Share

August 01, 2017; 89 (5) Article

Type 2 diabetes, glucose, insulin, BMI, and ischemic stroke subtypes

Mendelian randomization study

Susanna C. Larsson, Robert A. Scott, Matthew Traylor, Claudia C. Langenberg, George Hindy, Olle Melander, Marju Orho-Melander, Sudha Seshadri, Nicholas J. Wareham, Hugh S. Markus, For the METASTROKE Collaboration and NINDS Stroke Genetics Network (SiGN)
First published June 30, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004173
Full PDF
Citation
Permissions

Make Comment

See Comments

Downloads
337

Share

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Abstract

Objective: To implement a mendelian randomization (MR) approach to determine whether type 2 diabetes mellitus (T2D), fasting glucose, fasting insulin, and body mass index (BMI) are causally associated with specific ischemic stroke subtypes.

Methods: MR estimates of the association between each possible risk factor and ischemic stroke subtypes were calculated with inverse-variance weighted (conventional) and weighted median approaches, and MR-Egger regression was used to explore pleiotropy. The number of single nucleotide polymorphisms (SNPs) used as instrumental variables was 49 for T2D, 36 for fasting glucose, 18 for fasting insulin, and 77 for BMI. Genome-wide association study data of SNP-stroke associations were derived from METASTROKE and the Stroke Genetics Network (n = 18,476 ischemic stroke cases and 37,296 controls).

Results: Conventional MR analysis showed associations between genetically predicted T2D and large artery stroke (odds ratio [OR] 1.28, 95% confidence interval [CI] 1.16–1.40, p = 3.3 × 10−7) and small vessel stroke (OR 1.21, 95% CI 1.10–1.33, p = 8.9 × 10−5) but not cardioembolic stroke (OR 1.06, 95% CI 0.97–1.15, p = 0.17). The association of T2D with large artery stroke but not small vessel stroke was consistent in a sensitivity analysis using the weighted median method, and there was no evidence of pleiotropy. Genetically predicted fasting glucose and fasting insulin levels and BMI were not statistically significantly associated with any ischemic stroke subtype.

Conclusions: This study provides support that T2D may be causally associated with large artery stroke.

GLOSSARY

BMI=
body mass index;
CI=
confidence interval;
GWAS=
genome-wide association studies;
MR=
mendelian randomization;
NINDS=
National Institute of Neurologic Disorders and Stroke;
1KG=
1000 Genomes;
OR=
odds ratio;
SiGN=
Stroke Genetics Network;
SNP=
single nucleotide polymorphism;
TOAST=
Trial of Org 10172 in Acute Stroke Treatment;
T2D=
type 2 diabetes mellitus

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Coinvestigators are listed at Neurology.org.

  • Supplemental data at Neurology.org

  • Received October 10, 2016.
  • Accepted in final form May 4, 2017.
View Full Text

AAN Non-Member Subscribers

Purchase access

Letters: Rapid online correspondence

No comments have been published for this article.
Comment

REQUIREMENTS

You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

If you are responding to a comment that was written about an article you originally authored:
You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
and apply to letter.

Submission specifications:

  • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
  • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
  • Submit only on articles published within 6 months of issue date.
  • Do not be redundant. Read any comments already posted on the article prior to submission.
  • Submitted comments are subject to editing and editor review prior to posting.

More guidelines and information on Disputes & Debates

Compose Comment

More information about text formats

Plain text

  • No HTML tags allowed.
  • Web page addresses and e-mail addresses turn into links automatically.
  • Lines and paragraphs break automatically.
Author Information
NOTE: The first author must also be the corresponding author of the comment.
First or given name, e.g. 'Peter'.
Your last, or family, name, e.g. 'MacMoody'.
Your email address, e.g. higgs-boson@gmail.com
Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
Publishing Agreement
NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

Vertical Tabs

You May Also be Interested in

Back to top
Advertisement

Topics Discussed

Alert Me

Recommended articles