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

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.

Figure 1.

Flow diagram of randomized patients. FCP, fasting C-peptide.

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.

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).