Bromocriptine redirects metabolism and prevents seasonal onset of obese hyperinsulinemic state in Syrian hamsters

Bromocriptine reduced plasma concentration of insulin throughout the day, especially at light onset, by 78% without change in baseline glucose level and markedly decreased steady state plasma glucose (by 40%) during a continuous infusion of insulin and glucose. It also reduced the nocturnal plasma concentration of prolactin by 90%, cortisol by 70%, and thyroid hormones (thyroxine and triiodothyronine) by 50% and dramatically altered the circadian profiles of these hormones and insulin.

click here to read more....

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.

Valvular Heart Disease and dopamine agonists

Recently the possible correlation between dopamine agonists and valvular heart disease has been raised in a few conferences. Originally brought on by a recent article in NEJM by Zanettini et al in 2007 that looked at 11, 417 subjects who were prescribed anti-parkinsonian drugs and matched each case of valvular disease to 25 controls. Noted 31 cases of valvular diease and out of these 6 were given cabergoline, 6 pergolide, and 19 were not exposed to dopamine agonists. The rate of cardiac-valve regurgitation was increased with current use of pergolide (incidence-rate ratio, 7.1; 95% confidence interval [CI], 2.3 to 22.3) and cabergoline (incidence-rate ratio, 4.9; 95% CI, 1.5 to 15.6), but not with current use of other dopamine agonists.
Because of this higher incidence with cabergoline and pergolide as opposed to other dopamine agonists, the question is raised as to whether this is applicable to prolactinoma treatment in which we use much lower dosages of these agents.
To answer this Devin et al (Endocrine Practice Sept 2008) conducted a recent retrospective review of patients identified with hyperprolactinemia who underwent elective echocardiography. They noted valvular disease in 7% of cases (no different than the general population) and much less than close to 30% found in other studies.
Big differences were the mean dose of cabergoline was 0.91+/- 0.96mg per week, whereas the anti-parkinsonian doses may be as high as 3mg/d.