Neuropathy in Prediabetes and the Metabolic Syndrome

Abstract

The issue of neuropathy in prediabetes and the metabolic syndrome has been controversial, the major reasons being the difficulty in defining neuropathy and the failure to recognize that a substantial proportion of patients with prediabetes have a sensory neuropathy without evidence of abnormalities in nerve conduction studies—the hallmark of the neurologists’ definition of what constitutes neuropathy. Secondly, there is a large cadre of people with neuropathy or neuropathic pain in whom careful studies of the criteria for prediabetes including impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) as well as the lipid abnormalities of the metabolic syndrome (MS) such as elevated triglycerides and a low HDL-cholesterol have not been carried out. Taking these into consideration has vastly changed the appreciation of the relationship between neuropathy and the metabolic entities. Thus, it has been estimated that 24.6–62% of patients with chronic idiopathic symmetrical sensorimotor polyneuropathy (SPN) have prediabetes; as a corollary, of subjects with prediabetes, 11.2–24.3% exhibit SPN and 12.9–20.5% exhibit neuropathic pain. Population-based studies suggest a gradient for the prevalence of SPN, with the highest being in patients with diabetes, followed by IGT, IFG, and the lowest in normal glucose tolerance. The most sensitive test to evaluate glucose homeostasis is the oral glucose tolerance test (OGTT). The pathogenesis of neuropathy may be hyperglycemia, microvascular abnormalities, dyslipidemia, and the metabolic syndrome, with increasing evidence that oxidative and nitrosative stress may play a role. The characteristics of the neuropathy in prediabetes and the metabolic syndrome suggest that it may be a less severe neuropathy than in diabetes. Sensory modality findings prevail compared with motor, and small nerve fiber structure and function abnormalities may be the earliest findings. Diagnosis should rely on careful history and clinical examination, with emphasis on the evaluation of small fibers. A skin biopsy may be necessary to quantify intraepidermal nerve fiber density. An OGTT and fasting serum lipids should be performed in patients with idiopathic SPN to screen for prediabetes and the metabolic syndrome. Treatment should include hygienic measures such as diet and exercise. The only drug with potential for reversal of the neuropathy is Topiramate.