Polyneuropathy in the Metabolic Syndrome
By Michael Rubin, MD
Professor of Clinical Neurology, Weill Cornell Medical College
Dr. Rubin reports no financial relationships relevant to this field of study.
SYNOPSIS: The metabolic syndrome, independent of the diagnosis of diabetes, is associated with the development of polyneuropathy.
SOURCE: Hanewinckel R, Drenthen J, Ligthart S, et al. Metabolic syndrome is related to polyneuropathy and impaired peripheral nerve function: A prospective population-based cohort study. J Neurol Neurosurg Psychiatry 2016;87:1336-1342.
Updated by the International Diabetes Federation in 2006, criteria for diagnosing metabolic syndrome include central obesity based on waist circumference in addition to abnormalities in two of the following: triglycerides, (> 150 mg/dL), high-density lipoprotein cholesterol (HDL-C; < 40 mg/dL for men or < 50 mg/dL for women), blood pressure (systolic ≥ 130, diastolic ≥ 85), and fasting plasma glucose (≥ 100 mg/dL). Elevated fasting glucose and impaired glucose tolerance may increase the risk of polyneuropathy in prediabetes. What role, if any, apart from diabetes or prediabetes, does metabolic syndrome play as a risk factor for polyneuropathy?
Incorporated as part of the Rotterdam Study, a prospective, population-based cohort study, initiated in 1990 of all inhabitants ≥ 55 years of age living in the Ommoord district of Rotterdam, the Netherlands, and expanded in 2006 to include all persons ≥ 45 years of age, a polyneuropathy screen was implemented in June 2013, and the current study included patients enrolled up to October 2015. Among 1,544 persons screened for polyneuropathy, 234 were excluded for logistical reasons, with 1,256 of the remaining 1,310 lacking adequate information to be included in this analysis. Metabolic syndrome was diagnosed based on any three of the following five criteria: increased waist circumference (≥ 94 cm for males, ≥ 80 cm for females), elevated triglycerides, reduced HDL-C (< 39 mg/dL in males, < 50 mg/dL in females, or specific treatment for reduced HDL-C), elevated blood pressure, and elevated fasting glucose (≥ 216 mg/dL, or use of glucose-lowering medication). Neuropathy screening included a symptom questionnaire, neurological examination, and nerve conduction studies of the sural sensory nerves bilaterally and a unilateral peroneal motor nerve. Statistical analysis included logistic and linear regression analyses, adjusted for age, gender, and height, and splines regression for continuous glucose levels.
Among 1,256 subjects, 45.5% male (n = 571) and 54.5% female (n = 685), with mean age of 70 years, type 2 diabetes was present in 13.9%, impaired fasting glucose in 12.2%, and metabolic syndrome in 52.5% (n = 659). Definite polyneuropathy was present in 5.1% (n = 64); probable polyneuropathy in 7.3% (n = 92), diagnosed by the presence of two abnormal elements on nerve conduction studies; and possible polyneuropathy in 17.4% (n = 218), diagnosed by the presence of one abnormal or two slightly abnormal elements on nerve conduction studies. Regardless of gender, metabolic syndrome was associated with definite polyneuropathy (odds ratio, 1.92; 95% confidence interval, 1.09-3.38), particularly in those individuals who had increased waist circumference and elevated triglycerides, regardless of the presence of diabetes. Diabetes, but not impaired fasting glucose, also was strongly associated with polyneuropathy.
Polyneuropathy affects 2-7% of the population and is idiopathic in at least 30% of patients. Diabetes, both type 1 and 2, is the most common known cause, and although rigorous glucose control significantly reduces the incidence of neuropathy in type 1 diabetes, it does not have the same effect in type 2, implying that factors other than blood glucose are causative. Evidence now supports the notion that components of metabolic syndrome may be responsible, and efforts to address these may positively affect the incidence of neuropathy, not only in diabetes but in non-diabetic obese individuals as well.
The metabolic syndrome, independent of the diagnosis of diabetes, is associated with the development of polyneuropathy.
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