Factors influencing sweat gland innervation in diabetes

Factors influencing sweat gland innervation in diabetes
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DOI:
10.1212/wnl.0000000000001488
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发表时间:
2015-04-21
期刊:
影响因子:
9.9
通讯作者:
Polydefkis, Michael
Polydefkis, Michael
中科院分区:
医学1区
文献类型:
--
作者:
Liu, Ying;Billiet, Jennifer;Polydefkis, Michael

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背景:采用体视学方法,用蛋白基因产物(PGP)、酪氨酸羟化酶(TH)和血管活性肠肽(VIP)测定糖尿病患者和健康对照者支配汗腺(SG)片段的神经纤维密度,以确定哪种标记物最能检测组间差异。评估与SG神经纤维(SGNF)神经支配相关的因素,并确定1年内SG神经支配的变化。方法:采用横断面研究方法对92例对照组和2组DM患者共97例进行评估。通过免疫组织化学染色检测泛素水解酶、VIP和TH的腿部皮肤活检,测定表皮内神经纤维密度和SG神经支配。评估与SG神经支配相关的因素,并对15名受试者进行了1年的纵向随访。结果:与对照组相比,糖尿病患者的SGNF神经支配减少。较低的SG神经支配值与糖化血红蛋白A(1c)、体重指数(BMI)、男性与女性的比较以及烟草使用有关,但与糖尿病类型或年龄无关。性别、A(1c)和BMI在多变量模型中仍然具有重要意义。VIP+纤维测量的SG神经支配是比PGP或TH更敏感的神经病变标志物。15例糖尿病患者随访1年,SGNF神经支配明显减少,但表皮内神经纤维密度未见明显下降。结论:SG神经支配的立体测量是评估节后自主神经纤维密度的可行方法。与对照组相比,糖尿病患者的SG神经支配减少,并且在多变量模型中与性别、A(1c)和BMI相关。与基于TH+或PGP9.5+的评估相比,VIP+ SGNF在DM中的下降更为严重。1年内用SGNF检测糖尿病多发性神经病变的进展情况。
Background:Using a stereologic approach, the density of nerve fibers innervating sweat gland (SG) fragments in patients with diabetes mellitus (DM) and healthy controls using protein gene product (PGP), tyrosine hydroxylase (TH), and vasoactive intestinal peptide (VIP) was measured to determine which marker best detected differences between the groups. Factors associated with SG nerve fiber (SGNF) innervation were assessed and the change in SG innervation over a 1-year time period was determined.Methods:Ninety-two control subjects and 2 groups of subjects with DM totaling 97 were assessed in this cross-sectional study. Intraepidermal nerve fiber density and SG innervation were determined from leg skin biopsies that were immunohistochemically stained for ubiquitin hydrolase, VIP, and TH. Factors associated with SG innervation were assessed and 15 subjects were longitudinally followed for 1 year.Results:SGNF innervation was reduced in subjects with DM compared with controls. Lower SG innervation values were associated with increasing glycated hemoglobin A(1c), body mass index (BMI), men compared with women, and tobacco use, but not diabetes type or age. Sex, A(1c), and BMI remained significant in multivariate modeling. SG innervation measured by VIP+ fibers is a more sensitive marker for neuropathy than either PGP or TH. Fifteen subjects with DM followed for 1 year showed a significant decrease in SGNF innervation but not intraepidermal nerve fiber density.Conclusions:Stereologic measurement of SG innervation is feasible to assess postganglionic autonomic nerve fiber densities. SG innervation was reduced in subjects with DM compared with control subjects and was associated with sex, A(1c), and BMI in multivariate modeling. VIP+ SGNF is more severely reduced in DM than TH+ or PGP9.5+-based assessments. Progression of diabetic polyneuropathy was detected by SGNF over a 1-year time period.