Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women’s Health Initiative Memory Study

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Abstract

Context

The relations between dietary and/or circulating levels of fatty acids and the development of type 2 diabetes is unclear. Protective associations with the marine omega-3 fatty acids and linoleic acid, and with a marker of fatty acid desaturase activity delta-5 desaturase (D5D ratio) have been reported, as have adverse relations with saturated fatty acids and D6D ratio.

Objective

To determine the associations between red blood cell (RBC) fatty acid distributions and incident type 2 diabetes.

Design

Prospective observational cohort study nested in the Women’s Health Initiative Memory Study.

Setting

General population.

Subjects

Postmenopausal women.

Main Outcome Measures

Self-reported incident type 2 diabetes.

Results

There were 703 new cases of type 2 diabetes over 11 years of follow up among 6379 postmenopausal women. In the fully adjusted models, baseline RBC D5D ratio was inversely associated with incident type 2 diabetes [Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.81–0.95) per 1 SD increase. Similarly, baseline RBC D6D ratio and palmitic acid were directly associated with incident type 2 diabetes (HR 1.14, 95% CI 1.04–1.25; and HR 1.24, 95% CI 1.14–1.35, respectively). None of these relations were materially altered by excluding incident cases in the first two years of follow-up. There were no significant relations with eicosapentaenoic, docosahexaenoic or linoleic acids.

Conclusions

Whether altered fatty acid desaturase activities or palmitic acid levels are causally related to the development of type 2 diabetes cannot be determined from this study, but our findings suggest that proportions of certain fatty acids in RBC membranes are associated with risk for type 2 diabetes.

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Most cited references 43

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Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study.

Judith Hsia, William Sherwin, J. Hays … (2004)

The Women's Health Initiative Memory Study (WHIMS) previously reported that estrogen plus progestin therapy does not protect cognition among women aged 65 years or older. The effect of estrogen-alone therapy, also evaluated in WHIMS, on cognition has not been established for this population. To determine whether conjugated equine estrogen (CEE) alters global cognitive function in older women and to compare its effect with CEE plus medroxyprogesterone acetate (CEE plus MPA). A randomized, double-blind, placebo-controlled ancillary study of the Women's Health Initiative (WHI), WHIMS evaluated the effect of CEE on incidence of probable dementia among community-dwelling women aged 65 to 79 years with prior hysterectomy from 39 US academic centers that started in June 1995. Of 3200 eligible women free of probable dementia enrolled in the WHI, 2947 (92.1%) were enrolled in WHIMS. Analyses were conducted on the 2808 women (95.3%) with a baseline and at least 1 follow-up measure of global cognitive function before the trial's termination on February 29, 2004. Participants received 1 daily tablet containing either 0.625 mg of CEE (n = 1387) or matching placebo (n = 1421). Global cognitive function measured annually with the Modified Mini-Mental State Examination (3MSE). During a mean follow-up of 5.4 years, mean (SE) 3MSE scores were 0.26 (0.13) units lower than among women assigned to CEE compared with placebo (P =.04). For pooled hormone therapy (CEE combined with CEE plus MPA), the mean (SE) decrease was 0.21 (0.08; P =.006). Removing women with dementia, mild cognitive impairment, or stroke from the analyses lessened these differences. The adverse effect of hormone therapy was more pronounced among women with lower cognitive function at baseline (all P 2 SDs) was estimated to be 1.47 (95% confidence interval, 1.04-2.07). For women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment.

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Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study.

S. King, Xiaoling Song, D Siscovick … (2010)

Palmitoleic acid (cis-16:1n-7), which is produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative. To investigate whether circulating trans-palmitoleate is independently related to lower metabolic risk and incident type 2 diabetes. Prospective cohort study from 1992 to 2006. Four U.S. communities. 3736 adults in the Cardiovascular Health Study. Anthropometric characteristics and levels of plasma phospholipid fatty acids, blood lipids, inflammatory markers, and glucose-insulin measured at baseline in 1992 and dietary habits measured 3 years earlier. Multivariate-adjusted models were used to investigate how demographic, clinical, and lifestyle factors independently related to plasma phospholipid trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). Findings were validated for metabolic risk factors in an independent cohort of 327 women. In multivariate analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate levels. Higher trans-palmitoleate levels were associated with slightly lower adiposity and, independently, with higher high-density lipoprotein cholesterol levels (1.9% across quintiles; P = 0.040), lower triglyceride levels (-19.0%; P < 0.001), a lower total cholesterol-HDL cholesterol ratio (-4.7%; P < 0.001), lower C-reactive protein levels (-13.8%; P = 0.05), and lower insulin resistance (-16.7%, P < 0.001). Trans-palmitoleate was also associated with a substantially lower incidence of diabetes, with multivariate hazard ratios of 0.41 (95% CI, 0.27 to 0.64) and 0.38 (CI, 0.24 to 0.62) in quintiles 4 and 5 versus quintile 1 (P for trend < 0.001). Findings were independent of estimated dairy consumption or other fatty acid dairy biomarkers. Protective associations with metabolic risk factors were confirmed in the validation cohort. Results could be affected by measurement error or residual confounding. Circulating trans-palmitoleate is associated with lower insulin resistance, presence of atherogenic dyslipidemia, and incident diabetes. Our findings may explain previously observed metabolic benefits of dairy consumption and support the need for detailed further experimental and clinical investigation. National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

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Validity of diabetes self-reports in the Women's Health Initiative: comparison with medication inventories and fasting glucose measurements.

Lesley Tinker, Camenzind G Robinson, Lihong Qi … (2007)

Although diabetes is conveniently assessed by self-report, few validation studies have been performed. Therefore, we studied whether self-report of prevalent and incident diabetes in Women's Health Initiative (WHI) participants was concordant with other diagnostic evidence of diabetes. A total of 161 808 postmenopausal women aged 50-79 were enrolled at 40 clinical centers in the U.S. in 1993-1998 and followed prospectively. At baseline, prevalent medication treated diabetes was defined as a self-report of physician diagnosis and treatment with insulin or oral antidiabetic drugs. During followup, incident treated diabetes was defined as a self-report of a new physician diagnosis of diabetes treated with insulin or oral drugs. Diabetes self-reports were compared with medication inventories and fasting glucose levels at baseline and during follow-up. At baseline, self-reported treated diabetes was concordant with the medication inventory in 79% of clinical trial, and 77% of observational study participants. Self-reported incident treated diabetes was concordant with the medication inventory in 78% between baseline and Year 1 in the clinical trials, in 62% between Year 1 and Year 3 in the clinical trials, and in 72% between baseline and Year 3 in the observational study. Over similar periods, 99.9% of those who did not report treated diabetes had no oral antidiabetic drugs or insulin in the medication inventory. At baseline, about 3% not reporting diabetes had fasting glucose >126 mg/dl, and 88% of these subjects subsequently reported treated diabetes during 6.9 years of follow-up. Incident self-reported diabetes treated by lifestyle alone was not determined in WHI. Medication inventories may have been incomplete and fasting glucose may have been lowered by treatment; therefore, concordance with self-reported treatment or fasting glucose > or = 126 may have been underestimated. In the WHI, self-reported prevalent and incident diabetes was consistent with medication inventories, and a high proportion of those with undiagnosed diabetes subsequently reported diabetes treatment. Self-reports of ;treated diabetes' are sufficiently accurate to allow use in epidemiologic studies.

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Author and article information

Contributors

Christian Herder: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 16 February 2016

Publication date Collection: 2016

Volume: 11

Issue: 2

Electronic Location Identifier: e0147894

Affiliations

[1 ]Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, and OmegaQuant Analytics, LLC, Sioux Falls, South Dakota, United States of America

[2 ]Department of Epidemiology and Biostatistics, School of Public Health, Indiana University, Bloomington, Indiana, United States of America

[3 ]Department of Internal Medicine, Sanford School of Medicine, University of South Dakota, Sioux Falls, South Dakota, United States of America

[4 ]HealthPartners Foundation for Education and Research, Minneapolis, Minnesota, United States of America

[5 ]Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America

[6 ]Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City, Iowa, United States of America

German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Duesseldorf, GERMANY

Author notes

Competing Interests: WSH is the President of OmegaQuant Analytics, LLC and an employee of Health Diagnostic Laboratory, Inc. (HDL), two laboratories that offer blood fatty acid testing; the former for researchers and the latter for clinicians. JVP is an employee of HDL. None of the other authors have any potential conflicts to disclose. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Conceived and designed the experiments: WSH JVP MAE JGR. Performed the experiments: WSH MAE JGR. Analyzed the data: JVP JL. Wrote the paper: WSH JL JVP KLM MAE JGR.

* E-mail: bill@ 123456omegaquant.com

Article

Publisher ID: PONE-D-15-22484

DOI: 10.1371/journal.pone.0147894

PMC ID: 4755935

PubMed ID: 26881936

SO-VID: a94f8e88-1474-4765-a6bd-7b396499117d

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 25 May 2015

Date accepted : 11 January 2016

Page count

Figures: 1, Tables: 5, Pages: 17

Funding

Funding provided by National Heart Lung and Blood Institute, Broad Area Announcement 19. The sponsor had no role in study design, study conduct, data analysis or manuscript preparation. HDL, Inc. provided support in the form of salary for JVP and WSH, and OmegaQuant Analytics, LLC provided support for WSH as he has an ownership interest the laboratory. However, neither organization played any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Custom metadata

Data Availability WHI data are available to researchers via this website https://www.whi.org/researchers/data/Pages/WHIMS%20Data.aspx however some restrictions apply such as submitting a research and publication plan that is approved by the WHI Publications committee.

Red Blood Cell Fatty Acids and Incident Diabetes Mellitus in the Women’s Health Initiative Memory Study

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Abstract

Context

Objective

Design

Setting

Subjects

Main Outcome Measures

Results

Conclusions

Related collections

PLOS: COVID-19 pandemic

Most cited references 43

Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study.

Trans-palmitoleic acid, metabolic risk factors, and new-onset diabetes in U.S. adults: a cohort study.

Validity of diabetes self-reports in the Women's Health Initiative: comparison with medication inventories and fasting glucose measurements.

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