Dataset Information

Incident Diabetes and Mobility Limitations: Reducing Bias Through Risk-set Matching.

ABSTRACT:

Background

Increased prevalence of diabetes in the U.S. population could contribute substantially to increases in disability at older ages. Previous studies have examined the association between prevalent diabetes and various impairments and disabilities. Methods considering incident, rather than prevalent, diabetes as the exposure of interest can reduce bias in estimates of these associations.

Methods

Risk-set matching, a type of propensity score matching meant to handle time-varying exposures, was used to estimate the relationship between incident diabetes and mobility limitations among adults in the Health and Retirement Study. This approach ensures that covariates precede diabetes onset rather than follow it.

Results

Individuals who were diagnosed with diabetes during the study period accumulated more subsequent mobility limitations than were accumulated by matched controls. Among observationally similar pairs of individuals, those who developed diabetes reported an average of 24.9% more mobility limitations at study exit than those who did not.

Conclusions

The magnitude of the relationship between diabetes and limitations estimated in this article is smaller than that presented in previous studies, but the method presented here is likely to provide a less-biased estimate of the association between diabetes and accumulation of mobility limitations.

SUBMITTER: Fishman EI

PROVIDER: S-EPMC4481690 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Publications

Incident Diabetes and Mobility Limitations: Reducing Bias Through Risk-set Matching.

Fishman Ezra I EI Fishman Ezra I EI

The journals of gerontology. Series A, Biological sciences and medical sciences 20141119 7

<h4>Background</h4>Increased prevalence of diabetes in the U.S. population could contribute substantially to increases in disability at older ages. Previous studies have examined the association between prevalent diabetes and various impairments and disabilities. Methods considering incident, rather than prevalent, diabetes as the exposure of interest can reduce bias in estimates of these associations.<h4>Methods</h4>Risk-set matching, a type of propensity score matching meant to handle time-var ...[more]

PMID: 25414516

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Project description:Background: Somatic mutations in blood indicative of clonal hematopoiesis of indeterminate potential (CHIP), particularly in DNMT3A, TET2, and JAK2, are associated with an increased risk of hematologic malignancy, coronary artery disease, and all-cause mortality. However, whether CHIP is associated with increased risk of peripheral artery disease (PAD) remains unknown. In addition, chemotherapy frequently causes mutations in DNA Damage Repair (DDR) genes TP53 and PPM1D, and whether CHIP caused by somatic mutations in DDR genes results in increased risk of atherosclerosis is unclear. We sought to test whether CHIP, and CHIP caused by DDR genes, associates with incident peripheral artery disease (PAD) and atherosclerosis. Methods: We identified CHIP among 50,122 exome sequences in individuals from UK and Mass General Brigham Biobanks and tested CHIP status (N=2,851) with incident PAD and atherosclerosis across multiple arterial beds. To mimic the human scenario of clonal hematopoiesis and test whether the expansion of p53-deficient hematopoietic cells contributes to atherosclerosis, a competitive bone marrow transplantation (BMT) strategy was used to generate atherosclerosis-prone Ldlr-/- chimeric mice carrying 20% Trp53-/- hematopoietic cells (20% KO-BMT mice). We then evaluated aortic plaque burden and plaque macrophage accumulation 12 weeks after grafting. Results: CHIP associated with incident PAD (HR 1.7; P=2.2x10-5) and atherosclerosis in multiple beds (HR 1.3; P=9.7x10-5), with increased risk among individuals with DDR CHIP (HR 2.0; P=0.0084). Among atherosclerosis-prone Ldlr null mice, the p53 -/- 20% KO-BMT mice demonstrated increased aortic plaque size (p=0.013) and accumulation of p53-/- plaque macrophages (P<0.001), driven by an abundance of p53-deficient plaque macrophages. The expansion of p53-deficient cells did not affect the expression of the pro-inflammatory cytokines IL-6 and IL-1β in the atherosclerotic aortic wall. Conclusions: Our findings highlight the role of CHIP as a broad driver of atherosclerosis across the entire arterial system, with evidence of increased plaque among p53 -/- 20% KO-BMT mice via expansion of plaque macrophages. These observations provide new insight into the link between CHIP and cardiovascular disease, and lend human genetic support to the concept that post-cytotoxic chemotherapy patients may benefit from surveillance for atherosclerotic conditions in addition to therapy-related myeloid neoplasms.

Dataset Information

Incident Diabetes and Mobility Limitations: Reducing Bias Through Risk-set Matching.

Background

Methods

Results

Conclusions

Publications

Incident Diabetes and Mobility Limitations: Reducing Bias Through Risk-set Matching.

Similar Datasets

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