No evidence for a causal link between uric acid and type 2 diabetes: a Mendelian randomisation approach

Abstract

Aims/hypothesis Epidemiological and experimental evidence suggests that uric acid has a role in the aetiology of type 2 diabetes. Using a Mendelian randomisation approach, we investigated whether there is evidence for a causal role of serum uric acid for development of type 2 diabetes. Methods We examined the associations of serum-uric-acidraising alleles of eight common variants recently identified in genome-wide association studies and summarised this in a genetic score with type 2 diabetes in case-control studies including 7,504 diabetes patients and 8,560 non-diabetic controls. We compared the observed effect size to that expected based on: (1) the association between the genetic score and uric acid levels in non-diabetic controls; and (2) the meta-analysed uric acid level to diabetes association. Results The genetic score showed a linear association with uric acid levels, with a difference of 12.2 μmol/l (95% CI 9.3, 15.1) by score tertile. No significant associations were observed between the genetic score and potential confounders. No association was observed between the genetic score and type 2 diabetes with an OR of 0.99 (95% CI 0.94, 1.04) per score tertile, significantly different (p=0.046) from that expected (1.04 [95% CI 1.03, 1.05]) based on the observed uric acid difference by score tertile and the uric acid to diabetes association of 1.21 (95% CI 1.14, 1.29) per 60 μmol/l. Conclusions/interpretation Our results do not support a causal role of serum uric acid for the development of type 2 diabetes and limit the expectation that uric-acid-lowering drugs will be effective in the prevention of type 2 diabetes.

Hyperuricaemia as a Predictor of Complication in Type Ii Diabetes Mellitus

“…This is similar to the study by Sudhindra Rao, 14 M Modan, 15 Nakanishi, 16 Abbas D, 4 While R Pfister 17 found no correlation and Pavani Bandaru 18 found inverse correlation of level of uric acid and duration of diabetes. Our study confirms the finding of other studies that uric acid increases as the duration of diabetes increases.…”

Association between Hypouricemia and Reduced Kidney Function: A Cross-Sectional Population-Based Study in Japan

“…In contrast to previous observational findings, there is no strong evidence for causal associations between uric acid and ischemic heart disease or blood pressure [41]. The approach has also demonstrated that elevated serum uric acid is a consequence, rather than a cause, of adiposity [42,43], and is not a cause of type 2 diabetes [44] or metabolic syndrome [45]. Although we could not rely on Mendelian randomization due to the lack of genetic data, these reports and our results suggest that the association between uric acid levels and reduced kidney function is far more complex than what was previously thought.…”

Cross-sectional and longitudinal associations between serum uric acid and metabolic syndrome: Results from Fangchenggang Area Male Health and Examination Survey in China

“…However, the present study showed that increased concentrations of SUA did not lead to the increased glucose concentration (HR = 1.34, 95% CI, 0.93-1.95, P = NS). Some researchers also reported no association between them while others suggested a negative relationship [21,22]. Additionally, another previous study reported an inverse U-shaped association between fasting glucose and SUA concentrations, suggesting the positively relationship only existed when SUA concentration was b 8.0 μmol/l [23].…”

“…Yuri et al demonstrated that hyperuricemia induced oxidative stress in adiocytes [24], and insulin resistance causing the glucose metabolic disorder was partly mediated by oxidative stress [25]. Nonetheless, substantial evidence of confounding was found modifying the causality [22]. Other covariates, such as hypertension, alcohol drinking, BMI and Table 1 baseline characteristics of study population stratified for the absence and presence of MetS.…”