Quantification of heat shock proteins in the posterior interosseous nerve among subjects with type 1 and type 2 diabetes compared to healthy controls.

Introduction: Diabetic peripheral neuropathy (DPN) is a common complication of both type 1 (T1D) and type 2 diabetes (T2D). No cure for DPN is available, but several potential targets have been proposed for treatment. Heat shock proteins (HSPs) are known to respond to both hyper- and hypoglycemia. DPN can be diagnosed using electrophysiology and studied using peripheral nerve biopsies. Aim: This study aimed to analyze the presence and patterns of HSPs in peripheral nerve biopsies from subjects with T1D, T2D, and healthy controls. Methods: Posterior interosseous nerves (PIN) from a total of 56 subjects with T1D (n = 9), with T2D (n = 24), and without diabetes (i.e., healthy controls, n = 23) were harvested under local anesthesia and prepared for quantitative mass spectrometry analysis. Protein intensities were associated with electrophysiology data of the ulnar nerve and morphometry of the same PIN, and differences in protein intensities between groups were analyzed. Results: In total, 32 different HSPs were identified and quantified in the nerve specimens. No statistically significant differences were observed regarding protein intensities between groups. Furthermore, protein intensities did not correlate with amplitude or conduction velocity in the ulnar nerve or with the myelinated nerve fiber density of PIN. Conclusion: Quantitative proteomics can be used to study HSPs in nerve biopsies, but no clear differences in protein quantities were observed between groups in this cohort.

Vibrotactile sense might improve over time in paediatric subjects with type 1 diabetes-A mid-term follow-up using multifrequency vibrometry.

AIM: Impaired vibrotactile sense, mirroring diabetic peripheral neuropathy, is present among children and adolescents with type 1 diabetes. This study aims to re-examine the vibrotactile sense of paediatric type 1 diabetes subjects in order to evaluate any alterations in the vibrotactile sense over time. METHODS: A VibroSense Meter I device was used to determine the vibrotactile perception thresholds (VPTs) for seven frequencies from the pulp of index and little fingers and for five frequencies from metatarsal heads one and five on the sole of the foot, of 37 children and adolescents with type 1 diabetes, previously examined in a larger cohort. Subjects were followed up after a median time of 30 months. Z-scores of VPTs were calculated using previously collected normative data. RESULTS: Vibrotactile perception thresholds improved over time at low frequencies (especially 16 Hz) on the foot, while not being statistically significant different on the rest of the frequencies, either on hand or foot. VPTs were not correlated with HbA1c. CONCLUSION: A mid-term follow-up of vibrotactile sense in paediatric subjects with type 1 diabetes shows a conceivable normalization of previously impaired vibrotactile sense on some frequencies on the foot, indicating that vibrotactile sense might fluctuate over time.

Quantitative proteomic analysis of human peripheral nerves from subjects with type 2 diabetes.

AIMS: Diabetic peripheral neuropathy (DPN) is a common and severe complication to type 2 diabetes. The pathogenesis of DPN is not fully known, but several pathways and gene polymorphisms contributing to DPN are described. DPN can be studied using nerve biopsies, but studies on the proteome of the nerve itself, and its surrounding tissue as a whole, are lacking. Studies on the posterior interosseous nerve (PIN) have proposed PIN a useful indicator of DPN. METHODS: A quantitative mass spectrometry-based proteomics analysis was made of peripheral nerves from age- and gender-matched living human male tissue donors; nine type 2 diabetes subjects, with decreased sural nerve action potentials indicating DPN, and six controls without type 2 diabetes, with normal electrophysiology results. RESULTS: A total of 2617 proteins were identified. Linear regression was used to discover which proteins were differentially expressed between type 2 diabetes and controls. Only soft signals were found. Therefore, clustering of the 500 most variable proteins was made to find clusters of similar proteins in type 2 diabetes subjects and healthy controls. CONCLUSIONS: This feasibility study shows, for the first time, that the use of quantitative mass spectrometry enables quantification of proteins from nerve biopsies from subjects with and without type 2 diabetes, which may aid in finding biomarkers of importance to DPN development.

Impaired vibrotactile sense in children and adolescents with type 1 diabetes - Signs of peripheral neuropathy.

OBJECTIVE: To investigate whether multi-frequency vibrometry can identify individuals with elevated vibration perception thresholds (VPTs), reflecting impaired vibrotactile sense, among children and adolescents with type 1 diabetes. METHODS: In 72 pediatric patients with type 1 diabetes, VPTs were evaluated for seven frequencies on two sites of the hand, and five frequencies on two sites of the foot. Z-scores, based on previously collected reference data, were calculated. Perception to light touch was investigated using monofilaments. Subjects' characteristics were analyzed in comparison to normal and impaired vibrotactile sense. RESULTS: Subjects' median age, disease duration and age at disease onset were 12.8, 5.3 and 6.9 years, respectively. A total of 13 out of 72 (18%) subjects had impaired vibrotactile sense on at least one foot site. Impaired vibrotactile sense was more common among subjects treated with multiple daily insulin injections (MDI) compared to subjects treated with continuous subcutaneous insulin infusion (CSII) (p = 0.013). Age at disease onset was higher among subjects with impaired vibrotactile sense (p = 0.046). No significant correlations were found with gender, HbA1c or duration of diabetes. CONCLUSIONS: Impaired vibrotactile sense, mirroring diabetic peripheral neuropathy, was found in 1/5 of the children and adolescents in the study, and was more common in patients treated with MDI than in subjects treated with CSII.