Lactation Protects Against T2DM in Women With Recent GDM
Of the 304 women with GDM participating in the study, 272 (89.5%) were islet autoantibody-negative. Of women without islet autoantibodies, 92 required insulin during pregnancy, and 180 were sufficiently treated with diet (Supplementary Fig. 1). The median age of all participating women was 31 years (IQR 28–34 years).
(Enlarge Image)
Figure 1.
Cumulative life-table risk of postpartum diabetes in 304 women with GDM who were followed prospectively from delivery. Risk is shown for women who were islet autoantibody-positive (solid black line; n = 32); were islet autoantibody-negative, received insulin therapy during pregnancy, and had a BMI >30 kg/m (thick black dotted line; n = 39); were islet autoantibody-negative, received insulin therapy during therapy, and had a BMI <30 kg/m (thin gray dotted line; n = 53); were islet autoantibody-negative, did not receive insulin therapy during therapy, and had a BMI >30 kg/m (black dashed line; n = 48); and were islet autoantibody-negative, did not receive insulin therapy during therapy, and had a BMI <30 kg/m (thin gray dashed line; n = 132). Numbers below the graph indicate the number of subjects at each follow-up.
Postpartum diabetes was diagnosed in 147 women of the 304 women included in the study. The 15-year cumulative risk of postpartum diabetes in all women with GDM was 63.6% (95% CI 55.8–71.4), and the median diabetes-free duration was 7.9 years postpartum (95% CI 5.0–10.8; Supplementary Fig. 2). Diabetes was diagnosed at a median age of 34 years (IQR 30–38 years), and only a few women went through menopause during follow-up.
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Figure 2.
Cumulative life-table risk of postpartum diabetes in islet autoantibody-negative women with GDM who breastfed for >3 months (dashed line) compared with those who breastfed for ≤3 months (solid line; P = 0.029) or did not breastfeed (dotted line; P = 0.002). No significant difference was observed between women who breastfed >2 months compared with women who breast-fed ≤3 months (P = 0.2). Numbers below the graph indicate the number of subjects at each follow-up.
Postpartum diabetes risk was extremely high in the 32 islet autoantibody-positive women (Fig. 1). All but one of these patients developed diabetes postpartum, and their median diabetes-free duration postpartum was just 4.5 months (95% CI 2.5–6.5).
Among the 272 islet autoantibody-negative women, postpartum diabetes risk and the rate of diabetes development were stratified according to therapy received during pregnancy and BMI (Fig. 1). The highest risk was observed in 92 women without islet autoantibodies who required insulin during pregnancy (15 year risk 92.3% [95% CI 84.7–99.9]) compared with diet-treated women (39.7[28.8–50.6]). The median diabetes-free duration was 2.1 and 16.3 years, respectively (P = 10). Stratification for BMI (≤30 vs. >30 kg/m) did not affect the risk or rate of developing diabetes among women with GDM who were treated with insulin (median diabetes-free duration, 2.1 vs. 2.1 years; P = 0.4). In contrast, islet autoantibody-negative women who were treated with diet with a BMI >30 kg/m had a significantly increased postpartum risk for diabetes (15 year risk, 69.1% [95% CI 50.0–88.2] vs. 28.6 [16.5–40.7]; P = 0.002) and faster progression (median diabetes-free duration, 10.2 years) relative to women with BMI ≤30 kg/m (median diabetes-free duration, 18.2 years). None of the islet autoantibody-negative women with GDM developed islet autoantibodies during the follow-up.
Breastfeeding data were available for 264 women. Of these, 201 (76%) breastfed their child and 109 continued breastfeeding for >3 months (Supplementary Fig. 1). Full breastfeeding was practiced by 62% of the women and the duration of full breastfeeding was strongly correlated with any breastfeeding duration (r=0.71; P < 0.0001). These values are notably less than frequencies reported for women in Germany (). The median duration of breastfeeding in the women with GDM was 9 weeks (IQR 1–25 weeks), and the median duration of full breastfeeding was 4 weeks (0–16 weeks). Duration of breast-feeding was shorter in women who required insulin (median of 5 weeks vs. 12 weeks in those treated with diet; P = 0.003) and in women who were overweight (median 5 weeks vs. 12 weeks in women with BMI <30 kg/m; P = 0.003), but it was not associated with islet autoantibody positivity (positives breastfed for a median of 6 weeks vs. negatives, who breastfed for a median of 9 weeks; P = 0.47). No differences in breastfeeding were observed with respect to dropout status (median of 11 weeks in women who dropped out vs. 9 weeks in those who stayed in the study; P = 0.97). Women who entered the study during the second half of the recruitment period were more likely to breastfeed their child than women entering the study during the first half of the recruitment period (82 vs. 72%; P = 0.04), and this was most obvious for full breastfeeding (72 vs. 53%; P = 0.003).
Lactation did not affect diabetes development among islet autoantibody-positive women (data not shown). Among islet autoantibody-negative women, lactation was associated with a marked delay in diabetes development compared with women who did not breastfeed (median diabetes-free duration, 12.2 years [95% CI 7.7–16.8] vs. 2.2 [0.0–6.1]; P = 0.012). Notably, the duration of lactation was inversely associated with postpartum diabetes risk (P = 0.002), and women who breastfed for >3 months had the lowest postpartum diabetes risk (15-year risk: 42% [95% CI 28.9–55.1] vs. no or ≤3 months of breastfeeding, 72% [60.5–84.7]; P = 0.0002) and a longer diabetes-free duration (18.2 years [95% CI 10.4–25.9]; Fig. 2). Postpartum diabetes risk also was inversely associated with full breastfeeding duration (P = 0.001), with a lower 15-year risk in women who practiced full breastfeeding for at least 3 months (34.8% [95% CI 18.3–41.3] vs. 71.7 [60.3–83.1]; P = 0.001).
Multivariate analysis showed that insulin therapy (hazard ratio 5.5 [95% CI 3.7–8.2]; P = 10), BMI >30 kg/m (1.7 [1.1–2.5]; P = 0.009), and any breastfeeding >3 months (0.55 [0.35–0.85]; P = 0.009) were significantly and independently associated with the risk of postpartum diabetes in islet autoantibody-negative women with GDM, whereas age at delivery, parity status, year of study enrollment, and smoking during pregnancy were not (Table 1). Stratification of women into diet versus insulin-treated cases or BMI <30 versus BMI >30 suggested that breastfeeding may be more effective in reducing postpartum diabetes risk in women treated with diet than in women treated with insulin, but numbers after stratification were small in some groups (Supplementary Table).
Postpartum BMI was obtained in 289 of the women at a median of 4.85 years postpartum (IQR 2.0–7.4 years). Duration of lactation continued to be associated with postpartum BMI (P = 0.0006). However, lactation did not influence BMI trends postpartum, as proven by the lack of correlation between the duration of lactation and the delta postpregnancy BMI (r=0.01; P = 0.12; Supplementary Fig. 3). The mean delta postpregnancy BMI among women who breastfed for at least 3 months was 0.36 (SD 2.0) compared with 0.12 (2.6) in women who breastfed <3 months (P = 0.44).
Results
Of the 304 women with GDM participating in the study, 272 (89.5%) were islet autoantibody-negative. Of women without islet autoantibodies, 92 required insulin during pregnancy, and 180 were sufficiently treated with diet (Supplementary Fig. 1). The median age of all participating women was 31 years (IQR 28–34 years).
(Enlarge Image)
Figure 1.
Cumulative life-table risk of postpartum diabetes in 304 women with GDM who were followed prospectively from delivery. Risk is shown for women who were islet autoantibody-positive (solid black line; n = 32); were islet autoantibody-negative, received insulin therapy during pregnancy, and had a BMI >30 kg/m (thick black dotted line; n = 39); were islet autoantibody-negative, received insulin therapy during therapy, and had a BMI <30 kg/m (thin gray dotted line; n = 53); were islet autoantibody-negative, did not receive insulin therapy during therapy, and had a BMI >30 kg/m (black dashed line; n = 48); and were islet autoantibody-negative, did not receive insulin therapy during therapy, and had a BMI <30 kg/m (thin gray dashed line; n = 132). Numbers below the graph indicate the number of subjects at each follow-up.
Postpartum Diabetes Risk
Postpartum diabetes was diagnosed in 147 women of the 304 women included in the study. The 15-year cumulative risk of postpartum diabetes in all women with GDM was 63.6% (95% CI 55.8–71.4), and the median diabetes-free duration was 7.9 years postpartum (95% CI 5.0–10.8; Supplementary Fig. 2). Diabetes was diagnosed at a median age of 34 years (IQR 30–38 years), and only a few women went through menopause during follow-up.
(Enlarge Image)
Figure 2.
Cumulative life-table risk of postpartum diabetes in islet autoantibody-negative women with GDM who breastfed for >3 months (dashed line) compared with those who breastfed for ≤3 months (solid line; P = 0.029) or did not breastfeed (dotted line; P = 0.002). No significant difference was observed between women who breastfed >2 months compared with women who breast-fed ≤3 months (P = 0.2). Numbers below the graph indicate the number of subjects at each follow-up.
Stratification of Postpartum Diabetes Risk
Postpartum diabetes risk was extremely high in the 32 islet autoantibody-positive women (Fig. 1). All but one of these patients developed diabetes postpartum, and their median diabetes-free duration postpartum was just 4.5 months (95% CI 2.5–6.5).
Among the 272 islet autoantibody-negative women, postpartum diabetes risk and the rate of diabetes development were stratified according to therapy received during pregnancy and BMI (Fig. 1). The highest risk was observed in 92 women without islet autoantibodies who required insulin during pregnancy (15 year risk 92.3% [95% CI 84.7–99.9]) compared with diet-treated women (39.7[28.8–50.6]). The median diabetes-free duration was 2.1 and 16.3 years, respectively (P = 10). Stratification for BMI (≤30 vs. >30 kg/m) did not affect the risk or rate of developing diabetes among women with GDM who were treated with insulin (median diabetes-free duration, 2.1 vs. 2.1 years; P = 0.4). In contrast, islet autoantibody-negative women who were treated with diet with a BMI >30 kg/m had a significantly increased postpartum risk for diabetes (15 year risk, 69.1% [95% CI 50.0–88.2] vs. 28.6 [16.5–40.7]; P = 0.002) and faster progression (median diabetes-free duration, 10.2 years) relative to women with BMI ≤30 kg/m (median diabetes-free duration, 18.2 years). None of the islet autoantibody-negative women with GDM developed islet autoantibodies during the follow-up.
Lactation and Diabetes Outcome
Breastfeeding data were available for 264 women. Of these, 201 (76%) breastfed their child and 109 continued breastfeeding for >3 months (Supplementary Fig. 1). Full breastfeeding was practiced by 62% of the women and the duration of full breastfeeding was strongly correlated with any breastfeeding duration (r=0.71; P < 0.0001). These values are notably less than frequencies reported for women in Germany (). The median duration of breastfeeding in the women with GDM was 9 weeks (IQR 1–25 weeks), and the median duration of full breastfeeding was 4 weeks (0–16 weeks). Duration of breast-feeding was shorter in women who required insulin (median of 5 weeks vs. 12 weeks in those treated with diet; P = 0.003) and in women who were overweight (median 5 weeks vs. 12 weeks in women with BMI <30 kg/m; P = 0.003), but it was not associated with islet autoantibody positivity (positives breastfed for a median of 6 weeks vs. negatives, who breastfed for a median of 9 weeks; P = 0.47). No differences in breastfeeding were observed with respect to dropout status (median of 11 weeks in women who dropped out vs. 9 weeks in those who stayed in the study; P = 0.97). Women who entered the study during the second half of the recruitment period were more likely to breastfeed their child than women entering the study during the first half of the recruitment period (82 vs. 72%; P = 0.04), and this was most obvious for full breastfeeding (72 vs. 53%; P = 0.003).
Lactation did not affect diabetes development among islet autoantibody-positive women (data not shown). Among islet autoantibody-negative women, lactation was associated with a marked delay in diabetes development compared with women who did not breastfeed (median diabetes-free duration, 12.2 years [95% CI 7.7–16.8] vs. 2.2 [0.0–6.1]; P = 0.012). Notably, the duration of lactation was inversely associated with postpartum diabetes risk (P = 0.002), and women who breastfed for >3 months had the lowest postpartum diabetes risk (15-year risk: 42% [95% CI 28.9–55.1] vs. no or ≤3 months of breastfeeding, 72% [60.5–84.7]; P = 0.0002) and a longer diabetes-free duration (18.2 years [95% CI 10.4–25.9]; Fig. 2). Postpartum diabetes risk also was inversely associated with full breastfeeding duration (P = 0.001), with a lower 15-year risk in women who practiced full breastfeeding for at least 3 months (34.8% [95% CI 18.3–41.3] vs. 71.7 [60.3–83.1]; P = 0.001).
Multivariate analysis showed that insulin therapy (hazard ratio 5.5 [95% CI 3.7–8.2]; P = 10), BMI >30 kg/m (1.7 [1.1–2.5]; P = 0.009), and any breastfeeding >3 months (0.55 [0.35–0.85]; P = 0.009) were significantly and independently associated with the risk of postpartum diabetes in islet autoantibody-negative women with GDM, whereas age at delivery, parity status, year of study enrollment, and smoking during pregnancy were not (Table 1). Stratification of women into diet versus insulin-treated cases or BMI <30 versus BMI >30 suggested that breastfeeding may be more effective in reducing postpartum diabetes risk in women treated with diet than in women treated with insulin, but numbers after stratification were small in some groups (Supplementary Table).
Lactation and BMI Postpartum
Postpartum BMI was obtained in 289 of the women at a median of 4.85 years postpartum (IQR 2.0–7.4 years). Duration of lactation continued to be associated with postpartum BMI (P = 0.0006). However, lactation did not influence BMI trends postpartum, as proven by the lack of correlation between the duration of lactation and the delta postpregnancy BMI (r=0.01; P = 0.12; Supplementary Fig. 3). The mean delta postpregnancy BMI among women who breastfed for at least 3 months was 0.36 (SD 2.0) compared with 0.12 (2.6) in women who breastfed <3 months (P = 0.44).