Baseline HbA1c Greater than 6.0% Linked to "Exponential" Increase in T2D Risk for Adolescents with Obesity

Among adolescents with overweight and obesity, the increased risk of type 2 diabetes (T2D) was “exponential” in those with a baseline HbA1c greater than 6% according to researchers from Kaiser Permanente in San Francisco, CA.

In a cohort of nearly 75 000 youth aged 10 to 17 years researchers found that compared with those who had a baseline HbA1c level less than 5.5%, those with HbA1c between 6.3% and 6.4% were 72 times more likely to develop T2D. The risk for T2D was 23-fold for those with HbA1c levels of 6.1% to 6.2% and 9-fold among those with HbA1c from 5.9% to 6.0%. Investigators observed that risk varied by age, sex, BMI, and race and ethnicity.

Writing in JAMA Network Open Pediatrics, Francis M. Hoe, MD, a pediatric endocrinologist with Kaiser Permanente in Northern California, and colleagues observed that the absolute risk for developing T2D in the study was low (~2.0%), particularly for participants with HbA1c at the low end of the prediabetes range (5.7% to 5.8%). The significant increase at levels of 6% or greater, however, make HbA1c a very strong predictor for T2D, the investigators wrote, and suggest that diabetes surveillance in adolescents should be “tailored to optimize identification among high-risk subgroups.”

Hoe and fellow authors observed that compared to peers with type 1 diabetes, the burden of cardiovascular risk and microvascular complications is much greater in adolescents with T2D who then "become young adults with much higher rates of cardiovascular disease and mortality.” As the prevalence of both prediabetes and obesity increase among children and adolescents, the urgency to intervene as early as possible increases, they asserted.

Their findings are based on a retrospective cohort study that used electronic health record data from Kaiser Permanente Northern California from January 2010 to December 2019. Eligible participants were aged 10 to 17 years, had a BMI at or above the 85th percentile, a baseline HbA1c of less than 6.5%, and did not have preexisting diabetes.

The final cohort for analysis numbered 74 552, was approximately half women, and had a mean age of 13.4 years, according to the study. Among them, 26.9% had overweight, 42.3% had moderate obesity, and 30.8% had severe obesity. The majority of participants were Hispanic (43.6%), followed by White (21.6%), Asian or Pacific Islander (17.6%), Black (11.1%), and other or unknown race or ethnicity (6.1%). Just slightly less than one-quarter (22.9%) had baseline HbA1c in the prediabetes range (5.7% to 6.4%).

FINDINGS

Hoe and colleagues followed the adolescents through 2019 (median 3.5 years). During the follow-up, 0.9% developed diabetes, with 89.7% diagnosed as having T2D. The reported overall incidence of T2D was 2.1 (95% CI, 1.9-2.3) per 1000 person-years, and the 5-year cumulative T2D incidence was 1.0% (95% CI, 0.9%-1.1%).

The authors found that the higher the baseline HbA1c, the higher the 5-year cumulative incidence of T2D, reported as follows:

• <5.5%: 0.3% (95% CI, 0.2%- 0.4%)
• 5.5% to 5.6%: 0.5% (95% CI, 0.4%-0.7%)
• 5.7% to 5.8%: 1.1% (95% CI, 0.8%-1.3%)
• 5.9% to 6.0%: 3.8% (3.2%-4.7%)
• 6.1% to 6.2%; 11.0% (95% CI, 8.9%-13.7%)
• 6.3% to 6.4%: 28.5% (95% CI, 21.9%-36.5%)

In line with these findings, Hoe and colleagues also reported increased risk of incident T2D with increasingly higher baseline HbA1c, reported as the following hazard ratios (HR) compared with the reference HbA1c of 5.5%:

• 5.5% to 5.6%: HR, 1.7 (95% CI, 1.3-2.2)
• 5.7% to 5.8%: 2.8 (95% CI, 2.1-3.6)
• 5.9% to 6.0%: 9.3 (95% CI, 7.2-12.1)
• 6.1% to 6.2%: 23.3 (95% CI, 17.4-31.3)
• 6.3% to 6.4%: 71.9 (95% CI, 51.1-101.1)

The investigators identified a number of independent risk factors in addition to HbA1c for developing T2D. In their multivariable analyses adjusted for age, sex, race and ethnicity, and BMI category, Hoe et al found adolescents with moderate or severe obesity were at greater risk for T2D than participants classified as having overweight. Girls were at greater risk than boys and participants aged 15 to 17 years had a higher risk than those aged 10 to 11 years). Compared with White adolescents, Asian and Pacific Islanders also were at higher risk.

In their conclusion, Hoe and colleagues reiterated the importance of the strong association between HbA1c and T2D in evaluating adolescents at risk but also emphasized the characteristics just mentioned above. “Hence, T2D surveillance in adolescents should be primarily based on HbA1c but should also consider these other risk factors when optimizing prevention strategies for those at highest risk. Research is needed to determine which interventions (eg, lifestyle intervention, pharmacotherapy, or other treatment) are most effective in preventing progression to T2D among those at highest risk.”

Source: Hoe FM, Darbinian JA, Greenspan LC, Lo JC. Hemoglobin A1c and type 2 diabetes incidence among adolescents with overweight and obesity. JAMA Netw Open Pediatrics. 2024;7(1):e2351322. doi:10.1001/jamanetworkopen.2023.51322