Department of Internal Medicine 463, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB, Nijmegen, the Netherlands,
Diabetologia. 2013 Dec;56(12):2573-81. doi: 10.1007/s00125-013-3018-6. Epub 2013 Sep 25.
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.
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.
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/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.
ClinicalTrials.gov: NCT00781495.
The study was funded by European Foundation for the Study of Diabetes and the Dutch Diabetes Research Foundation.
目的/假设：在 2 型糖尿病患者中，胰岛素治疗伴随着以腹部脂肪量增加为特征的体重增加。脂肪组织量的扩张通常伴随着深刻的形态和炎症变化。我们假设，胰岛素相关的脂肪量增加也会导致人体皮下脂肪组织的形态发生变化，并增加炎症，尤其是当体重增加过多时。
我们研究了体重增加对 2 型糖尿病患者开始胰岛素治疗前后脂肪细胞大小、巨噬细胞浸润以及脂肪组织中关键炎症标志物的 mRNA 表达和蛋白水平的影响。
正如预期的那样，胰岛素治疗显著增加了体重。在皮下脂肪组织水平上，胰岛素治疗导致巨噬细胞浸润。当比较在 6 个月的胰岛素治疗后体重增加无或很少的患者与体重增加>4%的患者时，两个亚组均显示巨噬细胞浸润增加。然而，与体重未增加的患者相比，在 6 个月胰岛素治疗后，体重增加的患者单核细胞趋化蛋白-1、TNF-α 和 IL-1β 的蛋白水平更高。
结论/解释：我们得出结论，2 型糖尿病患者的胰岛素治疗改善了血糖控制，但也导致了体重增加和巨噬细胞涌入皮下脂肪组织。在以明显胰岛素相关体重增加为特征的患者中，巨噬细胞涌入脂肪组织伴随着更明显的炎症状态。
ClinicalTrials.gov：NCT00781495。
该研究由欧洲糖尿病研究基金会和荷兰糖尿病研究基金会资助。
