ABSTRACT
OBJECTIVE: Serum uric acid (SUA) has been associated with cardiometabolic conditions such as insulin resistance (IR) and visceral adipose tissue (VAT) accumulation. Here, we aimed to clarify a unifying mechanism linking elevated SUA to IR and VAT. METHODS: We conducted analyses in 226 subjects from the UIEM cohort with both euglycemic hyperinsulinemic clamp (EHC) and dual X-ray absorptiometry (DXA) measurements for IR and VAT accumulation and explored the role of SUA and adiponectin by developing a network of causal mediation analyses to assess their impact on IR and VAT. These models were then translated to two population-based cohorts comprising 6337 subjects from NHANES 2003-2004 and 2011-2012 cycles in the US and ENSANUT Medio Camino 2016 in Mexico, using HOMA2IR and adipoIR as indicators of peripheral and adipose tissue IR, and METS-VF as a surrogate for VAT accumulation. RESULTS: SUA has a mediating role inside a bidirectional relationship between IR and visceral obesity, which was similar using either gold standard measurements or surrogate measures for IR and VAT. Furthermore, adiponectin acts as a linking mediator between elevated SUA and both peripheral IR and VAT accumulation. The proportion of the mechanism for IR-mediated (in either peripheral or adipose tissue) VAT accumulation was greater, compared to VAT-mediated IR accumulation (10.53% [9.23%-12.00%] to 5.44% [3.78%-7.00%]). Normal-range SUA levels can be used to rule-out underlying cardio-metabolic abnormalities in both men and women. CONCLUSIONS: Elevated SUA acts as a mediator inside the bidirectional relationship between IR and VAT accumulation and these observations could be applicable at a phenotype scale.
Subject(s)
Insulin Resistance , Uric Acid , Adipose Tissue , Female , Glucose Clamp Technique , Humans , Intra-Abdominal Fat , Nutrition SurveysABSTRACT
OBJECTIVE: To evaluate the correlation between subrogate index for the evaluation of insulin resistance with the M value obtained with the euglycemic-hyperinsulinemic clamp as well as their sensitivity, specificity, and positive and negative predictive values. METHOD: The euglycemic-hyperinsulinemic clamp was performed in subjects having both normal fasting glucose and glycated hemoglobin concentrations. HOMA-IR, QUICKI, HOMA2%S, TyG, TyG*body mass index (BMI) and triglyceride/HDL indexes were calculated. Correlations coefficients were estimated between indexes results and the M-value adjusted by fat-free mass. Areas under the ROC curve were constructed to evaluate overall performance, sensitivity, specificity and predictive values of the subrogate indexes. RESULTS: 57 subjects, 68.4% women, with a mean age of 32.9 ± 11 years-old were included. The subrogate index with the best correlation with the M value was HOMA2%S (r = 0.428), HOMA-IR had the greatest area under the ROC curve (0.683; 95 % confidence interval: 0.503-0.864) and TyG*BMI the best sensitivity (98.2 %) and specificity (51.1 %). CONCLUSIONS: The surrogated indexes for the evaluation of insulin resistance show a significant correlation with the M value obtained with the gold standard. Additional studies are required to determine cut-off values in Mexican population.
OBJETIVO: Evaluar la correlación entre índices subrogados de resistencia a la insulina y el valor M obtenido mediante pinza euglucémica-hiperinsulinémica, así como su sensibilidad, especificidad y valores predictivos positivo y negativo, en mexicanos sin diabetes. MÉTODO: Se realizó una pinza euglucémica-hiperinsulinémica en individuos con glucosa en ayuno y hemoglobina glucosilada normales. Se estimaron los índices HOMA-IR, QUICKI, HOMA2%S, TyG, TyG*índice de masa corporal (IMC) y triglicéridos/colesterol ligado a lipoproteínas de alta densidad. Se estimaron coeficientes de correlación de Pearson entre los resultados y el valor M ajustado por masa libre de grasa. Se construyeron curvas ROC para evaluar su desempeño y se estimaron la sensibilidad, la especificidad y los valores predictivos de los índices. RESULTADOS: Se incluyeron 57 individuos, el 68.4 % mujeres, de 32.9 ± 11 años, con IMC de 26.5 ± 3.9 kg/m2. El índice subrogado con mejor correlación con el valor M fue HOMA2%S (r = 0.428), con la mayor área bajo la curva ROC (0.683; intervalo de confianza del 95 %: 0.503-0.864) HOMA-IR, y con mejor sensibilidad (92.8 %) y especificidad (51.1 %) TyG*IMC. CONCLUSIONES: Los índices subrogados para estimar la resistencia a la insulina muestran una correlación significativa con el valor M obtenido con el método de referencia. Se requieren más estudios para determinar puntos de corte en población mexicana.
