Monday, November 02, 2009

Book Review: Dan Hurley's book "Diabetes Rising" Disappoints (Just a Little)

I picked up an advanced copy of the book "Diabetes Rising" by Dan Hurley. I'm fortunate to live in the center of U.S. publishing, New York City, so there are many bookstores in town which have dozens of advanced copies of books which are sold as used -- I only paid $5 for a book with a list price of $26.95, although the book clearly states: "This is an advanced uncorrected proof. Please do not quote for publicity or publication without checking against the finished book. Not for reseale." (Since it was resold, I have few reservations about quoting from the advanced copy of the book, besides I can be a more objective reviewer this way) I bought an advanced copy well in advance of the official January 2010 release date, and many of the NYC bookstores will also sell to anyone with internet access, FYI). Amy Tenderich reviewed and subsequently interviewed the author back in September (see here, here and here).

After reading Amy's reviews, I was actually optimistic that this book would be along the lines of James Hirsch's "Cheating Destiny: Living With Diabetes, America's Biggest Epidemic" and take Hirsch's book to a new level. Hirsch's book, which IMHO is a very well-written account not so much about diabetes exclusively, but the state of the U.S. healthcare "system" (a term I use very loosely, because its really not so much a system as a collection of different interests that lack any sort of coordination at all) and how that "system", which was really built to address acute illnesses effectively short-changes patients with chronic illnesses in the process, and chronic illnesses are becoming ever more widespread in American society thanks to medicine transforming a number of formerly deadly diseases into chronic illnesses that have to be managed, rather than cured.

Anyway, with Mr. Hurley's book "Diabetes Rising", I was a bit disappointed, and I really wanted to LOVE this book. I didn't love this book. I didn't hate it, either, but I had a mixed opinion overall. I feel that the amount I paid for the book ($5) was worth it, but if I'd paid the list price ($26.95), I might have felt I'd been ripped off. Why? I was most struck by a few issues.

Issue #1: Too Much Coverage of Topics Which Aren't Interesting Reading

The first issue is that the author dedicates the first third of the book to the history of diabetes, along with countless factoids and statistics about the history and prevalence (the "Rising") of diabetes and the author's theories behind the growth of diabetes. Although interesting (Hurley is a good reporter), it does not add much to the story, I'm afraid. My impression that that this was kind of an effort to try and build a case for why diabetes should be cured as opposed to giving it chronic treatment without a cure, as is the case today. The author's writing style is interesting, but I have to admit that I found this section incredibly boring, and the information, while accurate, failed to convince me -- and I actually live with type 1 diabetes! I thought "Gee, if he can't win my support, then I question whether this book will help to convince policymakers and healthcare leaders?" He spent far too much time on this subject, which in my honest opinion, really wasn't necessary, but did increase the annoyance factor.

A lot of the time, he talks about diabetes collectively (type 1 and type 2) and that's part of the problem, although he clearly notes the differences when relevant. But the overwhelming consensus is that aside from sharing a similar similar name (due to an inaccurate historical medical assumption that it was, in fact, the same illness), but cures will likely require a very different approach for each type of diabetes thanks to the distinct and different underlying etiologies for both type 1 and type 2 diabetes. From my perspective, this part of the book was really a lost opportunity to make a more compelling case for why it makes sense to cure rather than continue treating diabetes, and from my perspective could have been addressed more succinctly. I sooooo wanted to skip ahead, but instead, I kept reading, but did not enjoy this section and really had to struggle not to skip ahead. It was like re-reading all the other annoying books diabetes, but I did not find this section enlightening or entertaining, just annoying.

By comparison, Jim Hirsch's book combined his own personal experience weaved together with actual facts makes for a more compelling and interesting story than Dan Hurley's does, which is written more as a third-party observer. Incidentally, if it wasn't in the forward section, throughout the entire first section, we'd hardly even know that Dan Hurley himself has type 1 diabetes. I can't be too critical, that's usually the way I write, too, except that I haven't been published. But I'll take that as a note should I ever decide to write a book that personal stories add infinitely to the credibility and readability to the story.

Issue #2: Too Much Focus on Disputed Theories Behind the Cause of Diabetes

The second key issue for me was addressed mainly in the next section of the book, which looks into the "Reasons" (hypotheses for what causes diabetes). In this section, Mr. Hurley focuses on a handful of theories (and they're are all just theories right now), but there is almost no justification for his selection of the particular theories he's selected, rather the reader is supposed to trust the author and those he's interviewed have made the correct assumptions. But faith in the author alone doesn't work for me.

This is, perhaps, my biggest gripe about the book.

First, I disagree with his selection of several theories, in part, because the logic behind why he chose those theories is a complete mystery, and the theories themselves are hardly the consensus view, and the evidence he presents is, in many cases, disputed.

One theory he posits, the so-called "Accelerator Hypothesis" (the word "hypothesis" should tell you something) which is summed up very succinctly in the journal Diabetes Care (published by the American Diabetes Association). I already wrote about this theory back on July 14, 2008, in which I called attention to that particular hypothesis' shortcomings, so my disdain for that particular theory is hardly new. Also, I don't need to tell anyone that the ADA's journals have been repeatedly subject to claims of lack of objectivity, occasional impropriety and frequent conflicts-of-interest among many of the journal's submissions, and while focused exclusively on diabetes, they remain less objective, than say, The New England Journal of Medicine or The Lancet would be. But beyond citing less credible sources (or certainly ones regarded as less subject to dispute), and the Accelerator Hypothesis is among the most provocative but disputed and contested theories even among diabetes researchers. When that theory first came out in 2003, I immediately questioned the core logic, and over the next few years, I read study after study which disputed various elements of the Accelerator Hypothesis.

In fact, Mr. Hurley spends considerable effort trying to build support for the Accelerator Hypothesis, and presents like it's presumed (or should be presumed) to be fact. My take on it is that the Accelerator Hypothesis predicts earlier diabetes onset in heavier and/or taller people, without necessarily a change in risk, and views type 1 and type 2 diabetes as the same disorder of insulin resistance, set against different genetic backgrounds. But the authors of that theory admit that most diabetes registries fail to track adults along with children, leaving them with little to substantiate their theory. But the basic logic is that if the age of diagnosis is becoming lower, there must be a reason; hence, the Accelerator Hypothesis. Early weight gain and increasing BMI of young children may lead to increased insulin resistance and an earlier destruction of pancreatic beta cells in a person who may be genetically predetermined to develop diabetes. But they fail to address the issue of autoimmunity and many doctors are left questioning the core logic behind the theory of insulin resistance based on basic dosage requirements among patients with type 1 relative to those with type 2, which are considerably smaller on a per kilogram basis, suggesting that insulin resistance is not the problem in type 1, insulin insufficiency caused by an autoimmune response is. Unfortunately, the authors of this theory also note that relatively few of the children in their own sample were overweight, raising even questions on the basic argument of the theory, as well as many other shortcomings. I find the use of largely disputed evidence to be perhaps the most troubling aspect of the book.

But this is not limited to the Accelerator Hypothesis alone. He also presents a few other theories, such as the Sunshine Hypothesis, also known as the Vitamin D hypothesis. Again, his selection of this particular theory is questionable or debatable, in part, because Vitamin D is among the most supplemented vitamins anywhere, although there are questions as to whether there's a legitimate difference between the vitamin D attained from the sun and the man-made supplements that exist in everyday foods. Unfortunately, hard evidence showing that low levels of vitamin D lead to disease or that high levels of Vitamin D prevent it are almost completely lacking, although it's presently a burgeoning area of research. As I've reported in the past, some (not necessarily the mainstream) organizations, such as the California-based Autoimmunity Research Foundation, posit just the opposite: that excessive amounts of vitamin D actually leads to an increase in a host of different autoimmune diseases, including type 1 diabetes mellitus. As I noted, that is subject to dispute as well, but exactly how much vitamin D children and adults should get, and defining when they are deficient, is also under widespread debate. Doctors use different definitions, and many are waiting for "official" guidance on the subject expected in an Institute of Medicine report on vitamin D which is due out in 2010. The institute is a government advisory group that sets dietary standards. (Author P.S.: On November 30, 2010, the IOM determined that too much vitamin D can indeed be counterproductive, see HERE for detail.) But to select this hypothesis, which is also subject to such widespread uncertainty, raises questions in my mind, but fails to answer anything for me.

The Cow's Milk Hypothesis, which asserts that giving babies cow's milk-based foods too early in life is what wreaks havoc on the immune system, is a somewhat more logical theory, but remains only a theory that has already been dismissed by some, although other studies seem to back this theory up. But if I were to make an argument on the reasons behind the rise of diabetes, I would try to choose some theories that were not the subject of such widespread conflicting evidence.

About the ONLY hypothesis Mr. Hurley presents as contributing to the rise of diabetes that I can even rest comfortably with is the POP (Persistent Organic Pollutants) Hypothesis, which assumes that man-made environmental toxins may be the cause. But an interesting and unexplained paradox of this theory is that many countries with the most pollutants on earth, such as China, also have some of the lowest incidences of type 1 diabetes anywhere on the planet. A more compelling argument might be made for a combination of different theories, rather than taking any of these unproven theories by themselves. Take the POP Hypothesis combined with the hygiene hypothesis, which Mr. Hurley fails to even address (even though it's perhaps among the most logical and least disputed theories around) is that when children are exposed to many viruses, bacteria, etc. at an early age, their immune systems are better able to distinguish "self" from "non-self", so kids growing up in say China, have immune systems that are less likely to attack themselves and cause type 1 diabetes than kids in places like Finland or Sweden, two countries that are really, really clean and affluent.

But even if these theories collectively make sense, the POP Hypothesis also remains one of the few theories where the resolution is perfectly clear. The problem is that world lacks any collective willingness to effectively address the problem. With that being the case, why spend so much time writing about it, when one country cannot do it alone (and often, the U.S. has been among the least willing countries to cooperate)? All of these strikes me as somewhat irrelevant to the case to be made as to why diabetes should actually be cured rather than maintaining the status quo, although he does raise a number of compelling arguments why treatment alone is insufficient.

But all of the theories "Diabetes Rising" presents, even if they are in dispute, also raise questions as to what relevance they even have on the current situation? Again, he spent a lot of time on this particular issue, and much more than I thought was really necessary.

Issue #3: A Lost Opportunity?

The core issue is that diabetes is extremely costly to treat using current methods, and the incidence of all types of diabetes is rising rapidly worldwide, which spells trouble. The sad fact is that we cannot prevent ourselves out of an epidemic already underway, its already a day late and a dollar short for that, something Hurley fails to even address. Therefore, the challenge is for society to evaluate the continued and growing cost of investments made in treating the disease relative to investments in finding cures for the disease. At present, investments in treatment relative to cures are about 500 times higher than cure-related research. That should, in theory, make curing diabetes easier to justify, and he should spend more time talking about misplaced research priorities in diabetes and why that is a poor use for limited research dollars, but he really doesn't spend much effort or focus on doing so, and I think misses a huge opportunity for what could have been a truly "epic" book as his publicist refers to it. Instead, I see it as yet another tome about diabetes that could have met the description, but instead misses the mark on several levels.

Positives: Coverage of Cure-Related Research & Progress

The third section of the book talks about what he suggests are the "Remedies" (theories that might lead to a cure). I would believe this section is the most interesting, most logical and best-written, and my preference would have been for him to spend far more time and effort to beef this section up, rather than having spent so much time and effort on the rising and even the reasons for the growth in all types of diabetes. This section, in my opinion, gets too little attention and detail, and again, contributes to a book that is less balanced overall.

For example, he talks somewhat about what he refers to as a "computer cure" (meaning the artificial pancreas) in which the author Dan Hurley himself was in a clinical study organized by the JDRF. ("For 15 hours, I was no longer diabetic," he wrote, and he also lamented about how the FDA has consistently dragged its feet on approving a simple but key feature: automatic shut-off for a combined glucose-insulin system that detects a low). Of course, he does not address the fact that the reliability of these devices is widely regarded as insufficient, and he also fails to address the tests that JDRF-funded researchers at Boston University (see JDRF's March 2007 Frontline for details) have done on combining insulin and glucagon in the same device, which I would call a significant research oversight on this very subject. JDRF's Aaron Kowalski was interviewed, and I think Aaron is a great personality who adds a great perspective (both Aaron, and his brother have type 1, and Aaron's brother suffers from hypoglycemia unawareness) so his perspective is very valuable to this topic.

It is in this section where Hurley is at his best, weaving parts of his own personal story in with the facts makes it much more interesting reading. But I also feel that Mr. Hurley does disjustice (is that even a word?) to the discussion on the controversy over bariatric surgery as surgical cure for type 2 diabetes, with an inappropriate comment "By golly, it works". Aside from the problems with this surgery, I think he places too much faith in a handful of studies undertaken by doctors who stand to benefit the most by performing this surgery, when, in fact, it's very radical surgery and not without risks (although he does nothing to address the risk of doing nothing as a point of comparison). Again, if he had focused only on type 1, that would be a non-issue, and I believe the subject of type 2 has less relevance to this book as an overview of the situation. Again, self-management pertains to both, but Hurley has no real expertise on the subject of type 2 and I don't think these two always fit together unless it's in the context of public policy and the tendency to blame the patient rather than the disease itself.

I did LOVE Hurley's personal observation on insulin pumps and closed-loop systems:

"I finally decided to go on a pump in 1999, after my insurance company agreed to pay much of the cost. On balance, I found it made life easier by allowing me to make minor adjustments in my insulin rates on the fly, but resulted in little change to my A1C numbers. And my lows remained every bit as common as my highs. Essentially, it was just another way, albeit incrementally better, to get the same old insulin I'd always used. And while friends and family often assumed that the pump worked like an artificial pancreas, giving me only as much insulin as I needed, in fact, it was as dumb as a brick, following only the instructions I gave it."

Finally, in the section which he describes as a "Biological Cure", he does address some of the potential autoimmunity treatments including lengthy coverage of teplizumab which is being developed by Macrogenics in combination with Eli Lilly & Co. thanks to a partnership facilitated by JDRF, but doesn't do sufficient (actually any) justice to the legitimate concerns about related to adverse effects. For example, I am fond of the quote of my friend Ellen Ullman, who wrote:

"Dr. Harlan from NIH wisely pointed out at Children Wtih Diabetes Friends For Life Conference that the anti-cd3 drugs [which includes teplizumab] can cause recurrent mononucleosis which can increase one's propensity to develop lymphoma. Why would someone put their child at risk for that simply for a year and a half of extended honeymoon?"

Of course, there are several other similar treatments now in late-stage clinical trials, included one by Tolerx, Inc. and GlaxoSmithKline called otelixizumab. In fact, Tolerx's CEO Doug Ringler's blog called "The Green Chair" recently wrote a posting entitled "Dose Optimization Presentations On Otelixizumab: Finally!" suggesting that the GSK/Tolerx treatment is further along in development that the Lilly/Macrogenics treatment teplizumab is. Whether that is true remains to be seen, it could just be that Tolerx is more forthcoming that Macrogenics is.

Still others have a few other products being tested, among them, including Denise Faustman's use of the BCG vaccine. Whether any of these treatments will work long-term in patients remains to be seen, and the adverse events, especially with repeated, long-term usage, remain hurdles that are worthy of further exploration. But as noted, I don't believe this section got the attention it really deserved, and this is an area patients with diabetes really want to know about. But he did spend too much time talking about stuff that many of us really don't care about.

Having said all of this, I DON'T want to give the impression that I completely disliked the book, or that I think it is poorly written.

Quite the contrary.

I believe Dan Hurley does an excellent job of researching those topics he chooses to focus on. My issue is that I think he focuses on some (OK, many) areas that I don't happen to agree with. That doesn't mean he's done a bad job. In fact, he writes in a manner that might make someone really believe the stuff he's written, which I think is part of the problem. I wouldn't want someone to walk into Barnes & Noble, pick this book up, and believe that he's answered everything, because he most certainly hasn't. As with anything, there are two sides to every story, and I believe he's done a good job of presenting one side of the facts. But as I am fond of saying, that might be "selective disclosure of the truth". Is it wrong? No. Is it always a fair representation of the facts? No, but it's a book, so it doesn't have to. Is it an interesting read? Certainly.

One thing I must give Mr. Hurley credit for is that he writes well, in a manner that is very readable and he does know how to interview (or give the impression when he hasn't interviewed) on various subjects all within the context of the subject he covers. He's obviously an experienced journalist.

I also agree wholeheartedly with his conclusion:

"But it's just as clear ... that focusing on personal responsibility alone has not stopped, and will never stop, the rise of diabetes. Something more is needed; recognition that forces beyond the individual's control are at play, and that united action is necessary to face down what is a public, and therefore political, danger to our well-being, and to the well-being of our children."

He probably could have dedicated an entire chapter to that subject, but only touches upon it, which is IMHO, another lost opportunity.

My Conclusion: A Good, But Not A GREAT, Book About Diabetes

My conclusion is that Mr. Hurley and his editor have chosen to focus on on certain topics, and he does present those subjects well. In fact, they are presented too well, so that an uninformed reader might reach the wrong conclusion about those topics. There's no shortage of opinion about the causes behind diabetes, or what to do about it. I just disagree with his theories on the causes. But I DO like his book overall, but I think he could cover some subjects in more depth and spends way too much time on some subjects that aren't really necessary. That doesn't make it a bad book; the goal of the publisher is to sell books, not be a balanced story. In fact, the book is quite well-written and researched, and the length is about right, I only wish he'd dedicated more time to certain content, and far less to other content.

"Diabetes Rising" is definitely worth reading, and there's definitely a big shortage of writing about diabetes. In spite of the amazing growth in diabetes prevalence, diabetes gets far less publishing coverage, than say, cancer, which has sooo many books, and too many of the diabetes books are about diet and cooking. I would have liked Mr. Hurley to focus more in-depth on topics where there's a genuine lack of coverage (such as cure-related research and progress being made there), and focus far less on those topics where there's no lack of coverage on (such as the disease history and prevalence of diabetes, both topics have been beaten to death by the press).

While I hope that Diabetes Rising sells well (because a success will pave the way for more to be written on this subject). Too often, books on the subject of diabetes don't sell well, which tells the publishing industry that its a subject that does not deserve more attention. Nothing could be further from the truth. We need more, much more to be written on the topic of diabetes, and some of that's because the books which have been written on diabetes have been poorly chosen. "Diabetes Rising" is definitely worthy of being published, and deserves to be a hit with booksellers. But my recommendation is NOT to buy the book at that ridiculous list price (maybe read your library's copy instead). Diabetes Rising a good book, but not a great book about diabetes.


Unknown said...

Hi Scott,

Hmm, I do agree with your criticisms about the author devoting too much time/effort to the history and theories in this book.

And yet, I didn't believe the book was meant to draw us in so emotionally as Jim Hirsch's book did. Dan Hurley is much more of an old school journalist type. What he does, he does well.

I think he was trying to reach beyond the passionate patient community with this book. I guess the question is: will it inspire passion in anyone? Sounds like you don't think so...

Scott S said...

Hi Amy, I agree with you in that Hurley's writing style is more journalistic, and less personal than Jim Hirsch's book. But when I look at the parts of Hurley's book I really liked, it was the sections where he includes his personal experience on a given topic. As for whether it will inspire passion, I'm not sure ... the question for me is what KIND of passion will it inspire; I don't sense that readers will feel compelled to see diabetes cured based on this, and as noted, I think that's really a lost opportunity. If he(we) can shift the opinion away from continued tolerance for diabetes and more towards curing the disease, then the book can truly be 'epic'. I'm just not certain it IS epic. I liked the book, but as noted, I didn't LOVE the book -- and I really wanted to!!

Melissa Lee said...

I'm only about 2/3rds of the way through the advance copy, but I personally enjoyed all the history. While I've seen similar details scattered throughout other sources over the years, he weaved it together well and I found myself engrossed in it.

There were two quotes that I had to highlight in my copy and share with friends. One was his description of diabetes as a crying infant that can't be soothed, and the other was his bit about how trying to gauge the rise on his cgms and dose accordingly was like aiming for a postage stamp in Panama. I loved that. He has a few really nice turns of phrase, in other words.

I do agree with you, Scott, on his odd choice of hypotheses to include. I, too, felt they were controversial and that he showed bias toward the accelerator theory.

Colleen said...

Thanks for an additional perspective! And a very well thought out one at that. Sparking debate is an important quality in a book, so I'll be very intrigued to assess it myself once my library gets it.

Catherine said...

I was a patient in a teplixumab study in 2001 (back before it had that name) -- i.e. the one that made huge waves in 2002 in the NEJM -- and just had a long conversation last night with a doctor who's an expert in the drug. While it's true that there have been a few reported cases of mono cropping up as a result of the drug, overall the side effects have been quite minimal. (My personal experience involved a very brief drop in my blood pressure and some mild peeling on my palms -- a reaction, I was told, that's thought to be associated with the same part of the immune system they're trying to target.) The doctor I spoke with said that now that the drug is in phase 3 trials, they're expecting to see more incidences of opportunistic infections as a result of the treatment, but that he doubts they'll be serious or common enough to prevent the medication from being approved. Remember, these anti-cd3 drugs are not long-term medications. You get them for one (maybe two) courses of treatment, they primarily affect only the particular cytotoxic cells that are going after your islets [all t cells have cd-3 receptors, but for some reason the drug is more active against the ones that are on the attack], and your white blood cells are back to normal within a couple weeks.

As for the idea that it only lasts for a year and a half, my personal experience has been quite different: I got the drug nearly nine years ago and am still producing a measurable amount of insulin.(I did a follow-up mixed meal tolerance test this summer, so I know this for certain.) What's more, two years out, my insulin production had actually increased. While I'm still reliant on insulin -- and my diabetes is a pain in the ass to deal with -- I know that it's much better than it would have been had I not taken the drug.

Lastly, one of the most exciting potential uses for this kind of drug is not just to prolong the honeymoon, but rather to use it in combination with other drugs -- or potentially stem cell transplants -- to treat (or maybe cure) diabetes. For example, Jeff Bluestone at UCSF and a company called Novocell just (as of oct 28) got a $20 million grant to pursue just that -- novocell is working on developing islet cells from embryonic stem cells and bluestone, the man who created the original anti-cd3 drug (now known as teplixumab), is working on tolerance.

Sorry for the long post -- I just wanted to give a bit more perspective on the study. (Also, I've read Hurley's book, too, and thought that while certain parts did drag a bit, overall it was quite good. Definitely would recommend it. And I loved the crying baby line, too.)

Anonymous said...

Scott: The statement that Teplizumab produces 1 1/2 year of extended honeymoon (and thus is not worth for the alleged risks of the treatment), was correct when the results of the trial weren't older than 1 1/2 years. There is quite more data now, and one of the last papers states "up to five years", because that's the span of time that was covered with the papers' patients. I'm glad to read Catherine post, because I'm involved in the trial, and barring the fears that something can happen in the future (I keep in mind that it is not the 150 year old aspirin, though there are no reports of anything too bad in the past, and zero dead people), we are frankly quite happy with it. Unfortunately, mab therapies seem to be exposed to rather subjective judgments for what they could possibly do in the future under the right set of circumstances, rather than being assessed for what they did in the past and the present available data.

Lee Ann Thill said...

I don't see myself reading it because it just doesn't sound like something in which I could get engaged (too much biology - I'm more a social sciences kind of girl), but I'm glad to catch reviews of it, especially yours as it's very thorough and well-considered. I'll actually be meeting Hurley tomorrow, so I'm grateful i caught this as I now know way more about his book than I would have otherwise.

And I will definitely agree with you that weaving some personal stories into a book like this significantly increases the readability, IMO.

Sarah Howard said...

I haven't read the book yet, but am interested in the link between type 1 and environmental contaminants. And that deserves more press, so I'm happy it's in this book.

Regarding your comments on China: people in developing countries actually have much lower levels of contaminants in their bodies than those of us in developed countries. Levels are rising everywhere (of both type 1 and contaminants), but China is only recently developing, so you may see more type 1 cases show up in the future. Whereas here in the US, for example, we have higher levels of many more (ie hundreds) of contaminants. In developing countries, they may have higher levels of DDT or one or two others, but generally not as many in combination.

I find it interesting that persistent organic pollutants migrate to the polar areas of the earth, where type 1 levels are higher. And interestingly, some can interfere with vitamin D production. Not to mention hormones-- also relevant in type 1.

Not only that, but contaminants may have an effect later in life after exposure in utero, or even in subsequent generations, which is rather scary as well has difficult to study.

Another book, "The Autoimmune Epidemic" talks about this in more detail.