Obesity is a chronic and complex disease characterized by excess adiposity that affects an individual's overall health. The increase in obesity prevalence is observed in adults, children and adolescents. Obesity is a fundamental pathophysiological factor in the development of cardiovascular risk factors, including type 2 diabetes mellitus (T2DM).1 Most patients with T2DM have insulin resistance and insulin secretion dysfunction, where the increased demand for insulin action caused by resistance is not compensated by insulin secretion.2 The Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) is widely used to assess insulin resistance and has been shown to be valid in adolescents compared to the gold standard method.3 Glycated hemoglobin (HbA1c) is the standard test for assessing glucose control in diabetes and also for diagnostic purposes.4

Data from the third National Health and Nutrition Examination Survey (NHANES III) demonstrated that the prevalence of diabetes remains high, making it one of the most common non-communicable diseases with a significant impact on the population's health.5 The increase in prevalence has also occurred in the pediatric population: recent data from the United States suggest an incidence of approximately 5000 new cases of type 2 diabetes per year in adolescents.4 In Brazil, recent studies suggest that 3.3 % of adolescents aged 12–17 years have type 2 diabetes.6 In addition, according to another study based on the same database, 1/5 of adolescents in Brazil have elevated levels of glycated hemoglobin (Hb1Ac).7 Thus, obesity can lead to an increased prevalence of cardiovascular risk factors in children and adolescents, which tend to persist into adulthood and continuously accelerate the process of vascular damage.6

In this context, exploring anthropometric indices that correlate with obesity, via inexpensive, practical, and safe tools for cardiovascular risk assessment, can greatly contribute to the prevention and early treatment of obesity and T2DM.8 The main accepted diagnostic tool and frequently used predictor of morbidity and mortality for various chronic diseases, including T2DM, is body mass index (BMI). However, limitations of BMI, such as the lack of accuracy in assessing adiposity and the fact that it does not reflect the regional distribution of body fat, are questioned.9 A systematic review with meta-analysis showed that paradoxically, those individuals who were overweight had lower all-cause mortality than the normal BMI group.10 Thus, individuals within the same BMI range can have distinct metabolic characteristics, which can be partially attributed to the presence of central obesity and abdominal fat deposition.11 In this regard, other anthropometric measures, such as waist circumference (WC), have gained importance in clinical research since it has been suggested as a more accurate indicator of visceral fat than BMI in adults.8 However, this relationship has not yet been fully explored in children and adolescents. Recent research has shown that children who had increased BMI at age 15 were more likely to have an increased risk of insulin resistance and waist circumference at age 16. Therefore, incorporating WC measurements alongside BMI could be a valuable tool for screening cardiovascular risk factors, such as T2DM in adolescents, especially in those with a normal BMI.12,13

This study aims to investigate the association between the combinations of BMI and WC with insulin resistance and T2DM, in a representative sample of Brazilian adolescents.

Table 1 demonstrates the main characteristics of the study population. Among the participants, over half were female, with a mean age of 14.6 (± 14.6; 14.7) years. The Northeast region had the highest number of participants. Most participants reported having mixed skin color and attended public schools. In terms of the total number of participants, 73.3 % were classified with a normal BMI, 17.5 % and 9.2 % with overweight and obesity, respectively. Regarding WC, 12.6 % had an increased WC. The prevalence of T2DM was 3.3 %, with most of the adolescents already having a prior diagnosis before the data collection (90 %, 1136 out of 1250), and 25 % of adolescents had insulin resistance.

Table 2 shows the prevalence of prediabetes, T2DM, and elevated HOMA-IR according to combinations of BMI and WC. There was no difference in T2DM prevalence between the groups. However, adolescents with obesity showed a higher prevalence of prediabetes, regardless of WC categories. Regarding insulin resistance, the group with the highest prevalence was the obesity and increased WC group (69.9 %; 95 %CI: 65.4; 74.1).

Table 3 shows the association of combinations of BMI and WC with prediabetes and T2DM. When evaluating the results, the authors observed that the only groups with a significant association with prediabetes and T2DM were those with obesity defined by BMI – obesity with normal WC and obesity with elevated WC. The results remained similar after adjusting for covariates (region, sex, age, self-reported skin color, type of school, and socioeconomic level). Coefficients for the covariates included in the adjusted model are shown in Supplementary Table 1.

Table 4 shows the association between combinations of BMI and WC with HOMA-IR as a continuous variable. Except for the group with normal BMI and increased WC, all other combinations showed a significant association compared to the reference group, with the highest association observed in the adolescents with obesity and with increased WC, even after adjusting for covariates. The coefficients for the covariates included in the adjusted model are presented in Supplementary Table 2.

This study demonstrates that in a representative sample of Brazilian adolescents, increased WC without being combined with obesity diagnosed by high BMI is not associated with the likelihood of an adolescent having prediabetes or T2DM. However, WC provided additional information on BMI, particularly in the obesity range, ensuring greater accuracy in assessing obesity as a risk factor. Furthermore, when analyzing the relationship of the same anthropometric measures with insulin resistance assessed by HOMA-IR, a similar pattern was observed.

Different findings have been described in the literature regarding the relationship between WC and cardiovascular risk factors. In adults, WC is a reliable marker of abdominal obesity as demonstrated by direct measurement methods such as magnetic resonance imaging.20 Abdominal fat is considered a complex and highly active endocrine organ, which, through the release of hormones and cytokines, plays an important role in the inflammatory and metabolic processes. Thus, visceral obesity is usually considered a risk factor for T2DM, metabolic syndrome, and atherosclerosis, being associated with overall and cardiovascular mortality, independent of BMI. Among children and adolescents there is divergence on the most accurate anthropometric measure to determine central obesity and its association with cardiovascular risk factors3 One study in Iranian adolescents (CASPIAN III) reported that the association between combinations of overall and abdominal obesity differs depending on the evaluated outcome or risk factor.21 Pazin et al., demonstrated that increased WC is associated with high blood pressure in children with normal BMI.22 Another study was conducted using data from The Bogalusa Heart Study, including children aged 4–18 years, also found an association between abdominal obesity, assessed according to waist-to-hip ratio, and some cardiovascular risk factors (increased LDL cholesterol and triglycerides, decreased HDL cholesterol, and higher prevalence of metabolic syndrome). Among participants with central obesity but normal weight, 5.88 % had metabolic syndrome, while only 0.26 % of those with normal weight but without central obesity had metabolic syndrome.23 This was also observed among Chinese children and adolescents, where the presence of abdominal obesity was more strongly associated with metabolic syndrome than BMI.24

The present results, consistent with other studies, demonstrate that increased WC is related to HOMA-IR when overweight or obesity is present according to BMI.3 These findings support the pathophysiological role of abdominal fat in determining outcomes related to higher cardiovascular risk (collectively recognized as metabolic syndrome). However, the results presented here demonstrate that having only an increased WC, without this alteration being combined with high BMI, does not increase the likelihood of an adolescent having prediabetes or T2DM. One explanation for this result is the latency period between the onset of obesity and the development of T2DM. Obesity and increased WC are determinants of insulin resistance, but due to the disease's pathogenesis involving compensatory beta-cell function and subsequent increased insulin secretion, the time until beta-cell failure and the consequent development of T2DM may be delayed. As hypothesized by Lee, the increase in obesity during adolescence probably leads to a higher prevalence of T2DM in young adults.25

Another point to consider is the pathophysiology of youth T2DM. Although it shares characteristics with T2DM in adults, some unique features have been identified. As demonstrated by studies such as TODAY (The Treatment Options for Type 2 Diabetes in Adolescents and Youth) and RISE (Restoring Insulin Secretion), there is a relatively rapid deterioration of beta-cell function in adolescents compared to the slower decline described in adults with T2DM. In these studies, deficient beta-cell function, rather than insulin sensitivity, was a determining factor for loss of glycemic control.26 As puberty is associated with physiological changes and a consequent increase in insulin resistance, regardless of changes in body composition, the demand on the pancreas may be higher during adolescence.27 Alternatively, a higher degree of obesity and insulin resistance may be required to develop T2DM in this age group, when compared to adults, where the pancreas may be less healthy.27 Although the authors did not stratify the present sample by pubertal status, another study using the same database reported that few adolescents (only 0.5 % of the sample) self-classified themselves as prepubertal (Tanner stage 1), so it is possible to infer that most of this sample were in puberty.7

The use of WC may be limited due to changes in body composition caused by growth and pronounced development during this period of life. When comparing anthropometric measures and assessment of abdominal fat using imaging methods in adolescents, WC showed a better correlation with visceral adiposity than other anthropometric parameters.20 On the other hand, in Mexican adolescents with obesity, the waist-to-hip ratio was superior to WC in identifying cardiovascular risk factors.28 The same was suggested by Robert Ross and colleagues, stating that in children and adolescents in the growth phase, the waist-to-height ratio may be more useful for classifying abdominal obesity than just WC.29 Nevertheless, although measuring WC is relatively simple, limitations such as the absence of a consensus on the best method of measurement and the existence of different cutoff points varying by sex, age, and ethnicity undermine the utility of this measure.29

The present study has some limitations. The relatively small number of individuals in the normal BMI/increased WC and obesity BMI/normal WC categories (0.7 % and 1.5 % of the sample, respectively) may have led to inaccuracies in the analysis. Another point to consider is the possibility of different types of diabetes, such as Maturity-Onset Diabetes of the Young (MODY) and Type 1 Diabetes (T1DM), being present in the sample. Although the study controlled for this bias by excluding patients using insulin, it is possible that some participants without prior knowledge of the disease and diagnosed through laboratory measurements are individuals with type 1 diabetes. Distinguishing MODY from T2DM can be difficult and often requires additional information and tests that are not typically included in large-scale population studies. However, its prevalence is low (2–5 % of diabetes), and, therefore, likely did not interfere with the results.30 The main strength of the present study lies in the large, nationally representative multiethnic sample of adolescents in a developing country. Additionally, data collection, anthropometric measurements, and biochemical analyses were standardized and followed specific protocols.

In conclusion, increased WC without association with obesity diagnosed by high BMI is not related to the likelihood of an adolescent having insulin resistance or T2DM. However, when used in conjunction with BMI, particularly in the overweight and obesity range, increased WC ensures greater accuracy in the associations found. Therefore, the combination of BMI and WC is better for evaluating adolescents at higher risk of developing T2DM and should be used together in clinical practice.

Brazilian Department of Science and Technology at the Secretariat of Science and Technology and Strategic Inputs of the Ministry of Health and Funding Authority for Studies and Projects (FINEP) (grant: 01090421) and by the Brazilian National Counsel of Technological and Scientific Development (CNPq) (grants: 565037/2010-2, 405009/2012-7 and 457050/2013-6) and hospital research incentive fund for Clinics in Porto Alegre (FIPE – HCPA) (grant: 09.098) and Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES AUXPE/CAPES n. 2426/2023).