The Chicken or the Egg

by Gretchen Becker Patient Expert

Type 2 diabetes starts because you gain weight, the weight gain causes insulin resistance (IR), and the IR causes the diabetes, right?

Wrong, according to researchers at the Harvard and Yale medical schools.

Gerald Shulman and colleagues found that IR in the muscles causes dietary carbohydrates to be converted into fat at a much higher rate than in people without IR. This increased fat synthesis in the liver, in turn, predisposes people to abdominal obesity, the notorious "beer belly" or "apple shape," and metabolic syndrome.

In other words, the apple shape doesn't cause IR. Rather, IR causes the apple shape.

Metabolic syndrome is like type 2 diabetes without high BG levels. Although different groups define the syndrome slightly differently, it usually includes IR, low HDL cholesterol (the good stuff), high triglycerides, high blood pressure, high uric acid levels, a prothrombotic state (tendency to form blood clots), and a proinflammatory state.

Not everyone with metabolic syndrome gets diabetes. People with metabolic syndrome who have normal beta cells are able to overcome the IR by grinding out tons of insulin, and they won't progress to overt diabetes. Their BG levels will remain in the normal ranges. However, they are at about the same risk of cardiovascular disease as people with diabetes.

But if the syndrome is accompanied by a genetic defect that makes the beta cells unable to produce all that extra insulin, it usually progresses to type 2 diabetes. Hence, anything we can do to diagnose and treat metabolic syndrome in the early stages would also help to reduce the incidence of type 2 diabetes.

Not everyone with type 2 diabetes has IR. Some people classified as type 2 are thin and don't have much IR, but they are not able to produce enough insulin to keep their BG levels in normal ranges even without the IR. They are considered type 2 because they don't have the autoimmune characteristics of type 1 and they are able to produce enough insulin to avoid ketoacidosis, a hallmark of type 1, even if their BG levels are higher than normal.

However, most people with type 2 do have the markers of metabolic syndrome and are at increased risk of cardiovascular disease. So this study is important to the majority of those with type 2 diabetes and their relatives, who, like more than 50% of the American public, are probably predisposed to developing metabolic syndrome.

These researchers studied young, lean, healthy volunteers both with and without IR and used sophisticated techniques to study various carbohydrate and lipid fractions, as well as the "de novo" synthesis of lipids by the liver after a mixed meal containing 55% carbohydrate, 10% protein, and 35% fat. De novo means the lipids aren't simply made by putting together preexisting fatty acids but are made from fatty acids newly synthesized from something else.

What they found was that people with IR, even healthy, lean young people without the other signs of metabolic syndrome, don't convert the carbohydrates they eat into glycogen---the storage form of glucose---as well as people without IR. Instead, they produce more than twice as much new fat.

This increased fat, in turn, results in lower HDL levels and increased deposition of that fat around the internal organs, in other words, abdominal obesity.

In the young, lean, healthy volunteers, however, there was no difference in the amount of abdominal fat in those with IR and those without it. In other words, the IR was not caused by abdominal fat. The apple shape occurs later in the course of the syndrome.

The researchers also found evidence that disproved another current dogma. This is the idea that various adipokines, or hormones synthesized by fat tissue (for example, tumor necrosis factor-alpha, resistin, and interleukin-6) are causing IR. The levels of these hormones were the same in those with and those without IR. So again, the IR was not caused by known adipokines. The increased levels of various adipokines found in people with metabolic syndrome or type 2 diabetes may instead be a result of obesity.

This is a good illustration of the pitfalls of confusing associated with with causes. For instance, we all know that obesity is associated with diabetes. A lot of people assume that because it's associated, it's causative. But this is probably not true, as many patients with type 2 diabetes have suspected for some time. They've always known that for some reason, when they ate the same things that their friends did, they got fatter, and their friends didn't.

Bottom line: What does this study mean for us? It means that first, you shouldn't blame yourself for having metabolic syndrome or type 2 diabetes. The underlying cause may be a metabolic defect that doesn't allow you to store excess carbohydrate very well and will turn it into abdominal fat instead.

The study also suggests that eating a lot of carbohydrate is probably not a good idea for the more than 50% of the American population predisposed to metabolic syndrome, as any excess will be converted to fat at more than twice the normal rate.

And it means that if your relatives or friends are starting to develop an apple shape, they are probably insulin resistant, and it's important for them to do whatever they can to reduce their IR. Many people who haven't yet been diagnosed with a disease don't want to take drugs that reduce IR, especially when the long-term effects of those drugs is not certain. But exercise is also a good way to get your IR down.

Unfortunately, increased exercise is never as exciting as a new drug that will let us all be couch potatoes with no risks of harming our health. But for now, in those with an apple shape, it's certainly the most prudent thing to do.

This research will be published in the July 31 issue of the Proceedings of the National Academy of Sciences. It is now available online.

Gretchen Becker
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Gretchen Becker

Gretchen wrote for HealthCentral as a patient expert for Diabetes.