Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance: Influence on muscle glycogen synthase and insulin receptor kinase activity

Breum, Leif; Bjerre, Ulla; Bak, Jens F.; Jacobsen, Søren; Astrup, Arne

« Previous Next »Metabolism - Clinical and Experimental
Volume 44, Issue 12 , Pages 1570-1576, December 1995

Long-term effects of fluoxetine on glycemic control in obese patients with non-insulin-dependent diabetes mellitus or glucose intolerance: Influence on muscle glycogen synthase and insulin receptor kinase activity☆

Leif Breum
- Address reprint requests to Leif Breum, MD, Department of Endocrinology E, Frederiksberg Hospital, University of Copenhagen, Ndr. Fasanvej 57, DK-2000 Frederiksberg C, Denmark.
- Departments of Internal Medicine and Endocrinology, Hvidovre Hospital and Frederiksberg Hospital, University of Copenhagen Copenhagen, Denmark
- Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Copenhagen, Denmark
- The University Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark
Ulla Bjerre
- Departments of Internal Medicine and Endocrinology, Hvidovre Hospital and Frederiksberg Hospital, University of Copenhagen Copenhagen, Denmark
- Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Copenhagen, Denmark
- The University Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark
Jens F. Bak
- Departments of Internal Medicine and Endocrinology, Hvidovre Hospital and Frederiksberg Hospital, University of Copenhagen Copenhagen, Denmark
- Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Copenhagen, Denmark
- The University Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark
Søren Jacobsen
- Departments of Internal Medicine and Endocrinology, Hvidovre Hospital and Frederiksberg Hospital, University of Copenhagen Copenhagen, Denmark
- Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Copenhagen, Denmark
- The University Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark
Arne Astrup
- Departments of Internal Medicine and Endocrinology, Hvidovre Hospital and Frederiksberg Hospital, University of Copenhagen Copenhagen, Denmark
- Research Department of Human Nutrition, Royal Veterinary and Agricultural University, Copenhagen, Denmark
- The University Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus, Denmark

Received 19 November 1994; accepted 28 March 1995.

Abstract

Fluoxetine (F) is a specific serotonin-reuptake inhibitor that has been shown to promote weight loss and improve glycemic control in obese diabetic patients. To study its long-term metabolic effect, 40 obese patients with non-insulin-dependent diabetes mellitus (NIDDM) or impaired glucose tolerance (IGT) were included in a 12-month, randomized, placebo-controlled study. Patients were assigned to receive either 60 mg F or placebo (P) daily in conjunction with a 5.0-MJ/d diet (> 50% carbohydrate). Both groups showed a significant weight loss, with a nadir after 6 months without group differences (mean ± SD: F, 10.1 ± 10.0 kg; P, 9.4 ± 11.5 kg). Fifteen patients from the F group and 14 from the P group completed the 12-month study without weight loss differences. Glycemic regulation improved along with the weight loss, but with a larger decline in plasma C-peptide and fasting glucose levels in the F group (P < .05). Total skeletal muscle glycogen synthase (GS) activity increased by 31% in the F group (P < .01) and by 17% in the P group (nonsignificant) after 6 months of treatment, but was still less than the activity in normal-weight controls (aged 28.0 ± 6.3 years; body mass index, 23.5 ± 2.2). After adjustment for fasting glucose, insulin, weight loss, and diabetic state, a positive effect of F remained on the total GS activity, which accounted for 27% of the variation (P < .05). The waist to hip ratio was reduced in P subjects as compared with F subjects (P < .05). Fat-free mass (FFM) tended to be more reduced in the F group as compared with P subjects (4.9 v 1.9 kg), although the difference did not reach statistical significance. In conclusion, F seems to improve insulin sensitivity beyond the effect mediated through weight loss by a possible effect on GS activity in skeletal muscle tissue.

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