Dataset Information

Pre-morbid type 2 diabetes mellitus is not a prognostic factor in amyotrophic lateral sclerosis.

ABSTRACT:

Introduction

The aim of this study was to determine whether a history of pre-morbid type 2 diabetes mellitus (DM2) is a prognostic factor in amyotrophic lateral sclerosis (ALS).

Methods

The relationship between DM2 and survival was analyzed in a study population consisting of 1,322 participants from 6 clinical trials.

Results

Survival did not differ by diabetes status (log-rank test, P = 0.98), but did differ by body mass index (BMI) (log-rank test, P = 0.008). In multivariate analysis, there was no significant association between diabetes and survival (P = 0.18), but the risk of reaching a survival endpoint decreased by 4% for each unit increase in baseline BMI (HR 0.96, 95% CI 0.94-0.99, P = 0.001). DM2 was less prevalent among ALS clinical trial participants than predicted.

Conclusions

A history of pre-morbid DM2 is not an independent prognostic factor in ALS clinical trial databases. The low DM2 prevalence rate should be examined in a large, prospective study to determine whether DM2 affects ALS risk.

SUBMITTER: Paganoni S

PROVIDER: S-EPMC4536144 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Publications

Pre-morbid type 2 diabetes mellitus is not a prognostic factor in amyotrophic lateral sclerosis.

Paganoni Sabrina S Hyman Theodore T Shui Amy A Allred Peggy P Harms Matthew M Liu Jingxia J Maragakis Nicholas N Schoenfeld David D Yu Hong H Atassi Nazem N Cudkowicz Merit M Miller Timothy M TM

Muscle & nerve 20150601 3

<h4>Introduction</h4>The aim of this study was to determine whether a history of pre-morbid type 2 diabetes mellitus (DM2) is a prognostic factor in amyotrophic lateral sclerosis (ALS).<h4>Methods</h4>The relationship between DM2 and survival was analyzed in a study population consisting of 1,322 participants from 6 clinical trials.<h4>Results</h4>Survival did not differ by diabetes status (log-rank test, P = 0.98), but did differ by body mass index (BMI) (log-rank test, P = 0.008). In multivari ...[more]

PMID: 25900666

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Project description:Significant progress has been made in understanding the pre-symptomatic phase of amyotrophic lateral sclerosis. While much is still unknown, advances in other neurodegenerative diseases offer valuable insights. Indeed, it is increasingly clear that the well-recognized clinical syndromes of Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal muscular atrophy and frontotemporal dementia are also each preceded by a pre-symptomatic or prodromal period of varying duration, during which the underlying disease process unfolds, with associated compensatory changes and loss of inherent system redundancy. Key insights from these diseases highlight opportunities for discovery in amyotrophic lateral sclerosis. The development of biomarkers reflecting amyloid and tau has led to a shift in defining Alzheimer's disease based on inferred underlying histopathology. Parkinson's disease is unique among neurodegenerative diseases in the number and diversity of non-genetic biomarkers of pre-symptomatic disease, most notably REM sleep behaviour disorder. Huntington's disease benefits from an ability to predict the likely timing of clinically manifest disease based on age and CAG-repeat length alongside reliable neuroimaging markers of atrophy. Spinal muscular atrophy clinical trials have highlighted the transformational value of early therapeutic intervention, and studies in frontotemporal dementia illustrate the differential role of biomarkers based on genotype. Similar advances in amyotrophic lateral sclerosis would transform our understanding of key events in pathogenesis, thereby dramatically accelerating progress towards disease prevention. Deciphering the biology of pre-symptomatic amyotrophic lateral sclerosis relies on a clear conceptual framework for defining the earliest stages of disease. Clinically manifest amyotrophic lateral sclerosis may emerge abruptly, especially among those who harbour genetic mutations associated with rapidly progressive amyotrophic lateral sclerosis. However, the disease may also evolve more gradually, revealing a prodromal period of mild motor impairment preceding phenoconversion to clinically manifest disease. Similarly, cognitive and behavioural impairment, when present, may emerge gradually, evolving through a prodromal period of mild cognitive impairment or mild behavioural impairment before progression to amyotrophic lateral sclerosis. Biomarkers are critically important to studying pre-symptomatic amyotrophic lateral sclerosis and essential to efforts to intervene therapeutically before clinically manifest disease emerges. The use of non-genetic biomarkers, however, presents challenges related to counselling, informed consent, communication of results and limited protections afforded by existing legislation. Experiences from pre-symptomatic genetic testing and counselling, and the legal protections against discrimination based on genetic data, may serve as a guide. Building on what we have learned-more broadly from other pre-symptomatic neurodegenerative diseases and specifically from amyotrophic lateral sclerosis gene mutation carriers-we present a road map to early intervention, and perhaps even disease prevention, for all forms of amyotrophic lateral sclerosis.

Dataset Information

Pre-morbid type 2 diabetes mellitus is not a prognostic factor in amyotrophic lateral sclerosis.

Introduction

Methods

Results

Conclusions

Publications

Pre-morbid type 2 diabetes mellitus is not a prognostic factor in amyotrophic lateral sclerosis.

Similar Datasets

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