How the November 3 Discussion Will Work

Submitted by Richard A. Aronson on Tuesday, 11/1/2011, at 10:39 AM

For November 3: Pretend that you are the author of the article that you reviewed and co-create a seminar at an actual conference!

In September 2010, Time Magazine featured an excerpt from a new book by Annie Murphy Paul called Fetal Origins: How the First Nine Months Shape Your Life. The book discusses the fetal origins of adult disease and features David Barker.

 Imagine that today is September 19, 2011. You are in Portland, Oregon, attending the 7th World Congress on Developmental Origins of Health and Disease, which is being held (really!) this year in Portland from September 18 to 21. Dr. Barker has just given a keynote presentation on the hypothesis that events during early development have a profound impact on one's risk for future adult disease. The focus of this year's conference is to explore what this concept means for addressing increasing rates of obesity, Type 2 Diabetes, and other chronic diseases throughout the world.

 Following Dr. Barker's presentation, you proceed to join a seminar on the stress of fetal starvation and its impact on adult health. The seminar includes an extensive discussion of an article by L.C. Matthews of the University of Manchester in England, "The stress of starvation: glucocorticoid restraint of beta cell development", recently published in the journal Diabetologia. The proceedings from this seminar, with recommendations for next steps, will be published in a future edition of the same journal, and several members of the press are covering the conference, including this seminar.

 The participants in the seminar include the primary authors of the articles cited in the Matthews article, of which you are one. To prepare for the seminar, the conference organizers asked you to consider the following questions and be  ready to discuss them:

 1. Did the Matthews article accurately cite your article? Explain why or why not.

2. Select one other key point from your article that you believe is important to share at the seminar,  an additional point beyond the content of the Matthews article that will enrich everyone’s understanding of the issue.

3. Pose one question, comment, or critique of the Matthews article that will add to the focus of the conference as a whole.

 For our class discussion on Thursday, November 3, carry out this seminar in real time  in other words, you are in Portland at the conference on September 19, and you are the actual author of the cited article that you reviewed for this class. Quickly decide on a facilitator, and start by introducing yourself as if you are, in fact the author of the article (If time allows, see what you can find out about your new self!)

The rest of the seminar is yours to create given the guidelines.

If you can't come to the evening session, we'll have a mini-seminar at 10 am.

 

Additional Points From October 27, 2011 Class

Submitted by Richard A. Aronson on Friday, 10/28/2011, at 11:58 AM

I’d like to clarify a few points and expand upon some questions that came up during our discussion classes on Thursday, October 27. Also, I posted the slides from my presentation on e-reserves, including the slide that wasn’t in the handout. I hope that these points will enrich next week’s discussion:

  1. Insulin Resistance Mechanisms: While low birth weight is clearly associated with insulin resistance, the search for a mechanism is evolving. Many investigators suggest that the pancreas is “programmed” resulting in decreased Beta-cell mass and function. The decrease in Beta-cell mass leads to decreased insulin secretion. Over time, fat and muscle cells become insulin resistant, leading eventually to Type 2 Diabetes (T2DM). In another model, deterioration in Beta-cell function is accompanied by mitochondrial dysfunction. When faced with undernutrition, cell division is slowed and cell function is altered.
  2. Fetal Insulin Hypothesis: While I focused on the Fetal Origins of Adult Disease (FOAD) hypothesis, an alternative hypothesis is called the fetal insulin hypothesis. T2DM is known to have a strong genetic component. Because insulin is key for fetal growth, any genetic variant that impairs insulin secretion may reduce birth weight and result in T2DM. According to this hypothesis, the genotype, not LBW, predisposes the baby to T2DM.
  3. Consequences of an Excessively High Fat, High Caloric Intake in Pregnancy: The question arose last night: What happens when there isn’t a nutritional mismatching between the fetal and extrauterine environment? When the mother consumes a McDonald’s-like fast food type diet during pregnancy and the offspring encounters a comparable nutritional environment outside of the womb, does that in some way “protect” the child from the increased likelihood of developing obesity, T2DM, coronary heart disease, etc.? The answer is no. Regardless of the mismatch concept and FOAD hypothesis, maternal obesity and consumption of an excessively high fat and high caloric intake in pregnancy puts the mother and her child at high risk for a variety of disorders, and doctors and other health providers should monitor and treat such patients with great care. These include, for the mother, gestational diabetes and other serious pregnancy complications; and, for the child, adverse birth outcomes resulting from such complications and the development of obesity early in life.
  4. Leptin: IUGR may also predispose the child to abnormally high leptin concentrations that represent a form of leptin resistance. Leptin concentrations correlate with satiety, and leptin resistance may further contribute to the development of T2DM in IUGR infants.
  5. Glucocorticoids and Autoimmune Disease: This also came up in last night’s discussion. In a certain kind of allostaic overload (not the primary model that we covered earlier), in which cortisol secretion does not increase in response to stress, secretion of inflammatory cytokines increases. The negative consequences of an enhanced inflammatory response as a result of increased cytokines may include autoimmune diseases.
  6. Historical Trauma: We discussed this in the morning class, but not at night. The Pima Indian Tribe in southern Arizona has one of the highest rates of T2DM in the U.S. and the world. The disease was virtually unknown there a century ago. During the 20th century, the diversion of river water to upstream white settlements severely disrupted the Pima’s agricultural economy and cultural traditions. The Pima Indians were plunged into poverty. This initially led to a period of undernutrition as they were unable to eat traditional foods such as beans and wild game. Eventually the U.S. government stepped in, and the tribe became dependent on surplus commodities like white flour, lard, processed cheese, and canned foods – a diabetic’s nightmare. Diabetes took hold, and the rates soared. Fortunately, as this has come to light, the tribe has succeeded in negotiating a large water settlement, and the Pima are beginning to return to farm again. However, this is an important example of how the toxic stress of historical trauma can harm human health across generations. One might conceive of how such trauma led to the surge in diabetes via both the FOAD and cortisol-mediated HPA Axis over activation mechanisms that we’ve discussed in this course.    

Alice Woolverton Source Choice

Submitted by Genevieve A. Woolverton on Thursday, 10/27/2011, at 8:09 PM

34- Impaired insulin secretion after prenatal exposure to the Dutch famine

Fabiana Kreines Source Choice

Submitted by Fabiana M. Kreines on Wednesday, 10/26/2011, at 5:30 PM

#36: Schacke H, Berger M, Rehwinkel H, Asadullah K (2007) Selective glucocorticoid receptor agonists (SEGRAs): novel ligands with an improved therapeutic index. Mol Cell Endocrinol 275:109-117

The stress of starvation: glucocorticoid restraint of beta cell development

Submitted by Patricia B. O'Hara on Monday, 10/24/2011, at 9:28 AM
by L. C. Matthews and N. A. Hanley

Diabetologia. 2011 February; 54(2): 223–226.
Published online 2010 November 12. doi:  10.1007/s00125-010-1963-x

For Thursday, 10.27.11, read this short review article and look through some of the references contained there-in.  By Thursday, we will ask each of you to choose one article from the references to further research regarding the effect of fetal starvation on future adult diseases.   If you can already identify a particular reference you wish to explore, claim it in the response column for the Stress and Starve found here.  By Thursday 11.03.11, post a short viewpoint (250 words or less) in which the biochemistry of fetal starvation is linked to adult disease. 

For our discussion Thursday, 10.27.11, in addition to reviewing this article, we will go over your responses to the last question on the mid-term exame. It was interesting to see what each of you focused on and how you framed your response. It will be creative to share your perspective.

Also, we'll talk briefly about the WIC (Women, Infants, and Children) Program for pregnant and post-partum women  and young children, about prenatal coordination, and other efforts to reduce stress during rpegnancy.