Doves, Diplomats, and Diabetes

In the past I have criticized evolutionary medicine for its tendency to rely on unverifiable “Just-So Stories,” but a new book has helped me appreciate what the best kind of evolutionary thinking can contribute to our understanding of medicine. Doves, Diplomats, and Diabetes: A Darwinian Interpretation of Type 2 Diabetes and Related Disorders by Milind Watve investigates diabetes from an evolutionary perspective, suggesting how it might have originated, why it persisted, and how it is related to survival advantages. Watve develops well-reasoned hypotheses that can be tested by examining their expected consequences. He believes it is impossible to understand metabolism without understanding behavioral ecology, and he makes a good case.

A reassessment of the evidence concerning Type II diabetes (T2D) reveals a number of paradoxes. Elevated blood glucose is the defining feature of T2D but controlling it doesn’t prevent all the complications of diabetes, and it doesn’t appear that elevated blood sugar could produce all the pathological changes of diabetes.  Insulin resistance is believed to be central to a cluster of deadly diseases in humans, but in other animals it has no adverse effects on health and even increases lifespan. Studying diabetes from an evolutionary perspective can shed light on such paradoxes.

Insulin resistance leads to type II diabetes and coronary heart disease. It is associated with obesity and is thought to have developed as a response to periodic starvation, but a close examination of the evidence really doesn’t support that interpretation. Instead, it may be a socio-ecological adaptation that mediates (1) a transition in reproductive strategy to a smaller number of offspring with larger investment in each, and (2) a transition from a relatively more muscle-dependent lifestyle to a more brain-dependent lifestyle (stronger to smarter, soldier to diplomat).

There is a mass of complex information in this book that I can’t hope to master. It runs 428 pages and is exhaustively referenced. I hesitated to write about it because I don’t think I can do it justice. I can only hope to present a simplified summary to whet the appetite of interested readers.

Old paradigm: Type I diabetes is a primary deficiency of insulin. Type II diabetes is a relative insulin deficiency.  It begins with insulin resistance that leads to increased production of insulin (hyperinsulinemia); eventually the pancreatic beta cells wear out and can no longer produce enough insulin to compensate for the increased insulin resistance. Then blood sugar rises and that causes inflammatory changes with damage to blood vessels, eyes, kidneys, and heart.  Obesity is thought to be a primary cause (along with a genetic predisposition), and as the incidence of obesity has increased, the incidence of diabetes has increased.

New paradigm:

  1. A plurality of behavioral strategies can exist in a population of animals, and a prominent dichotomy is between the hawks and the doves, between the soldier (physical strength and aggression) and the diplomat (cognitive abilities and social manipulation). The number of individuals following each strategy varies with environmental and social conditions.
  2. Behavior affects physiology. Numerous physiological adaptations support the different behavioral repertoires, and the diplomat option is accompanied by a divestment from muscle, an increase in visceral fat, elevated cholesterol, elevated insulin, and insulin resistance.
  3. Increased levels of insulin, cholesterol, leptin, and cortisol produce aggression suppression, physical risk aversion, and enhanced cognitive functions.
  4. Aggression anticipates injuries, and the soldier’s body prepares for wound healing; the diplomat’s body puts its resources elsewhere, and therefore becomes more susceptible to factors that tend to impair wound healing such as low-grade chronic inflammation and deficiency of many growth factors.
  5. Crowding in a population affects reproductive strategies, aggressive behavior, etc.
  6. Most of the complications of diabetes are due to growth factor deficiency, changes in immune response, oxidative stress, and angiogenesis dysfunction. Hyperglycemia aggravates these effects but is not the underlying cause.
  7. Beta cell degeneration is not due to the pancreas “wearing out” but to factors that may be reversible. Other body functions increase their response in the face of increased demand; they don’t “wear out” and stop responding. Something is going on here that we don’t understand.
  8. Insulin resistance can be decoupled from the mechanisms listed in 6, and it can promote health and longevity. It is not central to the pathology of diabetes.
  9. The rate of glucose transport from the brain capillaries affects plasma glucose levels. The key to glucose homeostasis is most likely to be found in the brain.
  10. Obesity is not central to T2D but is only a risk factor. It is associated with suppression of soldier behaviors, with two-way causality.
  11. Insulin sensitivity and insulin secretion respond to a large number of signaling molecules including sex hormones, endorphins, myokines, and many others. It’s fiendishly complicated.
  12. T2D is not primarily or mainly about insulin and glucose homeostasis.
  13. Glycemic control is not sufficient to prevent all the complications of diabetes.
  14. The pathophysiology of T2D originates from brain and behavior rather than from diet and energy imbalance.
  15. T2D is potentially curable.

What about obesity? Fat has multiple functions in the body. Obesity is an adaptation that favors survival through various mechanisms rather than the simplistic explanation of energy storage to buffer against periods of starvation.  Rather than obesity causing insulin resistance or insulin resistance causing obesity, there is likely a behavioral syndrome that precedes both; neuroendocrine processes driven by specific behavioral strategies may initiate pathways leading to obesity and T2D and the associated pathologies. Relative obesity is more important than absolute obesity: in countries where obesity is less prevalent, people become diabetic at lower BMI.

Watve introduces the concept of “behavioral deficiencies,” for instance of aggression, agility and rapid action, adventure, injury proneness, exposures to sun, weather, plants, microbes, and animals. He suggests that such behavioral deficiencies contribute to various diseases including cancer, skin disorders, hormonal dysfunctions, osteoporosis, chronic fatigue syndrome, depression, and various inflammatory conditions. He suggests that the typical exercise prescriptions are grossly inadequate, and that exercises should be designed specifically to supplement specific behavioral deficiencies.  Competitive sports probably do more good than treadmills.

Unfortunately the book is very expensive and is not likely to reach many of those who would benefit from it. The list price is $209, and $159 for the eBook version.  I didn’t know it or its author even existed until Watve e-mailed me out of the blue and kindly sent me the pdf. Its extensive references cover a broad gamut of scientific disciplines. I don’t feel qualified to judge how credible his hypotheses are, and I wish experts in the various fields could read the book, all put their heads together, and critique it more intelligently than I could hope to. I would love to see some of his research proposals carried out.

I wrote an article on “Bad Books” where I said:

There are two kinds of science book: one aims to educate the public by explaining the current state of evidence and the consensus of the scientific community. The other has an agenda: it uses (and mis-uses) science to persuade readers to believe something that the authors believe but that the scientific community as a whole has rejected.

This book doesn’t fall into either category. I don’t know whether its conclusions are correct, but I do know that its approach is unimpeachable. It epitomizes the best of scientific thinking. It doesn’t go beyond the evidence. It recognizes where the evidence is insufficient and how better evidence could be obtained by the proposed studies.

Watve is a professor of biology at the Indian Institute of Science Education and Research in Pune, India.  His home page says:

I specialize in not specializing. I used research more as a tool in education and tried to motivate undergraduates to identify novel problems and use a variety of tools to handle them including modeling, simulations, observations, surveys, meta-analysis, field experiments as well as lab experiments…there is a common theme that runs through all the work, the connecting thread being evolutionary biology.

He challenges his students to question everything they read in their textbooks and to examine the evidence behind the accepted wisdom. In the case of diabetes, the underlying evidence was marked by a number of flaws, paradoxes, anomalies, and contradictions. That eventually led to the present book. He located thousands of published studies from various fields and tried to evaluate the data with a fresh eye. He also had access to data from many unpublished studies. He located some fascinating evidence that directly contradicts the standard textbook story of T2D.

The best thing about this book is its humility. Instead of bragging that he has found “the answer,” he raises more questions. He suggests hypotheses that might better explain the known facts, and proposes specific experiments to test those hypotheses. He says the new paradigm answers more questions than the old one but is far from complete. He begs researchers to carry out the necessary experiments. He invites criticism from readers. He even includes an epilogue entitled “I May be Wrong After All!!” He is interested in finding the truth rather than vindicating his own ideas.

He says:

I keep the possibility open that I have actually got into a thinking trap from where it is really difficult to get out. But I would like someone to try and convince me that it is so. I tried doing it myself and it did not work…the possibility remains that I have made erroneous arguments out of inadequate knowledge of the field. I would be glad to correct myself if anyone points out specific problems in my way of thinking.

These are the words of a true scientist and a wise man. Whether or not you agree with his ideas, you have to respect Milind Watve’s approach. He sets a stellar example for every scientist and critical thinker to follow.

Posted in: Basic Science, Book & movie reviews, Evolution

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