Start of insulin therapy in patients with type 2 diabetes mellitus promotes the influx of macrophages into subcutaneous adipose tissue.
OBJECTIVE
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-α and IL-1β after 6 months of insulin therapy compared with those who had not gained weight.


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov: NCT00781495.


BACKGROUND
The study was funded by European Foundation for the Study of Diabetes and the Dutch Diabetes Research Foundation.
Department of Internal Medicine 463, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, the Netherlands, H.Jansen@jbz.nl.
H J
HJ
Jansen
R
R
Stienstra
J A
JA
van Diepen
A
A
Hijmans
J A
JA
van der Laak
G M M
GM
Vervoort
C J
CJ
Tack
D001786:Blood Glucose / Q000378:metabolism*; D001823:Body Composition; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000188:drug therapy*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D050151:Subcutaneous Fat / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha; D015430:Weight Gain / Q000187:drug effects* / Q000276:immunology
D001786:Blood Glucose; D007328:Insulin; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha