Breastfeeding is good!

The World Health Organization (WTO) recommends that breastfeeding infants within the first 6 months after delivery can benefit maternal and infant health, including reducing infant morbidity and mortality, preventing breast and ovarian cancer , and reducing the mother’s future of diabetes and other heart blood vessel disease risk
.

Nevertheless, in most countries, the breastfeeding rate of infants under 6 months is still far below 50%

Prevention of breast cancer ovarian cancer, diabetes, heart blood vessels

Women with a history of gestational diabetes (GDM) have a 7 times higher risk of type 2 diabetes (T2D)
.

It is estimated that 20-50% of women with a history of GDM will enter T2D within 10 years after delivery

There is a significant association between intensive breastfeeding and a reduction in the risk of T2D events

Lipids play an important role in the pathogenesis of T2D, and the metabolite characteristics in the early postpartum period may help to effectively predict the future onset of T2D
.

This study aims to determine the association between intensive lactation and metabolic characteristics in women who have recently become pregnant with GDM, and then use selected metabolites to predict the future risk of T2D

1.
Queue design

1.
Queue design 1.
Queue design

SWIFT is a prospective longitudinal study group of 1,035 women
.

Of the 1,035 women without diabetes, 1,010 were confirmed by a 2-hour 75-gram OGTT at baseline

SWIFT is a prospective longitudinal study group of 1,035 women

2.
Participants' clinical characteristics

2.
Participants' clinical characteristics

The prenatal and postnatal clinical, sociodemographic and biochemical data of 350 participants are summarized in Table 1
.

Compared with IBF women, IFF/mixed women had a slightly higher pre-pregnancy body mass index (mean ± SD: 34.

² p (FPG) (p (p (p

3.
Metabolic changes related to lactation intensity

3.
Metabolic changes related to lactation intensity

Between the IBF and IFF/mixed groups, 75 statistically significant metabolites were identified (FDR <0.
05)
.

All differentially expressed metabolites with FDR <0.

Differential expression of FDR <0.

( Onset 1-2 years after n baseline, n = 102 , n histidine, citrulline and total dma)

In order to further determine whether postpartum breastfeeding has a sustained effect on the long-term metabolism of the parturient, the 303 women were further stratified into subgroups without T2D (n = 152), short-term T2D (n = 102), and long-term T2D (n = 49), and Perform longitudinal analysis in each subgroup
.

During this period, no significant changes in metabolites were found
.

4.
Changes in lipid types related to baseline lactation intensity

4.
Changes in lipid types related to baseline lactation intensity

This study covered a wide range of lipid species (1008 lipid species in 15 categories and 296 fatty acids) to assess the baseline lipid changes associated with lactation intensity in 350 women (216IBF vs.
134 IFF/mix)
.
The final bioinformatics analysis included a total of 818 lipids
.
PCA and PLS-DA analysis showed that there is a clear separation between the two groups
.
Among 818 lipid species, 581 were significantly correlated with baseline lactation intensity (FDR <0.
05).
Compared with the IFF/mixed group, 183 lipids were regulated and 398 lipids were reduced in IBF (Figure 3A)
.

It is worth noting that 64% (328 out of 513 measured TAGs) and 83% (45 out of 54 measured DAGs) were significantly reduced in IBF women, indicating that the ratio of women with a higher baseline lactation intensity Women fed with intensive formula or mixed feeding have lower circulating TAG and DAG levels, which is consistent with clinical biochemical examination
.
We show the top 150 lipid species with the most significant differential expression (Figure 3C), of which 81 TAGs and 23 DAGs are always negatively correlated with the baseline lactation intensity
.
In contrast, 15 sphingomyelins, 20 phospholipids, and 11 CE have been positively correlated with intensive lactation (Figure 3C)
.

5.
The characteristics of lipid structure and composition related to lactation intensity

5.
Characteristics of lipid structure and composition related to lactation intensity 5.
Characteristics of lipid structure and composition related to lactation intensity

Check the number of carbon atoms and double bonds in lipids to gain insight into whether intensive lactation affects the composition of lipids
.
The TAGs measured in this study have 35 to 60 carbon atoms and double bonds of 0 to 12 carbon atoms
.
The TAG of women with IBF is significantly reduced, and they are concentrated in the range of carbon atoms 50-56, especially carbon atoms (50, 52, 54 and 60) (Figure 4)
.
Similarly, DAGs (32, 34, 36, 38, and 40) with a uniform number of carbon atoms are significantly negatively correlated with baseline intensive lactation
.
As for total FAs, most long-chain fatty acids (FA 16:0, FA 16:1, FA 17:0, FA 18:0, FA 18:1, FA 18:2, FA 20:1 and FA 20:2) There was a significant decrease in IBF, while most long-chain fatty acids (FA 22:0, FA 24:0, FA 24:1, FA 26:0, and FA 26:1) were adjusted higher
.
No changes were observed for medium chain fatty acids
.

6.
Metabolic pathways related to lactation intensity

6.
Metabolic pathways related to lactation intensity

The results showed that glycerolipid metabolism in women with IBF was significantly reduced, involving TAG/DAG biosynthesis (p = 0.
04) (Figure 5A)
.
In contrast, the metabolism of amphetamine (p  = 0.
002) and glycerophospholipid (p = 0.
01) was significantly down-regulated
.
These three significantly regulated pathways (glycemic acid, phospholipid, and glycerolipid metabolism) are closely linked because they share common substrates, such as phosphatidic acid and fatty acyl-CoA, indicating that carbon from TAG and DAG is converted to phospholipids and sphingolipids.
Path switch and flux of lipid transfer (Figure 5B)
.

(P (p (p because they share common substrates, such as phosphatidic acid and fatty acyl-CoA, indicating the switch and flux of the transfer of carbon from TAG and DAG to phospholipids and sphingolipids (Figure 5B)
.

7.
Genes and regulatory elements related to lactation-related lipid types

7.
Genes and regulatory elements related to lactation-related lipid types

The results of this study indicate that lactation intensity is related to changes in lipid metabolism
.
We found that 183 up-regulated lipids (mainly phospholipids and sphingomyelin) are linked to 296 genes.
These 296 genes match with 21 master regulators (such as PPARA, SREBF1, FOXO1, SOX9, STAT5A), most of which are involved Lipid metabolism (Figure 6)
.
The target gene clusters involved in lipid metabolism during lactation regulated by master regulators are shown in Figure 6B
.
In contrast, 398 down-regulated lipids (mainly TAG and DAG) are associated with only one gene, CEPT1 (Figure 6A)
.
CEPT1 encodes choline/ethanolamine phosphotransferase 1, indicating that there is a close connection between glycerolipids and phospholipids
.

The results of this study indicate that lactation intensity is related to changes in lipid metabolism
.
We found that 183 up-regulated lipids (mainly phospholipids and sphingomyelin) are linked to 296 genes.
These 296 genes match with 21 master regulators (such as PPARA, SREBF1, FOXO1, SOX9, STAT5A), most of which are involved Lipid metabolism (Figure 6)
.
The target gene clusters involved in lipid metabolism during lactation regulated by master regulators are shown in Figure 6B
.
In contrast, 398 down-regulated lipids (mainly TAG and DAG) are associated with only one gene, CEPT1 (Figure 6A)
.
CEPT1 encodes choline/ethanolamine phosphotransferase 1, indicating that there is a close connection between glycerolipids and phospholipids
.

8.
The effect of breastfeeding on the baseline lipid profile of T2D and non-T2D women in the future

8.
The influence of breastfeeding on the baseline lipid profile of future T2D and non-T2D women The influence of breastfeeding on the baseline lipid profile of future T2D and non-T2D women

Previous studies have shown that lactation intensity and duration are associated with a 34-57% reduction in the relative risk of T2D incidence within 2 years after delivery
.
We further stratified 350 recent GDM women according to their future T2D status, and checked whether intensive lactation affects the lipid profile of each subgroup
.
Of the 350 women, 171 developed T2D during the follow-up period (8 years after baseline), and 179 did not have T2D (Figure 7A)
.
In the future T2D group, 98 (57.
3%) women were classified as IBF, and 73 (42.
7%) women were classified as IFF/Mixed at baseline (Figure 7A)
.
In the T2D-free group, 118 (65.
9%) women were classified as IBF, while 61 (34.
1%) women were classified as IFF/Mixed at baseline (Figure 7)
.
In the non-T2D group, there were 552 lipids in IBF and IFF/mixed women ( Figure 7B-C) (FDR < 0.
05)
.
Figure 7D summarizes and shows that FDR < 0.
001 has differential lipids
.
Among these lipids, compared with the IFF/Mixed group, 185 TAG and 35 DAG were down-regulated in the IBF group, while 19 CEs, 55 phospholipids, and 33 sphingolipids were up-regulated (Figure 7D)
.
However, in the future, the lipids of the T2D subgroup will have significantly less differential expression than women without T2D
.
The same trend was also observed in metabolomics analysis, which indicates that women who are metabolically unresponsive to breastfeeding are likely to develop T2D in the future after pregnancy with GDM
.

Previous studies have shown that lactation intensity and duration are associated with a 34-57% reduction in the relative risk of T2D incidence within 2 years after delivery
.
We further stratified 350 recent GDM women according to their future T2D status, and checked whether intensive lactation affects the lipid profile of each subgroup
.
Of the 350 women, 171 developed T2D during the follow-up period (8 years after baseline), and 179 did not have T2D (Figure 7A)
.
In the future T2D group, 98 (57.
3%) women were classified as IBF, and 73 (42.
7%) women were classified as IFF/Mixed at baseline (Figure 7A)
.
In the T2D-free group, 118 (65.
9%) women were classified as IBF, while 61 (34.
1%) women were classified as IFF/Mixed at baseline (Figure 7)
.
In the non-T2D group, there were 552 lipids in IBF and IFF/mixed women ( Figure 7B-C) (FDR < 0.
05)
.
Figure 7D (FDR < 0.
05) summarizes and shows that FDR < 0.
001 has differential lipids
.
FDR < 0.
001 has differential lipids
.
Among these lipids, compared with the IFF/Mixed group, 185 TAG and 35 DAG were down-regulated in the IBF group, while 19 CEs, 55 phospholipids, and 33 sphingolipids were up-regulated (Figure 7D)
.
However, in the future, the lipids of the T2D subgroup will have significantly less differential expression than women without T2D
.
The same trend was also observed in metabolomics analysis, which indicates that women who are metabolically unresponsive to breastfeeding are likely to develop T2D in the future after pregnancy with GDM
.

9.
Prediction of future T2D for women who intensify breastfeeding

9.
Prediction of the future T2D of women with intensified breastfeeding 9.
Prediction of the future T2D of women with intensified breastfeeding

To further determine who is more likely to develop T2D in the future, even with intensive breastfeeding, we built a different prediction model using 10 analytes-1 acylcarnitine, 2 biogenic amines, 3 amino acids and 4 lipids Class (Figure 8A)
.
The median AUC value is 0.
78 (95% CI 0.
65-0.
91), which is far better than FPG (median AUC 0.
56, 95% CI 0.
39-0.
73) and 2 h-PG (median AUC 0.
62, 95% CI 0.
46-0.
78) (Figure 8B-D)
.
It is worth noting that after combining clinical variables with 10 analysis features, the prediction performance is slightly improved (median AUC 0.
80, 95% CI 0.
67-0.
92), suggesting the importance of metabolic features in predicting the future T2D of women with IBF
.
These data indicate that there are metabolic changes several years before the actual onset of T2D in intensive breastfeeding women, which allows us to predict T2D in this specific group and further study the underlying mechanisms related to the pathogenesis of T2D
.

To further determine who is more likely to develop T2D in the future, even with intensive breastfeeding, we built a different prediction model using 10 analytes-1 acylcarnitine, 2 biogenic amines, 3 amino acids and 4 lipids Class (Figure 8A)
.
The median AUC value is 0.
78 (95% CI 0.
65-0.
91), which is far better than FPG (median AUC 0.
56, 95% CI 0.
39-0.
73) and 2 h-PG (median AUC 0.
62, 95% CI 0.
46-0.
78) (Figure 8B-D)
.
It is worth noting that after combining clinical variables with 10 analysis features, the prediction performance is slightly improved (median AUC 0.
80, 95% CI 0.
67-0.
92), suggesting the importance of metabolic features in predicting the future T2D of women with IBF
.
These data indicate that there are metabolic changes several years before the actual onset of T2D in intensive breastfeeding women, which allows us to predict T2D in this specific group and further study the underlying mechanisms related to the pathogenesis of T2D
.

In summary, lactation intensity is closely related to the reduction of glycerolipids (TAGs/DAGs) and the increase of baseline phospholipids/phospholipids
.
This lipid profile indicates the shift from the glycerol and sugar metabolism pathway to the phospholipid/phospholipid metabolism pathway, as a component of the basic mechanism of breastfeeding benefits
.
Longitudinal analysis shows that this favorable lipid change is transient in 1-2 years postpartum
.
Importantly, in the follow-up process, when these 350 women were stratified by their future T2D status (171 future T2D and 179 no T2D), compared with women without T2D, women with T2D later were There are fewer lipid changes related to lactation intensity
.
Subsequently, we identified a cluster of metabolites closely related to the risk of future T2D.
From this set of metabolites, we developed a predictive metabolic feature with a discriminant power (AUC) of 0.
78, which is superior to common clinical variables (ie fasting glucose).
, AUC 0.
56 or 2 hours glucose, AUC 0.
62)
.

In general, intensive breastfeeding significantly changes the lipid profile of the early postpartum cycle, and women who do not have a metabolic response to breastfeeding are more likely to develop T2D
.
We also found a 10 analysis of metabolic characteristics that can predict the future risk of T2D in women with IBF
.

Intensive breastfeeding significantly changes the lipid profile of the early postpartum cycle, and women who do not have a metabolic response to breastfeeding are more likely to develop T2D
.
We also found a 10 analysis of metabolic characteristics that can predict the future risk of T2D in women with IBF
.

Original source:

Zhang et al.
Intensive lactation among women with recent gestational diabetes significantly alters the early postpartum circulating lipid profile: the SWIFT study BMC Medicine (2021) 19:241.

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