The Pro12Ala polymorphism of PPARγ2 modulates beta cell function and failure to oral glucose-lowering drugs in patients with type 2 diabetes

被引：2

作者：

Masulli, Maria ^{[1
]}

Della Pepa, Giuseppe ^{[1
]}

Cocozza, Sara ^{[1
]}

Capasso, Mario ^{[2
,3
]}

Pignataro, Piero ^{[2
]}

Vitale, Marilena ^{[1
]}

Gastaldelli, Amalia ^{[4
]}

Russo, Marco ^{[4
]}

Dolce, Pasquale ^{[5
]}

Riccardi, Gabriele ^{[1
]}

Rivellese, Angela A. ^{[1
]}

Vaccaro, Olga ^{[1
]}

机构：

[1] Univ Naples Federico II, Dept Clin Med & Surg, Via Pansini 5, I-80131 Naples, Italy

[2] Univ Naples Federico II, Dept Mol Med & Med Biotechnol, Naples, Italy

[3] CEINGE Adv Biotechnol, Naples, Italy

[4] CNR, Inst Clin Physiol, Pisa, Italy

[5] Univ Naples Federico II, Dept Publ Hlth, Naples, Italy

来源：

DIABETES-METABOLISM RESEARCH AND REVIEWS | 2021年 / 37卷 / 03期

关键词：

beta cell function; insulin sensitivity; pioglitazone; PPAR gamma 2; treatment failure; type; 2; diabetes; INSULIN SENSITIVITY; PIOGLITAZONE; SULFONYLUREA; SECRETION; METFORMIN;

D O I：

10.1002/dmrr.3392

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: We evaluate whether the Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) 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.

引用

页数：7

共 26 条

[1] Common polymorphisms of the PPAR-γ2 (Pro12Ala) and PGC-1α (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial [J].