A Discussion About New Hypotheses – Diabetes Daily

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This content originally appeared on Wildly Fluctuating. Republished with permission.

Sometimes it seems as if almost everything I was taught in school is now considered wrong. Well, OK, not everything. The letter still usually comes before e, except after and a ton of other exceptions including neither leisured foreigner seized the heifer on the weird heights, and no one cares about spelling today anyway.

Of course, in science, almost no theory is permanent. New evidence requires updating of current theories, somethings reversing them completely.

I just hope no one discovers that the universe isn’t expanding, but imploding toward another Big Bang! And if it is, I hope it doesn’t occur in my lifetime.

But on a more mundane level, three papers came in recently that are challenging accepted dogma.

The first suggests that lactate, a product of metabolizing glucose, isn’t a dead-end molecule produced only when there isn’t enough oxygen to metabolize it further, but rather is an important source of energy and a way to distribute this energy from one tissue to another. George Brooks of the University of California, Berkeley, has been proposing this idea for 40 years, but no one has been paying much attention, and most biochemistry sources still show it as a sort of waste product produced only in the absence of oxygen and causing pain after heavy exercise.

But the Brooks lab found that lactate is actually a preferred source of energy in some tissues like the brain and heart. Brooks calls the production, transport, and use in various tissues the lactose shuttle.

The whole review can be seen here.

A second paper suggests that it’s not a lack of insulin but insulin hypersecretion that causes insulin resistance and type 2 diabetes. Australian researcher Christopher Nolan is one of the authors of this paper, and I’ve written about some of his ideas before, namely the idea that insulin resistance is protective for some tissues.

Nolan and his coauthor support the idea that there are five subtypes of diabetes and says that the type that causes insulin hypersecretion is severe insulin-resistant diabetes (SIRD). If someone has this kind of type 2 diabetes, then he says treating it with insulin injections or sulfonylureas would be counterproductive.

People with other subtypes might benefit from such treatments.

I suspect that researchers will eventually discover even more subtypes of diabetes, with some overlap, but for now, we can stick to just five. Nolan says it’s “time for a conceptual framework shift” to consider the main driver of type 2 diabetes to be not insulin resistance but insulin oversecretion. It’s an interesting way of looking at the disease.

Finally, the third paper says that it isn’t high glucose levels but defects in mitochondria and elevations in some fat derivatives and their processing in the defective mitochondria that cause inflammation. The senior author of the paper, Barbara Nikolajczyk, kindly sent me the full text, but the research is so complex I can’t evaluate it and have to accept the summaries. There are 20 authors, and you can see the summary here.

In the past, there have been studies relating high blood glucose levels and inflammation, but as we all know, correlation is not causation, and it’s not always clear if the high A1cs caused the inflammation or if inflammation caused the high A1cs, or if a third factor caused them both. One study even suggested that low blood glucose levels, but not high blood glucose levels, caused inflammation in monocytes (a type of white blood cell). The Nikolajczyk study used peripheral blood mononuclear cells, which include monocytes and a few other cell types.

New hypotheses usually stimulate new research and often result in significant advances. Maybe I should hypothesize e before i, don’t ask me why, except for most words, that are known by all nerds and maybe I’d start a spelling revolution. At least no one would be hurt in such a revolution.

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