Posted by: notdeaddinosaur | January 2, 2015

Diets and Denominators

News non-flash: comparison of various diets (low carb/Atkins, low carb + low fat/South Beach, low calorie/Weight Watchers, and whatever-the-hell-the-Zone-diet is/protein-carb ratio) shows no difference in long term outcomes, defined as sustained weight loss, with the attendant presumed decrease in cardiovascular risk factors and events.

Sorry; no great surprise here. But I think it’s because nutrition research has a huge blind spot: not adequately controlling for type 2 diabetes/metabolic syndrome.

Let me explain.

I have a hypothesis that people with the inborn error of metabolism (insulin resistance) that in the setting of dietary carb overload and low levels of physical activity result in overt glucose intolerance and, eventually, diabetes, respond better to low-carb diets than people born with normal carbohydrate metabolism. By not carefully screening them out in the research, negative results are meaningless.

Current definitions of diabetes, “pre-diabetes”, metabolic syndrome, and so on center on blood sugar levels in both the short term (fingerstick glucose measurements) and long term (the 3-month horizon afforded by the hemoglobin A1c). The problem with this is that the increased cardiovascular risks from these conditions appear to manifest independently of actual blood sugar levels. Witness the disappointing results of studies of so-called “tight control”: modest reduction in microvascular disease (kidney failure and retinopathy) but no significant effect on macrovascular disease (heart attacks and strokes.) This says to me that there’s something more than just hyperglycemia going on in these patients.

We also know that lifestyle issues (read: exercise), not smoking, and treatment with lipid-lowering statin medications DO decrease these risks in these patients. But who are they?

Diabetics, of course. Pre-diabetics too, plus anyone with metabolic syndrome (high triglycerides/low HDL/abdominal or “apple” shaped fat). Women with PCOS and/or a history of gestational diabetes. These folks are relatively easy to identify, whether or not they’re excluded (or at least controlled for) in nutritional research. But I think there’s another group of folks who have this inborn metabolic error but who, because they’re already “living right” (exercising, maintaining ideal body weight, not overdoing dietary carbs) have perfectly normal blood sugar levels, and therefore completely normal A1c levels.

How to identify them? A few thoughts: family history. Anyone with any first degree relative with either diabetes or any of the above equivalents (PCOS, gestational diabetes). Or we can check insulin levels. Because the inborn metabolic error is that of resistance to insulin, these folks walk around with higher insulin levels in order to maintain normal blood sugar levels.

Control future dietary studies for diabetes — REALLY control for it — and see what turns up. Better still, select out people who don’t have it. I bet you’ll see better, more robust responses to any version of carb restriction. But until inborn errors of carbohydrate metabolism are adequately controlled for in dietary research, I don’t think there are any valid conclusions to be drawn.



  1. Hmmm… Maybe will fund a study like this…

  2. Cool. Kickstarter for science. Maybe I can use that to study Vitamin D (since there’s no money to be made, can’t expect anything from pharma).

  3. A very valid point. However, with all due respect, it’s culturally loaded to refer to the genetic background of a large majority of Pima Indians, for example, as an “inborn error of metabolism”, while the metabolism of most Westerners, which has been subject to centuries of selection via unusually high starch, and increasingly sugar, consumption, is “normal”. This implies that eating lots of processed grains and sweets is the natural human condition, comparable to calling lactose “intolerance” a “genetic defect” when it is in fact the human and mammalian norm. Presumably, the metabolic characteristics that cause most Pima to develop diabetes on a Western diet are (or were) beneficial to them in their traditional lifestyle; that’s why they became so common. “Errors” rarely move toward fixation in a large population.

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