Background and aims: The relationship between uric acid and insulin resistance has been widely studied, whereas little is known about a potential interaction between uric acid and beta-cell function. Goal of this study was to investigate the relationship, if any, between uricaemia and beta-cell function in patients with newly diagnosed type 2 diabetes. Materials and methods: In 569 GAD negative, drug naive patients (median [interquartile range]: age 60 [52-66] years, BMI 29.3 [26.6-32.9] kg/m2, HbA1c 6.6 [6.1-7.4]%, uric acid 0.32 [0.27-0.37] mmol/L) with newly diagnosed type 2 diabetes we assessed insulin sensitivity by the euglycemic insulin clamp (M clamp: 605 [381-845] μmol·min-1·m-2 BSA) and beta-cell function by state-of-art modelling of glucose/C-peptide curves during an oral glucose tolerance test (OGTT). There are two main outputs of the model: derivative control (DC: amount of insulin secreted in response to the rate of plasma glucose increase; median [interquartile range]: 444 [66-929] [pmol·m-2 BSA]/ [mM·min-1]) and proportional control of beta-cell function (PC: stimulusresponse curve linking glucose concentration to insulin secretion rate; mean ± SD at the preselected glucose concentrations of 5.5, 8.0, 11.0, 15.0 and 20.0 mM: 158±67, 228±124, 376±229, 602±397, 889±623 pmol·min-1·m-2 BSA). Results: In univariate analysis, serum uric acid concentration was positively related to both DC (p<0.01) and PC (p<0.01) of beta-cell function. In multiple regression analysis, after adjusting for age, gender, BMI, insulin sensitivity and glomerular filtration rate, this positive relationship stayed statistically significant (p<0.01 e p<0.01 for DC and PC respectively). Consistently with this result, uricaemia was inversely correlated to HbA1c (p<0.01), fasting glucose (p<0.01), 1-hour and 2-hour OGTT glucose (p<0.01 and p<0.01 respectively). Patients in the 3rd tertile of uric acid had a 37% increase in DC (p<0.01) and a 21-30% increase in PC (p<0.01) of beta-cell function, when compared to those in the 1st tertile. Conclusions: In patients with newly diagnosed type 2 diabetes there exists a strong positive correlation between serum uric acid concentration and betacell function. This finding might reflect antioxidant activity of uric acid. However, to determine whether uric acid improves beta-cell function per se or through other factors, mechanistic studies will be required.
Uric acid is a biomarker of beta cell function in patients with newly diagnosed type 2 diabetes
BOSELLI, Maria Linda;M. Dauriz;BONADONNA, Riccardo;BONORA, Enzo;TROMBETTA, Maddalena
2013-01-01
Abstract
Background and aims: The relationship between uric acid and insulin resistance has been widely studied, whereas little is known about a potential interaction between uric acid and beta-cell function. Goal of this study was to investigate the relationship, if any, between uricaemia and beta-cell function in patients with newly diagnosed type 2 diabetes. Materials and methods: In 569 GAD negative, drug naive patients (median [interquartile range]: age 60 [52-66] years, BMI 29.3 [26.6-32.9] kg/m2, HbA1c 6.6 [6.1-7.4]%, uric acid 0.32 [0.27-0.37] mmol/L) with newly diagnosed type 2 diabetes we assessed insulin sensitivity by the euglycemic insulin clamp (M clamp: 605 [381-845] μmol·min-1·m-2 BSA) and beta-cell function by state-of-art modelling of glucose/C-peptide curves during an oral glucose tolerance test (OGTT). There are two main outputs of the model: derivative control (DC: amount of insulin secreted in response to the rate of plasma glucose increase; median [interquartile range]: 444 [66-929] [pmol·m-2 BSA]/ [mM·min-1]) and proportional control of beta-cell function (PC: stimulusresponse curve linking glucose concentration to insulin secretion rate; mean ± SD at the preselected glucose concentrations of 5.5, 8.0, 11.0, 15.0 and 20.0 mM: 158±67, 228±124, 376±229, 602±397, 889±623 pmol·min-1·m-2 BSA). Results: In univariate analysis, serum uric acid concentration was positively related to both DC (p<0.01) and PC (p<0.01) of beta-cell function. In multiple regression analysis, after adjusting for age, gender, BMI, insulin sensitivity and glomerular filtration rate, this positive relationship stayed statistically significant (p<0.01 e p<0.01 for DC and PC respectively). Consistently with this result, uricaemia was inversely correlated to HbA1c (p<0.01), fasting glucose (p<0.01), 1-hour and 2-hour OGTT glucose (p<0.01 and p<0.01 respectively). Patients in the 3rd tertile of uric acid had a 37% increase in DC (p<0.01) and a 21-30% increase in PC (p<0.01) of beta-cell function, when compared to those in the 1st tertile. Conclusions: In patients with newly diagnosed type 2 diabetes there exists a strong positive correlation between serum uric acid concentration and betacell function. This finding might reflect antioxidant activity of uric acid. However, to determine whether uric acid improves beta-cell function per se or through other factors, mechanistic studies will be required.
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