The Diabetic Neuropathies

Practical and Rational Therapy

J. Robinson Singleton, M.D.; A. Gordon Smith, M.D.


Semin Neurol. 2012;32(3):196-203. 

In This Article

Metabolic Syndrome Features and Their Role in Diabetic Neuropathy

Glycemic control has long been the cornerstone of DSP therapy. However, large epidemiologic and treatment studies in patients with diabetes suggest obesity and dyslipidemia may be equally important risk factors. Hyperglycemia does not exist in isolation, and is one component of a broader metabolic syndrome with features initially identified due to their prediction for cardiovascular disease.[11] Metabolic syndrome is defined as the presence of three of the following, increased fasting glucose, hypertriglyceridemia, decreased high-density lipoprotein-C (HDL-C), ethnicity-specific central obesity, and elevated blood pressure. Active drug treatment for any of these conditions in a given patient also meets criteria.[12]

Several metabolic syndrome features have been linked to neuropathy, particularly obesity and dyslipidemia, independent of hyperglycemia.[13] The largest studies have examined metabolic syndrome contribution to neuropathy risk in patients with known diabetes. The EuroDiab study found DSP in 28% of type 1 diabetic patients. It was noted that many patients with good glucose control (hemoglobin A1c < 7%) had DSP, suggesting other risk factors were important. Among patients who did not have neuropathy at baseline, 23.5% developed neuropathy after an average follow up of 7.3 years. Hypertension, serum lipids and triglycerides, body mass index (BMI), and smoking were each identified as independent risk factors.[14,15] Other studies have noted higher obesity rates in patients with idiopathic neuropathy, both with and without abnormal glucose metabolism.[13,16] In addition, there is also evidence that obesity is associated with abnormal autonomic function, early or subclinical autonomic neuropathy.[17]

Hypertriglyceridemia is significantly more common in those with idiopathic neuropathy,[18] and may be involved in its development and progression. Among 28,700 diabetic patients, serum triglyceride level was an independent stepwise risk factor for lower extremity amputation, often a consequence of neuropathy.[19] In a cohort study of patients with mild to moderate diabetic neuropathy, elevated triglycerides significantly correlated with loss of sural nerve myelinated fiber density over the study duration (52 weeks), independently of disease duration, age, or diabetes control.[13,18,20]