"The association between Type 2 diabetes and depression, both major public health challenges, remains unclear," Dr. Mika Kivimaki, of University College London, UK, and colleagues write. In one recent report, for example, people with Type 2 diabetes were at increased risk for depression, while non-diabetics with higher fasting glucose levels appeared to be protected against depression.

For their current study, the researchers used data from the British Whitehall II study on 4,228 individuals between the ages of 50 and 74 years (mean, 60.7 years), with a mean fasting glucose level of 5.55 mmol/L.

Compared to subjects with normal fasting glucose, those with impaired fasting glucose had marginally reduced scores on the Center for Epidemiologic Studies Depression scale (CES-D) (9.9 versus 9.0, respectively; p = 0.05).

The CES-D score was elevated in patients with diabetes (11.2; p = 0.002). After adjustment, a U-shaped association was observed between fasting glucose and depression, with elevated CES-D scores at low (9.0 mmol/L) glucose levels (p = 0.001).

Curvilinear associations were also found between depression and 2-h postload glucose (p = 0.11) and A1C (p = 0.007).

Dr. Kivimaki stated that, "A U-shaped association is a potential reason for inconsistent findings" in earlier studies. "Given the age range of our cohort, it is possible that low glucose levels are related to underlying diagnosed or undiagnosed chronic diseases, which in turn increase the risk of depression."

"These findings should be replicated in other cohorts," Dr. Kivimaki said. "It would be important to examine whether there is a U-shaped association in younger cohorts in which chronic conditions are rare."