Youth living with type 2 diabetes (T2D) are at high risk of early renal injury. We evaluated interrelationships between biological, psychological, socioeconomic factors and prevalent albuminuria in youth with T2D in the Improving renal Complications in Adolescents with type 2 diabetes through REsearch (iCARE) cohort. We performed a cross-sectional structural equation model (SEM) analysis on 319 youth with T2D 10-24 years old from 8 Canadian sites involved in the iCARE cohort. The main outcome measure was non-orthostatic albuminuria (urine ACR >2mg/mmol). Main factors of interest (indicator variables) were blood pressure (daytime and night systolic and diastolic loads), urine cytokines (IL-6, RANTES, Fractalkine, ENA78, TNFα, IL-1βB, sTNFRI51, sTNFRII53, MCP1), systemic inflammatory markers (c-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen), mental health (Resiliency Scales for Children and Adolescents, Kessler-6, Perceived Stress Scale-14), and the Canadian Index of Multiple Deprivation (CIMD) scores. Additional covariates were hemoglobin A1c (HbA1c) and duration of diabetes. Multiple imputation addressed missing data. Youth were 15 ± 2.3 years old, lived with diabetes for 2.3 ± 1.9 years, 66% were female, and 33% had albuminuria. Factors significantly associated with albuminuria were blood pressure (standardized coefficient, b=0.31), urinary cytokines (IL-6, RANTES, Fractalkine, ENA78, TNFa, IL-1β) (b=0.34) and HbA1c (b=0.32); Residential Instability (b=0.21) and ethnic composition (b= -0.36). The factor mental health was positively correlated with systemic inflammation (CRP, ESR, fibrinogen), which was predictive of albuminuria (b=0.29). Diabetes duration was not associated with albuminuria. The model fit well per the CFI (0.988), RMSEA (0.012), and SRMR (0.057) statistics. The presence of albuminuria in youth with T2D is associated with blood pressure, HbA1c, renal and systemic inflammation and residential instability. Mental health was indirectly associated with albuminuria via systemic inflammation. Albuminuria is complex and requires multi-pronged approaches for prevention.
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