title: Weight-sparing effect of insulin detemir: a consequence of central nervous system-mediated reduced energy intake?
abstract: Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight-sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter-regulatory response to insulin through restoration of the hepatic-peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight-sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.
authors.affiliation: Diabetes and Endocrinology, Royal Surrey County Hospital and University of Surrey, Guildford, UK.
authors.forename: D
authors.initials: D
authors.lastname: Russell-Jones
authors.affiliation: Diabetes-Zentrum für Kinder und Jugendliche, Kinderkrankenhaus auf der Bult, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Danne
authors.affiliation: Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Hermansen
authors.affiliation: Tennessee Valley Healthcare System and Vanderbilt University School of Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: K
authors.initials: K
authors.lastname: Niswender
authors.affiliation: Royal Hospital for Sick Children, Glasgow, UK.
authors.forename: K
authors.initials: K
authors.lastname: Robertson
authors.affiliation: Jenny Lind Children's Department, Norfolk and Norwich University Hospital, Norwich, UK.
authors.forename: N
authors.initials: N
authors.lastname: Thalange
authors.affiliation: New York Obesity Nutrition Research Center, Columbia University, New York, NY, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Vasselli
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey.
authors.forename: B
authors.initials: B
authors.lastname: Yildiz
authors.affiliation: Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Member of the German Center for Diabetes Research (DZD), Tübingen, Germany.
authors.forename: H U
authors.initials: HU
authors.lastname: Häring
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D003920:Diabetes Mellitus / Q000188:drug therapy*; D002149:Energy Intake / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D000069057:Insulin Detemir / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000069057:Insulin Detemir
keywords: basal insulin; drug mechanism; weight loss therapy