Effects of progressive resistance training in individuals with type 2 diabetic polyneuropathy: a randomised assessor-blinded controlled trial.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the effects of progressive resistance training (PRT) on muscle strength, intraepidermal nerve fibre density (IENFD) and motor function in individuals with type 2 diabetic polyneuropathy (DPN) and to compare potential adaptations to those of individuals with type 2 diabetes without DPN and healthy controls. METHODS: This was an assessor-blinded trial conducted at the Neurology department, Aarhus University Hospital. Adults with type 2 diabetes, with and without DPN and healthy control participants were randomised to either supervised PRT or non-PRT for 12 weeks. Allocation was concealed by a central office unrelated to the study. The co-primary outcomes were muscle strength in terms of the peak torque of the knee and ankle extensors and flexors, and IENFD. Secondary outcome measures included the 6 min walk test (6MWT), five-time sit-to-stand test (FTSST) and postural stability index obtained by static posturography. RESULTS: A total of 109 individuals were enrolled in three groups (type 2 diabetes with DPN [n = 42], type 2 diabetes without DPN [n = 32] and healthy control [n = 35]). PRT resulted in muscle strength gains of the knee extensors and flexors in all three groups using comparative analysis (DPN group, PRT 10.3 ± 9.6 Nm vs non-PRT -0.4 ± 8.2 Nm; non-DPN group, PRT 7.5 ± 5.8 Nm vs non-PRT 0.6 ± 8.8 Nm; healthy control group, PRT 6.3 ± 9.0 Nm vs non-PRT -0.4 ± 8.4 Nm; p<0.05, respectively). Following PRT the DPN group improved the 6MWT (PRT 34.6 ± 40.9 m vs non-PRT 2.7 ± 19.6 m; p=0.001) and the FTSST (PRT -1.5 ± 2.2 s vs non-PRT 1.5 ± 4.6 s; p=0.02). There was no change in IENFD following PRT in any of the groups. CONCLUSIONS/INTERPRETATION: PRT improved muscle strength of the knee extensors and flexors and motor function in individuals with type 2 diabetic polyneuropathy at levels comparable with those seen in individuals with diabetes without DPN and healthy control individuals, while no effects were observed in IENFD. TRIAL REGISTRATION: ClinicalTrials.gov NCT03252132 FUNDING: Research reported in this paper is part of the International Diabetic Neuropathy Consortium (IDNC) research programme, supported by a Novo Nordisk Foundation Challenge Program grant (grant no. NNF14OC0011633) and Aarhus University.

Normative reference values for the dorsal sural nerve derived from a large multicenter cohort.

OBJECTIVES: Dorsal sural nerve conduction studies (NCS) may increase the sensitivity for the diagnosis of polyneuropathy, but clinical use is limited by a lack of reliable normative reference values in all age-groups. The aim of our study was to develop reference values for the dorsal sural nerve, based on a large multicenter cohort of healthy subjects. METHODS: Bilateral antidromic NCS were performed using standard surface electrodes in 229 healthy subjects (aged 21-80 years; median: 54 years). We assessed the normality of data distribution for amplitudes and conduction velocity (CV) and for their logarithmic (ln) transformation. The effects of age and height were determined using linear regression analysis. RESULTS: Sensory potentials were present in all subjects. Logarithmically transformed data were normally distributed. Age2 and height were most significantly associated with amplitude, and age and height with CV, respectively. There was no significant side-difference. Mean amplitudes (right and left) were 4.8 and 4.9 µV and mean CV 46.7 and 46.9 m/s. Reference limits were e (3.712515 - 0.0000956 * age2 - 0.0115883 * height ±â€¯1.96 * 0.51137) for amplitude and e (4.354374 - 0.0021081 * age - 0.0023354 * height ±â€¯1.96 * 0.11161) for CV. CONCLUSIONS: Dorsal sural nerve NCS are robust and have well defined normative limits. SIGNIFICANCE: The findings provide a basis for more sensitive NCS in clinical practice and future studies of the diagnostic accuracy of NCS in polyneuropathy.

Falls in individuals with type 2 diabetes; a cross-sectional study on the impact of motor dysfunction, postural instability and diabetic polyneuropathy.

AIM: To estimate the incidence of falls in individuals with type 2 diabetes compared to healthy controls and to describe the characteristics of fallers with type 2 diabetes in relation to motor dysfunction, postural instability and diabetic polyneuropathy (DPN). METHODS: This is a cross-sectional study of individuals with type 2 diabetes with DPN (n = 54), without DPN (n = 38) and healthy controls (n = 39). Falls were recorded within the preceding year. DPN was defined by clinical scores and nerve conduction studies. Motor function was assessed by a 6-min walk test (6 MWT), five-time sit-to-stand test (FTSST) and isokinetic dynamometry at the non-dominant ankle and knee. An instability index (ST) was measured using static posturography. Univariate and bivariate descriptive statistics were used for group comparisons. RESULTS: Compared with healthy controls, individuals with diabetes had a higher incidence of falls 36%, (n = 33) versus 15%, (n = 6), p = 0.02. There were no differences in falls when comparing individuals with and without DPN. Fallers had an impaired 6 MWT versus non-fallers (450 ± 153 m vs. 523 ± 97 m respectively), a slower FTSST (11.9 ± 4.2 s vs. 10.3 ± 2.9 s respectively) and a higher ST (53 ± 29 vs. 41 ± 17 respectively), p < 0.02 for all. CONCLUSION: Individuals with type 2 diabetes reported a higher number of falls within the preceding year compared to healthy controls, irrespective of the presence of DPN. The main factors associated with falls were increased postural instability, lower walking capacity and slower sit-to-stand movements. The 6 MWT, FTSST and posturography should be considered in future screening programs in identification of individuals at risk for falls.

MRI of Skeletal Muscles in Participants with Type 2 Diabetes with or without Diabetic Polyneuropathy.

BackgroundDiabetic polyneuropathy (DPN) is associated with loss of muscle strength. MRI including diffusion-tensor imaging (DTI) may enable detection of muscle abnormalities related to type 2 diabetes mellitus (DM2) and DPN.PurposeTo assess skeletal muscle abnormalities in participants with DM2 with or without DPN by using MRI.Materials and MethodsThis prospective cross-sectional study included participants with DM2 and DPN (DPN positive), participants with DM2 without DPN (DPN negative), and healthy control (HC) participants enrolled between August 2017 and June 2018. Muscle strength at the knee and ankle was determined with isokinetic dynamometry. MRI of the lower extremities included the Dixon sequence, multicomponent T2 mapping, and DTI calculated fat fractions (FFs), T2 relaxation of muscle (T2water), fractional anisotropy (FA), and diffusivity (mean, axial, and radial). One-way analysis of variance and Tukey honestly significant difference were applied for comparison between groups, and multivariate regression models were used for association between MRI parameters, nerve conduction, strength, and body mass index (BMI).ResultsTwenty participants with DPN (mean age, 65 years ± 9 [standard deviation]; 70% men; mean BMI, 34 kg/m2 ± 5), 20 participants without DPN (mean age, 64 years ± 9; 55% men; mean BMI, 30 kg/m2 ± 6), and 20 HC participants (mean age, 61 years ± 10; 55% men; mean BMI, 27 kg/m2 ± 5) were enrolled in this study. Muscle strength adjusted for age, sex, and BMI was lower in participants with DPN than in DPN-negative and HC participants in the upper and lower leg (plantar flexors [PF], 62% vs 78% vs 89%; P < .001; knee extensors [KE], 73% vs 95% vs 93%; P < .001). FF was higher in leg muscle groups of participants with DPN than in DPN-negative and HC participants (PF, 20% vs 10% vs 8%; P < .001; KE, 13% vs 8% vs 6%; P < .001). T2water was prolonged in leg muscle groups of participants with DPN when compared with HC participants (PF, 33 msec vs 31 msec; P < .001; KE, 32 msec vs 31 msec; P = .002) and in the lower leg when compared with participants without DPN (PF, 33 msec vs 32 msec; P = .03). In multivariate regression models, strength was associated with FA (b = -0.0004), T2water (b = -0.03 msec), and FF (b = -0.1%) at thigh level (P < .001). Furthermore, FA (b = -0.007), T2water (b = -0.53 msec), and FF (b = -4.0%) were associated with nerve conduction at calf level (P < .001).ConclusionMRI of leg muscle groups revealed fat accumulation, differences in water composition, and structural changes in participants with type 2 diabetes mellitus and neuropathy. Abnormalities were most pronounced in the plantar flexors.© RSNA, 2020Online supplemental material is available for this article.See also the editorial by Sneag and Tan in this issue.