糖尿病通过促进恶病质及其相关炎症状态增加了胰腺和结直肠癌患者的死亡率。

Diabetes increases mortality in patients with pancreatic and colorectal cancer by promoting cachexia and its associated inflammatory status.

机构信息

Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany; Joint Heidelberg-IDC Translational Diabetes Program, Heidelberg University Hospital, Heidelberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany.

Department of Surgery, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany; Institute of Experimental Oncology and Therapy Research, School of Medicine, Technical University of Munich, Munich, Germany.

出版信息

Mol Metab. 2023 Jul;73:101729. doi: 10.1016/j.molmet.2023.101729. Epub 2023 Apr 22.

DOI:10.1016/j.molmet.2023.101729

PMID:37094629

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10192649/

Abstract

OBJECTIVES

Cancer is considered an emerging diabetes complication, with higher incidence and worse prognosis in patients with diabetes. Cancer is frequently associated with cachexia, a systemic metabolic disease causing wasting. It is currently unclear how diabetes affects the development and progression of cachexia.

METHODS

We investigated the interplay between diabetes and cancer cachexia retrospectively in a cohort of 345 patients with colorectal and pancreatic cancer. We recorded body weight, fat mass, muscle mass, clinical serum values, and survival of these patients. Patients were grouped either into diabetic/non-diabetic groups based on previous diagnosis, or into obese/non-obese groups based on body mass index (BMI ≥30 kg/m was considered obese).

RESULTS

The pre-existence of type 2 diabetes, but not obesity, in patients with cancer led to increased cachexia incidence (80%, compared to 61% without diabetes, p ≤ 0.05), higher weight loss (8.9% vs. 6.0%, p ≤ 0.001), and reduced survival probability (median survival days: 689 vs. 538, Chi square = 4.96, p ≤ 0.05) irrespective of the initial body weight or tumor progression. Patients with diabetes and cancer showed higher serum levels of C-reactive protein (0.919 μg/mL vs. 0.551 μg/mL, p ≤ 0.01) and interleukin 6 (5.98 pg/mL vs. 3.75 pg/mL, p ≤ 0.05) as well as lower serum albumin levels (3.98 g/dL vs. 4.18 g/dL, p ≤ 0.05) than patients with cancer without diabetes. In a sub-analysis of patients with pancreatic cancer, pre-existing diabetes worsened weight loss (9.95% vs. 6.93%, p ≤ 0.01), and increased the duration of hospitalization (24.41 days vs. 15.85 days, p ≤ 0.001). Further, diabetes aggravated clinical manifestations of cachexia, as changes in the aforementioned biomarkers were more pronounced in patients with diabetes and cachexia co-existence, compared to cachectic patients without diabetes (C-reactive protein: 2.300 μg/mL vs. 0.571 μg/mL, p ≤ 0.0001; hemoglobin: 11.24 g/dL vs. 12.52 g/dL, p ≤ 0.05).

CONCLUSIONS

We show for the first time that pre-existing diabetes aggravates cachexia development in patients with colorectal and pancreatic cancer. This is important when considering cachexia biomarkers and weight management in patients with co-existing diabetes and cancer.

摘要

目的

癌症被认为是一种新兴的糖尿病并发症，在糖尿病患者中的发病率更高，预后更差。癌症常伴有恶病质，这是一种全身性代谢疾病，会导致消瘦。目前尚不清楚糖尿病如何影响恶病质的发展和进展。

方法

我们回顾性地在 345 名结直肠癌和胰腺癌患者的队列中研究了糖尿病和癌症恶病质之间的相互作用。我们记录了这些患者的体重、体脂肪量、肌肉量、临床血清值和生存情况。患者根据既往诊断分为糖尿病/非糖尿病组，或根据体重指数（BMI≥30 kg/m 为肥胖）分为肥胖/非肥胖组。

结果

患有癌症的患者中存在 2 型糖尿病（而非肥胖）会导致恶病质发病率增加（80%，而无糖尿病的患者为 61%，p≤0.05），体重下降更多（8.9% vs. 6.0%，p≤0.001），且生存概率降低（中位生存天数：689 天 vs. 538 天，卡方检验=4.96，p≤0.05），与初始体重或肿瘤进展无关。患有糖尿病和癌症的患者的血清 C 反应蛋白（0.919 μg/mL 比 0.551 μg/mL，p≤0.01）和白细胞介素 6（5.98 pg/mL 比 3.75 pg/mL，p≤0.05）水平更高，血清白蛋白水平更低（3.98 g/dL 比 4.18 g/dL，p≤0.05）。在胰腺癌患者的亚分析中，糖尿病的存在加重了体重下降（9.95% vs. 6.93%，p≤0.01），并增加了住院时间（24.41 天 vs. 15.85 天，p≤0.001）。此外，糖尿病加重了恶病质的临床表现，因为与没有糖尿病的恶病质患者相比，存在糖尿病和恶病质共存的患者上述生物标志物的变化更为明显（C 反应蛋白：2.300 μg/mL 比 0.571 μg/mL，p≤0.0001；血红蛋白：11.24 g/dL 比 12.52 g/dL，p≤0.05）。