The Chicken or the Egg

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.