Peripheral Neuropathy and Nerve Dysfunction in Individuals at High Risk for Type 2 Diabetes: The PROMISE Cohort

Abstract

OBJECTIVEEmerging evidence suggests that peripheral neuropathy begins in the early stages of diabetes pathogenesis. Our objective was to describe the prevalence of peripheral neuropathy and nerve dysfunction according to glucose tolerance and metabolic syndrome status and examine how these conditions are associated with neurological changes in individuals at risk for type 2 diabetes. RESEARCH DESIGN AND METHODSWe studied 467 individuals in the longitudinal PROMISE (Prospective Metabolism and Islet Cell Evaluation) cohort. Peripheral neuropathy was defined by Michigan Neuropathy Screening Instrument (MNSI) scores (>2), and the severity of nerve dysfunction was measured objectively by vibration perception thresholds (VPTs) using a neurothesiometer. Metabolic syndrome was defined using the International Diabetes Federation/American Heart Association harmonized criteria. RESULTSThe prevalence of peripheral neuropathy was 29%, 49%, and 50% for normal glycemia, prediabetes, and new-onset diabetes, respectively (P < 0.001 for trend). The mean VPT was 6.5 V for normal glycemia, 7.9 V for prediabetes, and 7.6 V for new-onset diabetes (P = 0.024 for trend). Prediabetes was associated with higher MNSI scores (P = 0.01) and VPTs (P = 0.004) versus normal glycemia, independent of known risk factors. Additionally, progression of glucose intolerance over 3 years predicted a higher risk of peripheral neuropathy (P = 0.007) and nerve dysfunction (P = 0.002). Metabolic syndrome was not independently associated with MNSI scores or VPTs. CONCLUSIONSIn individuals with multiple risk factors for diabetes, prediabetes was associated with similar risks of peripheral neuropathy and severity of nerve dysfunction as new-onset diabetes. Prediabetes, but not metabolic syndrome, was independently associated with both the presence of peripheral neuropathy and the severity of nerve dysfunction.Peripheral neuropathy is a serious complication of diabetes. It plays a major contributory role in the initiation of foot ulceration and the subsequent development of lowerextremity amputation, resulting in severe disability, reduced quality of life, and a significant economic burden to the health care system (1). Peripheral neuropathy is

Diabetes and obesity are the main metabolic drivers of peripheral neuropathy

“…We found that the prevalence of peripheral neuropathy was higher in those with prediabetes than those with normoglycemia, but the association was not significant in multivariable models. With many previous studies supporting,16, 32, 33 and some not supporting,23, 34 an association of prediabetes with peripheral neuropathy, our results do not push the overall level of evidence much in either direction. Our study is now the third to show an increased OR in those with prediabetes that does not meet statistical significance 22, 31.…”

Prevalence of neuropathy in type 2 diabetic patients and its association with other diabetes complications: The Verona Diabetic Foot Screening Program

“…Even if it dates back to 1994, MNSI clinical score is still considered valid: it was recently used to measure neuropathy in high-risk nondiabetic, prediabetic and new-onset diagnosed patients, showing a surprisingly high prevalence of neuropathy in these cohorts (Lee et al, 2015).…”

“…Moreover, the application of a quantitative tool (the biothesiometer) could make the method more objective, even if the chosen cutoff is not necessarily shareable. No standardized VPT cutoff value to define the presence of peripheral neuropathy has been published to date (Lee et al, 2015).…”

Screening tests for distal symmetrical polyneuropathy in Latin American patients with type 2 diabetes mellitus

“…Previous validation studies established a maximum score of 8 for the MNSI (15); however, they did not include the 10-g monofilament test. Here, we established a maximum possible score of 10, in accordance with recent epidemiological studies (8,16). In this analysis, the presence of DSPN was defined by a score greater than 2 (> 2) in the clinical examination component of MNSI (8).…”

“…One of this is the Michigan Neuropathy Screening Instrument (MNSI), which consists of a self-administered questionnaire and a 5-item physical examination. This tool has been widely validated (6,7) and used to determine the presence of peripheral diabetic neuropathy in various longitudinal studies (8).…”