Proinsulin associates with poor β‐cell function, glucose‐dependent insulinotropic peptide, and insulin resistance in persistent type 2 diabetes after Roux‐en‐Y gastric bypass in humans

Patel Kapila; Levesque Kiarra; Mark VictoriaPierini EsmeraldaRojas BetsyAhlers MichaelShah AnkitLaferrère Blandine

摘要

Abstract Background The determinants of type 2 diabetes (T2D) remission and/or relapse after gastric bypass (RYGB) remain fully unknown. This study characterized β‐ and α‐cell function, in cretin hormone release and insulin sensitivity in individuals with (remitters) or without (non‐remitters) diabetes remission after RYGB. Methods This is a cross‐sectional study of two distinct cohorts of individuals with or without diabetes remission at least 2?years after RYGB. Each individual underwent‐either an oral glucose (remitters) or a mixed meal (non‐remitters) test; glucose, proinsulin, insulin, C‐peptide, glucagon, incretins and leptin were measured. Results Compared to remitters (n = 23), non‐remitters (n = 31) were older (mean [±SD] age 56.1?±?8.2 vs. 46.0?±?8.9?years, P ??0.001), had longer diabetes duration (13.1?±?10.1 vs. 2.2?±?2.4?years, P ?0.001), were further out from the surgery (5.6?±?3.3 vs. 3.5?±?1.7?years, P ??0.01), were more insulin resistant (HOMA‐IR 4.01?±?3.65 vs. 2.08?±?1.22, P ??0.001), but did not differ for body weight. As predicted, remitters had higher β‐cell glucose sensitivity (1.95?±?1.23 vs. 0.86?±?0.55?pmol/kg/min/mmol, P ??0.001) and disposition index (1.55?±?1.75 vs 0.33?±?0.27, P = 0.003), compared to non‐remitters, who showed non‐suppressibility of glucagon during the oral challenge (time?×?group P = 0.001). Higher proinsulin (16.55?±?10.45 vs. 6.62?±?3.50 PM, P ??0.0001), and proinsulin: C‐peptide (40.83?±?29.43 vs. 17.13?±?7.16, P ?0.001) were strongly associated with non‐remission status, while differences in incretins between remitters and non‐remitters were minimal. Conclusions Individual without diabetes remission after gastric bypass have poorer β‐cell response and lesser suppression of glucagon to an oral challenge; body weight and incretins differ minimally according to remission status.

机译：抽象背景2型的决定因素糖尿病(T2D)缓解和/或复发胃旁路手术(RYGB)仍然是完全未知的。地理特征研究β和α细胞功能,白痴荷尔蒙的释放和胰岛素敏感性个人(汇款人)或没有(非必经汇款)糖尿病RYGB后缓解。方法这是一个横截面的研究不同的群个体有或没有糖尿病缓解至少2 ?每个人接受口服葡萄糖量(汇款人)或混合粉(非必经汇款)测试;葡萄糖,胰岛素原、胰岛素、C肽,应承担的胰高糖素、肠促胰岛素和瘦素测定。结果与汇款人(n = 23)相比,非必经汇款(n = 31)(平均(±SD)年龄老56 . 1±?美国8。2。46 . 0±,9月8日?糖尿病持续时间较长(±13.1 ? 10.1 vs。2.4±2.2 ? ?从手术(3.3 vs 3.5±5.6 ? ?±1.7吗?0.01 P & ?),更有胰岛素抵抗(HOMA IR 4.01±?‐26.4 vs 2.08±? 1.22,页0.001 & ?),但没有体重而有所不同。正如预测的那样,缓解率较高β细胞葡萄糖灵敏度(±1.95 ? 1.23 vs。0.55±0.86 ? ?提供索引(±1.55 ? 1.75 vs 0.33 ?±0.27,页= 0.003),而非高未显示非suppressibility等在口服胰高血糖素挑战(时间×?胰岛素原(10.45 vs 6.62±16.55 ? ?±3.50点,P0.0001 & ?),胰岛素原:C肽(40个。83 ? 29±?美国43。13 ?±7月17日,P ? 0.001)与非必经缓解密切相关地位,而肠促胰岛素差异汇款和非汇款是最小的。结论个体没有糖尿病缓解胃旁路手术后发生β细胞反应和较小的抑制胰高糖素口服挑战;最低限度根据缓解状态。

Proinsulin associates with poor β‐cell function, glucose‐dependent insulinotropic peptide, and insulin resistance in persistent type 2 diabetes after Roux‐en‐Y gastric bypass in humans

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