In:
Diabetes/Metabolism Research and Reviews, Wiley, Vol. 37, No. 3 ( 2021-03)
Abstract:
We evaluate whether the Pro12Ala polymorphism of peroxisome proliferator‐activated receptor γ2 (PPARγ2) has a role in the progression of diabetes by modulating the occurrence of treatment failure to glucose‐lowering drugs. Methods We studied 215 patients with type 2 diabetes participating in the Thiazolidinediones Or Sulphonylureas and Cardiovascular Accidents Intervention Trial study. All participants were insufficiently controlled (glycated haemoglobin [HbA 1c ] 7.0%‐9.0%) with metformin 2 g/day and were randomly allocated to add‐on pioglitazone or a sulfonylurea. Treatment failure was defined as HbA 1c ≥8% on two consecutive visits, 3 months apart. Results Carriers or non‐carriers of the polymorphism had similar age, body mass index, and diabetes duration. Ala carriers had lower fasting plasma insulin, better insulin sensitivity (Homeostasis Model Assessment [HOMA]2‐%S), and worse beta cell secretion (HOMA2‐%B) than non‐carriers. During 24 months of follow‐up, 32.5% among the Ala carriers and 8.6% among non‐carriers ( P 〈 0.001) developed treatment failure with a cumulative incidence of 18.6 vs 4.6/100 person‐years. Those patients who developed treatment failure were older, had a younger age at diabetes diagnosis (48 ± 10 vs 52 ± 7 years; P = 0.032), higher HbA 1c (8.1 ± 0.5 vs 7.7 ± 0.5%; P 〈 0.001), and lower HOMA2‐%B (30 ± 12 vs 46 ± 29; P = 0.015) at study entry, as compared to those who did not develop treatment failure. At multivariate analysis, the Pro12Ala polymorphism was significantly associated with treatment failure (hazard ratio [HR] 4.45; 95% confidence interval [CI] 1.79‐11.1; P 〈 0.001); HbA 1c at study entry was the other independent predictor of failure in this study population. Conclusion The Pro12Ala polymorphism is associated with a greater insulin sensitivity, reduced beta cell function and a substantially increased risk of treatment failure.
Type of Medium:
Online Resource
ISSN:
1520-7552
,
1520-7560
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
2001565-3
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