Sunday, November 4, 2012

DILEMMAS



“No one in this world, so far as I know, has ever lost money by underestimating the intelligence of the great masses of the plain people.”  H.L. MENCKEN, Chicago Tribune, September 19, 1926


The following article was originally a chapter in my second book, ESSENTIAL DIABETES LEADERSHIP (2010).  I still wonder whether or not I am making a mountain out of a molehill of it and whether the reaction to my definitely inelegant tables would be: “True; but, of course, all fairly obvious.”  As to the making of the mountain, if such it is, I am utterly tired of it and prefer to write novels.  Nonetheless, my increasing confidence in the basic application of low-, very low-, or near-zero-carbohydrate diets as a template for health—so many people are healthier for it—decided me that I’m probably not a crank.

It is hard even to feel and harder still to write in a way that runs counter to a current world view, especially a moral one, and it is all the harder when the way is re-shaping a plane of perfection to which all civilized cultures are thought to be striving.  A scientist or philosopher with a program of such heresy has to be tough if he or she is to communicate it and, while doing so and for long after, must endure the tortures of Orestes.

I do so love repurposing the elegant words of those I hold in high esteem and if you now think “kinship selection” and “evolution” instead of “low-carbohydrate diet” you will recognize that the above words were written by W.D. Hamilton and were sourced from several articles comprising NARROW ROADS OF GENE LAND.  They convey my feelings well, and, with them, I introduce you to my “Dilemmas.”  Best wishes… - lc


This book [ESSENTIAL DIABETES LEADERSHIP] was written in the conviction that an optimal solution to diabetes once presented a great mystery, but that it is a mystery no longer because it is solved.[1]  Dr. Richard Bernstein solved the problem by experimenting with his diet, notably by reducing his consumption of carbohydrates.  In so doing, Dr. Bernstein validated the work done nearly a century before him by Richard Thomas Williamson, Charles Purdy, and many others, who, of course, validated John Rollo’s solution recommended 100 years before them.  We have added, and shall continue to add, footnotes to the optimal solution, such as developing the insulins glargine & detemir that enable us type 1s to achieve a normal, stable blood sugar level in our sleep, upon awakening, and throughout the day.

Too, I wrote this book because I continue to be surprised and dismayed that so many people seem not only unaware of the elegant and beautiful dietary solution to our problem; but, incredibly, actually many are unaware what the problem is in the first place!

There are two problems, really.  First, diabetes mellitus manifests itself in our bodies as ineffective carbohydrate processing due to an insulin function disturbance; we produce too much, too little, or none at all.  And second, the optimal solution espoused by would-be health-providers may be optimal for their needs, not ours.  Humbly, though passionately, I hope that my books—and the citations therein—have removed all sane doubt as to the veracity of the first problem and its solution.  Explaining, proving then solving the second problem is the focus of this chapter.

So to present this material, let me briefly introduce an effective framework for understanding relationships between people with opposing interests, the basis of all dilemmas.  We will then apply this device to a couple of real-world scenarios.  “Game theory” is thus our topic, William Poundstone our teacher, PRISONER’S DILEMMA our textbook, and the decision strategy of a couple of imprisoned gang members our subject.

Two members of a criminal gang are arrested and imprisoned.  Each prisoner is in solitary confinement with no means of speaking to or exchanging messages with the other.  The police admit they don’t have enough evidence to convict the pair on the principal charge.  They plan to sentence both to a year in prison on a lesser charge.  Simultaneously, the police offer each prisoner a Faustian bargain.  If he testifies against his partner, he will go free while the partner will get three years in prison on the main charge.  Oh, yes, there is a catch.  If both prisoners testify against each other, both will be sentenced to two years in jail.[2]

The prisoners are given little time to think this over, but in no case may either learn what the other has decided until he has irrevocably made his decision.  Each is informed that the other prisoner is being offered the very same deal.  Each prisoner is concerned only with his own welfare—with minimizing his own prison sentence.  The below 2x2 matrix graphically depicts the scenario.  Note that the first number in each cell is the payoff in terms of jail time for the row player, “A,” and the second number in each cell is the payoff in terms of jail time for the column player, “B.”



The prisoners can reason as follows: “Suppose I testify and the other prisoner doesn’t.  Then I get off scot-free, rather than spending a year in jail.  Suppose I testify and the other prisoner does too.  Then I get two years, rather than three.  Either way I’m better off turning state’s evidence.  Testifying takes a year off my sentence, no matter what the other guy does.”

The trouble is, the other prisoner can and will come to the very same conclusion.  If both parties are rational, both will testify and both will get two years in jail.  If only they had both refused to testify, they would have got just a year each!

And so ends this short but prophetic tale.  For a great primer on game theory, you are encouraged to read William Poundstone’s classic book PRISONER’S DILEMMA: JOHN VON NEUMANN, GAME THEORY, AND THE PUZZLE OF THE BOMB (New York: Doubleday, 1992).  Here we will move from theoretical games to the actual challenge, for that is where we—fellow members of the club—find ourselves.

You go to your health-provider(s) with the classical triad of symptoms of polyuria, polydipsia, and polyphagia—respectively, frequent urination, increased thirst and consequent increased fluid intake, and increased appetite—with the hope that they are more knowledgeable than you and will help you find an optimal solution.  But therein lies the dilemma: your health-provider(s) may not be fully vested in your interests alone.

Much has been written on the subject.  In “Conflict of Interest in Clinical Practice,” (2007), first published in Chest, the author Mark R. Tonelli, M.D., M.A., FCCP, provides some background:

“The inherent tension built into remuneration for the healing arts has been recognized as far back as Plato, who devoted a small part of The Republic[3] to the issue.[4]  In a classic fee-for-service arrangement, physicians benefit financially from the provision of more interventions, with patients and the market poorly positioned to make judgments regarding the necessity of these services.[5]  Historically, a physician’s service largely equated with the physician’s presence, but systemic conflicts of interest could still arise, such as agreements for fee splitting from referrals or commissions from pharmacies. As the number and kinds of medical services have exploded over the last half-century, so has the potential for clinicians to profit from the profligate use of these services.  The practice of medicine now provides the entrepreneurial physician with ample opportunities to develop ancillary business interests, such as owning radiology and other diagnostic or therapeutic centers or equipment, even entire hospitals.[6]  Clearly, the attendant financial gain in “self-referring” a patient for testing or intervention under such circumstances creates a conflict of interest as, logically, only a subset of patients will be likely to benefit from the additional procedures, whereas all patients (at least all those with the ability to pay) sent for testing or intervention would financially benefit the physician-owner.  Empiric evidence amply demonstrates that such circumstances lead not simply to a perceived conflict of interest, but to a marked increase in utilization of services when compared to financially disinterested clinicians.[7],[8]

We’re primarily concerned with the ongoing treatment of diabetes, so, admittedly, there’s little to worry that your general practitioner will recommend visiting a radiologist in exchange for a small referral fee when presented with your potential blood sugar surges.  There are, however, other ancillary service providers in the supply chain that would be happy to pay a small referral fee for a new customer, e.g., an endocrinologist, dietician, exercise trainer, laboratory technician.  The predominant source of referrals, better stated, gifts, as the authors of the article suggest, are the pharmaceutical and medical device providers.

“Over the last several years, particular professional and public attention has been focused on conflicts of interest that arise from various relationships between the pharmaceutical and medical device industries and clinicians.[9]  Businesses that happen to make drugs or medical devices have interests that are no different than those of other businesses: maximizing shareholder value, generally by increasing sales.[10]  The profession of medicine, in general, and individual practitioners, in particular, continue to embrace a primary goal of improving and maintaining the health and well-being of individual patients.  A conflict of interest develops when interactions with industry create circumstances in which the individual physician’s interest coincides with that of business, not patients.  Beyond appearances, such conflicts have demonstrated the potential to alter physician practice in a manner that favors the pharmaceutical industry at the expense of the patient.  Multiple specific interactions between industry and clinicians, including gift giving, consultancy arrangements, support of CME and guideline development, create conflicts of interest that vary in terms of effect, but each acts to bias the clinician away from patients and toward the interests of industry.”[11],[12]

And, in case you wondering about the percentage of doctors receiving these gifts, there was a study performed recently that provides that information.  In “A National Survey of Physician-Industry Relationship,” (2007), the authors surveyed physicians to collect information about their financial associations with industry and the factors that predict those associations.  They conducted a national survey of 3,167 physicians in six specialties (anesthesiology, cardiology, family practice, general surgery, internal medicine, and pediatrics) in late 2003 and early 2004.  The raw response rate for this probability sample was 52%.  Here are the results:

“Most physicians (94%) reported some type of relationship with the pharmaceutical industry, and most of these relationships involved receiving food in the workplace (83%) or receiving drug samples (78%).  More than one third of the respondents (35%) received reimbursement for costs associated with professional meetings or continuing medical education, and more than one quarter (28%) received payments for consulting, giving lectures, or enrolling patients in trials.  Cardiologists were more than twice as likely as family practitioners to receive payments.  Family practitioners met more frequently with industry representatives than did physicians in other specialties, and physicians in solo, two-person, or group practices met more frequently with industry representatives than did physicians practicing in hospitals and clinics.”[13]

The results of this national survey indicate that relationships between physicians and industry are common and underscore the variation among such relationships according to specialty, practice type, and professional activities.

And as you delve deeper into the literature, specifically on the results of medical practice, the information can leave you feeling quite pessimistic.  According to Dr. Joseph Mercola, in his popular natural health website:

“The traditional medical paradigm contains fatal flaws that have led to this startling statistic: doctors are the third leading cause of death in this country killing a quarter million people a year.  Cancer and heart disease are the only two causes that have killed more people.  Drugs, surgeries and hospitals are rarely the answer to chronic health problems.  Diet, exercise, and lifestyle are the key components to staying healthy.”[14]

Hard to believe; but, if there was nothing to the theory of good doctors doing what they were trained to do with poor results, then surely if there were periods in recent memory without available doctors, we would see sickness and/or death rates increasing.  Alas, the evidence points in the opposite direction.  According to Barry Groves in TRICK AND TREAT: HOW ‘HEALTHY EATING’ IS MAKING US ILL, Israel, Canada, the US, and Columbia share a common occurrence:

“Doctors don’t often go on strike, but it has happened sufficiently often for a disturbing trend to be noticed.  During the rare times that they have gone on strike—in several countries—the death rate has always gone down.”[15]

Once again, you’re probably a step ahead of this writing, so, yes, a read of DO WE STILL NEED DOCTORS by John D. Lantos, MD, may be indicated here.[16]  Although it is an interesting book, the issues involved in the disintermediation of an entire channel from the marketplace are a bit overwhelming, so I won’t discuss here whether or not we need doctors other than to say that more likely than not—outside of acute emergency medical situations, and to prescribe basal insulin and delivery devices—as we will see, they probably need you more.  The plain and simple fact is: we will see a doctor.

Whatever it is that doctors do—primarily consult with patients—potential customers have the perception that doctors may provide hope; they know or can at least access information and products that patients do not know or cannot access without the aid and support of, yes, doctors.  We call this phenomenon “information asymmetry,” and sufficient demand for doctors is all the driving force necessary to incentivize a supply for them in the marketplace.  Vice-versa, a supply of doctors in the marketplace will induce demand.  When tastes, preferences, and population are held constant, the only true, measurable variables are the price paid for by patients, received by doctors, based upon the quantity of services exchanged between them.  Service quality may be an assumption by those on the demand side, but aside from government- and industry-mandated requirements, not much else enters into the equation.

So let us now return to discuss this specific, real-life diabetic’s dilemma.  There are two cases here: 1) you are not prepared with any information, or 2) you have done your homework.  Let’s take a look first at those that are not prepared and, instead, will rely on their doctor to give the optimal treatment with the intent on following it.



The above table shows the asymmetrical relationship.  Note that the real power comes from the health-provider’s strategy, as they ultimately decide which treatment the diabetic will follow, and, subsequently, the payoffs.  Although the payoffs noted in the table are assertions, those assertions are based upon the evidence presented in the previous chapter.  Recall that the first number is the payoff for the row player, the health-provider, and the second number is the payoff for the column player, the diabetic.  The numbers themselves are somewhat arbitrary, however, they are used here for illustrative purposes; namely, that a low-fat diet, with corresponding necessity for a high consumption of carbohydrates, will lead to an increase in free radicals and oxidative stress in the body, and, if bolus insulin is taken, the risk of hypoglycemia is ever-present.  When the health-provider recommends, and the diabetic follows, the low-fat diet, utilizing both basal and bolus insulin, and perhaps other drugs too, the diabetic’s payoff is -20.

“Health-provider” is a deliberately general title, as it may include all those influencers noted in the previous chapter and more, including pharmaceutical companies, pharmacists, researchers, doctors, endocrinologists, nutritionists, educators, the American Diabetes Association, the World Health Organization, medical schools, nurses, reference media such as the Physician’s Desk Reference, food manufacturers, food marketers, popular internet sites, print media, the news, friends, family, co-workers & acquaintances.

Moreover, the payoff at this point for the diabetic is -20 because the diabetic now returns again and again for checkups, providing a fee to the clinic each time; some of the stated health-providers, doctors especially, are in the business of patient management.  This system keeps the dutiful patient coming back for regular doctor appointments, while at the same time keeping the pharmacist busy refilling prescriptions.  And medical insurance coverage becomes an absolute necessity.  Of course, the health-provider’s payoff is +20, because they’re the ones being paid.  They espouse party-line mis-information due to the constraints of their clinical practice guidelines; and, given the perceived information asymmetry, most patients will believe them. The final irony is the report that physicians frequently choose low-carbohydrate diets for themselves while recommending low-fat for their patients.[17]

Now let’s imagine the case of a symmetrical relationship between health-providers and diabetics.  In the next table, we’ll enable the diabetic with power of his/her own: the ability to make an informed choice regarding their treatment, based upon the insight imparted by cited authors.



In PRISONER’S DILEMMA, William Poundstone described how Dr. John Nash[18] proved that every two-person finite game has at least one equilibrium point, but that there are a few catches.  These equilibrium points can have “strange and undesirable properties.”  In fact, sometimes Nash equilibriums appear to be distinctly irrational.

The best solution for our diabetic is to always “insist on a low-carbohydrate diet.”  This strategy earns, on average, 20 “points,” whereas, acquiescing to the health-provider earns, on average, zero.  But contrast that to the health-provider’s strategies.  On average, they receive 5 “points” for doing the right thing, whereas, if they always preach party-line, that is, advocate a low-fat diet with basal and bolus insulin, and perhaps other drugs, they will earn on average 12.5 “points.”

Is that not a strange and undesirable property?  The client-health-provider relationship is now on its head.  The payoff “incentivizes” all health-providers to advocate the deleterious diet plus ample meds.  We—the patients—are now responsible for teaching and training them.  And we pay the health-providers for the opportunity to do so.

Whether or not they can be trained is another matter entirely.  We’ve seen that it is in their best interest to always choose the “advocate low-fat diet” strategy, and this is the diet based upon certain standards of care.  Those standards of care, at least in North American and European societies, are called Clinical Practice Guidelines (CPGs), and they are intended to present a synthesis of current evidence and recommendations preformed by expert clinicians and may affect the practice of large numbers of physicians.  As a result, any influence that the authors of CPGs experience from their interactions with pharmaceutical companies may be transmitted many times over to the readers of CPGs.  Consequently, if individual authors have relationships that pose a potential conflict of interest, readers of these CPGs may wish to know about them to evaluate the merit of those guidelines.

In 2002, Niteesh K. Choudhry, M.D., Henry Thomas Stelfox, M.D., and Allan S. Detsky, M.D., Ph.D., surveyed authors of CPGs throughout North America and Europe to find out the extent to which the authors of CPGs interact with the pharmaceutical industry.  They were seeking to provide empirical evidence concerning this issue to improve the process of CPG development in the future.  Here are the conclusions from that study:

“Eighty-seven percent of authors had some form of interaction with the pharmaceutical industry.  Fifty-eight percent had received financial support to perform research and 38% had served as employees or consultants for a pharmaceutical company.  On average, CPG authors interacted with 10.5 different companies.  Overall, an average of 81% (95% confidence interval, 70%-92%) of authors per CPG had interactions.  Similarly, all of the CPGs for 7 of the 10 diseases included in our study had at least 1 author who had some interaction.  Fifty-nine percent had relationships with companies whose drugs were considered in the guideline they authored, and of these authors, 96% had relationships that predated the guideline creation process.  Fifty-five percent of respondents indicated that the guideline process with which they were involved had no formal process for declaring these relationships.  In published versions of the CPGs, specific declarations regarding the personal financial interactions of individual authors with the pharmaceutical industry were made in only 2 cases.  Seven percent thought that their own relationships with the pharmaceutical industry influenced the recommendations and 19% thought that their coauthors’ recommendations were influenced by their relationships.”[19]

Although the survey’s response rate was low,[20] there appears to be considerable interaction between CPG authors and the pharmaceutical industry.

The most interesting, and perhaps regrettable, part of the discussion on clinical practice guidelines, is that there isn’t one, universally accepted guideline for diabetes.  There is one universally established way of looking at gravitation & gravity—gravitation is a general term describing the phenomenon by which bodies with mass are attracted to one another, while gravity refers specifically to the net force exerted by the Earth on objects in its vicinity as well as by other factors, such as the Earth’s rotation—but, like politics, there are many diabetes treatment paradigms.

There are guidelines written for type 1 and 2 diabetes from the American Association of Clinical Endocrinologists, the American Academy of Family Physicians, the American Geriatrics Society, the Canadian Diabetes Association, the Institute for Clinical Systems Improvement, the National Institute for Health and Clinical Excellence, the Scottish Intercollegiate Guidelines Network, and the Veterans Health Administration.  In fact, each independent health-provider, or health-providing group may have their own clinical practice guidelines.  Utilizing GOOGLE for a quick internet search of “Clinical Practice Guidelines Diabetes” returned 1,500,000 hits, where I found the 2009 Clinical Practice Guidelines for Malaysia, which, by the way, and, of course, encouraged a balanced diet consisting of 50-60% energy from carbohydrate, 15-20% energy from protein and 25-30% energy from fats, not to mention a high fibre diet.[21]

But one organization, the American Diabetes Association, provides the most commonly cited and adopted guidelines in the US, and, perhaps, throughout the world.

According to their website:

“The Association funds research to prevent, cure and manage diabetes; delivers services to hundreds of communities; provides objective and credible information; and gives voice to those denied their rights because of diabetes.  Founded in 1940, our mission is to prevent and cure diabetes and to improve the lives of all people affected by diabetes.”[22]

Quite a noble mission.  In fact, they do allocate millions of dollars per year toward research; in 2008, it was approximately $43 million.[23]  But our focus here is not the relative good that they do in the world, for surely a person with type 1 diabetes that eats carbohydrates and undergoes an intensive insulin regimen is far better off than one that solely eats carbohydrates at will, given that their body’s cells lack an effective glucose uptake mechanism.  Rather, it is the inherent conflict between the ADA’s conclusions promulgated through guidelines, and who supports that platform, that is of particular concern.

Cutting to the chase, the ADA works in its own best interest as evidenced by the following, taken directly from their conflict of interest policy:

“The American Diabetes Association and its subsidiaries (collectively, the Association) requires all members of the Board of Directors, members of Board-appointed committees and staff to act solely in the best interest of the Association without regard to their personal or business interests.”[24]

The ADA isn’t as altruistic as one would like to believe.  They don’t act primarily in the interest of diabetics; but, instead, in their own best interest, and, at least in appearance, based upon their guidelines—as we will shortly see—in the interest of their main stakeholders.  But just who are their main stakeholders?  According to the ADA’s strategic plan, the folks that have the deepest pockets from which the ADA will base their growth upon are the corporate and pharmaceutical organizations, for whom the following strategy applies:

“Maximize corporate, pharmaceutical and foundation contributions to achieve revenue of $42 million, which reflects an annual compound growth rate of 9.1%.”[25]

Nothing at first can appear more difficult to believe than that the American Diabetes Association, a credible, long-standing institution in the community, does not necessarily act in the best interest of those most negatively affected by the complications of diabetes.  The truth of the following assertion, however, cannot be disputed: the only way to get pharmaceutical companies to contribute at that level, i.e., $42,000,000 per year, and at that growth rate, i.e., 9.1%, is to serve their interests; the only way to effect that is to directly or indirectly support the use of their products, which, of course, are the many insulins and their compliments.  And the only way to support that endeavor is to espouse carbohydrates as an essential source of energy.  A source of energy; yes, exogenous carbohydrates are that.  An essential source of energy?  No.  Homo sapiens can manufacture their own glucose in the liver after the ingestion and digestion of exogenous fat and protein.[26]

So let’s now look a little more closely at the ADA’s Guidelines.  I’ll call this story “The Tale of the Tell.”

As late as 2006 and 2007, the ADA’s position, promulgated sedulously through their guidelines, was that “Low-carbohydrate diets (restricting total carbohydrate to <130 g/day) are not recommended in the management of diabetes,” and that “Saturated fat intake should be <7% of total calories.”[27]  The ADA in 2006 wrote:

“Low-carbohydrate diets are not recommended in the management of diabetes.  Although dietary carbohydrate is the major contributor to postprandial glucose concentration, it is an important source of energy, water-soluble vitamins and minerals, and fiber.  Thus, in agreement with the National Academy of Sciences-Food and Nutrition Board, a recommended range of carbohydrate intake is 45–65% of total calories.  In addition, because the brain and central nervous system have an absolute requirement for glucose as an energy source, restricting total carbohydrate to <130 g/day is not recommended.”[28]

They went on to state:

“Similar to the general population, people with diabetes are encouraged to choose a variety of fiber-containing foods, such as legumes, fiber-rich cereals (≥5 g fiber/serving), as well as fruits, vegetables, and whole-grain products because they provide vitamins, minerals, fiber, and other substances important for good health.”[29]

And, of course, the Guidelines were based upon the DCCT:

“The DCCT clearly showed that intensive insulin therapy (three or more injections per day of insulin or continuous subcutaneous insulin infusion (CSII, or insulin pump therapy) was a key part of improved glycemia and better outcomes.  At the time of the study, therapy was carried out with short- and intermediate-acting human insulins.  Despite better microvascular outcomes, intensive insulin therapy was associated with a marked increase in severe hypoglycemia (62 episodes per 100 patient-years of therapy).  Since the time of the DCCT, a number of rapid-acting and long-acting insulin analogs have been developed.  These analogs were designed to be more “physiological” in their pharmacokinetics and pharmacodynamics and are associated with less hypoglycemia with equal A1C lowering in type 1 diabetes.

Therefore, recommended therapy for type 1 diabetes consists of the following components: 1) use of multiple dose insulin injections (3–4 injections per day of basal and prandial insulin) or CSII therapy; 2) matching of prandial insulin to carbohydrate intake, premeal blood glucose, and anticipated activity; and 3) for many patients (especially if hypoglycemia is a problem), use of insulin analogs.  There are excellent reviews available that guide the initiation and management of insulin therapy to achieve desired glycemic goals.”[30]

 And in 2007, not much had changed:

“Low-carbohydrate diets (restricting total carbohydrate to <130 g/day) are not recommended in the treatment of overweight/obesity [or in diabetes].  The long-term effects of these diets are unknown, and although such diets produce short-term weight loss, maintenance of weight loss is similar to that from low-fat diets and the impact on CVD risk profile is uncertain.”[31]

But then in 2008, what seems like a sea-change occurred in the ADA’s Guidelines.  For the first time, the ADA added the following:

“For weight loss, either low-carbohydrate or low-fat calorie-restricted diets may be effective in the short term (up to 1 year).”[32]

Though a subtle caveat was placed on the low-carbohydrate diet:

“For patients on low-carbohydrate diets, monitor lipid profiles, renal function, and protein intake (in those with nephropathy), and adjust hypoglycemic therapy as needed.”[33]

And although I have been able to find hundreds of studies concluding then espousing the efficacy of low-carbohydrate diets, the ADA justified their position with only three:

“The optimal macronutrient distribution of weight loss diets has not been established.  Although low-fat diets have traditionally been promoted for weight loss, several randomized controlled trials found that subjects on low-carbohydrate diets (<130 g/day of carbohydrate) lost more weight at 6 months than subjects on low-fat diets; however, at 1 year, the difference in weight loss between the low-carbohydrate and low-fat diets was not significant and weight loss was modest with both diets.  Another study of overweight women randomized to one of four diets showed significantly more weight loss at 12 months with the Atkins low-carbohydrate diet than with higher-carbohydrate diets.  Changes in serum triglyceride and HDL cholesterol were more favorable with the low-carbohydrate diets.  In one study, those subjects with type 2 diabetes demonstrated a greater decrease in A1C with a low-carbohydrate diet than with a low-fat diet.  A recent meta-analysis showed that at 6 months, low-carbohydrate diets were associated with greater improvements in triglyceride and HDL cholesterol concentrations than low-fat diets; however, LDL cholesterol was significantly higher on the low-carbohydrate diets.”[34]

Still, the ADA, in 2008, remained firmly planted in making sure folks ingest their 130 grams of carbohydrates per day:

“The recommended dietary allowance (RDA) for digestible carbohydrate is 130 g/day and is based on providing adequate glucose as the required fuel for the central nervous system without reliance on glucose production from ingested protein or fat.  Although brain fuel needs can be met on lower-carbohydrate diets, long-term metabolic effects of very-low-carbohydrate diets are unclear, and such diets eliminate many foods that are important sources of energy, fiber, vitamins, and minerals and are important in dietary palatability.”[35]

And the DCCT continued to be cited as the holy grail:

“Glycemic control is fundamental to the management of diabetes.  The DCCT, a prospective, randomized, controlled trial of intensive versus standard glycemic control in type 1 diabetes, showed definitively that improved glycemic control is associated with sustained decreased rates of microvascular (retinopathy and nephropathy) as well as neuropathic complications.  Follow up of the DCCT cohorts in the Epidemiology of Diabetes Interventions and Complications (EDIC) study has shown persistence of this effect in previously intensively treated subjects, even though their glycemic control has been equivalent to that of previous standard arm subjects during follow-up.  In addition, EDIC has shown a significant reduction of the rate of cardiovascular outcomes in the previous intensive arm.

The DCCT clearly showed that intensive insulin therapy (three or more injections per day of insulin or continuous subcutaneous insulin infusion [CSII, or insulin pump therapy]) was a key part of improved glycemia and better outcomes.  At the time of the study, therapy was carried out with short- and intermediate-acting human insulins.  Despite better microvascular outcomes, intensive insulin therapy was associated with a marked increase in severe hypoglycemia (62 episodes per 100 patient-years of therapy).   Since the time of the DCCT, a number of rapid-acting and long-acting insulin analogs have been developed.  These analogs were designed to be more “physiological” in their pharmacokinetics and pharmacodynamics, and are associated with less hypoglycemia with equal A1C lowering in type 1 diabetes.

Therefore, recommended therapy for type 1 diabetes consists of the following components: 1) use of multiple dose insulin injections (3–4 injections per day of basal and prandial insulin) or CSII therapy; 2) matching of prandial insulin to carbohydrate intake, premeal blood glucose, and anticipated activity; and 3) for many patients (especially if hypoglycemia is a problem), use of insulin analogs.  There are excellent reviews available that guide the initiation and management of insulin therapy to achieve desired glycemic goals.”[36]

The 2009 ADA Guidelines are replicated from those of 2008.  The DCCT continues to serve as the foundation of their Guidelines—the foundation to a house of cards—as it “clearly showed that intensive insulin therapy was a key part of improved glycemia and better outcomes.”  Yet I, and countless others, who simply don’t eat many carbohydrates, and therefore haven’t a need for an intensive insulin treatment, able to keep our glucose levels within a normal range, simply, effectively, and efficiently, wonder not who holds the extreme, unsupported view.

William Poundstone stated at the end of his book that “The only satisfying solution to the prisoner’s dilemma is to avoid prisoner’s dilemmas.”[37]  Options in applying that to our situation are rather limited.  Clearly, not getting diabetes is the ideal.  Not sure how to accomplish that with any level of confidence, so let’s move on to something a little more promising.  A vaccine—two such vaccines in the works are GAD-alum and BCMA—might be a little late for type 1s without any remaining beta function, but if they can save the beta cells of anyone, then I’m all for it.[38] 

One could simply live in a state of denial, eating carbohydrates at will, not checking their BG, too, not seeing any health providers.  Yes, it is a simple option, though, not very effective or efficient.

We’re really left with one simple, inexpensive, non-time consuming, effective, efficient option.  It is both the way to solve and the way to avoid the prisoner’s dilemma.  And we’ve known about it, sans the basal insulin, for centuries.





[1] The statements “This book is written…” and “shall continue to add footnotes…” and “I wrote this book…” are all from the first paragraph of the Preface to Dawkins, Richard.  The Blind Watchmaker: Why the Evidence of Evolution Reveals a Universe Without Design.  New York: W.W. Norton & Company, page XV.  Of course, he was referring to “our own existence” and not an optimal solution to diabetes, however, the constructs fit so well in this book’s context that I just had to use them.

[2] See Poundstone, William.  Prisoner’s Dilemma; John Von Neumann, Game Theory, and the Puzzle of the Bomb.  New York: Doubleday, 1992, pages 117-119.

[3]  For a particularly good discussion of Plato’s The Republic and the role of doctors, see Terence Irwin’s Plato’s Ethics (Oxford University Press, 1995, pages 351-352).  “Does Plato expect anything more from people with wisdom than he would expect from them if they simply had correct belief?  In some striking and important passages of the Laws, Plato makes it clear that he expects them to display one distinguishing feature of knowledge in contrast to belief.  They must understand why the things they are told are right and good really are right and good; they must not simply take other people’s word for it.  To explain this demand, Plato introduces a comparison with doctors.  On the one hand, the slave doctor, who also gives treatment to slaves, just gives instructions without giving any reason for them.  The free doctor, on the other hand, who treats free people, explains why the treatment prescribed is the best one for the patients.  Instead of simply giving orders, the free doctor discusses the patients’ conditions with them and tells them enough to persuade them that the treatment being prescribed is the best one for them (719e7-720e5 in The Republic).  This discussion involves communicating some theortetical understanding to the patient...” 

[4] Stell, L Two cheers for physicians’ conflicts of interest. Mt Sinai J Med 2004;71,236-242.  Available online at http://www.ncbi.nlm.nih.gov/pubmed/15365589?dopt=Abstract.  Retrieved on 3/14/09.

[5] McDowell, TJ Physician self referral arrangements: legitimate business or unethical “entrepreneurialism.” Am J Law Med 1989;15,61-109.  Available online at http://www.ncbi.nlm.nih.gov/pubmed/2764015?dopt=Abstract.  Retrieved on 3/14/09.

[6] Moore, N Entrepreneurial doctors and lawyers: regulating business activity in the medical and legal professions. Spece, R Shimm, D Buchanan, A eds. Conflicts of interest in clinical practice and research 1996,171-196, New York, NY: Oxford University Press.

[7] Kouri, B, Parsons, R, Alpert, H Physician self-referral for diagnostic imaging: review of the empiric literature. AJR Am J Roentgenol 2002;179,843-850.  Available online at http://www.ajronline.org/cgi/content/full/179/4/843?ijkey=9700ac1ab1459c8a27e2b9a0084d5137b80d8ec2&keytype2=tf_ipsecsha.  Retrieved on 3/14/09.  See also Mitchell, J, Sass, T Physician ownership of ancillary services: indirect demand inducement or quality assurance? J Health Econ 1995;14,263-289.  Available online at http://www.ncbi.nlm.nih.gov/pubmed/10145136?dopt=Abstract.  Retrieved on 3/14/09.  See also Nallamothu, B, Rogers, M, Chernew, M, et al Opening of specialty cardiac hospitals and use of coronary revascularization in Medicare beneficiaries. JAMA 2007;297,962-968.  Available online at http://jama.ama-assn.org/cgi/content/abstract/297/9/962?ijkey=bfc824f70f476933c2c4d63f1fa858999211ce44&keytype2=tf_ipsecsha.  Retrieved on 3/14/09.

[8] See Tonelli, M.D., M.A., FCCP, Mark R.  “Conflict of Interest in Clinical Practice,” Chest August, 2007, vol. 132, no. 2, 664-670.  doi: 10.1378/chest.07-0315.  Available online at http://www.chestjournal.org/content/132/2/664.full#ref-21.  Retrieved on 3/14/09.

[9] Angell, M The Truth About Drug Companies. 2004 Random House. New York, NY.  See also Kassirer, J On the Take: How Medicine’s Complicity with Big Business Can Endanger Your Health. 2004 Oxford University Press. New York, NY.  See also Blumenthal, D Doctors and drug companies. N Engl J Med 2004;351,1885-1890.  Available online at http://content.nejm.org/cgi/content/full/351/18/1885?ijkey=0423b68ab05b7d39ec9e9bbd72d1f905e82f10da&keytype2=tf_ipsecsha.  Retrieved on 3/14/09.  Interactions between drug companies and doctors are pervasive.  Relationships begin in medical school, continue during residency training, and persist throughout physicians’ careers.  The pervasiveness of these interactions results in part from a huge investment by the pharmaceutical industry in marketing.  In 2002, the industry expended 33 percent of its revenues on "selling and administration.”  In 2001, one company, Novartis, reported spending 36 percent of its revenues on marketing alone.  The marketing expenditures of the drug industry have been estimated variously at $12 billion to $15 billion yearly, or $8,000 to $15,000 per physician.  In 2001, the industry's sales force of drug detailers, whose job is to meet individually with physicians and promote company products, numbered nearly 90,000 in the United States—1 salesperson for every 4.7 office-based physicians.”

[10] Kassirer, J.  On the Take: How Medicine’s Complicity with Big Business Can Endanger Your Health.  New York: Oxford University Press, 2004.

[11] Moynihan, R Who pays for the pizza? Redefining the relationships between doctors and drug companies: 1. Entanglement. BMJ 2003;326,1189-1192.  Available online at http://www.bmj.com/cgi/content/full/326/7400/1189?ijkey=1d0ba84bbe6c5e26d9cc59d1ab5e10bef47b6921&keytype2=tf_ipsecsha.  Retrieved on 3/14/09.

[12] See Tonelli, M.D., M.A., FCCP, Mark R.  “Conflict of Interest in Clinical Practice,” Chest August, 2007, vol. 132, no. 2, 664-670.  doi: 10.1378/chest.07-0315.  Available online at http://www.chestjournal.org/content/132/2/664.full#ref-21.  Retrieved on 3/14/09.

[13] See “A National Survey of Physician-Industry Relationship,” Campbell EG, Gruen RL, Mountford J, Miller LG, Cleary PD, Blumenthal D.  N Engl J Med. 2007 Apr 26;356(17):1742-50.  Available online at http://content.nejm.org/cgi/content/full/356/17/1742.  Retrieved on 3/14/09.

[14] See “Why do Doctors Use Treatments That Don't Work?” online at http://articles.mercola.com/sites/articles/archive/2004/03/13/doctor-treatments.aspx.  Retrieved on 4/18/08.  There are many more articles available on Dr. Mercola’s website on point.  See, for example, “Medical Research or Drug Company Secrets?” online at http://articles.mercola.com/sites/articles/archive/2002/11/20/drug-companies-part-nine.aspx; “The Doors Of Perception: Why Americans Will Believe Almost Anything,” at http://articles.mercola.com/sites/articles/archive/2001/08/15/perception.aspx; “Drugs and Doctors May be the Leading Cause of Death in U.S.” at http://articles.mercola.com/sites/articles/archive/2003/01/15/doctors-drugs-part-two.aspx; “Doctors Are The Third Leading Cause of Death in the US, Causing 250,000 Deaths Every Year,” at http://articles.mercola.com/sites/articles/archive/2000/07/30/doctors-death-part-one.aspx; “Why Doctors Are 9,000 Times More Likely to Accidentally Kill You Than Gun Owners,” at http://articles.mercola.com/sites/articles/archive/2000/05/14/doctor-accidents.aspx; and “Shame: A Major Reason Why Most Medical Doctors Don't Change Their Views,” at http://articles.mercola.com/sites/articles/archive/2002/03/30/doctors-shame.aspx.  All online articles retrieved on 4/18/09.

[15] See Groves, Barry.  Trick and Treat: How ‘Healthy Eating’ is Making us Ill.  London, UK: Hammersmith Press Limited, 2008, pages 30-31.  Used by permission

[16] For a compeling discussion from the point of view of a practicing medical doctor and ethicist, see Lantos, John D.  Do We Still Need Doctors: A Physician’s Personal Account of Practicing Medicine Today.  New York: Routledge, 1997.

[17] See La Puma J, Szapary P, Maki KC. Physicians recommendations for and personal use of low-fat and low-carbohydrate diets. Int J Obes Relat Metab Disord. 2005;29:251–253. doi: 10.1038/sj.ijo.0802840.  Available online at http://www.ncbi.nlm.nih.gov/pubmed/15534615.  Retrieved on 7/29/09.

I am grateful to the authors Surender K Arora and Samy I McFarlane, as the quote comes from their article entitled: “The Case for Low Carbohydrate Diets in Diabetes Management,” Nutr Metab (Lond). 2005; 2: 16.   Published online 2005 July 14. doi: 10.1186/1743-7075-2-16.  PMCID: PMC1188071.  Available online at http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1188071.  Retrieved on 7/29/09.

[18] The subject of the film A Beautiful Mind was John Forbes Nash, Jr.  Dr. Nash did not have diabetes, but he was the most notable of the schizophrenic patients treated in the Insulin Coma Unit at Trenton Psychiatric Hospital (TPH) in West Trenton, New Jersey, in 1961.  An American mathematician and economist whose works in game theory, differential geometry, and partial differential equations provided insight into the forces that govern chance and events inside complex systems in daily life, his theories are still used today in market economics, computing, accounting and military theory.  Serving as a Senior Research Mathematician at Princeton University during the later part of his life, he shared the 1994 Nobel Memorial Prize in Economic Sciences with game theorists Reinhard Selten and John Harsanyi.

In 1961, John was committed by Alicia and his sisters to Trenton State Hospital in New Jersey.  There, he was subjected to insulin-coma therapy, which involved injecting the patient with large amounts of insulin to put them into a coma, often causing seizures.  His colleagues in mathematics were outraged and wrote a letter to the hospital, urging the doctors to protect his mind for the good of humanity.  He was discharged after six months of the insulin treatment and looked absolutely terrible to his family members.

Dr. Manfred Sakel, a Viennese psychiatrist, developed the technique of Insulin Coma Therapy (ICT) in 1928 and introduced it to the United States in 1936.  Nondiabetic patients with schizophrenia and major depression were treated with ICT 5 days a week for 6 weeks.

The insulin unit at TPH treated 24 males and 24 females daily in separate wards.  The initial dose of regular insulin was 10–20 units administered intramuscularly at 7:00 a.m. in the unit; the dose was increased by about 10 units per day to about 90–100 units until hypoglycemic coma developed.  A team of trained nurses and physicians supervised the care of the patients, who rested on litters.  In some patients, more than 100 units of insulin were needed to produce coma.

After 30–60 minutes of hypoglycemic coma, nurses reversed the condition by intragastric glucose solution or Karo syrup.  Patients were carefully observed until cognitive, returned to their room, and then provided meals and snacks.

In her book A Beautiful Mind, Sylvia Nasar reports that Dr. Nash first showed the overt signs of schizophrenia in 1959 when he began to see encrypted messages in newspaper stories.  He was teaching at the Massachusetts Institute of Technology and after a poorly presented lecture in March, he was involuntarily committed to the McLean Hospital, a private hospital for wealthy patients affiliated with the Harvard Medical School in Boston.

He received injections of chlorpromazine but the principal treatments offered were psychotherapy, group therapy, and counseling.  After a stay of 50 days, he was released.  In May, his wife gave birth to a son.  He was not able to return to work, and for the next two years, in the grip of a persistent psychosis, he roamed Europe.

He underwent 6 weeks of insulin coma treatment.  When he was released from the hospital, he was much improved.  His thoughts were under control and he was able to once again work on a scientific paper.  From July of 1961 to August 1962, he worked at Princeton.

His illness recurred and sadly, further treatment was refused.  He spent the next decades as a shadowy figure on the Princeton University campus.

Why was Dr. Nash treated with ICT?  In 1961, the options available for patients with schizophrenia were antipsychotic drugs, Electroconvulsive Therapy (ECT), insulin coma, and lobotomy.  The optimal treatment was believed to be chlorpromazine, although many psychiatrists still looked to ECT for its benefits.  When chlorpromazine failed, ECT was the realistic option.  While most psychiatric hospitals had abandoned ICT, it had persisted at Trenton State Hospital, and it was a logical offering when these other treatments were refused. (Lobotomy was no longer a realistic option, having been replaced by antipsychotic drugs.)

For biographical information see the Wikipedia article entitled “John Forbes Nash, Jr.” online at http://en.wikipedia.org/wiki/John_Forbes_Nash; see also http://nobelprize.org/nobel_prizes/economics/laureates/1994/nash-autobio.html.  Both retrieved on 3/14/09.  See also http://www.pbs.org/wgbh/amex/nash/filmmore/ps_ict.html.  Retrieved on 3/1/09.

For information about IST, see Sakel M: The Pharmacological Shock Treatment of Schizophrenia. New York, Nervous and Mental Diseases Publishing Co., 1938.  See also Sakel M: The Insulin Treatment of Schizophrenia.  In An Introduction to Physical Methods of Treatment in Psychiatry. 1st edition. Sargent W, Slater E, Eds. Edinburgh, U.K., E. & S. Livingstone, 1944.  See also Fink, M., Shaw, R., Gross, G., and F. S. Coleman. “Comparative study of chlorpromazine and insulin coma in the therapy of psychosis.” Journal of the American Medical Association. 1958; 166:1846-50.  See also Rinkel, M., and H. E. Himwich. Insulin Treatment in Psychiatry. New York: Philosophical Library, 1959.

See also Arthur Krosnick, MD, FACP, CDE, “Five Decades of Diabetes Patient Care: The Time of My Life,” Clinical Diabetes 20:173-178, 2002.

And see Nasar S.  A Beautiful Mind.  New York: Simon & Schuster, 1961, pages 288-294.

[19] See “Guidelines and the Pharmaceutical Industry Relationships Between Authors of Clinical Practice,” by Niteesh K. Choudhry, Henry Thomas Stelfox, and Allan S. Detsky.  JAMA. 2002;287(5):612-617; doi: 10.1001/jama.287.5.612.  Available online at http://jama.ama-assn.org/cgi/reprint/287/5/612.pdf.  Retrieved on 6/13/09.

[20]One hundred twenty CPGs were identified by our search strategy, of which 35 were excluded because a major North American or European society did not endorse the CPG and 38 were excluded because they were editorials about CPGs or comparisons of different CPGs.  Therefore, 47 CPGs were initially included.  Subsequently, 1 CPG was excluded because the authors could not be identified and 2 CPGs were excluded after the authors had been surveyed since these were evaluations of CPGs rather than actual CPGs.  Therefore, 44 CPGs with 192 authors were included in the study.

Current addresses of 13 authors could not be located and 3 authors had died, resulting in a total of 176 potentially contactable authors.  Of these, 107 authors (61%) responded representing 37 of the 44 CPGs included in our study.  Therefore, 7 guidelines were not represented in our final sample.  Despite this, all of the disease states that were initially included in our study protocol were still represented by at least 2 CPGs, with the exception of depression, for which there was only 1 CPG included in the sample and for which we received a response.  Seven respondents refused to participate, all of whom were involved with different guidelines.  Three of these 7 authors were from Europe, 2 were from the United States, and 2 were from Canada.  This left 100 completed surveys, which form the basis of our results.  Overall, the response rate was 57% of potentially contactable authors and 52% of all authors initially included in our sample.  The distribution of sex and disease to which the guidelines pertained was similar for respondents and nonrespondents; however, the distribution of current country of residence was not.  Sixty-three percent of authors currently residing in the United States did not respond whereas 29% of authors living in Canada did not respond (P=.001).  Twenty-eight (26%) of 107 authors responded with a letter attached to their survey.  These letters could be interpreted as being supportive (21%), neutral (57%), or critical (21%) of our study.  Of the 100 authors who completed the first survey, 1 had died and 1 had moved and was unreachable, leaving 98 potentially contactable authors for the second survey.  Of these, 82 (83%) responded.  One of these authors refused to participate and 1 could not recall the nature of the disclosure process and, therefore, left the survey blank.  Consequently, the response rate for the second survey was 82%.”  See Ibid.

[21] See “Clinical Practice Guidelines.  Management of Type 2 Diabetes Mellitus (4th Edition),” May, 2009.  Malaysian Endocrine & Metabolic Society, Ministry of Health Malaysia, Academy of Medicine Malaysia, and Persatuan Diabetes Malaysia.  Available online at http://www.diabetes.org.my/article.php?aid=590.  Retrieved on 7/27/09.

[22] Available online at http://www.diabetes.org/aboutus.jsp?WTLPromo=HEADER_aboutus&vms=302103524165.  Retrieved on 7/28/09.

[23] See the ADA 2008 Consolidated Financials online at http://www.diabetes.org/uedocuments/2008_ADA_ConsolidatedFinancialsFS_Final.pdf.  Retrieved on 7/38/09.

[24] See the American Diabetes Association “About Us” page online at http://www.diabetes.org/aboutus.jsp?WTLPromo=HEADER_aboutus&vms=302103523106.  Retrieved on 7/28/09.

[25] American Diabetes Association 2008-2011 Strategic Plan.  Available online at http://www.diabetes.org/uedocuments/2008-2011ADAStrategicPlan.pdf.  Retrieved on 7/28/09.

[26] What limits the liver’s capacity to convert amino acids to glucose?  “Conversion of amino acids to glucose involves several metabolic processes; deamination or transamination, conversion of the released NH4+ to urea and finally synthesis of glucose from amino acid residues.  The key to understanding the physiological limitation of glucose formation from amino acids lies in the large amount of energy required to fuel these processes.  Energy in the sense used here means the hydrolysis of adenosinetriphosphate (ATP) to either AMP + PPi or ADP + Pi.  Four ATP molecules are used to convert two NH4+ to urea and six more are required to convert the carbon skeletons of these amino acids to glucose.  One ATP is also required to add a glucosyl group to a glycogen molecule so, you see, a lot of energy is used in this process.  All cells and tissues are built up such that ATP levels are relatively stable.  This is a basic prerequisite for life.  Under gluconeogenesis the liver must rely upon aerobic metabolism to replace the ATP that is consumed.  By definition this is an oxygen-dependent process.  The “catch” is that the liver obtains most of its oxygen from the portal vein where the partial pressure of oxygen is rather low.  This limits uptake of oxygen, limits ATP production and, therefore, the synthesis of glucose from amino acids.   We have data about the total amount of oxygen supplied to the human liver.  Calculations based on this (and assuming that all of this oxygen goes to support conversion of amino acids to glucose) suggest that the maximum capacity of hepatic glucose synthesis from amino acids lies around 400 grams/day.  This is the equivalent of approximately 1600 kcal...” See “Rabbit Starvation: High Protein and High Fat Diets,” by Professor Emeritus Robert S. Horn.  Available online at http://www.medbio.info/Horn/PDF%20files/rabbit%20starvation.pdf.  Retrieved on 12/16.09.

[27] See “Standards of Medical Care in Diabetes—2006,” Diabetes Care, January, 2006, vol. 29, no. suppl 1 s4-s42.  Available online at http://care.diabetesjournals.org/content/29/suppl_1/s4.full.  Retrieved on 7/27/09.

[28] Ibid.

[29] Ibid.

[30] Ibid.

[31] See “Standards of Medical Care in Diabetes—2007,”doi: 10.2337/dc07-S004.  Diabetes Care, January, 2007, vol. 30, no. suppl 1 S4-S41.  Available online at http://care.diabetesjournals.org/content/30/suppl_1/S4.full.  Retrieved on 7/28/09.

[32] See “Standards of Medical Care in Diabetes—2008,”  doi: 10.2337/dc08-S012.  Diabetes Care, January, 2008, vol. 31, no. Supplement 1 S12-S54.  Available online at http://care.diabetesjournals.org/content/31/Supplement_1/S12.full.  Retrieved on 7/28/09.

[33] Ibid.

[34] Ibid.

[35] Ibid.

[36] Ibid.

[37] Poundstone, William.  Prisoner’s Dilemma: John Von Neumann, Game Theory, and the Puzzle of the Bomb.  New York: Doubleday, 1992, page 278.

[38] See “GAD Treatment and Insulin Secretion in Recent-Onset Type 1 Diabetes,” by Johnny Ludvigsson, M.D., Ph.D., Maria Faresjö, Ph.D., Maria Hjorth, M.Sc., Stina Axelsson, M.Sc., Mikael Chéramy, M.Sc., Mikael Pihl, M.Sc., Outi Vaarala, M.D., Ph.D., Gun Forsander, M.D., Ph.D., Sten Ivarsson, M.D., Ph.D., Calle Johansson, M.D., Agne Lindh, M.D., Nils-Östen Nilsson, M.D., Jan Åman, M.D., Ph.D., Eva Örtqvist, M.D., Ph.D., Peter Zerhouni, M.Sc., and Rosaura Casas, Ph.D.   The New England Journal of Medicine, Volume 359:1909-1920, October 30, 2008, Number 18.  Available online at http://content.nejm.org/cgi/content/full/359/18/1909.  Retrieved on 5/30/09.  See also http://www.dvdc.org.au/.  Retrieved on 5/30/09.  See also http://www.jdrf.org.au/news/view/research-breakthrough-type-1-diabetes-vaccine-a-step-closer.  Retrieved on 5/30/09.

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