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

J Diabetes. 2020 Jan;12(1):77-86. doi: 10.1111/1753-0407.12964. Epub 2019 Jul 24.

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.

背景: 目前尚未完全明确2型糖尿病(T2D)患者接受胃旁路术(RYGB)后病情缓解或复发的决定因素。这项研究描述了RYGB术后糖尿病缓解或未缓解个体的β-与α-细胞功能、肠促胰岛素激素释放及胰岛素敏感性。 方法: 这是一项横断面研究, 对RYGB术后至少2年后糖尿病缓解或未缓解的不同队列个体进行了研究。每个个体均进行口服葡萄糖(缓解者)或者混合餐(非缓解者)耐量试验;测量血糖、胰岛素原、胰岛素、C肽、胰高血糖素、肠促胰岛素以及瘦素水平。 结果: 与缓解者(n=23)相比, 未缓解者(n=31)年龄更大(平均[±SD]年龄56.1±8.2 vs. 46.0±8.9岁, P<0.001)、糖尿病病程更长(13.1±10.1 vs. 2.2±2.4年, P<0.001)、距离手术时间更长(5.6±3.3 vs. 3.5±1.7年, P<0.01)、胰岛素抵抗更严重(HOMA-IR为4.01±3.65 vs. 2.08±1.22, P<0.001), 但体重无差异。正如预期, 与未缓解者相比, 缓解者具有较高的β细胞葡萄糖敏感性(1.95±1.23 vs. 0.86±0.55 pmol/kg/min/mmol, P<0.001)以及处置指数(1.55±1.75 vs. 0.33±0.27, P=0.003), 后者在口服耐量试验期间的胰高血糖素水平并未受到抑制(时间×分组, P=0.001)。较高水平的胰岛素原(16.55±10.45 vs. 6.62±3.50PM, P<0.0001)以及胰岛素原:C肽比值(40.83±29.43与17.13±7.16, P<0.001)与未缓解状态密切相关, 但是缓解者与未缓解者之间的肠促胰岛素差异非常小。 结论: 胃旁路术后糖尿病无缓解的个体对口服耐量试验中β细胞的应答较差, 对胰高血糖素的抑制也较小;根据糖尿病缓解状态进行分组, 发现体重与肠促胰岛素的差异非常小。.

Keywords: diabetes remission; gastric bypass; incretins; proinsulin; β-Cell function; β细胞功能。; 糖尿病缓解; 肠促胰岛素; 胃旁路; 胰岛素原.

MeSH terms

  • Adult
  • Blood Glucose / analysis*
  • Body Weight
  • C-Peptide / blood
  • Cohort Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Female
  • Gastric Bypass*
  • Glucagon / blood
  • Glucose Tolerance Test*
  • Humans
  • Insulin / blood
  • Insulin Resistance
  • Insulin-Secreting Cells / metabolism
  • Male
  • Middle Aged
  • Recurrence

Substances

  • Blood Glucose
  • C-Peptide
  • Insulin
  • Glucagon