12.09.2013

by Kristina Fiore
Staff Writer, MedPage Today

Insulin therapy prompts a flood of macrophages into subcutaneous adipose tissue — an effect that appears to be independent of how much weight patients gain once they start the treatment, researchers found.

In a small observational study, levels of macrophages around fat cells rose similarly for all type 2 diabetes patients started on insulin, but those who gained more weight also had increased levels of other inflammatory markers, Henry Jansen, MD, of Radboud University and Nijmegen Medical Center in the Netherlands, and colleagues reported in Diabetologia.

“Pronounced insulin-associated weight gain might promote a more pro-inflammatory status of the adipose tissue that is independent of the absolute number of macrophages,” the researchers wrote.

More evidence has suggested that giving type 2 diabetics insulin suppresses the inflammatory process, but at the systemic level, these effects may be counteracted by pro-inflammatory changes associated with increased fat mass.

To assess the inflammatory response in these patients, Jansen and colleagues conducted a prospective multicenter observational study in which they focused on 43 patients with type 2 diabetes who were started on insulin and had adipose tissue biopsies. They also assessed a matched cohort of non-diabetic obese patients, and followed all patients for 6 months.

Overall, those on insulin gained weight — about 2 kg to 6 kg (4 to 13 lbs.) — and had increases in body mass index (BMI), waist circumference, and body fat mass (P<0.05 for all).

Insulin therapy had no effect on diameter or distribution of adipocytes, but Jansen and colleagues did find a significantly greater influx of macrophages into the adipose tissue among diabetics on insulin therapy than among controls.

When patients were broken into two groups — those who gained less than 4% of their body weight, and those who gained more than that amount — the researchers saw no differences in the level of macrophage influx.

This suggests that insulin therapy “independently of weight gain increases the number of macrophages within the adipose tissue,” they wrote.

There was, however, a more pronounced inflammatory response in patients who gained more weight. These patients had higher levels of monocyte chemoattractant protein-1 (MCP-1), TNF-alpha, and IL-1beta compared with those who put on fewer pounds.

“Pronounced insulin-associated weight gain might promote a more pro-inflammatory status of the adipose tissue that is independent of the absolute number of macrophages,” Jansen and colleagues wrote.

In this case, the macrophages’ tissue remodeling function could be at play, they suggested, noting that these immune cells play a bigger role than just mediating inflammatory responses.

They concluded that the “systemic anti-inflammatory effects of insulin therapy might be, at least partially, offset by the pro-inflammatory changes associated with increased fat mass.”