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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\u2010sparing 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 (\n                    <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>\n                    ); 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.\n                    <jats:styled-content style=\"fixed-case\">CNS<\/jats:styled-content>\n                    effects may be mediated by direct action, by indirect stimulation by peripheral mediators and\/or via a more physiological counter\u2010regulatory response to insulin through restoration of the hepatic\u2013peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight\u2010sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review.\n                  <\/jats:p>","DOI":"10.1111\/dom.12493","type":"journal-article","created":{"date-parts":[[2015,5,13]],"date-time":"2015-05-13T13:00:39Z","timestamp":1431522039000},"page":"919-927","source":"Crossref","is-referenced-by-count":28,"title":["Weight\u2010sparing effect of insulin detemir: a consequence of central nervous system\u2010mediated reduced energy intake?"],"prefix":"10.1111","volume":"17","author":[{"given":"D.","family":"Russell\u2010Jones","sequence":"first","affiliation":[{"name":"Diabetes and Endocrinology Royal Surrey County Hospital and University of Surrey  Guildford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Danne","sequence":"additional","affiliation":[{"name":"Diabetes\u2010Zentrum f\u00fcr Kinder und Jugendliche Kinderkrankenhaus auf der Bult  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Hermansen","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Internal Medicine Aarhus University Hospital  Aarhus Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Niswender","sequence":"additional","affiliation":[{"name":"Tennessee Valley Healthcare System and Vanderbilt University School of Medicine, Vanderbilt University  Nashville TN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"Robertson","sequence":"additional","affiliation":[{"name":"Royal Hospital for Sick Children  Glasgow UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Thalange","sequence":"additional","affiliation":[{"name":"Jenny Lind Children's Department Norfolk and Norwich University Hospital  Norwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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