Idiopathic neuropathy, prediabetes and the metabolic syndrome
Introduction
Peripheral neuropathy is one of the most common disorders seen in general neurology and neuromuscular specialty clinics, and foot numbness and pain is a frequent cause for referral for neurologic consultation. In our outpatient neuromuscular clinics, peripheral neuropathy is the most common diagnosis, accounting for over 20% of new patient visits. Despite its frequency, many neurologists approach the evaluation of peripheral neuropathy with ambivalence. While there are hundreds of causes for peripheral neuropathy, most patients present with symptoms of distal numbness and pain. Therefore, distinguishing one disorder from another can be challenging. Perhaps more discouraging is the mistaken perception that as many as two-thirds of neuropathy patients remain undiagnosed, relegated to the nebulous designation of “idiopathic” or “cryptogenic” neuropathy. Demonstration of familial, inflammatory, and toxic causes for neuropathy has chipped away at this large bloc of idiopathic patients, but in the past 25 years few novel causes of neuropathy have been recognized. However, recent work from our group and others suggests that impaired glucose tolerance (IGT or prediabetes) and other features of Metabolic Syndrome are important contributors to peripheral neuropathy [1], [2], [3], [4]. In this paper, we review the epidemiology of idiopathic neuropathy, discuss the evidence implicating prediabetes and Metabolic Syndrome, and suggest a unifying hypothesis and a means of testing it.
Section snippets
The problem of idiopathic neuropathy
Little population-based epidemiological data is available regarding the prevalence of idiopathic neuropathy. The Italian General Practitioner Study Group interviewed 4191 elderly subjects in northern Italy and demonstrated possible neuropathy in up to 8% [5]. The National Health and Nutrition Examination Survey (NHANES) demonstrated a 14% prevalence of peripheral neuropathy among 2873 individuals over 39 years of age. The risk among diabetics was approximately twice that of non-diabetic
Prediabetes and peripheral neuropathy
Diabetes is the most common cause of peripheral neuropathy worldwide. Diabetes affects over 14 million people in the United States alone and the number of diabetic patients is increasing by 5% each year. Half of diabetic patients develop peripheral neuropathy. Traditional view has held that diabetes only results in neuropathy after many years of sustained hyperglycemia. However, there is evidence that neuropathy occurs earlier in the course of hyperglycemia than other microvascular diabetic
Metabolic Syndrome as a contributor to neuropathy
Prediabetes is one component of an overall Metabolic Syndrome that also consists of obesity, elevated serum triglycerides, reduced serum high density lipoprotein levels, and hypertension. The Metabolic Syndrome is associated with an increased risk of large vessel atherosclerotic disease, but its relationship to microvascular outcomes (neuropathy, retinopathy, and nephropathy) outside of the setting of overt diabetes is unknown. In order to determine if other aspects of the Metabolic Syndrome
A unifying hypothesis and future directions
Epidemiologic data indicate peripheral neuropathy is a very common and clinically important entity. It often results in significant disability due to neuropathic pain. Patients with otherwise idiopathic neuropathy are more likely than the age matched general population to have prediabetes. There is evolving evidence that neuropathy is also associated with other features of the Metabolic Syndrome, and that treatment of hyperglycemia, hyperlipidemia, hypertension and smoking cessation may reduce
Acknowledgements
The authors would like to acknowledge Dr. Jack Petajan, who has been a role model during our tenure at the University of Utah. His intellectual curiosity and humanism have served as guiding principles. Dr. Petajan mentored Dr. Jasper Daube at the University of Wisconsin who subsequently trained Dr. James Albers at the Mayo Clinic. Dr. Albers in turn was our mentor at the University of Michigan. Therefore, all of our clinical and academic work, including that summarized in this paper, are a
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