A mind is a terrible thing to lose ..

[DianaCox]

I KNOW I saw an article and/or a post about the outcomes of the children of woman who had malabsorptive bariatric surgery (maybe even DS) before pregnancy being better than obese women. But I can't find it! I'm usually a master of Google-Fu, but I'm getting very frustrated at not being able to find it.

HELP! I'm trying to write to the author of this article and ask her if she knows about the other study, because I think it's important.
http://www.abstractsonline.com/pp8/#!/3699/presentation/9097

381-OR - Human Mesenchymal Stem Cells from Offspring of Obese Mothers Have Increased Adipogenesis and Evidence for Insulin Resistance: The Healthy Start Study
Itinerary
June 9, 2015, 11:00 - 11:15 AM
Authors
KRISTEN E. BOYLE, ZACHARY PATINKIN, ALLISON L. B. SHAPIRO, DANA DABELEA, JACOB E. (JED). FRIEDMAN, Aurora, CO
Disclosures
K.E. Boyle: None. Z. Patinkin: None. A.L. Shapiro: None. D. Dabelea: None. J.E. Friedman: None.
Maternal obesity may fundamentally change offspring risk for metabolic disease in later life, though the molecular mechanisms in human infants are poorly understood. We tested the novel hypothesis that mesenchymal stem cells (MSCs) derived from umbilical cord tissue of babies born to obese mothers would exhibit increased adipogenesis and decreased myogenesis in culture, and would show evidence for insulin resistance when differentiated to myocytes. MSCs were cultured from term (39.9 ± 0.2 wk) infants born to obese mothers (Ob MSC, n=12; pre-pregnancy (pp)BMI = 35.1 ± 1.3 kg/m2) or to normal weight mothers (NW MSC, n=12; ppBMI = 21.2 ± 0.3 kg/m2) participating in the Healthy Start Study. Prior to differentiation, Ob MSCs expressed 2-fold greater CD13, a cell surface marker linked with increased adipogenesis (P<0.05). MSCs were then differentiated to either adipocytes or myocytes for 21d and protein markers of adipogenesis (peroxisome proliferator-activated receptor [PPAR]γ) or myogenesis (myosin heavy chain [MHC]) were measured. Cells were stained with Oil Red O (ORO) to assess lipid accumulation. When differentiated to adipocytes, Ob MSCs expressed 50% more PPARγ protein content than NW MSCs (P<0.05). When the MSCs were differentiated to myocytes, there were no differences in MHC content, though ORO indicated a 50% higher lipid content in the Ob MSCs (P<0.05). In a subset of subjects (n=4-5/group) we observed lower mRNA content of the methylation/demethylation enzymes DNA methyltransferase 1 and lysine-specific demethylase 6A in Ob MSCs (-35%, P=0.06 and -40%, P<0.05; respectively). mRNA content of glucose transporter (GLUT)4 was 60% lower in Ob MSCs (P<0.05) and inversely correlated with ppBMI (r2=0.52, P<0.05). Our data suggest an inherent propensity for adipogenesis in Ob MSCs. Greater lipid content and reduced GLUT4 in myogenic Ob MSCs also suggest a programmed risk for insulin resistance that may be under epigenetic control.

 

[DianaCox]

Geez looeze - I'm losing my mind. I found the article, but it was something I had written to Marceau about MYOWNSELF, and never posted it (I don't think):
http://press.endocrine.org/doi/10.1...d=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed&

Discussion

Our results have three major implications by demonstrating 1) the importance of the intrauterine environment in the transmission of obesity and metabolic derangements; 2) the potentially epigenetic nature of severe obesity, which might provide encouragement to patients who are often blamed; and 3) the importance of providing special perinatal weight control in severely obese women as a tool to curb the present obesity epidemic (23, 24).

The etiology of obesity has been under intense scrutiny for the past several decades, yet the large amount of research has yielded little practical advice to those who are overweight (25). Emerging results, including data presented in this paper, provide further insight into the causes of obesity and offers potential preventative measures.

Obesity clusters within families and recent data show that this is not just due to traditional genetic transmission or similar familial environments but may also be due to epigenetic factors (26). The presence of obesity and accompanying metabolic derangements, especially insulin resistance, during pregnancy have been shown to transmit or imprint characteristics in offspring in numerous animal studies (27, 28, 29). Evaluating humans presents ethical and practical difficulties resulting in fewer available data. To our knowledge, our paper is the first to evaluate dramatic maternal weight loss and metabolic improvements on anthropometric and metabolic parameters in children.

Our population of children was not a randomly selected group: they were all born to severely obese and overweight mothers, even those born after maternal BPD. Whereas the mothers lost a clinically significant amount of weight after BPD, the average BMI postoperatively (30.7 ± 0.9 kg/m2) was still within the obese category (25). What is striking is that the insulin, glucose, and lipid parameters and adipokine levels reached to ranges for healthy lean individuals (13, 15) and improvements persisted over time. These metabolic changes translated into a large impact on offspring both metabolically and in prevalence of obesity.

The 3-fold decrease in the presence of severe obesity, as defined by age- and gender-adjusted parameters, in AMS children was striking. Whereas BMS children were older, both younger and older children were represented in the three body weight categories. In addition, we also confirmed changes in body weight status using several different age- and gender-adjusted anthropometric parameters and found similar results. Furthermore, whereas many of the parameters correlated both with age as well as body size (as evaluated by BMI z-score), multiple regression analysis indicated that the body size parameters played a much stronger predictive role.

Importantly, these differences were present right from birth: AMS children had a lower birth weight. Macrosomia was reduced, but prevalence of low birth weight was unchanged. Whereas initial studies on in utero environment observed that low-birth weight babies were more likely to become obese and insulin resistant as adults (30, 31), macrosomia is also related to increased obesity risk and insulin resistance (2). One of the greatest risk factors for macrosomia is gestational diabetes mellitus (2). These insightful observational human studies led to mechanistic animal studies showing that DNA modification during development alters future gene expression both centrally and peripherally and affects food preference, satiety, energy expenditure, spontaneous activity, and substrate storage vs. oxidation (26, 27, 28, 29,32). These mechanisms likely contribute to the changes noted in our study.

In addition to the dramatic anthropometric changes, numerous metabolic improvements in AMS children were noted including markers of insulin sensitivity. Dyslipidemias are an obesity comorbidity, and exposure time to deleterious lipid levels has an important impact on cardiovascular disease development (33). Not only did AMS children have improvements in lipid parameters including HDL-C and TC to HDL-C ratio, the lower TG and TC to HDL-C levels in SO AMS children compared with SO BMS children were improved more than could be explained based on body size. We conclude that severe obesity is higher in BMS children and that body weight or size differences alone were insufficient to explain the differences in insulin resistance and dyslipidemia between AMS and BMS children.

Obesity is a disease comprised of well-established facets (excess adipose tissue, defective insulin signaling, atherosclerosis) and more newly recognized facets (inflammation, altered adipose tissue function) (34). Measurements of clinically nontraditional markers involved in inflammation, energy substrate oxidation and storage, and hunger/satiety signals support our hypothesis that AMS children have a more favorable metabolic profile. AMS children had lower CRP, suggesting they have less chronic low-grade inflammation than is associated with obesity and insulin resistance (35). Higher leptin levels in BMS children also support a leptin-resistant state, common in obesity and insulin resistance (15). Furthermore, ghrelin, which decreases with obesity, was higher in AMS children relative to BMS (36).

Notwithstanding these striking results, the limitations of the study should be acknowledged. The groups of BMS and AMS children were comprised of both boys and girls and covered a wide age range. Furthermore, due to the sample size, partitioning into various gender- and age-matched groups was not practical. Analysis based on body size, using age- and gender-normalized BMI percentile or z-score, was chosen as the preferred analysis, and any differences according to age or gender were reported. In addition, we performed multiple regression analysis to better evaluate the impact of all parameters, including age. Furthermore, due to the nature of cross-sectional studies, direct cause and effect cannot be proven. Finally, we cannot specifically define the contributions that genetic and familial environment had vs. the impact of the in utero environment. We limited the influence of genetics and familial environment on our results by including as many siblings as possible.

These data have several important clinical implications. Severely obese women should be encouraged to lose weight before becoming pregnant; during pregnancy they should be encouraged to modify their weight gain. For those women interested in both a surgical treatment and having children, we believe surgery should be performed first. Second, we have shown that by reducing the exposure of fetuses to an obesigenic in utero environment, there is a dramatic decrease in the presence of severe obesity and accompanying metabolic disturbances in children. Because obese children often go on to become obese adults (37), exposing them to greater cumulative damage from years of metabolic derangements, these data emphasize how critical it is to prevent obesity and treat it effectively to prevent further transmission to future generations.

 

[aaa]

I remembered reading an article about this in the NYT a while ago and more recently. I found them. Link. Link.

 

[DianaCox]

Thanks - those were not about the study I was remembering, but also support the overall idea that WLS is in general (with proper nutrition) good for after-conceived babies. I was specifically looking for the study that addressed the obesity stats of post-WLS babies, which is the Marceau study.

 

[hilary1617]

While it may not be a direct connection, for sure, not being diabetic while pregnant is safer for babies and their moms. If WLS results in elimination or reduction in diabetes would that not be beneficial for future offspring?

I had gestational diabetes which was untreated for baby 1 (just below cutoff) and treated with insulin shots for baby 2. Baby 1 was subjected to frequent blood testing in his first few days of life as they were worried about potential for a blood sugar crash.... He is now overweight (though he was underweight until he went on steroids for asthma).