Bromocriptine: a novel approach to the treatment of type 2 diabetes

H. Pijl, S. Ohashi, M. Matsuda, Y. Miyazaki, A. Mahankali, V. Kumar, R. Pipek, P. Iozzo, J. L. Lancaster, A. H. Cincotta, R. A. DeFronzo
2000 Diabetes Care  
R.A.D. has served on the advisory board and as a paid consultant for Ergo Science. A.H.C. is a member of the Board of Directors of Ergo Science and holds stock in that company. Abbreviations: CV, coefficient of variation; EGP, endogenous glucose production; FFA, free fatty acid; FFM, fat-free mass; FPG, fasting plasma glucose; GIR, exogenous glucose infusion rate; MRI, magnetic resonance imaging; OGTT, oral glucose tolerance test; R a , rate of endogenous glucose appearance. A table elsewhere
more » ... A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Bromocriptine A novel approach to the treatment of type 2 diabetes O R I G I N A L A R T I C L E OBJECTIVE -In vertebrates, body fat stores and insulin action are controlled by the temporal interaction of circadian neuroendocrine oscillations. Bromocriptine modulates neurotransmitter action in the brain and has been shown to improve glucose tolerance and insulin resistance in animal models of obesity and diabetes. We studied the effect of a quick-release bromocriptine formulation on glucose homeostasis and insulin sensitivity in obese type 2 diabetic subjects. RESEARCH DESIGN AND METHODS -There were 22 obese subjects with type 2 diabetes randomized to receive a quick-release formulation of bromocriptine (n = 15) or placebo (n = 7) in a 16-week double-blind study. Subjects were prescribed a weight-maintaining diet to exclude any effect of changes in body weight on the primary outcome measurements. Fasting plasma glucose concentration and HbA 1c were measured at 2-to 4-week intervals during treatment. Body composition (underwater weighing), body fat distribution (magnetic resonance imaging), oral glucose tolerance (oral glucose tolerance test [OGTT]), insulin-mediated glucose disposal, and endogenous glucose production (2-step euglycemic insulin clamp, 40 and 160 mU и min Ϫ1 и m Ϫ2 ) were measured before and after treatment. RESULTS -No changes in body weight or body composition occurred during the study in either placebo-or bromocriptine-treated subjects. Bromocriptine significantly reduced HbA 1c (from 8.7 to 8.1%, P = 0.009) and fasting plasma glucose (from 190 to 172 mg/dl, P = 0.02) levels, whereas these variables increased during placebo treatment (from 8.5 to 9.1%, NS, and from 187 to 223 mg/dl, P = 0.02, respectively). The differences in HbA 1c (⌬ = 1.2%, P = 0.01) and fasting glucose (⌬ = 54 mg/dl, P Ͻ 0.001) levels between the bromocriptine and placebo group at 16 weeks were highly significant. The mean plasma glucose concentration during OGTT was significantly reduced by bromocriptine (from 294 to 272 mg/dl, P = 0.005), whereas it increased in the placebo group. No change in glucose disposal occurred during the first step of the insulin clamp in either the bromocriptine-or placebo-treated group. During the second insulin clamp step, bromocriptine improved total glucose disposal from 6.8 to 8.4 mg и min Ϫ1 и kg Ϫ1 fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg и min Ϫ1 и kg Ϫ1 FFM (P Ͻ 0.05), whereas both of these variables deteriorated significantly (P Յ 0.02) in the placebo group. CONCLUSIONS -Bromocriptine improves glycemic control and glucose tolerance in obese type 2 diabetic patients. Both reductions in fasting and postprandial plasma glucose levels appear to contribute to the improvement in glucose tolerance. The bromocriptine-induced E m e r g i n g T r e a t m e n t s a n d T e c h n o l o g i e s
doi:10.2337/diacare.23.8.1154 pmid:10937514 fatcat:yptaj5y4i5ddzofwxbozkteveu