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. 2020 Mar 1;105(3):e651-e659.
doi: 10.1210/clinem/dgz199.

Changes Over Time in Uric Acid in Relation to Changes in Insulin Sensitivity, Beta-Cell Function, and Glycemia

Alessandro Volpe  1 , Chang Ye  1 , Anthony J Hanley  1   2   3 , Philip W Connelly  2   4   5 , Bernard Zinman  1   2   6 , Ravi Retnakaran  1   2   6
Affiliations

Changes Over Time in Uric Acid in Relation to Changes in Insulin Sensitivity, Beta-Cell Function, and Glycemia

Alessandro Volpe et al. J Clin Endocrinol Metab. .

Abstract

Context: Serum uric acid has been linked to risk of type 2 diabetes (T2DM), but debate persists as to whether it plays a causal role. Indeed, it is unclear if changes in uric acid relate to the pathophysiologic determinants of T2DM (insulin resistance, beta-cell dysfunction), as would be expected if causal.

Objective: To evaluate the impact of changes in uric acid over 2 years on changes in insulin sensitivity, beta-cell function, and glycemia in women with and without recent gestational diabetes (GDM), a model of the early natural history of T2DM.

Design/setting/participants: At both 1 and 3 years postpartum, 299 women (96 with recent GDM) underwent uric acid measurement and oral glucose tolerance tests that enabled assessment of insulin sensitivity/resistance (Matsuda index, homeostasis model assessment of insulin resistance [HOMA-IR]), beta-cell function (insulin secretion-sensitivity index-2 [ISSI-2], insulinogenic index/HOMA-IR [IGI/HOMA-IR]), and glucose tolerance.

Results: Women with recent GDM had higher serum uric acid than their peers at both 1 year (281 ± 69 vs 262 ± 58 µmol/L, P = 0.01) and 3 years postpartum (271 ± 59 vs 256 ± 55 µmol/L, P = 0.03), coupled with lower insulin sensitivity, poorer beta-cell function, and greater glycemia (all P < 0.05). However, on fully adjusted analyses, neither uric acid at 1 year nor its change from 1 to 3 years was independently associated with any of the following metabolic outcomes at 3 years postpartum: Matsuda index, HOMA-IR, ISSI-2, IGI/HOMA-IR, fasting glucose, 2-hour glucose, or glucose intolerance.

Conclusion: Serum uric acid does not track with changes over time in insulin sensitivity, beta-cell function, or glycemia in women with recent GDM, providing evidence against causality in its association with diabetes.

Keywords: beta-cell dysfunction; gestational diabetes; insulin resistance; type 2 diabetes; uric acid.

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Figures

Figure 1.
Figure 1.
Comparison of mean adjusted serum uric acid between women with and without recent GDM at (Panel A) 1 year postpartum and (Panel B) 3 years postpartum after adjustment for age, ethnicity, family history of diabetes, current BMI, duration of breastfeeding in first year, and current glucose tolerance. Abbreviation: GDM, gestational diabetes mellitus.
See this image and copyright information in PMC

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