Association between normal range UACR and insulin resistance and prediabetes among US adults:

Abstract Background Recent studies have shown that urine albumin-to-creatinine ratio (UACR) within the normal range is associated with increased risk of hypertension, diabetes, cardiovascular death and all-cause death. However, the relationship between normal range UACR and the prevalence of insulin resistance (IR) and prediabetes has not been explored. Methods The study included 14,208 US adults with normal range UACR values and without diabetes from the National Health and Nutrition Survey (1999-2018). The outcome variables included IR and prediabetes, as defined by the 2013 American Diabetes Association guidelines. The weighted multivariate linear regression, weighted multivariate logistic regression, restricted cubic spline (RCS) regression, and subgroup analysis were conducted to examine the relationship of UACR with IR and prediabetes. Results The weighted multivariate linear regression analysis showed that a 1-standard deviation (SD) increment in ln (UACR) was positively associated with fasting plasma glucose (FPG) (β = 0.02, 95% CI: 0.01, 0.04), glycosylated hemoglobin (β = 0.01, 95% CI: 0.00, 0.02), fasting serum insulin (FSI) (β = 0.50, 95% CI: 0.31, 0.68), and homeostasis model assessment of insulin resistance (HOMA-IR) (β = 0.14, 95% CI: 0.09, 0.19). The weighted multivariate logistic regression analysis revealed that a 1-SD increment in ln (UACR) was significantly associated with an increased prevalence of prediabetes (OR = 1.10, 95% CI: 1.04-1.15), but not with IR (OR = 1.05, 95% CI: 0.99-1.12). With the lowest quartile of UACR as a reference, ORs (95% CIs) for IR in the second, third, and fourth quartiles were 1.10 (0.86, 1.15), 1.15 (0.98, 1.33), and 1.12 (0.95, 1.32), respectively, and ORs (95% CIs) for prediabetes were 1.35 (1.19, 1.52), 1.32 (1.14, 1.53), and 1.44 (1.24, 1.66), respectively. Subgroup analysis indicated that smoking had a significant impact on the association between UACR and prediabetes. The association between UACR and prediabetes was more significant in smokers than in non-smokers (P for interaction = 0.03). RCS regression analysis revealed a non-linear positive dose-response association between UACR and indicators of diabetes. Conclusion Elevated UACR, even within the normal range, was positively associated with indicators of diabetes and increased prevalence of prediabetes among US adults. Smoking had a significant impact on the association between UACR and prediabetes, with a more pronounced association observed among smokers.uacr with diabetes markersUacr with ir and prediabetes