In the present study we examined the longitudinal association between glucose metabolism and depressive symptoms in a large cohort of older British adults. We showed that A1C was associated with incident elevated depressive symptoms over 2 years follow up, especially in men.
Cross-sectionally, the probability of depressive symptoms increased with increasing HbA1c levels until approximately the value of 8% after which there was a plateau. In longitudinal analyses, we found a modest association between diagnosed diabetes at baseline and depressive symptoms at follow up. The magnitude of this association is comparable to a recent study that employed data from general practices to examine the association between diabetes and subsequent risk of depression (Aarts et al. 2009
). Injecting insulin and limited knowledge about diabetes management were both associated with greater risk of reporting depressive symptoms at baseline, but these factors did not predict subsequent depression at follow up after taking into account the baseline association. Consistent with cross-sectional findings from other recent studies (Adriaanse et al. 2008
; Gale et al. 2010
), participants with impaired glucose metabolism at baseline were at risk of subsequent depression. However, in several other studies impaired glucose tolerance or undiagnosed diabetes was associated with lower risk of depression (Golden et al. 2008
; Icks et al. 2008
) or not associated with depression at all (Knol et al. 2007
; Rhee et al. 2008
; Holt et al. 2009
; Aujla et al. 2009
). Indeed, when we used fasting glucose as an indicator of impaired fasting glucose there was no association with depression. Therefore these discrepancies might possibly be explained by differences in the methods to assess glucose metabolism, and also characteristics of the samples and measures of depression. However, given that the majority of previous studies have been cross-sectional, the prospective nature of our study adds considerably to the current evidence base.
The highest probability of depression was observed at A1C levels of 8 – 9%, which might reflect unrecognised, pre-clinical diabetes and the presence of undiagnosed symptoms. We did not observe increased risk of depressive symptoms among individuals with very low glucose levels. Such an association was previously observed in the Whitehall II cohort (Kivimaki et al. 2009
), but not in the Vietnam Experience Study, where study participants were, on average, 20 years younger (Gale et al. 2010
). The reason for this discrepancy was suggested to be a higher prevalence of underlying chronic conditions that potentially relate to low glucose and increased depression risk in Whitehall II. However, the participants in present study were older than those in both previous studies and we observed no elevation in depression towards the low end of the A1C distribution. Lastly, slightly stronger associations between A1C and depressive symptoms were observed among men, although these sex differences were not statistically significant (p=0.08 for sex interaction). The reasons for this possible sex difference remain unclear and the findings are not consistent with a recent study in women (Pan et al. 2010
). The mechanisms linking diabetes and depression also remain unclear. Depression could result from the biochemical changes directly caused by diabetes, its treatment, or from the distress associated with living with diabetes and its often debilitating consequences. For example, preliminary evidence found brain abnormalities, such as reduced white matter volume and enlarged cerebrospinal fluid space, in obese adolescents with type II diabetes, which might result from a combination of subtle vascular changes and glucose abnormalities (Yau et al. 2010
). A common causal pathway for depression and diabetes is also a possibility, with early factors, such as low birth weight and childhood adversity predisposing individuals to both obesity/type 2 diabetes (de Lauzon-Guillain et al. 2010
; Thomas et al. 2008
) and depression (Colman et al. 2007
The strengths of this study include the sampling of a large, representative general population-based group, and the well characterised study members which facilitates insights into the role of potential confounding factors, and the prospective element of the study design. The limitations of the present study should also be recognized. Participants retained in our analyses generally reported lower levels of depressive symptoms and better health compared with the overall sample, although the analytic approach that we used accounted for missing data in estimating the association between glucose indicators, diabetes and depression. In fact, weighting for non-response actually had a minimal impact on the results, providing evidence against bias due to selective sample retention. Although the definition of diabetes was not only based on self report but also on objective blood measures, we were unable to differentiate between type I and II. However, it is likely that the majority of cases were type II since this is by far the most prevalent condition in the general adult population.