Wednesday, March 24, 2010

A Role for Leptin in Type 1 Diabetes?

While glancing over today's science headlines, I noticed a write-up in Science Daily of a study from UT Southwestern Medical Center involving the administration of recombinant leptin (Amlylin Pharmaceuticals) to non-obese mice (which serve as a model for human type 1 diabetes).  Treating the mice with leptin alone, the researchers saw a return from a ketogenic state and a normalization of blood sugar levels, as evidenced by a normalized HbA1c.  They postulate that leptin mediates this effect by suppressing glucagon and therefore glucose production via glycogen breakdown in the liver.  The most exciting aspect of the study to me was that the improvement in blood glucose levels was not accompanied by the wild variability that people with type 1 diabetes deal with daily.  There were also improvements seen in lipid profiles and other biomarkers related to complications of type 1 diabetes--heart disease, in particular.  While insulin is a hormone that enhances fat storage (lipogenesis), leptin works in an opposing manner, suppressing lipogenesis.  Another effect of treatment with leptin was that the mice returned to a normal weight (vs those on "insulin monotherapy"). The authors found that a combination of leptin and a low dose of insulin led to significant improvements in blood glucose levels as well as in other metabolic markers. 

While I still maintain my wait-and-see approach--after all, how many times has the NOD mouse been cured?--this seems like one of the more interesting research headlines I've seen in a while.  There are some questions I have, such as whether leptin regulation is actually impaired in type 1 diabetes, and if additional administration could have unanticipated consequences.  After all, it clearly is potently bioactive.  Another huge caveat is that the mice started with very low blood leptin levels because they had a depletion of fat due to an initial state of uncontrolled diabetes.  So it is unknown whether leptin would have as strong of an effect in humans with type 1.  Still, I hope that clinical trials are already well into the planning stages.  It seems like a worthwhile avenue of pursuit.  Read the original study at PNAS for the many details that I have missed!