Accumulation of advanced glycation end products in the skin is accelerated in relation to insulin resistance in people with Type 1 diabetes mellitus.

AIM: To evaluate the association between skin advanced glycation end products and insulin resistance in Type 1 diabetes. METHODS: The study group consisted of 476 people with Type 1 diabetes (247 men) with a median (interquartile range) age of 42 (33-53) years, disease duration of 24 (19-32) years and HbA1c concentration of 63 (55-74) mmol/mol [7.9 (7.2-8.9)%]. Insulin resistance was assessed according to estimated glucose disposal rate. Advanced glycation product accumulation in the skin was measured by autofluorescence using an AGE Reader. The group was divided into three subgroups based on estimated glucose disposal rate tertiles (<5.5, 5.5-9.5 and >9.5 mg/kg/min, respectively). The higher the estimated glucose disposal rate, the lower the insulin resistance. RESULTS: Skin autofluoresence level decreased with increasing estimated glucose disposal rate; comparing people below the lower tertile, with those between the first and third tertiles, and with those above the third tertile, the median autofluoresences were, respectively: 2.5 (2.2-2.9) vs 2.3 (2.0-2.7) vs 2.1 (1.9-2.5) AU (P<0.0001). A negative correlation was observed between skin autofluorescence and estimated glucose disposal rate (Spearman's correlation coefficient=-0.31, P <0.001). Multiple logistic regression showed a significant, two-way association of insulin resistance with skin autofluorescence. CONCLUSION: The results of this study offer strong evidence for a two-way relationship between insulin resistance and advanced glycation product accumulation in the skin in people with Type 1 diabetes.

The relationship between sudomotor function and skin microvascular reactivity in individuals with type 1 diabetes of long duration.

AIM: The aim of this study was to assess the relationship between sudomotor function and microvascular perfusion in patients with type 1 diabetes (DM1). METHODS: We evaluated 415 patients (206 women), with DM1, median age of 41 (IQR: 33-53) years, disease duration of 25 (IQR: 20-32) years. We assessed metabolic control of diabetes and the presence of peripheral and cardiac autonomic neuropathy. Sudomotor function was assessed using Sudoscan device by electrochemical skin conductance (ESC). Microvascular function was measured by laser-Doppler flowmetry with basal perfusion, the peak flow after occlusion (PORHpeak) and THmax which is the percentage change between basal perfusion and the peak flow during thermal hyperemia (TH). The accumulation of advanced glycation end products in the skin was assessed by skin autofluorescence (AF) measurement using AGE Reader. We subdivided patients based on the presence of diabetic peripheral neuropathy (DPN), cardiac autonomic neuropathy (CAN) and according to normal value of ESC. RESULTS: Patients with abnormal ESC had higher skin AF [2.5 (2.1-2.9) vs 2.1 (1.9-2.5) AU, p < 0.001], lower eGFR [83 (72-96) vs 98 (86-108) ml/min/1.73 m2, p < 0.001], higher basal perfusion [25 (12-81) vs 14 (7-43) PU, p < 0.001], lower THmax [664 (137-1461) vs 1115 (346-1933) %, p = 0.002], higher PORHpeak [104 (59-167) vs 70 (48-135) PU, p < 0.001] as compared to subjects with normal ESC results. We found negative correlation between THmax and TG level (Rs = -0.14, p < 0.005), AF (Rs = -0.19, p = 0.001), vibration perception threshold - VPT (Rs = -0.24, p < 0.001) and positive correlation with HDL level (Rs = 0.14, p = 0.005), Feet ESC (Rs = 0.21, p < 0.001) and Hands ESC (Rs = 0.14, p = 0.004). We found positive correlation between PORHpeak and TG level (Rs = 0.14, p = 0.003), skin AF (Rs = 0.29, p < 0.001), VPT (0.27, p < 0.001) and negative correlation with eGFR (Rs = -0.2, p < 0.001), HDL (Rs = -0.12, p = 0.01), Feet ESC (Rs = -0.27, p < 0.001) and Hand ESC (Rs = -0.16, p = 0.002). CONCLUSION: Impaired microvascular reactivity is associated with sudomotor dysfunction in patients with type 1 diabetes.