Link between serum uric acid and pancreatic beta-cell function in drug naïve subjects with type 2 diabetes treated with sitagliptin

ABSTRACT

Aim: The objective of this study is to investigate the changes of UA with sitagliptin in relation to its glycemic/non-glycemic efficacies.

Methods: Drug naïve subjects with T2DM (n = 62) were administered 25–50 mg/day sitagliptin monotherapy for 3 months. The subjects were divided into two subgroups according to the changes in (Δ) UA (above the median [group A, n = 31]: ΔUA = 23.3%, p < 0.00001, and below the median [group B, n = 31]: ΔUA = −0.9%, n.s.). Changes in glycemic/non-glycemic parameters were compared between these two groups, which acted as a control for each other.

Results: In the overall subjects, UA significantly increased (10.8%, p < 0.00001). Significant correlations between ΔUA and ΔBMI (R = 0.252), ΔHOMA-B (R = 0.309) or ΔCPR-index (R = 0.258), and significant negative correlations between ΔUA and ΔHbA1c (R = −0.290) or ΔFFA (R = −0.271) were seen. Between group A and group B, some parameters displayed distinct regulatory patterns. HbA1c significantly decreased in both groups (group A: from 9.97% to 7.65%, group B: from 10.41% to 8.85%) with significant inter-group differences (higher reductions in group A, p < 0.05). C-peptide (+10.6%) and BMI (+1.7%) significantly increased, and FFA (−20.5%) decreased in group A. HOMA-R or 20/(C-peptide x FBG) had no changes in either group, while HOMA-B (group A: +85.1%, group B: +38.8%) or CPR-index (group A: +37.7%, group B: +20.5%) increased in both groups with significant inter-group differences (both p < 0.01). TG (−18.8%) significantly decreased, and T-C (−3.5%) and non-HDL-C (−4%) had a tendency to decrease in group B.

Conclusions: These results suggest that UA and beta-cell functions/glycemic efficacy are closely linked during sitagliptin therapy. Those with elevated UA had better beta-cell enhancing and glyemic efficacies. Body weights increased and FFA decreased in these populations. By contrast, those without changes in UA had favorable profiles in atherogenic lipids.

KEYWORDS:

• Sitagliptin
• DPP-4 inhibitor
• uric acid
• beta-cell function

Acknowledgments

The author thanks Drs. Kenji Kawashima, Hideki Yamashita, Shugo Yonezawa, Takashi Suzuki and Takashi Nakamura for discussions and useful advice.

Declaration of financial/other relationships

The contents of the paper and the opinions expressed within are those of the authors, and it was the decision of the authors to submit the manuscript for publication.

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Declaration of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

No funding was received in the preparation of this manuscript.