Discussion
We aimed at investigating the effect of diabetes mellitus on the gender gap in MDD. This is the first study showing that diabetes mellitus is a stronger risk factor for depression in women than in men. The gender gap in the diagnosis of depression is significantly larger in patients with diabetes than in the non-diabetic control group. Furthermore, there is an age peak in the gender gap of MDD at age 40–49 years, which is more pronounced among patients with diabetes than non-diabetic controls.
A gender gap in depression is a well-published finding;15 16 however, age-related changes in depression risk and the impact of diabetes have not been sufficiently investigated so far. In the present analysis, women with diabetes mellitus displayed an increased risk to develop depression compared with male patients with diabetes in all age groups. We observed a first rise in MDD around puberty, which was steeper in women than men and, thus, supports previous studies describing the emergence of a gender gap in MDD in this age group.17 18 Possible explanations are the earlier puberty onset in girls and gender differences in risk factors for depression during childhood combined with environmental stressors.17 18 In this analysis, the largest gender gap was found between 40 and 49 years. Correspondingly, women with diabetes mellitus in this age group had a higher OR for diseases that potentially promote depression compared with men. As cardiovascular diseases and obesity, among others, increase the risk for depression,19–21 their higher ORs at 40–49 years in women with diabetes might offer an explanation for the most prominent gender gap in MDD being at the same age. Furthermore, adult women are about two times more likely to be diagnosed with depression, have a higher prevalence of MDD due to biological factors and the psychological burden of the disease and/or men being underdiagnosed with depression.15 16 A perimenopausal rise in depression rates was demonstrated in longitudinal studies on premenopausal women22 23 and associated with hormonal fluctuations rather than absolute hormone values in previous studies.14 24 Concerning males, research suggests that men are under-reporting depressive symptoms and the severity thereof,25 are less likely to seek help16 and that the Diagnostic and Statistical Manual of Mental Disorders, fifth revision diagnostic criteria better reflects symptoms of depressed women than men.26 Therefore, a case of depression in a male patient is significantly less likely to be recognized by a healthcare professional than one in a female patient, which possibly contributes to the gender gap in depression.25–27
In order to investigate potential confounding factors for the wider gender gap among patients with diabetes mellitus, a sensitivity test on known important covariates for depression was conducted.20 21 28–32 The sensitivity analysis showed that female patients with diabetes are relatively more affected by overweight, obesity and alcohol-related disorders in the diagnosis of MDD than their male counterparts. Correspondingly, research suggests a strong interrelation between obesity and depression, especially in women, due to physical impairment, social dysfunction, emotional eating, biomolecular changes and both conditions being stigmatizing.19 21 33 Studies link abdominal obesity in women to an impaired hypothalamic–pituitary–adrenal axis stress response which, in turn, is related to psychiatric disorders such as MDD and anxiety disorders.3 However, alcohol-related disorders are typically more prevalent in men and men are more prone to cope with depression via increased alcohol consumption.34 35 Some studies, though, have demonstrated a link between alcohol-related disorders and depression in female adolescents, but not males.36–38 This gender-specific association is believed to decrease with age36; however, gender differences in alcohol-related disorders and MDD remain unclear.39 Furthermore, literature suggests a similar influence of PTSD on type 2 diabetes mellitus like MDD40; however, PTSD did not significantly impact our results according to the sensitivity analysis. Other potential influencing factors for a wider gender gap in patients with diabetes include women being psychologically more affected by diabetes distress.41–43 Furthermore, it has been reported in previous studies that the frequency of doctor visits increases the probability of being diagnosed with depression.44 Men are known to visit the doctor less often, possibly resulting in an underdiagnosis of depression in male patients.26 45–47 This effect might be even more prominent in a multimorbid condition such as diabetes mellitus, which requires an increased amount of medical care. Along these lines, we observed that female patients with diabetes have more hospital diagnoses and hospital days than men with diabetes in our cohort.
There are limitations and strengths to this study. We had access to hospital diagnoses of the whole Austrian population from 1997 to 2014, which is a large dataset with a high number of patients. However, due to the character of the dataset, outpatient visits were not recorded. Patients had to have been admitted to a hospital due to diabetes mellitus or any other disease at least once to be included in the analysis. A clear distinction between effects of a single episode (F32) compared with recurring depression (F33) on diabetes mellitus risk is hardly possible in this dataset. Both can only be analyzed as categorical diagnoses due to the cross-sectional nature of the data, which does not account for longitudinal changes or disease progression. Furthermore, data on glycemic control and medication would have opened possibilities to distinguish between patients with poor or good glycemic control and its potential effects on mental health.
In conclusion, diabetes mellitus appears to be a stronger risk factor for the diagnosis of MDD in women than in men. Obesity, overweight and alcohol-related disorders are more potent moderators of MDD risk in female than male diabetes patients. Therefore, we propose that high-risk patients such as overweight female patients with diabetes should be carefully assessed and monitored concerning their individual risk to develop depression.