Longitudinal phenotypes of type 1 diabetes in youth based on weight and glycemia and their association with complications.

CONTEXT: Subclinical and clinical complications emerge early in type 1 diabetes and may be associated with obesity and hyperglycemia.

OBJECTIVE: Test how longitudinal 'weight-glycemia' phenotypes increase susceptibility to different patterns of early/subclinical complications among youth with type 1 diabetes.

DESIGN: SEARCH for Diabetes in Youth observational study.

SETTING: Population-based cohort.

PARTICIPANTS: Youth with type 1 diabetes (n=570) diagnosed 2002-2006 or 2008.

MAIN OUTCOME MEASURES: Participants were clustered based on longitudinal BMI z-score and hemoglobin A1c from a baseline visit and 5+ year follow-up visit (mean diabetes duration: 1.4±0.4 years and 8.2±1.9 years, respectively). Logistic regression modeling tested cluster associations with seven early/ subclinical diabetes complications at follow-up, adjusting for sex, race/ethnicity, age, and duration.

RESULTS: Four longitudinal weight-glycemia clusters were identified: The Referent Cluster (n=195, 34.3%), the Hyperglycemia Only Cluster (n=53, 9.3%), the Elevated Weight Only Cluster (n=206, 36.1%), and the Elevated Weight with Increasing Hyperglycemia "EWH" Cluster (n=115, 20.2%). Compared to the Referent Cluster, the Hyperglycemia Only Cluster had elevated odds of 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 (DKD) (aOR 4.16, 95% CI 1.37-12.62). The EWH Cluster had elevated odds of 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 DKD (aOR 3.43, 95% CI 1.29-9.11).

CONCLUSIONS: Weight-glycemia phenotypes show different patterns of complications, particularly markers of subclinical macrovascular disease, even in the first decade of type 1 diabetes.