In diabetic Charcot neuroarthropathy impaired microvascular function is related to long lasting metabolic control and low grade inflammatory process

Abstract

Aims: The aim of this study was to assess microvascular function associated with the occurrence of Charcot neuroarthropathy (CN) in patients with diabetes.

Methods: We evaluated 70 diabetic patients (54 men) with Charcot neuroarthropathy (CN-DM), median age 59 (IQR: 51-62), mean disease duration 16±8years. The control group were 70 subjects with diabetes and without Charcot neuroarthropathy (DM), 54 men, median age 60 (54-62), mean diabetes duration 15±7years. We assessed metabolic control of diabetes, serum C-reactive protein concentration (CRP) and cardiovascular autonomic neuropathy (CAN). We used AGE-Reader to measure skin autofluorescence (AF) associated with accumulation of advanced glycation end products that reflects long lasting metabolic control. Microvascular function was examined by laser Doppler flowmetry (PERIFLUX 5000) with thermal hyperemia (TH) and postocclusive reactive hyperemia (PORH).

Results: CN-DM patients as compared to DM subjects had lower HbA1c level [7.6 (6.6-8.4) vs 8.4 (7.3-9.7)%, p<0.001], lower eGFR [75.9±24.1 vs 86.6±17.8ml/min/1.73m(2), p=0.003], higher CRP serum concentration [3.8 (2.3-10.1) vs 1.9 (0.8-4.4)mg/l, p<0.001] and higher skin autofluorescence [2.8 (2.5-3.1) vs 2.6 (2.3-2.9)AU, p=0.03]. The cardiovascular autonomic neuropathy (CAN) was more frequently diagnosed in CN-DM subjects [59 vs 27%, p<0.001]. The peak flow during thermal hyperemia (THmax) was lower in CN-DM subjects as compared to DM group [156 (93-240) vs 235 (155-300)PU, p=0.001]. We found negative correlation between THmax and CRP concentration (Rs=-0.34, p=0.003), TG concentration (Rs=-0.37, p=0.002) and skin AF (Rs=-0.32, p=0.04) and positive correlation between THmax and HDL cholesterol level (Rs=0.42, p<0.001) in CN-DM patients. There was also a positive correlation between PORHpeak and HDL cholesterol level (Rs=-0.23, p=0.04).

Conclusion: Deterioration of microvascular function and autonomic system dysfunction are present in Charcot neuroarthropathy. Impaired microvascular reactivity is associated with worse long lasting metabolic control of diabetes and low grade inflammatory process.

Keywords: Advanced glycation end products; Charcot neuroarthropathy; Inflammatory process; Laser Doppler flowmetry.