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Diabetes is a chronic disease characterized by hyperglycemia, caused by defects in the secretion or action of insulin. It is associated with a range of complications, including nerve damage, digestive issues, and urinary problems. Diabetic amyotrophy, for example, is a nerve disorder complication that causes muscle wasting and pain in the thighs, hips, buttocks, and legs. It is becoming more common for people with diabetes to experience muscle weakness, especially in the early stages of type 2 diabetes, where reduced grip strength may be observed. Recent studies have identified a gene linked to muscle weakness in type 2 diabetes, where the VPS39 gene is less active in muscle cells, preventing the production of a key protein for muscle regeneration.
| Characteristics | Values |
|---|---|
| Type | Type 2 diabetes |
| Muscle strength | Reduced |
| Glucose absorption | Impaired |
| Grip strength | Reduced |
| Diabetic amyotrophy | A complication of diabetes mellitus, causing muscle wasting and pain |
| Diabetic neuropathy | A complication of diabetes, causing nerve damage and pain |
| Diabetic polyneuropathy | Sensory and motor disturbances, leading to distal weakness and atrophy of lower leg and foot muscles |
| Diabetic radiculoplexus neuropathy (DLRN) | Affects nerves in thighs, hips, buttocks, and legs |
| Diabetic lumbosacral neuropathy | Affects lower legs, buttocks, hips, and thighs |
| Diabetic distal symmetric polyneuropathy | Progressive late complication, causing muscle weakness |
| Diabetic fatigue | Related to physiological, psychological, and lifestyle factors, leading to reduced muscle strength and fatigue |
| Sarcopenia | Chronic complication, associated with reduced muscle mass and strength, impaired mobility |
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What You'll Learn
Diabetic amyotrophy
The symptoms of diabetic amyotrophy typically start suddenly on one side of the body and can eventually spread to the other side. Initial pain can last for weeks to months, and weakness usually continues to progress for several months after the pain has improved. The pain eventually subsides, and muscular strength improves, although this may take months, and mild to moderate weakness may continue indefinitely. Symptoms can be managed through medication, diet, and exercise, and most patients recover completely.
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Diabetic neuropathy
There are four main types of diabetic neuropathy: peripheral neuropathy, autonomic neuropathy, proximal neuropathy, and diabetic amyotrophy. Peripheral neuropathy is the most common type, affecting the feet and legs first, followed by the hands and arms. Symptoms include tingling, pain, numbness, and weakness. Autonomic neuropathy affects the nerves controlling internal organs, leading to problems with the heart rate, blood pressure, digestive system, bladder, and sex organs. Proximal neuropathy is a rare and disabling type of nerve damage in the hip, buttock, or thigh. Diabetic amyotrophy, also known as diabetic lumbosacral radiculoplexus neuropathy (DLRN), causes a loss of muscle bulk due to damage to the motor nerve. It results in pain and muscle wasting in the thighs, hips, buttocks, and legs.
The symptoms of diabetic neuropathy depend on the type of neuropathy and the affected nerves. They may include loss of feeling or numbness, tingling or burning sensations, sharp pains or cramps, muscle weakness, and sensitivity to touch. Some people may also experience bladder or bowel problems, gastroparesis, trouble swallowing, changes in vision, and sexual response issues.
Tests can check for diabetic neuropathy before symptoms appear, and early detection is essential for easier treatment. Screening tests are recommended right after a type 2 diabetes diagnosis or five years after a type 1 diabetes diagnosis, followed by annual screenings.
While diabetic neuropathy can be a serious complication, it can often be prevented or managed through blood sugar control, a healthy lifestyle, a balanced diet, and consistent exercise.
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Impaired muscle regeneration
Diabetes is a degenerative disease that affects multiple organs and tissues, including musculoskeletal tissues. Both Type 1 and Type 2 diabetes are characterised by a progressive decline in skeletal muscle mass and function, known as diabetic myopathy. This is a severe skeletal muscle pathology that limits functional capacity and quality of life.
Diabetic amyotrophy is a nerve disorder complication of diabetes mellitus, which causes muscle wasting and pain in the thighs, hips, buttocks, and legs. Diabetic amyotrophy is thought to be caused by an abnormality in the immune system, which damages the blood vessels supplying nerves to the legs. Diabetic amyotrophy is more common in people with Type 2 diabetes, affecting around 1 in 100 people with the disease.
Research has shown that diabetes impairs skeletal muscle regeneration. In a study on mice, those with diabetes displayed a reduced ability for macrophage infiltration within the first few days after injury. This impaired muscle regeneration was also observed in mice lacking T cells, which are involved in modulating the microenvironment of the lesion site.
In humans, a gene linked to muscle regeneration is "silenced" in people with Type 2 diabetes. This gene normally plays an important role in muscle regeneration by producing the VPS39 protein, which is part of the molecular machinery that cells use to dispose of damaged components to regenerate themselves. When this gene is "silenced", muscle stem cells cannot develop into mature muscle cells, impairing muscle regeneration.
The impaired muscle regeneration observed in diabetes has also been linked to alterations in myosin ATPase activity, myokine secretion, and lipid accumulation in skeletal muscle cells. These changes are not solely due to increased body weight, as they were observed in patients with obesity and diabetes compared to BMI-matched controls.
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Reduced muscle mass
Diabetes can cause reduced muscle mass, a condition known as sarcopenia. Sarcopenia is a chronic complication of type 2 diabetes mellitus and is characterised by a reduction in muscle mass and strength. It results in worse morbidity in chronic diseases. Diabetic patients are at an increased risk of impaired mobility and strength due to sarcopenia.
Sarcopenia is associated with a decrease in muscle strength and/or performance. It is diagnosed through the presence of pre-sarcopenia, which is identified by a tendency to have an altered BMD, lower BMI, osteoporosis, a past history of fractures, weak grip strength, and an unhealthy diet. Sarcopenia is also associated with body mass index and osteoporosis, which increase the likelihood of the condition.
Diabetes accelerates the reduction of muscle mass and strength due to several factors. Poor glycaemic control, which is a result of acute or chronic hypo- or hyperglycemia, the variability of blood glucose, and diabetes symptom distress, can cause a decrease in muscle mass. Complications of neuropathy or vasculopathy can also lead to reduced muscle mass.
Additionally, overweight or obesity, insulin resistance, inflammatory cytokines, and endocrine changes are all associated with the adverse effects of premature loss of muscle and normal function in diabetic patients. Intermuscular fat can also reduce blood flow to the muscles and increase the inflammatory process, further contributing to muscle mass loss.
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Impaired glucose absorption
Diabetes mellitus is a disease caused by insufficient action of the hormone insulin. Insulin lowers blood sugar levels and promotes the growth and proliferation of cells. Insufficient insulin has been thought to result in the suppression of growth and proliferation of muscle cells, which in turn contributes to the decline in skeletal muscle mass.
In type 2 diabetes, muscle strength is reduced, and the ability of the muscles to absorb glucose is impaired. This is due to the gene that makes VPS39 being less active in the muscle cells of people with type 2 diabetes. VPS39 is part of the molecular machinery that cells use to dispose of damaged components to regenerate themselves. This process is called autophagy. When the VPS39 gene is "silenced", the ability of muscle tissue to generate new muscle fibres is inhibited, and its glucose uptake is reduced.
Diabetic amyotrophy is a nerve disorder complication of diabetes mellitus that affects the thighs, hips, buttocks, and legs, causing pain and muscle wasting. Diabetic amyotrophy is thought to be caused by an abnormality in the immune system, which damages the tiny blood vessels supplying nerves to the legs. This is called microvasculitis. Diabetic amyotrophy is harder to prevent than other complications of diabetes, but the outlook is usually good, with most patients recovering completely.
The proteins KLF15 and WWP have been shown to contribute to diabetes-induced muscle mass loss. Professor Ogawa's research team found that an increase in blood sugar levels triggers a decline in muscle mass. They also discovered that the KLF15 protein increases in the skeletal muscle of diabetic mice, and that this increase is due to elevated blood sugar levels slowing down the degradation of the KLF15 protein. WWP1, a ubiquitin ligase protein, plays a key role in regulating the degradation of KLF15.
There is evidence that resistance exercise can lower the risk of developing type 2 diabetes and resistance to insulin.
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Frequently asked questions
Yes, muscle weakness is a symptom of diabetes. Diabetic amyotrophy, for example, is a nerve disorder complication of diabetes mellitus that causes muscle wasting, usually in the thighs, hips, buttocks, and legs.
Signs of muscle weakness in diabetic patients include impaired mobility, functional limitation, weight loss, and loss of independence. There may also be a decrease in muscle strength and quality, leading to muscle fatigue and a reduction in work capacity.
There are several factors that can cause muscle weakness in diabetic patients, including physiological factors such as hypo- or hyperglycemia, psychological factors such as depression or emotional distress, and lifestyle factors such as sedentary behavior. Additionally, diabetes-related nerve damage can lead to muscle weakness.
