Clinical research study
Serum Uric Acid Levels and the Risk of Type 2 Diabetes: A Prospective Study

https://doi.org/10.1016/j.amjmed.2010.03.027Get rights and content

Abstract

Purpose

To evaluate the impact of serum uric acid levels on the future risk of developing type 2 diabetes independent of other factors.

Methods

We used prospective data from the Framingham Heart Study original (n = 4883) and offspring (n = 4292) cohorts to examine the association between serum uric acid levels and the incidence of diabetes. We used Cox proportional hazards models to estimate the relative risk of incident diabetes adjusting for age, sex, physical activity, alcohol consumption, smoking, hypertension, body mass index, and blood levels of glucose, cholesterol, creatinine, and triglycerides.

Results

We identified 641 incident cases of diabetes in the original cohort and 497 cases in the offspring cohort. The incidence rates of diabetes per 1000 person-years for serum uric acid levels <5.0, 5.0-5.9, 6.0-6.9, 7.0-7.9 and ≥8.0 mg/dL were 3.3, 6.1, 8.7, 11.5, and 15.9, respectively, in the original cohort; and 2.9, 5.0, 6.6, 8.7, and 10.9, respectively, in the offspring cohort (P-values for trends <.001). Multivariable relative risks per mg/dL increase in serum uric acid levels were 1.20 (95% confidence interval; 1.11-1.28) for the original cohort and 1.15 (95% confidence interval; 1.06-1.23) for the offspring cohort.

Conclusions

These prospective data from 2 generations of the Framingham Heart Study provide evidence that individuals with higher serum uric acid; including younger adults, are at a higher future risk of type 2 diabetes independent of other known risk factors. These data expand on cross-sectional associations between hyperuricemia and the metabolic syndrome, and extend the link to the future risk of type 2 diabetes.

Section snippets

Study Population

We conducted analyses of the prospectively collected data in the Framingham Heart Study original and offspring cohorts, using the datasets obtained from the National Heart, Lung and Blood Institute (NHLBI). The Framingham Heart Study–original cohort is an ongoing longitudinal study of 5209 men and women from the town of Framingham, Massachusetts, aged 29-62 years at time of recruitment in 1948. Subjects have been followed biennially, with data from a detailed medical history, a physical

Results

The baseline characteristics of original and offspring cohorts are shown in Table 1. The mean baseline ages were 45 years in the original cohort (45% men) and 37 years in the offspring cohort (48% men).

We identified 641 incident type 2 diabetes cases (320 men) in the original cohort over a 28-year median follow-up, and 497 incident cases (287 men) in the offspring cohort over a 26-year median follow-up. In both cohorts, the incidence of type 2 diabetes increased with increasing serum uric acid

Discussion

In this prospective study of two generations of the Framingham Heart Study, we found that higher levels of serum uric acid were associated with an increasing risk of developing type 2 diabetes. Specifically, for every mg/dL increase in serum uric acid level, the risk of type 2 diabetes was increased by 20% in the original cohort and 15% in the offspring cohort. These associations persisted in both sexes and were independent of other known risk factors of type 2 diabetes, including age, BMI,

Acknowledgment

The authors thank the Framingham Heart Study coordinators for access to the dataset. The Framingham Heart Original and Offspring studies are conducted and supported by the NHLBI in collaboration with the Framingham Heart Study Investigators. This manuscript has been reviewed by the NHLBI before submission for publication. NHLBI had no role in the design, conduct, analyses, and reporting of the study or in the decision to submit the manuscript for publication. The authors would also like to

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      Meanwhile, studies found that IR caused by accumulation of visceral fat may affect urinary tubules to decrease excretion of UA in the urine [8]. What’s more, hyperuricemia has recently been reported as an independent risk factor for T2D [30]. Evidence from experimental studies revealed that UA could increase the risk of T2D through different potential pathogenic factors.

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    Funding: This work was supported in part by grants from the National Institutes of Health (AR047785). Dr. Bhole receives postdoctoral training fellowship support from the Canadian Arthritis Network/The Arthritis Society of Canada. Ms. De Vera receives training support from the Canadian Arthritis Network/The Arthritis Society of Canada, the Michael Smith Foundation for Health Research, and the Canadian Institutes of Health Research.

    Conflict of Interest: Dr. Choi has received research funding from Takeda Pharmaceuticals North America Inc. for an unrelated project. No conflicts of interest for any of the authors.

    Authorship: All authors had access to the data and were involved in drafting the article and revising it critically for important intellectual content.

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