Women who breastfeed have a reduced risk of developing diabetes

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A team of South Korean researchers found that lactation can lower the incidence and reduce the risk of maternal postpartum diabetes.

The researchers identified that lactation increases the mass and function of pancreatic beta cells through serotonin production.

The team suggested that sustained improvements in pancreatic beta cells, which can last for years even after the cessation of lactation, improve mothers’ metabolic health in addition to providing health benefits for infants.

Pregnancy imposes a substantial metabolic burden on women through weight gain and increased insulin resistance.

Various other factors, including a history of gestational diabetes, maternal age, and obesity, further affect women’s risk of progressing to diabetes after delivery, and the risk of postpartum diabetes increases more in women who have had gestational diabetes and/or repeated deliveries.

Diabetes-related complications include damage to blood vessels, which can lead to cardiovascular and cerebrovascular diseases such as heart attack and stroke, and problems with the nerves, eyes, kidneys, and many more.

Since diabetes can pose a serious threat to mothers’ metabolic health, the management of maternal metabolic risk factors is important, especially in the peripartum period. Previous epidemiological studies have reported that lactation reduces the risk of postpartum diabetes, but the mechanisms underlying this benefit have remained elusive.

The study, published in Science Translational Medicine on April 29, explains the biology underpinning this observation on the beneficial effects of lactation. Professor Hail Kim from the Graduate School of Medical Science and Engineering at KAIST led and jointly conducted the study in conjunction with researchers from the Seoul National University Bundang Hospital (SNUBH) and Chungnam National University (CNU) in Korea, and the University of California, San Francisco (UCSF) in the US.

In their study, the team observed that the milk-secreting hormone ‘prolactin’ in lactating mothers not only promotes milk production, but also plays a major role in stimulating insulin-secreting pancreatic beta cells that regulate blood glucose in the body.

This is a diagram from the study
Lactation reduces the risk of diabetes by improving pancreatic beta cell mass and function. Image is credited to Hail Kim, KAIST.

The researchers also found that ‘serotonin’, known as a chemical that contributes to wellbeing and happiness, is produced in pancreatic beta cells during lactation. Serotonin in pancreatic beta cells act as an antioxidant and reduce oxidative stress, making mothers’ beta cells healthier.

Serotonin also induces the proliferation of beta cells, thereby increasing the beta cell mass and helping maintain proper glucose levels.

The research team conducted follow-up examinations on a total of 174 postpartum women, 85 lactated and 99 non-lactated, at two months postpartum and annually thereafter for at least three years.

The results demonstrated that mothers who had undergone lactation improved pancreatic beta cell mass and function, and showed improved glucose homeostasis with approximately 20mg/dL lower glucose levels, thereby reducing the risk of postpartum diabetes in women. Surprisingly, this beneficial effect was maintained after the cessation of lactation, for more than three years after delivery.

Professor Kim said, “We are happy to prove that lactation benefits female metabolic health by improving beta cell mass and function as well as glycemic control.”

“Our future studies on the modulation of the molecular serotonergic pathway in accordance with the management of maternal metabolic risk factors may lead to new therapeutics to help prevent mothers from developing metabolic disorders,” he added.

Funding: This work was supported by grants from the National Research Foundation (NRF) and the National Research Council of Science and Technology (NST) of Korea, the National Institutes of Health (NIH), the Larry L. Hillblom Foundation, and the Health Fellowship Foundation.


Atherosclerotic cardiovascular diseases are the leading cause of death globally, with an estimated 17.3 million deaths per year.1 Hypertension and diabetes are associated with an increased risk of atherosclerotic cardiovascular diseases and cardiovascular mortality,2 and presence of diabetes may be considered a coronary artery disease equivalent in terms of cardiovascular risk.3

Moreover, both diabetes and hypertension independently account for the 7th and 13th leading causes of death in the United States, respectively.4

Cardiovascular disease remains the leading cause of death in women as well.5 Women share many of the traditional risk factors for cardiovascular disease; however, they also have unique cardiovascular and metabolic stresses in the setting of pregnancy and the puerperium.5

Lactation has been thought to be associated with positive effects on the postpartum state and is thought to work as a physiological reset to the adverse effects of pregnancy.6

However, sample sizes from various studies of lactation and cardiovascular risk have been relatively small, and there is disparity in the outcomes reported.

The aim of this systematic review and meta-analysis was to determine whether lactation is associated with reduced rates of maternal diabetes and hypertension.

Literature Search
The initial literature search yielded a total of 1558 records; after removing 442 duplicates, 1116 studies remained (eFigure 1 in the Supplement). The reviewers screened the titles and abstracts of the 1116 studies, and a total of 107 full-text articles were reviewed for eligibility.

Twenty-two studies went through a qualitative analysis, and 6 of the studies met full inclusion criteria and underwent quantitative synthesis or meta-analysis.14,15,16,17,18,19 A Preferred Reporting Items for Systematic Review and Meta-Analyses statement (PRISMA) flowchart20 is provided in eFigure 1 in the Supplement.

Systematic Review of 22 Studies
The details and characteristics of the 22 studies14,15,16,17,18,19,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37 included in the qualitative analysis are shown in eTable 2 in the Supplement. Each study was designed differently. The 16 studies that were not included in the final meta-analysis still provided valuable information in support of the results, so we discuss them here.

Bajaj et al32 found that the prevalence of diabetes was lower in women who had breastfed for more than 12 months compared with women who had breastfed for less than 3 months. Liu and colleagues14 used data from the Australian 45 and Up Cohort Study.

The authors found that total breastfeeding duration and duration per child was associated with a reduction in the risk of development of diabetes by approximately 14% per year of breastfeeding.

Schwarz et al15 concluded that breastfeeding for 12 or more months was associated with a decreased risk of hypertension, diabetes, hyperlipidemia, and cardiovascular disease. Unusually, the study population included women aged 50 to 79 years who were followed up for 7.9 years.

On closer inspection, however, it was found that in addition to prospectively analyzing outcomes, retrospective analysis of data gathered on recruitment was also performed. In a cross-sectional study, Zhang and colleagues16 showed that women who breastfed were less likely to develop hypertension and diabetes.

This remained significant when results were analyzed based on breastfeeding intervals of 0 to 6, 6 to 12, and more than 12 months, as well as when results were adjusted for confounding variables.

Choi and colleagues17 showed that breastfeeding for 12 or more months was associated with a lower risk of diabetes and metabolic syndrome. The Shanghai Women’s Health Study24 found that not only did women who breastfed have a lower risk of diabetes, increasing duration of breastfeeding was associated with a lower risk as well.

Similarly, Jäger et al30 concluded that breastfeeding for 6 or more months may be associated with a lower risk of diabetes. Breastfeeding was associated with protective effects against the development of atherosclerotic disease, with shorter duration of lactation associated with subclinical atherosclerosis as determined by measuring carotid intima media thickness.33 Stuebe et al23 found that at 3 years post partum, women who breastfed for more than 6 months had lower weight retention.

However, in a multivariate analysis, no consistent trend was found relating the association between breastfeeding and maternal metabolism in general. Schwarz and colleagues21 compared parous women who breastfed for 1 month or more and nulliparous women, and concluded that parous women who never breastfed had a higher risk of developing diabetes. Interestingly, women who engaged in exclusive breastfeeding for 1 to 3 months had a lower risk of developing diabetes compared with those who engaged in nonexclusive breastfeeding.

Breastfeeding initiation was associated with a reduced risk of diabetes in women with and without a history of gestational diabetes in a study by Martens et al.35 This association also remained significant after adjusting for confounding variables. Kirkegaard and colleagues26 concluded there was a strong, graded inverse association between lactation and incidence of diabetes when looking at various breastfeeding durations ranging from 0 to 6 months, 6 to 12 months, and longer than 12 months.

Similarly, the Study of Women’s Health Across the Nation (SWAN)36 found that breastfeeding was associated with a lower prevalence of diabetes in a dose-response manner as well.

Using data from the Nurses’ Health Study, a large prospective cohort with more than 44 000 participants, Stuebe et al29 found that exclusive breastfeeding for longer than 6 months or total breastfeeding for longer than 12 months was associated with a lower risk of developing hypertension later in life compared with no breastfeeding or breastfeeding for less than 6 months.

These findings remained significant after adjusting for confounders. Similarly, the Korean Women’s Study27 suggested that breastfeeding for 1 to 6 months or longer was associated with a lower risk of hypertension compared with no history of lactation. This study also found that the combination of obesity and gestational hypertension was associated with a higher risk of developing hypertension.

Park and Choi28 found that a greater number of breastfed children and longer duration of breastfeeding were associated with a lower risk of hypertension. This association was moderated by the degree of obesity and insulin resistance.

A study by Kirkegaard et al26 studied the association between breastfeeding and hypertension as well as the development of cardiovascular disease and found that longer duration of breastfeeding was associated with a lower risk of hypertension and cardiovascular disease.

Kim and Kim25 showed that any breastfeeding was better than none when assessing the association between breastfeeding and metabolic syndrome. Interestingly, a cross-sectional study31 of more 900 women in Iran did not support the protective associations of breastfeeding with development of metabolic syndrome.

Chetwynd et al18 used data from the Black Women’s Health Study and found that breastfeeding was associated with reduced risk of hypertension at ages 40 to 49 years, but not necessarily at older ages.

Increasing the duration of breastfeeding was associated with a lower risk of developing hypertension in this age group, with the strongest association seen in women who breastfed for a cumulative time of 24 months or more. Lupton and colleagues19 used data from the Australian 45 and Up Study.

Data from more than 74 000 women aged 45 years and older were analyzed to determine the association of parity and breastfeeding with maternal hypertension. The authors observed that lifetime breastfeeding for longer than 6 months or more than 3 months per child was associated with lower odds of having high blood pressure.

Conclusions

Breastfeeding for longer than 12 months was associated with a 30% lower risk of diabetes and a 13% lower risk of hypertension in mothers after adjusting for confounding variables. The prenatal and antenatal period is an important opportunity to educate women about lifestyle interventions that may protect their health in the future.

In addition to weight loss, smoking cessation, and exercise, breastfeeding should also be recommended owing to its benefits for the mother. Because this meta-analysis showed association but not causation, further research is needed to better understand this result.

However, given the low-risk nature of this intervention, educating mothers about the potential benefits of breastfeeding for their cardiovascular health can be easily introduced into clinical practice when addressing prevention of cardiovascular outcomes in women.


Source:
KAIST

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