High-Risk Childhood Diabetes Could Be “Seen at A Glance”! Continuous Glucose Monitoring(CGM) Opens the Era of Precise Early Warning

Over the past 60 years, the prevalence of type 2 diabetes mellitus (T2DM) has been undergoing a subversive change—it is no longer an "exclusive disease" of the elderly, but has gradually and acceleratingly spread to young people! Data shows ^[1] that about 233 million people in China are affected by early-onset T2DM, and on average, 1 out of every 6 patients develops the disease in their young and middle-aged years. What is more alarming is that among the 15–39 age group, the growth rate of new cases of T2DM has reached three times the average level of all age groups, making it the fastest-growing group!

Furthermore, population screening studies have found ^[2-3] that children who are positive for multiple islet autoantibodies——stage 1 of type 1 diabetes mellitus(T1DM) ——have an extremely high risk of progressing to clinical T1DM(stage 3). However, the process from "immune abnormalities" to "clinical manifestation" is often insidious and complex. How to accurately predict the progression of the disease in the asymptomatic stage, seize the intervention window, and prevent the progression of diabetes in advance has long been a key problem perplexing clinicians...

The Lancet:Early-Onset T2DM is More Harmful! Clinical Practice Requires Early Intervention

This challenge exists not only in T1DM but also commonly in early-onset T2DM. Pathological mechanisms indicate that early impairment of β-cell function is the core link driving disease progression. Among adolescents and young adults, the rapid increase in early-onset T2DM exposes pancreatic islet β-cells to long-term and more prolonged high metabolic load at an earlier age, making functional impairment increasingly prominent. Studies have shown that the rate of β-cell failure in children and adolescents (<18 years old) is almost three times that of adult patients ^[4], with an annual functional decline of 20%–35%, compared to only 7%–11% in adults ^[5]. The same disease with faster progression suggests that clinical practice requires earlier intervention, close monitoring, and active management.

With the gradual increase of early-onset T2DM among young people worldwide, it has become a focus of clinical and public health attention. Recently, The Lancet published two consecutive reviews ^[7-8], focusing on early-onset T2DM, providing the latest evidence for understanding its driving factors, clinical risks, and long-term health impacts. Studies indicate that the incidence rate of early-onset T2DM is gradually increasing, and this trend is mainly driven by the rising obesity rate among young people.

Moreover, even with the same body mass index(BMI), Asians are more prone to the body composition characteristic of "more fat and less muscle" — their liver fat content can be about 30% higher, while their skeletal muscle mass is relatively insufficient. This difference in body composition significantly exacerbates insulin resistance, further increasing the risk of early-onset T2DM.

Compared to late-onset T2DM, early-onset T2DM poses greater risks:

• β-cell function declines more rapidly;
• Obesity-related insulin resistance is more severe;
• The risk of macrovascular and microvascular complications increases significantly;
• The utilization rate of medical resources is higher

In addition, patients with early-onset disease also face greater challenges in terms of reproductive health (such as during the periconceptional and postpartum periods), metabolic-associated fatty liver disease, mental health (including diabetes-related psychological distress, depression, and anxiety), and the risk of certain malignant tumors.

Figure:Characteristics of Complications in Early-Onset T2DM

Long-term exposure to high blood glucose and the cumulative risks brought by early diagnosis at a young age will interact with other cardiometabolic risk factors, further amplifying the risk of adverse effects of the disease. Therefore, for high-risk groups of early-onset T2DM (such as obese adolescents), screening should be initiated as early as possible, taking advantage of the intervention window before puberty, and combining with multidisciplinary team management, from lifestyle intervention to individualized treatment, to achieve early prevention and disease delay, and maximize the protection of future health.

CGM: An "Early Warning Radar" for Preventing Diabetes Progression

All the above evidence reminds us that among high-risk groups for early-onset diabetes, children and adolescents are often the "key nodes" in the progression of the disease, and it is particularly important to promptly identify children who are about to develop clinical diabetes! This is of great significance for early intervention, delaying the course of the disease, and formulating individualized management and prevention strategies.

Recently, a prospective cohort study published in Diabetes Care has provided us with vivid evidence ^[6]... The study recruited 91 children who were persistently positive for islet auto antibodies (stage 1 of T1DM) (with a median age of 11.5 years and 57% being female). By continuously wearing CGM, the changes in blood glucose and disease progression were tracked, with a median follow-up time of 6 months.

Inclusion Criteria:

• Aged 1-17 years;
• Persistent positive auto antibodies;
• Complete baseline CGM monitoring (data with less than 96 hours of valid data will not be included).

The study compared multiple CGM indicators between children who progressed to T1DM (stage 3) and those whose condition did not progress, in order to evaluate the best predictive indicators for the progression from stage 1 to stage 3 of T1DM in children.

Main Indicators:

• Average glucose;
• TAR: TA140 (>7.8mmol/L), TA160 (>8.9mmol/L), TA180 (>10mmol/L), TA200 (>11.1mmol/L);
• Area Under the Curve (AUC);
• Standard Deviation (SD), Coefficient of Variation (CV);
• Mean Amplitude of Glycemic Excursions (MAGE), Mean of Daily Differences (MODD);
• HbA1c as a traditional control indicator.

Research Results:

16 children (18%) progressed to T1DM (stage 3) during the follow-up period, with a median time of only 4.5 months. Compared with children who did not progress to T1DM (stage 3), all monitoring indicators of those who progressed were significantly higher:

• Higher average blood glucose;
• Greater blood glucose variability (SD, CV, MAGE);
• Higher proportion of TAR (TA140, TA160, TA180);
• Higher HbA1c but lower sensitivity;

Figure: Scatter Plots of Various CGM Indicators between Progressors and Non-Progressors of T1DM

ROC analysis showed that both the use of a single CGM monitoring index alone and the combination of multiple indices can efficiently predict disease progression.

Table 1. ROC Analysis for Predicting T1DM

Subsequently, the study conducted further analysis on the CGM indicators with good predictive performance (AUC ≥ 0.88), and found a key conclusion——in the CGM monitoring results:

• If the proportion of time a child's blood glucose level is >7.8mmol/L exceeds 10%, then the risk of progressing to diabetes (stage 3) within one year will be as high as 80%.
• In contrast, if the time during which a child's blood glucose is > 7.8 mmol/L accounts for ≤10%, the risk of progression within one year is only about 5%.

Figure. Evaluation of Diabetes Development through Various CGM Indicators

Studies clearly indicate that CGM metrics should serve as a core tool for continuous monitoring of diabetes in high-risk children, and can also be used as a potential criterion for enrollment in prevention trials. A time proportion (TA140) of children’s blood glucose exceeding 7.8 mmol/L greater than 10% may serve as a criterion for identifying high-risk children.

Compared with the traditional oral glucose tolerance test (OGTT), CGM can not only continuously and dynamically capture blood glucose changes, but also has a higher acceptance among children, who are more willing to cooperate with wearing it, enabling non-invasive and accurate blood glucose monitoring. This finding provides a practical tool and basis for clinical early identification of high-risk children, individualized intervention, and formulation of prevention strategies.

CGM——A Core Weapon in the Prevention and Control of Early-Onset Diabetes, Achieving Better Prognostic Outcomes!

To sum up, high-risk children face the dual challenges of rapid β-cell failure and accelerated disease progression. Traditional blood glucose detection methods struggle to achieve accurate early warning of disease progression. As a dynamic and continuous blood glucose tracking tool, CGM provides an "early warning radar" for early-onset diabetes. By correlating CGM data with β-cell function decline and insulin resistance in obese children, it provides a basis for screening high-risk groups.

In the future, promoting CGM screening for high-risk groups such as obese children and adolescents, and establishing multidisciplinary teams to carry out early intervention for affected populations may be an effective way to curb this public health crisis. Although early-onset diabetes is menacing, the combination of precise monitoring and scientific intervention can promptly "step on the brakes" to halt the progression of the disease, providing young diabetes patients with an opportunity to break through the predicament.

Reference：

[1]. Zhou YC, Liu JM, Zhao ZP, Zhou MG, Ng M. The national and provincial prevalence and non-fatal burdens of diabetes in China from 2005 to 2023 with projections of prevalence to 2050. Mil Med Res. 2025 Jun 2;12(1):28. doi: 10.1186/s40779-025-00615-1

[2]. 1. Ziegler AG, Rewers M, Simell O, et al. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA2013;309:2473–2479 2.

[3]. Insel RA, Dunne JL, Atkinson MA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Soc iety, and the American Diabetes Association. Diabetes Care 2015;38:1964–1974.

[4]. TODAY Study Group. Effects of metformin, metformin plus rosiglitazone, and metformin plus lifestyle on insulin sensitivity and β-cell function in TODAY. Diabetes Care 2013; 36: 1749–57

[5]. Kahn SE, Lachin JM, Zinman B, et al. Effects of rosiglitazone, glyburide, and metformin on β-cell function and insulin sensitivity in ADOPT. Diabetes 2011; 60: 1552–60.

[6]. Steck AK, Dong F, Geno Rasmussen C, et al. CGM Metrics Predict Imminent Progression to Type 1 Diabetes: Autoimmunity Screening for Kids (ASK) Study. Diabetes Care. 2022;45(2):365-371. doi:10.2337/dc21-0602.

[7]. Luk A, Wild SH, Jones S, Anjana RM, Hivert MF, McCaffrey J, Gregg EW, Misra S. Early-onset type 2 diabetes: the next major diabetes transition. Lancet. 2025 Jun 28;405(10497):2313-2326. doi: 10.1016/S0140-6736(25)00830-X. Epub 2025 Jun 23. Erratum in: Lancet. 2025 Oct 11;406(10512):1564. doi: 10.1016/S0140-6736(25)02057-4.

[8]. https://doi.org/10.1016/S0140-6736(25)01012-8