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Lactation and Progression to Type 2 Diabetes Mellitus After Gestational Diabetes Mellitus: A Prospective Cohort StudyLactation and Incidence of Diabetes After GDM

Erica P. Gunderson, PhD, MPH, MS, RD; Shanta R. Hurston, MPA; Xian Ning, MS; Joan C. Lo, MD; Yvonne Crites, MD; David Walton, MD; Kathryn G. Dewey, PhD; Robert A. Azevedo, MD; Stephen Young, MD; Gary Fox, MD; Cathie C. Elmasian, MD; Nora Salvador, MD; Michael Lum, MD; Barbara Sternfeld, PhD; Charles P. Quesenberry Jr., PhD, for the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy Investigators*
[+] Article, Author, and Disclosure Information

This article was published online first at www.annals.org on 24 November 2015.

* For a list of the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy investigators, see the Appendix.


From Kaiser Permanente Northern California and the Permanente Medical Group, Oakland, and University of California, Davis, Davis, California.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Grant Support: By the National Institute of Child Health and Human Development (R01 HD050625 to Dr. Gunderson); the National Center for Research Resources, National Institutes of Health (UCSF-CTSI UL1 RR024131); the Kaiser Permanente Northern California Community Benefit Program; and the W.K. Kellogg Foundation.

Disclosures: Dr. Gunderson reports grants from the National Institute of Child Health and Human Development, Kaiser Permanente Community Benefit Program, W.K. Kellogg Foundation, National Institutes of Health National Center for Research Resources, and American Diabetes Association during the conduct of the study. Dr. Lo reports grants from the National Institutes of Health during the conduct of the study and grants from Sanofi outside the submitted work. Dr. Fox reports grants from the National Institute of Child Health and Human Development, Kaiser Permanente Community Benefit Program, W.K. Kellogg Foundation, National Institutes of Health National Center for Research Resources, and the American Diabetes Association during the conduct of the study. Dr. Quesenberry reports grants from the National Institute of Child Health and Human Development during the conduct of the study and grants from Takeda, Merck, Sanofi–Aventis, Lilly, Genentech, Valeant, and Pfizer outside the submitted work. Authors not named here have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0807.

Reproducible Research Statement:Study protocol, statistical code, and data set: Available from Dr. Gunderson (e-mail,Erica.Gunderson@kp.org).

Requests for Single Reprints: Erica P. Gunderson, PhD, MPH, MS, RD, Senior Research Scientist, Division of Research, Cardiovascular and Metabolic Conditions Section, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA 94612; e-mail, Erica.Gunderson@.kp.org.

Current Author Addresses: Drs. Gunderson, Lo, Sternfeld, and Quesenberry; Ms. Hurston; and Ms. Ning: Division of Research, Kaiser Permanente Northern California, 2000 Broadway, Oakland, CA 94612.

Dr. Crites: Maternal-Fetal Medicine, Perinatology, Kaiser Permanente, 710 Lawrence Expressway, Santa Clara, CA 95051.

Dr. Walton: Director of Perinatal Services, Kaiser Foundation Hospital, Oakland Medical Center, 3779 Piedmont Avenue, Oakland, CA 94611.

Dr. Dewey: Distinguished Professor, Department of Nutrition, University of California, Davis, 1 Shields Avenue, Davis, CA 95616-8669.

Dr. Azevedo: Physician-in-Chief, Sacramento Medical Center, Kaiser Permanente, 2025 Morse Avenue, Sacramento, CA 95825.

Dr. Young: Senior Consultant, Department of Obstetrics and Gynecology, Union City Medical Offices, Kaiser Permanente, 3555 Whipple Road, Building A, Union City, CA 94587.

Dr. Fox: Chief, Department of Obstetrics and Gynecology, South Sacramento Medical Center, Kaiser Permanente, 6600 Bruceville Road, Sacramento, CA 95823.

Dr. Elmasian: Folsom Medical Offices, Kaiser Permanente, 2155 Iron Point Road, Folsom, CA 95630.

Dr. Salvador: Richmond Medical Center, Kaiser Permanente, 901 Nevin Avenue, Richmond, CA 94801.

Dr. Lum: Department of Obstetrics and Gynecology, San Jose Medical Center, Kaiser Permanente, 276 International Circle, San Jose, CA 95119.

Author Contributions: Conception and design: E.P. Gunderson, C.P. Quesenberry.

Analysis and interpretation of the data: E.P. Gunderson, S.R. Hurston, X. Ning, J.C. Lo, D. Walton, B. Sternfeld, C.P. Quesenberry.

Drafting of the article: E.P. Gunderson.

Critical revision of the article for important intellectual content: E.P. Gunderson, J.C. Lo, D. Walton, K.G. Dewey, B. Sternfeld.

Final approval of the article: E.P. Gunderson, S.R. Hurston, X. Ning, J.C. Lo, Y. Crites, D. Walton, K.G. Dewey, R.A. Azevedo, S. Young, G. Fox, C.C. Elmasian, N. Salvador, M. Lum, B. Sternfeld, C.P. Quesenberry.

Provision of study materials or patients: E.P. Gunderson, Y. Crites, D. Walton, S. Young, C.C. Elmasian, N. Salvador, M. Lum.

Statistical expertise: C.P. Quesenberry.

Obtaining of funding: E.P. Gunderson, C.P. Quesenberry.

Administrative, technical, or logistic support: S.R. Hurston, J.C. Lo, K.G. Dewey, G. Fox, C.C. Elmasian.

Collection and assembly of data: E.P. Gunderson, S.R. Hurston, J.C. Lo.


Ann Intern Med. 2015;163(12):889-898. doi:10.7326/M15-0807
Text Size: A A A

Background: Lactation improves glucose metabolism, but its role in preventing type 2 diabetes mellitus (DM) after gestational diabetes mellitus (GDM) remains uncertain.

Objective: To evaluate lactation and the 2-year incidence of DM after GDM pregnancy.

Design: Prospective, observational cohort of women with recent GDM. (ClinicalTrials.gov: NCT01967030)

Setting: Integrated health care system.

Participants: 1035 women diagnosed with GDM who delivered singletons at 35 weeks' gestation or later and enrolled in the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy from 2008 to 2011.

Measurements: Three in-person research examinations from 6 to 9 weeks after delivery (baseline) and annual follow-up for 2 years that included 2-hour, 75-g oral glucose tolerance testing; anthropometry; and interviews. Multivariable Weibull regression models evaluated independent associations of lactation measures with incident DM adjusted for potential confounders.

Results: Of 1010 women without diabetes at baseline, 959 (95%) were evaluated up to 2 years later; 113 (11.8%) developed incident DM. There were graded inverse associations for lactation intensity at baseline with incident DM and adjusted hazard ratios of 0.64, 0.54, and 0.46 for mostly formula or mixed/inconsistent, mostly lactation, and exclusive lactation versus exclusive formula feeding, respectively (P trend = 0.016). Time-dependent lactation duration showed graded inverse associations with incident DM and adjusted hazard ratios of 0.55, 0.50, and 0.43 for greater than 2 to 5 months, greater than 5 to 10 months, and greater than 10 months, respectively, versus 0 to 2 months (P trend = 0.007). Weight change slightly attenuated hazard ratios.

Limitation: Randomized design is not feasible or desirable for clinical studies of lactation.

Conclusion: Higher lactation intensity and longer duration were independently associated with lower 2-year incidences of DM after GDM pregnancy. Lactation may prevent DM after GDM delivery.

Primary Funding Source: National Institute of Child Health and Human Development.

Figures

Grahic Jump Location
Figure.

Study flow diagram.

DM = diabetes mellitus; GDM = gestational diabetes mellitus; KPNC = Kaiser Permanente Northern California; OGTT = oral glucose tolerance test; SWIFT = Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy.

Grahic Jump Location

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References

Letters

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Win-win for both babies and mothers.
Posted on December 21, 2015
Wataru Nagahori1, MD, Hiromasa Takenoshita2, MD, Kataoka Yuki3, MD/MPH, Miho Kimachi3, MD
1. Department of Cardiology, Hokkaido Ohno Hospital, Sapporo, Japan 2. Department of internal medicine Karatsu Red Cross Hospital, Saga, Japan 3. Department of Healthcare Epidemiology, Graduate School
Conflict of Interest: None Declared
This prospective cohort study1 clearly demonstrated an inverse relationship between lactation intensity/duration and the incidence of newly diagnosed diabetes mellitus among women diagnosed with gestational diabetes mellitus (GDM). These results provide strong evidence that breast milk-based feeding in patients with GDM protects against progression to type 2 diabetes mellitus. However, we offer two comments on the study design and analysis.
First, the study protocol planned for lactation intention to be estimated using an infant feeding intention scale2, but the paper provided no data on this. We consider that lactation intensity could not have been accurately evaluated using categories based on a daily amount of formula only; rather, the authors should have performed sensitivity analysis using categories based on breastfeeding frequency and quantity as measured by feeding diaries. Additionally, if study period data from feeding diaries are available, we would like to know whether the four categories reflect the total amount of breast feeding. We propose that the operationally-defined main exposure, lactation intensity, should be clinically reasonable or more directly reflect what authors aim to assess. Any difference between the definition and what the authors aimed to assess would have likely lead to information bias or misclassification3.
Second, we would like to know why 83 women with a mixed feeding or inconsistent lactation pattern at 4-6 weeks after delivery were excluded from the study population at enrollment. Lactation intensity was classified into four groups, including a mixed or inconsistent lactation group; the excluded population could have been included in this group.

1. Gunderson EP, Hurston SR, Ning X, Lo JC, Crites Y, Walton D, et al. Lactation and Progression to Type 2 Diabetes Mellitus After Gestational Diabetes Mellitus: A Prospective Cohort Study. Ann Intern Med. 2015; 163(12): 889-98
2. Nommsen-Rivers LA, Dewey KG. Development and validation of the infant feeding intentions scale. Matern Child Health J. 2009; 13(3): 334-42.
3. Kraemer HC1, Stice E, Kazdin A, Offord D, Kupfer D. How do risk factors work together? Mediators, moderators, and independent, overlapping, and proxy risk factors. Am J Psychiatry. 2001 Jun;158(6):848-56.
Author's Response
Posted on February 19, 2016
Erica P. Gunderson, PhD, MS, MPH
Kaiser Permanente
Conflict of Interest: None Declared
Dear Dr. Nagahori,
The rationale for the SWIFT study eligibility criteria and methods for the detailed assessments have been published previously.(1;2) The SWIFT study design sought to contrast extremes of infant feeding by a priori selection of women who were fully exposed versus unexposed to lactation, and efficiently achieve statistical power to evaluate our primary outcome, incident type 2 diabetes.(1) Our screening telephone call at 4-6 weeks postpartum determined the woman’s eligibility for enrollment based on her infant feeding practices since birth and future intentions (Online Supplement). There were 83 women who reported “mixed or inconsistent” feeding, or expressed their intention to decrease breastfeeding at the 4-6 weeks telephone screening interview. They were designated as “ineligible” per study protocol and did not enroll in the study (Figure). Therefore, they were not “excluded”. However, there were 101 women who reported mostly or exclusively breastfeeding at the screening phone interview, but later transitioned to “mixed or inconsistent” feeding by the 6-9 weeks postpartum in-person enrollment visit. These women were enrolled and are included in follow up.
This study design took into account infant feeding “intention” at screening and enrollment to define lactation intensity. Infant feeding intention is an integral feature of the study design and intensity definition thereby obviating any sensitivity analysis and minimizing misclassification. Most importantly, we directly measured metabolic parameters and perinatal outcomes that can lead to reverse causation for lactation and diabetes (worse health causes lactation failure), and our findings remained robust.
Our definition of lactation intensity is highly clinically relevant, because we account for the quantity of formula intake during 24 hours corresponding to the energy needs at 2 months of age.(3;4) Formula intake ≤ 6 ounces per 24 hours represents ≤25% of the average infant’s energy intake. Formula intake >17 ounces per day represents at least 70% or more of the average infant’s energy intake. These cut points clearly distinguish between mostly breastfeeding, mixed feeding, and mostly formula feeding groups. We also calculated lactation intensity scores based on frequency of feeding and formula intake relative to total number of feedings of any type per 24 hours based on the method of Piper et al. (5). Our lactation intensity based on quantity of formula relative to infant energy intake was closely related to lactation duration (Online Supplement), and the intensity ratio scores. In our opinion, the lactation intensity based on the daily quantity of formula intake is more easily communicated by clinicians to breastfeeding women during the prenatal and early postpartum periods.
Sincerely,
Erica P. Gunderson, PhD., MS, MPH,
Principal Investigator, SWIFT study
On behalf of the SWIFT Investigators

References
(1) Gunderson EP, Matias SL, Hurston SR, Dewey KG, Ferrara A, Quesenberry CP, Jr. et al. Study of Women, Infant Feeding, and Type 2 diabetes mellitus after GDM pregnancy (SWIFT), a prospective cohort study: methodology and design. BMC Public Health 2011; 11(1):952.
(2) Gunderson EP, Hedderson MM, Chiang V, Crites Y, Walton D, Azevedo RA et al. Lactation Intensity and Postpartum Maternal Glucose Tolerance and Insulin Resistance in Women With Recent GDM: The SWIFT cohort. Diabetes Care 2012; 35(1):50-56.
(3) Lucas A, Ewing G, Roberts SB, Coward WA. How much energy does the breast fed infant consume and expend? Br Med J (Clin Res Ed) 1987; 295(6590):75-77.
(4) Stunkard AJ, Berkowitz RI, Stallings VA, Schoeller DA. Energy intake, not energy output, is a determinant of body size in infants. Am J Clin Nutr 1999; 69(3):524-530.
(5) Piper S, Parks PL. Use of an intensity ratio to describe breastfeeding exclusivity in a national sample. J Hum Lact 2001; 17(3):227-232.

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Summary for Patients

Screening for Abnormal Blood Glucose and Type 2 Diabetes: U.S. Preventive Services Task Force Recommendation

The full report is titled “Screening for Abnormal Blood Glucose and Type 2 Diabetes Mellitus: U.S. Preventive Services Task Force Recommendation Statement.” It is in the 1 December 2015 issue of Annals of Internal Medicine (volume 163, pages 861-868). The author is A.L. Siu, on behalf of the U.S. Preventive Services Task Force.

This article was published online first at www.annals.org on 27 October 2015.

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