Human milk imparts higher insulin concentration in infants born to women with type 2 diabetes mellitus.

OBJECTIVE: Human milk (HM) insulin plays many roles for the infant, especially for the newborn. We hypothesized HM insulin in women with type 2 diabetes (T2DM) would be higher than BMI-matched women with either gestational diabetes (GDM) or normal glucose tolerance (NGT). In T2DM, we also assessed macronutrient composition and relationships between maternal glycemic control and HM insulin. STUDY DESIGN: HM was characterized at 2-weeks postpartum among three BMI-matched groups: T2DM (n= 12), diet-controlled GDM (n= 12), and NGT (n= 12). In T2DM, additional fasting and postprandial HM samples were collected while wearing a continuous glucose monitor (CGM), as well as fasting and 90-minute postprandial samples after a standardized meal at 1-2 weeks postpartum. RESULTS: Fasting HM insulin was two times higher in T2DM compared to GDM and NGT (p < .001), which were not different from each other. Among T2DM, fasting (p < .001) and postprandial (p = .01) HM insulin levels were between 2 and 5× higher than plasma. Postprandial HM insulin (p = .03) and glucose (p < .001) were increased compared to fasting. Mean nocturnal glucose (p < .01) and maternal hemoglobin A1c (p < .01) positively associated with fasting HM insulin. CONCLUSIONS: These data are the first to show HM insulin concentrations are doubled in T2DM compared to BMI-matched GDM and NGT. In HM of T2DM, insulin increases postprandially, may be concentrated relative to plasma, and is influenced by maternal glycemic control, with potential clinical implications that merit further study.

Effect of type 2 diabetes mellitus on placental expression and activity of nutrient transporters and their association with birth weight and neonatal adiposity.

AIMS: Infants born to women with Type 2 Diabetes Mellitus (T2DM) are at risk of being born large for gestational age due to excess fetal fat accretion. Placental nutrient transport determines fetal nutrient availability, impacting fetal growth. The aims of the study were to evaluate the effect of T2DM on placental insulin signaling, placental nutrient transporters and neonatal adiposity. METHODS: Placentas were collected from BMI-matched normoglycemic controls (NGT, n = 9) and T2DM (n = 9) women. Syncytiotrophoblast microvillous (MVM) and basal (BM) plasma membranes were isolated. Expression of glucose (GLUT1, -4), fatty acid (FATP2, -4, -6, FAT/CD36), amino acid (SNAT1, -2, -4, LAT1, -2) transporters, insulin signaling, and System A transporter activity was determined. Neonatal fat mass (%) was measured in a subset of neonates born to T2DM women. RESULTS: GLUT1 protein expression was increased (p = 0.001) and GLUT4 decreased (p = 0.006) in BM from T2DM. MVM FATP6 expression was increased (p = 0.02) and correlated with birth weight in both T2DM and NGT groups (r = 0.65, p = 0.02). BM FATP6 expression was increased (p = 0.01) in T2DM. In MVM of T2DM placentas, SNAT1 expression was increased (p = 0.05) and correlated with birth weight (r = 0.84, p = 0.004); SNAT2 was increased (p = 0.01), however System A transporter activity was not different between groups. MVM LAT1 expression was increased (p = 0.01) in T2DM and correlated with birth weight (r = 0.59, p = 0.04) and neonatal fat mass (r = 0.76, p = 0.06). CONCLUSION: In pregnancies complicated by T2DM placental protein expression of transporters for glucose, amino acids and fatty acids is increased, which may contribute to increased fetal growth and neonatal adiposity.

Obstructive Sleep Apnea Is Associated With Altered Glycemic Patterns in Pregnant Women With Obesity.

OBJECTIVE: Often unrecognized, obstructive sleep apnea (OSA) worsens over pregnancy and is associated with poorer perinatal outcomes. The association between OSA in late pregnancy and metabolic biomarkers remains poorly understood. We tested the hypothesis that OSA in pregnant women with obesity is positively correlated with 24-hour patterns of glycemia and IR despite controlling for diet. DESIGN: Pregnant women (32 to 34 weeks' gestation; body mass index, 30 to 40 kg/m2) wore a continuous glucose monitor for 3 days. OSA was measured in-home by WatchPAT 200™ [apnea hypopnea index (AHI), oxygen desaturation index (ODI; number per hour)]. Fasting blood was collected followed by a 2-hour, 75-g, oral glucose tolerance test to measure IR. Association between AHI and 24-hour glucose area under the curve (AUC) was the powered outcome. RESULTS: Of 18 women (29.4 ± 1.4 years of age [mean ± SEM]), 12 (67%) had an AHI ≥5 (mild OSA). AHI and ODI were correlated with 24-hour glucose AUC (r = 0.50 to 0.54; P ≤ 0.03) and mean 24-hour glucose (r = 0.55 to 0.59; P ≤ 0.02). AHI and ODI were correlated with estimated hepatic IR (r = 0.59 to 0.74; P < 0.01), fasting free fatty acids (fFFAs; r = 0.53 to 0.56; P < 0.05), and waking cortisol (r = 0.49 to 0.64; P < 0.05). CONCLUSIONS: Mild OSA is common in pregnant women with obesity and correlated with increased glycemic profiles, fFFAs, and estimates of hepatic IR. OSA is a potentially treatable target to optimize maternal glycemia and metabolism, fetal fuel supply, and pregnancy outcomes.

Postprandial Triglycerides Predict Newborn Fat More Strongly than Glucose in Women with Obesity in Early Pregnancy.

OBJECTIVE: Maternal obesity (OB) accounts for the majority of large-for-gestational-age infants, and newborn percent fat (NB%fat) correlates strongest with childhood OB. In addition to maternal glucose, fasting triglycerides (TGs) may contribute, but postprandial triglycerides (PPTGs) are unstudied. It was hypothesized that fasting TGs and PPTGs are higher in women with OB compared with women with normal weight (NW) throughout pregnancy, correlate more strongly with NB%fat than glucose, and may relate to dietary chylomicron TGs. METHODS: Fasting TGs and PPTGs, free fatty acids, glucose, and insulin were prospectively measured 10 times over 4 hours after a controlled liquid breakfast early (14-16 weeks) and later (26-28 weeks) in pregnancy in 27 mothers with NW and 27 with OB. NB%fat was measured by dual x-ray absorptometry. RESULTS: Fasting TGs and PPTGs were already ≥ 30% higher in mothers with OB at 14 to 16 weeks (P < 0.001) versus mothers with NW. In mothers with OB, a simple 1-hour (r = 0.71; P < 0.01) or 2-hour (r = 0.69; P < 0.01) PPTG at 14 to 16 weeks correlated strongest with NB%fat. In mothers with NW, the increase in TGs from early to later pregnancy correlated strongest with NB%fat (r = 0.57; P < 0.01). Maternal glucose did not statistically add to prediction models. CONCLUSIONS: These novel data suggest that 1- or 2-hour PPTGs might be a new target for early intervention in pregnancies with OB to prevent excess newborn adiposity and attenuate child OB risk.