Lactation Intensity and Fasting Plasma Lipids, Lipoproteins, Non-esterified Free Fatty Acids, Leptin and Adiponectin in Postpartum Women with Recent Gestational Diabetes Mellitus: The SWIFT cohort. Erica P. Gunderson, Catherine Kim, Charles P. Quesenberry Jr., Santica Marcovina, David Walton, Robert A. Azevedo, Gary Fox, Cathie Elmasian, Stephen Young, Nora Salvador, Michael Lum, Yvonne Crites, Joan C. Lo, Xian Ning, Kathryn G. Dewey PII: DOI: Reference:
S0026-0495(14)00114-0 doi: 10.1016/j.metabol.2014.04.006 YMETA 53012
To appear in:
Metabolism
Received date: Revised date: Accepted date:
20 November 2013 8 April 2014 8 April 2014
Please cite this article as: Gunderson Erica P., Kim Catherine, Quesenberry Jr. Charles P., Marcovina Santica, Walton David, Azevedo Robert A., Fox Gary, Elmasian Cathie, Young Stephen, Salvador Nora, Lum Michael, Crites Yvonne, Lo Joan C., Ning Xian, Dewey Kathryn G., Lactation Intensity and Fasting Plasma Lipids, Lipoproteins, Nonesterified Free Fatty Acids, Leptin and Adiponectin in Postpartum Women with Recent Gestational Diabetes Mellitus: The SWIFT cohort., Metabolism (2014), doi: 10.1016/j.metabol.2014.04.006
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1 Title: Lactation Intensity and Fasting Plasma Lipids, Lipoproteins, Non-esterified Free Fatty Acids, Leptin and Adiponectin in Postpartum Women with Recent Gestational Diabetes Mellitus
T
: The SWIFT cohort.
RI P
Authors: Erica P. Gunderson, PhD1, Catherine Kim, MD, MPH 2, Charles P. Quesenberry, Jr, PhD1 , Santica Marcovina, PhD, ScD, 3 David Walton, MD 4, Robert A. Azevedo, MD 4, Gary
SC
Fox, MD 4, Cathie Elmasian, MD 4, Stephen Young, MD 4, Nora Salvador, MD 4, Michael Lum,
NU
MD 4, Yvonne Crites, MD 4, Joan C. Lo, MD1, Xian Ning, MS1 and Kathryn G. Dewey, PhD 5. Affiliations:
Kaiser Permanente Northern California, Division of Research, Oakland, CA
2
The University of Michigan, Ann Arbor, Michigan
3
The University of Washington, Northwest Lipid Metabolism and Diabetes Research
ED
MA
1
PT
Laboratory, Seattle, Washington
The Kaiser Permanente Northern California Medical Group, Oakland, CA
5
Department of Nutrition, University of California, Davis, One Shields Ave., Davis, CA 95616
CE
4
AC
Corresponding Author: Erica P. Gunderson, Ph.D., Senior Research Scientist/Investigator, Kaiser Permanente Northern California, Division of Research, 2000 Broadway, Oakland, CA 94612. Telephone (510) 891-5917, Fax (510) 891-3805, e-mail: [email protected] Brief title: Lactation and Biomarkers for Diabetes in Women with Recent GDM Word Count Text: 3,985 Tables: 3 Figures: 2 Disclosure statement: The authors have no conflicts of interest to disclose. ClinicalTrial.gov ID number: NCT01967030
ACCEPTED MANUSCRIPT 2 Abstract: 250 Objectives: Lactation may influence future progression to type 2 diabetes after gestational
T
diabetes mellitus (GDM). However, biomarkers associated with progression to glucose
RI P
intolerance have not been examined in relation to lactation intensity among postpartum women with previous GDM. This study investigates whether higher lactation intensity is
SC
related to more favorable blood lipids, lipoproteins and adipokines after GDM pregnancy
NU
independent of obesity, socio-demographics and insulin resistance. Methods: The Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT) is a prospective
MA
cohort study that recruited 1,035 women diagnosed with GDM by the 3-hour 100 g oral glucose tolerance tests (OGTTs) after delivery of a live birth in 2008-2011. Research staff
ED
conducted 2-hour 75 gram OGTTs, and assessed lactation intensity, anthropometry, lifestyle
PT
behaviors and socio-demographics at 6-9 weeks postpartum (baseline). We assayed fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin from stored
CE
samples obtained at 6-9 weeks postpartum for in 1,007 of the SWIFT participants who were free
AC
of diabetes at baseline. Mean biomarker concentrations were compared among lactation intensity groups using multivariable linear regression models. Results: Increasing lactation intensity showed graded monotonic associations with fully adjusted mean biomarkers: 5-8% higher high-density lipoprotein cholesterol (HDL-cholesterol), 20-28% lower fasting triglycerides, 15-21% lower leptin (all trend P-values6 to ≤ 17 ounces per 24 hours) or inconsistent feeding method, 4) mostly formula feeding >17 ounces per 24 hours, and 5) exclusive formula feeding.(12) The mixed/inconsistent group included women who had transitioned to higher formula supplementation between the 4-5 weeks postpartum screening interview and the 6-9 weeks postpartum exam. Trained research assistants asked women to recall the duration of fasting and breastfeeding during the fasting period prior to the OGTT, recorded breastfeeding episodes during the 2-hour 75 g OGTT as described previously,(19) and measured weight, height and
ACCEPTED MANUSCRIPT 8 waist circumference via standardized methods using calibrated research quality scales (Tanita WB-100A, Tanita Corp, Toyko, Japan), stadiometer equipment (SECA, Model 67029, United
T
Kingdom, www.seca.com), and measuring tapes (Gulick, 67019, Country Technology, Inc.,
RI P
United States). Interviewer and self-administered questionnaires collected information on sociodemographics, enrollment in Women’s, Infants and Children (WIC) special supplemental
SC
nutrition program, medical history, contraception, depression, and lifestyle behaviors. We
NU
utilized KPNC electronic medical records to obtain prenatal laboratory results and dates of GDM diagnosis (3-hour 100 g OGTT), GDM treatment, as well as maternal body weights. Gestational
MA
weight gain (kg) was defined as the last weight before delivery minus reported pre-pregnancy weight. Postpartum weight loss (kg) was calculated as the difference between the woman’s
PT
ED
weight measured at 6-9 weeks postpartum and her last weight before delivery.
Biochemical Assays
CE
For this analysis, we utilized fasting plasma collected at 6-9 weeks postpartum
AC
(baseline in-person exam) to measure lipids, lipoproteins, non-esterified FFA and adipokines (adiponectin, leptin). Assays were performed on thawed frozen fasting plasma stored at -70º C from the SWIFT baseline. The specimens were shipped to the University of Washington, Northwest Lipid Metabolism and Diabetes Research Laboratory and analyzed for insulin, glucose, lipids, lipoproteins, non-esterified FFA, leptin and adiponectin. Plasma glucose was analyzed enzymatically using Roche reagent on a Roche Modular P autoanalyzer. The method is based on the combined catalytic activities of hexokinase and gluco se-6phosphate-dehydrogenase. Total immunoreactive insulin (μU/mL) was assayed using a double-antibody radioimmunoassay with high precision. The assay is a 48-hour
ACCEPTED MANUSCRIPT 9 Polyethylene glycol (PEG)-accelerated assay involving a primary antibody, guinea pig antihuman insulin, and a secondary antibody, goat anti-guinea pig immunoglobulin.
T
Measurements of total cholesterol in plasma and cholesterol in the lipoprotein fractions
RI P
and triglycerides were performed enzymatically using Roche reagent on the Roche Modular P autoanalyzer by methods standardized to the Centers for Disease Control and Prevention
SC
Reference Methods. Determination of HDL-cholesterol was performed after precipitation of
NU
apo B-containing particles by dextran sulfate Mg2+. LDL-cholesterol was calculated by the Friedewald equation. The Friedewald equation for the estimation of LDL-cholesterol is
MA
inaccurate when triglycerides are >400 mg/dL. In this case, a complete lipoprotein separation by ultracentrifugation, which allows quantitation of the individual lipoprotein classes, was
ED
performed using the Lipid Research Clinics Beta Quantification procedure. The inter-assay
PT
coefficients of variation (CVs) are consistently
S0026-0495(14)00114-0 doi: 10.1016/j.metabol.2014.04.006 YMETA 53012
To appear in:
Metabolism
Received date: Revised date: Accepted date:
20 November 2013 8 April 2014 8 April 2014
Please cite this article as: Gunderson Erica P., Kim Catherine, Quesenberry Jr. Charles P., Marcovina Santica, Walton David, Azevedo Robert A., Fox Gary, Elmasian Cathie, Young Stephen, Salvador Nora, Lum Michael, Crites Yvonne, Lo Joan C., Ning Xian, Dewey Kathryn G., Lactation Intensity and Fasting Plasma Lipids, Lipoproteins, Nonesterified Free Fatty Acids, Leptin and Adiponectin in Postpartum Women with Recent Gestational Diabetes Mellitus: The SWIFT cohort., Metabolism (2014), doi: 10.1016/j.metabol.2014.04.006
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT 1 Title: Lactation Intensity and Fasting Plasma Lipids, Lipoproteins, Non-esterified Free Fatty Acids, Leptin and Adiponectin in Postpartum Women with Recent Gestational Diabetes Mellitus
T
: The SWIFT cohort.
RI P
Authors: Erica P. Gunderson, PhD1, Catherine Kim, MD, MPH 2, Charles P. Quesenberry, Jr, PhD1 , Santica Marcovina, PhD, ScD, 3 David Walton, MD 4, Robert A. Azevedo, MD 4, Gary
SC
Fox, MD 4, Cathie Elmasian, MD 4, Stephen Young, MD 4, Nora Salvador, MD 4, Michael Lum,
NU
MD 4, Yvonne Crites, MD 4, Joan C. Lo, MD1, Xian Ning, MS1 and Kathryn G. Dewey, PhD 5. Affiliations:
Kaiser Permanente Northern California, Division of Research, Oakland, CA
2
The University of Michigan, Ann Arbor, Michigan
3
The University of Washington, Northwest Lipid Metabolism and Diabetes Research
ED
MA
1
PT
Laboratory, Seattle, Washington
The Kaiser Permanente Northern California Medical Group, Oakland, CA
5
Department of Nutrition, University of California, Davis, One Shields Ave., Davis, CA 95616
CE
4
AC
Corresponding Author: Erica P. Gunderson, Ph.D., Senior Research Scientist/Investigator, Kaiser Permanente Northern California, Division of Research, 2000 Broadway, Oakland, CA 94612. Telephone (510) 891-5917, Fax (510) 891-3805, e-mail: [email protected] Brief title: Lactation and Biomarkers for Diabetes in Women with Recent GDM Word Count Text: 3,985 Tables: 3 Figures: 2 Disclosure statement: The authors have no conflicts of interest to disclose. ClinicalTrial.gov ID number: NCT01967030
ACCEPTED MANUSCRIPT 2 Abstract: 250 Objectives: Lactation may influence future progression to type 2 diabetes after gestational
T
diabetes mellitus (GDM). However, biomarkers associated with progression to glucose
RI P
intolerance have not been examined in relation to lactation intensity among postpartum women with previous GDM. This study investigates whether higher lactation intensity is
SC
related to more favorable blood lipids, lipoproteins and adipokines after GDM pregnancy
NU
independent of obesity, socio-demographics and insulin resistance. Methods: The Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT) is a prospective
MA
cohort study that recruited 1,035 women diagnosed with GDM by the 3-hour 100 g oral glucose tolerance tests (OGTTs) after delivery of a live birth in 2008-2011. Research staff
ED
conducted 2-hour 75 gram OGTTs, and assessed lactation intensity, anthropometry, lifestyle
PT
behaviors and socio-demographics at 6-9 weeks postpartum (baseline). We assayed fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin from stored
CE
samples obtained at 6-9 weeks postpartum for in 1,007 of the SWIFT participants who were free
AC
of diabetes at baseline. Mean biomarker concentrations were compared among lactation intensity groups using multivariable linear regression models. Results: Increasing lactation intensity showed graded monotonic associations with fully adjusted mean biomarkers: 5-8% higher high-density lipoprotein cholesterol (HDL-cholesterol), 20-28% lower fasting triglycerides, 15-21% lower leptin (all trend P-values6 to ≤ 17 ounces per 24 hours) or inconsistent feeding method, 4) mostly formula feeding >17 ounces per 24 hours, and 5) exclusive formula feeding.(12) The mixed/inconsistent group included women who had transitioned to higher formula supplementation between the 4-5 weeks postpartum screening interview and the 6-9 weeks postpartum exam. Trained research assistants asked women to recall the duration of fasting and breastfeeding during the fasting period prior to the OGTT, recorded breastfeeding episodes during the 2-hour 75 g OGTT as described previously,(19) and measured weight, height and
ACCEPTED MANUSCRIPT 8 waist circumference via standardized methods using calibrated research quality scales (Tanita WB-100A, Tanita Corp, Toyko, Japan), stadiometer equipment (SECA, Model 67029, United
T
Kingdom, www.seca.com), and measuring tapes (Gulick, 67019, Country Technology, Inc.,
RI P
United States). Interviewer and self-administered questionnaires collected information on sociodemographics, enrollment in Women’s, Infants and Children (WIC) special supplemental
SC
nutrition program, medical history, contraception, depression, and lifestyle behaviors. We
NU
utilized KPNC electronic medical records to obtain prenatal laboratory results and dates of GDM diagnosis (3-hour 100 g OGTT), GDM treatment, as well as maternal body weights. Gestational
MA
weight gain (kg) was defined as the last weight before delivery minus reported pre-pregnancy weight. Postpartum weight loss (kg) was calculated as the difference between the woman’s
PT
ED
weight measured at 6-9 weeks postpartum and her last weight before delivery.
Biochemical Assays
CE
For this analysis, we utilized fasting plasma collected at 6-9 weeks postpartum
AC
(baseline in-person exam) to measure lipids, lipoproteins, non-esterified FFA and adipokines (adiponectin, leptin). Assays were performed on thawed frozen fasting plasma stored at -70º C from the SWIFT baseline. The specimens were shipped to the University of Washington, Northwest Lipid Metabolism and Diabetes Research Laboratory and analyzed for insulin, glucose, lipids, lipoproteins, non-esterified FFA, leptin and adiponectin. Plasma glucose was analyzed enzymatically using Roche reagent on a Roche Modular P autoanalyzer. The method is based on the combined catalytic activities of hexokinase and gluco se-6phosphate-dehydrogenase. Total immunoreactive insulin (μU/mL) was assayed using a double-antibody radioimmunoassay with high precision. The assay is a 48-hour
ACCEPTED MANUSCRIPT 9 Polyethylene glycol (PEG)-accelerated assay involving a primary antibody, guinea pig antihuman insulin, and a secondary antibody, goat anti-guinea pig immunoglobulin.
T
Measurements of total cholesterol in plasma and cholesterol in the lipoprotein fractions
RI P
and triglycerides were performed enzymatically using Roche reagent on the Roche Modular P autoanalyzer by methods standardized to the Centers for Disease Control and Prevention
SC
Reference Methods. Determination of HDL-cholesterol was performed after precipitation of
NU
apo B-containing particles by dextran sulfate Mg2+. LDL-cholesterol was calculated by the Friedewald equation. The Friedewald equation for the estimation of LDL-cholesterol is
MA
inaccurate when triglycerides are >400 mg/dL. In this case, a complete lipoprotein separation by ultracentrifugation, which allows quantitation of the individual lipoprotein classes, was
ED
performed using the Lipid Research Clinics Beta Quantification procedure. The inter-assay
PT
coefficients of variation (CVs) are consistently
