Several diseases including microbial infection, rheumatoid arthritis, multiple sclerosis, and cancer have been linked to fatigue. They all have in common an upregulation of cytokines, including interleukin (IL)-1β and tumor necrosis factor-α (TNF-α), which may interfere with clock gene functions (1). Increasing evidence associates type 2 diabetes with inflammatory processes characterized by elevated production of proinflammatory cytokines and infiltration of immune cells. Reducing IL-1 activity in prediabetes and diabetes improves insulin secretion, glycemic control, and markers of systemic inflammation (2–4). Given this background, we hypothesized that fatigue levels may be increased in type 2 diabetes and may be improved by IL-1β antagonism.

Within a placebo-controlled, doubleblind study of IL-1β antagonism with a monoclonal anti–IL-1β antibody, XOMA052, involving 30 patients with type 2 diabetes (4), we evaluated fatigue using the Fatigue Scale for Motor and Cognitive functions (5). Besides differentiating between cognitive and motor fatigue, this scale offers a subdivision into different grades of fatigue severity. At baseline, according to predefined cutoff values, 47% of the patients had no, 20% had mild, 17% had moderate, and 16% had severe fatigue, meaning that more than half of the patients suffered from considerable fatigue symptoms compared with a healthy population (5). A significant correlation between fatigue and duration of diabetes was evident (R 5 0.532, P 5 0.002). This correlation was stronger for cognitive fatigue (R 5 0.541, P 5 0.002) compared with motor fatigue (R 5 0.486, P 5 0.007). No correlation between fatigue and age, HbA1c, body weight, body temperature, and C-reactive protein was found. One month after