The feasibility of exploiting genomic information for individualized treatment of @entity66 remains uncertain. A genetic variant in @entity23510 , which encodes the a2A-adrenergic receptor (a2AAR), was recently associated with type 2 @entity6 . This variant causes receptor overexpression and @entity73 ; thus, we hypothesized that blocking a2AAR pharmacologically could improve insulin secretion in @entity1 with the risk genotype. A total of 50 type 2 @entity6 @entity1 were recruited on the basis of @entity23510 genotype for a randomized placebo-controlled intervention study with the a2AAR antagonist @entity3160 . The @entity1 received 0, 10, or 20 mg of @entity3160 at three separate visits. The primary endpoint was insulin secretion at 30 min (Ins30) during an oral @entity413 tolerance test (OGTT). @entity1 with the risk variant had 25% lower Ins30 than those without risk genotype. After administration of 20 mg of @entity3160 , Ins30 was enhanced by 29% in the risk group, making secretion similar to @entity1 carrying the low-risk allele. The corrected insulin response and disposition index in individuals with the high-risk (but not low-risk) allele were improved by 59    18% and 43    14%, respectively. The beneficial effect of @entity3160 was not a consequence of improved insulin sensitivity. In summary, the data show that the insulin secretion defect in @entity1 carrying the @entity23510 risk genotype can be corrected by a2AAR antagonism. The findings show that knowledge of genetic risk variants can be used to guide therapeutic interventions that directly target the underlying pathophysiology and demonstrate the potential of individualized genotype-specific treatment of type 2 @entity6 .

Genotype-based treatment of type 2 XXXX with an a2A-adrenergic receptor antagonist.

@entity1 :: ('9606', 'Species') :: ['Patients', 'patients'] @entity3160 :: ('MESH:D015016', 'Chemical') :: ['yohimbine'] @entity66 :: ('MESH:D004194', 'Disease') :: ['polygenic diseases'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity73 :: ('MESH:D003072', 'Disease') :: ['impaired insulin secretion'] @entity23510 :: ('150', 'Gene') :: ['ADRA2A'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity6 :: (MESH:D003920,Disease) :: ['diabetes']
