# Discovery of Novel Benzamide-Based Sigma-1 Receptor Agonists with Enhanced Selectivity and Safety.

Patrick Vermersch, Pascal Carato, Bénédicte Oxombre, Severine Ravez, Rajaa Boulahjar, Marion Donnier-Maréchal, Amélie Barczyk, Maxime Liberelle, Patricia Melnyk

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## To cite this version:

Patrick Vermersch, Pascal Carato, Bénédicte Oxombre, Severine Ravez, Rajaa Boulahjar, et al., Discovery of Novel Benzamide-Based Sigma-1 Receptor Agonists with Enhanced Selectivity and Safety. Molecules, 2025, Molecules, 30 (17), pp.3584. 10.3390/molecules30173584. hal-05301387

HAL Id: hal-05301387

https://lilloa.hal.science/hal-05301387v1

Submitted on 7 Oct 2025

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# Exploring gender differences in physical activity and related barriers in children and adults living with type 1 diabetes: A narrative review

Elsa Heyman<fnref n="1" />,<fnref n="2" /> | Tricia M. Peters<fnref n="3" />,<fnref n="4" /> | Elodie Lespagnol<fnref n="1" /> | Cassandra Parent<fnref n="1" /> |
Anne-Sophie Brazeau<fnref n="5" /> | Jane E. Yardley<fnref n="6" />,<fnref n="7" />,<fnref n="8" />,<fnref n="9" />,<fnref n="10" />,<fnref n="11" />

## Correspondence

Elsa Heyman, URePSSS—Unité de Recherche Pluridisciplinaire Sport Santé Société, F-59000 Lille, France, EURASPORT, 413 avenue Eugène Avinée, 59120, Loos, France.

Email: elsa.heyman@univ-lille.fr

## Abstract

**Aims:** In the general population, individuals who self-identify as girls and women are typically less active and report more barriers to physical activity (PA), often influenced by gender stereotypes and sociocultural norms. These barriers may be accentuated in individuals with type 1 diabetes (T1D), who face additional diabetes-related barriers to engaging in PA.

**Methods:** In this narrative review, electronic databases were searched using keywords related to PA barriers and T1D. Titles, abstracts and full texts were screened to select articles analysing gender effects or reporting specific data on girls/women with T1D versus peers without diabetes.

**Results:** While many studies have examined gender effects on PA levels in T1D (consistently reporting lower overall and vigorous-intensity PA in girls/women), few have explored gender effects on barriers to PA. Among the ten barrier-related studies, some (but not all) suggest that girls/women report higher overall PA barrier scores and diabetes-related concerns, such as fear of hypoglycaemia,

References quoted in the manuscript that deal with individuals without diabetes or with individuals with type 1 diabetes (T1D) but without consideration of gender effect on physical activity (PA) levels or on barriers to PA are available in the supporting information file. They are identified in the text as 'Supporting reference'.

This is an open access article under the terms of the [Creative Commons Attribution-NonCommercial License](http://creativecommons.org/licenses/by-nc), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

© 2025 The Author(s). *Diabetic Medicine* published by John Wiley & Sons Ltd on behalf of Diabetes UK.

<footnote n="1">¹Univ. Lille, Univ. Artois, Univ. Littoral Côte d'Opale, ULR 7369—URePSSS—Unité de Recherche Pluridisciplinaire Sport Santé Société, Lille, France</footnote>

<footnote n="2">²Institut Universitaire de France, Paris, France</footnote>

<footnote n="3">³Division of Endocrinology, Jewish General Hospital, McGill University, Montreal, Quebec, Canada</footnote>

<footnote n="4">⁴Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, Quebec, Canada</footnote>

<footnote n="5">⁵School of Human Nutrition, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Quebec, Canada</footnote>

<footnote n="6">⁶Augustana Faculty, University of Alberta, Camrose, Alberta, Canada</footnote>

<footnote n="7">⁷Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada</footnote>

<footnote n="8">⁸Women and Children's Health Research Institute, University of Alberta, Edmonton, Alberta, Canada</footnote>

<footnote n="9">⁹Faculty of Kinesiology, Sport and Recreation, University of Alberta, Edmonton, Alberta, Canada</footnote>

<footnote n="10">¹⁰Ecole de kinésiologie et des sciences de l'activité physique, Université de Montréal, Montreal, Quebec, Canada</footnote>

<footnote n="11">¹¹Institut de recherches cliniques de Montréal, IRCM, Montreal, Quebec, Canada</footnote>
hyperglycaemia or losing control over diabetes management, compared with boys/men. The interactions between PA barriers and PA levels appear complex and may vary between adults and children. However, these interactions remain understudied from a gender perspective.

**Conclusions:** Fear of glycaemic challenges related to PA appears to be a greater barrier for girls/women with T1D versus boys/men. However, further research is needed to examine universal barriers to PA. Interactions between diabetes-related or universal barriers with lower habitual PA also require exploration as a first step towards developing appropriate PA promotion initiatives, whether focused on glycaemic management education or social factors.

KEYWORDS

diabetes mellitus type 1, exercise, gender identity, hyperglycaemia, hypoglycaemia, sports, women

# 1 | INTRODUCTION

In general, regular PA provides numerous benefits, including improved cardiovascular health, functional capacity, lipid profile, body mass and composition, and quality of life (Supporting references 1–5). Some cardiovascular (Supporting references 6–10), metabolic (Supporting references 11–14) or genetic/epigenetic (Supporting reference 15) training adaptations show clear sex-related differences. Metabolically, female participants experience less fat-free mass gain and anabolism than male participants in response to exercise training (Supporting references 13 and 14), while their shift toward fat catabolism at a given relative workload is more pronounced (Supporting references 11–13). Additionally, female-specific challenges (e.g. pre-menstrual distress symptoms) (Supporting reference 16) or health risk factors (e.g. high endogenous oestrogen levels) may be mitigated through regular PA (Supporting reference 17).

In people with T1D (pwT1D), regular PA is important for improving health and reducing long-term diabetes-related micro- and macrovascular complications risk (Supporting reference 18). Numerous studies exploring exercise training effect in children/adolescents (Supporting references 19–28) or adults (Supporting references 21, 22, and 27–36) living with T1D suggest improvements in aerobic fitness (Supporting references 20–22, 25, and 29–31), body mass index (Supporting references 21, 23, and 35), body composition (Supporting references 20 and 25), total cholesterol (Supporting references 2, 23 and 35), triglycerides (Supporting references 21 and 23), lipid profile (Supporting references 20, 21, 25, 31, and 35), insulin sensitivity (Supporting references 26 and 31), insulin dose (Supporting references 21,

## What's new?

* Girls and women with type 1 diabetes generally engage in less physical activity (PA) than boys and men, especially at vigorous intensity.

* To explore this gender gap, we reviewed studies on perceived barriers to PA. Existing studies generally suggest that diabetes-related barriers—such as fear of hypoglycaemia—may be more common in girls and women, while non-diabetes-related barriers remain underexplored.

* The relationship between PA and perceived barriers appears complex, with inverse patterns in children versus adults. Future research should examine these dynamics through a gender lens to support personalized strategies for promoting PA.

22, 26, 29, and 31), long-term mean glycaemia ($HbA_{1c}$) (Supporting references 19, 22, 23, 27–29, and 35) and micro- or macrovascular complications (Supporting references 32–36).

PA encompasses any bodily movement produced by skeletal muscles that requires energy expenditure, including movement during leisure time, for active transport or during work and domestic activities. International PA guidelines provide recommendations for children and adults regarding the types/amounts of activity needed for health benefits (Supporting references 37 and 38). For pwT1D, the only additional specific recommendation is to distribute PA over at least 3 days per week, with no more than two consecutive days without exercise (Supporting reference 37).
Notably, there are no specific PA recommendations according to sex/gender, except for some guidance specific to pregnancy (Supporting reference 38). However, in the general population, those who self-identify as girls and women (hereafter referred to as 'girls' and 'women') are generally less active and less likely to meet PA recommendations. This trend has been highlighted in studies across different age groups, including children (Supporting reference 39), adolescents (Supporting reference 40), adults (Supporting reference 41) and the elderly (Supporting reference 42) without diabetes and is often attributed to self reported barriers influenced by gender stereotypes and sociocultural norms (Supporting references 43 and 44).

It remains unclear whether gender differences in PA barriers are amplified or mitigated in pwT1D. Beyond the barriers observed in the wider population, pwT1D face diabetes-specific barriers to PA, such as fear of hypoglycaemia/hyperglycaemia and fear of loss of agency over diabetes management (Supporting references 45 and 46). Importantly, some diabetes-related barriers are perceived as more significant than general PA barriers. This is particularly true for fear of hypoglycaemia, which is consistently reported as the main PA barrier in both children and adults with T1D (Supporting reference 47), as PA is among the main daily-life situations that can trigger hypoglycaemia (Supporting reference 48). Importantly, after experiencing clinically relevant or severe hypoglycaemia (regardless of whether it was PA-induced), women with T1D are more likely than men to report persistent fatigue or anxiety (Supporting reference 49). This raises the possibility that PA-related hypoglycaemic episodes may also be perceived differentially by active women versus men, potentially contributing to additional gender differences in PA barriers. This narrative review aims to examine gender differences in PA barriers among children and adults with T1D and to discuss potential interactions between these barriers and the actual PA levels.

## 2 | METHODS

Two separate searches were conducted. First, a comprehensive literature search was performed by EH up to July 2025, using PubMed and Google Scholar, to identify observational studies describing PA barriers in pwT1D using the keywords 'barriers' AND 'physical activity' AND 'type 1 diabetes'. The results were screened, and retrieved studies were reviewed to select those including a gender comparison. Second, to explore possible implications of gender differences on usual PA levels (assessed with questions/ questionnaires or measured with movement trackers), we

performed a limited PubMed search using the terms ('physical activity[Title]) AND (type 1 diabetes[Title])' with the addition of one of the following keywords: 'gender', 'sex', 'girls', 'women', 'female'. For both searches, there were no exclusion criteria for the pwT1D (children and adults without any restriction on participants' age or diabetes duration). We did not retain studies not published in English language or only published as conference abstracts/theses. The results detailed below include a summary of the findings on PA levels in pwT1D with a specific focus on girls and women and on gender's impact, followed by the results of the comprehensive search on gender differences in barriers to PA among these individuals.

## 3 | RESULTS

### 3.1 | Gender's impact on PA levels in children and adults with T1D

#### 3.1.1 | PA levels in girls or women with T1D compared to individuals without diabetes

Among the studies comparing PA levels in pwT1D versus without diabetes, seven (four in children, three in adults) reported results specifically for girls or women. In children and adolescents, one study found no impact of T1D on PA levels in girls (assessed by questionnaire¹), while all other studies reported lower PA levels in girls with T1D compared to those without diabetes. This finding was consistent among adolescents (total PA² and moderate to vigorous PA (MVPA)³ measured by accelerometery), children and adolescents aged 6–18 years (MVPA by accelerometry³) and very young children (<7 years old; total PA and MVPA measured by accelerometry⁴). This discrepancy between results obtained via accelerometry and self reported questionnaires aligns with the overestimation of PA observed by Fintini et al. in children with T1D (without gender distinction) (Supporting reference 50). Their study found that self reported PA (questionnaire) was comparable between children with T1D and peers without diabetes, whereas objectively measured PA (accelerometry) was lower in those with T1D (Supporting reference 50). However, in all studies, girls with T1D did not use continuous glucose monitoring (CGM) in daily life. Given that CGM technology has recently become widely available in some developed countries, it is possible that its use could help increase PA levels (Supporting references 51 and 52).

Among the studies on adults, findings suggest no significant difference in PA levels in women⁵,⁶ or pregnant women⁷ with T1D versus those without diabetes. PA
levels were assessed either subjectively using a question-
naire (International PA questionnaire [IPAQ] score<sup>5,7</sup>) or
objectively with accelerometry (PA level score<sup>6</sup>).

3.1.2 | Impact of gender on PA levels among individuals with T1D

We found twenty-one studies in adults, one in adoles-
cents/adults and eighteen in children/adolescents includ-
ing results about gender impact on PA levels in pwT1D.

*Impact of gender on overall PA levels in T1D*

A significant portion of the literature (14 studies in adults; 11 in children) highlights lower total PA levels in women with T1D compared to men, as assessed through questionnaires<sup>5,8-14</sup> (Supporting reference 35) or measured with objective movement recordings.<sup>15-18</sup> Similarly, girls with T1D tend to engage in less PA than boys, as shown in studies using questionnaires<sup>13,19-24</sup> and objective movement recordings.<sup>3,25,26</sup> This gender difference is evident from early childhood (accelerometry<sup>4</sup>) and in newly diagnosed adults (T1D for <3 months; assessed by accelerometry<sup>27</sup>). These findings align with research on gender differences in PA levels among children (Supporting reference 39), adolescents (Supporting reference 40) and adults (Supporting reference 41) without diabetes.

A smaller number of studies in pwT1D (four in adults, six in children, one in adolescents and adults) did not reveal significant gender differences in total PA or MVPA levels in children/adolescents,<sup>28-31</sup> adolescents or adults,<sup>32</sup> adults<sup>33,34</sup> and, in rare cases, reported higher PA levels in women versus men (adolescents<sup>35</sup>; adults<sup>36-38</sup>). Among these studies, only four relied on objective PA measurements.<sup>30,31,33,34</sup>

*Impact of gender on PA intensity in T1D*

It is noteworthy that the above-mentioned studies did not systematically distinguish specific PA intensities in their analyses of total PA based on questionnaire data. This omission may explain some discrepancies in the findings. Several studies suggest that girls and women with T1D engage in less vigorous-intensity PA compared with boys and men, as observed in children/adolescents,<sup>39</sup> adolescents/ adults<sup>13</sup> and adults.<sup>18,40,41</sup> Similarly, girls and women with T1D participate less in competitive sports (children/adolescents<sup>29</sup>) while spending more time in light-intensity PA (children/adolescents<sup>4,42</sup>; adults<sup>18,40</sup>). These studies primarily relied on questionnaires<sup>13,29,39-42</sup> or more rarely on accelerometry or movement sensors.<sup>4,18</sup> The intensity-modulating effect of gender on PA appears consistently in the literature, with some exceptions: Three studies found no gender differences in participation in light-intensity PA in adolescents<sup>31</sup> or adults.<sup>33,34</sup>

*Impact of gender on PA domains (professional, leisure time, domestic and gardening, or active transport) and types of exercises in T1D*

Gender can impact PA domains. Using the long version of the IPAQ questionnaire, Gomez-Peralta et al. found that women, including adolescents and adults, reported spending less time per week engaging in PA at work, in active transport and during leisure time (recreation, sport, exercise or leisure PA but not domestic and gardening activity) compared with men.<sup>13</sup> However, women engaged more in domestic and gardening activities (i.e. in/around home, like housework, gardening, yard work, general maintenance work, caring for family).<sup>13</sup> Gender effects are also observed in types of exercise engagement during leisure-time PA, as explored by Logan et al. through semi-structured interviews with a small sample of women and men with T1D. Their findings suggested similar levels of resistance training by both genders, whereas women reported more aerobic exercise and high-intensity interval training, while men reported being more involved in sports.<sup>38</sup> However, Yardley et al. did not find any differences in types of exercises undertaken in women versus men, who self reported their PA on a study-developed, cloud-connected smartphone application during 4 weeks.<sup>43</sup>

*Impact of gender on sedentary behaviours and inactivity in T1D*

Sedentary behaviour and time spent inactive may also vary by gender. To our knowledge, three studies examined this topic in adults with T1D. Using accelerometry, Al-Ozairi et al. found that although women engaged in less moderate and vigorous PA than men, they compensated by spending more time in light-intensity PA. Consequently, women spent less overall time inactive compared with men.<sup>18</sup> The same authors, in another study on a smaller sample size, found less time spent inactive among women, but this was not compensated by higher levels of light-intensity PA.<sup>34</sup> Moura et al. recently found no gender difference in inactive time with accelerometers, consistent with their results of no gender differences in light-intensity PA and MVPA levels.<sup>33</sup>

In children/adolescents with T1D, questionnaire-based studies suggest that girls accumulate less screen time compared with boys,<sup>39</sup> especially on computers.<sup>20,21</sup> However, findings from studies using different methodologies are inconsistent. Using a 3-day subjective record (logged every 15 min), Miculis et al.<sup>42</sup> reported that girls spent more time in sedentary behaviours than boys. Similarly, Czenczek-Lewandowska et al.<sup>3</sup> found a higher percentage of sedentary time in girls compared with boys using 7-day accelerometry. By contrast, other studies using accelerometry in adolescents<sup>30,31</sup> or very young children (<7 years old)<sup>4</sup> detected no significant gender differences in sedentary time. These discrepancies may stem from differences in assessment
methods. Fintini et al. (Supporting reference 50) showed that sedentary time was underestimated in self reported questionnaires compared to accelerometry, with an even greater underestimation observed in children with T1D compared to their peers without diabetes. Further research is needed in both children and adults with T1D to clarify possible gender differences in sedentary time, as prolonged sedentary behaviour had detrimental health consequences independent of PA levels (Supporting references 53 and 54).

Overall, most studies examining gender influence on PA levels among pwT1D indicate that girls/women engage in less PA than boys/men, particularly at vigorous intensities. Even if these lower activity levels in girls/women may partly stem from gender differences in economic status (e.g. income level, employment status) as suggested in some studies,¹¹,¹⁷ gender-related barriers to PA participation may also exist. Therefore, a discussion of the impact of gender on PA barriers in T1D (whether real or perceived) is warranted.

## 3.2 | Impact of gender on barriers to PA in T1D

Among the 39 studies examining PA barriers in pwT1D (twenty one in adults, seventeen in children/adolescents, one including both children/adolescents and adults), only 10 included detailed results about the impact of gender (six in adults,¹⁰,¹⁴,³⁸,⁴⁴⁻⁴⁶ three in children/adolescents,⁴⁷⁻⁴⁹ one including both children/adolescents and adults⁵⁰). The participant characteristics in these studies and their main findings are presented in Table S1. No study in very young children (<6 years old) was available. Five of the ten studies used the Barriers to Physical Activity in Diabetes (type 1) (BAPAD-1) scale. This self-administered questionnaire, developed by Dubé et al. in 2006 (Supporting reference 55), asks participants to rate the likelihood (from 1 = extremely unlikely to 7 = extremely likely) that each of the 11 items will prevent them from engaging in regular PA over the next 6 months. The total BAPAD-1 score is derived from 4 items related to diabetes-specific barriers and 7 items applicable to both individuals with and without diabetes. Only one among the ten studies used semi-structured interviews to explore PA barriers.³⁸

### 3.2.1 | Impact of gender on overall perception of PA barriers among pwT1D

In children and adolescents with T1D, Parent et al.⁵⁰ found no gender differences in total BAPAD-1 score. Similarly, no gender difference in global score was detected by Garcia-Hermoso et al.⁴⁹ among children/adolescents using an 18-item questionnaire that they developed.

However, the four studies in adults consistently reported a tendency for higher⁴⁵ or significantly higher¹⁰,⁴⁶,⁵⁰ total BAPAD-1 scores in women compared with men. Notably, Keshwaraz et al.,⁴⁴ who restricted their analysis with BAPAD-1 to diabetes-specific barrier items in adults, found no gender differences in the proportion of individuals identifying at least one diabetes-specific item as a barrier to PA. In children, the subscore about diabetes-related barriers in the questionnaire used by Garcia-Hermoso et al. did not show any gender difference.⁴⁹

### 3.2.2 | Impact of gender on fear of hypoglycaemia as a barrier to PA in T1D

Among diabetes-specific barriers, fear of hypoglycaemia is a key focus of several studies and is often identified as the primary perceived barrier to PA in children and adults with T1D.⁴⁵,⁵⁰ In children/adolescents with T1D, Giblin et al.⁴⁷ and Huerta-Uribe et al.⁴⁸ found no significant gender differences in the perception of hypoglycaemia as a PA barrier. By contrast, Parent et al.⁵⁰ reported that girls rated the BAPAD-1 'fear of hypoglycaemia' subscore higher than boys.

In the subsample of adults, Parent et al.⁵⁰ found no significant gender differences in the BAPAD-1 'fear of hypoglycaemia' subscore. However, in a larger sample, Prevost et al.¹⁰ reported that women rated this barrier higher than men.

### 3.2.3 | Impact of gender on other diabetes-related barriers to PA

Only two studies¹⁰,⁵⁰ have investigated the influence of gender on other diabetes-specific PA barriers identified in the BAPAD-1 questionnaire (i.e. risk of hyperglycaemia, loss of agency over diabetes management and having diabetes). Parent et al.⁵⁰ found that women, but not girls, rated higher hyperglycaemic risk and loss of agency over diabetes management as barriers to PA compared with men and boys, respectively. These findings highlight the clinical relevance of research on exercise-induced hyperglycaemic risk, which is often overlooked in favour of hypoglycaemia prevention. By contrast, Prevost et al.¹⁰ found no significant gender differences in the fear of hyperglycaemia among adults. This differs from a study in adult athletes which found, using interviews, that women tended to be more worried about their hyperglycaemic events throughout their training phases than men (Supporting reference 56). Given these mixed findings, further research is needed to explore gender differences in perceptions of hyperglycaemia as a PA barrier in more detail.
### 3.2.4 | Impact of gender on non-diabetes-related barriers to PA in T1D

Prévost et al.¹⁰ examined gender differences in non-diabetes-related PA barriers using the BAPAD-1 questionnaire in a large sample of adults with T1D from Québec (Canada). They found that women reported weather conditions as a greater barrier than men and that this was the second most frequently cited barrier (for both genders), following fear of hypoglycaemia. However, this finding may be country-specific, as meteorological conditions likely influence perceptions of weather-related barriers. By contrast, Logan et al.,³⁸ using another methodology (semi-structured interviews) with a small number of participants from a different region of the same country (a majority being from Alberta), did not identify gender differences with respect to limited access to exercise spaces, especially during colder seasons. Besides specific geographic meteorological conditions, the impact of weather may be influenced by other factors as ethnicity (Supporting reference 57), which was reported to be 94.5% Caucasian participants in the study of Prevost et al.¹⁰ but was not reported in the study of Logan et al.³⁸ Beyond weather-related concerns, Prevost et al.,¹⁰ found no significant gender differences in other non-diabetes-specific barriers, including fear of tiredness, fear of injury, fear of a heart attack, low fitness level, gym location and physical health status (excluding diabetes). Garcia-Hermoso et al., in children/adolescents, also did not find gender differences in a score averaging subscores of five items about physical and health (other than T1D)-related barriers.⁴⁹ The questionnaire used in children/adolescents by Garcia-Hermoso et al. included an item about ‘school schedule or lack of time’, but the subscore was averaged with another item on family-related barrier and the global score did not reveal a gender difference.⁴⁹ Through their semi-structured interviews, Logan et al. found that ‘limited time’ was a common barrier to PA for both women and men.³⁸

## 4 | DISCUSSION

### 4.1 | Gender influence on barriers to PA in T1D

As outlined in Section 3, only a limited number of studies have investigated the impact of gender on barriers to PA in pwT1D. Some, but not all, studies suggest that global barrier score (examined in five studies¹⁰,⁴⁵,⁴⁶,⁴⁹,⁵⁰), or specific diabetes-related items (fear of hypoglycaemia assessed in five studies¹⁰,³⁸,⁴⁷,⁴⁸,⁵⁰); fear of

hyperglycaemia or of loss of agency over diabetes management assessed in two studies¹⁰,⁵⁰), is rated higher by girls/women compared with boys/men. The lack of consensus across studies may be due to the variety of methods used, including semi-structured interviews in one study,³⁸ yes-no responses in three studies¹⁴,⁴⁷,⁴⁸ and self-administered questionnaire in six studies (BAPAD-1¹⁰,⁴⁴⁻⁴⁶,⁵⁰; PABS-1⁴⁹). In addition, in their subscores or total score calculations, four¹⁰,⁴⁵,⁴⁶,⁵⁰ of the five studies using the validated BAPAD-1 questionnaire did not distinguish ratings reflecting that an item is a barrier (ratings from 5 to 7) from ratings indicating that an item is unlikely to be a barrier (ratings from 1 to 3). The fifth study⁴⁴ considered subscores ≥4 but only examined the presence/absence of a diabetes-related barrier.

Gender differences in non-diabetes-related PA barriers among pwT1D have been sparsely studied, with findings remaining inconsistent. For example, meteorological conditions were identified as a greater barrier for women in one study¹⁰ but not in another.³⁸ As previously mentioned, this discrepancy may be region-specific, as meteorological conditions vary across study locations. Similarly, the only study that specifically examined lack of time as a PA barrier in pwT1D was performed in adults and found no gender differences.³⁸ However, the broad age range (25–70 years old) in this study makes it difficult to compare findings directly with research on young adult women without diabetes, where lack of time has been identified as one of the main barriers to PA (Supporting reference 44). This issue should be considered in light of women's social roles between the ages of 18 and 40. Transitions into higher education, employment and/or motherhood introduce shifting responsibilities and lifestyle changes, with these social roles progressively overlapping rather than being interchanged (Supporting reference 44). Studies that assessed gender differences in PA barriers using the BAPAD-1 questionnaire did not include the ‘lack of time’ item. In the original study on the development of the BAPAD-1 scale, work schedule was ranked as the most significant barrier but was ultimately removed due to its low discriminatory power (Supporting reference 55). Thus, future research should also compare the relative importance of universal barriers to PA in girls/women with T1D versus those without diabetes, as well as in boys/men with and without T1D.

No study focused on very young children (<6 years old), while previous literature suggests that girls with T1D are less active than boys even in early childhood.⁴ In very young children, only barriers to PA as perceived by the parents (and not by the children themselves) would be investigable. In the four studies considering the gender effect on PA barriers in children, the questionnaires
or questions were answered by the children themselves since they were all older than 6 years. Only two among these studies included completing the same questionnaire⁵⁰ or answering the same questions⁴⁷ by the parents about their child. However, there was no indication about the effect of child gender on the parents' results. In addition, only two among the four studies provided information about how the children were assisted in questionnaire completion. In the study of Parent et al.⁵⁰ the parents did not help their child since the scientific team was available if the children did not understand a question; in the study of Giblin et al.,⁴⁷ assistance from the parents of younger children was mentioned. Future studies should account for parental influence on item responses and implement methodological safeguards (e.g. interviewer-assisted formats) to mitigate this potential source of bias.

Only one study included both children/adolescents and adults.⁵⁰ Yet, distinguishing barriers by both age and gender is crucial for tailoring PA promotion strategies effectively. Research on individuals without diabetes suggests that the relative importance of PA barriers varies across age groups. While sociocultural reasons are the primary influence on PA participation in young adult women (Supporting reference 44), older women more frequently report health-related barriers, including physical limitations and fear of injury, particularly for intense PA (Supporting reference 58). Among children/adolescents without diabetes, gendered parental attitudes may limit PA engagement. Girls are often assigned more household chores or expected to do more homework, reducing their available time for PA. Additionally, some parents view certain sports (e.g. soccer) as being ‘not for girls’ (Supporting reference 43). Compared with boys, adolescent girls without diabetes report feeling less supported by their families, friends and teachers in their efforts to be physically active (Supporting references 43 and 59). Ultimately, whether the perceived PA barriers directly influence actual PA participation differently by gender remains an open question that requires further investigation.

## 4.2 | Impact of gender on the interaction between ‘barriers to PA’ and ‘PA levels’ in T1D

### 4.2.1 | Interactions between ‘barriers to PA’ and ‘PA levels’ explored in T1D without gender distinction

To date, very few studies have examined the relationship between reported PA barriers and measured PA levels in pwT1D, and findings remain inconsistent. In adults, some

studies have found no association between PA levels and perceived barriers, whether considering the BAPAD-1 total score¹⁵,⁵⁰ or diabetes-specific barriers.⁵⁰ By contrast, other studies have reported an inverse association between PA levels and perceived barriers, meaning that higher barriers corresponded to lower PA levels, whether for the BAPAD-1 total score¹⁷,⁴⁶ or diabetes-specific barriers.⁴⁴ One study even reported contradictory findings depending on the PA measure used: While BAPAD-1 total scores were not associated with step count, they were negatively associated with daily PA energy expenditure.¹⁶

In children/adolescents, findings are similarly complex. In very young children, only one study is available and showed no correlation between total score of barriers (BAPAD-1) perceived by the parents and objectively measured MVPA (Supporting reference 60). In children older than 6 years, results are heterogeneous. Garcia-Hermoso et al. found a negative correlation between barriers (PABS-1) total score and MVPA through accelerometry.⁴⁹ However, this negative association was fully explained by a negative correlation of MVPA with the motivational barriers subscore (i.e. one among the four factors explored with PABS-1 questionnaire) and not with subscores of diabetes-related barriers, physical and health-related barriers or environmental and family-related barriers.⁴⁹ Two studies using objective PA measurements unexpectedly found a positive association between PA levels and perceived PA barriers.⁴⁸,⁵⁰ This association was particularly evident for exercise-induced glycaemic variation barriers (Parent et al.,⁵⁰ association with BAPAD-1 total score, fear of hypoglycaemia, fear of hyperglycaemia and loss of diabetes control; Huerta-Uribe et al.,⁴⁸ association with fear of hypoglycaemia). Rather than discouraging PA participation, the identification of glycaemic-related barriers in children may instead reflect that being more active heightens their awareness of potential glycaemic challenges. However, the findings in children and adolescents described above contrast with a recent study that reported slightly higher scores for fear of hypoglycaemia in adolescents with T1D who self reported fewer competitive and high-intensity exercise events, as well as fewer evening exercise sessions (Supporting reference 61). To better understand the interactions between PA barriers and PA levels, future studies should differentiate PA intensity and timing in their analyses.

### 4.2.2 | Gender modulating impact on relationships between ‘barriers to PA’ and ‘PA levels’ among pwT1D

The previously mentioned positive or negative associations between self reported PA barriers and PA
levels in children/adolescents, and the negative associa-
tion in adults, highlight the complexity of the relationship.
Barriers to PA can act as obstacles to engagement, but at
the same time, individuals who are more physically ac-
tive may also be more aware of the challenges they face
in maintaining their activity levels. Gender may influ-
ence these two paradigms in different ways. In the study
of Prevost et al. in adults with T1D,¹⁰ women reported
more PA barriers than men, including higher BAPAD-1
total scores and greater perceived barriers related to fear
of hypoglycaemia and weather conditions (see Table S1).
However, despite these differences, the proportion of par-
ticipants reporting at least 150 min of weekly PA was com-
parable between genders.

It is noteworthy that experiencing significant hypogly-
caemia, which likely contributes to fear of hypoglycaemia
(Supporting reference 49), may influence commitment to
PA differently by gender. In the study by Sander et al.,¹⁴
women reported more PA-related blood glucose chal-
lenges than men, yet there was no gender difference in
the likelihood that these high or low glucose fluctuations
prevented them from exercising. Similarly, Keshawarz
et al.⁴⁴ found that frequent hypoglycaemic episodes (as-
sessed outside the context of PA) were associated with
less time spent in MVPA 10-min bouts per week, but
this effect was only significant in men. In the same way,
Bohn et al. (Supporting reference 35) reported that men
reporting more severe hypoglycaemia events were more
inactive, while women reporting more severe hypoglyca-
mic events were actually more active. Thus, even if future
studies confirm that fear of hypoglycaemia is reported as
a greater barrier to PA in girls and women with T1D, it
remains uncertain whether this perception actually pre-
vents them from engaging in PA.

5 | CONCLUSIONS AND FUTURE DIRECTIONS

Concerning PA levels, studies in pwT1D align with find-
ings in populations without diabetes, consistently show-
ing that total PA levels are lower in girls and women
compared with boys and men. However, this difference
appears to be more pronounced for vigorous-intensity PA,
whereas light-intensity PA levels have been reported to be
higher in girls/women than in boys/men. These findings
suggest that the greatest potential for improvement lies
in increasing vigorous-intensity PA among girls/women.
This underscores the need for healthcare profession-
als and public health policies to prioritize strategies that
specifically promote vigorous-intensity PA as a means
of enhancing overall PA levels in this population. This
is clinically important, as reduced PA is associated with

poorer health outcomes in women, sometimes to a greater extent than in men (Supporting reference 34).

In this manuscript, we focused on perceived PA barri-
ers, as a T1D-specific tool (BAPAD-1) is available to assess
them. However, the current literature on gender differ-
ences in barriers to PA (whether diabetes- or non-diabetes-
related) remains inconclusive, mostly due to a limited
number of studies and inconsistencies in study design.
Future studies using the BAPAD-1 questionnaire should
ensure that analyses specifically distinguish ratings that
genuinely indicate barriers to PA from those that reflect
the unlikelihood of an item being a barrier. Furthermore,
it would be important to combine semi-structured inter-
views with self-administered questionnaires or questions.
These interviews may help to understand the reasons why
an item is differently perceived as a barrier according to
gender and may also identify other barriers, which are
not included in the questionnaires. For example, Logan
et al. were able to detect ‘hormonal fluctuations affecting
glycaemia’ as a barrier specific to women.³⁸ Moreover,
the BAPAD-1 questionnaire was developed at a time
when CGM was not widely available and automated in-
sulin delivery systems did not exist, while new barriers
to PA related to the use of new technologies may emerge
(Supporting reference 62).

Ultimately, the interactions between barriers to PA and PA levels in pwT1D appear to be complex, and the role of gender in these interactions remains largely unexplored. Experiencing more hypoglycaemic episodes or rating higher ‘fear of hypoglycaemia’ as a barrier to PA does not necessarily translate into lower PA commitment in women, probably in contrast to men. It is therefore possible that lower habitual PA levels consistently observed in girls and women with T1D are driven more from social factors than by the heightened perception of glycaemic challenges related to PA. However, this assumption is based on a limited available literature and requires confirmation through future studies combining objective evaluation of habitual PA levels with evaluations of perceived barriers to PA in larger sample sizes. Objective methods (using movement trackers) could indeed be preferred for quantification of PA as subjective methods may imply overestimation, which may differ according to gender, as already reported outside the context of diabetes (Supporting references 63 and 64). Gathering these data will be essential for developing targeted strategies to promote PA participation in girls and women with T1D, ensuring that they can fully benefit from the positive effects of regular physical activity.

ACKNOWLEDGEMENTS

We would like to thank S. Platt (International Eyes) for
revising the English. E.L. was recruited as a postdoctoral
researcher thanks to a grant from Lille University through the 'Plan d'investissement France 2030' (I-SITE ULNE, International Chair WILL 'SPORT-1') and C.P. as a PhD student through a grant from Hauts-de-France Region and from IRCM (Montreal).

## FUNDING INFORMATION

This work was not supported by any specific grant from public, commercial or not-for-profit funding agencies.

## CONFLICT OF INTEREST STATEMENT

No potential conflicts of interest relevant to this article were reported.

## REFERENCES

1. Lukacs A, Mayer K, Juhasz E, Varga B, Fodor B, Barkai L. Reduced physical fitness in children and adolescents with type 1 diabetes. *Pediatr Diabetes*. 2012;13(5):432-437.

2. Sarnblad S, Ekelund U, Aman J. Physical activity and energy intake in adolescent girls with type 1 diabetes. *Diabet Med*. 2005;22(7):893-899.

3. Czenczek-Lewandowska E, Leszczak J, Baran J, et al. Levels of physical activity in children and adolescents with type 1 diabetes in relation to the healthy comparators and to the method of insulin therapy used. *Int J Environ Res Public Health*. 2019;16(18):3498. doi:10.3390/ijerph16183498

4. Sundberg F, Forsander G, Fasth A, Ekelund U. Children younger than 7 years with type 1 diabetes are less physically active than healthy controls. *Acta Paediatr*. 2012;101(11):1164-1169.

5. Murillo S, Brugnara L, Rios S, Ribas V, Servitja JM, Novials A. People with type 1 diabetes exhibit lower exercise capacity compared to a control population with similar physical activity levels. *Diabetes Res Clin Pract*. 2024;211:111655. doi:10.1016/j.diabres.2024.111655

6. Brazeau AS, Leroux C, Mircescu H, Rabasa-Lhoret R. Physical activity level and body composition among adults with type 1 diabetes. *Diabet Med*. 2012;29(11):e402-e408.

7. Thomson RL, Brown JD, Oakey H, et al. Dietary patterns during pregnancy and maternal and birth outcomes in women with type 1 diabetes: the environmental determinants of islet autoimmunity (ENDIA) study. *Diabetologia*. 2024;67(11):2420-2432. doi:10.1007/s00125-024-06259-5

8. Gutierrez Manzanedo JV, Carral San Laureano F, Garcia Dominguez G, Ayala Ortega C, Jimenez Carmona S, Aguilar Diosdado M. High prevalence of inactivity among young patients with type 1 diabetes in south Spain. *Nutr Hosp*. 2014;29(4):922-928. doi:10.3305/nh.2014.29.4.7225

9. McCarthy MM, Whittemore R, Grey M. Physical activity in adults with type 1 diabetes. *Diabetes Educ*. 2016;42(1):108-115. doi:10.1177/0145721715620021

10. Prevost MS, Rabasa-Lhoret R, Talbo MK, Yardley JE, Curry EG, Brazeau AS. Gender differences in strategies to prevent physical activity-related hypoglycemia in patients with type 1 diabetes: a BETTER study. *Diabetes Care*. 2022;45(3):e51-e53. doi:10.2337/dc21-1899

11. Plotnikoff RC, Taylor LM, Wilson PM, et al. Factors associated with physical activity in Canadian adults with diabetes.

Med Sci Sports Exerc. 2006;38(8):1526-1534. doi:10.1249/01.mss.0000228937.86539.95

12. Johansen RF, Caunt S, Heller S, et al. Factors influencing physical activity level in adults with type 1 diabetes: a cross-sectional study. *Can J Diabetes*. 2024;48(7):431-438. doi:10.1016/j.jcjd.2024.06.002

13. Gomez-Peralta F, Menendez E, Conde S, Conget I, Novials A, Sed, investigators; S. E. D. s. Physical activity patterns in type 1 diabetes in Spain: the SED1 study. *BMC Sports Sci Med Rehabil*. 2023;15(1):92. doi:10.1186/s13102-023-00695-3

14. Sander SE, Johansen RF, Caunt S, et al. A cross-sectional study on the impact of educational status on physical activity level in Danish and English adults with type 1 diabetes. *Can J Diabetes*. 2024;48(3):204-210.e1. doi:10.1016/j.jcjd.2024.01.002

15. Finn M, Sherlock M, Feehan S, Guinan EM, Moore KB. Adherence to physical activity recommendations and barriers to physical activity participation among adults with type 1 diabetes. *Ir J Med Sci*. 2022;191(4):1639-1646. doi:10.1007/s11845-021-02741-w

16. Brazeau AS, Mircescu H, Desjardins K, et al. The barriers to physical activity in type 1 diabetes (BAPAD-1) scale: predictive validity and reliability. *Diabetes Metab*. 2012;38(2):164-170.

17. McCarthy MM, Whittemore R, Gholson G, Grey M. Self-management of physical activity in adults with type 1 diabetes. *Appl Nurs Res*. 2017;35:18-23. doi:10.1016/j.apnr.2017.02.010

18. Al-Ozairi E, Irshad M, Al-Ozairi A, et al. Seasonal differences in physical activity, sedentary behaviour, and sleep patterns in people with type 1 diabetes in Kuwait. *Diabetes Metab Syndr*. 2024;18(6):103046. doi:10.1016/j.dsx.2024.103046

19. Herbst A, Kordonouri O, Schwab KO, Schmidt F, Holl RW. Impact of physical activity on cardiovascular risk factors in children with type 1 diabetes: a multicenter study of 23,251 patients. *Diabetes Care*. 2007;30(8):2098-2100.

20. Aman J, Skinner TC, de Beaufort CE, Swift PG, Aanstoot HJ, Cameron F. Associations between physical activity, sedentary behavior, and glycemic control in a large cohort of adolescents with type 1 diabetes: the Hvidoere study group on childhood diabetes. *Pediatr Diabetes*. 2009;10(4):234-239.

21. Overby NC, Margeirsdottir HD, Brunborg C, Anderssen SA, Andersen LF, Dahl-Jorgensen K. Physical activity and overweight in children and adolescents using intensified insulin treatment. *Pediatr Diabetes*. 2009;10(2):135-141.

22. Fainardi V, Scarabello C, Cangelosi A, et al. Physical activity and sedentary lifestyle in children with type 1 diabetes: a multicentre Italian study. *Acta Biomed*. 2011;82(2):124-131.

23. Beraki A, Magnuson A, Sarnblad S, Aman J, Samuelsson U. Increase in physical activity is associated with lower HbA1c levels in children and adolescents with type 1 diabetes: results from a cross-sectional study based on the Swedish pediatric diabetes quality registry (SWEDIABKIDS). *Diabetes Res Clin Pract*. 2014;105(1):119-125. doi:10.1016/j.diabres.2014.01.029

24. Valerio G, Spagnuolo MI, Lombardi F, Spadaro R, Siano M, Franzese A. Physical activity and sports participation in children and adolescents with type 1 diabetes mellitus. *Nutr Metab Cardiovasc Dis*. 2007;17(5):376-382.

25. Edmunds S, Roche D, Stratton G. Levels and patterns of physical activity in children and adolescents with type 1 diabetes and associated metabolic and physiologic health outcomes. *J Phys Act Health*. 2010;7(1):68-77.
26. O'Neill JR, Liese AD, McKeown RE, et al. Physical activity and self-concept: the SEARCH for diabetes in youth case control study. *Pediatr Exerc Sci.* 2012;24(4):577-588.

27. Matson RIB, Leary SD, Cooper AR, Thompson C, Narendran P, Andrews RC. Objective measurement of physical activity in adults with newly diagnosed type 1 diabetes and healthy individuals. *Front Public Health.* 2018;6:360. doi:10.3389/fpubh.2018.00360

28. Livny R, Said W, Shilo S, et al. Identifying sources of support and barriers to physical activity in pediatric type 1 diabetes. *Pediatr Diabetes.* 2020;21(1):128-134. doi:10.1111/pedi.12938

29. Bernardini AL, Vanelli M, Chiari G, et al. Adherence to physical activity in young people with type 1 diabetes. *Acta Biomed.* 2004;75(3):153-157.

30. Tilden DR, Noser AE, Jaser SS. Sedentary behavior and physical activity associated with psychosocial outcomes in adolescents with type 1 diabetes. *Pediatr Diabetes.* 2023;2023:1395466. doi:10.1155/2023/1395466

31. Marlow AL, King BR, Trost SG, Weaver N, Smart CE. Healthy weight and overweight adolescents with type 1 diabetes mellitus do not meet recommendations for daily physical activity and sleep. *Diabetes Res Clin Pract.* 2023;203:110879. doi:10.1016/j.diabres.2023.110879

32. Thomas N, Alder E, Leese GP. Barriers to physical activity in patients with diabetes. *Postgrad Med J.* 2004;80(943):287-291.

33. Moura BPD, Colombo BP, Miranda VPN, Caetano IT, Sasaki JE, Amorim PRDS. Sociodemographic factors associated with physical activity and sedentary behavior in Brazilian adults living with type 1 diabetes: a cross-sectional study. *Sao Paulo Med J.* 2025;143(3):e2024215. doi:10.1590/1516-3180.2024.0215. r1.27112024

34. Al Ozairi E, Irshad M, Alkandari J, et al. Association of device measured physical activity with liver fat and stiffness in people with type 1 diabetes. *Diabetes Obes Metab.* 2025;27(9):5302-5310. doi:10.1111/dom.16584

35. Mohammed J, Deda L, Clarson CL, Stein RI, Cuerden MS, Mahmud FH. Assessment of habitual physical activity in adolescents with type 1 diabetes. *Can J Diabetes.* 2014;38(4):250-255.

36. Ligtenberg PC, Blans M, Hoekstra JB, van der Tweel I, Erkelens DW. No effect of long-term physical activity on the glycemic control in type 1 diabetes patients: a cross-sectional study. *Neth J Med.* 1999;55(2):59-63.

37. Mavridis A, Viktorisson A, Reinholdsson M, Eliasson B, Abzhandadze T, Sunnerhagen KS. Physical activity trajectories and all-cause mortality in type 1 diabetes: a nationwide longitudinal study. *Diabetes Res Clin Pract.* 2024;212:111702. doi:10.1016/j.diabres.2024.111702

38. Logan JE, Prevost M, Brazeau AS, et al. The impact of gender on physical activity preferences and barriers in adults with type 1 diabetes: a qualitative study. *Can J Diabetes.* 2024;48:401-408. doi:10.1016/j.jcjd.2024.05.003

39. Lobelo F, Liese AD, Liu J, et al. Physical activity and electronic media use in the SEARCH for diabetes in youth case-control study. *Pediatrics.* 2010;125(6):e1364-e1371.

40. Waden J, Tikkanen H, Forsblom C, et al. Leisure time physical activity is associated with poor glycemic control in type 1 diabetic women: the FinnDiane study. *Diabetes Care.* 2005;28(4):777-782. doi:10.2337/diacare.28.4.777

41. Carral F, Gutierrez JV, Ayala Mdel C, Garcia G, Aguilar M. Intense physical activity is associated with better metabolic

control in patients with type 1 diabetes. *Diabetes Res Clin Pract.* 2013;101(1):45-49. doi:10.1016/j.diabres.2013.04.006

42. Miculis C, De Campos W, da Silva Boguszewski M. Correlation between glycemic control and physical activity level in adolescents and children with type 1 diabetes. *J Phys Act Health.* 2015;12:232-237.

43. Yardley JE, Li Z, Zaharieva DP, Riddell MC, Gal RL, Calhoun P. Sex differences in glycemia and self-management strategies for exercise in an active adults cohort with type 1 diabetes. *J Clin Endocrinol Metab.* 2024;110:2182-2192. doi:10.1210/clinem/dgae792

44. Keshawarz A, Piropato AR, Brown TL, et al. Lower objectively measured physical activity is linked with perceived risk of hypoglycemia in type 1 diabetes. *J Diabetes Complicat.* 2018;32(11):975-981. doi:10.1016/j.jdiacomp.2018.05.020

45. Brazeau AS, Rabasa-Lhoret R, Strychar I, Mircescu H. Barriers to physical activity among patients with type 1 diabetes. *Diabetes Care.* 2008;31(11):2108-2109.

46. Guédet C, Alexandre-Heymann L, Yardley JE, et al. Exploring perceived barriers to physical activity among individuals with type 1 diabetes in the era of new technologies: an analysis from the BETTER registry. *Diabetes Metab.* 2025;51(5):101677. doi:10.1016/j.diabet.2025.101677

47. Giblin S, Scully P, Dalton N, et al. Parent and child perceptions of physical activity with type 1 diabetes. *BMJ Open Diabetes Res Care.* 2022;10(6):e002977. doi:10.1136/bmjdrc-2022-002977

48. Huerta-Uribe N, Chueca-Guindulain MJ, Berrade-Zubiri S, Burillo-Sanchez E, Izquierdo M, Garcia-Hermoso A. Is fear of hypoglycemia a major barrier to an active lifestyle in children and adolescents with type 1 diabetes? The D inactive-1 study. *Scand J Med Sci Sports.* 2023;33(8):1431-1438. doi:10.1111/sms.14369

49. García-Hermoso A, Huerta-Uribe N, Hormazábal-Aguayo I, et al. Development and validation of a scale measuring perceived barriers to physical activity in Spanish for children and adolescents with type 1 diabetes: the physical activity barriers scale for pediatric type 1 diabetes (PABS-1) questionnaire. *Diabetes Res Clin Pract.* 2025;224:112223. doi:10.1016/j.diabres.2025.112223

50. Parent C, Lespagnol E, Berthoin S, et al. Barriers to physical activity in children and adults living with type 1 diabetes: a complex link with real-life glycemic excursions. *Can J Diabetes.* 2023;47(2):124-132. doi:10.1016/j.jcjd.2022.10.006

## SUPPORTING INFORMATION

Additional supporting information can be found online in the Supporting Information section at the end of this article.

**How to cite this article:** Heyman E, Peters TM, Lespagnol E, Parent C, Brazeau A-S, Yardley JE. Exploring gender differences in physical activity and related barriers in children and adults living with type 1 diabetes: A narrative review. *Diabet Med.* 2025;00:e70132. doi:10.1111/dme.70132