What Causes Type 2 Diabetes?

Insulin resistance and high levels of insulin and lipids all precede the development of metabolic dysfunction. Which metabolic factor is to blame?

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FAT TRIANGLE: Fat cells (left) release lipids into the bloodstream. High lipid levels, in turn, can trigger the release of insulin from pancreatic β cells (middle). Insulin then travels to cells of the liver (right) and to the body’s periphery. Understanding the cause of metabolic dysfunction and diabetes will require a detailed understanding of how these different tissues and organs work together to regulate blood sugar.DANIELA MALIDE, NATIONAL HEART, LUNG, AND BLOOD INSTITUTE; NIH; © SCOTT CAMAZINE/SCIENCE SOURCE; © ISTOCK.COM/MAXPDIA

Type 2 diabetes is a multifactorial metabolic disease.1 Obesity, elevated levels of lipids and insulin in the blood, and insulin resistance all accompany the elevated blood glucose that defines diabetes. (Diabetes is defined as fasting blood glucose concentrations above 7 millimolar (mM), or above 11 mM two hours after ingestion of 75 grams of glucose.) But while researchers have made much progress in understanding these components of the metabolic dysfunction, one major question remains: What serves as the primary driver of disease?

Lifestyle choices characterized by inactivity have been postulated as one possible cause. Researchers have also pointed the finger at nutrition, postulating that poor food choices can contribute to metabolic disease. However, there is thus far weak support for these hypotheses. Changing to a ...

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