Haemoglobin A1c, Fasting Glucose, Serum C-peptide and Insulin Resistance in Relation to Serum Uric Acid Levels--the Third National Health and Nutrition Examination Survey

Objective: To evaluate haemoglobin A1c (HbA1c), fasting glucose, serum C-peptide and insulin resistance in relation to serum uric acid levels in a nationally representative sample of men and women.

Methods: Using data from 14,664 participants aged 20 yrs and older in The US Third National Health and Nutrition Examination Survey (1988-1994), we examined the relation between the levels of HbA1c, other biomarkers and serum uric acid levels using multivariate linear regressions stratified by gender.

Results: The serum uric acid levels increased with increasing serum HbA1c levels up to the category of 6-6.9%, and thereafter decreased with further increasing HbA1c levels (a bell-shaped relation). Compared with a HbA1c level of < 5%, the multivariate differences among women were 26.8 micromol/l for HbA1c of 6-6.9% and -25.6 micromol/l (95% CI -42.8, -8.3) for HbA1c > or = 9%. The corresponding multivariate differences among men were 8.3 micromol/l (95% CI -3.0, 19.6) and -64.8 micromol/l (95% CI -46.0, -84.5), which were both significantly different from those among women (P-values for interaction by sex <0.001). Fasting glucose levels also showed a bell-shaped relation with serum uric acid levels. Individuals with diabetes showed lower serum uric acid levels and the association was larger among men (P-value for interaction, 0.007). Serum uric acid levels increased linearly with increasing fasting serum C-peptide levels, serum insulin levels or insulin resistance (multivariate P-values for trend, <0.001).

Conclusions: Individuals with moderately elevated HbA1c levels (i.e. pre-diabetes) may be at a higher risk of hyperuricaemia and gout, particularly in women, whereas individuals with diabetes or highly elevated HbA1c levels may be at a lower risk of these conditions, particularly in men.