plasma tCys in diabetic patients (266.1 mu mol/liter) was also lower than in normal persons (281.9 mu mol/liter, P = 0.0005). Seventy-three percent of the diabetic patients had relative hyperfiltration. Plasma tHcy and tCys were closely and independently associated with GFR, serum folate, and serum B12. However, plasma tHcy was not independently associated with any of the 22 other variables tested, including age, serum creatinine concentration, UAER, total daily insulin dose, and glycemic control.Conclusions. Glomerular filtration rate is an independent determinant of plasma tHcy and tCys concentrations, and GFR is rate limiting for renal clearance of both homocysteine and cysteine in diabetic patients without overt nephropathy. Declining GFR explains the age-related increase in plasma tHcy, and hyperfiltration explains the lower than normal mean plasma tHcy and tCys concentrations in populations of diabetic patients.