Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The vast majority of cases of diabetes mellitus (DM) falls into two broad etiopathogenetic categories: Type 1 (T1DM) and Type 2 (T2DM) (1). DM is a complex, chronic illness requiring continuous medical care with multifactorial risk-reduction strategies beyond glycemic control (1) to maintain well-being and quality of life over time, to control risks, to manage disease symptoms, and to reduce the incidence of complications (2).

Patients with DM are at risk of physical and psychological complications. The short-term complications include hypoglycemia, and the long-term complications include cardiovascular disease, neuropathy, nephropathy, and retinopathy.

The prevalence of depression and psychiatric diseases among adults with T1DM or T2DM is approximately double that observed in the general population (3, 4).

Depression has a negative impact on self-care (5) and has been shown to be related to poorer glycemic outcomes and therefore increased risk of complications (6).

The presence of psychopathological symptoms, feeling of hopelessness, and fears of chronic nature of the disease may predispose the patient to the risk of suicidal ideations (SIs) and suicidal behavior, but also to neglect health care and lack motivation to adhere to the medical regimen (7). Suicide risk is considered a major psychiatric emergency in patients diagnosed with chronic illnesses (8). DM and particular aspects of living with DM are known to be associated with greater SI (9–12). Chung et al. found that DM was associated with a marked increase in suicidal behaviors (13).

There are few studies on suicidal risk factors in the patient with DM. The risk factors may be related to the patient’s characteristics, such as coping skills, personality profile, additional psychiatric illness including depression and alcohol use, and the feeling of hopelessness. Other risk factors could be a family history of attempted suicide and completed suicide. This is raised by furthermore the chances of suicide are increased by illness-related and situational risk factors such as adverse events, lack of social support, exacerbation of the illness, and gradual increase of DM complications. Another risk factor could be the easy access to means of self-harm by patients with DM (14).

Suicide is one of the highest public health priorities worldwide. The World Health Organization objectives for suicide prevention emphasize identification of high-risk groups (15).

Recognizing the clinical features associated with suicidal risk in patients with DM is crucial in order to realize screening and interventions aimed at prevention that should also take into account SI and suicidal behaviors.

In light of the above, the aim of this manuscript is to provide new insights for performing a systematic review by reporting the most relevant studies analyzing the clinical characteristics of the association between DM and suicide risk.

Based both on inclusion and exclusion criteria, a total of 568 original research studies were identified and selected for inclusion in the systematic review, as reported in the flowchart displayed in Figure 1. After removing the duplicates (N = 77) 491 papers remained. After that, reviews, meta-analyses, commentaries, letters to the editor, books or book chapters, abstracts, non-English language, clearly irrelevant papers were eliminated (N = 471). Twenty full text articles were assessed for eligibility and were read and surveyed by all the authors. Three articles were excluded because they did not respect the eligibility criteria. At the end of this process of examination, 17 studies were included in the qualitative synthesis of the systematic review.

Literature analysis has shown that the severity of DM can increase the risk of mental health disorders, such as depression and suicide risk. Suicide risk is a multifaceted issue that involves bio-psychosocial and cultural factors that interfere with the individual abilities of patients. Taking the potential clinical implications related to suicide risk in diabetic patients, the present study is a review manuscript aimed at systematically investigating the published original research reports evaluating the emerging clinical links between DM and suicidal factors.

Despite limited and contrasting studies, DM per se does not appear to be associated with SI and suicide. However, SI is more prominent among patients with DM than in those without [i.e., Ref. (11, 24, 26)], and this prevalence is associated with the depressive symptoms and the severity of illness, such as duration of DM, poor glycemic control, use of insulin treatment (17). In line with these results, a previous study in 2012 (11) showed that patients with more comorbid conditions were more likely to report depressive disorders and SI versus individuals without DM. Chung et al. (13) further demonstrated that depressive mood, SI, and suicide attempts increased in association with blood glucose levels. Furthermore, in 2004, one study (20) measured insulin concentration in cerebrospinal fluid in 74 suicide attempters to clarify the role of insulin in major depressive disorder and violent suicide attempt and found that cerebrospinal fluid insulin is involved in violent behavior but not in major depressive disorder.

When taking into consideration, the duration of DM as a risk factor for suicide, several studies have investigated the incidence of suicidal behavior (i.e., ideation, attempts, and acts) among adults and elderly patients with T1DM (12, 19). Other studies have highlighted that T1DM patients were three to four times more likely to attempt suicide during their lifetime than subjects without DM (18) and that a higher occurrence appeared in subjects with T1DM and a greater diabetes-related disease burden (10, 19).

Chronic disease causes a major emotional impact, which appears most dangerous during adolescence. When focusing on adolescents with T1DM, a hopeless feeling regarding the illness might be associated with risk of suicide attempts, and also with neglect of health care and lack of motivation to adhere to medical instructions (25). The lifetime prevalence of SI in diabetic youths was 26.4% (7); among patients 13–17 years of age, it was demonstrated that SI was endorsed in 7% of the sample assessed (26).

By focusing on clinical samples consisting of patients with DM and mood disorders, several studies evaluated the association between suicidality and DM. Depressive symptoms were the most prominent predictor of SI in diabetic patients (17). Given the relationships between depression and suicidality, and between depression and DM, some studies examined the mediation role of depressive symptoms, finding that depression mediates the relationship between DM, suicide (21) and non-compliant behavior with the medical regimen (17). In support of these findings, recent studies observed that the coexistence of DM and depression was associated with a much higher risk factor for SI (12, 23) and suicide attempts (13) than with DM alone. In fact, it has also been reported that subjects with an increased prevalence of endocrine abnormalities such as diabetes may be at increased risk of depression and/or anxiety disorders (27). Major depression is also correlated with well-known deficiency in serotonergic neurotransmission, as reported by Müller et al. (28). Neurotransmitter alterations and immune dysregulation lead to an increased generation of proinflammatory cytokines which play a crucial role in anxiety and depression (28, 29). It is interesting that patients with schizophrenia and other severe mental disorders have an increased risk of developing diabetes and hyperlipidemia and initiating medication for these diseases (30).

These findings are important, suggesting that the higher prevalence of suicidal risk observed among people with DM may be attributable to the increased prevalence of depressive symptoms. On the other hand, the study conducted by Pompili et al. (9), observing a sample of patients with DM controlled for mood disorders, found that patients with DM perceived a poor quality of life, which was related to low self-efficacy, high hopelessness, and suicidality. In other terms, the results indicate that DM is associated with an increased risk of suicide, independently from the severity of depressive condition (9).

According to Gois et al. (31), depressive temperament may also be important to better understand the interplay between depression and diabetes.

Protective factors for suicidal risk were higher household income, higher education, social and emotional support (8, 12), and marriage or cohabitation. Being single was a risk factor for suicide (17); furthermore, suicide risk includes also gender, developmental, and substance abuse determinants (18, 21, 23). Recent studies have raised concern on the role of insulin and other antidiabetic medication use as a suicide method in patients with DM (21, 22). Having the means close at hand to commit suicide can represent a major risk for these patients.

Understanding the clinical features that can lead the patient with DM to have SI or suicidal behavior is an important objective to identify patients at higher risk and to promote well-being and adhering to antidiabetic medication. The present review of the relevant literature supports the need for further investigation into the severity and nature of disabilities associated with DM and other chronic diseases (32) and their relationships with SI and suicidal behaviors. From the clinical point of view, when treating patients with DM, it is important to emphasize that only a very small minority of patients eventually dies from suicide. However, given that DM per se is known to increase the risk of suicidal behavior and that depression is one of the most important single risk factors for suicide, it is important to be highly aware of co-occurring depressive symptoms in patients with DM.

These findings have implications for health-care professionals, pointing out the importance of adequate psychological screening and action plans for appropriate follow-up to reduce the suicide risk in diabetic patients.

All authors participated in the concept and writing of this manuscript; approved the final version of the manuscript.

The authors declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict of interest.