Accepted Manuscript The effect of peripheral neuropathy on lower limb muscle strength in diabetic individuals
Jean P. Ferreira, Cristina D. Sartor, Ângela M.O. Leal, Isabel C.N. Sacco, Tatiana O. Sato, Ivana L. Ribeiro, Alice S. Soares, Jonathan E. Cunha, Tania F. Salvini PII: DOI: Reference:
S0268-0033(17)30048-7 doi: 10.1016/j.clinbiomech.2017.02.003 JCLB 4286
To appear in:
Clinical Biomechanics
Received date: Accepted date:
26 August 2016 7 February 2017
Please cite this article as: Jean P. Ferreira, Cristina D. Sartor, Ângela M.O. Leal, Isabel C.N. Sacco, Tatiana O. Sato, Ivana L. Ribeiro, Alice S. Soares, Jonathan E. Cunha, Tania F. Salvini , The effect of peripheral neuropathy on lower limb muscle strength in diabetic individuals. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Jclb(2017), doi: 10.1016/j.clinbiomech.2017.02.003
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT The effect of peripheral neuropathy on lower limb muscle strength in diabetic individuals
Jean P. Ferreira1, Cristina D. Sartor2, Ângela M. O. Leal3, Isabel C. N. Sacco2, Tatiana O.
Laboratory of Skeletal Muscle Plasticity, Department of Physical Therapy, Federal
RI
1
PT
Sato1, Ivana L. Ribeiro1, Alice S. Soares1, Jonathan E. Cunha1, Tania F. Salvini1
2
Physical Therapy, Speech and Occupational Therapy Department, School of Medicine,
NU
University of São Paulo, São Paulo, SP, Brazil;
Department of Medicine, Federal University of São Carlos, São Carlos, SP, Brazil.
MA
3
SC
University of São Carlos, SP, Brazil;
Address for correspondence:
D
Tania F. Salvini, PT, MS, PhD
PT E
Laboratory of Skeletal Muscle Plasticity, Department of Physical Therapy, Universidade Federal de São Carlos, São Carlos, SP, Brazil
CE
Zip code: 13565-905; Phone: +55 16 33518345
AC
E-mail: [email protected]
Word Count: 4.145 Figure count: 1 Table count: 4
1
ACCEPTED MANUSCRIPT Abstract Background: Skeletal muscle strength is poorly described and understood in diabetic participants with diabetic peripheral neuropathy. This study aimed to investigate the extensor and flexor torque of the knee and ankle during concentric, eccentric, and isometric contractions in men with diabetes mellitus type 2 with and without diabetic
PT
peripheral neuropathy.
RI
Methods: Three groups of adult men (n= 92), similar in age, body mass index, and
SC
testosterone levels, were analyzed: 33 non-diabetic controls, 31 with type 2 diabetes mellitus, and 28 with diabetic peripheral neuropathy. The peak torques in the
NU
concentric, eccentric, and isometric contractions were evaluated using an isokinetic dynamometer during knee and ankle flexion and extension.
MA
Findings: Individuals with diabetes and diabetic peripheral neuropathy presented similar low concentric and isometric knee and ankle torques that were also lower than
PT E
contractions, and the joints.
D
the controls. However, the eccentric torque was similar among the groups, the
Interpretation: Regardless of the presence of peripheral neuropathy, differences in
CE
skeletal muscle function were found. The muscle involvement does not follow the same pattern of sensorial losses, since there are no distal-to-proximal impairments. Both knee
AC
and ankle were affected, but the effect sizes of the concentric and isometric torques were found to be greater in the participants’ knees than in their ankles. The eccentric function did not reveal differences between the healthy control group and the two diabetic groups, raising questions about the involvement of the passive muscle components. Keywords: Muscle strength; polyneuropathy; diabetes; muscle function; low limbs; motor function. 2
ACCEPTED MANUSCRIPT INTRODUCTION Diabetes mellitus type 2 (DM2) and diabetic peripheral neuropathy (DPN) have been correlated to metabolic and inflammatory changes that lead to a reduction in muscle mass and strength (Bouchard and Janssen, 2010; Zamboni et al., 2008). DPN has been associated with the loss of tactile, thermal, and vibratory sensitivities (Boulton
PT
et al., 2005) in addition to a reduction in motor nerve conduction velocity in latter stages
RI
leading to changes in the movement of the lower limbs and the dynamic stability during
SC
locomotion (Fernando et al., 2013). Even when DM2 is not associated with DPN, it is known that it can cause loss of mass and muscle strength (Andreassen et al., 2014;
NU
Hilton et al., 2008), which may be related to subclinical inflammation (Bouchard and Janssen, 2010; Stenholm et al., 2008; Zamboni et al., 2008) as well as degeneration of
MA
the sarcoplasmic proteins associated with insulin resistance (Cruz-Jentoft et al., 2010). A few studies (Li et al., 2016; Lee et al., 2013; Peterson et al., 2016) that followed
D
patients with DM2 and DPN reported muscle mass losses. Some reported functional
PT E
changes in elderly women with DM2 over a six-year course of the disease (Lee et al., 2013), such as reduced gait velocity, decreased grip strength (Fernando et al., 2013;
CE
Joule J. et al., 2016), and a 50% reduction in concentric knee extensor torque in men with DM2 over a three-year period (Park et al., 2007). However, the presence of DPN
AC
was unconfirmed in those studies; the observed functional deficits could also be associated with both DPN and DM2. Individuals that had DM2 for more than 10 years showed less muscle strength, regardless of the presence of DPN (Hatef et al., 2014). Andreassen et al. (2014) found a lower concentric torque of the plantar flexors in individuals with DM2 compared to individuals with diabetes mellitus type 1 (DM1) and non-diabetics, but they reported no difference between diabetics with and without DPN. It has been reported that only 3
ACCEPTED MANUSCRIPT individuals with DM2 had a reduction in the diameter of type I and type II muscle fibers of the gastrocnemius, indicating that torque reduction is associated with atrophy (Andreassen et al., 2014). In a correlational study, Andersen et al. (2004) found that, as DPN became more severe, the flexor and extensor concentric torque at the knee and ankle joints decreased in individuals with DM2. However, in that study, no difference
PT
was found in knee extension torque between the diabetic individuals with and without
RI
DPN.
SC
One of the first studies that evaluated the torque of diabetic individuals that had the disease for more than 20 years noted that the reduction of concentric torque of the
NU
knee flexors and extensors, at 90°/s, and of the ankle dorsiflexors and plantar flexors at 60º/s, was inversely correlated to DPN (Andersen, 1996). However, individuals of both
MA
sexes, with DM1 and DM2, were included in the same group (Andersen, 1996). Other results indicated that DM1 and DM2 could affect the skeletal muscle properties via
D
different mechanisms (Bouchard and Janssen, 2010; D’Souza et al., 2013). DM1 has
PT E
been associated with hyperglycemia and protein alterations, and DM2 has been associated with inflammation that causes atrophy (D’Souza et al., 2013).
CE
Gender is another important factor that should be considered in the studies, since there are differences in muscle strength between males and females (Cruz-Jentoft et al.,
AC
2010). Lowe et al. (2011) reported that estrogen benefits muscle strength, and that estrogen receptors are involved in the underlying mechanism to improve muscle quality. Thus, the influence of gender on muscle performance is highly dependent on the types and levels of hormones. Other studies have suggested that other female hormones could also influence muscle strength, but more research is needed on that topic (Tiidus, 2011). Although some studies have reported torque reduction and functional losses in the lower limbs of diabetic individuals with and without DPN (Andersen et al., 2004; 4
ACCEPTED MANUSCRIPT Andreassen et al., 2014; Bouchard and Janssen, 2010; Fernando et al., 2013; Hatef et al., 2014; Hilton et al., 2008; Park et al., 2007; Petrofsky et al., 2005), so far none of the studies that investigated knee and ankle torques considered all the anthropometric (sex, mass, height, and body mass index [BMI]) and clinical characteristics (type of DM and testosterone and glycated hemoglobin levels) previously discussed. Considering that all
PT
types of muscle contractions are important for gait and the activities of daily living, our
RI
aim was to investigate the knee flexor and extensor torques and the ankle dorsiflexion
male subjects with DM2, with and without DPN.
SC
and plantar flexion torques during concentric, eccentric, and isometric contractions in
NU
Previous studies (Joule J. et al., 2016; Lee et al., 2013; Peterson et al., 2016, Fernando et al., 2013, Park et al., 2007; Hatef et al., 2014) have found a reduction of
MA
muscle strength in diabetic individuals, even when DPN was not present, but in several uncontrolled conditions, and this reductions were attributed to be caused by different
D
mechanisms. After the onset of DPN, the subsequent nerve damage contributes to an
PT E
even greater decrease in muscle function. Thus, by controlling for sex, age, testosterone and glycated hemoglobin levels, and the clinical characterization of DPN, we
CE
hypothesized that individuals with DM2 would have lower peak torque than individuals without DM2 and individuals that also had DPN would have even lower torque than
AC
subjects with DM2 while performing three types of muscle contraction. Moreover we hypothesized that a decrease in the peak torques would be similar during all three different muscle contractions, since they depend on muscle tropism and muscle activation mechanisms.
5
ACCEPTED MANUSCRIPT METHODS
Participants Males between the ages of 18 and 65 were included in this study. Participants were recruited at the Endocrinology Clinic at the Health School Unit of the Federal
PT
University of São Carlos and at the local Medical Specialties Center. Exclusion criteria
RI
included the presence of cardiovascular diseases with systemic repercussions (unstable
SC
angina, uncontrolled hypertension); pre-diabetes; renal insufficiency; skeletal muscle diseases (rheumatoid arthritis, osteoarthritis, joint endoprosthesis, tendinitis, bursitis,
NU
disk herniation, gout, anterior cruciate ligament rupture or cruciate reconstruction, malalignment of the lower limbs); liver disease; hypogonadism (total testosterone level
MA
of
Jean P. Ferreira, Cristina D. Sartor, Ângela M.O. Leal, Isabel C.N. Sacco, Tatiana O. Sato, Ivana L. Ribeiro, Alice S. Soares, Jonathan E. Cunha, Tania F. Salvini PII: DOI: Reference:
S0268-0033(17)30048-7 doi: 10.1016/j.clinbiomech.2017.02.003 JCLB 4286
To appear in:
Clinical Biomechanics
Received date: Accepted date:
26 August 2016 7 February 2017
Please cite this article as: Jean P. Ferreira, Cristina D. Sartor, Ângela M.O. Leal, Isabel C.N. Sacco, Tatiana O. Sato, Ivana L. Ribeiro, Alice S. Soares, Jonathan E. Cunha, Tania F. Salvini , The effect of peripheral neuropathy on lower limb muscle strength in diabetic individuals. The address for the corresponding author was captured as affiliation for all authors. Please check if appropriate. Jclb(2017), doi: 10.1016/j.clinbiomech.2017.02.003
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT The effect of peripheral neuropathy on lower limb muscle strength in diabetic individuals
Jean P. Ferreira1, Cristina D. Sartor2, Ângela M. O. Leal3, Isabel C. N. Sacco2, Tatiana O.
Laboratory of Skeletal Muscle Plasticity, Department of Physical Therapy, Federal
RI
1
PT
Sato1, Ivana L. Ribeiro1, Alice S. Soares1, Jonathan E. Cunha1, Tania F. Salvini1
2
Physical Therapy, Speech and Occupational Therapy Department, School of Medicine,
NU
University of São Paulo, São Paulo, SP, Brazil;
Department of Medicine, Federal University of São Carlos, São Carlos, SP, Brazil.
MA
3
SC
University of São Carlos, SP, Brazil;
Address for correspondence:
D
Tania F. Salvini, PT, MS, PhD
PT E
Laboratory of Skeletal Muscle Plasticity, Department of Physical Therapy, Universidade Federal de São Carlos, São Carlos, SP, Brazil
CE
Zip code: 13565-905; Phone: +55 16 33518345
AC
E-mail: [email protected]
Word Count: 4.145 Figure count: 1 Table count: 4
1
ACCEPTED MANUSCRIPT Abstract Background: Skeletal muscle strength is poorly described and understood in diabetic participants with diabetic peripheral neuropathy. This study aimed to investigate the extensor and flexor torque of the knee and ankle during concentric, eccentric, and isometric contractions in men with diabetes mellitus type 2 with and without diabetic
PT
peripheral neuropathy.
RI
Methods: Three groups of adult men (n= 92), similar in age, body mass index, and
SC
testosterone levels, were analyzed: 33 non-diabetic controls, 31 with type 2 diabetes mellitus, and 28 with diabetic peripheral neuropathy. The peak torques in the
NU
concentric, eccentric, and isometric contractions were evaluated using an isokinetic dynamometer during knee and ankle flexion and extension.
MA
Findings: Individuals with diabetes and diabetic peripheral neuropathy presented similar low concentric and isometric knee and ankle torques that were also lower than
PT E
contractions, and the joints.
D
the controls. However, the eccentric torque was similar among the groups, the
Interpretation: Regardless of the presence of peripheral neuropathy, differences in
CE
skeletal muscle function were found. The muscle involvement does not follow the same pattern of sensorial losses, since there are no distal-to-proximal impairments. Both knee
AC
and ankle were affected, but the effect sizes of the concentric and isometric torques were found to be greater in the participants’ knees than in their ankles. The eccentric function did not reveal differences between the healthy control group and the two diabetic groups, raising questions about the involvement of the passive muscle components. Keywords: Muscle strength; polyneuropathy; diabetes; muscle function; low limbs; motor function. 2
ACCEPTED MANUSCRIPT INTRODUCTION Diabetes mellitus type 2 (DM2) and diabetic peripheral neuropathy (DPN) have been correlated to metabolic and inflammatory changes that lead to a reduction in muscle mass and strength (Bouchard and Janssen, 2010; Zamboni et al., 2008). DPN has been associated with the loss of tactile, thermal, and vibratory sensitivities (Boulton
PT
et al., 2005) in addition to a reduction in motor nerve conduction velocity in latter stages
RI
leading to changes in the movement of the lower limbs and the dynamic stability during
SC
locomotion (Fernando et al., 2013). Even when DM2 is not associated with DPN, it is known that it can cause loss of mass and muscle strength (Andreassen et al., 2014;
NU
Hilton et al., 2008), which may be related to subclinical inflammation (Bouchard and Janssen, 2010; Stenholm et al., 2008; Zamboni et al., 2008) as well as degeneration of
MA
the sarcoplasmic proteins associated with insulin resistance (Cruz-Jentoft et al., 2010). A few studies (Li et al., 2016; Lee et al., 2013; Peterson et al., 2016) that followed
D
patients with DM2 and DPN reported muscle mass losses. Some reported functional
PT E
changes in elderly women with DM2 over a six-year course of the disease (Lee et al., 2013), such as reduced gait velocity, decreased grip strength (Fernando et al., 2013;
CE
Joule J. et al., 2016), and a 50% reduction in concentric knee extensor torque in men with DM2 over a three-year period (Park et al., 2007). However, the presence of DPN
AC
was unconfirmed in those studies; the observed functional deficits could also be associated with both DPN and DM2. Individuals that had DM2 for more than 10 years showed less muscle strength, regardless of the presence of DPN (Hatef et al., 2014). Andreassen et al. (2014) found a lower concentric torque of the plantar flexors in individuals with DM2 compared to individuals with diabetes mellitus type 1 (DM1) and non-diabetics, but they reported no difference between diabetics with and without DPN. It has been reported that only 3
ACCEPTED MANUSCRIPT individuals with DM2 had a reduction in the diameter of type I and type II muscle fibers of the gastrocnemius, indicating that torque reduction is associated with atrophy (Andreassen et al., 2014). In a correlational study, Andersen et al. (2004) found that, as DPN became more severe, the flexor and extensor concentric torque at the knee and ankle joints decreased in individuals with DM2. However, in that study, no difference
PT
was found in knee extension torque between the diabetic individuals with and without
RI
DPN.
SC
One of the first studies that evaluated the torque of diabetic individuals that had the disease for more than 20 years noted that the reduction of concentric torque of the
NU
knee flexors and extensors, at 90°/s, and of the ankle dorsiflexors and plantar flexors at 60º/s, was inversely correlated to DPN (Andersen, 1996). However, individuals of both
MA
sexes, with DM1 and DM2, were included in the same group (Andersen, 1996). Other results indicated that DM1 and DM2 could affect the skeletal muscle properties via
D
different mechanisms (Bouchard and Janssen, 2010; D’Souza et al., 2013). DM1 has
PT E
been associated with hyperglycemia and protein alterations, and DM2 has been associated with inflammation that causes atrophy (D’Souza et al., 2013).
CE
Gender is another important factor that should be considered in the studies, since there are differences in muscle strength between males and females (Cruz-Jentoft et al.,
AC
2010). Lowe et al. (2011) reported that estrogen benefits muscle strength, and that estrogen receptors are involved in the underlying mechanism to improve muscle quality. Thus, the influence of gender on muscle performance is highly dependent on the types and levels of hormones. Other studies have suggested that other female hormones could also influence muscle strength, but more research is needed on that topic (Tiidus, 2011). Although some studies have reported torque reduction and functional losses in the lower limbs of diabetic individuals with and without DPN (Andersen et al., 2004; 4
ACCEPTED MANUSCRIPT Andreassen et al., 2014; Bouchard and Janssen, 2010; Fernando et al., 2013; Hatef et al., 2014; Hilton et al., 2008; Park et al., 2007; Petrofsky et al., 2005), so far none of the studies that investigated knee and ankle torques considered all the anthropometric (sex, mass, height, and body mass index [BMI]) and clinical characteristics (type of DM and testosterone and glycated hemoglobin levels) previously discussed. Considering that all
PT
types of muscle contractions are important for gait and the activities of daily living, our
RI
aim was to investigate the knee flexor and extensor torques and the ankle dorsiflexion
male subjects with DM2, with and without DPN.
SC
and plantar flexion torques during concentric, eccentric, and isometric contractions in
NU
Previous studies (Joule J. et al., 2016; Lee et al., 2013; Peterson et al., 2016, Fernando et al., 2013, Park et al., 2007; Hatef et al., 2014) have found a reduction of
MA
muscle strength in diabetic individuals, even when DPN was not present, but in several uncontrolled conditions, and this reductions were attributed to be caused by different
D
mechanisms. After the onset of DPN, the subsequent nerve damage contributes to an
PT E
even greater decrease in muscle function. Thus, by controlling for sex, age, testosterone and glycated hemoglobin levels, and the clinical characterization of DPN, we
CE
hypothesized that individuals with DM2 would have lower peak torque than individuals without DM2 and individuals that also had DPN would have even lower torque than
AC
subjects with DM2 while performing three types of muscle contraction. Moreover we hypothesized that a decrease in the peak torques would be similar during all three different muscle contractions, since they depend on muscle tropism and muscle activation mechanisms.
5
ACCEPTED MANUSCRIPT METHODS
Participants Males between the ages of 18 and 65 were included in this study. Participants were recruited at the Endocrinology Clinic at the Health School Unit of the Federal
PT
University of São Carlos and at the local Medical Specialties Center. Exclusion criteria
RI
included the presence of cardiovascular diseases with systemic repercussions (unstable
SC
angina, uncontrolled hypertension); pre-diabetes; renal insufficiency; skeletal muscle diseases (rheumatoid arthritis, osteoarthritis, joint endoprosthesis, tendinitis, bursitis,
NU
disk herniation, gout, anterior cruciate ligament rupture or cruciate reconstruction, malalignment of the lower limbs); liver disease; hypogonadism (total testosterone level
MA
of
