Dataset Information

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.

SUBMITTER: Yang L

PROVIDER: S-EPMC7993585 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe pathogenesis of the progressive loss of beta cell function latent autoimmune diabetes in adults (LADA) remains still elusive. We aim to study the fatty acid (FA) profile in LADA.Subjects and methodsData from 116 patients with diabetes and GADA and 249 diabetes controls without GADA selected by Propensity Score Matching were collected. FA was analyzed with liquid chromatography-tandem mass spectrometry analysis.ResultsPrincipal factor analysis found component 1 explains 82.6% of total variance contained fatty acids from a mixed of lard oil, seafood, and vegetable diet, followed by diet predominantly from vegetable oil, a diet of high fat diet, and a diet of seafood diet. The FA heatmap looked clearly different among the three groups with more similar type 1 (t1dm) and LADA fatty acid profile. n-3 α-linolenic acid (ALA), n-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA), such as Eicosapentaenoic Acid and Docosapentaenoic Acid, n-3/n-6 ratio and triene/tetraene ratio were higher in patients with type 2 diabetes (t2dm) compared with LADA and t1dm. Saturated FAs were lower in t2dm than t1dm and LADA. Arachidic acid and n-6 LC-PUFAs were lower in t2dm than in t1dm and LADA. The characteristics of FAs in LADA were in between of classical t1dm and t2dm. Patients were classified into 6 clusters by FA clusters. Only cluster 2, 3, 5 contained enough patients to be analyzed. Cluster 5 showed an insulin deficient phenotype containing more than 60% of patients with t1dm and LADA and only 12.8% of t2dm. Cluster 2 and 3 were similar. β cell function and glycemic control was better in cluster 3 homing 25% of t2dm. Cluster 2 held 28% of t1dm and LADA, in this cluster more than 60% of patients was t2dm. n-3 linolenic acid, n-3 LC-PUFAs, some n-6 LC-PUFAs, n-3/n-6 ratio and triene/tetraene ratio were negatively associated with GADA positivity while n-6 Arachidonic Acid was associated positively with GADA. Similar findings were found for insulin sensitivity and beta cell function.ConclusionPUFA are associated with insulin sensitivity and beta cell function, and like other clinical features, FA profile distributed differently, but could not be used as makers to differentiate LADA from t1dm and t2dm.Ethics and disseminationThis study has been approved by the Ethical Review Committee of Second Hospital of Dalian Medical University (approval number: 2021-005).Clinical trial registrationnone.