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The possibility of depression causing diabetes was first advanced in 1684 by Thomas Willis, who wrote that diabetes was the result of "sadness, or long sorrow." Over the years, this view enjoyed little popular support, and depression more often was seen as something that occurred secondary to diabetes—a natural reaction to the arduous nature of the medical illness and its complications. In most cases, this view proved to be oversimplified or plainly mistaken. Studies dating the onsets of depression and diabetes in type 2 diabetes showed a distinct tem- poral relationship, wherein depression preceded diabetes in 90% of cases by 8-10 years. Subsequent longitudinal studies (reviewed in the previous articles) con- firmed the prognostic significance of depression by showing that it is an independent risk factor both for the development of type 2 diabetes and for the development of complications of type 1 or type 2 diabetes, particularly coronary heart disease. The mecha- nisms by which depression imposes these risks have not been clearly estab- lished. The list of candidate mediators is long and varied, reflecting multifac- eted effects of depression on behav- ioral and physiological factors that may interact with one another or change over time (Table 1). Identification of depression mech- anisms that are relevant to medical outcome is the focus of much current research. And while the mechanisms involved remain to be clarified, the story outlined in the preceding sec- tions has evolved sufficiently to sug- gest that potential benefits of depres- sion treatment likely surpass expect- ed improvements in mood and quali- ty of life. Successful treatment of depression also may improve glycemic control, insulin effective- ness, and other measures of diabetes and cardiovascular risk and thereby

Section III: Practical Considerations in the Management of Depression in Diabetes