The database search yielded 4,273 potentially relevant articles (Fig. 1). Of these, 31 primary studies (39 publications) [4, 6–9, 14–47] fulfilled the inclusion criteria.
Characteristics of primary studies
In most cases, depression was studied (n = 27) [4, 8, 9, 14–16, 18, 20, 21, 23, 25–31, 33, 34, 37, 39–42, 44–46], followed by mental disorders not further specified (n = 5) [6, 7, 9, 19, 43], anxiety disorders (n = 4) [9, 14, 18, 36] and post-traumatic stress disorder (PTSD) (n = 3) [14, 18, 45] (ESM Table 1). Of the primary studies, 27 were based on a sample of persons with either type 1 or type 2 diabetes [4, 6–9, 14, 16, 18–21, 23, 25–30, 33, 34, 37, 40–43, 45, 46]. Four studies investigated type 2 diabetes only [15, 31, 39, 44]. Healthcare costs were examined in various facets in the studies included. Inpatient costs were assessed in terms of hospitalisation rates or hospitalisation costs (n = 15) [4, 6, 8, 15, 20, 25, 29, 31, 34, 37, 39, 42–44, 46], and length of stay (n = 9) [7, 15, 19, 20, 25, 26, 30, 42, 46]. Outpatient costs were assessed in terms of frequency and costs of outpatient visits (n = 19) [4, 6–8, 14, 15, 18–21, 23, 25, 26, 30, 31, 34, 37, 42, 45], mental health specialist visits and costs (n = 4) [4, 7, 8, 21, 36], emergency department visits (n = 11) [4, 16, 20, 21, 29, 30, 34, 37, 39, 42, 44] and medication costs (n = 6) [4, 20, 31, 34, 37, 40]. Total healthcare costs or utilisation were studied in 13 primary studies [4, 8, 9, 14, 20, 25, 27, 28, 31, 34, 37, 40, 41] and diabetes-related preventive services in five studies [7–9, 19, 23]. Indirect costs of absence from work were investigated in seven studies [6, 22, 33, 41, 42, 46, 47] (ESM Table 1). Most primary studies were conducted in the USA (n = 24). The other studies were located in Canada (n = 1), China (n = 1), Finland (n = 1), Germany (n = 1), UK (n = 1), Hungary (n = 1) and Singapore (n = 1).
Direct costs
Inpatient healthcare
Increased hospitalisation rates were found in six primary studies of depressed patients with diabetes compared with diabetic patients without depression, with SMDs ranging from 0.40 to 0.68 (ESM Fig. 1) [15, 29, 31, 39, 42, 46]. One study did not find an increased hospitalisation rate in a population sample of patients with diabetes and unspecified mental health problems [6]. Two other studies reporting β coefficients derived from regression analyses did not find a significant association between depression and hospitalisation rates in patients with diabetes [25, 37]. One study reported insufficient information to compute effect sizes [44]. Another study reported a decreased hospital admission rate directly following an emergency department visit [36].
Hospitalisation costs were examined in seven studies, yielding inconsistent results. Effect sizes of four studies of patients with diabetes and depression vs those without depression ranged from SMD 0.09 to 0.20, indicating slightly increased hospitalisation costs in diabetic patients with depression [4, 8, 20, 31]. One study reporting a β coefficient found a significant association between depression and hospitalisation costs in patients with diabetes [25], whereas another study did not find a significant association [37]. One study did not report sufficient information to compute effect sizes [34].
The primary studies examining length of stay yielded inconsistent results (ESM Fig. 2). In patients with diabetes and depression, length of stay was increased in three studies compared with diabetic patients without depression (SMD 0.34–0.40) [15, 42, 46]. One study found no differences between the groups [20]. Another study reporting a β coefficient found a significant association between depression and length of stay in depressed patients with diabetes [25], whereas another study failed to find such an association [30]. Patients with diabetes and any mental health problem were found to have a slightly increased length of stay compared with those without mental comorbidity in one study [19], whereas another study of patients with diabetes and any mental health problem did not find a significant difference between the groups [7]. One study did not report sufficient information to compute an effect size [26].
Outpatient healthcare
Patients with diabetes and comorbid mental disorders (depression, any mental disorder and PTSD) had more outpatient visits than diabetic patients without mental comorbidity, with SMD ranging from 0.09 to 0.64 [6–8, 15, 19–21, 23, 31, 42, 45] (ESM Fig. 3). Two other studies reporting β coefficients derived from regression analyses did not find a significant association between depression and outpatient visits in depressed patients with diabetes [30, 37], whereas another study of patients with diabetes and depression found a significant association between depression and increased outpatient visits [25]. A study investigating depressive, bipolar and anxiety disorder, as well as PTSD, found significant associations (β coefficients) with decreased outpatient visits, except for depressive disorder, in patients with diabetes [18]. One study did not report sufficient information to compute an effect size [26].
Five studies investigating costs of outpatient visits showed SMDs from 0.11 to 0.43, indicating increased costs in patients with diabetes and mental disorders (depression, anxiety disorder and PTSD) compared with diabetic patients without [4, 8, 14, 20, 31] (ESM Fig. 4). One study reporting a β coefficient found a significant association between depression and outpatient costs in patients with diabetes and depression [25], whereas another study did not find a significant association [37]. One study did not report sufficient information to compute an effect size [34].
The frequency of mental health specialist visits was examined in three primary studies investigating comorbid depression and panic episodes [7, 8, 21, 36], in which effect sizes varied between 0.35 and 1.26. Patients with diabetes and comorbid mental disorders showed higher rates of mental health specialist visits than diabetic patients without mental comorbidity. Costs of mental health treatments were higher in patients with diabetes and depression based on two primary studies showing effect sizes of SMD 0.33 [4] and SMD 0.58 [8].
The primary studies investigating frequency of emergency department visits reported increased rates in patients with diabetes and depression compared with diabetic patients without depression (SMD 0.10–0.82) (ESM Fig. 5) [16, 20, 21, 29, 39, 42]. Two other studies reporting β coefficients derived from regression analyses did not find a significant association between depression and emergency department visits in depressed patients with diabetes [30, 37]. One study did not report sufficient information to compute an effect size [44].
Ciechanowski et al. [4] reported slightly increased emergency department costs in patients with diabetes and comorbid mental disorders (SMD 0.17), whereas Egede et al. [20] did not find differences in costs of emergency room visits between the two groups (SMD 0.01). One other study reporting a β coefficient did not find a significant association between depression and emergency department costs in depressed patients with diabetes [37]. One study did not report sufficient information to compute an effect size [34].
Three studies reported increased costs of medications (SMD 0.40–0.48) in patients with diabetes and comorbid depression compared with diabetic patients without [4, 31, 40]. Another study reporting a β coefficient derived from regression analysis did not find a significant association between depression and medication costs in patients with diabetes and depression [37]. Two studies did not report sufficient information to compute effect sizes [20, 34].
Diabetes-related preventive services
Simon et al. [8] found a decreased rate of outpatient preventive care visits in patients with diabetes and depression compared with those without depression (SMD −0.09 [95% CI −0.16, −0.01]). The frequency of foot examinations was decreased in patients with diabetes and depression compared with those without depression (OR 0.86 [95% CI 0.81, 0.93) in one study [23], whereas two other studies of patients with diabetes and any comorbid mental health problem did not find differences between the groups (OR 0.84 [95% CI 0.40, 1.75] and OR 0.98 [0.88, 1.08]) [7, 19]. Foot sensory examinations were not associated with comorbid mental disorders in patients with diabetes (OR 1.06 [95% CI 1.00, 1.12]) [19], whereas rates of pedal pulse examinations were decreased (OR 0.72 [95% CI 0.68, 0.77]) [19]. Studies of receipt of eye examinations yielded inconsistent results (OR [range] 0.69–1.59) [7, 9, 19, 23, 35]. The rate of urine protein tests did not differ between patients with diabetes and any mental disorder [9] or depression [35] compared with those without mental disorders. Jones et al. [9] reported a lower rate of HbA1c determinations in patients with diabetes and mental disorders compared with diabetic patients without, whereas Desai et al. [19] found no differences. Two studies reported lower rates of HbA1c tests in patients with diabetes and comorbid depression than in those without depression (OR 0.90 [95% CI 0.84, 0.96]) and 0.61 [0.42, 0.90] respectively) [23, 35], whereas Desai et al. [19] did not find differences for patients with diabetes and any mental disorder.
Total healthcare costs
Seven studies reported increased total healthcare costs in patients with diabetes and mental disorders (depression, anxiety disorders, PTSD) compared with those without mental comorbidities (SMD [range] 0.04–0.86) (ESM Fig. 6) [4, 8, 14, 27, 28, 31, 40]. Three studies did not report sufficient information to compute effect sizes [20, 34, 37].
Indirect costs
Work absence
Absence from work was increased in patients with diabetes and depression compared with diabetic patients without depression in five primary studies (SMD [range] 0.15–0.98) [22, 41, 42, 46, 47] (ESM Fig. 7). In line with these findings, Kivimäki and colleagues [33] reported an increased HR for absence from work in patients with diabetes and depression (HR 1.98 [95% CI 1.52, 2.59]). Patients with diabetes and any mental disorder had a higher rate of absence from work than those without mental comorbidity (SMD 1.13 [95% CI 0.41, 1.85]) [6].