Posts Tagged ‘diabetes’

I don’t believe in time travel, of course, so when somebody sent me the following article that was supposed to be a chapter from a Study of the History of Diabetes published in 2018, I didn’t think about it much.  Then I read an article about a woman who had been charged with neglect in the death of her son from complications due to diabetes.  It seems she “was trying to live by faith and felt like God would heal him.”

For some reason, that made me think of the Future History, so here is a chapter from the History.

Chapter IV.  ACCORD to The Court

We have seen how, early in the history of medicine, diabetes was recognized as a disease of carbohydrate intolerance and how, until the discovery of insulin, removing carbohydrate from the diet became the major treatment (Chapters I and II).  We chronicled the shift away from this medical practice under the influence of low fat recommendations and the ascendancy of pharmacology that followed the discovery of insulin.  Nonetheless, it persisted in the popular mind that you don’t give candy to people with diabetes, even as health agencies seemed to encourage sucrose (sugar) consumption.

The rather sudden reappearance of carbohydrate restriction, the so-called modern era in diabetes treatment, is usually dated to 2008, the precipitating event, publication of the ACCORD study in which a group undergoing  “intensive treatment” to lower blood glucose showed unexpected deaths [1].  ACCORD concluded that “These findings identify a previously unrecognized harm of intensive glucose lowering in high-risk patients with type 2 diabetes.” The intensive treatment turned out to be intensive pharmacologic therapy and this flawed logic lead to a popular uprising of sorts, a growing number of patients claiming that they had been hurt by intensive drug treatment and typically that they had only been able to get control of their diabetes by adherence to low carbohydrate diets. Blogs compared the ACCORD conclusion to an idea that alleviating headaches with intensive aspirin led to bleeding and we should therefore not treat headaches.

The conflict culminated in the large judgment for the plaintiff in Banting v. American Diabetes Association (ADA) in 2017, affirmed by the Supreme Court in 2018.  Dalton Banting, coincidentally a distant relative of the discoverer of insulin, was an adolescent with diabetes who took prescribed medications and followed a diet consistent with ADA recommendations.  He experienced worsening of his symptoms and ultimately had a foot amputated. At this point his parents found a physician who recommended a low carbohydrate diet which led to rapid and sustained improvement.  The parents claimed their son should have been offered carbohydrate-restriction as an option.  The case was unusual in that Banting had a mild obsessive-compulsive condition, expressed as a tendency to follow exactly any instructions from his parents or other authority figures.  Banting’s lawyers insisted that, as a consequence, one could rely on his having complied with the ADA’s recommendations.  Disputed by the defense, this was one of several issues that made Banting famous for vituperative courtroom interactions between academics.

Banting was a person with type 2 diabetes.  Unlike people with type 1 diabetes, he was able to produce insulin in response to dietary (or systemic) glucose but his pancreas was progressively dysfunctional and his body did not respond normally, that is, he was insulin-resistant.  Although most people with type 2 diabetes are at least slightly overweight, Banting was not, although he began gaining weight when treated with insulin.

The phrase “covered with insulin…” rocked the court: the president of the ADA, H. Himsworth, Jr., was asked to  read from the 2008 guidelines [2], never rescinded: “Sucrose-containing foods can be substituted for other carbohydrates in the meal plan or, if added to the meal plan, covered with insulin or other glucose lowering medications.”

Jaggers (attorney for Banting): “Are there other diseases where patients are counseled to make things worse so that they can take more drugs.”

Himsworth: “We only say ‘can be.’  We don’t necessarily recommend it.  We do say that ‘Care should be taken to avoid excess energy intake.’”

It soon became apparent that Himsworth was in trouble.  He was asked to read from the passage explaining the ADA’s opposition to low carbohydrate diets:

“Low-carbohydrate diets might seem to be a logical approach to lowering postprandial glucose. However, foods that contain carbohydrate are important sources of energy, fiber, vitamins, and minerals and are important in dietary palatability.”

Jaggers: “Important sources of energy?  I thought we wanted to avoid excess energy,” and “would you say that taking a vitamin pill is in the same category as injecting insulin?”

Finally,

Jaggers: “Dr. Himsworth, as an expert on palatability, could you explain the difference between Bordelaise sauce and Béarnaise sauce?” [laughter]

Damaging as this testimony was, the tipping point in the trial is generally considered to have been the glucometer demonstration.  Banting consumed a meal typical of that recommended by the ADA  and glucometer readings were projected on a screen for the jury, showing, on this day, so-called “spikes” in blood glucose.  The following day, Banting consumed a low carbohydrate meal and the improved glucometer readings were again projected for the jury.  Defense argued that one meal did not prove anything and that one had to look at the whole history of the lifestyle intervention but was unable to show any evidence of harm from continued maintenance of low blood sugar despite testimony of several expert witnesses.  In the end, the jury agreed that common sense overrides expert testimony and that Banting should have been offered the choice of a carbohydrate-restricted diet.

Banting was held in New York State which adheres to the Frye standard: in essence, the idea that scientific evidence is determined by “general acceptance.” The explicit inclusion of common sense was, in fact, a legal precedent [3].   The Supreme Court ultimately concurred and held that the more comprehensive standards derived from Daubert v. Merrill-Dow, could sensibly be seen to encompass common sense.

The final decision in Banting lead to numerous law suits.  The ADA and other agencies changed their tactics claiming that they never were opposed to low carbohydrate diets and, in fact, had been recommending them all along [4].  This is discussed in the next chapter.

References

1. Gerstein, H. C. et al., Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358 (24), 2545 (2008).

2. American Diabetes Association, Nutrition Recommendations and Interventions for Diabetes–2008. Diabetes Care 31 (Suppl 1), S61 (2008).

3. Berger, M, Expert Testimony: The Supreme Court’s Rules Issues in Science and Technology (2000).

4. American Diabetes Association, Nutrition Recommendations and Interventions for Diabetes–2018. Diabetes Care 40 (Suppl 1), S12 (2018).

Stepping back and looking at the recent scientific literature, I am struck with how life is a miracle.  How could humans have evolved in the face of threats from red meat, from eggs, even from the dangers of shaving?  (If you write about nutrition you have to create a macro that types out “I’m not making this up:” the Caerphilly Study [1] shows you the dangers of shaving… or is it the dangers of not shaving?).  With 28% greater risk of diabetes here, 57 % greater risk of heart disease there how could our ancestors have ever come of child-bearing age?  With daily revelations from the Harvard School of Public Health showing the Scylla of saturated fat and the Carybdis of sugar between which our forefathers sailed, it is amazing that we are here.

These studies that the media writes about, are they real?  They are certainly based on scientific papers.  If the media is not always able to decipher them, reporters do generally talk to the researchers. And the papers must have gone through peer review and yet many actually defy common sense.   Can the medical literature have such a high degree of error?  Could there be a significant number of medical researchers who are not doing credible science?  How can the consumer decide?  I am going to try to answer these questions.  When people ask questions like “could the literature be wrong?,” the answer is usually “yes” and I will try to explain what’s wrong and how to read the nutritional literature in a practical way. I am going to try to make it simple.  It is science, but it is pretty simple science.  I am going to illustrate the problem with the example of a paper by Djoussé [2].  But first, a joke.

It was a dumb joke. In my childhood, there was the idea, probably politically incorrect, that Indians, that is, Native Americans, always said “how” as a greeting.  The joke was about an Indian with a great memory who is asked what he had for breakfast on New Years day the previous year.  He says “eggs.”  They are then interrupted by an earthquake or some natural disaster and the interviewer and the Indian don’t meet again for ten years.  When they meet, the interviewer says “how.”  The Indian answers “scrambled.”

If the interviewer had been an epidemiologist he might have asked if he had developed diabetes.   Djoussé, et al. [2] asked participants about how many eggs they ate and then ten years later, if they developed diabetes it was assumed to be because of the eggs.  Is this for real?  Do eggs cause changes in your body that accumulate until you develop a disease, a disease that is, after all, primarily one of carbohydrate intolerance?  The condition is due either to the inability of the pancreas to produce insulin in response to carbohydrate (type 1) or to impaired response of the body to the insulin produced and a deterioration of the insulin-producing cells of the pancreas (type 2).  Common sense says that there is something suspicious about the idea that eggs would play a major role.  It is worth trying to understand the methodology and see if there is a something beyond common sense, and whether this is a problem in other studies besides   Djoussé’s.

What did the experimenters actually do.  First, people were specifically asked “to report how often, on average, they had eaten one egg during the past year,” and “classified each subject into one the following categories of egg consumption: 0, < 1 per week, 1 per week, 2-4 per week, 5-6 per week, and 7+ eggs per week.”  They collected this data every two years for ten years.  With this baseline data in hand they then followed subjects “from baseline until the first occurrence of a) type 2 diabetes, b) death, or c) censoring date, the date of receipt of the last follow-up questionnaire” which for men was up to 20 years.  Thinking back over a year: is there any likelihood that you might not be able to remember whether you had 1 vs. 2 eggs on average during the year?  Is there any possibility that some of the men who were diagnosed with diabetes ten years after their report on eggs changed their eating pattern in the course of ten years?  Are you eating the same food you ate ten years ago?  Quick, how many eggs/week did you eat last year?

Reading a scientific paper: the Golden Rule.

Right off, there is a problem in people reporting what they ate but this is a limitation of many nutritional studies and, while a source of error, it is depends on how you interpret the data.  All scientific measurements have error.  It is not a matter of ignoring the data but rather not interpreting results beyond measurement.  So, here’s how I read a scientific paper.   First, I look for the pictures.  What? A professor of biochemistry looks for the pictures first?  In a scientific paper, of course, they are called figures but it’s not just saving a thousand words.  (I get a thousand emails every couple of weeks). It’s about presentation of the data.

The principle is that a scientific paper is supposed to explain. The principle is laid out in what I call the golden rule of scientific papers.  It comes from the Book PDQ Statistics by Geoffrery Norman and David Streiner.  PDQ stands for Pretty Darned Quick and some of the humor is pretty sophomoric (e.g. it has Convoluted Reasoning or Anti-intellectual Pomposity detectors) but it is an excellent introductory statistics book.  Here’s the Golden Rule:

“The important point…is that the onus is on the author to convey to the reader an accurate impression of what the data look like, using graphs or standard measures, before beginning the statistical shenanigans.  Any paper that doesn’t do this should be viewed from the outset with considerable suspicion.”

— Norman & Streiner, PDQ Statistics [3]

In other words: teach.  Make it clear.  Eye-balling Djoussé, et al., we see that there are no figures.     A graph of number of eggs consumed vs number of cases of diabetes is what would be expected of the golden rule.  The results, instead are stated in the Abstract of the paper as the following mind-numbing statistics. (You don’t really have to read this)::

“Compared with no egg consumption, multivariable adjusted hazard ratios (95% CI) for type 2 diabetes were 1.09 (0.87-1.37), 1.09 (0.88-1.34), 1.18 (0.95-1.45), 1.46 (1.14-1.86), and 1.58 (1.25-2.01) for consumption of <1, 1, 2-4, 5-6, and 7+ eggs/week, respectively, in men (p for trend <0.0001). Corresponding multivariable hazard ratios (95% CI) for women were 1.06 (0.92-1.22), 0.97 (0.83-1.12), 1.19 (1.03-1.38), 1.18 (0.88-1.58), and 1.77 (1.28-2.43), respectively (p for trend <0.0001).”

What does all this mean? I will just state what the statistics mean because it is worth considering the conclusion as stated by the authors.

The meaning of the statistics is that there was no risk of consuming 1 egg/week compared to eating none.  Similarly, there was no risk in eating 2-4 eggs/week or 5-6 eggs/week.  But when you up your intake to 7 eggs or more per week, that’s it.  Now, you are at risk for diabetes.  The relative risk is small but there it is. You are now at greater risk.

Since I like pictures, I will try to illustrate this with a modified still from the movie, The Seventh Seal directed by Ingemar Bergman.  Very popular in the fifties and sixties, these movies had a captivating if pretentious style: they sometimes seemed to be designed for Woody Allen’s parodies.  One of the famous scenes in The Seventh Seal is the protagonist’s chess game with Death.  A little PhotoShop and we have a good feel for what happens if you go beyond 5-6 eggs/week.

 

1. Ebrahim S, Smith GD, May M, Yarnell J: Shaving, coronary heart disease, and stroke: the Caerphilly Study. Am J Epidemiol 2003, 157(3):234-238.

2. Djoussé L, Gaziano JM, Buring JE, Lee IM: Egg consumption and risk of type 2 diabetes in men and women. Diabetes Care 2009, 32(2):295-300.

3. Norman GR, Streiner DL: PDQ statistics. 3rd edition. Hamilton, Ont.: B.C. Decker; 2003.