The Association of Serum Uric Acid with Beta-Cell Function and Insulin Resistance in Nondiabetic Individuals: A Cross-Sectional Study

Abstract

Purpose Higher serum levels of uric acid (SUA) are associated with an increased risk of developing type 2 diabetes. Meanwhile, insulin resistance and beta-cell dysfunction are critical factors that mediate the progression from normal glucose tolerance to impaired fasting glucose (IFG) and type 2 diabetes. We aimed to investigate the association between SUA levels and insulin resistance and beta-cell dysfunction in individuals without diabetes, thus explicating the role of uric acid in the early stage of the natural history of type 2 diabetes. Patients and Methods We used cross-sectional data from the China Health and Nutrition Survey to examine the association. Insulin resistance and beta-cell dysfunction were estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index and homeostasis model assessment of beta-cell function (HOMA-beta) index, respectively. The associations were analyzed by using partial correlation analysis and multivariate logistic regressionl analysis. Results SUA levels were positively associated with fasting glucose, fasting insulin, HOMA-IR in the total population. After adjustment for age, drinking, smoking, living area, daily dietary nutrient intake, body mass index (BMI), estimated glomerular filtration rate (eGFR), hypertension, and dyslipidemia, compared with participants in the lowest quartile of SUA, the adjusted odds ratios for the fourth quartiles were 1.56(1.09-2.24) for IFG, 1.51(1.27-1.78) for insulin resistance, and 1.06(0.88-1.27) for beta-cell dysfunction. In the subgroup analysis, no interactions were found between serum uric acid and age, drinking status, smoking status, BMI, hypertension, or dyslipidemia (all p for interaction>0.05). Conclusion In nondiabetic individuals, SUA levels are independently associated with IFG and insulin resistance, while no significant association exists between SUA and beta-cell dysfunction.

Hyperuricemia and Associated Cardiometabolic Factors: A Cross-sectional Study on Taxi-motorbike Drivers Working in Cotonou, Benin

“…Multivariate logistic regression showed a decrease in OR, but the association remained statistically significant. This observation suggests that none of the potential confounders impacted the link between UA and IR similar to what was reported in previous studies (28,(30)(31)(32)(33). It was suggested that HUA, as a strong predictor of diabetes, precedes the development of both IR and T2D (11).…”

Hyperuricemia as an effect modifier of the association between metabolic phenotypes and nonalcoholic fatty liver disease in Chinese population

“…Some reports suggested that serum uric acid per se might inhibit insulin receptor substrate 1 (IRS1) and Akt insulin signaling and induce insulin resistance [ 44 , 45 ]. Additionally, hyperuricemia could increase the production of reactive oxygen species (ROS), and both uric acid and ROS could activate the pro-inflammatory factors, which played an important role in the development or worsening of insulin resistance [ 46 – 48 ]. Therefore, the co-occurrence of elevated uric acid and metabolically healthy/unhealthy overweight and obesity may jointly increase the risk of prevalent NAFLD through worsened insulin resistance.…”

Hyperuricemia, a Non-Independent Component of Metabolic Syndrome, Only Predicts Renal Outcome in Chronic Kidney Disease Patients without Metabolic Syndrome or Diabetes

“…Studies have pointed out a significant correlation between uric acid levels and homeostatic model assessment (HOMA) scores in patients with obesity or at risk for T2DM [ 46 , 47 ]. One study of 6027 nondiabetic individuals demonstrated that serum UA is independently associated with impaired fasting glucose (IFG) and insulin resistance but not with beta-cell dysfunction [ 48 ]. A study of 174,695 adults without self-reported use of ULA, hypoglycemic agents, or lipid-lowering drugs demonstrated that noninsulin-based IR indices were significantly associated with hyperuricemia [ 49 ].…”