Does diabetic neuropathy cause elevated creatine kinase (CK) levels?

Diabetic Neuropathy and Creatine Kinase Levels

Diabetic neuropathy itself does not typically cause elevated creatine kinase (CK) levels, but elevated CK may occur in approximately 20% of diabetic patients due to associated metabolic myopathy that requires further neurologic evaluation. 1

Relationship Between Diabetic Neuropathy and CK Levels

• Diabetic neuropathy is a heterogeneous group of disorders with diverse clinical manifestations affecting peripheral and autonomic nervous systems, but it does not directly cause CK elevation 2
• Elevated CK levels in diabetic patients are more likely attributable to a primary metabolic myopathy rather than the neuropathy itself 1
• In a prospective study of diabetic patients, approximately one-fifth (19 of 99) had elevated CK levels, suggesting this is a relatively common finding in the diabetic population 1

Types of Diabetic Neuropathy and Their Manifestations

• Diabetic peripheral neuropathy (DPN) primarily affects sensory and motor nerves, presenting with pain, dysesthesia, numbness, and loss of protective sensation 2
• Diabetic autonomic neuropathy affects the cardiovascular, gastrointestinal, and genitourinary systems, manifesting as orthostatic hypotension, gastroparesis, and erectile dysfunction 2
• Neither of these neuropathy types directly causes CK elevation in clinical practice 1

Potential Causes of Elevated CK in Diabetic Patients

• Diabetic myopathy may occur in patients with diabetes and can present with muscle inflammation, ischemia, hemorrhage, infarction, necrosis, fibrosis, and fatty atrophy 3
• Metabolic abnormalities associated with diabetes, particularly in poorly controlled cases, may lead to muscle damage and subsequent CK elevation 1, 3
• Medication effects, particularly statins commonly prescribed to diabetic patients, can cause CK elevation but this is not directly related to neuropathy 1

Clinical Implications and Management

• When elevated CK is found in diabetic patients, further neurologic evaluation is recommended to identify potential underlying metabolic myopathy 1
• Optimizing glucose control is essential to prevent or delay the development of neuropathy in type 1 diabetes and slow progression in type 2 diabetes 2
• Treatment of neuropathic symptoms focuses on pain management with medications such as pregabalin, duloxetine, or gabapentin, but these do not address CK elevation 2

Important Considerations and Pitfalls

• Do not assume that elevated CK in diabetic patients is benign or directly related to their neuropathy; further investigation is warranted 1
• Lactate levels may also be elevated in approximately 25% of diabetic patients, which could be related to metformin use or underlying metabolic abnormalities 1
• Diabetic myopathy may be more common in type 2 diabetes than previously reported and can coexist with nephropathy (50%), neuropathy (50%), and retinopathy (38%) 3

In summary, while diabetic neuropathy is a common complication of diabetes affecting the peripheral and autonomic nervous systems, it does not directly cause CK elevation. When CK elevation is found in diabetic patients, it likely indicates an underlying metabolic myopathy that requires further neurologic evaluation to determine its specific cause and appropriate management.