High Insulin Levels in Nondiabetics

Patient Expert

Many of us think that using insulin before it's necessary will help to "rest" our beta cells so they'll last longer.

But now comes a research paper showing that excess insulin actually causes diabetes in nondiabetic mice fed a chow diet. The chow diet is the normal diet given to mice unless you want to fatten them up and give them diabetes, in which case you feed them a high-fat, high-carbohydrate diet.

The high insulin levels were caused by injecting these normal mice with insulin glargine (Lantus). This injected insulin did not seem to cause hypoglycemia, although the researchers measured only fasting blood glucose (BG) levels and watched for signs of severe hypoglycemia.

The injected insulin did cause insulin resistance, as might be expected as it's common for mammals to develop resistance to hormones whose levels are high. Most of the increased insulin resistance was in the liver. But instead of "resting" the beta cells, it also caused loss of beta cells and hence insulin deficiency.

The insulin also caused higher cholesterol levels and fat accumulation in the liver. Although the mice that got the insulin were only slightly fatter than the control mice at some times, their ratio of white fat to body weight was significantly increased.

It's important to understand that these mice were not diabetic; they didn't need extra insulin in order to keep their BG levels in a normal range. But the chronic elevation in insulin levels made them store more fat and eventually develop type 2 diabetes.

It's also important to understand that these were mice. Humans don't always respond the same way that mice do, so mouse studies are simply suggestive, no proof of anything.

But could this experiment have any relation to the type 2 diabetes epidemic we're seeing today? When nondiabetic people follow the government-recommended low-fat, high-carbohydrate diet, their insulin levels will be high after meals, especially with relatively little fat to slow down the release of glucose into the intestine.

As long as the insulin levels go down fairly quickly after the meal, as they usually do in healthy people, these people won't be exposed to the chronic high insulin levels these mice were, so these results wouldn't apply to them. In many cultures, people eat mostly carbohydrates and don't have high diabetes rates.

But how many Americans today eat only at mealtimes? Not a lot. Snacking has become the norm. And most of those snacks are high in carbohydrate, usually starchy, sugary treats. In that case, the insulin levels could be elevated for most of the day, as they were in these mice.

And that could cause insulin resistance and eventually loss of beta cells and hence type 2 diabetes.

Again, note that these mice were not diabetic to begin with. Once we have developed diabetes, or even prediabetes, we don't have enough insulin to keep our BG levels down after meals, and injected insulin (or insulin produced as a result of a sulfonylurea drug) is a crude means of trying to normalize the insulin levels.

So in this case, the benefits of insulin in keeping BG levels down would most likely outweigh any effects of insulin on causing insulin resistance, which such people most likely already have anyway. Normalizing BG levels, no matter how it is achieved, reduces the toxic effects of high BG levels that can damage beta cells. And studies have shown that intensive BG control in newly diagnosed type 2s can result in improved control for a long time afterward. This is one such study.

One recent study in humans showed that giving Lantus to people with impaired fasting glucose or impaired glucose tolerance decreased the number who progressed to overt diabetes.

Thus whether chronically high insulin levels cause or prevent diabetes in nondiabetic humans is a question with no clear answer today.

Interestingly, at about the same time as the mouse study came out, another study was published that showed that giving insulin to type 2 diabetes patients with certain risk factors for type 1 diabetes accelerated the rate at which they developed type 1.

Note that these results would not apply to everyone with type 2, just those with genes that predispose them to type 1.

What all this means is that insulin is powerful. It saves lives and can help people recently diagnosed with diabetes to normalize their BG levels for long periods of time. But overindulging in high-carbohydrate foods throughout the day, causing chronic high insulin levels, could be contributing to our high diabetes rates. It's worth thinking about.