The current study provides evidence that children’s depressive symptoms are a prospective risk factor for worsening insulin resistance. Even when accounting for known additional risk factors, including family history of type 2 diabetes, children’s baseline BMI, and changes in children’s BMI over time, depressive symptoms were associated with greater insulin resistance ~6 years later. Depressive symptoms’ impact on insulin resistance was clinically meaningful such that depressive symptoms were associated with a significantly greater likelihood of developing clinically elevated HOMA-IR (defined as ≥3.16). Of note, children’s degree of insulin resistance is a significant predictor of type 2 diabetes onset in young adulthood, even after accounting for BMI (17
The current findings are consistent with previous cross-sectional studies demonstrating a link between depressive symptoms or negative affect and insulin resistance in youth independent of body composition (12
). Moreover, the present results are consistent with adult data demonstrating that depressive symptoms are related to greater odds of developing type 2 diabetes (9
). The mechanisms explaining the relationship between depressive symptoms and insulin resistance are not well understood. Symptoms of depression, including fatigue, lack of energy, or anhedonia (referring to loss of pleasure over activities that one previously found enjoyable), may prompt behavioral decreases in voluntary energy expenditures, such as exercise, which, in turn, may heighten insulin resistance. Consistent with this notion, adolescent depressive symptoms are associated with poorer cardiorespiratory fitness (18
). Depressive symptoms also have been concurrently related to emotional eating patterns (19
), which possibly may promote insulin resistance independent of weight gain. From a neurohumoral framework, depressive symptoms are hypothesized to promote insulin resistance by upregulating cortisol and enhancing its downstream effects, including increasing the production of the neurotransmitter neuropeptide Y (10
Strengths of the current investigation include the longitudinal nature of data, the examination of depressive symptoms and insulin resistance in a sizeable sample of children, and the adjustment for important covariates, including measured BMI and BMI change. Study limitations include the use of surrogate measures for assessing insulin resistance and depression. The measure of insulin resistance was derived from fasting values, which, although highly related to clamp-derived measures, is not considered as precise an assessment. Likewise, although the CDI is a widely used, reliable, and valid measure of depressive symptoms, it does not provide a diagnostic assessment of clinical depression. Future longitudinal studies examining the impact of depressive symptoms on insulin resistance using criterion measures are warranted. Another significant study shortcoming was the very high degree of attrition that diminished the sample size at follow-up. Although the greater likelihood of dropout among youth with greater baseline depressive symptoms and higher insulin resistance could be expected to attenuate the significance of the results, this pattern, as well as the nature of the sample being oversampled to include youth at risk for adult obesity, may limit the generalizability of the findings. In addition, the effect of depressive symptoms on insulin resistance was small relative to the effect of anthropometric variables. Youth with major depression or active suicidal ideation were excluded from participation. Examination of the depression-insulin resistance relationship in samples of adolescents with clinically elevated symptomatology may shed more light on the magnitude of the depression-insulin relationship.
Adolescence marks a developmental period notable for a normative increase in insulin resistance that typically resolves by the end of puberty (22
). Yet, youth vulnerable for type 2 diabetes may display the largest increases in insulin resistance and continued progression of worsening insulin resistance throughout late adolescence and possibly into young adulthood. Therefore, investigation of the impact of child or adolescent depressive symptoms on the progression of insulin resistance during an even longer follow-up interval would be important to clarify the role of pediatric depressive symptoms in the development of type 2 diabetes. An equally important task for future research is to elucidate the mechanisms by which depressive symptoms may impact insulin resistance. An understanding of the putative behavioral and/or physiological factors that explain how depression relates to insulin resistance is crucial to the design of effective interventions.
In the current study, we observed that depressive symptoms begin to exert an impact on insulin resistance early in life. Among adults, interventions targeting depressive symptoms among adults with type 2 diabetes and/or major depression have been shown to improve indices of glucose impairment or insulin resistance even without altering body weight or adiposity (1
). Research is needed to determine whether early interventions to decrease youths’ depressive symptoms will ameliorate worsening insulin resistance and consequently lessen the risk of developing type 2 diabetes. If treating or preventing the onset of major depression in adolescents improves insulin resistance, routine depression screening in primary care settings, especially among youth at risk for type 2 diabetes, might have the potential to delay or possibly prevent type 2 diabetes onset in a considerable subset of individuals.