Bromocriptine treatment over 12 years in acromegaly: effect on glucose tolerance and insulin secretion

Abstract

It is not known whether the beneficial effect of bromocriptine on glucose homeostasis in acromegaly is limited by a certain duration of therapy. To elucidate this problem, oral glucose tolerance tests were performed in 12 acromegaly patients before bromocriptine medication, under therapy (15.0-I-6.8 mg/day for 12+3 years), and during a 2-week drug withdrawal after long-term treatment. Initially altered glucose tolerance was normalized in 4 of 5 patients under bromocriptine therapy. During drug withdrawal the mean fasting glucose level and the mean glucose concentration at 120 rain after oral glucose load increased from 5.05_+0.61 to 5.77+0.78 mmol/1 and from 5.61 __ 2.05 to 7.55 +_ 3.05 mmol/1, respectively. A deterioration in glucose homeostasis was observed in 9 patients, and impaired glucose tolerance was ameliorated (but not to normal range) in 2 when bromocriptine was withdrawn. The proportion of alterations in glucose tolerance during drug withdrawal corresponded to that before the beginning of long-term bromocriptine treatment. Impaired glucose tolerance, observed in 2 patients under bromocriptine treatment, seemed to be compensated because a distinct elevation of glycosylated hemoglobin Ale was not observed. Bromocriptine led to a significant decrease in basal as well as glucosestimulated insulin levels, and growth hormone secretion during oral glucose load was reduced in all 12 patients. Similarly to the increased growth hormone secretion after drug withdrawal in 11 patients, a rise in glucose-stimulated insulin secretion was found in all patients; hereby, the mean insulin levels at 0 and 120 min during oral glucose load rose significantly from 7.5+2.6 to 12.1 _+5.1 mU/1 (P<0.01) and from 71.3___52.1 to 101.4_ 50.7mU/1 (P<0.02), respectively. A direct relaAbbreviations: AUC = area under the curve; GH = growth hormone; PRL =prolactin * Dedicated to Prof. Dr. N. Z611ner on the occasion of his 70th birthday tionship between disturbance in glucose homeostasis and degree of hypersomatotropism was not observed. Our data confirm that the beneficial effect of bromocriptine therapy on glucose homeostasis in selected patients with acromegaly is still present after dopaminergic treatment over a mean period of 12 years. Compared with the published rates on improved glucose homeostasis under octreotide, the effect of bromocriptine seems to be more favorable.

Pharmacological Modulation of Dopamine Receptor D2-Mediated Transmission Alters the Metabolic Phenotype of Diet Induced Obese and Diet Resistant C57Bl6 Mice

“…In accordance, short-term administration of bromocriptine ameliorates various metabolic anomalies in obese humans without affecting body weight [18] and longer term treatment improves glycemic control and serum lipid profiles in patients with type 2 diabetes [68]. In addition, DRD2 agonists improve glucose and lipid metabolism in patients with hyperprolactinemia [69, 70] and acromegaly [71–73]. Although DRD2 agonists generally benefit nutrient metabolism, the use of these drugs is sometimes associated with the development of impulse control disorders, including binge and compulsive eating, in patients with Parkinson's disease, which may lead to excessive weight gain and insulin resistance [74, 75].…”

Insulin Resistance in Patients With Acromegaly

“…Table 1 summarizes the effects of acromegaly-specific therapies on glucose metabolism. The relationship between dopamine agonist therapy and glucose metabolism has been subject to only a few reports, showing a reduction in basal and stimulated insulin levels (130, 144). Nevertheless, the impact of dopamine agonists on glucose metabolism was extensively studied in patients with prolactinomas, confirming their positive effect in reducing insulin resistance and ameliorating beta-cell function (145).…”

A háziorvos szerepe az acromegaliás betegek gondozásában, fókuszban a szénhidrát-anyagcsere zavara

“…A gyógyszerek közül a dopaminagonisták valószínűleg a perifériás és a splanchnicus területek glükózfelvételének fokozásával és a májban a glükoneogenezis csökkentésével javítják a glükózanyagcserét [9,10]. A bromokriptin mérsékelten javítja a glükóztoleranciát acromegaliás betegekben [11]. Fontos megemlíteni, hogy a bromokriptin egyéb indikációs körben történő alkalmazására, a 2-es típusú diabetes bromokriptinnel történő kezelésére vizsgálatok történtek, és az amerikai Gyógyszer-és Élelmiszer-ellenőrző Hatóság már engedélyezte ez irányú felhasználását [12].…”