· Prediabetes in youth is strongly influenced by pubertal insulin resistance and often remits spontaneously.

· Risk factor–based screening is recommended, and weight gain predicts progression to type 2 diabetes mellitus.

· Pediatric-specific definitions and effective interventions for dysglycemia remain unmet needs.

Pediatric obesity is increasing annually worldwide and is associated with an elevated risk of glucose abnormalities, including dysglycemia (an intermediate stage of glucose dysregulation) and type 2 diabetes (T2DM). Both T2DM and obesity are also associated with other cardiovascular risk factors, such as dyslipidemia, hypertension, metabolic dysfunction–associated steatotic liver disease (formerly nonalcoholic fatty liver disease), and sleep disturbances [1]. Insulin resistance has been shown to be the primary pathophysiologic contributor to the development of those risk factors [2].

The SEARCH for Diabetes in Youth study estimated that the prevalence of T2DM in the United States will double or quadruple by 2050 [3]. In Korea, the prevalence of dysglycemia (prediabetes) among adolescents rose from 5.86% in 2007–2009 to 12.08% in 2016–2018, an increase of 106% over ten years [4]. Although prediabetes and T2DM are increasing remarkably in the pediatric population worldwide, the pathophysiology and progression of glucose dysregulation in youth are only beginning to be understood. For example, the definitions currently applied for dysglycemia, prediabetes, and diabetes in the pediatric population are the same as those used in adults, have been derived from outcome trials in populations older than 18 years [5,6] , and have not yet been validated for use in prepubertal, pubertal, and newly post-pubertal populations.

Importantly, differences between pediatric and adult populations in β‑cell function and insulin sensitivity have now been well demonstrated, and puberty has emerged as a critical factor in insulin resistance among adolescents, giving this population unique characteristics [7]. For this reason, questions have been raised about the wisdom of extrapolating adult definitions to youth and the potential need for alternative ways to predict the risk of diabetes and other complications associated with excess adiposity in pediatric patients [8].

The American Diabetes Association (ADA) criteria for diabetes are as follows: (1) random plasma glucose ≥ 11.1 mmol/L (200 mg/dL) in a patient with symptoms of hyperglycemia; (2) fasting plasma glucose (i.e., no caloric intake for at least 8 hours) ≥ 7.0 mmol/L (126 mg/dL); (3) 2‑h plasma glucose (2‑hour PG) ≥ 11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test (OGTT); or (4) a hemoglobin A1c (HbA1c) ≥ 6.5% using a method certified by the National Glycohemoglobin Standardization Program and standardized to the Diabetes Control and Complications Trial assay. If the clinical presentation does not provide unequivocal evidence of hyperglycemia, the diagnosis must be confirmed by an additional abnormal test result from the same sample or in two separate test samples. There has been some debate about using HbA1c to diagnose T2DM in youth [9,10]; however, both HbA1c and OGTT have been shown to perform equally well in predicting abnormal glucose profiles detected by continuous glucose monitoring in at‑risk youth [11], although the identified individuals differ slightly in features of their dysregulation.

In adults, prediabetes refers to an intermediate state of glucose dysregulation in which individuals have higher glucose concentrations than normal but do not meet the criteria for diabetes [12]. Within the definition of prediabetes are two specific abnormalities: impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), which is defined as an abnormal 2‑h PG in a 75 g OGTT. There are slight differences in the diagnostic criteria for prediabetes among the ADA [12], the International Expert Committee [13], and the World Health Organization [14]. Compared with people with normal glucose regulation, individuals with prediabetes have dysregulation due to a combination of hepatic insulin resistance, decreased peripheral glucose uptake, increased gluconeogenesis, and reduced hepatic glucose clearance. Individuals with IFG also have impaired β‑cell function, whereas delayed skeletal muscle glucose uptake and β‑cell dysfunction have been demonstrated in IGT [15] .

The ADA criteria for prediabetes in adults are as follows: (1) IFG — fasting glucose of 5.6–6.9 mmol/L (100–125 mg/dL); (2) IGT — 2‑hour PG in an OGTT of 7.8–11.0 mmol/L (140–199 mg/dL); or (3) the combination of IFG and IGT. In adult populations, all of those conditions are associated with an increased risk of progressing to diabetes [12]. In 2010, the ADA updated its criteria for using HbA1c in screening and diagnosis to include a definition for prediabetes [16]. It now defines prediabetes in adults as an HbA1c of 5.7%–6.4%; those with an HbA1c of 6.0%–6.5% have a 25%–50% risk of developing diabetes within five years.

When considering prediabetes and diabetes in the pediatric population, it is important to remember that the cut‑off values that define diabetes are based on longitudinal outcome studies in adults. Those studies demonstrated the relationship between hyperglycemia and the development of complications and thus selected thresholds for glucose or HbA1c at which the incidence of microvascular complications, primarily retinopathy, clearly accelerates. Similarly, the cutoff values that define prediabetes have been established based on data showing an increased risk for progression to diabetes, again derived from adult longitudinal studies. In clinical practice, the ADA applies those adult glycemic thresholds to children and adolescents when defining prediabetes. They include fasting plasma glucose concentrations of 100–125 mg/dL, a 2-hour PG level of 140–199 mg/dL during an OGTT, or an HbA1c value between 5.7% and 6.4%. Although those criteria are widely used for screening and diagnosis in youth, it should be noted that those cutoffs have not been validated against long-term outcomes in pediatric populations.

There is a substantial physiological reduction in insulin sensitivity during the rapid growth and development of puberty, likely related to alterations in growth hormone, insulin‑like growth factor 1, and sex steroids [17,18]. During this period, insulin sensitivity decreases by approximately 50% and is compensated by an approximate doubling of insulin secretion [17]. Individuals who have other risk factors, such as obesity, genetic predisposition, or medication use, might be unable to compensate adequately by increasing insulin secretion and can develop varying degrees of dysglycemia, including diabetes, during this period of pubertal insulin resistance. However, as insulin sensitivity improves with the completion of puberty, the demand for compensatory insulin secretion decreases. Because of this dynamic pattern, many adolescents who develop glucose dysregulation due to insufficient compensatory secretion regain normal glucose metabolism once the additional burden of puberty subsides. This high rate of normalization has a significant effect on the predictive value of intermediate elevations in glucose and, by extension, the concept of prediabetes in youth, underscoring the need for new ways to identify the risk of diabetes in this population [19].

Few available data address the risk factors for progression from prediabetes to T2DM in youth, although obesity and excess adipose tissue are clearly critical components of that risk [5]. In one large cohort study conducted at an inner‑city hospital pediatric clinic, a linear relationship was observed between increasing body mass index (BMI) and rising HbA1c across the cohort [20]. Among the 547 youth with baseline dysglycemia (age 14.5±2.2 years, 70% Hispanic), 4% of those with an HbA1c of 5.7%–5.9%, 8% with an HbA1c of 6.0%–6.4%, and 33% with an HbA1c > 6.5% were diagnosed with diabetes during follow‑up, with a median time to progression of 12–22 months. During follow-up, the starting HbA1c and changes in BMI were associated with outcomes, and stabilization of BMI was most strongly associated with improvement in dysglycemia. In a similar study of 552 youth with obesity and evidence of dysglycemia at the initial visit, 6.5% progressed to T2DM during the following 2.4±1.5 years [21]. Individuals who progressed had higher starting BMI, HbA1c, 2-hour glucose, and C‑peptide levels than those who did not progress. To address the current gap in knowledge about the unique risk factors for progression to diabetes among youth with obesity entering puberty, the National Institute of Diabetes, Digestive, and Kidney Diseases is sponsoring the DISCOVERY study, which is enrolling more than 3,000 youth with obesity early in puberty across 15 sites in the United States. This study is undertaking comprehensive, longitudinal evaluation and data collection to identify biomarkers of diabetes risk as participating individuals experience pubertal progression. When they are available, those data might enable the development of a youth-specific definition of prediabetes and improve the targeting of interventions to prevent disease progression.

Given the low prevalence of diabetes among asymptomatic youth, even those at high risk, no evidence supports general population screening, with the exception of certain populations with higher than usual prevalence [22-24]. The ADA and International Society for Pediatric and Adolescent Diabetes (ISPAD) recommend that screening for type 2 diabetes be considered in asymptomatic youth after the onset of puberty or after 10 years of age in those who are overweight (≥ 85th percentile) or obese (≥ 95th percentile) and have one or more of the following risk factors: (1) maternal diabetes or gestational diabetes during the child’s gestation (strongest risk); (2) family history of T2DM in a first‑ or second‑degree relative; (3) relevant genetic ancestry; or 4) signs or conditions associated with insulin resistance (e.g., polycystic ovary syndrome, hypertension, dyslipidemia, or being born small for gestational age). Testing should be repeated if clinical suspicion persists, when risk factors evolve, or every 2–3 years if their BMI increases or risk factors progress [12,25]. The screening criteria summarized in Table 1 are based on current recommendations from the ADA Standards of Care in Diabetes 2026 and the ISPAD Clinical Practice Consensus Guidelines 2024 [12,25].

General screening or clinical testing specifically to identify prediabetes is not currently recommended in youth because the best approach for reliably identifying individuals at high risk for clinically significant progression of dysglycemia has yet to be defined, and the use of adult definitions is questionable, given the high rate of normalization of pubertal dysglycemia without intervention. The proposed approach to screening, risk stratification, and follow-up monitoring of dysglycemia in at-risk youth is summarized in Fig. 1.

Relatively few clinical trials have explored treatments for youth with dysglycemia, and most of those few report only short-term outcomes. Small studies have examined the effects of multidisciplinary lifestyle modification, metformin, insulin sensitizers, and weight‑loss medications not commonly used in pediatric patients, all of which have shown modest effects.

Whereas prediabetes in adults has a strong physiological basis and an evidence base supporting its predictive value for the subsequent development of diabetes, several fundamental differences in glucose regulation during puberty challenge this concept and its associated criteria in youth. Studies are ongoing to better understand the trajectory of dysglycemia in youth and validate developmental risk factors. Currently, the available evidence supports a few basic principles: some degree of dysglycemia is common during adolescence, especially in those living with obesity; dysglycemia returns to normal without intervention in the majority of adolescents; more severe degrees of dysglycemia are more likely to progress to diabetes; continued weight gain is a predictor of progression to diabetes; no specific lifestyle or pharmacologic intervention is clearly effective at preventing progression to diabetes in youth with dysglycemia.

Until an improved understanding is achieved, guidelines for monitoring and management need to be seen as empiric and open to modification, and they should be individualized based on a clinician’s assessment of risk. An initial test of glycemic status at the onset of puberty is warranted for those at risk due to excess weight, birth history, or family history, and it should be supplemented by assessments of other markers of dysmetabolism (lipids, liver transaminases, blood pressure, and sleep). Subsequent testing should be determined by the initial results and changes in clinical status. Although specific lifestyle interventions have not yet been shown to slow the progression to diabetes, they remain highly beneficial for overall health in at-risk youth. However, evidence supporting pharmacological interventions is still lacking. Further research is essential to establish pediatric-specific criteria for dysglycemia and identify effective prevention strategies.