A1c level strongly predicts the risk of developing type 2 diabetes among adolescents with overweight or obesity, new data suggested.
In a large California healthcare database over a 10-year period, the incidence of type 2 diabetes was relatively low overall among adolescents with overweight and obesity. However, the risk increased with baseline A1c levels above 6.0% as well as in those with more severe obesity, women, and Asian or Pacific Islanders.
The new findings were published online on January 17, 2024, in JAMA Network Open by pediatric endocrinologist Francis M. Hoe, MD, of Kaiser Permanente Roseville Medical Center, Roseville, California, and colleagues.
Previous studies have examined the incidence of type 2 diabetes among all youth, regardless of weight class. This is one of the first large population studies to examine the incidence and risk for type 2 diabetes by incremental level of A1c in a racially and ethnically diverse group of youth with overweight and obesity, Hoe told Medscape Medical News in an interview.
“This study was only possible to do because Kaiser Permanente Northern California has nearly 1 million pediatric members. The biggest thing we learned is that risk for type 2 diabetes is low in overweight and obese youth, especially those with an HbA1c less than 5.9%,” he said.
Asked to comment, Megan Moriarty Kelsey, MD, Professor of Pediatrics and Medical Director of Lifestyle Medicine and of Adolescent Bariatric Surgery at the Children’s Hospital Colorado, Aurora, told Medscape Medical News, “This is the largest and cleanest data set used to assess HbA1c and obesity as predictors of incident diabetes, with an advantage of being in a system that provides comprehensive care and with HbA1cs from a central lab.”
And, she added that the study also, “suggests that perhaps the threshold for diagnosis of prediabetes should be higher in youth, maybe 5.9%.”
Zeroing in on Those at Greatest Risk for Type 2 Diabetes
Currently, the American Diabetes Association (ADA) recommends screening for type 2 diabetes in adolescents with overweight (body mass index [BMI], 85th percentile or greater) or obesity (≥ 95th) who have at least one additional risk factor, including family history of type 2 diabetes and Native American, Black, or Hispanic ethnicity. About one in four US adolescents qualify by those criteria, the authors noted in the paper.
And, as for adults, ADA recommends subsequent annual diabetes screening in youth identified as having “prediabetes,” that is, a A1c level between 5.7% and 6.5%.
The new study confirmed that adolescents with A1c in the upper end of the prediabetes range were at a greater risk for type 2 diabetes. But those individuals were the minority. Adolescents with overweight/obesity who had baseline A1c levels in the lower end of the prediabetes range, 5.7%-5.8%, accounted for two thirds of those with prediabetes in the study population and had a very low incidence of type 2 diabetes compared with those with higher A1c levels.
“Specifically, we found an annual type 2 diabetes incidence of 0.2% for HbA1c of 5.7%-5.8%, which is much lower than adults. These adolescents will likely benefit from lifestyle intervention. But because their risk of developing type 2 diabetes is lower, they probably don’t need to be screened annually, as currently recommended by the ADA,” Hoe said.
Similarly, he added, “since obesity severity was associated with a higher risk for type 2 diabetes, increases in BMI percentile should also prompt consideration of repeat diabetes screening.”
Large Database Allows for Detailed Findings
The study population was 74,552 adolescents aged 10-17 years with overweight or obesity, of whom 49.4% were male, 64.6% were younger than 15 years, and 73.1% had obesity. Only 21.6% were White, while 43.6% were Hispanic, 11.1% Black, and 17.6% Asian or Pacific Islander.
Nearly a quarter, 22.9%, had baseline A1c in the prediabetes range of 5.7%-6.4%. Mean A1c rose with BMI category from overweight to moderate to severe obesity (P < .001 for each comparison). Baseline A1c was highest (5.53%) in Black adolescents and lowest in White teens (5.38%), also significant differences by group (P <.001).
Of the total 698 who developed diabetes during the follow-up, 89.7% were classified as having type 2 diabetes, with a median 3.8 years from baseline to diagnosis.
The overall incidence rate of type 2 diabetes during the follow-up was 2.1 per 1000 person-years. As the baseline A1c rose from less than 5.5% to 6.0%, from 6.1% to 6.2%, and from 6.3% to 6.4%, those incidence rates were 0.8, 8.1, 21.8, and 68.9 per 1000 person-years, respectively.
In a multivariate analysis, compared to baseline A1c below 5.5%, increased risk was ninefold for A1c 5.9%-6.0%, 23-fold for 6.1%-6.2%, and 72-fold for 6.3%-6.4%.
The incidence rates were higher in female than in male adolescents (2.4 vs 1.8 per 1000 person-years) and increased by BMI category from 0.6 to 1.3 to 4.3 for those with overweight, moderate obesity, and severe obesity, respectively.
Type 2 diabetes incidence per 1000 person-years also varied by race and ethnicity, ranging from 1.3 for White adolescents to 3.0 for Asian or Pacific Islander adolescence.
Kelsey pointed out that “When you put all the risk factors together, Hispanic ethnicity and Black race do not independently predict diabetes, even though diabetes is more common in these populations. This means that those populations are just more likely to have the other risk factors and may not be ‘inherently predisposed’ to diabetes.”
In addition, she noted that the proportion with elevation of A1c was highest in the 12- to 13-year-old age group. “Those are cross-sectional data. However, they suggest that there may be transient elevations in HbA1c during puberty in a subset of individuals. It will be important to tease out differences between ‘regressors’ and ‘progressors’ in terms of change in A1c over time. This means that other risk factors may be beneficial for diabetes prediction in these populations.”
Hoe told Medscape Medical News, “We plan on further exploring the effect of the weight and BMI change over time and how that may affect type 2 diabetes risk.”
January 17, 2024 — Editor’s note: This article has been updated to include an interview with an independent commentator.
This study was supported by a grant from the Kaiser Permanente Northern California Community Health program. Hoe and his coauthors had no further disclosures. Kelsey is a site investigator for clinical trials related to obesity (sponsored by Rhythm Pharmaceuticals) and type 2 diabetes (Eli Lilly).
Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape Medical News, with other work appearing in the Washington Post, NPR’s Shots blog, and Diabetes Forecast magazine. She is on X (formerly known as Twitter): @MiriamETucker.