Thursday, July 26, 2018

Nondiabetic blood glucose levels

The internet is buzzing with articles saying that nondiabetics can have high blood glucose (BG) levels after meals but they don't know it. Big news. Most people with diabetes already know that, because most have tested "nondiabetic" friends and relations and have seen some readings that are higher than is considered normal.

I found that some friends would go up to over 160 mg/dL after meals. But unlike most people with diabetes, they'd then return to baseline in a couple of hours. I confess I didn't do exhaustive testing because most people I know don't especially like to have their fingers pricked.

One friend seemed to get diabetes complications without having been diagnosed; for example he had frozen shoulder and trigger finger, both more common in people with diabetes. So I tested him. His fasting number was 71. An hour after a breakfast of white bread, jam, and honey,  his BG was 101, hardly a diabetic number. As it took him about 5 minutes to get up the courage to prick his finger, I didn't do more testing.

But of course all this is annecdotal. Some researchers have also tested people who are considered nondiabetic. Some time ago (2006) a Swedish researcher named Christiansen hooked a bunch of people up with continuous glucose monitors (CGMs) and looked at what their BG levels did over the course of a day. After a high-carbohydrate breakfast, the BG levels of some of them went quite high, although the average was only about 120. There was a lot of variation, some people's BG  hardly budging and others going high. I hope you can see this here (click on thumbnails). The one that looks like tangled shoelaces shows the individual variation. I can't get the lecture to play anymore, or get the URL of single slides.

Here's a German study of nondiabetics.

But the recent research that is causing so much comment was done by Michael Snyder's group at Stanford. Snyder is the geneticist who had his own DNA studied and in the process discovered that an infection had triggered a sharp rise in his BG levels, leading to a diagnosis of type 2 diabetes. Because he was diagnosed at such an early stage, he was able to reverse the condition with diet and exercise, although it took six months for his BG levels to return to normal.

This new research hooked people, mostly nondiabetic according to standard tests, up to CGMs and studied what happened with their BG levels for 2.5 hours in their normal environment. They found that people tended to fall into three clusters, which they named glucotypes. Some had relatively flat curves, which they called L, some had "severe" curves (S), and some had in-between or moderate ones (M), as shown here.

 From Hall et al., PLOS Biology  

They said that recent evidence suggests that glucose variability, more than fasting BG or hemoglobin A1c, predicts the development of cardiovascular disease. And they found that more than 25% of the "normoglycemic" individuals were in the S category.

 Then they studied how a smaller group of people would react to standard meals: cornflakes and milk, a peanut butter sandwich, or a PROBAR protein bar (an odd choice in my opinion; why not use real food?). Oddly, the "protein bar" had less protein than the other meals. They discovered what most people with diabetes already know: a breakfast of cereal and milk will make your BG soar. In this study that happened even with many of the people who were not supposed to be diabetic. Christiansen showed the same thing.

This study produced a lot of data. How much can be used in the real world is unclear. For example, they suggest that using CGMs in people before they're diagnosed with full-blown diabetes would help identify those at the highest risk, so they could make changes before it was too late. This is true. But insurance often won't pay for CGMs even for people with diabetes. Are they apt to pay for them in people without a diagnosis? Maybe some day, but probably not now.

And how many people warned that they were on the path to diabetes would actually do something about it? We all know that overeating tends to make people put on weight. But when offered the choice of cheesecake or an apple, how many people choose the apple?

The data do show clearly how different people vary in their insulin resistance and BG control. An earlier study showed how different people vary in their BG responses to different carbohydrate foods, sometimes showing opposite responses to rice vs bread, for example.

Insulin release is biphasic, and most people with type 2 diabetes lack the rapid phase 1 response that knocks down the BG before it gets too high, but they still have the phase 2 response that kicks in later and lasts as long as the food is being digested. This study did not differentiate (which would not be easy to do).

If you want to slog through the full text, it's available. But I warn you, it's slow going. There is lots of complex statistics, much of the supporting information is in supplementary material, and the figure legends are sometimes on different pages from the relevant text, so you have to go back and forth. But I suppose going from page to page is a lot easier than doing this exhaustive research, so I shouldn't whine.

One interesting sentence in the article is ". . .  American Diabetes Association dietary recommendations are based mainly on reduction of carbohydrate content." When I was diagnosed in 1996 we were told to increase our intake of carbohydrates, and a standard ADA breakfast if you were hospitalized was orange juice, toast and jam, cereal, and skim milk. A friend was told to add raisins to her oatmeal "to get the carb count up." Luckily, I never listened to the ADA and went on a low-carb diet about 6 months after diagnosis.

The essence of this research is that type 2 diabetes is complex, there are different manifestations of the disease, and it would be nice if we could all have the tools to decipher them. Someday we will, but likely not in the near future.