Diabetic polyneuropathy (DPN) is the most common neuropathy in the Western world, developing eventually in approximately 50% of all diabetes patients. DPN is most commonly characterized by a progressive loss of distal sensation correlating with loss of sensory axons, followed, in severe cases, by motor weakness and motor axonal loss.
As with most complications of diabetes, duration and severity of hyperglycemia is directly correlated with degree of symptomatology. However, given that up to 18% of patients with newly diagnosed diabetes already have symptoms of pain in their lower extremities, is DPN occurring during the prediabetic stage?
When attempting to answer this question, it’s enlightening to look at the relationship between DPN and impaired glycemia (IG). IG characterizes the prediabetic stage, and includes impaired fasting glucose and/or an abnormal oral glucose tolerance test (OGTT). The correlation of DPN with IG is important for two reasons; it could potentially alter how the diagnosis of diabetes should be made and it would provide a reason to treat IG with medications versus the currently recommended approach of lifestyle change alone.
This correlation has been controversial due to methodologic concerns and varied results. However, one recent study set out to clarify this controversy, hypothesizing that since IG typically evolves into type 2 diabetes mellitus (T2DM), that IG itself causes micro-vessel complications.
In this trial, Mayo Clinic researchers identified 174 patients with IG (fasting glucose 100 to126 mg/dL, 2-hour OGTT glucose levels 140 to 200 mg/dL and HbA1c <6.5%), 218 patients with newly diagnosed overt diabetes, and 150 patients with normal fasting glucose and normal 2-hour OGTT. The frequency of abnormal electrodiagnostic and quantitative sensory testing was similar in the normal and IG groups (2.0% and 1.7%), and was significantly lower in both groups than in the overt diabetes group (7.8%). Thus, data did not support the hypothesis that IG causes DPN.
This Mayo Clinic study implies that IG likely does not independently cause DPN — but what are current clinical practices for evaluating distal symmetric polyneuropathy? A University of Michigan study examined how the diagnostic approach differs among physicians. They found that neurologists were significantly more likely to order more overall tests than internists (16.5% vs 14.5%), and in particular, significantly more oral glucose tolerance tests than internists (28.6% vs 4.1%). Conversely, there was a nonsignificant trend for internists being more likely to order brain and spine MRIs than neurologists (19.8% vs 12.8%).
The implications of these studies are revealing. If IG is not associated with DPN, then why perform diagnostic tests such as OGTT as part of the DPN workup? Apparently, internists are appropriately abstaining from ordering these tests when they are not otherwise suspicious for diabetes. The practical implication is that patients without diabetes with IG that present with a distal symmetric polyneuropathy should have investigations done to seek out a non-diabetes-related cause. IG and overt diabetes are not one and the same to our knowledge, and practitioners should adhere to American Diabetes Association guidelines when trying to relate DPN symptoms to blood sugar abnormalities.
Dyck PJ, et al. The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the rochester diabetic neuropathy study. Neurology. 1993;43:817-824. Edwards JL, et al. Diabetic neuropathy: mechanisms to management. Pharmacol Ther. 2008;120:1-34.