High HbA1c, glucose variability predict comorbidity risk in youth-onset type 2 diabetes
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Young people with youth-onset type 2 diabetes are more likely to have comorbidities if they have a higher HbA1c and greater glucose variability after diagnosis, according to findings from the TODAY study.
“We provide the first evidence, to our knowledge, of a relationship between patterns of glycemic control with diabetic complications over a period of 10 years in a well-characterized sample of individuals with youth-onset type 2 diabetes,” Laure El Ghormli, MS, senior research scientist at the George Washington University Biostatistics Center, and colleagues wrote in a study published in Diabetes Care. “Over 10 years of study participation, the uncontrolled diabetes group had a high prevalence for all complications and comorbidities measured, particularly for nephropathy, dyslipidemia, neuropathy and progressive retinopathy. Maintaining glycemic control over the first 4 years of the study was protective against these conditions at 10 years.”
Researchers analyzed data from 457 participants in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. The cohort included youths diagnosed with type 2 diabetes at younger than 18 years and a diabetes duration of less than 2 years at enrollment. The analysis included only participants with a minimum of 10 years of follow-up.
Participants were grouped according to glycemic control: stable, with HbA1c not 8% or higher for 6 consecutive months and less than 0.5% change in HbA1c from baseline to 4 years; rising, with HbA1c not 8% or higher for 6 consecutive months but at least 0.5% rise in HbA1c at 4 years; uncontrolled, with HbA1c greater than 8% for 6 straight months. Fasting glucose coefficient of variation was calculated as the ratio of the standard deviation to the mean of fasting glucose concentrations, with a higher percentage dictating higher glucose variability.
Stable HbA1c linked to lower comorbidity prevalence
Of the study cohort, 32.4% were in the stable HbA1c group, 17.4% were in the rising HbA1c group and 50.2% were in the uncontrolled group. HbA1c and mean fasting glucose at 10 years were different between the three groups. The stable group had the lowest HbA1c and fasting glucose concentrations and the highest beta-cell function indices, whereas the uncontrolled group had the highest HbA1c level and lowest indices of beta-cell function. The uncontrolled group also had the lowest levels of inverse insulin and fasting C-peptide of the three groups at 10 years.
At 10 years, the stable HbA1c group had fewer measured comorbidities than the other two groups with the exception of inflammation markers. The prevalence of nephropathy was lower in the stable HbA1c group compared with the uncontrolled group (2.6% vs. 12%; P = .003). Similar findings were observed with the prevalence of dyslipidemia, neuropathy and retinopathy. The prevalence of nephropathy, neuropathy and retinopathy for the rising HbA1c group was in between the figures for the stable HbA1c group and the uncontrolled group.
Glucose variability predicts comorbidity risk
Fasting blood glucose variability was lowest in the stable and rising HbA1c groups and highest in the uncontrolled group (P < .001 for all). First-year fasting glucose coefficient of variation was only associated with increasing fasting glucose in people in the uncontrolled group who exceeded an HbA1c of 8% in their first year of follow-up. First-year fasting glucose coefficient of variation was predictive of a loss of glycemic control in uncontrolled participants who exceeded an HbA1c of 8% after 1 year (area under the curve = 0.7; 95% CI, 0.64-0.76; P < .0001). According to the Youden’s index, a fasting glucose coefficient of variation cutoff of 8.3% is predictive of long-term comorbidities at 10 years.
“Our study not only affirms the high rate of comorbidities observed in this population, but also shows that those at highest risk can be identified by assessment of beta-cell function and glycemic variability,” the researchers wrote. “This suggests that more aggressive therapy is warranted for that group. SGLT2 inhibitors and GLP-1 agonists have been shown to have organ-protective effects in adults with type 2 diabetes; thus, these agents may play important therapeutic roles in youth-onset type 2 diabetes in the future.”
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TODAY Study Group. Diabetes Care. 2022;doi:10.2337/dc22-0784.
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