Vascular read-out for TRP channel functionality on distal peripheral nerve endings in healthy men.

BACKGROUND: Quantification of the vasodilation after topical application of capsaicin or cinnamaldehyde is often implemented to indirectly assess Transient Receptor Potential (TRP) Vanilloid 1 (TRPV1) or Ankyrin 1 (TRPA1) functionality respectively. This method has been well-established on the human forearm. However, to enable TRP functionality assessments in distal peripheral neuropathy, the vascular response upon TRP activation on dorsal finger skin was characterized. METHODS: Two doses of cinnamaldehyde (3 % and 10 % v/v) and capsaicin (300 µg and 1000 µg) were topically applied (20 µL) on the skin of the mid three proximal phalanges in 17 healthy men. The dose-response, and inter-hand and inter-period reproducibility of the dermal blood flow (DBF) increase was assessed using Laser Speckle Contrast Imaging (LSCI) during 60 min post-application. Linear mixed models explored dose-driven differences, whereas the intra-class correlation coefficient (ICC) estimated the reproducibility of the vascular response. RESULTS: Both doses of cinnamaldehyde and capsaicin induced a robust, dose-dependent increase in DBF. The vascular response to cinnamaldehyde 10 % on finger skin, expressed as area under the curve, correlated well over time (ICC = 0.66) and excellently between hands (ICC = 0.87). Similarly, the response to capsaicin 1000 µg correlated moderately over time (ICC = 0.50) and well between hands (ICC = 0.73). CONCLUSION: The vascular response upon topical cinnamaldehyde and capsaicin application on finger skin is an alternative approach for measurements on forearm skin. Thereby, it is a promising vascular read-out to investigate the pathophysiology, and TRP involvement in particular, of specific peripheral neuropathic pain syndromes.

Glucose control using fast-acting insulin aspart in a real-world setting: A 1-year, two-centre study in people with type 1 diabetes using continuous glucose monitoring.

AIM: To evaluate the efficacy and safety of switching from traditional mealtime insulins to fast-acting insulin aspart (Fiasp) in a "real-world" clinical practice setting in adult people with type 1 diabetes (PWD1) who were using intermittently scanned or real-time continuous glucose monitoring (isCGM or rtCGM, respectively). MATERIALS AND METHODS: Data from 438 adult PWD1 (60% men, age 44.6 ± 16.2 years, diabetes duration 21.5 ± 14.0 years, isCGM/rtCGM: 391/47, multiple daily injections/continuous subcutaneous insulin infusion: 409/29), who initiated Fiasp from January 2018 to May 2020, were analysed. The primary objective was the evolution of time in range (TIR; 70-180 mg/dL) at 6 and 12 months. Secondary objectives included change in HbA1c, body mass index (BMI), insulin doses, time below range (<70 and <54 mg/dL), and time above range (>180 and >250 mg/dL). RESULTS: TIR improved from 50.3% ± 15.6% to 54.3% ± 15.1% at 6 months (n = 425) and to 55.5% ± 15.2% at 12 months (n = 385) (P < .001), corresponding to 57 min/d at 6 months and 75 min/d at 12 months. Time spent below 54 mg/dL evolved from 3.1% ± 3.3% to 3.1% ± 3.7% and 2.5% ± 3.0% at 6 and 12 months, respectively (P = .011). Also, time spent above 180 mg/dL decreased from 42.3% ± 16.7% at start by 4.2% at 6 months and by 4.6% at 12 months (P < .001). The proportion of people reaching TIR more than 70% increased from 11.0% to 14.8% (P = .002), and those spending less than 4% at time less than 70 mg/dL increased from 36.1% to 42.1% (P = .002). After 12 months, HbA1c, insulin doses, and BMI did not change significantly. CONCLUSIONS: In a Belgian real-world setting of adult PWD1, switching to Fiasp was associated with a 5% increased TIR after 12 months, corresponding to 75 min/d, in combination with less time spent below and above range.