Dubrey S W, Beetham R, Miles J, Noble M I, Rowe R, Leslie R D
Academic Unit of Cardiovascular Medicine, Charing Cross Hospital, London, U.K.
Diabetes Care. 1997 Jan;20(1):84-9. doi: 10.2337/diacare.20.1.84.
Indexes of early renal glomerular and tubular dysfunction have been demonstrated in type I diabetes, but it remains uncertain whether such changes are genetically determined or are secondary to the disease process. We therefore undertook to study whether early markers of renal dysfunction are a consequence of type I diabetes or inherited.
We estimated both urinary albumin excretion (UAE) and urinary retinol-binding protein (RBP) in 51 identical twin pairs discordant for type I diabetes and in 51 matched control subjects.
UAE and RBP were significantly higher in the diabetic twins than in their nondiabetic co-twins (P < 0.0001 and P < 0.0002, respectively). Seven diabetic twins had elevated UAE, but none of the nondiabetic co-twins did. In a subgroup of 44 twins with normal UAE (albumin excretion rate < 20 micrograms/min), diabetic twins had both a higher albumin excretion function (median [range]; 0.64 [0.18-2.74] mg/mmol creatinine) than their nondiabetic co-twins (0.48 [0.24-1.40], P < 0.01) and higher levels of RBP excretion (10.4 [4.0-167.0] micrograms/mmol creatinine) than their nondiabetic co-twins (7.5 [0.97-23.0], P < 0.05). Values between twins of a pair were significantly correlated for RBP (r = 0.36, P < 0.05) but not for UAE (r = 0.13).
These results suggest that in type I diabetes, an index of renal tubular function (RBP), but not glomerular function (UAE), is influenced by shared genetic and nongenetic factors. Type I diabetes can affect renal tubular function even when glomerular function is normal. We conclude that neither the increased UAE nor urinary RBP found in type I diabetes is inherited independently of the diabetes process.
I型糖尿病患者已出现早期肾小球和肾小管功能障碍指标，但这些变化是由基因决定还是继发于疾病进程仍不确定。因此，我们着手研究肾功能障碍的早期标志物是I型糖尿病的结果还是遗传所致。
我们对51对I型糖尿病不一致的同卵双胞胎和51名匹配的对照受试者进行了尿白蛋白排泄量（UAE）和尿视黄醇结合蛋白（RBP）的评估。
糖尿病双胞胎的UAE和RBP显著高于其非糖尿病的同卵双胞胎（分别为P < 0.0001和P < 0.0002）。7名糖尿病双胞胎的UAE升高，但非糖尿病的同卵双胞胎均未出现这种情况。在44名UAE正常（白蛋白排泄率<20微克/分钟）的双胞胎亚组中，糖尿病双胞胎的白蛋白排泄功能（中位数[范围]；0.64[0.18 - 2.74]毫克/毫摩尔肌酐）高于其非糖尿病的同卵双胞胎（0.48[0.24 - 1.40]，P < 0.01），RBP排泄水平（10.4[4.0 - 167.0]微克/毫摩尔肌酐）也高于其非糖尿病的同卵双胞胎（7.5[0.97 - 23.0]，P < 0.05）。一对双胞胎之间的RBP值显著相关（r = 0.36，P < 0.05），但UAE不相关（r = 0.13）。
这些结果表明，在I型糖尿病中，肾小管功能指标（RBP）而非肾小球功能指标（UAE）受共同的遗传和非遗传因素影响。即使肾小球功能正常，I型糖尿病也可影响肾小管功能。我们得出结论，I型糖尿病中发现的UAE增加和尿RBP增加均不是独立于糖尿病进程而遗传的。
