title: Relationships Between Type 2 Diabetes, Neuropathy, and Microvascular Dysfunction: Evidence From Patients With Cryptogenic Axonal Polyneuropathy.
abstract: This study investigated whether the relationship between neuropathy and microvascular dysfunction in patients with type 2 diabetes is independent of diabetes-related factors. For this purpose, we compared skin microvascular function in patients with type 2 diabetes with that of patients with cryptogenic axonal polyneuropathy (CAP), a polyneuropathy of unknown etiology.
  
  
  
  Cross-sectional information was collected from 16 healthy controls (HCs), 16 patients with CAP, 15 patients with type 2 diabetes with polyneuropathy (DPN), and 11 patients with type 2 diabetes without polyneuropathy. Axonal degeneration was assessed with skin biopsy and nerve conduction studies. Microvascular skin vasodilation was measured using laser Doppler fluxmetry combined with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP).
  
  
  
  Patients with CAP and DPN demonstrated a similar decrease in intraepidermal nerve fiber density and sural sensory nerve action potential compared with HCs. The vasodilator response to ACh was similar among patients with CAP (relative mean difference based on log values 13.3%; 95% CI -35.0 to 97.7%;P= 0.652) but was lower in the patients with diabetes with neuropathy (157.5%; 42.0-366.7%;P= 0.003) and without neuropathy (174.2%; 44.2-421.3%;P= 0.003) compared with HCs. No significant differences were found between the groups of patients with diabetes (P= 0.845). The vasodilator response to SNP was not significantly different among the groups (P= 0.082).
  
  
  
  In this study, endothelium-dependent vasodilation was reduced in patients with type 2 diabetes regardless of the presence of polyneuropathy, whereas microvascular vasodilation was normal in patients with CAP. These data suggest that in type 2 diabetes, neuropathy does not contribute to impaired microvascular endothelium-dependent vasodilation and vice versa. In addition, this study suggests that impaired microvascular vasodilation does not contribute to CAP.
authors.affiliation: VU University Medical Center, Amsterdam, the Netherlands a.emanuel@vumc.nl.
authors.forename: Anna L
authors.identifier: 0000-0002-9436-503X
authors.initials: AL
authors.lastname: Emanuel
authors.affiliation: Centre for Human Drug Research, Leiden, the Netherlands.|Erasmus MC University Medical Center, Rotterdam, the Netherlands.
authors.forename: Mariska D
authors.initials: MD
authors.lastname: Nieuwenhoff
authors.affiliation: Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Erica S
authors.initials: ES
authors.lastname: Klaassen
authors.affiliation: Biogen, Cambridge, MA.
authors.forename: Ajay
authors.initials: A
authors.lastname: Verma
authors.affiliation: VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Mark H H
authors.initials: MH
authors.lastname: Kramer
authors.affiliation: VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Rob
authors.initials: R
authors.lastname: Strijers
authors.affiliation: University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Alexander F J E
authors.initials: AF
authors.lastname: Vrancken
authors.affiliation: VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Etto
authors.initials: E
authors.lastname: Eringa
authors.affiliation: VU University Medical Center, Amsterdam, the Netherlands.|Centre for Human Drug Research, Leiden, the Netherlands.
authors.forename: Geert Jan
authors.initials: GJ
authors.lastname: Groeneveld
authors.affiliation: VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Erik H
authors.initials: EH
authors.lastname: Serné
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007478:Iontophoresis; D008297:Male; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D011115:Polyneuropathies / Q000150:complications / Q000188:drug therapy*; D012867:Skin / Q000187:drug effects / Q000503:physiopathology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D055815:Young Adult
chemical_list: D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine