High prevalence of metabolic comorbidities in Asian children with type 1 diabetes and obesity
Article information
Abstract
Purpose
This study aims to examine the prevalence of overweight and obesity in children with type 1 diabetes mellitus (T1DM) in Hong Kong and to evaluate the association between obesity, glycemic control, and metabolic comorbidities.
Methods
A retrospective cross-sectional study was conducted from 2022–2023 at the Hong Kong Children’s Hospital, enrolling all children with T1DM. Anthropometric measurements and biochemical data were extracted from medical records, and prevalence rates of metabolic complications were compared.
Results
One hundred twenty-six children (41% male, 89% Asian) with a median age of 12.8 years were included. Of these, 17.5% were either overweight or obese. There were no significant differences in hemoglobin A1c values between the normal-weight and overweight/obesity groups, though the latter group required higher total daily insulin doses. Children with overweight/obesity had higher prevalence rates of hypertension (28.6% vs. 2.9%) and dyslipidemia (90.5% vs. 71.9%). They were also more likely to have hypertension (adjusted odds ratio [aOR], 18.48; 95% confidence interval [CI], 3.42–99.94) and hypertriglyceridemia (aOR, 7.71; 95% CI, 1.66–35.76). The overweight/obese group also exhibited significantly higher alanine aminotransferase levels (median, 18 IU/L vs. 14 IU/L), non–high-density lipoprotein cholesterol (HDL-C) levels (median, 3.3 mmol/L vs. 2.9 mmol/L), and triglyceride/HDL-C ratios (median, 1.09 vs. 0.52) and lower HDL-C levels (median, 1.4 mmol/L vs. 1.6 mmol/L). Among those with dyslipidemia, only 8% were started on lipid-lowering agents, while none of those with hypertension were started on antihypertensive agents.
Conclusions
Despite a lower prevalence of overweight/obesity in Asian children with T1DM compared to Western populations, metabolic comorbidities occur at an exceptionally high rate. Early interventions to tackle these modifiable cardiovascular risk factors are crucial to prevent long-term complications.
Highlights
· The prevalence of obesity in Asian children with type 1 diabetes is increasing.
· Asian children with type 1 diabetes develop more metabolic complications than their Western counterparts despite similar glycaemic control and BMI.
· Early identification and targeted intervention are essential to reduce long-term cardiovascular complications.
Introduction
The rising prevalence of childhood obesity has emerged as a pressing public health issue worldwide. Consistent with the global trend, data from the Centre for Health Protection in Hong Kong revealed a rise in the prevalence of overweight/obesity among local students, from 18.7% in 2010–2011 to 22.6% in 2020–2021, and the trend has been further exacerbated by the coronavirus disease 2019 pandemic [1]. Concurrently, the prevalence of type 1 diabetes mellitus (T1DM) in Hong Kong doubled from 2.2 to 4.3 per 100,000 people per year between 2008 and 2017 [2]. While obesity is historically associated with type 2 diabetes mellitus (T2DM), its escalating prevalence in children with T1DM is concerning. Studies from the United States and Europe reported that as much as one-third of children with T1DM were either overweight (22%–22.9%) or obese (10%–13.1%) [3,4]. T1DM independently increases the risk of serious cardiometabolic consequences, and obesity in these children may further elevate cardiovascular risks and impact mortality in young adulthood. Overweight/obesity in children with T1DM is influenced by multiple demographic and socioeconomic factors; in the Western world, for example, female gender, Hispanic/Latino ethnicity, older age at T1DM diagnosis, and lower parental education and household income have been linked to obesity in children with T1DM [3].
Studies on the prevalence of obesity among children with T1DM in Asia remain limited. Region-specific data about the characteristics and consequences of obesity, along with its contributing factors, in children with T1DM are also scarce. Hence, this study aimed to investigate the prevalence of obesity and cardiovascular risk factors among children with T1DM in Hong Kong and to determine the associations of sociodemographic and clinical factors on weight status.
Materials and methods
All children aged ≤18 years with T1DM who attended the Hong Kong Children's Hospital between 2022 and 2023 were included in this study. T1DM was diagnosed according to the International Society for Paediatric and Adolescent Diabetes (ISPAD) 2022 guidelines [5]. Children lacking height and weight data, those diagnosed with other types of diabetes, those with a disease duration of <6 months, and those with underlying genetic conditions or who were taking chronic medications that may impact weight were excluded.
Anthropometric, clinical, and biochemical data were obtained from electronic medical records. Information on sports participation, parental education levels, and frequency of blood glucose monitoring were retrospectively gathered from routine nursing assessment forms. Regular physical exercise was defined by ≥60 minutes of moderate-to-vigorous activity per day according to the World Health Organization's (WHO) recommendation [6]. Data on total caloric intake was extracted from the most recent dietitian assessment. Responses to the Pediatric Quality of Life Inventory (PedsQL), the generalized anxiety disorder-7 (GAD-7), and the Patient Health Questionnaire-9 (PHQ-9) were collected through standard screening questionnaires.
1. Anthropometric assessment
Body mass index (BMI) was calculated based on height and weight, while age- and sex-specific BMI z-scores were derived using the Hong Kong 2020 Growth references [7]. Overweight was defined as body weight >91st percentile for children aged 5–18 years and >98th percentile for children aged 0–60 months, which correspond to >1 standard deviation and >2 standard deviations from normal values on the WHO child growth reference chart, respectively. Obesity was defined as body weight >98th percentile for children aged 5–18 years and >99.6th percentile for children aged 0–60 months, which correspond to >2 standard deviations and >3 standard deviations from normal values on the WHO child growth reference chart, respectively [7]. This classification aligns with the WHO definitions of childhood overweight and obesity.
2. Clinical assessment
Hypertension was defined based on the guidelines of the American Academy of Pediatrics. For children <13 years of age, hypertension was identified when the blood pressure was in the ≥95th percentile for sex, age, and height. For those >13 years of age, it was defined as a blood pressure exceeding 130/80 mmHg [8].
3. Biochemical assessment
The average hemoglobin A1c (HbA1c) level was calculated from all the HbA1c measurements taken in the preceding 12 months. Plasma lipid profile was measured after an 8-hour fast. Hypertriglyceridemia was defined as a triglyceride (TG) level of ≥0.8 mmol/L for children <10 years of age or ≥1 mmol/L for those aged ≥10 years old. A low high-density lipoprotein cholesterol (HDL-C) was defined as an HDL-C level of ≤1.2 mmol/L, and a high low-density lipoprotein cholesterol (LDL-C) was defined as an LDL-C level of >2.6 mmol/L. In addition, a high non–HDL-C level was defined as a non–HDL-C level of ≥3.1 mmol/L. A TG/HDL-C ratio of ≥2.2 was also considered to be high.
High alanine transaminase (ALT) levels were defined by age- and sex-specific cutoffs from the local laboratory. Moderately increased albuminuria (formerly microalbuminuria) was defined as a spot urine albumin-to-creatinine ratio between 3 and 30 mg/mmol, while severely increased albuminuria (formerly macroalbuminuria) was defined as spot urine albumin-to-creatinine ratio of >30 mg/mmol.
4. Psychological and mental health assessments
PedsQL assesses health-related quality of life in children, with higher scores denoting better health-related quality of life [9]. Separately, GAD-7 is designed to evaluate the severity of generalized anxiety disorder, with a score of ≥10 points suggesting a need for further evaluation [10]. Finally, PHQ-9 is used to detect major depression, where scores of 5, 10, 15, and 20 points correspond to mild, moderate, moderately severe, and severe depression, respectively [11]. These questionnaires were routinely completed annually by all patients and/or their caretakers as part of our standard assessment.
5. Statistical analyses
Data were analyzed using IBM SPSS Statistics ver. 27.0 (IBM Co., USA). Children who were overweight or obese were categorized as a group and compared to normal-weight children. Continuous variables were expressed using mean and standard deviation values when normally distributed, while medians and interquartile ranges were used for nonnormally distributed data. The Mann-Whitney U-test was used to analyze continuous variables. Categorical data were expressed using absolute numbers or proportions and compared using Fisher exact test.
Univariable odds ratios (ORs) were used to evaluate the association between each diabetes-related comorbidity and overweight/obesity, as well as other patient characteristics. Multiple logistic regression analysis was performed using a backward stepwise regression approach, incorporating all the variables with a statistically significant Phi coefficient. P<0.05 was considered indicative of statistical significance.
6. Ethical statement
The study protocol was approved by the Hospital Authority Clinical Research Ethics Committee and Central Institutional Review Board (PAED-2024-028) on April 29, 2024. The study was conducted in accordance with the Declaration of Helsinki.
Results
A total of 126 children with T1DM (41% male; 89% Asian and 11% Caucasian) were included. The median age was 12.8 (interquartile range [IQR], 10.1–16.6) years, and the median disease duration was 4 (IQR, 1.9–8.0) years. Further, the median HbA1c level was 7.6% (IQR, 6.8%–8.1%). Clinical characteristics of the studied children are summarized in Table 1. Among them, 17.5% were either overweight (11.9%) or obese (5.6%). A greater prevalence of overweight/obesity was observed among the older age group (6.9% in children <10 years, 18.2% in those 10–14 years, 22.7% in those ≥15 years), with an age of >13 years being significantly associated with overweight/obesity (OR, 2.7; 95% confidence interval [CI], 1.02–7.18; P<0.05). Parents of children who were overweight/obese were reported to have lower levels of education (40.9% of these parents received tertiary education or above vs. 52.9% of parents of normal-weight children, P=0.35). There were no significant differences in gender, ethnicity, age of disease onset, disease duration, or total caloric intake per day between the group with normal weights versus the overweight/obese group.
Baseline demographics of children included in the study according to weight status
Data on disease control and management in the 2 groups of children are summarized in Table 2. The majority of children in both groups (72.7% vs. 78.6%) used continuous glucose monitoring on a regular basis. They also had similar HbA1c levels (7.6% vs. 7.6%, P=0.56). Children who were overweight/obese required a higher total daily dose of insulin (median [IQR], 52 [41.3–70.8] vs. 39 [25.4–55] units/day; P<0.05). In addition, a greater proportion of the overweight/obese children were prescribed oral antidiabetic agents (18.2% vs. 0%, P<0.05). Though statistically insignificant, fewer overweight/obese children reported regular participation in sports compared to those with normal BMIs (33.3% vs. 56.1%, P=0.09).
Disease control and diabetes management according to BMI status
Concerning cardiovascular health, higher prevalence rates of hypertension (28.6% vs. 2.9%, P<0.05) and dyslipidemia (90.5% vs. 71.9%, P<0.05) were observed in the overweight/obese children. Specifically, these children had higher triglyceride levels (median [IQR], 1.2 [0.9–1.7] mmol/L vs. 0.8 [0.6–1.1] mmol/L; P<0.05), lower HDL-C levels (median [IQR], 1.4 [1.2–1.7] mmol/L vs. 1.6 [1.4–2] mmol/L; P<0.05), and higher non–HDL-C levels (median [IQR], 3.3 [2.8–3.7] mmol/L vs. 2.9 [2.5–3.3] mmol/L; P<0.05). They also had higher TG/HDL-C ratios (median [IQR], 1.09 [IQR, 0.64–1.32] vs. 0.52 [IQR, 0.39–0.77]; P<0.05). Among those with dyslipidemia, only 8% were started on lipid-lowering agents, while none of those with hypertension were started on antihypertensive agents (Table 3).
Complications of children according to BMI status
Additionally, overweight/obese children had significantly higher ALT levels (median [IQR], 18 [15–30] IU/L vs. 14 [10–19] IU/L; P<0.05), and a greater proportion of these children also had elevated ALT levels (19% vs. 1.1%, P<0.05). Among those with elevated ALT levels, 1 patient was diagnosed with metabolic dysfunction-associated liver disease (MASLD) during the study period via ultrasound. The prevalence of other metabolic comorbidities, including albuminuria, retinopathy, neuropathy, polycystic ovarian syndrome, and obstructive sleep apnea, were similar between the 2 groups.
In the multivariate analysis, overweight/obese children had significantly increased odds of hypertriglyceridemia (adjusted OR [aOR], 4.54; 95% CI, 1.37–14.99; P<0.05) and hypertension (aOR, 18.48; 95% CI, 3.42–99.94; P<0.05). More frequent blood glucose monitoring (≥4 times per day) or the use of a continuous glucose monitoring system lowered the odds of having hypertriglyceridemia (aOR, 0.19; 95% CI, 0.04–0.96; P<0.05) and high non–HDL-C levels (aOR, 0.31; 95% CI, 0.12–0.82; P<0.05). Regular participation in sports also lowered the odds of having high non–HDL-C levels (aOR, 0.32; 95% CI, 0.13–0.75; P<0.05). ORs and aORs for the development of metabolic comorbidities are presented in Table 4.
Univariate and multivariate analysis with adjusted odd ratios for metabolic complications associated with obesity
Discussion
In this study consisting of primarily Asian children with T1DM, the prevalence of overweight/obesity was 17.5%. Notably, this prevalence is slightly lower than that of our local pediatric population [1]. Our findings align with reports from Japan and Malaysia, which documented prevalence rates of overweight/obesity of 17.2% and 17.5%, respectively, in people with T1DM [12,13]. A summary of the literature on the prevalence of overweight/obesity in children with T1DM in various populations is presented in Table 5. Compared to the Western population studied in the SWEET Registry or in the United States, our prevalence of obesity in children with T1DM remains low [3,14]. The observed differences may be attributed to the higher overall prevalence of pediatric obesity in Western countries. The prevalence of pediatric overweight/obesity in the general population ranges from 17%–27% in Japan, while a similar prevalence of 25.9 % was reported in Malaysia [15,16]. In contrast, up to 34.5 % of children in the United States have been classified as obese, highlighting a stark contrast with Asian countries [3]. This could be attributed to various factors, including different dietary habits, sedentary lifestyles, and socioeconomic influences in Western populations. Nevertheless, despite the lower prevalence of overweight/obesity in Asians, ample studies have demonstrated their higher levels of visceral adiposity at comparable BMIs or waist circumferences relative to Caucasians. As increased visceral adiposity is strongly linked to insulin resistance and cardiometabolic risks, Asian children with T1DM might be at heightened risk of cardiovascular events at lower BMIs [17]. Our study also supports this notion and recorded a much higher rate of metabolic comorbidities compared to Western populations despite an overall healthier weight status [3,14]. Findings from our study should encourage early identification of weight problems in Asian children with T1DM such that early interventions can be initiated.
Summary of recent studies on prevalence of overweight/obesity and metabolic complications in children with type 1 diabetes mellitus
Our study identified higher prevalence rates of hypertension and dyslipidemia in overweight/obese children and T1DM compared to those with normal weights, consistent with previous literature. A study in the United States similarly reported a 3.5 times greater likelihood of hypertension among individuals with obesity [18]. In recent years, higher systolic blood pressure in childhood has been shown to predict atherosclerosis in adulthood, as reflected by an elevated carotid intima media thickness (cIMT) [19]. A study by the American Heart Association also further demonstrated that the risk of atherosclerosis is diminished if blood pressure normalizes by adulthood. The pathophysiological link between increased BMI, hypertension, and cardiovascular risk is well-established in the general population and appears relevant to individuals with T1DM [20,21]. The fact that none of our children with hypertension were treated with antihypertensive medications was concerning. To lessen the risk of future coronary artery diseases, and stroke, more vigilant identification and intensive treatment of hypertension are essential in this group of at-risk youth.
Despite having a lower rate of obesity compared to the Western populations, our group had an exceptionally high prevalence of dyslipidemia (90.5%), exceeding that reported in Western countries [22]. This finding concurs with the understanding that, despite lower BMI values, Asians tend to exhibit higher levels of visceral adiposity and metabolic risk [17]. This is particularly concerning in Asian children with T1DM, especially among those with suboptimal diabetes control. Chronic hyperglycemia exacerbates dyslipidemia associated with obesity by glycosylating LDL particles, which in turn reduces their recognition by LDL receptors and impairs their uptake and degradation. This modification also makes glycated LDL more easily recognized by macrophages, leading to increased foam cell formation through non-specific scavenger receptors [23]. Thus, dyslipidemia in the context of T1DM significantly increases the risk of cardiovascular events to a much greater extent than the risk conferred by simple obesity alone. Besides, it has been shown that elevated triglyceride levels compound the already increased risk of retinopathy and nephropathy in T1DM, resulting in the development of these complications at even younger ages [24]. Heightened TG/HDL ratios in overweight/obese children were also recorded in our study. Following a recent investigation, TG/HDL ratios of ≥2.2 were associated with cardiometabolic risk factors, preclinical signs of liver steatosis, increased cIMT values, and concentric left ventricular hypertrophy [25]. Similar to hypertension, dyslipidemia was undertreated in our children. These results underscored the need for a more proactive approach in managing this cardiovascular risk factor to alleviate risk of end-organ damage in the future.
Our study also highlighted an increase in ALT levels among the overweight/obese children, potentially indicating MASLD [26]. While MASLD has traditionally been associated with T2DM, recent studies showed that patients with T1DM and obesity were also at increased risk of developing liver changes. A systematic review by de Vries et al. [27] reported a pooled MASLD prevalence of 19.3% among patients with T1DM, with elevated ALT levels found in 10% of cases. There is currently no recommendations on screening for MASLD under the ISPAD guidelines, meaning that the condition might be underdiagnosed [28]. Although there is a lack of data on liver-specific mortality and morbidity in patients with T1DM and MASLD, MASLD can progress from simple steatosis and nonalcoholic steatohepatitis to cirrhosis or even hepatocellular carcinoma. With the increasing prevalence of obesity among children with T1DM, periodic surveillance of liver function tests to identify early MASLD might be warranted. Further diagnostic investigations, such as ultrasound, FibroScan, or liver biopsy, should be considered in those with abnormal blood test results.
Our study showed that overweight/obese children required higher total daily insulin doses. Insulin imposes an anabolic effect on our body and promotes weight gain, creating a vicious cycle for people with obesity. Real-world data in an international study involving 17 countries also demonstrated the link to greater weight gain in children treated with higher insulin doses [29]. Similar findings were reported in the Diabetes Control and Complication Trial, which showed that intensive insulin therapy increased the mean adjusted risk of overweight by 33% [30]. There are a few proposed mechanisms behind this. With improved glycemic control from intensive insulin therapy, blood glucose levels fall below the renal threshold and trigger energy conservation from the ingested calories. Overtreating hypoglycemia with the consumption of excess calories also causes weight gain [29]. Even further, subcutaneously administered insulin directly enters the systemic circulation, bypassing hepatic metabolism and contributing to hyperinsulinemia and fat accumulation in peripheral tissues [31,32]. Hence, the use of high doses of insulin in overweight/obese children not only results in untoward weight gain but may further worsen insulin resistance, contribute to increased adiposity, and ultimately increase the risk of cardiovascular complications.
To tackle coexisting insulin resistance and promote weight loss, 18.2% of our overweight/obese children with T1DM were treated with adjunctive oral antidiabetic drugs, with the most common agent being metformin. Recent trials on the use of oral antidiabetic drugs in children with T1DM have demonstrated benefits in weight and glycemic control as well as reductions in insulin requirements. The EMERALD study (Effects of Metformin on Cardiovascular Function in Adolescents With T1DM), a randomized controlled trial investigating the role of metformin in people with T1DM, showed that the use of metformin improved insulin sensitivity, reduced BMI and fat mass, and enhanced vascular health in adolescents [33]. Beyond metformin, there has been increasing evidence compiled on the use of glucagon-like peptide-1 (GLP-1) receptor agonists as add-on therapy in children with T1DM and obesity. Evidence for these medications in adults with T1DM has shown a reduction in total insulin dose, as well as improvements in body weight and glycemic control [34]. As of now, liraglutide is only approved for pediatric patients with T2DM and/or obesity [35]. With growing research in children suggesting the potential benefits in T1DM, this class of medication may be considered as adjunctive therapy in the future. However, it must be emphasized that both metformin and GLP-1 receptor agonists are currently used off-label in children with T1DM, and further randomized controlled trials to establish their efficacy and safety in this group are warranted.
Apart from pharmacological treatment, exercise is a cornerstone for weight control in children with T1DM [36]. As in many developed countries in Asia, the majority of school-aged children in Hong Kong fail to meet ISPAD and WHO exercise recommendations due to tight academic schedules, contributing to excess weight gain [37]. This also held true for our studied population with T1DM, where a lack of participation in exercise was observed among the overweight/obese children.
In addition to the well-known benefits of exercise on body weight, our study demonstrated that regular exercise significantly reduced the odds of developing elevated non–HDL-C levels. A large multinational study from North America, Europe, and Australia established a strong association between non–HDL-C levels and long-term cardiovascular disease risk, with early reductions in non–HDL-C levels significantly lowering the lifetime risk of complications [38]. Hence, the benefit of exercise goes beyond maintaining a healthy weight status and should be promoted as a strategy to mitigate risk of future cardiometabolic consequences.
With this, promoting physical activity during regular medical consultations in the diabetes clinic is crucial. Healthcare teams should routinely discuss insulin adjustments and nutritional strategies with families to alleviate concerns about exercise-induced hypoglycemia. This approach facilitates the safe incorporation of physical activity into diabetes management. By better addressing modifiable risk factors, we hope to effectively prevent dyslipidemia and reduce the risk of subsequent adverse cardiovascular events.
Finally, our study revealed higher PHQ-9 scores among overweight/obese children, though the difference between groups was not statistically significant. Previous research has shown that childhood obesity is associated with psychiatric comorbidities, including depression, anxiety, and eating disorders [39]. On the other hand, a meta-analysis suggested that the prevalence of depressive symptoms in children with T1DM was as high as 30%, regardless of their weight status [40]. However, available data regarding psychiatric comorbidities in children with both T1DM and overweight/obesity are limited. Given the high psychological burden of both conditions, there is imminent need to conduct further research focusing on the mental health of children with T1DM who are overweight/obese.
Our study is particularly noteworthy due to several strengths. It is one of the few studies in Asia that examines the prevalence of overweight/obesity in children with T1DM. Additionally, it is the only study assessing comorbidities specifically among children with both T1DM and obesity in Asia, revealing possibly a more pronounced impact of increased adiposity on the development of metabolic complications in Asian children. Moreover, our routine clinical pathway incorporates assessments of exercise habits and mental health questionnaires, enabling us to explore the relationship between weight status and these factors.
However, our study has several limitations that warrant consideration. The sample size was relatively small. Some data were self-reported by patients and parents, which may have introduced recall bias and resulted in missing or inaccurate information. The cross-sectional and retrospective design of this study also limits our ability to establish causal relationships between overweight/obesity and metabolic complications. We also conducted abdominal ultrasound imaging in only a limited number of children, which may have contributed to an underdiagnosis of MASLD. Notably, surveillance with regard to the risk of MASLD is currently not included in the ISPAD guidelines. Given the rising prevalence of obesity, there is a pressing need for clearer guidance on monitoring this vulnerable population. Finally, measurements of waist circumference and waist-to-height ratio were not performed in our study. The inclusion of these indexes may complement BMI to ensure a better assessment of adiposity of children, which is then linked to the risk of developing cardiometabolic disorders.
In conclusion, our study demonstrated a much lower prevalence of overweight/obesity but a substantially higher rate of metabolic comorbidities in Asian children with T1DM. This underscores the need for early interventions to tackle obesity, a critical yet modifiable factor in the development of cardiometabolic complications, especially in the Asian population. Implementing targeted strategies for weight management, promoting physical activity, and ensuring regular monitoring of key metabolic parameters are vital for reducing the long-term risks associated with obesity in this population. Follow-up studies are warranted to investigate the potential factors that contribute to overweight/obesity in Asian children with T1DM. Addressing these modifiable risk factors might prevent the progression of cardiovascular complications and ultimately enhance overall health outcomes for children with T1DM.
Notes
Conflicts of interest
No potential conflict of interest relevant to this article was reported.
Funding
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Data availability
The data that support the findings of this study can be provided by the corresponding author upon reasonable request.
Author contribution
Conceptualization: JKYW, SWYP, GSWP, JYJT; Data curation: JKYW, SWYP, JYJT; Formal analysis: JKYW, SWYP, JYJT; Methodology: JKYW, GSWP, JYJT; Project administration: JKYW, SWYP, GSWP, JYJT; Visualization: JKYW, GSWP; Writing - original draft: JKYW; Writing - review & editing: JKYW, SWYP, GSWP, JYJT