Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial

Lin Yang, Huiying Liang, Xinyuan Liu, Xia Wang, Ying Cheng, Yunjuan Zhao, Lingjiao Liu, Gan Huang, Xiangbing Wang, Zhiguang Zhou, Lin Yang, Huiying Liang, Xinyuan Liu, Xia Wang, Ying Cheng, Yunjuan Zhao, Lingjiao Liu, Gan Huang, Xiangbing Wang, Zhiguang Zhou

Abstract

Context: The long-term effects of dipeptidyl peptidase-4 inhibitors on β-cell function and insulin sensitivity in latent autoimmune diabetes in adults (LADA) are unclear.

Objective: To investigate the effects of sitagliptin on β-cell function and insulin sensitivity in LADA patients receiving insulin.

Design and setting: A randomized controlled trial at the Second Xiangya Hospital.

Methods: Fifty-one patients with LADA were randomized to sitagliptin + insulin (SITA) group or insulin alone (CONT) group for 24 months.

Main outcome measures: Fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP) during mixed-meal tolerance test, △CP (2hCP - FCP), and updated homeostatic model assessment of β-cell function (HOMA2-B) were determined every 6 months. In 12 subjects, hyperglycemic clamp and hyperinsulinemic euglycemic clamp (HEC) tests were further conducted at 12-month intervals.

Results: During the 24-month follow-up, there were no significant changes in β-cell function in the SITA group, whereas the levels of 2hCP and △CP in the CONT group were reduced at 24 months. Meanwhile, the changes in HOMA2-B from baseline were larger in the SITA group than in the CONT group. At 24 months, first-phase insulin secretion was improved in the SITA group by hyperglycemia clamp, which was higher than in the CONT group (P < .001), while glucose metabolized (M), insulin sensitivity index, and M over logarithmical insulin ratio in HEC were increased in the SITA group (all P < .01 vs baseline), which were higher than in the CONT group.

Conclusion: Compared with insulin intervention alone, sitagliptin plus insulin treatment appeared to maintain β-cell function and improve insulin sensitivity in LADA to some extent.

Trial registration: ClinicalTrials.gov NCT01159847.

Keywords: insulin sensitivity; islet β-cell function; latent autoimmune diabetes in adults; sitagliptin.

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.
Figure 1.
Flow diagram of randomized patients. FCP, fasting C-peptide.
Figure 2.
Figure 2.
Islet β-cell function evaluated by hyperglycemic clamp. Black circles: SITA group (n=6); white squares: CONT group (n=6). Fasting insulin (FINS, A), the first-phase insulin secretion (1PH, B), the second-phase insulin secretion (2PH, C) and the maximum insulin secretion (MIS, D) were calculated at the indicated month. Data were expressed as mean and SEM. *P < .05, **P < .01, ***P < .001 vs CONT group (MANOVA), △P < .05 vs the baseline in SITA group and #P < .05, ##P < 0.01 vs the baseline in CONT group (repeated measures ANOVA).
Figure 3.
Figure 3.
Insulin sensitivity evaluated by hyperinsulinemic euglycemic clamp. Black circles: SITA group (n=6); white squares: CONT group (n=6). Glucose metabolized (M, A), insulin sensitivity index (ISI, B) and M/log I ratio were calculated at the indicated month. Data were presented as mean and SEM. *P < .05 vs CONT group (MANOVA), △P < .05, △△P < .01 vs the baseline in SITA group and #P < .05, ##P < .01 vs the baseline in CONT group (repeated measures ANOVA).

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