Thursday, January 16, 2020

Retrospective #334: A Unifying Hypothesis of Chronic Disease: Part 1

I don’t remember how, but in early 2016, I landed on South African blogger Marika Sboros’s site, FOODMED.NET. I loved it and signed up for regular delivery. The blog’s subtitle is “Let food be your medicine,” so you can see my affinity. The first post I read, in her “Managing Your Blood Sugar” series, was titled “NOAKES: IT'S THE FATTY LIVER DISEASE, STUPID' PART 2,” tagged “LCHF.” Marika explains that LCHF in her lexicon means “Low Carb Healthy Fats.”
The author of this particular post was world-renowned scientist and University of Cape Town Professor Emeritus Dr. Tim Noakes. Noakes introduces his subject with a discussion of the misunderstood term “risk factors,” frequently used in epidemiology and “observational” or “associational” studies. He delves briefly into “hazard ratios” (HRs), relative and absolute risk, and related subjects to show how data is commonly manipulated and misused.
“This is intellectually absurd,” Noakes says. “How can everything be a risk factor for everything else?” he asks. He answers, “The answer can be found in the ignored work of Dr. Gerald Reaven, Emeritus Professor of Medicine at Stanford University.” “Reaven has spent the past 60 years studying the condition that intellectually he now owns, insulin resistance.” (As I rewrite this in 2020 for the Retrospective Series, I note that Gerald Reaven died in 2019.)
Reaven’s interest in insulin resistance was piqued by the distinction between Type 1 and Type 2 diabetes. Type 1 is characterized by the (almost) total absence of endogenous insulin; Type 2, insulin resistant diabetes, by “abnormally high amounts [of insulin] because the target cells on which the insulin normally acts are resistant to its action; hence the condition of insulin resistance or carbohydrate intolerance. Persons with insulin resistance have blood insulin concentrations that are elevated most of the time, a condition known as hyperinsulinemia.” (my emphases).
Noakes says, “Reaven’s great contribution has been to show this persistent hyperinsulinemia in insulin resistance, whether or not associated with t2dm, produces a collection of grave secondary consequences.”
Noakes then says, “But Reaven’s greatest (and bravest) intellectual contribution is to suggest that insulin resistance and hyperinsulinemia are the necessary biological precursors definitely for four and perhaps for all six of the most prevalent chronic conditions of our day: 1) Obesity; 2) Arterial disease (local: heart attack or stroke; disseminated: T2DM; 3) High blood pressure; 4) Non-Alcoholic Fatty Live Disease (NAFLD); Cancer; and Dementia (Alzheimer’s Disease, also known as Type 3 Diabetes).
Reaven gave the keynote Banting lecture at the 1988 American Diabetes Association annual meeting. His talk explained the underlying factor for a constellation of abnormalities: glucose intolerancehyperinsulinemia, hypercholesterolemiahypertriglyceridemia, and hypertension.  Reaven named it “Syndrome X”; it was also given the moniker Reaven’s syndrome. Today it is simply called Metabolic Syndrome.
“The key finding from Reaven’s work,” Noakes says, “is that these conditions are not separate – they are different expressions of the same underlying condition. Thus, a patient should not be labeled as having high blood pressure or heart disease or diabetes or NAFLD (or perhaps even cancer or dementia).”
“Instead,” Noakes continues, “the patient should be diagnosed with the underlying condition – insulin resistance – with the realization that the high blood pressure, the obesity, the diabetes, the NAFLD, or the heart attack or the stroke are simply markers, symptoms if you will, of the basic condition.”
“And that basic condition,” Noakes concludes, “is insulin resistance which, simply put, is the inability of the body to tolerate more than an absolute minimum amount of carbohydrates eaten each day. “
Thus, we have it: Reaven’s unifying hypothesis of chronic disease: “One disease, one cause, many symptoms.” Tomorrow’s post will offer insight into the profound implications of this fundamental advance in medical science.
Aside: This column was based on Noakes’s 2016 “Part 2” in a Series. By sheer coincidence, a link to “Part 4,” recently published by Tim Noakes, appeared on Twitter on January 13, 2020. It is a long encomium to the late Gerald Reaven.

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