Bromocriptine and diabetes

Diabetes Care. 2000 Aug;23(8):1154-61. Links

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

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 x min(-1) x m(-2)) 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) (delta = 1.2%, P = 0.01) and fasting glucose (delta = 54 mg/dl, P < 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 x min(-1) kg(-1) fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg min(-1) x kg(-1) FFM (P < 0.05), whereas both of these variables deteriorated significantly (P < or = 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 improvement in glycemic control is associated with enhanced maximally stimulated insulin-mediated glucose disposal.