Tuesday, May 08, 2007

Making Light of Hypoglycemia

Some of my readers have probably gathered that I'm a HUGE cynic when it comes to diabetes research. This skepticism comes from experience, including decades of unfulfilled promises that were given to me (sadly, I continue to hear these) as a 7-year old child back in 1976 (some bi-centennial celebration, huh?) about how close they were to finding a cure. At this point in time, I can honestly say that while they are closer, I have little confidence I'll be cured unless I get a pancreas transplant. Also, I see millions wasted on stupid or unnecessary studies that keep researchers working yet provide little if any benefit to patients. Today, I continue to hear statements of unbridled (or is that irrational?) enthusiasm from parents of children with type 1 diabetes (who have several decades less experience than me) about the promise of Dr. Faustman's research, and frankly, its concerning.

Don't get me wrong, I think the approach Dr. Faustman is taking is absolutely the right way to go, but I'm also convinced that many are setting themselves up for a HUGE letdown if they don't look at it with at least a hint of skepticism. Its morally contemptible to set another generation up for such disappointment, however well-meaning the enthusiasm may be.

You will note that I haven't even mentioned treatment. That's probably because treatment today has fundamentally changed very little since insulin was discovered 85 years ago, at least according to Dr. C. Ronald Kahn, M.D., former President and Director Joslin Diabetes Center and Professor of Medicine at Harvard Medical School (see "Conquering Diabetes: A Strategic Plan for the 21st Century" report from the Congressionally-appointed Diabetes Working Group, p. 27).

I'll spare you a debate about insulin pumps and insulin analogs, but lets just say that besides home blood glucose testing (yes, I began this trip using Clinitest urine testing,) I make no reference to the so-called tremendous breakthroughs in treating type 1 diabetes because none of those "breakthroughs" have done much to life any easier than it was back in 1976, yet the trade-off imposed by treatment regimens in terms of psychological damage to patients has yet to be quantified.

So, you might be asking, what's today's diatribe all about?

Well, while I'm on the subject of unacknowledged psychological damage imposed by diabetes treatment, in the May 3, 2007 edition of The New England Journal of Medicine, there is an article about the Epidemiology of Diabetes Interventions and Complications study (EDIC), which was in reality not a new study, but yet another follow-up to the original Diabetes Complications and Control Trial (DCCT).

Naturally, the press picked the story up with quotes from the study's authors. One of those quotes was as follows:

"The EDIC study provides further support for the safety of intensive diabetes therapy and the benefits of maintaining good glycemic control," says the study's principal investigator, according to Alan M. Jacobson, M.D. (who serves on the medical boards for Pfizer and Amylin Pharmaceuticals), head of Joslin's Behavioral and Mental Health Research Section and Professor of Psychiatry at Harvard Medical School. Preliminary findings from the EDIC study were presented at the June 2006 Scientific Sessions of the American Diabetes Association. "While acute episodes of hypoglycemia can impair thinking and can even be life-threatening, type 1 diabetes patients do not have to worry that such episodes will impair their long-term abilities to perceive, reason and remember."

To paraphrase, "There's little need to worry about hypoglycemia, as it does no long-term brain damage. Its really just an inconvenience, so relax, current treatment is completely safe."

Safe? Vioxx had a better safety record than insulin. Even more troubling was the fact that 40% of the cohort of more than 1,000 patients reported having had at least 1 incident of hypoglycemic coma or seizure. That is noteworthy, yet somehow never made it into the press release. But the study's authors did conveniently note that in people who had higher blood glucose levels (or HbA1c levels above 8.8%), some experienced a marginal decline in 2 particular measures of cognitive ability, specifically in psychomotor efficiency by claiming that DCCT (reported in The New England Journal of Medicine) showed intensive control yields definitive proof of cardiovascular benefit, including statistically significant reductions in both heart attacks and strokes.

Diabetes Self-Management went even further, by stating that "These results show that consistently higher blood glucose levels appear [emphasis is mine] to be more of a threat to long-term brain function than occasional episodes of severe hypoglycemia," although at least they acknowledged the issue of hypoglycemia unawareness, which by some accounts, impacts as much as 10% of all patients with long-standing type 1 diabetes. The debate over whether high blood glucose levels is the cause, or merely a co-morbidity due to the disease itself has yet to be resolved.

But the most obvious question is if patients could always maintain ideal blood glucose levels, it would be similar to not being a diabetic, so isn't it obvious that doing so reduces (but unfortunately does not eliminate) complications, including cardiovascular damage? Why do we continue to study this question, rather than asking what's wrong with current treatments? As anyone with type 1 diabetes knows, its virtually impossible to always maintain euglycemic blood glucose levels with current treatment modalities, so what are they going to resolve that issue -- anything? I guess they would first have to acknowledge that a problem exists.

Less anyone overlook it, the DCCT reported that the incidence of severe hypoglycemia increased threefold in intensively treated patients. Less frequently acknowledged is the fact that the DCCT began in 1983 with only 278 participants and the first 2 years were devoted to planning and feasibility studies. Of the original 278 participants in the DCCT, 8 dropped out (3%) and 11 died (4%) caused in large part by severe hypoglycemia. Changes were subsequently made to the eligibility criteria for the full-scale trial to exclude anyone with this very common short-term issue with today's insulin replacement therapy, which raises questions about exactly how random the DCCT was. Further, it suggests that in spite of a statistically significant increase in the incidence, severe hypoglycemia remains severely underestimated as an "adverse effect" even today, especially considering that intensive treatment is now the standard treatment for virtually everyone with type 1 diabetes.

According to an October 18, 2006 study published in Journal of the American Medical Association (JAMA), an estimated 56,000 "adverse events" requiring patient emergency room treatment (most due to hypoglycemia) are reported each year, making insulin the medicine with the highest level of adverse effects. No other medicine even matches it!

To be fair, Catherine Cowie, Ph.D., who oversees EDIC for the NIH and one of the study's co-authors did acknowledge that "Hypoglycemia is a serious, frightening experience" she said. "However, given the importance of intensive blood glucose control in preventing the complications of diabetes, it is tremendously heartening to know that such episodes have no long-term cognitive effects in the age groups studied in the DCCT/EDIC." Also, the researchers did acknowledge that the limitations of the study included a lack of data for young children diagnosed with type 1 diabetes before they entered the study, the effect of intensive therapy on the elderly, or those living for more than 30 years with diabetes.

But I am not heartened by these results nor do I find them re-assuring. I am deeply troubled by how much time and effort the NIH put into perpetuating the notion that the current type 1 diabetes treatment is little more than an inconvenience to patients, rather than a dangerous tightrope act that carries some very real dangers which patients are expected to simply tolerate for the rest of their lives. Sorry, but that doesn't fly with me.


Jonah said...

Spot on!

Anonymous said...

Fabulous post, Scott. You said it perfectly!

Major Bedhead said...

I always feel like such a wet blanket when I try to dissuade newly diagnosed type 1s from thinking a cure is just around the corner. I don't believe that.

I read that study, too, and had similar thoughts to yours. I don't know why more people aren't irate about this.

Carol said...

Scott, you put that so well when you said "a dangerous tightrope act that carries some very real dangers which patients are expected to simply tolerate for the rest of their lives. Sorry, but that doesn't fly with me."

It doesn't fly with me either. I don't really care whether hypos do damage long term or not, because the short term damage is so immediate and intense, both physically and psychologically. Like this morning at 4:15 am....

Vivian said...

I could absolutely read your posts all day. Thank you for your blog.

BetterCell said...

What many Physicians will not admit to even those with T1DM themselves is that Diabetes by the very nature of the Disease itself, will cause "Complications" despite having good bs numbers. More so now, since C-peptide has been removed from insulin.
It is part of the rhetoric and PR to keep saying to patients with Diabetes, "keep good numbers, and watch what you eat". This is as you very much know the same "words of wisdom" that has been spoken for at least the past 60 years...........Nothing has changed, not the complications, or lack of wisdom.
Just better tools to "manage" the Disease.

Bernard said...


Great post. And I heard the same story when I was first diagnosed in 1972.

Let me just point out that although I'm biking again this year to support Denise Faustman's research, I don't expect a cure to come directly out of this. But I'll bet we learn useful stuff because of it.

As for big improvements in diabetes treatment. I've visited Lilly's diabetes museum with its vials of chopped up pancreas. We've barely moved from there. And I don't see it happening because the manufacturers are making far too much money with current treatments.

Anonymous said...

I have walked in your moccasins since 1956; a cure has always been “5 years away” since my diagnosis. It would appear that someone at NIH needed a study to spend/justify their research dollars. The death rate, hypoglycemia unawareness, increased hypoglycemic events and numbers of diabetics eliminated from the study because they didn’t “fit the parameters” of the study DID make the results skewed. NIH seemed to find a study which even further distorted the results. Leaving out young children and older diabetics from this latest study basically made the results useless. Hypoglycemia unawareness seems to occur most often in older diabetics (if they live that long) and the youngster/teenager with developing autonomic systems.

Your figures showing insulin as one of the most dangerous drugs in America should be considered in light of this fact: probably only 5 million Americans take insulin. These represent ½ of 1% of the population. The fact that this group reports more adverse events with insulin than, for example, much larger groups that consume BP or ED meds, is astounding. At one time, newer insulins ranked 8th among drugs reported to our adverse-events data collectors. (For those unfamiliar with the AE system, it is estimated that ONLY 10% of actual adverse events are reported).

Something your readers might want to consider: older people and children suffer most from finger sticks/(any punctures). I have a friend with a non-invasive blood glucose monitor—accurate to a 1% plus/minus range. This device provides continuous 5-minute-interval glucose readings and uses Blackberry technology as a printout/receiver. His son is long-time diabetic, and strip/meter makers have tried to buy the technology (for shelving purposes?). Approval of this meter is now being delayed by the FDA regulatory process. Follow the money; this device requires little maintenance and/or replacement equipment on an annual basis. Could it be the pain suffered by small children and the unpredictable protocols that lead to hypo unawareness are nothing more than money in the pocket of diabusiness? Couldn’t we all hope that the test strip/meter business could become as obsolete as Clinitest or TesTape?


Anonymous said...


Absolutely terrific article! Many other “diabetic” sites seem to promote unbridled optimism that reinforces a viewpoint more tilted toward “making lemonade out of lemons” than exposing the manner in which pro-industry manipulation of “facts” directs unneeded and meaningless studies. Instead of preaching to a sycophantic choir that wants to hear the “good news,” you strike right to the heart of the issue. Keep up the good work—truthful advocates like you are few and far between. The only thing I can say to neophytes who blissfully advance diabusiness/medical propaganda is this: we (long-time Type 1’s) have already walked in your shoes; you haven’t yet walked in ours.

Anonymous said...

Its really thought provoking. Since I got diabetic, I've been hearing about the reducing proximity to a cure, but there is a part in me that always wonders if the giant sharks out there who've been feeding and growing on diabetic's money will ever let any break-through come in public? Won't these companies shut down if some treatment renders the exogenous insulin useless? How will they sell the test strips for over a dollor per strip if an instruments doesn't require pricks? I didn't know there's already one before reading the previous post!! When the money involved is so huge, ruthlessness comes really handy to keep it flowing.