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Lowering Uric Acid With Allopurinol Improves Insulin Resistance and Systemic Inflammation in Asymptomatic Hyperuricemia
  1. Mumtaz Takir, MD*,
  2. Osman Kostek, MD,
  3. Abdullah Ozkok, MD,
  4. Omer Celal Elcioglu, MD,
  5. Ali Bakan, MD,
  6. Aybala Erek, MD§,
  7. Hasan Huseyin Mutlu, MD,
  8. Ozge Telci, MD,
  9. Aysun Semerci, MD,
  10. Ali Riza Odabas, MD,
  11. Baris Afsar, MD,
  12. Gerard Smits, PhD**,
  13. Miguel ALanaspa, PhD**,
  14. Shailendra Sharma, MD**,
  15. Richard J. Johnson, MD**,
  16. Mehmet Kanbay, MD††
  1. From the *Department of Medicine, Division of Endocrinology, †Department of Medicine, ‡Department of Medicine, Division of Nephrology, and §Departments of Biochemistry and ¶Family Medicine, Istanbul Medeniyet University, Goztepe Training and Research Hospital, Istanbul; and ∥Department of Medicine, Division of Nephrology, Konya Numune State Hospital, Konya, Turkey; **Division of Renal Diseases and Hypertension, University of Colorado, Denver, CO; and ††Department of Medicine, Division of Nephrology, Koc University School of Medicine, Istanbul, Turkey.
  1. Reprints: Mumtaz Takir, MD, Goztepe Training and Research Hospital, Department of Medicine, Division of Endocrinology, Kadikoy, Istanbul, Turkey. E-mail: mumtaztakir{at}
  2. Dr Johnson is an inventor of a patent at the University of Florida on lowering uric acid in the treatment of insulin resistance (US 2014/0107136 A1) that has been licensed to XORT Therapeutics.


Background Hyperuricemia is an independent predictor of impaired fasting glucose and type 2 diabetes, but whether it has a causal role in insulin resistance remains controversial. Here we tested the hypothesis that lowering uric acid in hyperuricemic nondiabetic subjects might improve insulin resistance.

Methods Subjects with asymptomatic hyperuricemia (n = 73) were prospectively placed on allopurinol (n = 40) or control (n = 33) for 3 months. An additional control group consisted of 48 normouricemic subjects. Serum uric acid, fasting glucose, fasting insulin, HOMA-IR (homeostatic model assessment of insulin resistance), and high-sensitivity C-reactive protein were measured at baseline and at 3 months.

Results Allopurinol-treated subjects showed a reduction in serum uric acid in association with improvement in fasting blood glucose, fasting insulin, and HOMA-IR index, as well as a reduction in serum high-sensitivity C-reactive protein. The number of subjects with impaired fasting glucose significantly decreased in the allopurinol group at 3 months compared with baseline (n = 8 [20%] vs n = 30 [75%], 3 months vs baseline, P < 0.001). In the hyperuricemic control group, only glucose decreased significantly and, in the normouricemic control, no end point changed.

Conclusions Allopurinol lowers uric acid and improves insulin resistance and systemic inflammation in asymptomatic hyperuricemia. Larger clinical trials are recommended to determine if lowering uric acid can help prevent type 2 diabetes.

Key Words
  • uric acid
  • allopurinol
  • insulin resistance
  • inflammation

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