1559-P: Heterogeneity of Trajectories of Metabolic Parameters after 50% Beta-Cell Mass Loss by Pancreatectomy

IF 6.2 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Pub Date : 2024-07-19 DOI:10.2337/db24-1559-p

ROBERTO BIZZOTTO, GIANFRANCO DI GIUSEPPE, LAURA SOLDOVIERI, FRANCESCA CINTI, SIMONA MOFFA, MICHELA BRUNETTI, GEA CICCARELLI, SERGIO ALFIERI, GIUSEPPE QUERO, ANDREA MARI, ANDREA GIACCARI, TERESA MEZZA

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引用次数: 0

Abstract

Temporal trajectories of metabolic parameters in the onset of dysglycemia are heterogeneous. We aimed to characterize the temporal trajectories of metabolic parameters after β cell mass reduction by pancreatectomy and to study their heterogeneity. Individuals without known diabetes diagnosis (N = 83) underwent mixed-meal/oral glucose tolerance tests (MMTT/OGTT) and/or hyperglycemic/euglycemic clamp (HC/EC) procedures, before and after surgery. We performed stepwise multivariate linear regression analysis on the glucose tolerance (GT) class (treated as ordinal number, 1 to 3) after surgery, using as independent variables the baselines and changes with surgery of anthropometrics and MMTT- and HC-derived functional parameters of insulin secretion, clearance, and sensitivity (IS), imputed via missForest algorithm when missing. We used the variables selected in this analysis (p<0.01) as input for the reversed graphed embedding (RGE) framework, to identify groups of individuals with extreme combinations of the variables (archetypes). Independent associations with after-surgery GT class (cross-validated R2 = 0.57) were observed for changes in IS and β cell glucose sensitivity (GS), and for baseline IS, GS, 1st phase insulin secretion, insulin secretion at 6 mmol/L glucose, and insulin clearance. IS and the β cell function parameters showed different trajectories combinations in each of the 5 archetypes identified via RGE (median adjusted Rand index = 0.88; N = 16, 8, 15, 13, 18). After surgery, all archetypes included individuals in each of the 3 GT classes (all proportions > 0 at 95% CI). The same β cell mass reduction determines a variety of combinations in changes of IS and β cell functional mechanisms. We identified five archetypes underlying these combinations. The same final GT class can be reached by individuals in any of the archetypes, which shed light on the hidden heterogeneity of glycaemic deterioration. Disclosure R. Bizzotto: None. G. Di Giuseppe: None. L. Soldovieri: None. F. Cinti: None. S. Moffa: None. M. Brunetti: None. G. Ciccarelli: None. S. Alfieri: None. G. Quero: None. A. Mari: Consultant; Lilly Diabetes. A. Giaccari: None. T. Mezza: None.

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1559-P：胰腺切除术导致 50%β细胞质量丧失后代谢参数轨迹的异质性

血糖异常发病过程中代谢参数的时间轨迹具有异质性。我们旨在描述胰腺切除术导致β细胞质量减少后代谢指标的时间轨迹，并研究其异质性。未确诊糖尿病的患者（83 人）在手术前后接受了混合餐/口服葡萄糖耐量试验（MMTT/OGTT）和/或高血糖/血糖钳夹（HC/EC）程序。我们对术后的葡萄糖耐量（GT）分级（按序数处理，1 到 3）进行了逐步多变量线性回归分析，将人体测量和 MMTT 和 HC 衍生的胰岛素分泌、清除和敏感性（IS）功能参数的基线和手术后的变化作为自变量，缺失时通过 missForest 算法进行归类。我们将分析中选择的变量（p<0.01）作为反向图形嵌入（RGE）框架的输入，以识别具有极端变量组合（原型）的个体群体。在IS和β细胞葡萄糖敏感性（GS）的变化以及基线IS、GS、第一阶段胰岛素分泌、6 mmol/L葡萄糖时的胰岛素分泌和胰岛素清除率方面，观察到了与术后GT等级的独立关联（交叉验证R2 = 0.57）。在通过 RGE 确定的 5 个原型中，每个原型的 IS 和 β 细胞功能参数都显示出不同的轨迹组合（调整后 Rand 指数中值 = 0.88；N = 16、8、15、13、18）。手术后，所有原型都包括 3 个 GT 类别中的每个类别（所有比例 > 0，95% CI）。同样的 β 细胞质量减少决定了 IS 和 β 细胞功能机制变化的各种组合。我们确定了这些组合的五种原型。任何一种原型的个体都能达到相同的最终 GT 等级，这揭示了血糖恶化的隐蔽异质性。披露 R. Bizzotto：无。G. Di Giuseppe：无。L. Soldovieri：无。F. Cinti：无：无。S. Moffa：无：无。M. 布鲁内蒂无。G. Ciccarelli：无。S. Alfieri: None.G. Quero：无：无。A. Mari：顾问；礼来糖尿病公司。A. Giaccari：无。T. Mezza：无。

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来源期刊

Diabetes 医学-内分泌学与代谢

CiteScore

12.50

自引率

2.60%

发文量

1968

审稿时长

1 months

期刊介绍： Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.