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

Aims/hypothesis: 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/interpretation: 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.

Trial registration: ClinicalTrials.gov NCT01957930.