Longitudinal Study of Associations of Microalbuminuria With the Insulin Resistance Syndrome and Sodium-Lithium Countertransport in Nondiabetic Subjects

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Abstract
Abstract Microalbuminuria in diabetic patients is associated with ischemic heart disease and insulin resistance. We previously found a 9% prevalence of microalbuminuria in a nondiabetic population that we have reassessed, investigating associations of microalbuminuria with hypertension, dyslipidemia, hyperinsulinemia, and sodium-lithium countertransport. Of 125 subjects reexamined, 42 had been microalbuminuric 3 years previously. Twelve of these (29%) were microalbuminuric on at least one sample at follow-up, and 30 (76%) were normoalbuminuric on two. Of the 79 previously normoalbuminuric subjects, 12 (15%) became microalbuminuric on one sample, while 67 (85%) remained normoalbuminuric. Subjects who were microalbuminuric at both screening and recall were older (mean±SD, 65.9±11 versus 59.1±10.2 years, P =.04), with a higher waist-to-hip ratio (0.93±0.09 versus 0.86±0.08, P =.008) and at recall, on univariate analysis, had higher specific insulin (44.2 [range, 16.9 to 157.0] versus 28.4 [7.4 to 129.0] pmol/L, P =.005), intact proinsulin (5.1 [1.5 to 11.0] versus 3.0 [0.8 to 14.6] pmol/L, P =.003), and des-31,32-proinsulin (5.0 [0.5 to 9.8] versus 1.0 [0.5 to 12.2] pmol/L, P =.004) concentrations. There was also a significant difference in des-31,32-proinsulin concentration, after adjustment for covariates ( P =.013), between subjects classified either as microalbuminuric or as normoalbuminuric at screening. There was no difference in body mass index; fasting blood glucose; systolic or diastolic blood pressure; total, HDL, or LDL cholesterol; triglycerides; plasminogen activator inhibitor-1; or sodium-lithium countertransport activity between consistently normoalbuminuric and persistently microalbuminuric subjects. We found a positive relationship of changes in albumin excretion rate with those in HDL cholesterol concentrations over the follow-up period ( r =.25, P =.009) but none with changes in fasting blood glucose, blood pressure, other lipids, insulin, or proinsulin-like molecules. In conclusion, microalbuminuria is an unstable phenomenon over a period of 3 years in nondiabetic subjects, with a coefficient of variation of ≈60% on two paired samples over this time. It is associated with increased concentrations of insulin and of proinsulin-like molecules but not with other features of the insulin resistance syndrome.