Muscle

Linking DM Molecular Events to Insulin Resistance and Muscle Atrophy

Published on Tue, 04/23/2019

Muscle metabolic defects have been suspected as contributors toward the pathogenesis of DM. Recent studies have suggested that cellular/molecular mechanisms underlying reduced insulin sensitivity in skeletal muscle of both DM1 and DM2 may be more complex that has been appreciated. Specifically, prior findings suggested that perturbations of post-INSR signaling may be a key factor in development of insulin resistance (Renna et al., 2017). A new publication builds on these data to better establish the link between DM splicopathy and the development of insulin resistance and skeletal muscle atrophy.

Linking DM Molecular Biology to Metabolic Dysfunction

Drs. Laura Renna, Giovanni Meola, and Rosanna Cardani and colleagues (IRCCS-Policlinico San Donato and University of Milan) investigated events downstream from DM-associated mis-splicing of the insulin receptor (INSR) to identify pathways underlying insulin resistance and skeletal muscle wasting (Renna et al., 2019). Specifically, the team asked whether a lack of insulin pathway activation could contribute to skeletal muscle atrophy. Dr Renna was the recipient of an MDF Fellowship in support of this work.

The research team evaluated muscle biopsies from 8 DM1 and 3 DM2 genetically confirmed patients enrolled in a national registry. Biopsies were assessed for muscle fiber type and morphometrics, insulin receptor protein expression, INSR alternative splicing, and signaling pathway response to insulin stimulation.

Skeletal muscle atrophy was detected in nearly all DM1 (type 1 and/or type 2 fiber atrophy) and DM2 (type 2 fiber atrophy) patients. In contrast to the pattern seen in controls (including samples from unaffected controls, motoneuron disease, and type 2 diabetics), RT-PCR analysis showed predominance of the fetal insulin receptor isoform transcript in both types of DM. When examined by fiber type, DM skeletal muscle exhibited a lower expression of insulin receptor protein than all controls for type 1 (slow oxidative) muscle fibers. The team found a negative correlation between type 1 fiber insulin receptor protein level and level of fetal insulin receptor transcript.

A means of assessing insulin pathway activation was identified and validated by the research team. Their results showed that defective activation of insulin signaling led to lower activation of mTOR accompanied by increases in MuRF1 and Atrogin-1/MAFbx expression—all key regulators known to act through insulin signaling to modulate skeletal muscle mass.

Modeling the Impact on Skeletal Muscle in DM

Taken together, these findings further advance understanding of the linkage between insulin receptor mis-splicing, metabolic dysfunction, and skeletal muscle atrophy. In terms of the insulin receptor, predominance of the fetal insulin receptor isoform in DM was observed, and an overall reduction in insulin receptor protein level in DM skeletal muscles was linked to reductions in receptor expression in type 1 fibers.

Based on these data, the research team suggests that reduced insulin receptor levels are responsible for the observed defect in insulin pathway activation in DM and a metabolic imbalance in protein synthesis/degradation—these, in turn, indicate a potential link to skeletal muscle weakness and atrophy, but causality has not yet been established.

Finally, another recent publication (Vujnic et al., 2018) expands upon this theme of metabolic dysfunction in DM, reporting an increased incidence of metabolic syndrome (i.e., co-occurrence of at least 3 of 5 symptoms: central obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein) in DM2. Thus, there’s a clear case for increased research and patient management efforts directed toward metabolic dysfunction in DM.

References:

Receptor and post-receptor abnormalities contribute to insulin resistance in myotonic dystrophy type 1 and type 2 skeletal muscle.
Renna LV, Bosè F, Iachettini S, Fossati B, Saraceno L, Milani V, Colombo R, Meola G, Cardani R.
PLoS One. 2017 Sep 15;12(9):e0184987. doi: 10.1371/journal.pone.0184987. eCollection 2017.

Aberrant insulin receptor expression is associated with insulin resistance and skeletal muscle atrophy in myotonic dystrophies.
Renna LV, Bosè F, Brigonzi E, Fossati B, Meola G, Cardani R.
PLoS One. 2019 Mar 22;14(3):e0214254. doi: 10.1371/journal.pone.0214254. eCollection 2019.

Metabolic impairments in patients with myotonic dystrophy type 2.
Vujnic M, Peric S, Calic Z, Benovic N, Nisic T, Pesovic J, Savic-Pavicevic D, Rakocevic-Stojanovic V.
Acta Myol. 2018 Dec 1;37(4):252-256. eCollection 2018 Dec.

Flexibility and Chair Yoga - 2025 Myotonic Dystrophy In Motion Awareness Month

Presented on July 28, 2025.

Join Mariah Santellan for a calming, accessible chair yoga class that emphasizes flexibility and breath. This session will help you stretch, relax, and stay in motion.

Mariah Santellan, Registered Yoga Teacher & Rehabilitation Therapies Aide
Mariah Santellan is a registered yoga teacher and rehabilitation therapies aide at Iowa HealthCare in the Iowa City area. She has a background and experience in working with diverse populations and is passionate about holistic health & wellness. Last April, Mariah led the Movement Moment, an accessible chair yoga session, at MDF's Iowa City conference. Mariah currently teaches yoga classes at a local community center where she strives to create an inclusive, accessible, & safe space for all. She integrates mindfulness and breathing techniques within her personal practice and the classes she teaches to encourage students to explore their body-mind connection. 

Myotonic Dystrophy In Motion Awareness Month

Each Monday in July 2025 featured a movement expert exploring one of the Pillars of Movement from MDF’s Exercise Guide for People Living with DM. These 30-minute sessions are designed to be accessible and adaptable—whether you’re just getting started or looking to enhance your regular routine.

Click here to learn more about the 2025 Myotonic Dystrophy In Motion Awareness Month!

Participation Disclaimer

Before participating in any MDIM Awareness Month programming, it is important to consult with your physician or other qualified healthcare professional to ensure that exercise is safe and appropriate for your individual needs. The information provided in this exercise program is for educational and informational purposes only and should not be construed as medical advice or a substitute for professional medical expertise or treatment.

By participating in this exercise program, you acknowledge that there are inherent risks involved in any physical activity, and you voluntarily assume full responsibility for any and all risks. You agree to release, discharge, and hold harmless Myotonic Dystrophy Foundation and any contractors from any and all claims, liabilities, or damages arising out of your participation in the program.

If at any time during the exercise program you feel discomfort, pain, dizziness, or any other unusual symptoms, you should stop immediately and consult with a medical professional.

Resistance Training - 2025 Myotonic Dystrophy In Motion Awareness Month

Presented on July 7, 2025.

Led by Dr. Tina Duong, this session focuses on strength training using resistive exercises. You can follow along with weights, elastic bands, or everyday household items—whatever works for you.

Tina Duong, MPT, PhD, Stanford University
Dr. Tina Duong is a Research Scientist and Director of Clinical Outcomes and Research Development at Stanford University School of Medicine, where she conducts and oversees clinical trials, natural history studies, exercise and clinical outcomes research in neuromuscular disorders. Her core competencies include designing, implementing, and analyzing clinical research studies and trial design, collaborating with multidisciplinary teams of researchers, clinicians, and patients, and disseminating findings through publications and presentations. She is passionate about improving the quality of life and health outcomes of people with neuromuscular diseases. She is motivated by the mission of advancing the field of rehabilitation science and contributing to the development of novel clinical outcomes and effective interventions and therapies.

Myotonic Dystrophy In Motion Awareness Month

Click here to learn more about the 2025 Myotonic Dystrophy In Motion Awareness Month!

Participation Disclaimer

If at any time during the exercise program you feel discomfort, pain, dizziness, or any other unusual symptoms, you should stop immediately and consult with a medical professional.

Understanding Myotonic Dystrophy: Inheritance of Myotonic Dystrophy Type 2 (DM2)

Published on Wed, 09/24/2025

The Myotonic Dystrophy Foundation is excited to introduce Understanding Myotonic Dystrophy, a new series of short educational animations designed to educate people living with myotonic dystrophy (DM) and their healthcare providers!

Our third animation “Understanding Myotonic Dystrophy – Inheritance of Myotonic Dystrophy Type 2 (DM2)”, explains how DM2 is passed down from generation to generation and highlights the importance of genetic testing. This animation is a valuable resource for individuals and families living with DM2, helping them deepen their understanding of DM, raise awareness within their families, and educate others about myotonic dystrophy.

Interested in learning about Myotonic Dystrophy Type 1 (DM1)? Click here to watch "Understanding Myotonic Dystrophy: Inheritance of Myotonic Dystrophy Type 1 (DM1)"!

We are sincerely thankful to all physicians, care providers, and patients for their help providing suggestions, opinions, and input regarding content and design throughout this process. Please let us know what topics you would like us to cover in a future animation. Click here to share your feedback!

Read the Transcript - Understanding Myotonic Dystrophy: Inheritance of Myotonic Dystrophy Type 2 (DM2)

Doctor: "David, we may have figured out the cause of your muscle pain and stiffness, as well as your GI issues and early cataracts. Your genetic test results confirm that you have Myotonic Dystrophy Type 2. Known also as DM2, it is typically an adult-onset muscular dystrophy."

David: "Wait… what? I had no idea all of those symptoms are related."

Doctor: "DM2 is an inherited genetic condition caused by an expanded repeat in the CNBP gene. It affects many body systems, most commonly the muscles, heart, eyes, and the endocrine system, which controls your hormones."

Lisa: "How did he get it?"

Doctor: "DM2 is inherited. Either your father or mother can have it. If either one of the parents has it, there’s a 50% chance of passing it to their children with each pregnancy. This is known as autosomal dominance. In DM2, symptoms usually don't get worse from one generation to the next."

David: "Wait… my dad always complained about muscle pain and he had early cataracts. Could that have been DM2?"

Doctor: "It’s possible. DM2 often goes misdiagnosed for many years."

Lisa: "What about our kids, could they have it too?"

Doctor: "Each of your children has a 50% chance of inheriting DM2. If they are affected they may also develop symptoms like insulin insensitivity, muscle weakness, daytime sleepiness, or heart conditions."

David: "What do we do now?"

Doctor: "I recommend seeing a genetic counselor for your children, so they can learn about their disease risks, genetic testing, family planning, and potential symptom management options."

Lisa: "Could David’s symptoms get worse?"

Doctor: "Yes, David’s symptoms may get worse. But, there are things we can do. We will need to have a multidisciplinary care team monitor him regularly. DM2 progresses differently for everyone. Some people develop significant weakness, pain, fatigue, or other symptoms, while other people may only experience mild muscle pain and stiffness for years. Getting your genetic test was an important first step. Now, we can make a clinical care and monitoring plan specific to you."

Nutrition and Swallowing in Myotonic Dystrophy - 2024 MDF Regional Conference in Houston, TX

Presented at the 2024 MDF Regional Conference on Saturday, May 4, 2024 at the Dunn Tower at Houston Methodist in Houston, TX.

Learn about nutrition and swallowing difficulties in myotonic dystrophy. The session will cover adaptive eating techniques and dietary recommendations that cater to the unique swallowing challenges faced by individuals with DM. Gain practical guidance on enhancing nutritional intake and managing dysphagia, improving overall health and daily functioning.

Speakers: Anna Miller, MS, RD, LD, Senior Clinical Dietitian & Carolyn Martinez, M.A., CCC-SLP, Speech Pathologist, Houston Methodist

Click here to learn more about the 2024 MDF Regional Conference in in Houston, TX!

Exercise & Myotonic Dystrophy - 2024 MDF Regional Conference in Gainesville, FL

Presented at the MDF 2024 Regional Conference in Gainesville, FL, on Saturday, March 23, 2024 at the Harrell Medical Education Building at the University of Florida.

Learn how moderate exercise can be safe and helpful for people with myotonic dystrophy. Learn about the latest studies on DM and exercise, how to choose exercises with your healthcare team, and some examples of DM-friendly exercises.

Speaker: Donovan J. Lott, PT, PhD, CSCS, Research Professor, Department of Physical Therapy, University of Florida

Click here to learn more about the 2024 MDF Regional Conference in Gainesville, FL at!

Patterns:

Skeletal muscle weakness is not usually a major feature of childhood-onset DM1 but can be functionally limiting in those with CDM.
Children with CDM have delayed gross motor skills, but almost all obtain independent ambulation.
Children with CDM have improving motor function during the first few years of life, even those with profound hypotonia at birth. They benefit from promotion of motor function through therapy and other activities.
Myotonia can become problematic in late childhood or adolescence. Myotonia can contribute to muscle stiffness, pain, prolonged hand grip, speech and swallowing difficulties, and GI issues. Myotonia in DM1 is most prominent in the forearm and finger muscles, where it causes locking of the grip (“grip lock”). It sometimes affects tongue and jaw muscles, leading to difficulty with speech and chewing.

Symptoms:

Weakness and atrophy of the jaw and facial muscles has the greatest functional impact and results in a number of manifestations
- Reduced facial expression.
- Weakness of the facial, tongue and palatal muscles, leading to dysarthria, dysphagia, and jaw tightness.
- Weakness of the eyelid muscles, leading to drooping of the eyelids (eyelid ptosis).
- Orthopedic complications may occur in children with CDM. The most common complication is talipes equinovarus, though children may develop knee or hip contractures and scoliosi.
Delayed relaxation after grip or percussion, difficulty related to activities of daily life, progressive speech impairment, or profound irritable bowel symptoms.

Diagnosis:

Discuss the following tests with your doctor:
- Grip myotonia can be observed by tightly gripping the clinician’s fingers, and then relaxing the hand after a sustained grip; the hand muscles will typically take 20 seconds or more to fully relax. Percussion myotonia can be demonstrated by a sustained contraction after the muscle is tapped with a reflex hammer. Electrical myotonia can also be demonstrated by abnormal, spontaneous muscle fiber discharges seen on a needle electromyogram (EMG).
- Physical, occupational, and speech therapy needs early and often with specific attention to:
  - Feeding concerns and dysphagia.
  - Gross motor delay.
  - Gross and fine motor weakness.
  - Dysarthria and potential augmentative and alternative communication (AAC) needs.
  - Language acquisition delays.
- Scoliosis; if necessary, consider bracing or referral to orthopedic surgeon.
- Crowded teeth that benefit from orthodontic treatment. The goal of such treatment is to facilitate oral hygiene. Caregivers should be counseled to proactively maintain oral hygiene.

Treatment:

Surgical correction of talipes equinovarus or other contractures early in evaluation if these changes prevent appropriate biomechanical alignment for mobility, cause pain, or limit functional mobility.
Speech therapy targeting speech, language, and communication from a very early age.
Augmentative and alternative communication (AAC) therapy individualized for their linguistic and cognitive abilities if appropriate or necessary.
Newborns with CDM often have difficulty feeding and alternative nutrition should be considered/ After about a year of actively working with a speech therapist or OT, most children can generally start on PO feeding.
Children with CDM experience progressive improvement in their proximal strength until adolescence, at a minimum. Children should therefore be encouraged to participate in physical activity.
Assessment of joint arthokinematics and range of motion should be observed to manage development of joint contracture.
Prevention of joint contractures is key to management and should be closely monitored with early initiation of stretching.
Treatment of talipes equinovarus and other joint contractures should include initial stretching regiment and appropriate ankle bracing (for talipes equinovarus). Serial casting may be considered.
Drugs affecting ion channels, such as mexiletine (Mexitil), can improve myotonia, although their potential for causing cardiac arrhythmias must be weighed against their possible benefits.

Patterns:

Skeletal muscle weakness and myalgia are major features of DM2.
The weakness is bilateral and progresses at the relatively slow rate of 1 to 3 percent per year. Involvement of distal and facial muscles is usually absent. Initial weakness is in proximal hip girdle and neck (flexors > extensors) muscles. Axial muscle weakness is frequent in DM2 and may result in lower back pain.
Myotonia – sustained muscle contraction and difficulty relaxing muscles may be absent. Even if it is not the most disabling aspect of the disease, myotonia can contribute to muscle stiffness, pain, prolonged hand grip, speech and swallowing difficulties, and GI issues, and may be associated with hand tremor.

Symptoms:

Myalgic pains, which can be the most prominent clinical feature in the early stages and may severely affect occupational performance.
Neck flexor weakness, causing difficulty raising the head from a surface.
Impacts to employment and activities of daily living due to proximal and axial muscle weakness (e.g. climbing stairs, standing up from the floor, etc.).
Difficulty with myalgia, mobility, balance and falls.
Need for assistive devices or modifications in the home, school or workplace.

Diagnosis:

Discuss the following tests with your doctor:
- Needle electromyogram (EMG) in proximal muscles.

Treatment:

Moderate- or low-intensity aerobic and resistance exercise minimizing sedentary activities, if possible.
Obtain a cardiac evaluation prior to starting a new exercise routine.
Orthoses, braces.
Walking aids such as a walking cane or walker.
Home modifications as necessary.
Evaluate annually through the primary care provider or by appropriate specialists, including physical therapists/physiotherapists, occupational therapists, speech/language pathologists, dietitians/nutritionists, social workers, nurses/nurse practitioners, physiatrists and orthopedists.
Mexiletine as an option for myotonia, if myotonia is present and is distressing. As mexiletine is an antiarrhythmic, obtain a electrocardiogram (ECG) prior to use.
Drugs affecting ion channels can improve myotonia, although their potential for causing cardiac arrhythmias must be weighed against their possible benefits.

Patterns:

Skeletal muscle weakness is a major feature of DM1.
The weakness progresses at the relatively slow rate of 1 to 3 percent per year. With time, it impedes mobility and activities of daily living.
In general, flexors weaken more than extensors, and distal muscles weaken before proximal muscles.
Bone abnormalities of the skull create elongated facial features and other impacts including jaw and palate abnormalities. Some may require surgical intervention.
Myotonia – sustained muscle contraction and difficulty relaxing muscles – is a hallmark of DM1 and is an aspect of the disease that distinguishes it from other forms of muscular dystrophy. It affects nearly 100 percent of adult-onset DM1.
Myotonia can contribute to muscle stiffness, pain, prolonged hand grip, speech and swallowing difficulties, and GI issues.

Symptoms:

Typical effects of adult-onset DM1 on skeletal muscle include the following:
- Weakness and atrophy of the jaw and facial muscles, leading to thinning of the facial contour and reduced facial expression.
- Weakness of the facial, tongue and palatal muscles, leading to indistinct speech and chewing and swallowing difficulties.
- Weakness of the eyelid muscles, leading to drooping of the eyelids.
- Neck flexor weakness, causing difficulty raising the head from a surface.
- Neck extensor weakness, leading to a dropped head posture and difficulty holding the head up.
- Abdominal and spine erectors weakness.
- Weakness of the diaphragm and other breathing muscles, causing respiratory symptoms.
- Distal upper limb muscle weakness, interfering with dexterity, handwriting and activities of daily living.
- Weakness of the foot dorsiflexor muscles, leading to ankle foot drop and subsequent difficulties of balance and walking.
- Calf muscle weakness, causing difficulty with jumping or rising up on toes and running.
- Impacts to employment and activities of daily living due to loss of ambulation The combination of weak calf muscles and foot drop can lead to instability of the ankles, difficulty standing still, frequent falls and difficulty with walking and stair climbing. As proximal knee and hip muscles are affected, greater difficulty rising from a seated position is experienced.

Diagnosis:

Discuss the following tests with your doctor:
- Assessment of difficulty related to activities of daily life.
- Grip myotonia test.
- Percussion myotonia test.
- Needle electromyogram (EMG).

Treatment:

Assistive devices or modifications in the home, school or workplace.
Evaluate annually through the primary care provider or appropriate specialists, including physical therapists/physiotherapists, occupational therapists, speech/language pathologists, dietitians/nutritionists, social workers, nurses/nurse practitioners, physiatrists and orthopedists, to monitor the above.
Moderate- or low-intensity aerobic and resistance exercise, minimizing sedentary activities, if possible.
Consider a cardiac evaluation prior to starting a new exercise routine.
Assistive and adaptive devices such as orthoses, braces, canes, walkers, hand-splints, etc.
Home and environmental modifications as necessary.
Mexiletine is often recommended for the treatment of myotonia.