It was a cross-sectional study performed between January 2019 and February 2022 in the pediatric department of the Farhat HACHED Sousse university hospital, Tunisia. The study’s ethical approval was obtained from the ethics committee of the faculty of medicine of Sousse (Reference: CEFMS 61/2021). After obtaining their agreement, the parents of the children/adolescents signed a consent form. In addition, adolescents over 13 years old signed the consent form. The children/adolescents and their parents were informed about the i) study protocol and its aims, and ii) possibility of withdrawal from the research project at any time. During the period between June 2020 and February 2022, all recommended preventive measures to fight against the transmission of the severe acute respiratory syndrome coronavirus 2 were applied (eg; physical distancing of at least one meter, wearing a fitted facemask properly and cleaning hands frequently with alcohol-based hand rub or soap and water), During each study step, all recommended preventive measures to fight against COVID-19 transmission were applied. The study was conducted following the guidelines established by the STROBE statement. ²⁵ In order to respect the anonymity and confidentiality of the data, a code was assigned to each patient.

The source population was the children/adolescents (and their parents) attending pediatric outpatient consultations at the above cited hospital. The target population was the children/adolescents with T1DM who were consulted during the study period. Only children/adolescents aged 8 to 18 years, who were accompanied by their parents, who had a medical diagnosis of T1DM at least one year before the inclusion in the study, and who received only insulin analogues for at least three months were included in the study. Children/adolescents who had a mental retardation, a sensor neural disorder that interferes with normal communication; or another chronic disease, such as celiac disease, were not included in this study. Children/adolescents who participated in another experimental survey during the study period were excluded from the statistical analysis. Figure 1 exposes the study flow chart.

The sample size was appraised according to the following formula ²⁶ : N = ( Z _α ) ² s ²/ d ², where “ s ” is the standard deviation (SD= 9.79) and “ d ” is the accuracy of estimate or how close it is to the true mean (= 76.51). Given the pioneering nature of this study, the above “ s ” and “ d ” data were collected from a previous work including 503 adolescents with T1DM, ²⁷ aiming to evaluate the HRQoL via the diabetes quality of life instrument for youth. ²⁸ In the aforementioned study, the percentage mean score of the total HRQoL for all adolescents was 76.51±9.79. “Z _α” is the normal deviate for a one-tailed alternative hypothesis at a level of significance (Z _α equal to 1.28 at an error rate of 0.10%). The appraised sample size gives a sample of 116 patients. The assumption of 25% for the non-inclusion and exclusion criteria gives a revised sample of 154 patients (154 =116/ (1.0-0.25)).

One investigator ( IBA in the authors’ list) was in charge of administering and explaining the different components of the questionnaire to children/adolescents and their parents. On the beginning of the consultation day, the questionnaire was given to patients and parents independently in order to improve the response rate. The questionnaire was then collected at the end of the morning of the same day. The questionnaire included two parts and the time taken to complete it was 15 minutes.

The first part of the questionnaire, which was written in Arabic, was pretested, structured, and self-administered by the researcher ( IBA in the authors’ list). It was related to personal data of both diabetic patients and their parents. For parents, the following data were collected: accompanying tutor ( ie ; mother; father), marital status ( ie ; married; divorced), schooling-level ( ie ; illiterate or primary or secondary school; university), and socio-economic level [ ie ; low ( eg ; unskilled worker, jobless); high ( eg ; skilled worker, farmer, manager)]. For patients, the following data were collected: sex ( ie ; male; female), age ( ie ; years, children (8 to 12 years), adolescents (13 to 18 years)); BMI (kg/m ²), corpulence status ( ie ; normal weight; overweight or obese), ²⁹ siblings in the family ( ie ; number sibling > 2), schooling-level [ ie ; low (primary or preparatory school) and high (secondary school)], schooling-performance ( ie ; normal; repeating or stop); family history of diabetes mellitus ( ie ; yes, no), onset age and seniority of T1DM ( ie ; year), person in charge of insulin injection ( ie ; patient, parents), dietetic education ( ie ; yes, no), diet ( ie ; yes, no), hypoglycemia episodes during the last three months before the inclusion in the study ( ie ; number, yes, no), average glycaemia during the hypoglycemia episodes ( ie ; g/l), home self-monitoring ( ie ; yes, no), home self-monitoring frequency ( ie ; never, > 1), most recent HbA ₁C level ( ie ; %), duration of HbA ₁C control ( ie ; control < 3 months, control > 6 months), lipodystrophy ( ie ; yes, no), previous hospitalization ( ie ; yes, no), and etiologies of hypoglycemia ( ie ; lipodystrophy, diet, stop insulin). Two subgroups of patients ( ie ; non-active; active) were formed according to regular sports activity based on the response to the following question ³⁰ : do you practice any sports activities outside of school? Some data ( eg ; family history of T1DM, HbA ₁C levels and potential previous hospitalizations) were extracted from the patients’ medical records.

The second part of the questionnaire was reserved to the PedsQL4.0. ^{10 , 31} The latter was developed to assess the HRQoL of children/adolescents (self-reported) as well as their parents’ (proxy-report). ^{10 , 31} HRQoL is assessed in four domains: physical function (8 items), emotional function (5 items), social function (5 items), and school function (5 items). ^{10 , 31} The following three scores are determined: total score, physical health score, and psychosocial health score (covering emotional, social and academic function). ^{10 , 31} Total scores are obtained by adding the scores and dividing them by the total number of items completed. Patients and parents were asked to rate the ‘problem in the past three months’ on 5 Likert scales from 0 to 4 ( 0 = never a problem; 1 = almost never a problem; 2 = sometimes a problem; 3 = often a problem, 4 = almost always a problem). Then each item was scored backwards and linearly transformed on a scale of 0 to 100 ( 0 = 100, 1 = 75, 2 =50, 3 = 25, 4 = 0), so that the highest score indicates better HRQoL. ^{10 , 31} The PedsQL4.0 has appropriate forms for child self-assessments and parent proxy reports, ³¹ and has shown good internal consistency, reliability and validity. ¹⁰ The validated Arabic version of the PedsQL4.0 was applied. ¹⁵ Permission to use the PedsQL 4.0 was obtained from the authors.

Data expression. The Kolmogorov Smirnov test was used to analyze quantitative data’s distribution. All quantitative data have a normal distribution, and therefore were expressed as means ± standard deviation. Categorical data were expressed as number (frequency).

Comparisons parents vs. patients. Comparisons of the PedsQL4.0 scores between parents and patients were performed by the Student-T test.

Univariate and multiple regression analysis (influencing factors). The dependent variable ( ie ; PedsQL4.0 total scores of patients and parents) was normally distributed. Student-T test were used to evaluate the associations between the PedsQL4.0 total score and categorical data [ ie , parents’ data (accompanying tutor, marital status, schooling-level, and socio-economic-level); patients’ data (sex, age range, siblings in the family, schooling-level, schooling-performance, corpulence status, charge of injections, dietetic education, diet, regular physical activity, hypoglycemia, home self-monitoring, frequency of home self-monitoring, duration of the control of HbA ₁C, lipodystrophy, previous hospitalizations, and family history of diabetes mellitus)]. The Pearson product-moment correlation coefficients (r) evaluated the associations between the PedsQL4.0 total score and continuous data [ ie ; age, siblings, BMI, hypoglycemia episodes, average glycaemia during hypoglycemia episodes, HbA ₁C, onset age of T1DM, and seniority of T1DM]. The linearity of the association between the PedsQL4.0 total scores and the continuous data was checked graphically by plotting each regressor against the PedsQL4.0 total scores. Only significantly and linearly associated data were entered into the model.

Linear regression models were used to evaluate the independent data explaining the variance in PedsQL4.0 total scores. Candidate data were put into the model with a stepwise selection method. To determine entry and removal from the model, significant levels of 0.15 and 0.05 were used, respectively. No colinearity between predictors was detected with variance inflation factors. The linear regression models were evaluated by the (r) and the standard error. All statistical procedures were performed using a statistical software (StatSoft, Inc. (2014). STATISTICA (data analysis software system), version 12. www.statsoft.com, RRID: SCR_014213). The significance level was set at p<0.05.

Table 1 illustrates the parents’ and patients characteristics, respectively. Its main conclusions were: i) almost 92% of parents have a low socio-economic-level; ii) there was a predominance of adolescents and females (63% and 64%, respectively), iii) 56% of patients have normal weight, iv) the mean of siblings was 3±1, and 71% of patients had more than 2 siblings in the family, v) the means of hypoglycemia episodes and HbA ₁C were 4.3±1.5, and 10±1, respectively, and vi) 69% of patients have lipodystrophy.

Patients and parents had comparable scores of physical health (67±20 vs. 70±21, p=0.271, respectively), emotional function (53±20 vs. 57±21, p=0.074, respectively), social function (81±18 vs. 83±18, p=0.502, respectively), academic function (70±21 vs. 70±21, p=0.886, respectively), and total score (68±13 vs. 70±14, p=0.180, respectively).

Tables 2 and 3 expose the univariate analysis between PedsQL4.0 total scores of patients and parents and categorical and quantitative data, respectively. Among patients, the following four data influence the PedsQL4.0 total score: siblings in the family, dietetic education, lipodystrophy, and HbA ₁C. In parents, the following eight data influence the PedsQL4.0 total score: siblings in the family, corpulence status, dietetic education, lipodystrophy, siblings, BMI, hypoglycemia episodes, and HbA ₁C.

Table 4 exposes the multivariate linear regression analysis. Among patients, only three data influence the PedsQL4.0 total score: siblings in the family, lipodystrophy and HbA ₁C. Altogether, they explain 34.84% of the PedsQL4.0 total score variance. In parents, only five data influence the PedsQL4.0 total score: lipodystrophy, siblings, BMI, hypoglycemia episodes, and HbA ₁C. Altogether, they explain 56.92% of the PedsQL4.0 total score variance.

The Arabic version of PedsQL4.0 is understandable and usable in Tunisia. ¹⁵ It has a high validity and reliability. ¹⁵ Table 5 exposes the PedsQL4.0 scores among different populations of diabetic children/adolescents with TIDM. ^{2 , 6 , 8 , 10 – 16}

In this study, the patients’ total score was 68±13 ( Table 5). In the one hand, it was comparable to the one of the Iranian population of patients aged 8 to 18 years ¹³ who has a score of 68±14 ( Table 5). In the other hand, our score was lower than the ones reported in similar studies [ ie , score ranging from 76±11 ¹⁶ to 88±11 ⁸ ]. In this study, while the patients’ social function score was high at 81±18, this of the emotional function was low at 53±20. Our results are intermediate with those reported in literature ( Table 5). First, almost all previous studies ^{2 , 6 , 8 , 10 – 16} reported that the social function score was the highest [ ie ; ranging from 77±18 ¹³ to 95±10 ⁸ ( Table 5)]. Second, while some previous studies, ^{2 , 10 , 11 , 13 – 16} reported that the emotional function score was the lowest [ ie ; ranging from 60±20 ¹³ to 76±16 ¹¹ ( Table 5)], three studies ^{6 , 12 , 13} identified that the academic function score was the lowest [ ie ; ranging from 67±18 ¹³ to 72±16 ⁶ ( Table 5)].

The discrepancy between results could be explained partly by the age of included patients ranging from 2-18 years ^{11 , 15 , 16} to 8-18 years. ^{2 , 6 , 13} In addition, according to Abderrassoul et al., ¹⁶ impaired emotional function may be explained by the lack of autonomy and preoccupation with chronic complications. In order to increase the emotional function score, and to early detect and solve problems that children/adolescents may encounter, we recommend that HRQoL assessment after T1DM diagnosis should be a routine practice.

The PedsQL4.0 scores of diabetic patients were comparable with those of their parents. This result is inconsistent with previous studies, which reported a significant difference between patients and their parents’ subjective perception of T1DM and the impact of the disease on their daily life. ^{2 , 6 , 16 , 27} The concordance between patient and parents results observed in this study can be explained by different factors, such as the presence of communication between parents and their children/adolescents, especially among children, who do not present generally a withdrawal and oppositional behavior before the pubertal period. ^{2 , 14} Moreover, parents seem to have more concern about their children/adolescents health when they reach school age, given the fact that kids haven’t yet developed an independent personality and weren’t became self-sufficient around this range of age.

Table 5 exposes the influencing factor of the patients’ PedsQL4.0 scores among different populations of diabetic children/adolescents with TIDM. It appears that the following factors are independent predictors of HRQoL as perceived by diabetic patients: HbA ₁C, ^{2 , 6 , 12 , 14 , 16} age, ^{2 , 14 , 16} sex, ^{6 , 14 , 16} siblings, ^{2 , 6} depression, ¹² adherence to treatment, ¹² hypoglycemia, ¹⁴ hyperglycemia, ¹⁴ onset of T1DM, ¹⁴ duration of T1DM, ¹⁶ socioeconomic level, ⁶ therapeutic education, ⁶ hospitalization, ⁶ mothers’ and fathers’ educational status, ⁸ fathers’ occupation, ⁸ monitoring blood glucose. ⁸ In the present study, among all studies data, siblings in the family, lipodystrophy and HbA1C were independent predictors of HRQoL as perceived by diabetic patients, and lipodystrophy, siblings, BMI, hypoglycemia episodes, and HbA ₁C were independent predictors of HRQoL as perceived by parents ( Table 4). The following sentences will discuss the aforementioned factors.

An increase in the number of children in the family had a statistically significant effect on the HRQoL of children/adolescents as well as their parents ( Table 4). A number of “siblings higher than 2” reduces the patients’ HRQol total score by 6.84, and one unit of sibling reduced the parents’ HRQoL total score by 3.73 ( Table 4). Our results, which are in line with the findings of some studies from Turkey ² and Ethiopia, ⁶ could be explained by the fact that increasing number of children in family may reduce parental support. Thus, siblings should be included in diabetes health education and diabetic children/adolescents should be supported by all family members. ⁶

Lipodystrophy was an independent predictor of HRQoL as perceived by both patients and parents ( Table 4). It appears that the presence of lipodystrophy reduces the patients and parents’ HRQoL total scores by 4.29 and 6.97, respectively. Besides, the changes of the skin and the unsightly aspect of lipodystrophy can also perturb the body image, especially among adolescents, and thus decreases the emotional function in HRQoL. To the best of the authors’ knowledge, no previous study has found an association between lipodystrophy and HRQoL ( Table 5).

HbA ₁C level (%) was an independent predictor of HRQoL as perceived by both patients and parents ( Table 4). One unit of HbA ₁C reduces the patients and parents’ HRQoL total scores by 1.20 and 0.96, respectively ( Table 4). Our result is in line with the findings of some previous studies reporting an association between lower HRQoL of patients and higher HbA ₁C levels. ^{2 , 6 , 9 , 12 , 14 , 16}

BMI (kg/m ²) was an independent predictor of HRQoL as perceived by parents ( Table 4). In our study, we observed a noteworthy and positive correlation (r = 0.526), one unit of BMI increases the parents’ HRQoL total score by 1.03 ( Table 4). This finding aligns with two previous studies conducted in Saudi Arabia ³³ and in Egypt. ⁵

Hypoglycemic episodes was an independent predictor of HRQoL as perceived by parents ( Table 4). Each hypoglycemic episode decreases the parents’ HRQoL total score by 1.69 ( Table 4). Our finding was consistent with other studies that indicated that treatment ongoing risk of hypoglycemia (especially nocturnal hypoglycemia) negatively affect the HRQOL of patients and their families. ²⁰ In fact, hypoglycemia episodes are uncomfortable experiences and could cause an important psychological impact on the children/adolescents. Therefore, assessment of psychosocial burden, including fear of hypoglycemia, should be part of the management of T1DM. ²⁰ Our findings suggest that motivating a child/adolescent to achieve optimal glycaemia levels and incorporating routine clinical assessment of HRQoL as an important component of diabetes management are necessary to determine the appropriate intervention to improve HRQoL. ²⁰ Contrary to the present study, one Greece study ¹⁴ identified hypoglycemia as an independent predictor of HRQoL as perceived by diabetic patients ( Table 5).

Additional factors, such as age, ^{2 , 14 , 16} sex, ^{6 , 14 , 16} and socioeconomic data, ^{6 , 8} need to be discussed. First, in the present study, and similar to other studies, ^{3 , 9 , 34 – 36} there were no effects of age or sex on HRQoL. However, some previous studies reported that girls have lower total HRQoL scores than boys. ^{6 , 9 , 15 , 16 , 18 , 37} In general population, during adolescence, girls tend to have less self-esteem than boys, ³⁸ and present more signs of depression, ²³ which may constitute factors of a lower HRQoL. Moreover, adolescent girls with T1D are reported to be more anxious and less satisfied than boys, ¹⁶ and experience hormonal changes with an increase of insulin require. In our study, there was no significant association between socioeconomic status and patients’ HRQoL. This is consistent with the finding of a Norwegian study. ³⁶ However, some other studies reported that a low socioeconomic level was significantly associated with sub-optimal management of T1DM, and this may negatively affect quality of life. ^{6 , 8 , 9 , 39}

The main two strengths of our study were the high enrolment rate (76%) and its pioneer character. Since it is the first study from the Great Maghreb, which assessed HRQoL and associated factors in a pediatric diabetic population.

Our study has three main limitations. The first limitation is related to the lack of a control group. The second limitation concerns the non-evaluation of some other potential determinant of HRQoL such as family and psychological relationships. The third limitation is related to the recruitment method from one center. Since all our patients were recruited from a single pediatric hospital, our results may not be easily generalized to children/adolescents with T1DM living in other locations in Tunisia or North Africa.

In clinical practice, providing support to patients with T1DM to guide them in reducing the risk of acute and chronic complications. Involving parents in the management of their children/adolescents’ disease and more particularly encouraging a constant commitment for the potential disease progression would eventually improve the HRQoL of children/adolescents as well as their parents. Therefore, our research emphasizes the significance of adequate management of diabetes for improved HRQoL, and conversely, the importance of good HRQoL for maintaining good diabetic control. To improve the low emotional and school function scores identified in the study, it is advisable to regularly evaluate the HRQoL of these children to detect any significant deterioration early on. This will facilitate the implementation of appropriate interventions that can enhance the overall management of the disease. Additionally, in families with multiple children/adolescents, it is essential to involve the siblings in diabetes education and empower them to take responsibility. Providing families with information on available social support resources can also be helpful.