Bromocriptine

A novel approach to the treatment of type 2 diabetes

Hanno Pijl, Shinichiro Ohashi, Masafumi Matsuda, Yoshinori Miyazaki, Archana Mahankali, Vineeta Kumar, Ruben Pipek, Patricia Iozzo, Jack L Lancaster, Anthony H. Cincotta, Ralph A Defronzo

Research output: Contribution to journalArticle

153 Citations (Scopus)

Abstract

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 · min-1 · 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) (Δ = 1.2%, P = 0.01) and fasting glucose (Δ = 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 · min-1 ·kg-1 fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg · min-1 · kg-1 FFM (P < 0.05), whereas both of these variables deteriorated significantly (P ≤ 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.

Original languageEnglish (US)
Pages (from-to)1154-1161
Number of pages8
JournalDiabetes Care
Volume23
Issue number8
StatePublished - 2000

Fingerprint

Bromocriptine
Type 2 Diabetes Mellitus
Glucose
Placebos
Insulin
Therapeutics
Fasting
Glucose Tolerance Test
Body Weight Changes
Body Composition
Insulin Resistance
Fats
Body Fat Distribution
Glucose Clamp Technique
Double-Blind Method
Neurotransmitter Agents

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Pijl, H., Ohashi, S., Matsuda, M., Miyazaki, Y., Mahankali, A., Kumar, V., ... Defronzo, R. A. (2000). Bromocriptine: A novel approach to the treatment of type 2 diabetes. Diabetes Care, 23(8), 1154-1161.

Bromocriptine : A novel approach to the treatment of type 2 diabetes. / Pijl, Hanno; Ohashi, Shinichiro; Matsuda, Masafumi; Miyazaki, Yoshinori; Mahankali, Archana; Kumar, Vineeta; Pipek, Ruben; Iozzo, Patricia; Lancaster, Jack L; Cincotta, Anthony H.; Defronzo, Ralph A.

In: Diabetes Care, Vol. 23, No. 8, 2000, p. 1154-1161.

Research output: Contribution to journalArticle

Pijl, H, Ohashi, S, Matsuda, M, Miyazaki, Y, Mahankali, A, Kumar, V, Pipek, R, Iozzo, P, Lancaster, JL, Cincotta, AH & Defronzo, RA 2000, 'Bromocriptine: A novel approach to the treatment of type 2 diabetes', Diabetes Care, vol. 23, no. 8, pp. 1154-1161.
Pijl H, Ohashi S, Matsuda M, Miyazaki Y, Mahankali A, Kumar V et al. Bromocriptine: A novel approach to the treatment of type 2 diabetes. Diabetes Care. 2000;23(8):1154-1161.
Pijl, Hanno ; Ohashi, Shinichiro ; Matsuda, Masafumi ; Miyazaki, Yoshinori ; Mahankali, Archana ; Kumar, Vineeta ; Pipek, Ruben ; Iozzo, Patricia ; Lancaster, Jack L ; Cincotta, Anthony H. ; Defronzo, Ralph A. / Bromocriptine : A novel approach to the treatment of type 2 diabetes. In: Diabetes Care. 2000 ; Vol. 23, No. 8. pp. 1154-1161.
@article{ba3bd1d99bac4e5f9d7f59df0395011e,
title = "Bromocriptine: A novel approach to the treatment of type 2 diabetes",
abstract = "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 · min-1 · 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) (Δ = 1.2{\%}, P = 0.01) and fasting glucose (Δ = 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 · min-1 ·kg-1 fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg · min-1 · kg-1 FFM (P < 0.05), whereas both of these variables deteriorated significantly (P ≤ 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.",
author = "Hanno Pijl and Shinichiro Ohashi and Masafumi Matsuda and Yoshinori Miyazaki and Archana Mahankali and Vineeta Kumar and Ruben Pipek and Patricia Iozzo and Lancaster, {Jack L} and Cincotta, {Anthony H.} and Defronzo, {Ralph A}",
year = "2000",
language = "English (US)",
volume = "23",
pages = "1154--1161",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "8",

}

TY - JOUR

T1 - Bromocriptine

T2 - A novel approach to the treatment of type 2 diabetes

AU - Pijl, Hanno

AU - Ohashi, Shinichiro

AU - Matsuda, Masafumi

AU - Miyazaki, Yoshinori

AU - Mahankali, Archana

AU - Kumar, Vineeta

AU - Pipek, Ruben

AU - Iozzo, Patricia

AU - Lancaster, Jack L

AU - Cincotta, Anthony H.

AU - Defronzo, Ralph A

PY - 2000

Y1 - 2000

N2 - 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 · min-1 · 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) (Δ = 1.2%, P = 0.01) and fasting glucose (Δ = 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 · min-1 ·kg-1 fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg · min-1 · kg-1 FFM (P < 0.05), whereas both of these variables deteriorated significantly (P ≤ 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.

AB - 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 · min-1 · 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) (Δ = 1.2%, P = 0.01) and fasting glucose (Δ = 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 · min-1 ·kg-1 fat-free mass (FFM) (P = 0.01) and nonoxidative glucose disposal from 3.3 to 4.3 mg · min-1 · kg-1 FFM (P < 0.05), whereas both of these variables deteriorated significantly (P ≤ 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.

UR - http://www.scopus.com/inward/record.url?scp=0033861067&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033861067&partnerID=8YFLogxK

M3 - Article

VL - 23

SP - 1154

EP - 1161

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 8

ER -