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Anxiety and Depression May Increase Mortality Risk in Type 2 Diabetes

Symptoms of anxiety found to be independent of symptoms of depression

Type 2 diabetes (T2D) which affects >9% of the population, and depression, which affects >5% of the population, are the leading global causes of morbidity and mortality. Patients with T2D experience depression five-times higher than the general population. Due to the symptomatic similarities between anxiety and depression, they are often documented together. Mortality studies have shown a consistent association between depression and excess mortality, but the evidence relating anxiety and mortality risk remains inconsistent. Recent studies reflect a higher relative risk of mortality associated with depression than anxiety in the general population.

Studies have demonstrated that the mortality risk associated with depression varies according to the severity of disorder and sex. On one hand, major depression increases mortality risk in both men and women, but minor depression increases risk only in men. On the other hand, a study showed excess mortality with anxiety associated in men than women. However, studies rarely consider the presence of anxiety or depression as comorbid, thus the ability to attribute risk to either disorder is obscured. Due to greater risk of noncompliance, depression is a concern in T2D patients who self-manage their treatment. The purpose of the study was to examine the mortality risk associated with T2D and comorbid symptoms of depression and anxiety between men and women in a large general population to determine whether they are differentially affected. The primary outcome of interest was all-cause mortality. The study data was obtained from a large population-based survey conducted over three waves of the Norwegian Nord-Trøndelag Health Study (HUNT1, 2, and 3).

The study data included 64,177 Norwegian adults from the HUNT2 with linkage to the Norwegian Causes of Death Registry. The study consisted of participants with or without T2D, but excluded subjects with type 1 or other types of diabetes. The primary exposures included T2D status, level of depression and anxiety symptoms. Individuals received a final classification of T2D and confirmed having not begun insulin treatment within 1 year of diagnosis. Depression and anxiety symptoms were measured using the seven-item Cohort Norway Mental Health Index (CONOR-MHI). Subjects with mean scores of depression above 2.15 were classified as having “high” symptom levels and the ones falling below this score were classified as having “low or no” affective symptoms. Three mutually exclusive variables were generated to compare independent categories of depression, anxiety, and T2D status. Covariates included age, education, waist circumference, physical activity, smoking, history of diabetes, antidepressant use, insulin use, and comorbid chronic conditions. Cox proportional hazards models were used to examine mortality risk over 18 years associated with T2D status and the presence of comorbid affective symptoms at baseline.

The study results showed increase in the mortality risk in individuals with diabetes in the presence of depression or anxiety, or both. Mortality risk was lowest for symptoms of anxiety, higher for comorbid depression-anxiety, and highest for depression. Also, excess mortality risk associated with depression and anxiety was observed in men with diabetes, but not in women. The highest risk of death was observed in men with diabetes and symptoms of depression only (hazard ratio 3.47, 95% CI 1.96, 6.14), compared to depression-anxiety (HR 3.42 [95% CI 1.84, 6.38]), and, to a lesser extent, comorbid anxiety (HR 2.14 [95% CI 1.41, 3.27]). Compared with having diabetes alone, mortality risk in women increased in the presence of depression (HR 1.86 [95% CI 1.53, 2.26] vs. HR 2.05 [95% CI 1.22, 2.72]), but was lowered in the presence of symptoms of anxiety (HR 1.38 [95% CI 0.95, 2.01]) and comorbid depression-anxiety (HR 1.14 [95% CI 0.57, 2.29]).

The study cannot be generalized to other populations because Nord-Trondelag demonstrates limited ethnic heterogeneity and a lower prevalence of diabetes than the developed areas. Another limitation includes self-reported symptoms of depression and anxiety and the duration of diabetes or affective symptoms at baseline were also excluded. However, the study included comprehensive range of confounders and a reliable source of mortality data.

In conclusion, depression had been strongly linked to increased mortality in individuals with T2D. The study acknowledged the excess mortality risk associated with symptoms of depression and/or anxiety comorbid with T2D and provided evidence that symptoms of anxiety affect mortality risk in individuals with T2D independently of symptoms. Further study is required for a clearer understanding of anxiety symptoms and its correlation to explain the differences and to clarify the inconsistent findings around anxiety and mortality that persist in the literature.

Practice Pearls:

  • Depression and/or anxiety may increase mortality in men with T2D. Mortality risk associated with depression varies with the severity of depressive disorder and sex.
  • Major depression increases mortality risk in both men and women, but minor depression increases risk only in men.
  • Despite high rates of co-occurring anxiety and depression, the risk of death associated with comorbid anxiety in individuals with T2D is poorly understood.

References:

  1.  Hirschfeld RM. The comorbidity of major depression and anxiety disorders: recognition and management in primary care. Prim Care Companion. J Clin Psychiatry. 2001;3:244–254.
  2.  Naicker K, Johnson JA, Skogen JC, Manuel D, Overland S, Sivertsen B, and Colman I. Type 2 diabetes and comorbid symptoms of depression and anxiety: Longitudinal associations with mortality risk. Diabetes Care. 2017;40:352-358.
  3.  Semenkovich K, Brown ME, Svrakic DM, Lustman PJ. Depression in type 2 diabetes mellitus: Prevalence, impact, and treatment. Drugs. 2015;75:577–587.