In young patients with type 1 diabetes (T1D), phenotype clusters of body mass index (BMI) and glycemic control are associated with patterns of early diabetes complications, especially markers of subclinical macrovascular disease, according to study results published in The Journal of Clinical Endocrinology & Metabolism.

This study included participants diagnosed with T1D before age 20 years (n=570; mean age at diagnosis, 9.7 years). Patients were clustered based on longitudinal BMI z score and hemoglobin A1c (HbA1c) levels at baseline and follow-up. On average, baseline and follow-up visits occurred at 1.4 and 8.2 years after the initial diabetes diagnosis, respectively. The researchers used logistic regression modeling to test cluster associations with 7 early/subclinical diabetes complications at follow-up, adjusting for sex, race/ethnicity, age, and disease duration.

The researchers identified 4 longitudinal weight-glycemia clusters with significant between-group differences in HbA1c and BMI severity: the referent cluster, with stable low BMI z scores and fair glycemic control (n=195, 34.3%); the hyperglycemia-only cluster, with low BMI z scores and stable high HbA1c (n=53, 9.3%); the elevated weight-only cluster (n=206, 36.1%), with elevated BMI z scores and moderate HbA1c values; and the elevated weight/increasing hyperglycemia cluster (n=115, 20.2%), with both high BMI z scores and increasing HbA1c over time.

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Compared with the referent cluster, patients in the hyperglycemia-only cluster had an increased risk for dyslipidemia (adjusted odds ratio [aOR], 2.22; 95% CI, 1.15-4.29), retinopathy (aOR, 9.98; 95% CI, 2.49-40.0), and diabetic kidney disease (aOR, 4.16; 95% CI, 1.37-12.62).

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In a similar fashion, compared with the referent cluster, patients in the elevated weight/increasing hyperglycemia cluster had an increased risk for hypertension (aOR, 2.18; 95% CI 1.19-4.00), dyslipidemia (aOR, 2.36; 95% CI 1.41-3.95), arterial stiffness (aOR, 2.46; 95% CI 1.09-5.53), retinopathy (aOR, 5.11; 95% CI 1.34-19.46), and diabetic kidney disease (aOR, 3.43; 95% CI 1.39-9.11).

Of note, the study was limited to patients with a disease duration ≥12 months and may not be generalizable to all patients with T1D.

“The variable patterns of [BMI severity] and HbA1c and differential risk profiles captured from the first eight years of diabetes underscore the tremendous challenges and complexity associated with diabetes management, as well as the need for clinical practice guidelines for weight management specifically in the setting of pediatric-onset type 1 diabetes,” wrote the researchers.

“More work is needed to identify therapeutic approaches tailored to the needs and prognoses of each subgroup for interventions that can be implemented early in the natural history of type 1 diabetes,” they concluded.

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Kahkoska AR, Nguyen CT, Adair LA, et al. Longitudinal phenotypes of type 1 diabetes in youth based on weight and glycemia and their association with complications [published online July 10, 2019]. J Clin Endcrinol Metab. doi:10.1210/jc.2019-00734