Journal of Psychosomatic Research 76 (2014) 352–360
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Journal of Psychosomatic Research
Review
Suicide risk in type 1 diabetes mellitus: A systematic review Maurizio Pompili a,⁎, Alberto Forte a, David Lester b, Denise Erbuto a, Fabiana Rovedi a, Marco Innamorati a, Mario Amore c, Paolo Girardi a a b c
Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, Italy The Richard Stockton College of New Jersey, USA Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genova, Italy
a r t i c l e
i n f o
a b s t r a c t Background: Research has shown that suicide risk is often present in patients suffering from type 1 diabetes mellitus (DM-1). Objectives: The aim of the present paper was to investigate whether there was a relationship between DM-1 and suicidal behavior and to determine whether or not people affected by DM-1 are at an increased risk of completed suicide, attempted suicide, and suicidal ideation. Data sources: We performed a careful MedLine, ExcerptaMedica, PsycLit, PsycInfo and Index Medicus search to identify all papers on the topic for the period 1970 to 2013 written in English. The following search terms were used: (suicide OR suicide attempt OR ideation) AND (diabetes mellitus). Where a title or abstract seems to describe a study eligible for inclusion, the full article was examined. Eligibility criteria: We included only original articles published in English peer-reviewed journals. We excluded meta-analyses and systematic reviews, studies that were not clear about follow-up times, the method of statistical analysis, diagnostic criteria or the number of patients included, and studies only on patients affected by type 2 diabetes mellitus (DM-2). Results: The research reviewed indicated that patients with DM-1 are at an increased risk for suicide, although no clear consensus exists regarding the level of the increased risk. Limitations: The studies used different measurement techniques and different outcomes, and they assessed patients at different time points. Conclusions and implications: Our findings support the recommendation that a suicide risk assessment of patients with DM-1 should be part of the routine clinical assessment. The assessment of patients at risk should consist of the evaluation of current and previous suicidal behaviors (both suicidal ideation and attempted suicide). © 2014 Elsevier Inc. All rights reserved.
Article history: Received 7 July 2013 Received in revised form 20 February 2014 Accepted 20 February 2014 Keywords: Diabetes type I Suicide Prevention
Contents Introduction . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . Study design and quality assessment . . Results . . . . . . . . . . . . . . . . . . Search strategy . . . . . . . . . . . . Adults: completed suicide . . . . . . . Adults: non-fatal suicidal behavior . . . Adolescents: completed suicide . . . . Adolescents: non-fatal suicidal behavior Children: completed suicide . . . . . . Children: non-fatal suicidal behavior . . Discussion . . . . . . . . . . . . . . . . Limitations . . . . . . . . . . . . .
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⁎ Corresponding author at: Department of Neuroscience, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, 1035-1039, Via di Grottarossa, 00189 Rome, Italy. Tel.: +39 0633775675; fax: +39 0633775342. E-mail address: [email protected] (M. Pompili).
http://dx.doi.org/10.1016/j.jpsychores.2014.02.009 0022-3999/© 2014 Elsevier Inc. All rights reserved.
M. Pompili et al. / Journal of Psychosomatic Research 76 (2014) 352–360
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Introduction Research has documented high rates of psychiatric disorders among medical patients in general [1–4]. Suicidal ideation, which is frequently present in patients with major depression [5], is also common in patients suffering from medical illnesses [6], and this suicidal ideation in medically ill patients may arise from a comorbid depression [7]. There are more than 30 million people worldwide suffering from type 1 diabetes mellitus (DM-1) [8], an illness resulting in autoimmune damage to the insulin-secreting islet cells and caused by a mixture of genetic and non-genetic factors [9]. DM-1 is often characterized by multi-organ involvement, and the damage to the primary target organ typically drives the clinical presentation and distinguishes the disease. Patients with DM-1 have almost doubled risk of depression compared to the general population [10], and psychiatric symptoms are frequent in patients with DM-1 and other autoimmune diseases [11]. The aims of the present paper were to examine research on the association between DM-1 and suicidal behavior and to determine whether or not people affected by DM-1 are at an increased risk of completed suicide, attempted suicide, and suicidal ideation. Methods In order to provide a systematic review about DM-1 and suicidal behavior, we performed a careful MedLine, ExcerptaMedica, PsycLit, PsycInfo and Index Medicus search to identify all papers in English for the period 1970 to 2013. The following search terms were used: (suicide OR suicide attempt OR ideation) AND (diabetes mellitus). The articles were restricted to those published in English peer-reviewed journals. Where a title or abstract seems to describe a study eligible for inclusion, the full article was examined to consider its relevance on the basis of the inclusion criteria. Any discrepancies between the two reviewers who, blind to each other, examined the studies for possible inclusion were resolved by consultation with the senior authors. Textbooks were also consulted in order to locate articles. In addition, we also examined reference lists and contacted experts in the field. Abstracts that did not refer to suicide and diabetes mellitus were excluded. We excluded meta-analyses and systematic reviews, studies that were not clear about follow-up times, the method of statistical analysis, diagnostic criteria or the number of patients included, and studies which included only patients affected by diabetes type II (DM-2) because the age of onset and pathogenesis of DM-2 is different from that of DM-1. The principal reviewer (MP) inspected all items. Then, three reviewers (AF, FR, MP) independently inspected all citations of the studies identified by the search and grouped them according to topic. Reviewers acquired the full article for all papers. Where discrepancies occurred, they were resolved by discussion with the principal reviewer who independently inspected all articles and grouped them into the major areas of interest identified. Study design and quality assessment A quality assessment was performed as shown in Table 1. Studies were rated for the quality assessment using the following criteria: (i) representativeness of the sample (1 point), (ii) presence of a control group (1 or 2 points), (iii) n N 1000 subjects (1 or 2 points); (iv) duration of follow-up N 1 year (1 or 2 points),(v) evidence-based measures of assessment (1 or 2 points), (vi) data presentation (1 or 2 points), and (vii) evidence-based measures assessing suicidal behavior (1 or 2 points). Quality ratings could range from 0 to 8 for each study.
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359 360 360
Most of the studies were characterized by good data presentation and evidenced-based measures for the assessment of DM-1. The retrospective studies and cohort studies included were characterized by large sample sizes and representative samples. Eight studies had a sample size of more than 1000 subjects. On the other hand, the quality of the studies was often compromised by the absence of evidence-based measures assessing suicidal behavior. One of the retrospective studies was compromised by an unrepresentative sample. Three cross-sectional studies were characterized by good data presentation and evidencebased measures assessing suicidal behavior, but small sample sizes limited the quality of these studies. Results Search strategy The combined search strategies yielded a total of 331 records to be screened. We first reviewed titles and abstracts and applied the selection criteria outlined above with the exception of study design. This process led to the exclusion of 291 records from the 331 originally selected. The large majority of studies excluded failed to mention in the title or abstract any of the outcome indicators specified above. In the second stage of the screening process, two new reviewers read the full articles and coded them based on the methodology. Studies that did not meet the methodological standards set by the reviewers were excluded, resulting in the inclusion of 20 studies for the final review. The different stages of the screening process are illustrated in Fig. 1. Of the twenty studies included in this review, seventeen were longitudinal studies, and three were cross-sectional studies. The seventeen longitudinal studies included 4 prospective studies (including 2 cohort studies), 12 retrospective studies (including 8 cohort studies) and 1 mixed prospective/retrospective study. Adults: completed suicide An evaluation of the causes of mortality in patients with DM-1 was conducted in Japan, Israel, the United States, and Finland [12]. In Finland, the major cause of death was suicide (36% of the deaths). In Japan, deaths were most often attributed to DM-1 complications and kidney disease, while in the other countries mortality was most often attributed to acute complications of diabetes. Kyvik et al. [13] found that young men with DM-1 had a higher risk of suicide than expected. For the 153 deaths of men with DM-1, 12 were classified as suicides (SMR = 1.6, 0.05 b p b 0.10). For the group aged 20–24 years, the SMR was 2.98 (p b 0.05). Muhlhauser et al. [14] followed a cohort of 3674 patients with DM-1 in which 251 patients died, including 22 by suicide. They found that classification of the cause of death based on death certificates or on ICD-codes was unreliable in adult patients with DM-1. They suggested that it is necessary for researchers to re-examine the cause of death for each patient. A prospective study [15] evaluated 4174 subjects with DM-1 (51% men, age: 39 ± 12 years, DM-1 duration: 22 ± 12 years) for depression and cause of death. Depression was operationally defined as purchasing antidepressant medications. It was found that antidepressant purchasers had a higher mortality rate than did non-purchasers. In the total sample, 474 died. The cumulative mortality rate was highest among subjects taking antidepressant at baseline. Six suicides occurred, two in each of the three groups: patients who had not purchased antidepressant agents at baseline (3.4% of the deaths), those without any purchase of antidepressants during the study (0.7% of the deaths) and those who purchased antidepressant during the follow-up (1.7% of the deaths). Some studies have found a higher risk of suicide in patients with DM-1 and also patients with DM-2. Batty et al. [16] conducted a retrospective cohort study to examine the relationship between DM-1 and suicide risk. The sample consisted of a cohort of 1,329,525 individuals aged 30–95 years at baseline (of whom 482,618 were women). There were 472 deaths due to suicide (389 men and 83 women). The highest suicide rates were in men and women with DM-2. Moreover, there was no confirmation of a high suicide rate in the impaired glucose/prediabetes group. Wibell et al. [17] examined the mortality rate in the first year after a diagnosis of DM-1 in 4097 new cases of patients with DM-1. Their results showed that 58 patients died (SMR = 3.5) (95% CI = 2.7 ± 4.5). Suicide was more common in the men. Nine cases of suicide occurred compared to 4.5 expected (SMR = 2.0; 95% CI = 1.0 ± 3.8). A retrospective study examined mortality rates and causes of death among patients with DM-1 aged b29 years [18]. Among 4246 individuals, 108 patients died, including 24 (22%) from accidents or violence. Among these 24 deaths were six suicides. Harjutsalo et al. [19] examined mortality trends among 17,306 patients with early onset DM-1 (age: 0–14 years) and late onset DM-1 (15–29 years). One hundred and ten suicides occurred. Half of the suicides took place during the first 20 years of the illness.
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Table 1 Summary of the study outcomes and quality assessment. Study
Quality Scorea
Study design
Wibell et al. [17]
Muhlhauser et al. [14]
Pompili et al. [20]
Roy et al. [21]
I=1 II = 1 III = 2 IV = 0 V=1 VI = 0 Total score = I=0 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = I=1 II = 1 III = 1 IV = 0 V=1 VI = 1 Total score = I=1 II = 1 III = 2 IV = 2 V=1 VI = 0 Total score =
Results Overall rate –Suicide (N = 557) Diabetics: 557; non-diabetics: 0 –Suicide attempted (N = 70) Diabetics: 56; non-diabetics: 14 –Suicide ideation (N = 23) Diabetics: 23; non-diabetics: 0 Finland: 33% of deaths due to accidents, suicide and homicide.
Risk or protective factors — SMR
Conclusions
Not reported
High rate of suicide in DM-1 patients in Finland
Retrospective cohort study: 4 population cohorts
8137 diabetics
No
Cross-cultural study with population in 4 different countries. Cases diagnosed from 1965 to 1979.
Retrospective cohort study
1682 diabetic men
Yes
All Danish men born between 1949 and 1964 who were diagnosed with DM-I. Record linkage with the Danish Civil Registration System. Death certificates scrutinized.
Retrospective cohort study
4097 diabetics
Yes
58 patients died, including 10 cases Nationwide Cause of Death Registry. Underlying cause of death of suicide. based on the ICD.
Prospective cohort study
3674 diabetic adults
Yes
Causes of death assessed by a clinical review committee. Information provided by death certificates and ICD-9 codes; Information provided by death certificates available for 73% and ICD-9 codes for 79% of the patients.
251 (7%) patients died, including 22 suicides. Only 7 of the 17 cases with ICD codes were classified as suicides.
Case–control study
100 patients with diabetes and 100 controls who sought consultation at an internal medicine outpatient clinic
No
Assessment: Suicide Score Scale (SSS), Beck Hopelessness Scale (BHS), SF-36 Health Survey Questionnaire and General Self-Efficacy Scale.
Not reported Patients with diabetes had a moderate-to-high average score for hopelessness. Women had greater suicidality than men. DM-2 patients had a lower score on the BHS.
Case–control study
412 AfricanAmerican diabetics and 404 controls
Yes
Instruments: Childhood Trauma Questionnaire (CTQ), Hostility and Direction of Hostility Questionnaire (HDHQ), and Beck Depression Inventory (BDI).
More diabetic patients attempted suicide: 55 of 412 diabetics (13.3%) and 14 of 404 controls (3.5%). African-Americans with DM-1 had an increased risk of attempting suicide.
5 12 suicides. 28 unknown causes of 12 suicides, SMR = 1.6. For those aged death (expected 0.83) and 22 from 20–24, SMR was significantly increased (SMR = 2.98). accidents (expected 17.97). 3 possible suicides and 2 probable suicides. One accidental death was probably suicide.
Risk increased in Danish men, especially those in the age-group 20–24 years with disease onset at age 15–19.
6 Early mortality was increased threefold.
7 Not reported
The assessment of causes of death based on death certificates or on ICD-codes is unreliable in adult patients with DM-1.
7 Patients with diabetes showed greater hopelessness and suicide ideation than internal medicine outpatients.
5
7
Risk factors for a suicide attempt: female, smoker, abusing alcohol, a lifetime history of drug abuse, hostility, and childhood trauma. The risk is tripled with a BDI depression score ≥14.
Suicide risk in diabetics appears to be multifactorial and includes gender, developmental, personality, psychiatric, and substance abuse factors.
M. Pompili et al. / Journal of Psychosomatic Research 76 (2014) 352–360
Kyvik et al. [13]
Follow- Methods up
–Diabetics: 1,257,303 –Controls: 604 –Total: 1,257,907
Adults
No authors listed [12]
Sample
Study Quality Scorea Ahola et al. [15]
Batty et al. [16]
Risk or protective factors — SMR
Conclusions
Yes
Data obtained from National Register. Data on all-cause mortality and cause of death obtained from the Finnish Cause of Death Register.
474 deaths: 19.8% antidepressants at baseline, 16.2% antidepressants during follow-up and 9.3% no antidepressant. 6 suicides.
10-Year cumulative mortality rate highest among purchasers of antidepressant agents at baseline (95% CI = 18.1–26.6).
The purchase of antidepressant agents in patients with DM-1 was associated with increased mortality in women, but not in men.
1,234,927 diabetics
Yes
Data taken from the Korean Cancer 472 suicides (389 in men and 83 in women). In men, suicide rates are Prevention Study: 1,329,525 individuals (482,618 women), aged high in DM-2 patients. 30–95 years, who participated in at least one biennial medical evaluation.
The highest suicide rates were in men and women with an existing or new diagnosis of DM-2. No association between impaired glucose/prediabetes and suicide.
Diabetes, but not raised blood glucose, was a risk factor for completed suicide.
200 subjects: 100 with DM-1 and 100 with DM-2
Yes
DM 1 patients had a higher prevalence of psychiatric disorders than DM-2 patients. The most prevalent disorders were generalized anxiety disorder (21%), dysthymia (15%), social phobia (7%), current depression (5.5%), lifelong depression (3.5%), panic disorder (2.5%), and risk of suicide (2%). Overall rate –Suicides (N = 121) Diabetics: 121; non-diabetics: 0 –Suicide attempted (N = 20) Diabetics: 5; non-diabetics: 15 –Suicide ideation (N = 63) Diabetics: 37; non-diabetics: 26 The one-year prevalence of suicidal Semistructured and structured ideation: 13.2% (n = 12 of 91); 2 interview instruments and selfreport questionnaires to determine (2.2%) reported thoughts of suicide in the 2 weeks prior to the assesshistory of suicidal thoughts and ment. Lifetime prevalence of suibehavior, serious noncompliance with the medical regimen, current cidal ideation among diabetic psychiatric disorder, hopelessness, youths: 26.4% (n = 24 of 91). and self-efficacy expectations Interviews and medical 19 adolescents with unusual examinations. frequency of coma; 16 admitted surreptitious self-administration of insulin. Those 16 adolescents were mainly girls, with a higher frequency of coma and a lower insulin declared dose than the remaining 136. 141 deaths; 71 (53%) unrelated to Thirteen population-based diabetes; and for 16 (12%) the role EURODIAB registers in 12 countries; record linkage to population played by diabetes was uncertain. registers or through contact with doctors providing care.
Risk of suicide was found to be approximately 2%, which can be considered high, emphasizing the need for attention to this population
High prevalence of psychiatric disorders in diabetic patients highlights the need for accurate assessments of symptoms related to mental health.
Both one-year and lifetime suicidal thoughts related to noncompliance with the medical regimen, even after controlling for the presence of psychiatric disorder (p = .056 and p b .001, respectively)
Suicidal thoughts were related and serious noncompliance with the medical regimen are strongly associated in diabetic teenagers, and psychiatric disorder is a common correlate of both. The 16 cases were characterized by a large predominance of girls, frequent use of low insulin doses, frequent familial difficulties, and major fears of complications.
Followup
I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = 7 I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = 7 I=1 II = 1 III = 1 IV = 1 V=1 VI = 1 Total score = 6
Prospective– retrospective study
4174 diabetics
Retrospective cohort study
Cross-sectional observational study and comparative study
–Diabetics: 46,749 –Controls: 82,984 –Total: 129,733
Adolescents
Goldston et al. [24]
Results
Sample
I=1 II = 0 III = 1 IV = 0 V=1 VI = 1 Total score = 4 Boileau et al. [25] I=1 II = 0 III = 1 IV = 2 V=1 VI = 0 Total score = 4 Patterson et al. [23] I = 1 II = 0 III = 2 IV = 2 V=1 VI = 0 Total score = 6
Observational study
91 diabetic adolescents (39 f. 52 m)
Yes
Prospective cohort study
149 diabetic adolescents
No
Retrospective cohort study
28,887 diabetic children
Yes
Data collection form for identification and social data, Mini International Neuropsychiatric Interview [10] (MINI).
Not reported
The number of deaths from suicide was similar to that expected from national rates (11 observed vs. 10.2 expected; SMR = 1.1; 95% CI = 0.5–1.9). Deaths from accidents and violence, including suicides, was marginally greater than the number expected from national rates (48 observed vs. 40.7 expected; SMR = 1.2; 95% CI = 0.9–1.6)
M. Pompili et al. / Journal of Psychosomatic Research 76 (2014) 352–360
de Ornelas Maia et al. [22]
Methods
Study design
Significant excess mortality following the diagnosis of DM-1 in childhood occurs in most European countries.
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Table 1 (continued)
Fuller-Thomson et al. [26]
Radobuljac et al. [27]
Harjutsalo et al. [19]
Quality Scorea
Study design
I=0 II = 1 III = 2 IV = 0 V=0 VI = 0 Total score = 3 I=1 II = 1 III = 2 IV 0 V=1 VI = 1 Total score = 6 I=1 II = 0 III = 2 IV = 0 V=1 VI = 0 Total score = 4
Cross-sectional study 82,675 respondents, 190 with DM-1 and 82,485 without DM1
No
Cross-sectional study 126 patients, 499 controls
No
Population based nationwide cohort study
Results
Risk or protective factors — SMR
Conclusions
Microdata file of the Canadian Community Health Survey. Prevalence of suicidal ideation was estimated for those with and without DM-1.
Prevalence of suicidal ideation among patients with DM-1 was 15.0% (95% CI = 7.1%, 22.9%), and for those without DM-1 9.4% (95% CI = 9.0%, 9.8%).
The age and sex-adjusted odds of suicidal ideation are 1.61 (95% CI = 1.08, 2.42), for individuals with DM-1 in comparison to those without.
Subjects with DM-1 had a 61% higher probability of reporting suicidal thoughts than individuals without DM-1.
Self-reported questionnaire on demographic data, family and living circumstances, school, health, social support, substance use and abuse, psychosocial help, friends, self-esteem, depression symptoms, and suicidal behavior.
DM-1 is protective against suicidality Females reported a higher in adolescent males, but not in females. incidence of suicidal ideation and behavior.
All Finnish patients diagnosed as having DM-1 below age 30 years between 1970 and 1999
The lowest prevalence of suicidal ideation and intended suicide was in males with diabetes. Females with diabetes reported the highest prevalence of suicidal ideation (p b 0.001), intended suicide (p b 0.01), and attempted suicide (p b 0.05) 110 suicides. Increased mortality due to suicide in the late onset cohort
Nationwide population-based registry: time period from 1973 through 1982
Overall rate –Suicide (N = 60) Diabetics: 16; non-diabetics: 54 –Suicide attempted (N = 6) Diabetics: 6; non-diabetics: 0 –Suicide ideation (N = 19) Diabetics: 19; non-diabetics: 0 40% deaths were from accidents Overall SMR for all-cause mortality was Accidents and suicides and suicides. No females. 2 suicides. 207 (95% CI = 126–319). comprise the majority of the deaths.
Follow- Methods up
Yes 17,306 diabetics; 10,492 were in the early onset cohort and 6814 were in the late onset cohort.
–Diabetics: 18,303 –Controls: 378 –Total: 18,681
Children
Joner et al. [28]
Sample
I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = 7
Retrospective study
1908 diabetics
No
Suicide rate was increased only in women with early onset diabetes, SMR = 3.3 (1.9 to 4.7).
Significantly higher rates of depression in DM-1 patients than in patients without DM-1.
M. Pompili et al. / Journal of Psychosomatic Research 76 (2014) 352–360
Study
Study Study design
Results
Risk or protective factors — SMR
Conclusions
Yes
Children admitted to a pediatric endocrinology unit. Inclusion criteria: newly diagnosed with classic, acute-onset, ketosis-prone DM-I; no other systemic illness.
Suicidal ideation: higher rate than expected (n = 15). Attempted suicide (n = 6): relatively few over the follow-up; diabetes-related methods commonly were used.
Suicidal ideation shortly after DM onset related only to concurrent severity of depressive symptoms. Suicidal ideation associated with later noncompliance with treatment.
Clinicians should be alert to the possibility of suicidal ideation among children with DM
Yes
Diabetes register records: all children with DM-I diagnosed under age 17. Three independent sources: pediatricians, physicians, and diabetes nurse specialists; general practitioner records; hospital discharge data.
26 deaths identified. 15 deaths (58%) were attributed to diabetes or its complications; 11 (42%) were unrelated to diabetes and included one suicide.
For mortality from all causes, SMR = 247 (95% CI = 163 to 362). Mortality was significantly increased for those under 34. The largest number of deaths (n = 10) occurred in the 15–19 year age range, with an SMR of 442 (95% CI = 209 to 802).
Increased mortality for young people with DM, particularly in the “transition” age range.
Among diabetics, 23 deaths clearly related to diabetes. 20 deaths were classified as having an uncertain relationship to diabetes; 7 of them died by suicide. No significant difference in traffic accidents (odds ratio: 1.02 [95% CI = 0.40 to 2.37]). 54 control subjects committed suicide Population based register; children 108 deaths, 22% (n = 24) from diagnosed between 1978 and 2004 accidents or violence, 6 suicides. were linked to the U.K. National 16% of all deaths related to drug Health Service Central Register for misuse (including insulin but death notifications. Deaths were excluding tobacco and alcohol). 74 coded using ICD-9 (1979–2000) deaths were children between the ages 0 and 14 years and 34 aged and ICD-10 (2001–2005). 15–29 years
The SMR for all causes was higher for females than males (2.65 vs. 1.93, p = 0.05). SMR controlling for age and sex was 2.15 (95% CI = 1.70 to 2.68)
Significant excess mortality in young DM-1 patients. There was a large proportion of unexplained deaths in bed, which should be further studied. There was no clear excess death rate caused by suicide or traffic accidents Subjects under 30 years of age had a 4.7 times excess mortality risk. Drug misuserelated deaths may be an emerging trend in this population, warranting further investigation.
Followup
I=1 II = 0 III = 1 IV = 2 V=1 VI = 1 Total score = 6 Warner et al. [32] I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = 7 Dahlquist et al. [29] I = 1 II = 1 III = 2 IV = 0 V=1 VI = 0 Total score = 5
Prospective study
95 diabetic children (51 f; 44 m)
Retrospective cohort study
1854 diabetic children
Retrospective cohort study and case– control study
Yes Cohort: 10,200 diabetic children. 78 died with previously diagnosed diabetes; 378 died without previous diagnosis of diabetes (control group)
Feltbower et al. [18]
Retrospective cohort study
4246 diabetics
Goldston et al. [30]
I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = 7
Yes
Population-based incident childhood diabetes register, covering onset cases since 1 July 1977, linked to the Swedish Cause of Death Register up to 31 December 2000.
SMR for suicide = 2.1 (95% CI = 1.4 to 3.2); SMR for deaths resulting from drug misuse (including insulin) 6.4 (95% CI = 3.7 to 10.2); the SMR increased with increasing disease duration.
Quality ratings reported have 8 as maximum score. a Studies were rated for the quality assessment using the following criteria specified below: I) II) III) IV) V) VI)
representativeness of the sample to the general population (1 point): 0 points not representative; 1 representative presence of a control group (1 point): 0 points without control group, 1 point with control group number of subjects in treatment group (1 or 2 points). 0 points if N b 100; 1 point if N b 500; 2 points if N N 500 duration (years) of follow-up (1 or 2 points). 1 point b 1 year; 2 points N 1 year data presentation (1 point). 0 points, unclear data presentation in the text; 1 point, clear data presentation in the text evidence-based measures assessing suicide or suicide attempts (1 point): 0 points absence of evidence-based measures assessing suicide or suicide attempts; 1 point presence of evidence-based measures assessing suicide or suicide attempts.
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Methods
Sample
Quality Scorea
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The patients with late onset DM-1 showed an increased mortality from suicide, with an SMR of 2.8 (95% CI = 2.6 to 3.0). In patients with early-onset DM-1, only females had an increased mortality from suicide, with an SMR of 3.3 (95% CI = 1.9 to 4.7). Adults: non-fatal suicidal behavior Pompili et al. [20] investigated the quality of life and its association with suicide risk among 100 patients with DM-1 and DM-2 (52 women and 48 men). Patients with DM1 had a moderate-to-high average score for hopelessness. Women with DM-1 had more suicidal ideation than men, and patients with DM-1 had higher hopelessness and suicidal ideation scores than patients with DM-2. Roy et al. [21] studied 412 African-Americans with DM-1 and 404 African-American controls. DM-1 patients were more likely to attempt suicide than controls (13.3% vs. 3.5%, respectively, p b 0.001). Suicide attempters were more frequently female, hostile and depressed, and they were more likely to have a history of childhood trauma, alcohol abuse, drug abuse and smoking than were the non-attempters. A recent study compared the prevalence of psychiatric disorders in patients with DM1 and DM-2 [22]. The risk of suicide (assessed by the Mini International Neuropsychiatric Interview) was higher in patients with DM-1 than in patients with DM-2 (3% vs. 1%). The most common psychiatric disorders in the patients with DM-1 were generalized anxiety (21%), dysthymia (15%), social phobia (7%), current depression (5.5%), lifelong depression (3.5%), and panic disorder (2.5%). Adolescents: completed suicide Patterson and colleagues [23] studied causes of death in Europe in patients with DM-1 under the age of 15 (N = 28,887). There were 141 deaths, with an SMR of 2.0. They did not find an excess of deaths related to suicide (11 observed, 10.2 expected; SMR = 1.1; 95% CI = 0.5–1.9). Adolescents: non-fatal suicidal behavior Goldston et al. [24] studied a sample of 91 adolescents with DM-1. They found that suicidal ideation was more frequent than expected, but the rate of suicide attempts was not higher than in the general population. However, the duration of DM-1 was associated with suicidal ideation (in the prior year and lifetime). The results of this study also indicated that suicidal ideation is associated with serious noncompliance with the medical treatment. Boileau et al. [25] evaluated 322 cases of recurring hypoglycemic comas in 149 adolescents with DM-1. Sixteen patients admitted self-injections in order to attempt suicide. This group reported a higher frequency of coma, a lower declared insulin dose, and more frequent family difficulties than the other patients with repeated hypoglycemic coma. Fuller-Thomson et al. [26] compared the lifetime prevalence of suicidal ideation among patients with and without DM-1. The prevalence of suicidal ideation, in patients with DM-1 was 15.0% (95% CI = 7.1% to 22.9%), while those without DM-1 had a prevalence of suicidal ideation of 9.4% (95% CI = 9.0% to 9.8%). Thus, the DM-1 patients had a 61% higher risk of reporting suicidal thoughts than did individuals without this illness. Radobuljac et al. [27] found that adolescents with DM-1 tended to have a lower lifetime prevalence of all suicidal behaviors and self-injurious behaviors. The lowest prevalence of all suicidal behaviors was found in males with DM-1, significantly lower than in males without DM-1 for suicidal ideation (p b 0.05) and intended suicide (evaluated by the question: “Have you once or on more occasions intended to end your own life and changed your mind in the last moment?”) (p b 0.05). This reduced rate of suicidal ideation was found in the adolescent males but not in the adolescent females. Children: completed suicide Joner and Patrick [28] studied the mortality rate in 1908 children with DM-1. Twenty had died at follow-up. Forty percent of the deaths were from accidents or suicide, and these occurred only in the boys. No girls were recorded as dying from accidents or suicide. Dahlquist et al. [29] evaluated mortality rate in a cohort of young patients with DM-1. They found a significant excess of mortality in patients with DM-1 even before the development of late complications. In the 78 patients who had died, 23 deaths were clearly related to DM-1. Twenty died of diabetic ketoacidosis, 7 died by suicide, and 14 died from accidents, but the number of suicides was not significantly greater than expected. Children: non-fatal suicidal behavior Goldston et al. [30] found that young patients with DM-1 have a higher than expected rate of suicidal ideation, but relatively few of the patients attempted suicide. Among those who attempted suicide, DM-1-related methods were commonly used (such as misuse of insulin). Suicidal ideation after DM-1 onset seemed to be related only to the severity of depressive symptoms.
Discussion The research reviewed above has indicated that, in general, patients with DM-1 have a higher risk for suicide than the general population does [13,19,21,24,30,31]. Patients with DM-1 are 3 to 4 times
more likely to attempt suicide than the general population [21], and patients with DM-1 have a 61% higher risk of experiencing suicidal thoughts than individuals without DM-1 [26]. On the other hand, not all research reports a higher risk of suicide in patients with DM-1 [16,27,29]. As shown in Table 1, six studies [12–17] reported the number of suicides in adult samples of diabetics. These studies reported 1079 suicides out of 2,506,180 patients included in the samples, that is, 43.1 suicides per 100,000 patients. For adolescents and children, 6 studies [18,19,23,28,29,32] reported numbers of suicide with DM-1. These studies reported 32 suicides out of 36,711 adolescent patients, that is, 87.2 suicides per 100,000 patients. We did not carry out a meta-analysis because the data differed between studies, and only a few studies reported the number of suicides. The relationship between DM-1 and suicide can be understood in the light of neurobiological correlates. Several studies have demonstrated the presence of low levels of tryptophan in patients with DM-1 [33,34]. In particular there appears to be a deterioration of brain serotonergic neurotransmission in patients with DM-1 who are depressed, as well as decreased brain uptake of tryptophan and lowered brain 5hydroxytryptamine levels. Reduced free tryptophan could lead to a reduced synthesis of central serotonin [35], and it is well known that reduced serotonin levels are associated with an increased risk for suicide [36]. The results of the research reviewed suggest that young men with DM-1 may show a higher risk for suicide than expected [13,30], especially patients aged between 15 and 29 years [19]. Moreover suicidal thoughts, noncompliance with the medical regimen and psychiatric disorder are common in diabetic teenagers [24]. Professionals working with adolescents with DM-1 should always consider the risk of suicide [27]. Despite some evidence showing that men with DM-1 are at increased risk for suicide, a few studies showed that patients with DM-1 who attempted suicide are significantly more likely to be female. Thus, there was no clear consensus regarding sex as a risk factor for suicide. Suicidal patients with DM-1 were also more likely to be depressed and to report a history of childhood trauma, smoking, alcohol abuse, and drug abuse [27]. It was also reported that African-Americans with DM-1 have an increased risk of attempting suicide [21]. Among young people who attempt suicide, methods related to DM-1 (such as misuse of insulin) were commonly used. Research has also found an association between suicidal thoughts and serious noncompliance with the medical regimen among teenagers. Not adhering to the medical regimen could be considered another form of self-destructive behavior and one that must be taken seriously. In particular, adolescents who have a lifetime history of suicidal ideation were found to be more likely to be noncompliant with their medical regimen [24]. Physicians should routinely ask their young patients about suicidal thoughts, given the relationship of these thoughts to adherence with the medical treatment. Pompili et al. [20] found an increased risk for hopelessness and suicidal ideation among patients with DM-1 over the age of 50, and they also reported an association between polytherapy and hopelessness. These findings highlight the need for an accurate assessment of suicide risk among adults affected by DM-1. From our review, we can conclude that the causes of suicide in patients with DM-1 appear to be multifactorial, and prevention strategies are of great importance. Every year, a large number of patients with DM-1 present to emergency departments with hypoglycemic episodes of “unknown” etiology, and it is possible that a significant proportion of them could be intentional overdoses [37]. Thus, suicide risk may be underestimated in patients with DM-1. Some authors have argued also that there could be a substantial underestimation of suicide as a cause of deaths in patients with DM-1 because the certification of causes of death based on death certificates or on ICD-codes may be unreliable in adult patients with DM-1 [14].
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Records identified through database searching (n= 331)
359
Additional records identified through other sources (n= 4)
Records after duplicates removed (n= 331)
Records screened (n= 40)
Records excluded (n= 291)
Full-text articles assessed for eligibility (n= 37)
Full text articles excluded with reason (n= 17)
Studies included in the qualitative synthesis (n= 20)
Reasons for exclusion of full text articles: • 3 studies were not clear about follow-up time • 1 study had no clear method of statistical analysis • 3 studies had no clear diagnostic criteria or the number of patients included • 4 studies were only of patients affected by DM-2. • 6 studies were only of patients affected by Wolfram syndrome Fig. 1. Different stages of the screening process.
Limitations
Conclusions
The present paper should be considered in the light of some limitations. First of all, we did not carry out a meta-analysis because the data from most of the studies did not permit this. In particular, the samples included different measurements and different outcomes, and patients were assessed at different time points. Another limitation is that the inclusion and exclusion of studies may reflect the authors' bias. The research on identifying risk factors for suicide in DM-1 had some shortcomings. Some studies had small sample sizes and small numbers of suicides. Moreover, methodological problems in the research often made the results difficult to interpret. For example, not all studies specified follow-up periods and, additionally, not all studies mentioned the exact number of suicide attempts and completed suicides. Some of the studies had retrospective designs, and the absence of strategies to ensure both inter-rater reliability and the validity of the data made drawing reliable conclusions difficult. Most of the studies investigated a mix of age groups, and future research should take into account the age of the patients with DM-1. Finally, some of the studies were carried out with heterogeneous samples, mixing patients at different stages of their illness.
Given the association between DM-1 and suicide, it is of great importance to prevent suicide in these patients. The results of this review support the recommendation that a suicide risk assessment of patients with DM-1 should be part of the routine clinical assessment. The assessment of patients at risk should include an evaluation of current suicidal ideation and previous suicidal behavior since premorbid suicidal ideation is an important risk factor for later completed suicide. Preventive strategies should involve general practitioners and other specialists, along with referral to psychiatrists for treatment. Further work is needed to understand the mechanisms underlying the association between DM-1 and suicidal behavior and to better identify a demographic, physiological and psychosocial profile that could predict patients at high risk for suicide. Screening for suicidal ideation and depression among individuals with DM-1 can be an effective strategy for early identification and intervention by clinicians. Early treatment of depression may prevent progression from depressed mood to active suicidal behavior and may also reduce long-term diabetesrelated complications.
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Conflict of interest statement The authors declare no conflict of interest. References [1] Lin EHB, Von Korff M, Wagner EH. Identifying suicide potential in primary care. J Gen Intern Med 1989;4:1–6. [2] Lish JD, Zimmerman M, Farber NJ, Lush DT, Kuzma MA, Plescia G. Suicide screening in a primary care setting at a Veterans Affairs Medical Center. Psychosomatics 1996;37:413–24. [3] Hendin H. Suicide, assisted suicide, and medical illness. J Clin Psychiatry 1999;60:46–50. [4] Stenager EN, Stenager E. Physical illness and suicidal behavior. In: Hawton KvH K, editor. The international handbook of suicide and attempted suicide. New York: Wiley; 2000. [5] Lönnqvist JK. Psychiatric aspects of suicidal behaviour: depression. In: Hawton KvH K, editor. International handbook of suicide and attempted suicide. Chichester: John Wiley & Sons; 2000. [6] Gupta M, Gupta A. Depression and suicidal ideation in dermatology patients with acne, alopecia areata, atopic dermatitis and psoriasis. Br J Dermatol 1998;139:846–50. [7] Carson A, Best S, Warlow C, Sharpe M. Suicidal ideation among outpatients at general neurology clinics: prospective study. Br Med J 2000;320:1311–2. [8] Todd JA. Etiology of type 1 diabetes. Immunity 2010;32:457–67. [9] Leslie R, Delli Castelli M. Age-dependent influences on the origins of autoimmune diabetes: evidence and implications. Diabetes Dec 2004;53:3033–40. [10] Rush WA, Whitebird RR, Rush MR. Depression in patients with diabetes: does it impact clinical goals? J Am Board Fam Med 2008;21:392–7. [11] Weiss DB, Dyrud Jl, House RM, Beresford TP. Psychiatric manifestations of autoimmune disorders. Curr Treat Options Neurol 2005;7:413–7. [12] International evaluation of cause-specific mortality and IDDM. Diabetes Care January 1991;14. [13] Kyvik KO, Stenager EN, Green A, Svendsen A. Suicides in men with IDDM. Diabetes Care 1994;17:210–2. [14] Mühlhauser I, Sawicki PT, Blank M, Overmann H, Richter B, Berger M. Reliability of causes of death in persons with Type I diabetes. Diabetologia 2002;45:1490–7. [15] Ahola AJ, Harjutsalo V, Saraheimo M, Forsblom C, Groop PH. Purchase of antidepressant agents by patients with type 1 diabetes is associated with increased mortality rates in women but not in men. Diabetologia 2012;55:73–9. [16] Batty GD, Kivimaki M, Park IS, Jee SH. Diabetes and raised blood glucose as risk factors for future suicide: cohort study of 1 234 927 Korean men and women. J Epidemiol Community Health 2012;66:650–2. [17] Wibell L, Nyström L, Ostman J, Arnqvist H, Blohmé G, Lithner F, et al. Increased mortality in diabetes during the first 10 years of the disease. A population-based study (DISS) in Swedish adults 15–34 years old at diagnosis. J Intern Med 2001;249:263–70. [18] Feltbower RG, Bodansky HJ, Patterson CC, Parslow RC, Stephenson CR, Reynolds C, et al. Acute complications and drug misuse are important causes of death for children and young adults with Type 1 diabetes. Diabetes Care 2008;31:922–6.
[19] Harjutsalo V, Forsblom C, Groop PH. Time trends in mortality in patients with type 1 diabetes: nationwide population based cohort study. Br Med J Sep 2011;8:343. [20] Pompili M, Lester D, Innamorati M, De Pisa E, Amore M, Ferrara C, et al. Quality of life and suicide risk in patients with diabetes mellitus. Psychosomatics Jan-Feb 2009;50:16–23. [21] Roy A, Roy M, Janal M. Suicide attempts and ideation in African-American type 1 diabetic patients. Psychiatry Res 2010;179:53–6. [22] de Ornelas Maia ACC, Braga Ade A, Brouwers A, Nardi AE, Oliveira AC, Silva AC. Prevalence of psychiatric disorders in patients with diabetes types 1 and 2. Compr Psychiatry 2012;53:1169–73. [23] Patterson CC, Dahlquist G, Harjutsalo V, Joner G, Feltbower RG, Svensson J, et al. Early mortality in EURODIAB population-based cohorts of type 1 diabetes diagnosed in childhood since 1989. Diabetologia 2007;50:2439–42. [24] Goldston DB, Kelley AE, Reboussin DM, Daniel SS, Smith JA, Schwartz RP, et al. Suicidal ideation and behavior and noncompliance with the medical regimen among diabetic adolescents. J Am Acad Child Adolesc Psychiatry 1997;36:1528–36. [25] Boileau P, Aboumrad B, Bougneres P. Recurrent comas due to secret selfadministration of insulin in adolescents with type 1 diabetes. Diabetes Care 2006;29. [26] Fuller-Thomson E, Sawyer JL. Lifetime prevalence of suicidal ideation in a representative sample of Canadians with type 1 diabetes. Diabetes Res Clin Pract 2009;83:9–11. [27] Radobuljac MD, Bratina NU, Battelino T, Tomori M. Lifetime prevalence of suicidal and self injurious behaviors in a representative cohort of Slovenian adolescents with type 1 diabetes. Pediatr Diabetes 2009;10:424–31. [28] Joner G, Patrick S. The mortality of children with Type 1 (insulin-dependent) diabetes mellitus in Norway, 1973–1988. Diabetologia 1991;34:29–32. [29] Dahlquist G, Bengt KA. Mortality in childhood-onset type 1 diabetes: a populationbased study. Diabetes Care 2005;28:2384–7. [30] Goldston DB, Kovacs M, Ho VY, Parrone PL, Stiffler L. Suicidal ideation and suicide attempts among youth with insulin-dependent diabetes mellitus. J Am Acad Child Adolesc Psychiatry 1994;33:240–6. [31] Westling S, Ahrén B, Träskman-Bendz L, Westrin A. High CSF-insulin in violent suicide attempters. Psychiatry Res 2004;129:249–55. [32] Warner D, McKinney P, Law G, Bodansky H. Mortality and diabetes from a population based register in Yorkshire 1978–93. Arch Dis Child May 1998;78:435–8. [33] Manjarrez-Gutierrez G, Marquez R, Mejenes-Alvarez S, Godinez-Lopez T, Hernandez R. Functional change of the auditory cortex related to brain serotonergic neurotransmission in type 1 diabetic adolescents with and without depression. World J Biol Psychiatry 2009;10:877–83. [34] Ahmad S, Tabassum S, Haider S. Role of decreased plasma tryptophan in memory deficits observed in type-I diabetes. J Pak Med Assoc Jan 2013;63:65–8. [35] Golomb B, Tenkanen L, Alikoski T, Niskanen T, Manninen V, Huttunen M, et al. Insulin sensitivity markers: predictors of accidents and suicides in Helsinki Heart Study screenees. J Clin Epidemiol Aug 2002;55:767–73. [36] Roy A, Virkkunen M, Linnoila M. Serotonin in suicide, violence, and alcoholism. In: Coccaro E, Murphy P, editors. Serotonin in major psychiatric disorders. Washington, DC: American Psychiatric Association; 1991. p. 187–208. [37] Russell KS, Stevens JR, Stern TA. Insulin overdose among patients with diabetes: a readily available means of suicide. Prim Care Companion J Clin Psychiatry 2009;11:258–62.
Contents lists available at ScienceDirect
Journal of Psychosomatic Research
Review
Suicide risk in type 1 diabetes mellitus: A systematic review Maurizio Pompili a,⁎, Alberto Forte a, David Lester b, Denise Erbuto a, Fabiana Rovedi a, Marco Innamorati a, Mario Amore c, Paolo Girardi a a b c
Department of Neurosciences, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, Italy The Richard Stockton College of New Jersey, USA Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Section of Psychiatry, University of Genova, Italy
a r t i c l e
i n f o
a b s t r a c t Background: Research has shown that suicide risk is often present in patients suffering from type 1 diabetes mellitus (DM-1). Objectives: The aim of the present paper was to investigate whether there was a relationship between DM-1 and suicidal behavior and to determine whether or not people affected by DM-1 are at an increased risk of completed suicide, attempted suicide, and suicidal ideation. Data sources: We performed a careful MedLine, ExcerptaMedica, PsycLit, PsycInfo and Index Medicus search to identify all papers on the topic for the period 1970 to 2013 written in English. The following search terms were used: (suicide OR suicide attempt OR ideation) AND (diabetes mellitus). Where a title or abstract seems to describe a study eligible for inclusion, the full article was examined. Eligibility criteria: We included only original articles published in English peer-reviewed journals. We excluded meta-analyses and systematic reviews, studies that were not clear about follow-up times, the method of statistical analysis, diagnostic criteria or the number of patients included, and studies only on patients affected by type 2 diabetes mellitus (DM-2). Results: The research reviewed indicated that patients with DM-1 are at an increased risk for suicide, although no clear consensus exists regarding the level of the increased risk. Limitations: The studies used different measurement techniques and different outcomes, and they assessed patients at different time points. Conclusions and implications: Our findings support the recommendation that a suicide risk assessment of patients with DM-1 should be part of the routine clinical assessment. The assessment of patients at risk should consist of the evaluation of current and previous suicidal behaviors (both suicidal ideation and attempted suicide). © 2014 Elsevier Inc. All rights reserved.
Article history: Received 7 July 2013 Received in revised form 20 February 2014 Accepted 20 February 2014 Keywords: Diabetes type I Suicide Prevention
Contents Introduction . . . . . . . . . . . . . . . Methods . . . . . . . . . . . . . . . . . Study design and quality assessment . . Results . . . . . . . . . . . . . . . . . . Search strategy . . . . . . . . . . . . Adults: completed suicide . . . . . . . Adults: non-fatal suicidal behavior . . . Adolescents: completed suicide . . . . Adolescents: non-fatal suicidal behavior Children: completed suicide . . . . . . Children: non-fatal suicidal behavior . . Discussion . . . . . . . . . . . . . . . . Limitations . . . . . . . . . . . . .
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⁎ Corresponding author at: Department of Neuroscience, Mental Health and Sensory Organs, Suicide Prevention Center, Sant'Andrea Hospital, Sapienza University of Rome, 1035-1039, Via di Grottarossa, 00189 Rome, Italy. Tel.: +39 0633775675; fax: +39 0633775342. E-mail address: [email protected] (M. Pompili).
http://dx.doi.org/10.1016/j.jpsychores.2014.02.009 0022-3999/© 2014 Elsevier Inc. All rights reserved.
M. Pompili et al. / Journal of Psychosomatic Research 76 (2014) 352–360
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Introduction Research has documented high rates of psychiatric disorders among medical patients in general [1–4]. Suicidal ideation, which is frequently present in patients with major depression [5], is also common in patients suffering from medical illnesses [6], and this suicidal ideation in medically ill patients may arise from a comorbid depression [7]. There are more than 30 million people worldwide suffering from type 1 diabetes mellitus (DM-1) [8], an illness resulting in autoimmune damage to the insulin-secreting islet cells and caused by a mixture of genetic and non-genetic factors [9]. DM-1 is often characterized by multi-organ involvement, and the damage to the primary target organ typically drives the clinical presentation and distinguishes the disease. Patients with DM-1 have almost doubled risk of depression compared to the general population [10], and psychiatric symptoms are frequent in patients with DM-1 and other autoimmune diseases [11]. The aims of the present paper were to examine research on the association between DM-1 and suicidal behavior and to determine whether or not people affected by DM-1 are at an increased risk of completed suicide, attempted suicide, and suicidal ideation. Methods In order to provide a systematic review about DM-1 and suicidal behavior, we performed a careful MedLine, ExcerptaMedica, PsycLit, PsycInfo and Index Medicus search to identify all papers in English for the period 1970 to 2013. The following search terms were used: (suicide OR suicide attempt OR ideation) AND (diabetes mellitus). The articles were restricted to those published in English peer-reviewed journals. Where a title or abstract seems to describe a study eligible for inclusion, the full article was examined to consider its relevance on the basis of the inclusion criteria. Any discrepancies between the two reviewers who, blind to each other, examined the studies for possible inclusion were resolved by consultation with the senior authors. Textbooks were also consulted in order to locate articles. In addition, we also examined reference lists and contacted experts in the field. Abstracts that did not refer to suicide and diabetes mellitus were excluded. We excluded meta-analyses and systematic reviews, studies that were not clear about follow-up times, the method of statistical analysis, diagnostic criteria or the number of patients included, and studies which included only patients affected by diabetes type II (DM-2) because the age of onset and pathogenesis of DM-2 is different from that of DM-1. The principal reviewer (MP) inspected all items. Then, three reviewers (AF, FR, MP) independently inspected all citations of the studies identified by the search and grouped them according to topic. Reviewers acquired the full article for all papers. Where discrepancies occurred, they were resolved by discussion with the principal reviewer who independently inspected all articles and grouped them into the major areas of interest identified. Study design and quality assessment A quality assessment was performed as shown in Table 1. Studies were rated for the quality assessment using the following criteria: (i) representativeness of the sample (1 point), (ii) presence of a control group (1 or 2 points), (iii) n N 1000 subjects (1 or 2 points); (iv) duration of follow-up N 1 year (1 or 2 points),(v) evidence-based measures of assessment (1 or 2 points), (vi) data presentation (1 or 2 points), and (vii) evidence-based measures assessing suicidal behavior (1 or 2 points). Quality ratings could range from 0 to 8 for each study.
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Most of the studies were characterized by good data presentation and evidenced-based measures for the assessment of DM-1. The retrospective studies and cohort studies included were characterized by large sample sizes and representative samples. Eight studies had a sample size of more than 1000 subjects. On the other hand, the quality of the studies was often compromised by the absence of evidence-based measures assessing suicidal behavior. One of the retrospective studies was compromised by an unrepresentative sample. Three cross-sectional studies were characterized by good data presentation and evidencebased measures assessing suicidal behavior, but small sample sizes limited the quality of these studies. Results Search strategy The combined search strategies yielded a total of 331 records to be screened. We first reviewed titles and abstracts and applied the selection criteria outlined above with the exception of study design. This process led to the exclusion of 291 records from the 331 originally selected. The large majority of studies excluded failed to mention in the title or abstract any of the outcome indicators specified above. In the second stage of the screening process, two new reviewers read the full articles and coded them based on the methodology. Studies that did not meet the methodological standards set by the reviewers were excluded, resulting in the inclusion of 20 studies for the final review. The different stages of the screening process are illustrated in Fig. 1. Of the twenty studies included in this review, seventeen were longitudinal studies, and three were cross-sectional studies. The seventeen longitudinal studies included 4 prospective studies (including 2 cohort studies), 12 retrospective studies (including 8 cohort studies) and 1 mixed prospective/retrospective study. Adults: completed suicide An evaluation of the causes of mortality in patients with DM-1 was conducted in Japan, Israel, the United States, and Finland [12]. In Finland, the major cause of death was suicide (36% of the deaths). In Japan, deaths were most often attributed to DM-1 complications and kidney disease, while in the other countries mortality was most often attributed to acute complications of diabetes. Kyvik et al. [13] found that young men with DM-1 had a higher risk of suicide than expected. For the 153 deaths of men with DM-1, 12 were classified as suicides (SMR = 1.6, 0.05 b p b 0.10). For the group aged 20–24 years, the SMR was 2.98 (p b 0.05). Muhlhauser et al. [14] followed a cohort of 3674 patients with DM-1 in which 251 patients died, including 22 by suicide. They found that classification of the cause of death based on death certificates or on ICD-codes was unreliable in adult patients with DM-1. They suggested that it is necessary for researchers to re-examine the cause of death for each patient. A prospective study [15] evaluated 4174 subjects with DM-1 (51% men, age: 39 ± 12 years, DM-1 duration: 22 ± 12 years) for depression and cause of death. Depression was operationally defined as purchasing antidepressant medications. It was found that antidepressant purchasers had a higher mortality rate than did non-purchasers. In the total sample, 474 died. The cumulative mortality rate was highest among subjects taking antidepressant at baseline. Six suicides occurred, two in each of the three groups: patients who had not purchased antidepressant agents at baseline (3.4% of the deaths), those without any purchase of antidepressants during the study (0.7% of the deaths) and those who purchased antidepressant during the follow-up (1.7% of the deaths). Some studies have found a higher risk of suicide in patients with DM-1 and also patients with DM-2. Batty et al. [16] conducted a retrospective cohort study to examine the relationship between DM-1 and suicide risk. The sample consisted of a cohort of 1,329,525 individuals aged 30–95 years at baseline (of whom 482,618 were women). There were 472 deaths due to suicide (389 men and 83 women). The highest suicide rates were in men and women with DM-2. Moreover, there was no confirmation of a high suicide rate in the impaired glucose/prediabetes group. Wibell et al. [17] examined the mortality rate in the first year after a diagnosis of DM-1 in 4097 new cases of patients with DM-1. Their results showed that 58 patients died (SMR = 3.5) (95% CI = 2.7 ± 4.5). Suicide was more common in the men. Nine cases of suicide occurred compared to 4.5 expected (SMR = 2.0; 95% CI = 1.0 ± 3.8). A retrospective study examined mortality rates and causes of death among patients with DM-1 aged b29 years [18]. Among 4246 individuals, 108 patients died, including 24 (22%) from accidents or violence. Among these 24 deaths were six suicides. Harjutsalo et al. [19] examined mortality trends among 17,306 patients with early onset DM-1 (age: 0–14 years) and late onset DM-1 (15–29 years). One hundred and ten suicides occurred. Half of the suicides took place during the first 20 years of the illness.
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Table 1 Summary of the study outcomes and quality assessment. Study
Quality Scorea
Study design
Wibell et al. [17]
Muhlhauser et al. [14]
Pompili et al. [20]
Roy et al. [21]
I=1 II = 1 III = 2 IV = 0 V=1 VI = 0 Total score = I=0 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = I=1 II = 1 III = 1 IV = 0 V=1 VI = 1 Total score = I=1 II = 1 III = 2 IV = 2 V=1 VI = 0 Total score =
Results Overall rate –Suicide (N = 557) Diabetics: 557; non-diabetics: 0 –Suicide attempted (N = 70) Diabetics: 56; non-diabetics: 14 –Suicide ideation (N = 23) Diabetics: 23; non-diabetics: 0 Finland: 33% of deaths due to accidents, suicide and homicide.
Risk or protective factors — SMR
Conclusions
Not reported
High rate of suicide in DM-1 patients in Finland
Retrospective cohort study: 4 population cohorts
8137 diabetics
No
Cross-cultural study with population in 4 different countries. Cases diagnosed from 1965 to 1979.
Retrospective cohort study
1682 diabetic men
Yes
All Danish men born between 1949 and 1964 who were diagnosed with DM-I. Record linkage with the Danish Civil Registration System. Death certificates scrutinized.
Retrospective cohort study
4097 diabetics
Yes
58 patients died, including 10 cases Nationwide Cause of Death Registry. Underlying cause of death of suicide. based on the ICD.
Prospective cohort study
3674 diabetic adults
Yes
Causes of death assessed by a clinical review committee. Information provided by death certificates and ICD-9 codes; Information provided by death certificates available for 73% and ICD-9 codes for 79% of the patients.
251 (7%) patients died, including 22 suicides. Only 7 of the 17 cases with ICD codes were classified as suicides.
Case–control study
100 patients with diabetes and 100 controls who sought consultation at an internal medicine outpatient clinic
No
Assessment: Suicide Score Scale (SSS), Beck Hopelessness Scale (BHS), SF-36 Health Survey Questionnaire and General Self-Efficacy Scale.
Not reported Patients with diabetes had a moderate-to-high average score for hopelessness. Women had greater suicidality than men. DM-2 patients had a lower score on the BHS.
Case–control study
412 AfricanAmerican diabetics and 404 controls
Yes
Instruments: Childhood Trauma Questionnaire (CTQ), Hostility and Direction of Hostility Questionnaire (HDHQ), and Beck Depression Inventory (BDI).
More diabetic patients attempted suicide: 55 of 412 diabetics (13.3%) and 14 of 404 controls (3.5%). African-Americans with DM-1 had an increased risk of attempting suicide.
5 12 suicides. 28 unknown causes of 12 suicides, SMR = 1.6. For those aged death (expected 0.83) and 22 from 20–24, SMR was significantly increased (SMR = 2.98). accidents (expected 17.97). 3 possible suicides and 2 probable suicides. One accidental death was probably suicide.
Risk increased in Danish men, especially those in the age-group 20–24 years with disease onset at age 15–19.
6 Early mortality was increased threefold.
7 Not reported
The assessment of causes of death based on death certificates or on ICD-codes is unreliable in adult patients with DM-1.
7 Patients with diabetes showed greater hopelessness and suicide ideation than internal medicine outpatients.
5
7
Risk factors for a suicide attempt: female, smoker, abusing alcohol, a lifetime history of drug abuse, hostility, and childhood trauma. The risk is tripled with a BDI depression score ≥14.
Suicide risk in diabetics appears to be multifactorial and includes gender, developmental, personality, psychiatric, and substance abuse factors.
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Kyvik et al. [13]
Follow- Methods up
–Diabetics: 1,257,303 –Controls: 604 –Total: 1,257,907
Adults
No authors listed [12]
Sample
Study Quality Scorea Ahola et al. [15]
Batty et al. [16]
Risk or protective factors — SMR
Conclusions
Yes
Data obtained from National Register. Data on all-cause mortality and cause of death obtained from the Finnish Cause of Death Register.
474 deaths: 19.8% antidepressants at baseline, 16.2% antidepressants during follow-up and 9.3% no antidepressant. 6 suicides.
10-Year cumulative mortality rate highest among purchasers of antidepressant agents at baseline (95% CI = 18.1–26.6).
The purchase of antidepressant agents in patients with DM-1 was associated with increased mortality in women, but not in men.
1,234,927 diabetics
Yes
Data taken from the Korean Cancer 472 suicides (389 in men and 83 in women). In men, suicide rates are Prevention Study: 1,329,525 individuals (482,618 women), aged high in DM-2 patients. 30–95 years, who participated in at least one biennial medical evaluation.
The highest suicide rates were in men and women with an existing or new diagnosis of DM-2. No association between impaired glucose/prediabetes and suicide.
Diabetes, but not raised blood glucose, was a risk factor for completed suicide.
200 subjects: 100 with DM-1 and 100 with DM-2
Yes
DM 1 patients had a higher prevalence of psychiatric disorders than DM-2 patients. The most prevalent disorders were generalized anxiety disorder (21%), dysthymia (15%), social phobia (7%), current depression (5.5%), lifelong depression (3.5%), panic disorder (2.5%), and risk of suicide (2%). Overall rate –Suicides (N = 121) Diabetics: 121; non-diabetics: 0 –Suicide attempted (N = 20) Diabetics: 5; non-diabetics: 15 –Suicide ideation (N = 63) Diabetics: 37; non-diabetics: 26 The one-year prevalence of suicidal Semistructured and structured ideation: 13.2% (n = 12 of 91); 2 interview instruments and selfreport questionnaires to determine (2.2%) reported thoughts of suicide in the 2 weeks prior to the assesshistory of suicidal thoughts and ment. Lifetime prevalence of suibehavior, serious noncompliance with the medical regimen, current cidal ideation among diabetic psychiatric disorder, hopelessness, youths: 26.4% (n = 24 of 91). and self-efficacy expectations Interviews and medical 19 adolescents with unusual examinations. frequency of coma; 16 admitted surreptitious self-administration of insulin. Those 16 adolescents were mainly girls, with a higher frequency of coma and a lower insulin declared dose than the remaining 136. 141 deaths; 71 (53%) unrelated to Thirteen population-based diabetes; and for 16 (12%) the role EURODIAB registers in 12 countries; record linkage to population played by diabetes was uncertain. registers or through contact with doctors providing care.
Risk of suicide was found to be approximately 2%, which can be considered high, emphasizing the need for attention to this population
High prevalence of psychiatric disorders in diabetic patients highlights the need for accurate assessments of symptoms related to mental health.
Both one-year and lifetime suicidal thoughts related to noncompliance with the medical regimen, even after controlling for the presence of psychiatric disorder (p = .056 and p b .001, respectively)
Suicidal thoughts were related and serious noncompliance with the medical regimen are strongly associated in diabetic teenagers, and psychiatric disorder is a common correlate of both. The 16 cases were characterized by a large predominance of girls, frequent use of low insulin doses, frequent familial difficulties, and major fears of complications.
Followup
I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = 7 I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = 7 I=1 II = 1 III = 1 IV = 1 V=1 VI = 1 Total score = 6
Prospective– retrospective study
4174 diabetics
Retrospective cohort study
Cross-sectional observational study and comparative study
–Diabetics: 46,749 –Controls: 82,984 –Total: 129,733
Adolescents
Goldston et al. [24]
Results
Sample
I=1 II = 0 III = 1 IV = 0 V=1 VI = 1 Total score = 4 Boileau et al. [25] I=1 II = 0 III = 1 IV = 2 V=1 VI = 0 Total score = 4 Patterson et al. [23] I = 1 II = 0 III = 2 IV = 2 V=1 VI = 0 Total score = 6
Observational study
91 diabetic adolescents (39 f. 52 m)
Yes
Prospective cohort study
149 diabetic adolescents
No
Retrospective cohort study
28,887 diabetic children
Yes
Data collection form for identification and social data, Mini International Neuropsychiatric Interview [10] (MINI).
Not reported
The number of deaths from suicide was similar to that expected from national rates (11 observed vs. 10.2 expected; SMR = 1.1; 95% CI = 0.5–1.9). Deaths from accidents and violence, including suicides, was marginally greater than the number expected from national rates (48 observed vs. 40.7 expected; SMR = 1.2; 95% CI = 0.9–1.6)
M. Pompili et al. / Journal of Psychosomatic Research 76 (2014) 352–360
de Ornelas Maia et al. [22]
Methods
Study design
Significant excess mortality following the diagnosis of DM-1 in childhood occurs in most European countries.
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Table 1 (continued)
Fuller-Thomson et al. [26]
Radobuljac et al. [27]
Harjutsalo et al. [19]
Quality Scorea
Study design
I=0 II = 1 III = 2 IV = 0 V=0 VI = 0 Total score = 3 I=1 II = 1 III = 2 IV 0 V=1 VI = 1 Total score = 6 I=1 II = 0 III = 2 IV = 0 V=1 VI = 0 Total score = 4
Cross-sectional study 82,675 respondents, 190 with DM-1 and 82,485 without DM1
No
Cross-sectional study 126 patients, 499 controls
No
Population based nationwide cohort study
Results
Risk or protective factors — SMR
Conclusions
Microdata file of the Canadian Community Health Survey. Prevalence of suicidal ideation was estimated for those with and without DM-1.
Prevalence of suicidal ideation among patients with DM-1 was 15.0% (95% CI = 7.1%, 22.9%), and for those without DM-1 9.4% (95% CI = 9.0%, 9.8%).
The age and sex-adjusted odds of suicidal ideation are 1.61 (95% CI = 1.08, 2.42), for individuals with DM-1 in comparison to those without.
Subjects with DM-1 had a 61% higher probability of reporting suicidal thoughts than individuals without DM-1.
Self-reported questionnaire on demographic data, family and living circumstances, school, health, social support, substance use and abuse, psychosocial help, friends, self-esteem, depression symptoms, and suicidal behavior.
DM-1 is protective against suicidality Females reported a higher in adolescent males, but not in females. incidence of suicidal ideation and behavior.
All Finnish patients diagnosed as having DM-1 below age 30 years between 1970 and 1999
The lowest prevalence of suicidal ideation and intended suicide was in males with diabetes. Females with diabetes reported the highest prevalence of suicidal ideation (p b 0.001), intended suicide (p b 0.01), and attempted suicide (p b 0.05) 110 suicides. Increased mortality due to suicide in the late onset cohort
Nationwide population-based registry: time period from 1973 through 1982
Overall rate –Suicide (N = 60) Diabetics: 16; non-diabetics: 54 –Suicide attempted (N = 6) Diabetics: 6; non-diabetics: 0 –Suicide ideation (N = 19) Diabetics: 19; non-diabetics: 0 40% deaths were from accidents Overall SMR for all-cause mortality was Accidents and suicides and suicides. No females. 2 suicides. 207 (95% CI = 126–319). comprise the majority of the deaths.
Follow- Methods up
Yes 17,306 diabetics; 10,492 were in the early onset cohort and 6814 were in the late onset cohort.
–Diabetics: 18,303 –Controls: 378 –Total: 18,681
Children
Joner et al. [28]
Sample
I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = 7
Retrospective study
1908 diabetics
No
Suicide rate was increased only in women with early onset diabetes, SMR = 3.3 (1.9 to 4.7).
Significantly higher rates of depression in DM-1 patients than in patients without DM-1.
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Study
Study Study design
Results
Risk or protective factors — SMR
Conclusions
Yes
Children admitted to a pediatric endocrinology unit. Inclusion criteria: newly diagnosed with classic, acute-onset, ketosis-prone DM-I; no other systemic illness.
Suicidal ideation: higher rate than expected (n = 15). Attempted suicide (n = 6): relatively few over the follow-up; diabetes-related methods commonly were used.
Suicidal ideation shortly after DM onset related only to concurrent severity of depressive symptoms. Suicidal ideation associated with later noncompliance with treatment.
Clinicians should be alert to the possibility of suicidal ideation among children with DM
Yes
Diabetes register records: all children with DM-I diagnosed under age 17. Three independent sources: pediatricians, physicians, and diabetes nurse specialists; general practitioner records; hospital discharge data.
26 deaths identified. 15 deaths (58%) were attributed to diabetes or its complications; 11 (42%) were unrelated to diabetes and included one suicide.
For mortality from all causes, SMR = 247 (95% CI = 163 to 362). Mortality was significantly increased for those under 34. The largest number of deaths (n = 10) occurred in the 15–19 year age range, with an SMR of 442 (95% CI = 209 to 802).
Increased mortality for young people with DM, particularly in the “transition” age range.
Among diabetics, 23 deaths clearly related to diabetes. 20 deaths were classified as having an uncertain relationship to diabetes; 7 of them died by suicide. No significant difference in traffic accidents (odds ratio: 1.02 [95% CI = 0.40 to 2.37]). 54 control subjects committed suicide Population based register; children 108 deaths, 22% (n = 24) from diagnosed between 1978 and 2004 accidents or violence, 6 suicides. were linked to the U.K. National 16% of all deaths related to drug Health Service Central Register for misuse (including insulin but death notifications. Deaths were excluding tobacco and alcohol). 74 coded using ICD-9 (1979–2000) deaths were children between the ages 0 and 14 years and 34 aged and ICD-10 (2001–2005). 15–29 years
The SMR for all causes was higher for females than males (2.65 vs. 1.93, p = 0.05). SMR controlling for age and sex was 2.15 (95% CI = 1.70 to 2.68)
Significant excess mortality in young DM-1 patients. There was a large proportion of unexplained deaths in bed, which should be further studied. There was no clear excess death rate caused by suicide or traffic accidents Subjects under 30 years of age had a 4.7 times excess mortality risk. Drug misuserelated deaths may be an emerging trend in this population, warranting further investigation.
Followup
I=1 II = 0 III = 1 IV = 2 V=1 VI = 1 Total score = 6 Warner et al. [32] I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = 7 Dahlquist et al. [29] I = 1 II = 1 III = 2 IV = 0 V=1 VI = 0 Total score = 5
Prospective study
95 diabetic children (51 f; 44 m)
Retrospective cohort study
1854 diabetic children
Retrospective cohort study and case– control study
Yes Cohort: 10,200 diabetic children. 78 died with previously diagnosed diabetes; 378 died without previous diagnosis of diabetes (control group)
Feltbower et al. [18]
Retrospective cohort study
4246 diabetics
Goldston et al. [30]
I=1 II = 0 III = 2 IV = 2 V=1 VI = 1 Total score = 7
Yes
Population-based incident childhood diabetes register, covering onset cases since 1 July 1977, linked to the Swedish Cause of Death Register up to 31 December 2000.
SMR for suicide = 2.1 (95% CI = 1.4 to 3.2); SMR for deaths resulting from drug misuse (including insulin) 6.4 (95% CI = 3.7 to 10.2); the SMR increased with increasing disease duration.
Quality ratings reported have 8 as maximum score. a Studies were rated for the quality assessment using the following criteria specified below: I) II) III) IV) V) VI)
representativeness of the sample to the general population (1 point): 0 points not representative; 1 representative presence of a control group (1 point): 0 points without control group, 1 point with control group number of subjects in treatment group (1 or 2 points). 0 points if N b 100; 1 point if N b 500; 2 points if N N 500 duration (years) of follow-up (1 or 2 points). 1 point b 1 year; 2 points N 1 year data presentation (1 point). 0 points, unclear data presentation in the text; 1 point, clear data presentation in the text evidence-based measures assessing suicide or suicide attempts (1 point): 0 points absence of evidence-based measures assessing suicide or suicide attempts; 1 point presence of evidence-based measures assessing suicide or suicide attempts.
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Methods
Sample
Quality Scorea
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M. Pompili et al. / Journal of Psychosomatic Research 76 (2014) 352–360
The patients with late onset DM-1 showed an increased mortality from suicide, with an SMR of 2.8 (95% CI = 2.6 to 3.0). In patients with early-onset DM-1, only females had an increased mortality from suicide, with an SMR of 3.3 (95% CI = 1.9 to 4.7). Adults: non-fatal suicidal behavior Pompili et al. [20] investigated the quality of life and its association with suicide risk among 100 patients with DM-1 and DM-2 (52 women and 48 men). Patients with DM1 had a moderate-to-high average score for hopelessness. Women with DM-1 had more suicidal ideation than men, and patients with DM-1 had higher hopelessness and suicidal ideation scores than patients with DM-2. Roy et al. [21] studied 412 African-Americans with DM-1 and 404 African-American controls. DM-1 patients were more likely to attempt suicide than controls (13.3% vs. 3.5%, respectively, p b 0.001). Suicide attempters were more frequently female, hostile and depressed, and they were more likely to have a history of childhood trauma, alcohol abuse, drug abuse and smoking than were the non-attempters. A recent study compared the prevalence of psychiatric disorders in patients with DM1 and DM-2 [22]. The risk of suicide (assessed by the Mini International Neuropsychiatric Interview) was higher in patients with DM-1 than in patients with DM-2 (3% vs. 1%). The most common psychiatric disorders in the patients with DM-1 were generalized anxiety (21%), dysthymia (15%), social phobia (7%), current depression (5.5%), lifelong depression (3.5%), and panic disorder (2.5%). Adolescents: completed suicide Patterson and colleagues [23] studied causes of death in Europe in patients with DM-1 under the age of 15 (N = 28,887). There were 141 deaths, with an SMR of 2.0. They did not find an excess of deaths related to suicide (11 observed, 10.2 expected; SMR = 1.1; 95% CI = 0.5–1.9). Adolescents: non-fatal suicidal behavior Goldston et al. [24] studied a sample of 91 adolescents with DM-1. They found that suicidal ideation was more frequent than expected, but the rate of suicide attempts was not higher than in the general population. However, the duration of DM-1 was associated with suicidal ideation (in the prior year and lifetime). The results of this study also indicated that suicidal ideation is associated with serious noncompliance with the medical treatment. Boileau et al. [25] evaluated 322 cases of recurring hypoglycemic comas in 149 adolescents with DM-1. Sixteen patients admitted self-injections in order to attempt suicide. This group reported a higher frequency of coma, a lower declared insulin dose, and more frequent family difficulties than the other patients with repeated hypoglycemic coma. Fuller-Thomson et al. [26] compared the lifetime prevalence of suicidal ideation among patients with and without DM-1. The prevalence of suicidal ideation, in patients with DM-1 was 15.0% (95% CI = 7.1% to 22.9%), while those without DM-1 had a prevalence of suicidal ideation of 9.4% (95% CI = 9.0% to 9.8%). Thus, the DM-1 patients had a 61% higher risk of reporting suicidal thoughts than did individuals without this illness. Radobuljac et al. [27] found that adolescents with DM-1 tended to have a lower lifetime prevalence of all suicidal behaviors and self-injurious behaviors. The lowest prevalence of all suicidal behaviors was found in males with DM-1, significantly lower than in males without DM-1 for suicidal ideation (p b 0.05) and intended suicide (evaluated by the question: “Have you once or on more occasions intended to end your own life and changed your mind in the last moment?”) (p b 0.05). This reduced rate of suicidal ideation was found in the adolescent males but not in the adolescent females. Children: completed suicide Joner and Patrick [28] studied the mortality rate in 1908 children with DM-1. Twenty had died at follow-up. Forty percent of the deaths were from accidents or suicide, and these occurred only in the boys. No girls were recorded as dying from accidents or suicide. Dahlquist et al. [29] evaluated mortality rate in a cohort of young patients with DM-1. They found a significant excess of mortality in patients with DM-1 even before the development of late complications. In the 78 patients who had died, 23 deaths were clearly related to DM-1. Twenty died of diabetic ketoacidosis, 7 died by suicide, and 14 died from accidents, but the number of suicides was not significantly greater than expected. Children: non-fatal suicidal behavior Goldston et al. [30] found that young patients with DM-1 have a higher than expected rate of suicidal ideation, but relatively few of the patients attempted suicide. Among those who attempted suicide, DM-1-related methods were commonly used (such as misuse of insulin). Suicidal ideation after DM-1 onset seemed to be related only to the severity of depressive symptoms.
Discussion The research reviewed above has indicated that, in general, patients with DM-1 have a higher risk for suicide than the general population does [13,19,21,24,30,31]. Patients with DM-1 are 3 to 4 times
more likely to attempt suicide than the general population [21], and patients with DM-1 have a 61% higher risk of experiencing suicidal thoughts than individuals without DM-1 [26]. On the other hand, not all research reports a higher risk of suicide in patients with DM-1 [16,27,29]. As shown in Table 1, six studies [12–17] reported the number of suicides in adult samples of diabetics. These studies reported 1079 suicides out of 2,506,180 patients included in the samples, that is, 43.1 suicides per 100,000 patients. For adolescents and children, 6 studies [18,19,23,28,29,32] reported numbers of suicide with DM-1. These studies reported 32 suicides out of 36,711 adolescent patients, that is, 87.2 suicides per 100,000 patients. We did not carry out a meta-analysis because the data differed between studies, and only a few studies reported the number of suicides. The relationship between DM-1 and suicide can be understood in the light of neurobiological correlates. Several studies have demonstrated the presence of low levels of tryptophan in patients with DM-1 [33,34]. In particular there appears to be a deterioration of brain serotonergic neurotransmission in patients with DM-1 who are depressed, as well as decreased brain uptake of tryptophan and lowered brain 5hydroxytryptamine levels. Reduced free tryptophan could lead to a reduced synthesis of central serotonin [35], and it is well known that reduced serotonin levels are associated with an increased risk for suicide [36]. The results of the research reviewed suggest that young men with DM-1 may show a higher risk for suicide than expected [13,30], especially patients aged between 15 and 29 years [19]. Moreover suicidal thoughts, noncompliance with the medical regimen and psychiatric disorder are common in diabetic teenagers [24]. Professionals working with adolescents with DM-1 should always consider the risk of suicide [27]. Despite some evidence showing that men with DM-1 are at increased risk for suicide, a few studies showed that patients with DM-1 who attempted suicide are significantly more likely to be female. Thus, there was no clear consensus regarding sex as a risk factor for suicide. Suicidal patients with DM-1 were also more likely to be depressed and to report a history of childhood trauma, smoking, alcohol abuse, and drug abuse [27]. It was also reported that African-Americans with DM-1 have an increased risk of attempting suicide [21]. Among young people who attempt suicide, methods related to DM-1 (such as misuse of insulin) were commonly used. Research has also found an association between suicidal thoughts and serious noncompliance with the medical regimen among teenagers. Not adhering to the medical regimen could be considered another form of self-destructive behavior and one that must be taken seriously. In particular, adolescents who have a lifetime history of suicidal ideation were found to be more likely to be noncompliant with their medical regimen [24]. Physicians should routinely ask their young patients about suicidal thoughts, given the relationship of these thoughts to adherence with the medical treatment. Pompili et al. [20] found an increased risk for hopelessness and suicidal ideation among patients with DM-1 over the age of 50, and they also reported an association between polytherapy and hopelessness. These findings highlight the need for an accurate assessment of suicide risk among adults affected by DM-1. From our review, we can conclude that the causes of suicide in patients with DM-1 appear to be multifactorial, and prevention strategies are of great importance. Every year, a large number of patients with DM-1 present to emergency departments with hypoglycemic episodes of “unknown” etiology, and it is possible that a significant proportion of them could be intentional overdoses [37]. Thus, suicide risk may be underestimated in patients with DM-1. Some authors have argued also that there could be a substantial underestimation of suicide as a cause of deaths in patients with DM-1 because the certification of causes of death based on death certificates or on ICD-codes may be unreliable in adult patients with DM-1 [14].
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Records identified through database searching (n= 331)
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Additional records identified through other sources (n= 4)
Records after duplicates removed (n= 331)
Records screened (n= 40)
Records excluded (n= 291)
Full-text articles assessed for eligibility (n= 37)
Full text articles excluded with reason (n= 17)
Studies included in the qualitative synthesis (n= 20)
Reasons for exclusion of full text articles: • 3 studies were not clear about follow-up time • 1 study had no clear method of statistical analysis • 3 studies had no clear diagnostic criteria or the number of patients included • 4 studies were only of patients affected by DM-2. • 6 studies were only of patients affected by Wolfram syndrome Fig. 1. Different stages of the screening process.
Limitations
Conclusions
The present paper should be considered in the light of some limitations. First of all, we did not carry out a meta-analysis because the data from most of the studies did not permit this. In particular, the samples included different measurements and different outcomes, and patients were assessed at different time points. Another limitation is that the inclusion and exclusion of studies may reflect the authors' bias. The research on identifying risk factors for suicide in DM-1 had some shortcomings. Some studies had small sample sizes and small numbers of suicides. Moreover, methodological problems in the research often made the results difficult to interpret. For example, not all studies specified follow-up periods and, additionally, not all studies mentioned the exact number of suicide attempts and completed suicides. Some of the studies had retrospective designs, and the absence of strategies to ensure both inter-rater reliability and the validity of the data made drawing reliable conclusions difficult. Most of the studies investigated a mix of age groups, and future research should take into account the age of the patients with DM-1. Finally, some of the studies were carried out with heterogeneous samples, mixing patients at different stages of their illness.
Given the association between DM-1 and suicide, it is of great importance to prevent suicide in these patients. The results of this review support the recommendation that a suicide risk assessment of patients with DM-1 should be part of the routine clinical assessment. The assessment of patients at risk should include an evaluation of current suicidal ideation and previous suicidal behavior since premorbid suicidal ideation is an important risk factor for later completed suicide. Preventive strategies should involve general practitioners and other specialists, along with referral to psychiatrists for treatment. Further work is needed to understand the mechanisms underlying the association between DM-1 and suicidal behavior and to better identify a demographic, physiological and psychosocial profile that could predict patients at high risk for suicide. Screening for suicidal ideation and depression among individuals with DM-1 can be an effective strategy for early identification and intervention by clinicians. Early treatment of depression may prevent progression from depressed mood to active suicidal behavior and may also reduce long-term diabetesrelated complications.
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