Nephropathy (NP) is a frequent, devastating consequence of non-insulin- dependent diabetes mellitus (NIDDM) and hypertension (HTN). The prevalence of NP is particularly high among African Americans (AAs). AA women with a history of gestational diabetes mellitus (GDM) are at high risk for NIDDM and HTN and probably NP. Persistant urinary albumin excretion (UAE), microalbumnuria (MA), is the earliest clinical evidence of many cases of NP. MA may proceed the onset of clinical diagnosis of NIDDM and/or HTN. The frequence of MA prior to the onset of these clinical disorders in this high risk population is unknown. The proposed study will estimate these rates. The factors which cause MA are uncertain. We propose to test the hypothesis that insulin resistance (IR) is a phenotype influenced by genes in or near the Major Histocompatibility Complex (MHC) that results in increased occurrence and rate of progression of kidney dysfunction and this relationship is in part independent of the relationship between IR and two of its hypothesized sequellae, HTN and dyslipidemia, both of which have been hypothesized as causes of MA. The statistical analyses are designed to determine the influence of IR and the relative contribution of each of its sequellae and their interaction in the occurrence of MA and the change in UAE rate and creatinine clearance over time. The goal is to understand the role of these factors that lead to MA and ultimately to prevent NP.
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