Albuminuria According to Status of Autoimmunity and Insulin Sensitivity Among Youth With Type 1 and Type 2 Diabetes

OBJECTIVE

To evaluate whether etiologic diabetes type is associated with the degree of albuminuria in children with diabetes.

RESEARCH DESIGN AND METHODS

SEARCH is an observational, longitudinal study of children with diabetes. Youth with newly diagnosed diabetes were classified according to diabetes autoantibody (DAA) status and presence of insulin resistance. We defined insulin resistance as an insulin sensitivity score <25th percentile for the United States general youth population. DAA status was based on positivity for the 65-kD isoform of glutamate decarboxylase and insulinoma-associated protein 2 antigens. The four etiologic diabetes type groups were as follows: DAA⁺/insulin-sensitive (IS) (n = 1,351); DAA⁺/insulin-resistant (IR) (n = 438); DAA⁻/IR (n = 379); and DAA⁻/IS (n = 233). Urinary albumin:creatinine ratio (UACR) was measured from a random urine specimen. Multivariable regression analyses assessed the independent relationship between the four diabetes type groups and magnitude of UACR.

RESULTS

Adjusted UACR means across the four groups were as follows: DAA⁺/IS = 154 μg/mg; DAA⁺/IR = 137 μg/mg; DAA⁻/IR = 257 μg/mg; and DAA⁻/IS = 131 μg/mg (P < 0.005). Only DAA⁻/IR was significantly different. We performed post hoc multivariable regression analysis restricted to the two IR groups to explore the contribution of DAA status and insulin sensitivity (continuous) to the difference in UACR between the IR groups. Only insulin sensitivity was significantly associated with UACR (β = −0.54; P < 0.0001).

CONCLUSIONS

In youth with diabetes, the DAA⁻/IR group had a greater UACR than all other groups, possibly because of the greater magnitude of insulin resistance. Further exploration of the relationships between severity of insulin resistance, autoimmunity, and albuminuria in youth with diabetes is warranted.Previous reports suggested that the clinical course and factors contributing to the development and progression of diabetic nephropathy did not differ by diabetes type and that diabetic nephropathy was preceded by albuminuria that worsened over time (1,2). More recent data have further elucidated the natural history of diabetic kidney disease. In the absence of albuminuria, a significant number of people with diabetes, especially type 2, still develop a decline in glomerular filtration rate (3,4). Thus, there may be identifiable differences in the natural history of nephropathy inherent to the underlying diabetes type. Multiple pediatric diabetes cohorts have found a higher prevalence of albuminuria and progressive kidney failure in youth with a clinical diagnosis of type 2 diabetes than with type 1 diabetes (5–7). Such data suggest that insulin resistance, a key component of the pathophysiology of type 2 diabetes, may be an important contributor to diabetic nephropathy in youth with diabetes.The epidemic of overweight and obesity has made it increasingly difficult to clinically diagnose diabetes type, because insulin resistance and autoimmunity often coexist (8,9). Cohort studies of youth with type 1 diabetes have found a significant increase in microvascular and macrovascular diseases in those with concurrent insulin resistance (10–12). The prevalence of albuminuria in insulin-resistant (IR) individuals with type 1 diabetes has not been compared with individuals with type 2 diabetes. Thus, the role of autoimmunity and insulin resistance across the spectrum of diabetes types and the risk for microvascular complications warrant investigation. Herein, we investigate the magnitude of albuminuria according to the status of autoimmunity and insulin resistance in youth with newly diagnosed type 1 and type 2 diabetes.