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.