title: Intensified insulin treatment is associated with improvement in skin microcirculation and ischaemic foot ulcer in patients with type 1 diabetes mellitus: a long-term follow-up study.
abstract: OBJECTIVE
  We investigated skin microcirculation and its association with HbA1c and the incidence of ischaemic foot ulcer in patients with type 1 diabetes formerly randomised (1982-1984) to intensified conventional treatment (ICT) or standard treatment (ST) with insulin for a mean of 7.5 years.
  
  
  METHODS
  We re-determined the skin microcirculation of 72 patients (ICT 35 vs ST 37) from the original Stockholm Diabetes Intervention Study with iontophoresis topically applied with the following vasoactive stimuli: acetylcholine (ACh) (endothelial-dependent vasodilatation), sodium nitroprusside (SNP) (endothelial-independent vasodilatation), and capsaicin (C-nociceptive-dependent vasodilatation). HbA1c levels (mean of 14 values/patient) were prospectively collected between 1990 and 1995 and tested for association with skin microcirculation. The patients were followed until first hospitalisation for an ischaemic foot ulcer or until 2011.
  
  
  RESULTS
  During the median 28 years of follow-up, three patients developed ischaemic foot ulcers in the ICT group compared with ten in the ST group (logrank, p = 0.035). At the time of iontophoresis, HbA1c was lower in the ICT group (median 57 mmol/mol [minimum-maximum 40-79 mmol/mol]) compared with the ST group (68 mmol/mol [41-96 mmol/mol], p < 0.01) (DCCT: ICT 7.4% [5.8-9.4%] vs ST 8.4% [5.9-10.9%]). Stimulated blood flow was higher in the ICT vs ST group with significantly increased perfusion units (PU) for: ACh (8.1 PU [4.6-24.7 PU] vs 5.3 PU [1.7-21.4 PU], p < 0.01); SNP (8.1 PU [2.2-20.1 PU] vs 5.6 PU [2.3-19.2 PU], p = 0.03); and capsaicin (5.0 PU [1.7-22.9 PU] vs 3.4 PU [1.5-8.4 PU], p < 0.01). HbA1c was associated with vasodilatation induced by ACh (b = -0.02, p < 0.01) and capsaicin (b = -0.02, p = 0.03). HbA1c was independently associated with ACh (b = -1.48, p < 0.01) and capsaicin-induced vasodilatation (b = -1.45, p < 0.01).
  
  
  CONCLUSIONS
  Improved glycaemic control in patients with type 1 diabetes is associated with an improvement in skin microcirculation and with a lower incidence of ischaemic foot ulcers.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01957930.
authors.affiliation: Department of Clinical Science and Education, Sachs' Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Rathsman
authors.forename: Kerstin
authors.initials: K
authors.lastname: Jensen-Urstad
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D017719:Diabetic Foot / Q000188:drug therapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D007328:Insulin / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008875:Middle Aged; D012867:Skin / Q000098:blood supply*; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin