The Impact of the Covid-19 Pandemic on the Well-Being and Diabetes Management of Adolescents With Type 1 Diabetes and Their Caregivers: A Scoping Review

The Covid-19 pandemic and its related restriction measures might negatively impact diabetes management and well-being of adolescents with Type 1 Diabetes Mellitus (T1DM) and their caregivers. Accordingly, the present scoping review is aimed at mapping the literature in line with the question “How has the Covid-19 influenced diabetes management and well-being of adolescents with T1DM and their caregivers?”. A systematic search has been conducted through three academic databases. Studies carried out during the Covid-19 pandemic focused on adolescents aged between 10 and 19 years with T1DM and/or their caregivers were included. A total of 9 studies, performed between 2020 and 2021, have been identified. In particular, N = 305 adolescents with T1DM and N = 574 caregivers were considered. Overall, studies were not specific in reporting adolescents’ age, and only 2 studies were primarily focused on the adolescent population with T1DM. In addition, studies were mainly focused on evaluating adolescents’ glycemic control, which remained stable or has improved throughout the pandemic. Contrarily, psychosocial variables have been marginally considered. Indeed, only one study investigated adolescents’ diabetes distress, which remained stable from pre-to during post-lockdown, albeit improving among girls, specifically. As regards caregivers of adolescents with T1DM, studies showed mixed results concerning their psychological state during the Covid-19 pandemic. Prevention measures, which are aimed at supporting adolescents with T1DM during the lockdown, were considered by one study only, showing the favorable role of telemedicine during lockdown for adolescents’ glycemic control. Altogether, the current scoping review has identified many shortcomings of the available literature, which are given by the limited specificity of the age group considered and by the limited consideration of psychosocial variables, particularly their interplay with the medical ones.


INTRODUCTION
Covid-19, the respiratory illness caused by the SARS-CoV-2 virus, was declared a global pandemic in March 2020 by the World Health Organization (1) due to its extremely contagious nature and associated high mortality rates. Although pediatric patients with Type 1 Diabetes Mellitus (T1DM) seem not to be at an increased risk of morbidity and mortality for Covid-19 compared to adults (2), they still are deemed as a particularly vulnerable population, especially considering that DM was found to be one of the most frequent comorbidities among people who got infected with Covid-19 (3). When it comes to diabetes management, which consists of the day-to-day actions required from patients with DM to consistently keep their disease under control, such as undertaking daily insulin shots, regularly monitoring their blood glucose, and maintaining a healthy lifestyle by being physically active and following a balanced dietary regimen (4,5), adolescents already represent an at-risk group. Indeed, on top of having to deal with the multiple biopsychosocial changes (6) typical of this developmental phase, they are also required to take on a greater sense of responsibility for their daily diabetes management (7).
Before the Covid-19 pandemic, plenty of evidence had already been gathered on how T1DM is a challenging condition for adolescents to live with: its management is often regarded as tedious, complex and time-consuming, and may potentially lead to the development of mental health issues (8,9). More specifically, Rechenberg and colleagues (8) highlighted how adolescents with T1DM experience heightened levels of anxiety symptoms regarding both the disease itself and diabetesmanagement specific tasks; other recent studies also confirmed the high prevalence of depression and anxiety symptoms in youth with T1DM and pointed out how these can lead to poorer diabetes management and glycemic control (10,11).
Within this context, the recent outbreak of the Covid-19 pandemic may become an additional risk factor for adolescents with T1DM. Indeed, restrictions put in place to contain the spread of Covid-19 have implied major repercussions in terms of access to the healthcare system and its resources (12,13), hindering the possibility for patients to keep up with their follow-up visits with the healthcare professionals. In addition, the lockdown measures imposed to contain the spread of the virus have led to drastic and abrupt changes in adolescents' lifestyles, which could be a further risk factor considering that a consistent daily routine, physical activity, and a healthy diet are pivotal in enabling more efficacious diabetes management among adolescents (14). Nonetheless, the greater closeness between adolescents and their families imposed by the lockdown might be regarded as a favorable aspect for diabetes management, since previous studies have shown that increased and constant family involvement within adolescents' diabetes management was predictive of better blood glucose monitoring and glycemic control (15). However, existing literature highlighted how parents of a child with chronic disease are themselves at increased risk for mental health issues: the burden of partaking in their offspring's everyday disease management can determine high levels of stress, anxiety, and depression symptoms (16)(17)(18). Recent literature (19) also shows how parents' and their child's well-being are strictly intertwined: as mentioned above, adolescents' DM often has a detrimental effect on their parents' well-being; this, on its part, can reflect in low parental self-efficacy, which in turn was shown to have negative effects on their child's self-management and metabolic control (19). On the other hand, there is evidence that adolescents with strong family support display better adherence and glycemic control (20). This, overall, illustrates how both parents and their child with T1DM are involved in maintaining positive diabetes management, which is therefore deemed as a "family disease" (21,22).
The aforementioned evidence highlights the need to investigate how the ongoing pandemic has affected and still affects adolescents with T1DM, verifying how this topic has been explored within the literature in order to collect evidence and suggestions on which to base and tailor future research and interventions. Therefore, the current scoping review was conducted to map the relevant literature related to the impact of the Covid-19 pandemic on adolescents with T1DM and their caregivers. The broader question guiding this scoping review is "How has the Covid-19 influenced diabetes management and well-being of adolescents with T1DM and their caregivers?". In this regard, it should be noted that the present study followed the definition of adolescence proposed by WHO, according to which it is a period that covers the age from 10 to 19 years (23). Three different and more specific questions were further outlined under this umbrella:

Scoping Review
Scoping reviews are aimed at mapping the core concepts that underlie a precise research topic by analyzing its nature, features as well as the amount of investigation conducted (24), while providing a global overview of the content and/or findings of it. Indeed, scoping reviews are commonly applied "for reconnaissance" (22, p. 141), that is, to allow for clarification when a body of literature has not yet been reviewed or when there may be inconsistencies and/or heterogeneity on a topic (25).

Search Strategy
The current scoping review was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) extension for Scoping Reviews (PRISMA-ScR) guidelines (26), as shown in Figure 1.
Three electronic bibliographic databases, specifically Web of Science, PubMed and PsycINFO, were screened to identify studies published during the years 2020 and 2021, to ensure they were conducted during the Covid-19 pandemic. Studies were identified using the following MeSH terms: type 1 diabetes mellitus, adolescent* OR adolescence, caregiver* OR parent*, well-being, anxiety, stress, depression, health-related quality of life, quality of life, COVID-19, diabetes management.

Study Screening
The titles and abstracts retrieved from the above-mentioned electronic databases were independently screened by one author (GDA) and any doubt has been solved by consulting two other authors (GB and EM). This initial screening has been conducted by a single author because of its preliminary nature. The more thorough full-text screening needed to assess studies eligibility, in line with inclusion and exclusion criteria, has been performed independently by two authors (GB and EM) through a doubleblind process; any doubt or conflict has been solved by consulting a third author (SS).

Inclusion Criteria
Studies were included in the present study if they fulfilled the following inclusion criteria: (I) focused on adolescents with T1DM aged 10 to 19 years [according to the WHO's definition of adolescence (23)]; (II) focused on the caregivers of adolescents

Data Extraction and Management
Data extraction was independently performed by two authors (GB and GDA) and any disagreement was resolved by consulting a third author (EM). The data extracted were the studies' DOI, first author's surname, year of publication, country of origin, study design, period (date and month) of the Covid-19 pandemic in which the study was conducted, adolescents and/or caregivers' characteristics (e.g., sample size, age, gender), diabetes duration, assessment instruments used to investigate the mentioned variables and, lastly, outcomes of interest (i.e., adolescents and/ or caregivers diabetes management, well-being, depression, anxiety, stress, diabetes distress, quality of life, adolescents' health-related quality of life and prevention measures divulged to adolescents with T1DM).

Search Process Results
The search process results are shown in Figure 1. A total of 5062 studies were identified following the initial database search. After duplicate removal, the preliminary screening of titles and abstracts was performed on a total of 4408 studies, resulting in 46 studies, which were further evaluated for eligibility through full-text screening. In line with the inclusion and exclusion criteria, 9 studies were included, and 37 studies were excluded; the full list of reasons for exclusion is reported within the supplementary material (Supplementary Material Table S1).

Studies' Characteristics
Characteristics of the included studies are summarized in Tables 1A, B. Studies were published between 2020 and 2021 and were all conducted in 2020, thus during the first wave of the Covid-19 pandemic, including the lockdown period. A total of N = 305 adolescents (50.07% female) and N = 574 caregivers (95.45% female) were identified.
Among the included studies, N = 2 (30, 35) were specifically focused on adolescents, N = 4 (29, 32-34) compared children and adolescents, N = 1 (31) compared children, adolescents, and adults, and N = 2 (27, 28) compared caregivers of children with T1DM vs. caregivers of adolescents with T1DM. In this regard, it should be noted that high heterogeneity has emerged within studies' reporting of adolescents' age: only one study (35) provided mean, standard deviation (SD) and specific age range of participants, one study (30) provided mean age and SD, yet not the age range, and one (29), albeit providing this information for the aggregated sample comprising both children and adolescents, did not mention the specific demographic characteristics of the adolescent subsample. About the remaining included studies, only N = 2 reported the sample's age range (32,34), while N = 2 (31,33) reported the sample's median age, IQR and age range. Furthermore, the two studies, which focused on caregivers (27,28), did not report information regarding their child's age. Lastly, information on the household's socio-economic status was reported by N = 2 studies only (29,35).
Both studies, which focused on caregivers (27,28), evaluated their emotional burden and worries referred to their child's diabetes management. One also evaluated caregivers' likelihood of developing mental health issues during lockdown (28). It is noteworthy that one study (32) evaluated perceived stress, but unclearly reported if it was assessed referring to adolescents with T1DM or to their caregivers.

Results of Individual Evidence and Overall Synthesis
The results of the included studies are charted in tabular form (Tables 2A-C) in line with the research questions posed by the current scoping review.
Many inconsistencies and overall heterogeneity in information reporting have emerged, in particular regarding adolescents' age.
Notwithstanding this, for what concerns diabetes management, included studies showed a stable and even improved glycemic control among adolescents with T1DM throughout the pandemic. Notably, a study has reported stable TIR and HbA1c values from pre-lockdown (31), while others have shown improved TIR between the two periods (29, 30) as well as improved TIR (30,34) and HbA1c (34) from pre-and post-lockdown. However, one study (32) reported a worsening in glycemic control as indexed by increased HbA1c from pre-to post-lockdown. None of the included studies has investigated differences in metabolic control based either on the type of insulin therapy regimen or the type of glucose monitoring.
The protective or risk factors for adolescents' adjustment throughout the pandemic have not been specifically evaluated by the included studies, as they have mainly focused on providing a descriptive "overview" of the situation by mostly referring to the medical aspect of T1DM. Nonetheless, the need to take action as regards the much-reduced physical activity during the lockdown period was reported (34,35), particularly in light of a foreseen continuation of pandemic-related restrictions. Despite this, some authors (30,31,34) have developed a "positive lockdown effect" hypothesis, whereby more stable and constant life routines and reduced everyday life stress might have accounted for the abovereported stable or improved glycemic control shown by adolescents with T1DM. It is noteworthy that the psychological impact of both the pandemic and lockdown has been investigated by one study only (33), which has compared adolescents' DD levels pre-and during the lockdown, showing a decrease between these two periods, especially in girls. In this regard, the authors (33) pointed out that before the Covid-19 pandemic neither adolescents' nor their parents' DD was influenced by their mode of insulin therapy (i.e., multiple daily injections vs. continuous subcutaneous insulin infusion) nor by the type of glucose monitoring [continuous glucose monitoring (CGM) vs. self-monitoring of blood glucose (SMBG)]. Comparably, during the lockdown period, they observed no changes in DD levels neither among adolescents who had changed the type of glucose monitoring (from SMBG to CGM) nor among those continuing with SMBG.
In line with the scarce investigation of adolescents' psychological adjustment, no specific prevention measures seem to have been deployed and evaluated during the pandemic to specifically support the overall adjustment of adolescents with T1DM. However, Ceconi and colleagues (30), stressed the potentiality of telemedicine to support adherence and self-efficacy during the lockdown.  The impact of the pandemic upon caregivers was mainly reflected in increased perceived burden in both diabetes management and child-related worry and burden (27,28). Still, results also showed that caregivers of adolescents with T1DM did not significantly differ from parents in general in the likelihood of presenting mental health issues during a lockdown.

DISCUSSION
The present scoping review is aimed at evaluating evidence useful to answer the previously reported three questions that fall within the broader question "How has Covid-19 influenced diabetes management and well-being among adolescents with T1DM and their caregivers?". To reach this goal, five thousand sixty-two titles were initially identified; yet only nine studies were eligible to be included. Notably, during the full-text screening, several studies were removed since their attention was directed towards children with T1DM under or equal to 9 years of age. Indeed, the adolescent group with T1DM was scarcely taken into consideration within the literature, and the studies who did often showed results aggregated with those of children under the age of 9 (see Supplementary Material): among the included studies, only 23% (two studies) were specifically oriented towards the effect of Covid-19 on adolescents with T1DM (30,35).
Overall, the included studies have depicted the general scenario of the effect of Covid-19 among adolescents with T1DM and their caregivers: this lays the basis for the development of future research, which, beyond the reported choice of age group to investigate, should also be more careful and comprehensive in defining the outcomes to investigate. On this matter, the majority of the included studies focused on evaluating the impact of Covid-19 on medical indices among adolescents with T1DM. In general, they underlined a stable and even improved TIR and HbA1c pre-, during and post-lockdown (29)(30)(31)34), except for one study that showed a downward trend of glycemic control pre-and post-lockdown (32). Another relevant result that emerged was the reduction in physical  activity, which reflects the fact that the lockdown period has led to a more sedentary lifestyle (34,35). In this scenario, only one study evaluated the effect of Covid-19 on DD among adolescents with T1DM, thereby taking into account the psychosocial side. Authors pointed out that adolescents experienced moderate DD levels, which although decreased only among girls from pre-toduring lockdown (33). Nonetheless, before the Covid-19 pandemic, girls showed significantly higher DD than boys (33), which suggests that the more stable life routine allowed by lockdown, as reported by other authors (27,30,34) referring to its effect upon glycemic control, was much needed and useful for female adolescents as regards their DD. Referring, instead, to diabetes management and glycemic control, evidence suggested that being older adolescents favored improved TIR and reduced glucose variability expressed both as the glucose SD and the CV% throughout the Covid-19 pandemic. In addition to their greater maturity, the increased detachment from the family unit and the increased sense of responsibility that can be observed during late adolescence might further push adolescents toward a greater and more autonomous diabetes management, which in turn leads to improved glycemic control. Contrarily, lower socio-economic status and higher BMI might represent risk factors leading to worsened glycemic levels. Altogether, this evidence provides some preliminary evidence to answer the first specific question of the current scoping review (i.e., What are the protective and risk factors among adolescents with T1DM in the context of Covid-19)?.
It is also worth noting that the complexity of diabetes management also necessitates continuous caregivers' involvement in adolescents' care in order to establish adaptive family teamwork, that sees the joint effort of both the adolescent and the caregiver and thereby prevent the worsening of glycemic control and the maintenance of adherence (14). Indeed, the family provides key support for the optimal management of a child's diabetes, whereby if family conflicts occur, the adolescent's psychophysical health might be affected as well. In this regard, the second specific question to be answered in the present scoping review is "How did Covid-19 influence the role of caregivers in supporting their adolescents with T1DM?". Three studies assessed the emotional impact of Covid-19 (27,28,33) upon the caregivers of adolescents with T1DM, also investigating their incidence of mental health disorders as compared to parents from the general population (28). These authors showed mixed results: on the one hand, caregivers have experienced symptoms of anxiety, uncertainty and worries related to the suspension of medical appointments, along with an augmented need to provide care to their child (27,28); on the other hand, caregivers did not show any worries specifically related to Covid-19 and their DD levels have even decreased (33). As regards this latter result, and as previously pointed out, some studies have speculated a "positive lockdown effect" (28,30,34), suggesting that a more stable routine in adolescents and caregivers resulting from the limitations imposed by the pandemic may underline the positive and favorable evidence identified regarding glycemic control and DD. Notwithstanding, given the little research identified and evaluated, the need for prevention interventions and support programs directed to all adolescents with T1DM and their caregivers should still be considered, particularly taking into account the current continuous changes in the pandemic-related restrictions, which strongly limits the possibility for stable lifestyle routines. Therefore, following this line, intervention measures represent the next step to be taken into consideration and subsequently implemented, as a mean of support and/or prevention for adolescents with T1DM and their caregiver(s).
In the context of the Covid-19 pandemic, it is even more necessary to encourage and increase, pediatric access to CGM devices, in order to favor glycemic monitoring and data sharing with healthcare professionals and the caregivers that assist the adolescent with T1DM. In this regard, it is worth mentioning that mental health professionals should be intended as active components of the multidisciplinary team, equally involved in providing psychosocial support to all caregivers and adolescents with T1DM (14). Accordingly, digital health solutions directed to  both psychosocial and medical aspects should also be developed and promulgated. Indeed, the third and last specific question to be answered in the current scoping review is "Which prevention measures have been implemented so far to support adolescents with T1DM in the context of Covid-19?". Only one of the included studies has investigated the role of telemedicine in monitoring adolescents' glycemic control. The authors found an improvement in the glycemic control among adolescents via the continuous assistance deployed through telemedicine during and even post-lockdown, speculating a "dragging effect" (5, p. 5). Nonetheless, the authors themselves stated that there is no evidence to prove the efficacy of this digital intervention on adolescents' improved glycemic levels (30). Still, the literature shows that most eHealth interventions are predominantly oriented towards adults with diabetes, and they are mainly pilot or proof-of-concept studies (36)(37)(38).

LIMITATIONS
The present scoping review allowed for the delineation of a comprehensive picture of the available literature on the impact of ▪ Being an older adolescent was associated with improved TIR, lower glucose SD, and reduced CV.
▪ A lower socioeconomic position was associated with increased delta-mean glucose.
▪ Glucose variability was more stable among adolescents compared to children, both before and during lockdown. ▪ Adolescents, compared to children, showed improved variability markers during lockdown.
▪ Only considered patients that used CGM*. ▪ During lockdown, being female was associated with significantly decreased DD.
▪ High adolescents' DD before the pandemic was associated with reduced changes in DD scores during the lockdown.
▪ Before the pandemic, adolescents' and their caregivers' DD positively associated with adolescents' BMI. ▪ Adolescents showed reduced DD during lockdown, especially girls. ▪ Females presented significantly greater DD than boys before the pandemic. ▪ DD remained unchanged among male adolescents from before to during lockdown.
▪ DD assessment during lockdown was performed by phone*. ▪ The protective role played by physical activity that emerged was solely evaluated considering the aggregated sample. Telford et al. (35) _ ▪ Having T1DM predicted increased BMI during lockdown.▪ Belonging to a lower socio-economic position and higher BMI is associated with poorer glycemic control.
▪ Adolescents with T1DM showed significantly higher BMI compared to the control group. ▪ Physical activity level showed no association with adolescents' socioeconomic position, HbA1c levels, or the method of insulin delivery. ▪ BMI was negatively associated with physical activity during lockdown. ▪ All participants showed reduced physical activity during lockdown; rates did not differ between the T1DM and control group, nor between males and females.
▪ No information about prelockdown physical activity levels*. Covid-19 upon adolescents with T1DM and their caregivers; however, this review did not provide a quantitative synthesis of effect sizes. Moreover, diabetic ketoacidosis (DKA), a complication of T1DM, was not included as an outcome in the present study for its specific characteristics, thus, being DKA a rather common and relevant complication in adolescents with T1DM. Future research is needed to consider DKA weight in diabetes management among adolescents. Lastly, only one author (GDA) independently screened the titles and abstracts. However, this phase of the search process was a preliminary step based only on the evaluation of title and abstract, while the more specific and thorough full-text screening has been conducted following a double-blind process.

CONCLUSIONS
The main and broader question of the present scoping review was: "How has Covid-19 influenced diabetes management and well-being among adolescents with T1DM and their caregivers?". It is interesting to note that during the lockdown period a stable routine seems to have played a protective role towards glycemic control and DD among adolescents with T1DM, to the point that the term "positive lockdown effect" was employed. Furthermore, being an older adolescent has also emerged as a possible protective factor for glycemic control, which might be given by the greater psycho-neurological maturity of older adolescents compared to younger ones. On the contrary, a higher BMI was associated with worsened glycemic levels, which stresses the need to carefully monitor eating habits as well as physical activity with prompt attention and intervention.  being of both adolescents and caregivers during the Covid-19 pandemic should be strengthened, and new and effective interventions, both in digital and in traditional settings, should be developed. A further important aspect that has emerged from the current scoping review is the need to conduct studies that more carefully distinguish between children and adolescents with T1DM, as their developmental challenges are distinct and have different implications, even more so if a chronic disease is involved. Lastly, this scoping review permitted to highlight the need to also consider psychosocial variables relevant to T1DM when investigating the impact of Covid-19, as the psychosocial components of the disease are influenced by the medical ones and vice versa. Indeed, both psychosocial and medical variables are bidirectionally associated (39) and they are comparably relevant for the investigation, prevention, and promotion of the broader well-being of adolescents with T1DM. In addition, the joint consideration of the two may be of practical benefit in better comprehending the whole functioning of adolescents with T1DM. This would allow to further tailor interventions upon the specific characteristics of this age group, which would be of great value particularly during the pandemic period.

AUTHOR CONTRIBUTIONS
GB and EM defined the search strategy. GD'A did the first article screening. GB and EM did the full-text screening and their selection. GB and GD'A did the data extraction. EM conducted the synthesis and GB wrote the narrative summary. SS critically revised the summary and manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.
Health care continuous assistance through telemedicine N/R • Telemedicine conducted during the lockdown period and the month following the relaxation of restrictions favored stable and improved glycemic control among adolescents with T1DM.

•
Hypothesized "dragging effect" of improved glycemic control following lockdown as consequent to constant telemedicine interactions with the physician.
• Not possible to assess telemedicine efficacy on glycemic control (e.g., no control group)*. • Insufficient information on the procedure and overall unclear methodology.

•
No information on the analysis was performed. *Authors' reported study limit relevant to the current scoping review. N. R., not reported.