Issue 144 Item 11 Beta-Cell Death Outpaces Replacement in Type 2 Diabetes

Approaches designed to arrest beta-cell apoptosis could be a “significant new development in the management of type 2 diabetes. Despite an increase in beta-cell formation, beta-cell mass is decreased in patients with type 2 diabetes as a result of increased beta-cell apoptosis, results of a study in the January issue of the journal Diabetes indicate.

Based on their finding, the authors say therapeutic approaches designed to arrest beta-cell apoptosis could be a "significant new development in the management of type 2 diabetes, because this approach might actually reverse the disease to a degree rather than just palliate glycemia."

Dr. Peter C. Butler from the University of Southern California in Los Angeles and colleagues examined pancreatic tissue from 124 autopsies. Of the 91 obese subjects, 41 had type 2 diabetes, 15 had impaired fasting glucose (IFG), and 35 were nondiabetic. Of the 33 lean patients, 16 had type 2 diabetes and 17 were nondiabetic.

Compared with their nondiabetic age- and weight-matched counterparts, obese and lean diabetics had a deficit in relative beta-cell volume of 63% and 41%, respectively.

Obese subjects with IFG had a 40% deficit in beta-cell mass, "suggesting that this is an early process and mechanistically important in the development of type 2 diabetes," the authors say.

According to the team, an observed 3- to 10-fold increase in the rate of beta-cell apoptosis in diabetics, rather than a decrease in beta-cell formation, is the reason for decreased beta-cell mass.

Dr. Butler said a "major finding" of this study is that humans produce new islet cells throughout their lives. "We used to think that the islets were fixed in number at birth," he said. In this study, new islet formation, while increased with obesity, was comparable in all subjects.

"In people who are relatively insulin resistant, the rate at which we make new islets adaptively increases and so we end up with more of them. This is a little like muscle increasing in response to exercise," Dr. Butler explained.

"In people with type 2 diabetes, the rate at which new islets are formed is the same as nondiabetic individuals, but despite this they have an ~70% deficit in the cells that make insulin. This is because the cells are dying 5-10 times faster than in nondiabetic people."

"The exciting thing about this is that if we could prevent this increased rate of cell death, then people with type 2 diabetes could be cured by replacing their own islets," he said. Diabetes 2003;52:102-110.