Psychiatric Disorders and Health-Related Quality of Life in Children With Type 1 Diabetes Mellitus

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Psychiatric Disorders and Health Related Quality of Life in Children with Type 1 Diabetes Mellitus Agnieszka Butwicka MD, PhD, Wojciech Fendler MD, PhD, Adam Zalepa MHA, Agnieszka Szadkowska MD, PhD, Malgorzata ZawodniakSzalapska MD, PhD, Agnieszka Gmitrowicz MD, PhD, Wojciech Mlynarski MD, PhD

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S0033-3182(15)00194-2 http://dx.doi.org/10.1016/j.psym.2015.11.001 PSYM590

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Psychosomatics

Cite this article as: Agnieszka Butwicka MD, PhD, Wojciech Fendler MD, PhD, Adam Zalepa MHA, Agnieszka Szadkowska MD, PhD, Malgorzata ZawodniakSzalapska MD, PhD, Agnieszka Gmitrowicz MD, PhD, Wojciech Mlynarski MD, PhD, Psychiatric Disorders and Health Related Quality of Life in Children with Type 1 Diabetes Mellitus, Psychosomatics, http://dx.doi.org/10.1016/j. psym.2015.11.001 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Running title: Psychiatric Disorders and Health related Quality of Life in Type 1 Diabetes

Psychiatric Disorders and Health related Quality of Life in Children With Type 1 Diabetes Mellitus

Agnieszka Butwicka, MD, PhD 1,2 Wojciech Fendler, MD, PhD 3 Adam Zalepa, MHA 2 Agnieszka Szadkowska, MD, PhD 3 Malgorzata Zawodniak-Szalapska, MD, PhD 4 Agnieszka Gmitrowicz, MD, PhD, Prof 5 Wojciech Mlynarski MD, PhD, Prof 3

1- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 2- Department of Child Psychiatry, Medical University of Warsaw, Warsaw, Poland 3-Department of Paediatrics, Oncology, Haematology and Diabetology, Medical University of Lodz, Lodz, Poland 4-Department of Endocrinology and Metabolic Diseases, Polish Mother's Memorial Hospital, Lodz 5-Department of Adolescent Psychiatry, Medical University of Lodz, Lodz, Poland

Corresponding author: Agnieszka Butwicka, M.D., Ph.D, Karolinska Institutet, Department of Medical Epidemiology

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[email protected]; Tel: +46 852 48 24 28; Fax: +46 831 49 75 E-mail addresses of co-authors in order of appearance: [email protected]; [email protected]; [email protected]; [email protected]; [email protected]; [email protected];

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Abstract Background: Type 1 diabetes mellitus (T1DM) is a chronic condition with major impact on healthrelated quality of life (HRQoL) and mental health. In 90’s, high rates of psychiatric disorder were reported among children with T1DM. Little is known, however, about current prevalence of psychiatric disorders in children with T1DM and the relation between psychiatric diagnosis and HRQoL. The aim of the study was to determine the prevalence of DSM-IV-TR psychiatric disorders and the association between psychiatric comorbidity and HRQoL in the paediatric population with T1DM. Methods: This is a crosssectional study of 207 children, aged 8-18 years, diagnosed with T1DM. The presence of psychiatric disorders has been assessed by the standard diagnostic interview according to DSM-IV-TR criteria. HRQoL was measured by the general and diabetes-specific modules of the Paediatric Quality of Life Inventory (PedsQL). Results: Of the evaluated patients, 26.6% (N=55) met the criteria for psychiatric disorders at the time of evaluation. The most common diagnoses were: anxiety (N=32; 15.5%) and mood disorders (N=8; 3.9%). One-third of the patients (N=66, 31.9%) met the criteria for at least one psychiatric diagnosis in a lifetime period. The presence of psychiatric disorders was related with elevated HbA1c (8.6% vs. 7.6%) and lowered HRQoL in the general PedsQL. In the diabetes-specific PedsQL children with psychiatric disorders revealed more symptoms of diabetes, treatment barriers and lower adherence than children without psychiatric disorders. Conclusions: T1DM in children is associated with a very high prevalence of psychiatric co-morbidity, which is related to elevated HbA1c and lower HRQoL.

Keywords: Child & Adolescent Psychiatry, Consultation Liaison Psychiatry, Diabetes

Introduction For decades, clinicians have observed emotional and behavioural problems in children with Type 1 Diabetes Mellitus (T1DM) (1). But until the 1990’s it is has not been certain whether those psychiatriclike symptoms reflect actual psychiatric disorders as medical diagnosis based on standardised criteria such as The Diagnostic and Statistical Manual of Mental Disorders (DSM). The pioneer works of Kovacs and her colleagues, showed that 27 (36%) out of 74 evaluated children with newly diagnosed T1DM met

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DSM-III diagnostic criteria for psychiatric disorders. When followed over 10 years, nearly half of this cohort had psychiatric disorders at some point of observation (2). This observations were confirmed with the updated DSM-III-R criteria by Blanz et al., who showed that 31 out of 93 children with T1DM had psychiatric disorders (3). Both reports were based on contemporary DSM criteria and employed semistructured psychiatric interview carried out by clinicians both with children and their parents and due to those methodological strengths remain the most influential studies on the prevalence of psychiatric disorders in children with T1DM. But over a quarter of a century, a great deal of progress has been made both in the both diabetology and child psychiatry. In the former, intensive insulin therapy has offered better prognosis (4), but requirement of patients’ and parental involvement may cause additional burden and psychological distress (5). In the later, substantial development in the diagnostic classification and methods of assessment has given rise to increase in both prevalence of childhood psychiatric disorders (6) and the number of diagnoses assigned to each patient (7). At a time of renewed interest in mental-health issues in T1DM followed by a recent discussion on integration of psychiatric screening and mental health service into routine diabetes medical care (8, 9), it is very pertinent to revise and update our knowledge on the prevalence of psychiatric disorders in children with T1DM. The primary aim of the present study was to evaluate the prevalence of psychiatric disorders according to DSM-IV TR criteria in children with T1DM. We hypothesised that the current prevalence should be higher than previously observed, as such secular trend has been observed in general population (6). In addition, we assumed that diagnosis of psychiatric disorders would be related to lower healthrelated quality of life (HRQoL). Previous reports showed a relationship between lower HRQoL and selfreported problems such as depressive, anxiety symptoms, family conflicts(10-14). There are no studies, however, which evaluate the association between the HRQoL in T1DM and psychiatric disorders, assessed with structured diagnostic interview carried-out by experienced clinicians, both with parents and their children.

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Patients and Methods Study group The patients were enrolled in a long-term study on psychiatric co-morbidity in T1DM, thus preliminary data on behavioural problems and screening for mood disorders were published previously, reporting 7% and 3% frequency, respectively for disruptive behavioural and mood disorders. (15, 16). The inclusion criteria were as follows: 1) 8-18 years old; 2) duration of T1DM of at least one year; and 3) lack of significant coexisting diseases necessitating additional medical treatment or rehabilitation procedure. Among the 806 children treated with T1DM in the Lodzkie administrative region in central Poland, 615 children met the pre-defined inclusion criteria. Between July 2008 and December 2011, 306 children from the region were consecutively admitted as in patients to the study centre, which served as the tertiary referral centre for paediatric diabetes services in the Lodzkie voivodeship (administrative region). In this region inhabited by approximately 2.5 million people, children with T1DM are routinely admitted to the hospital to perform screening tests for chronic diabetic complications, common autoimmune diseases and, if required, insulin regimen adjustment along with re-education. All patients admitted throughout the study period were invited to participate in the study. Ultimately however, 207 patients agreed to participate: 23 declined to participate and 76 could not be assessed due to other reasons (i.e. short hospitalization, uncertain legal guardian, admission when none of the research team members were available on site) (Figure 1). No significant differences were noted between the studied group and those patients who did not participate in the project in terms of age, duration of diabetes, gender distribution or metabolic control (all p values > 0.3). We were not able to calculate HRQoL scores for five children and three parents from different families due to incomplete questionnaires. The Ethics Committee of the Medical University of Lodz approved this study, and the parents or legal guardians of all participants provided written informed consent prior to the initiation of any study procedures. Children who met the diagnostic criteria for psychiatric diagnoses during the course of the study were referred to the Child Psychiatry Centre for further evaluation and treatment.

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Measures The Schedule for Affective Disorders and Schizophrenia for Children – Present and Lifetime version (KSADS-PL) is a semi-structured diagnostic interview designed to assess both the current and lifetime history of Axis I psychiatric diagnoses(17). The final diagnosis is based on the clinician’s synthesis of independently conducted child and parent interviews and the DSM-IV TR criteria. The validated Polish version of the KSADS-PL was used to separately evaluate the patients and their parents were separately in private. Both interviews were performed by a child and adolescent psychiatrist (AB) or a clinical psychologist (AZ) not involved in the T1DM treatment of the patient. The KSADS-PL was used to evaluate both the presence of disorders at the time of examination and their lifetime prevalence. The Paediatric Quality of Life Inventory (The PedsQL) is a modular tool designed to measure the health-related quality of life (HRQoL) in children and adolescents by integrating both generic core scales and disease-specific modules into one measurement system. In this study, we used validated Polish versions of the PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Diabetes Module Scales for children (8-12 yrs.) and adolescents (13-18 yr.). Both tools consisted of self-report (child) and proxy report (parent) scales. The PedsQL 4.0 Generic Core Scales is a 23-item measure which covers scales for physical health, psychosocial health (including emotional function, social function and school function subscales). The PedsQL 3.0 Diabetes Module Scale consists of 28 items assigned to five scales: diabetes symptoms, treatment barriers, treatment adherence, worry and communication (18). Polish versions of both HRQoL tools were obtained from copyright holders. To comprehend the child’s and parental perspectives we have collected data from both sources (19, 20). Haemoglobin A1c (HbA1c) assays were performed by ion-exchange HPLC (Variant Haemoglobin A1c Program; Bio-Rad Laboratories, Hercules, CA, USA) as in previous studies performed in the centre (21). The method was certified by the National Glycohaemoglobin Standardization Program (NGSP) as meeting the Diabetes Control and Complications Trial standard. Reference values for healthy people estimated by the local laboratory were from 4.3 to 5.7%. The within-run CV (Coefficient of Variation)

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determined by the manufacturer was 1.05% for people without diabetes and 0.94% for people with diabetes; the between-run CV was 1.61% and 1.16% respectively. Statistical analysis Categorical variables were compared using the two-tailed Fisher's exact test. The age at diagnosis of T1DM, and the psychiatric evaluation, duration of diabetes and HbA1c levels of children with and without psychiatric comorbidities were compared using the Mann–Whitney’s U test. A linear regression model was used to assess the associations between current psychiatric comorbidities and child-reported and parent-reported HRQoLs. Each PedsQL scale was treated as dependent variable in a separate model, whereas psychiatric comorbidity and possible confounders constituted the independent variables. Confounders encompassed: gender, age, socioeconomic status, duration of disease or type of treatment (20, 22). Age and duration of diabetes were treated as continuous data. Correlations were evaluated using the Pearson’s correlation coefficient. Missing data were not replaced by any method. P values lower than 0.05 were considered to be significant, and all calculations were performed using the STATISTICA 10.0 PL statistical package (StatSoft, Tulsa, OK, USA).

Results Current comorbid psychiatric disorders The mean age of the subjects was 13.5±2.7 years, and 42.0% of them (N=87) were female. Among the evaluated patients, 26.6% (95%CI=20.6-32.6%; N=55) met the criteria for psychiatric disorders at the time of evaluation. The most common diagnoses were: anxiety (including separation anxiety N=32; 15.5%), disruptive behavioural disorders (N=11; 5.3%) and mood disorders (N=8; 3.9%). Eating disorders was diagnosed in four children (1.9%). Another four patients admitted to misuse psychoactive substances. Eight patients met the criteria of more than one (current) psychiatric diagnosis, and detailed descriptions of the disorders were presented in Table 1. There were no differences between children with current psychiatric comorbidities and ones without psychiatric disorders with regard to

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gender, parental education, type of insulin treatment, age, duration of diabetes and age at diagnosis of diabetes (Table 2). Children with psychiatric disorders had a significantly higher level of HbA1c (8.6±2.0 vs. 7.6±1.4; p<0.001) when compared to their peers with no psychiatric comorbidities (Table 2). Lifetime comorbid psychiatric disorders Nearly one in three patients (N=66, 31.9%; 95%CI=25.6-38.3%) met the criteria for at least one lifetime DSM-IV diagnosis. Anxiety disorders (with separation anxiety), present in 40 (19.3%) of the children, were the most common comorbidity. Disruptive behavioural (N=11; 5.3%) and mood disorders (N=9; 4.3%) were also commonly observed (Table 1).The lifetime presence of psychiatric disorders was not related to the patients’ gender, parental education, age, age at diabetes diagnosis or duration of diabetes (Table 2; p>0.10). Patients with a lifetime-history of psychiatric disorders, however, had higher levels of HbA1c (8.5±1.9 vs. 7.6±1.4; p<0.001) than their peers without psychiatric comorbidities (Table 2).

Discussion This study confirms high prevalence of psychiatric disorders in children with T1DM based on objective measures of psychiatric diagnosis. This report also demonstrates an association between having diagnosis of psychiatric disorders and poor HRQoL in T1DM. Results in relation to other studies This study showed the prevalence of psychiatric disorders in children with T1DM to be 27% and 32% for current and lifetime, respectively. These percentages seem to be slightly lower than reported for previous versions of the DSM - 48% (2), 34% (3), 37% (23), respectively for DSM-III, DSM-IIIR and previous version of DSM-IV. A similar tendency was observed for specific diagnostic categories. The current prevalence of anxiety (16%), mood (4%) and behavioural disorders - 8% in our study was lower than 17%, 17%, 20%, respectively for the same groups of disorders reported by Northam et al. (23). Similarly, life-time prevalence of mood (4%) and behavioural disorders (8%) was lower than (20% and

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16%) found by Kovacs et al. in their 10-year follow-up study. Only 19% of life-time prevalence of anxiety disorders seemed to match 19% reported by Kovacs et al. (2). These differences are unlikely to be related to changes in the diagnostic classification, which would likely lead to an increase in the prevalence of psychiatric disorders (6). Observed decrease in the prevalence of psychiatric disorders might, however, reflect the advances in diabetes care such as the introduction of an intensive insulin treatment in children allowing more flexible lifestyle and dietary freedom than previous conventional insulin regimen. Nevertheless, we cannot exclude that the differences in prevalence are caused by discrepancies in the study methodologies; The clinician-based assessment, used in our study, depends on clinical judgment to assess present or absent of symptoms after having face-to-face interviewed both parent and child, while prevalence in study by Northam et al. was estimated on computer-based questionnaire administrated solely to the children. Our report shows the association between psychiatric disorders and the HRQoL in children with T1DM. Significant of this observation was affected neither by adjustment to gender, age duration of diabetes and type of insulin treatment nor to parental education. Interestingly, psychiatric disorders were more often related to HRQoL measures reported by children than ones reported by their parents. For example, psychiatric disorders were linked to school functioning, diabetes symptoms, treatment barriers and adherence in the child, but not in parent, report. Similar discrepancies between child and parent reports have been reported in previous studies. For example, psychological control was not associated with HRQoL described by parents, but it was related to child reports.(13) Modest correlation between parent and child report suggests that perception of HRQoL in T1DM may differ between children and their caregivers (12). This may be explained by the fact that children report better on their own internal states and feelings than their parents. Consequently, while reporting HRQoL, the child’s report may be more informative about emotional or social functioning (19). Thus, low scores on child-reported HRQoL measures, should warn clinicians about possible psychiatric comorbidity.

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Strength and limitations The strengths of this report include the use of standardised psychiatric interviews performed by a qualified child and adolescent psychiatrist or psychologist, diagnoses based on the DSM-IV TR criteria, analyses adjusted for possible socioeconomic or treatment-related confounders, and vast sample size for this methodology. The study does have limitations related to its design and generalizing of these findings warrants caution. First and foremost, due to the time-consuming procedure of the psychiatric interview, we studied a group of subjects who were referred for inpatient treatment. Unknown factors may have resulted in a selection bias distinguishing these individuals from a wider population of children with T1DM in the region. Secondly, the interviewers were not blinded to the purpose of the study, and we cannot exclude that this information may have influenced their clinical judgment. To mitigate this, training and calibration procedures were implemented as countermeasures against this bias. Thirdly, due to the lack of a healthy control group, we can only speculate that the presented prevalence of psychiatric disorders in T1DM is higher than among children without T1DM, as no recent diagnosis-specific data are available for Polish children in the general population. At the beginning of the 21st century the frequency of psychiatric morbidity in the general Polish paediatric population was estimated at the level of 9% (24). Those results, however, are not directly comparable with our values, as they were not based on psychiatric diagnoses assessed by DSM-oriented interview of any kind, but on problematic behaviours measured by Achenbach System of Empirically Based Assessment.(25, 26) Similarly, we were not able to assess whether T1DM or psychiatric comorbidity is primarily related to decrease in HRQoL, as no comparison with psychiatricallytreated control group without T1DM could be performed. Finally, as we studied children living in Poland, our results may not be directly transferred to the US population. Paediatric diabetes service is publically funded and centralized around specialist-based health care centres in each region. Paediatric Diabetes Departments are responsible for managing both inpatient and outpatient treatment of children with T1DM, where continuity of care is prioritized. Each patient is assigned to his/her doctor who carries on outpatient diabetes care until patient’s adulthood;

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decides on the need for re-education, routine hospital referrals and is responsible for inpatient treatment. Although differences in health care systems and cultural setting may limit our study’s generalizability to other counties, they undoubtedly show a major impact of psychiatric comorbidity in T1DM on health related quality of life. Additionally, there were also missing data for parent-reported HRQoL in 3 cases and child-reported HRQoL in 5 cases, but considering the robust differences observed in all comparisons and significant correlations these were unlikely to have had a major impact upon the general results shown in our study. Last, All patients were evaluated with the KSADS-PL, but recently, in 2013 the American Psychiatric Association published the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). At the time when the study was performed (July 2008- December 2011), and even at the moment of submission of the manuscript, assessment measures have yet to be updated or developed for this edition. Therefore, even though DSM-V may have new implications for prevalence of psychiatric disorders, results of our analysis will provide a useful reference range for many years to come. Our study confirms the high prevalence of psychiatric disorders comorbid with T1DM as seen in previous studies using older versions of the DSM criteria. These findings highlight the need of multidisciplinary team approach. The study demonstrates that routine assessment of HRQoL may provide information on risk of underlying psychiatric comorbidity, suggesting more careful psychological assessment in individuals with low HRQoL. Findings have also implication for researchers using HQoL measures. Although generic measures of HRQoL seemed to be more informative regarding psychiatric comorbidity then diabetes specific ones, presence of psychiatric comorbidity may underlie lower scores in diabetesspecific measures reported by the child. This supports the importance of careful choice of assessment measures and collecting information from both children and their parents. Funding: This study was funded by a research grant from the Polish Ministry of Science and Higher Education (IP2012 006972). WM and WF received financial support from the Innovative Economy Operational Programme – Activity 1.2 (TEAM Programme coordinated by the Foundation for Polish Science). Conflict of Interest: The authors declare that they have no conflict of interest.

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References 1. Falstein EI, Judas I. Juvenile diabetes and its psychiatric implications. The American journal of orthopsychiatry. 1955;25(2):330-42. 2. Kovacs M, Goldston D, Obrosky DS, Bonar LK. Psychiatric disorders in youths with IDDM: rates and risk factors. Diabetes care. 1997;20(1):36-44. 3. Blanz BJ, Rensch-Riemann BS, Fritz-Sigmund DI, Schmidt MH. IDDM is a risk factor for adolescent psychiatric disorders. Diabetes care. 1993;16(12):1579-87. 4. Gubitosi-Klug RA, Group DER. The diabetes control and complications trial/epidemiology of diabetes interventions and complications study at 30 years: summary and future directions. Diabetes care. 2014;37(1):44-9. 5. Reynolds KA, Helgeson VS. Children with diabetes compared to peers: depressed? Distressed? A meta-analytic review. Annals of behavioral medicine : a publication of the Society of Behavioral Medicine. 2011;42(1):29-41. 6. Cawthorpe D. A novel population-based health index for mental disorder. The Permanente journal. 2013;17(2):50-4. 7. Lauth B, Levy SR, Juliusdottir G, Ferrari P, Petursson H. Implementing the semi-structured interview Kiddie-SADS-PL into an in-patient adolescent clinical setting: impact on frequency of diagnoses. Child and adolescent psychiatry and mental health. 2008;2(1):14. 8. Ducat L, Philipson LH, Anderson BJ. The mental health comorbidities of diabetes. Jama. 2014;312(7):691-2. 9. Ducat L, Rubenstein A, Philipson LH, Anderson BJ. A review of the mental health issues of diabetes conference. Diabetes care. 2015;38(2):333-8. 10. Hilliard ME, Herzer M, Dolan LM, Hood KK. Psychological screening in adolescents with type 1 diabetes predicts outcomes one year later. Diabetes research and clinical practice. 2011;94(1):39-44. 11. Laffel LM, Connell A, Vangsness L, Goebel-Fabbri A, Mansfield A, Anderson BJ. General quality of life in youth with type 1 diabetes: relationship to patient management and diabetes-specific family conflict. Diabetes care. 2003;26(11):3067-73. 12. Nansel TR, Weisberg-Benchell J, Wysocki T, Laffel L, Anderson B, Steering Committee of the Family Management of Diabetes S. Quality of life in children with Type 1 diabetes: a comparison of general and diabetes-specific measures and support for a unitary diabetes quality-of-life construct. Diabetic medicine : a journal of the British Diabetic Association. 2008;25(11):1316-23. 13. Weissberg-Benchell J, Nansel T, Holmbeck G, Chen R, Anderson B, Wysocki T, et al. Generic and diabetes-specific parent-child behaviors and quality of life among youth with type 1 diabetes. Journal of pediatric psychology. 2009;34(9):977-88. 14. Hassan K, Loar R, Anderson BJ, Heptulla RA. The role of socioeconomic status, depression, quality of life, and glycemic control in type 1 diabetes mellitus. The Journal of pediatrics. 2006;149(4):526-31. 15. Butwicka A, Fendler WM, Zalepa A, Szadkowska A, Gmitrowicz A, Mlynarski WM. Sweet sins: frequency and psychiatric motivation for theft among adolescents with type 1 diabetes. Pediatric diabetes. 2011;12(4 Pt 2):424-8. 16. Butwicka A, Fendler W, Zalepa A, Szadkowska A, Mianowska B, Gmitrowicz A, et al. Efficacy of metabolic and psychological screening for mood disorders among children with type 1 diabetes. Diabetes care. 2012;35(11):2133-9. 17. Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, et al. Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry. 1997;36(7):980-8. 18. Varni JW, Burwinkle TM, Jacobs JR, Gottschalk M, Kaufman F, Jones KL. The PedsQL in type 1 and type 2 diabetes: reliability and validity of the Pediatric Quality of Life Inventory Generic Core Scales and type 1 Diabetes Module. Diabetes care. 2003;26(3):631-7.

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19. Eiser C, Varni JW. Health-related quality of life and symptom reporting: similarities and differences between children and their parents. European journal of pediatrics. 2013;172(10):1299-304. 20. Bianchini JA, da Silva DF, Nardo CC, Carolino ID, Hernandes F, Nardo N, Jr. Parent-proxy perception of overweight adolescents' health-related quality of life is different according to adolescent gender and age and parent gender. European journal of pediatrics. 2013;172(10):1371-7. 21. Mianowska B, Fendler W, Szadkowska A, Baranowska A, Grzelak-Agaciak E, Sadon J, et al. HbA(1c) levels in schoolchildren with type 1 diabetes are seasonally variable and dependent on weather conditions. Diabetologia. 2011;54(4):749-56. 22. Muller-Godeffroy E, Treichel S, Wagner VM, German Working Group for Paediatric Pump T. Investigation of quality of life and family burden issues during insulin pump therapy in children with Type 1 diabetes mellitus--a large-scale multicentre pilot study. Diabetic medicine : a journal of the British Diabetic Association. 2009;26(5):493-501. 23. Northam EA, Matthews LK, Anderson PJ, Cameron FJ, Werther GA. Psychiatric morbidity and health outcome in Type 1 diabetes--perspectives from a prospective longitudinal study. DiabetMed. 2005;22(2):152-7. 24. Wolanczyk T. Zaburzenia emocjonalne i behawioralne u dzieci i młodzieĪy w Polsce. Warszawa: Akademia Medyczna w Warszawie; 2003. 25. Ivanova MY, Achenbach TM, Rescorla LA, Dumenci L, Almqvist F, Bilenberg N, et al. The generalizability of the Youth Self-Report syndrome structure in 23 societies. Journal of consulting and clinical psychology. 2007;75(5):729-38. 26. Rescorla L, Achenbach TM, Ivanova MY, Dumenci L, Almqvist F, Bilenberg N, et al. Epidemiological comparisons of problems and positive qualities reported by adolescents in 24 countries. Journal of consulting and clinical psychology. 2007;75(2):351-8.

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Table 1. Prevalence of psychiatric disorders diagnosed according to the DSM-IV TR classification in the studied group of patients with type 1 diabetes. Diagnostic categories

Diagnoses

Prevalence Current N (%)

Lifetime N (%)

Generalized Anxiety Disorder

4 (1.9)

6 (2.9)

Phobias

8 (3.9)

9 (4.3)

Social Phobia

3 (1.4)

3 (1.4)

Panic Disorder

2 (1.0)

2 (1.0)

Obsessive-Compulsive Disorder

1 (0.5)

2 (1.0)

Post-traumatic Stress Disorder

4 (1.9)

8 (3.9)

Acute Stress Disorder

3 (1.4)

3 (1.4)

24 (11.6)

31 (15.0)

Attention-Deficit/Hyperactivity Disorder

5 (2.4)

5 (2.4)

Oppositional Defiant Disorder

5 (2.4)

5 (2.4)

Conduct Disorder

1 (0.5)

1 (0.5)

Disorders Usually First

Separation Anxiety Disorder

8 (3.9)

9 (4.3)

Diagnosed in Childhood

Transient Tic Disorder

3 (1.4)

3 (1.4)

Enuresis

0 (0.0)

1 (0.5)

22 (10.6)

24 (11.6)

Major Depressive Disorder

4 (1.9)

5 (2.4)

Dysthymic Disorder

3 (1.4)

3 (1.4)

Cyclothymic Disorder

1 (0.5)

1 (0.5)

Number of patients with Mood Disorders

8 (3.9)

9 (4.3)

Eating disorder not otherwise specified

4 (1.9)

4 (1.9)

Alcohol Dependence

1 (0.5)

1 (0.5)

Alcohol Abuse

2 (1.0)

2 (1.0)

Cannabis Abuse

1 (0.5)

1 (0.5)

Number of patients with Substance Misuse

4 (1.9)

4 (1.9)

Schizophrenia

1 (0.5)

1 (0.5)

Total number of patients with disorders *

55 (26.6)

66 (31.9)

Anxiety Disorders

Number of patients with Anxiety Disorders

Number of patients with disorders diagnosed in childhood

Mood Disorders

Eating Disorders

Substance Misuse

Psychotic Disorders

*The total number of patients with disorders is lower than the number of diagnoses due to co-morbidity in eight individuals.

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Table 2. Clinical characteristics of the studied group divided depending on the current and lifetime presence of psychiatric disorders. Data were presented as numbers and percentages or means with standard deviations. MDI - Multiple Daily Injections; CSII – Continuous Subcutaneous Insulin Infusion Total

Current

No Current

Comorbid

P level

Lifetime

No Lifetime

Psychiatric

Psychiatric

Psychiatric

Psychiatric

Disorders

Disorders

Disorders

Disorders

N=152

N=66

N=141

P level

N=55 Sex

120/87

28/27

92/60

(58.0/42.0)

(50.9/49.1)

(60.5/39.5)

32/175

7/48

25/127

(15.5/84.5)

(12.7/83.3)

(16.4/83.6)

Maternal

45/162

12/43

33/119

education

(21.7/78.3)

(21.8/78.2)

(21.7/78.3)

93/114

28/27

65/87

(44.9/55.1)

(50.9/49.1)

(42.8/57.2)

13.5±2.7

13.4±2.7

13.6±2.7

9.5±3.2

9.4±3.2

4.0±2.1

4.0±2.2

(Male/Female),

0.22

36/30

84/57

0.47

(54.5/45.5)

(59.6/49.4)

9/57

23/118

(13.6/86.4)

(19.5/81.5)

14/52

31/110

(21.2/78.8)

(30.0/70.0)

35/31

58/83

(53.0/47.0)

(41.1/59.9)

0.77

13.8±2.7

13.4±2.7

0.36

9.5±3.2

0.89

9.6±3.2

9.4±3.2

0.58

4.0±2.0

0.95

4.1±2.2

4.0±2.0

0.85

N (%) Paternal education

0.66

0.77

(>high school/ ”high school), N (%) 0.86

0.96

(>high school/ ”high school), N (%) Insulin Treatment

0.30

0.11

(MDI/CSII), N (%) Age, Mean±SD [years] Age at diagnosis of diabetes , Mean±SD [years] Duration of diabetes, Mean±SD [years]

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Glycated

7.9±1.6

8.6±2.0

7.6±1.4

<0.001

8.5±1.9

7.6±1.4

<0.001

62.6±17.7

69.9±22.1

60.0±15.0

<0.001

70.0±21.0

59.6±15.1

<0.001

haemoglobin Mean±SD [%] Glycated haemoglobin Mean±SD [mmol/mol]

15

Table 3. The PedsQL 4.0 Generic Core Scales in children with type 1 diabetes mellitus with and without current psychiatric disorders. The emotional, social and school functioning scores represent subscales of the Psychosocial health scale of PedsQL. Scale

Comorbid Psychiatric

No Psychiatric

P level

Regression coefficient for

Disorders

Disorders

the effect of psychiatric

N=55

N=152

comorbidity*

Mean (95%CI)

Mean (95%CI)

(95%CI)

P level

Self-report Total score

Physical health

Psychosocial health Emotional functioning Social functioning School functioning

78.6

85.1

(75.4 - 81.9)

(83.2 - 87.1)

83.8

88.8

(80.6 - 87.1)

(86.8 - 90.8)

75.7

83.1

(72.1 - 79.4)

(80.9 - 85.3)

69.8

78.8

(64.6 - 74.9)

(75.6 - 81.9)

88.6

93.3

(85.4 - 91.8)

(91.4 - 95.3)

68.8

77.1

(64.0 - 73.6)

(74.2 - 80.0)

<0.001

-3.2 (-5.1 to -1.3)

<0.01

<0.05

-2.3 (-4.2 to -0.4)

<0.05

<0.001

-3.7 (-5.9 to -1.6)

<0.001

<0.01

-4.4 (-7.5 to -1.4)

<0.01

<0.05

-2.3 (-4.2 to -0.4)

<0.05

<0.01

-4.4 (-7.3 to -1.6)

<0.01

<0.001

-2.6 (-4.8 to -0.3)

<0.05

<0.01

-2.3 (-4.4 to -0.1)

<0.05

<0.05

-2.8 (-5.3 to -0.2)

<0.05

<0.05

-3.7 (-6.8 to -0.7)

<0.05

<0.05

-2.8 (-5.5 to -0.1)

<0.05

0.24

-1.7 (-4.8 to 1.4)

0.29

Proxy report Total score

Physical health

Psychosocial health Emotional functioning Social functioning School functioning

75.2

81.1

(71.3 - 79.0)

(78.8 - 83.4)

81.7

87.5

(78.0 - 85.5)

(85.3 - 89.8)

71.5

77.7

(67.2 - 75.8)

(75.0 - 80.2)

68.1

75.8

(63.0 – 73.2)

(72.7 – 78.9)

79.3

86.0

(74.7 – 83.8)

(83.2 – 88.7)

67.2

70.9

(61.8 – 72.5)

(67.7 – 74.2)

* adjusted for gender, age, duration of diabetes and type of insulin therapy.

16

Table 4 – The PedsQL 3.0 Diabetes Module Scales in children with type 1 diabetes mellitus with and without current psychiatric disorders. Data were presented as means with 95% Confidence Intervals (95%CI) and regression coefficients with 95%CI. Scale

Comorbid

No Psychiatric

P level

Regression coefficient for

Psychiatric

Disorders

the effect of psychiatric

Disorders

N=152

comorbidity*

P level

N=55

Self-report Diabetes symptoms

Treatment barriers

a

67.9

77.3

(63.6 - 72.3)

(74.7 - 80.0)

72.0

81.3

(66.4 - 77.7)

(77.8 - 84.8)

80.1

86.0

(75.5 - 84.6)

(83.2 - 88.8)

73.2

79.2

(67.3 - 79.1)

(75.6 - 82.8)

84.2

86.7

(79.1 - 89.2)

(83.6 - 89.8)

b

Treatment adherence c

Worry

d

Communication

e

<0.001

-4.6 (-7.2 to -2.0)

<0.001

<0.01

-4.7 (-8.0 to 1.3)

<0.01

<0.05

-2.3 (-5.7 to -0.3)

<0.05

0.09

-3.3 (-6.7 to 0.2)

0.07

0.41

-1.3 (-4.3 to 1.8)

0.42

0.28

-1.4 (-4.2 to 1.5)

0.35

0.78

-0.1 (-4.1 to 4.0)

0.98

0.46

-0.5 (-3.8 to 2.8)

0.76

0.43

2.7 (-1.6 to 7.1)

0.22

0.61

1.3 (-1.7 to 4.4)

0.38

Proxy report Diabetes symptoms

Treatment barriers

a

68.5

71.5

(63.7 - 73.3)

(68.6 - 74.5)

69.7

70.9

(62.9 - 76.4)

(66.7 - 74.9)

74.5

77.0

(68.9 - 80.1)

(73.6 - 80.4)

69.5

66.0

(62.1 - 76.9)

(61.5 - 70.5)

84.3

82.8

(79.2 - 89.4)

(79.6 - 85.8)

b

Treatment adherence c Worry d

Communication

e

* adjusted for gender, age, duration of diabetes and type of insulin therapy, a - higher score indicates fewer symptoms of diabetes,

b

- higher score indicates fewer problems with barriers,

c

- higher score

17

indicates fewer problems with adherence, d - higher score indicates less worry, e - higher score indicates better communication.

18

Assessed for eligibility (n=806)* Children with type 1 diabetes treated with in the Lodzkie administrative region between July 2008 and December 2011

Excluded (n=191) · Age <8 or >18 years of age (n=80) · Rediagnosed as having other than type 1 diabetes (n=20) · Significant somatic comorbidity (n=91): - treated for asthma- 28, - psoriasis- 23, -caeliac disease confirmed by biopsy- 22, - mental retardation- 11, - juvenile rheumatoid arthritis- 6, - cystic fIbrosis-1,

Eligible (n=615)

Admitted to the paediatric diabetological centre between July 2008 and December 2011(n=306)

· ·

Evaluated (n=207)

Declined to participate (n=23) Failed to recruit (n=76)