title: Factors influencing sweat gland innervation in diabetes.
abstract: 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 A1c, body mass index (BMI), men compared with women, and tobacco use, but not diabetes type or age. Sex, A1c, 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, A1c, 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.
authors: From the Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors: Ying
authors: Y
authors: Liu
authors: From the Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors: Jennifer
authors: J
authors: Billiet
authors: From the Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors: Gigi J
authors: GJ
authors: Ebenezer
authors: From the Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors: Baohan
authors: B
authors: Pan
authors: From the Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors: Peter
authors: P
authors: Hauer
authors: From the Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors: Jiaxi
authors: J
authors: Wei
authors: From the Department of Neurology, Johns Hopkins University, Baltimore, MD. mpolyde@jhmi.edu.
authors: Michael
authors: M
authors: Polydefkis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003929:Diabetic Neuropathies / Q000175:diagnosis* / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin; D006801:Humans; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000473:pathology*; D013545:Sweat Glands / Q000294:innervation* / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase; D043222:Ubiquitin Thiolesterase; D014660:Vasoactive Intestinal Peptide; D055815:Young Adult
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D014446:Tyrosine 3-Monooxygenase; D043222:Ubiquitin Thiolesterase; D014660:Vasoactive Intestinal Peptide; C482860:UCHL1 protein, human