Possible Molecular Cause of Diabetes and Hypertension

Possible Molecular Cause of Diabetes and Hypertension
JournalWATCH

A new class of oral agents for type 2 diabetes mellitus -- the thiazolidinediones ("glitazones," in clinical shorthand) -- bind to a nuclear receptor called peroxisome proliferator-activated receptor gamma (PPAR(gamma)). A new study provides direct evidence of the importance of this molecule.

A British team followed 85 subjects with severe insulin resistance, characterized by severe hyperinsulinemia and acanthosis nigricans. They examined the gene for PPAR(gamma) in all the subjects and found 3 patients with mutations in this gene. A mother and son had the same mutation, whereas unaffected members of their family did not. A third, unrelated patient had a different mutation. Each mutation involved a single base pair; no mutations were found in 314 control subjects. The patients with PPAR(gamma) mutations exhibited not only severe insulin resistance but also marked hypertension. Interestingly, they were not obese, as are many patients with type 2 diabetes.

Comment: This observation suggests that the PPAR(gamma) protein may play an important role in type 2 diabetes and hypertension, at least in some patients. Because these researchers did not try to overcome the effect of the PPAR(gamma) mutation in these subjects, this study does not prove that the mutations were the cause of the insulin resistance and hypertension. However, these results are likely to provoke even greater interest in drugs that alter the expression of PPAR(gamma), such as the glitazones.

Â© 2000. Massachusetts Medical Society. All rights reserved.