Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue

H.J. Jansen, R. Stienstra, J.A. van Diepen, A. Hijmans, J.A. van der Laak, G.M. Vervoort, C.J. Tack

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

Aims/hypothesis Insulin therapy in patients with type 2 diabetes mellitus is accompanied by weight gain characterised by an increase in abdominal fat mass. The expansion of adipose tissue mass is generally paralleled by profound morphological and inflammatory changes. We hypothesised that the insulin-associated increase in fat mass would also result in changes in the morphology of human subcutaneous adipose tissue and in increased inflammation, especially when weight gain was excessive. Methods We investigated the effects of weight gain on adipocyte size, macrophage influx, and mRNA expression and protein levels of key inflammatory markers within the adipose tissue in patients with type 2 diabetes mellitus before and 6 months after starting insulin therapy. Results As expected, insulin therapy significantly increased body weight. At the level of the subcutaneous adipose tissue, insulin treatment led to an influx of macrophages. When comparing patients gaining no or little weight with patients gaining >4% body weight after 6 months of insulin therapy, both subgroups displayed an increase in macrophage influx. However, individuals who had gained weight had higher protein levels of monocyte chemoattractant protein-1, TNF-a and IL-1ß after 6 months of insulin therapy compared with those who had not gained weight. Conclusions/interpretation We conclude that insulin therapy in patients with type 2 diabetes mellitus improved glycaemic control but also induced body weight gain and an influx of macrophages into the subcutaneous adipose tissue. In patients characterised by a pronounced insulin-associated weight gain, the influx of macrophages into the adipose tissue was accompanied by a more pronounced inflammatory status.
Original languageEnglish
Pages (from-to)2573-2581
JournalDiabetologia
Volume56
Issue number12
DOIs
Publication statusPublished - 2013

Keywords

  • predicting body density
  • adipocyte differentiation
  • generalized equations
  • weight-gain
  • obese mice
  • inflammation
  • adipogenesis
  • activation
  • humans

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