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骨代谢关键标志物骨钙素与中国2型糖尿病患者胰岛β细胞和α细胞分泌功能之间的关联:一项观察性研究。

Association between osteocalcin, a pivotal marker of bone metabolism, and secretory function of islet beta cells and alpha cells in Chinese patients with type 2 diabetes mellitus: an observational study.

作者信息

Lei Haiyan, Liu Jun, Wang Wei, Yang Xinyi, Feng Zhouqin, Zang Pu, Lu Bin, Shao Jiaqing

机构信息

Department of Endocrinology, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, 305 East Zhongshan Road, Nanjing, 210002, Jiangsu, People's Republic of China.

Department of Endocrinology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, 210002, People's Republic of China.

出版信息

Diabetol Metab Syndr. 2022 Oct 28;14(1):160. doi: 10.1186/s13098-022-00932-8.

Abstract

BACKGROUND

Several recent studies have found that Osteocalcin (OCN), a multifunctional protein secreted exclusively by osteoblasts, is beneficial to glucose metabolism and type 2 diabetes mellitus (T2DM). However, the effects of OCN on islets function especially islet ɑ cells function in patients with type 2 diabetes mellitus characterized by a bi-hormonal disease are still unclear. The purpose of this cross-sectional study was to investigate the relationship between serum OCN and the secretion of islet β cells and ɑ cells in Chinese patients with type 2 diabetes mellitus.

METHODS

204 patients with T2DM were enrolled. Blood glucose (FBG, PBG0.5h, PBG1h, PBG2h, PBG3h), insulin (FINS, INS0.5h, INS1h, INS2h, INS3h), C-peptide (FCP, CP0.5h, CP1h, CP2h, CP3h), and glucagon (GLA0, GLA0.5 h, GLA1h, GLA2h, GLA3h) levels were measured on 0 h, 0.5 h, 1 h, 2 h, and 3 h after a 100 g standard bread meal load. Early postprandial secretion function of islet β cells was calculated as Δcp0.5h = CP0.5-FCP. The patients were divided into low, medium and high groups (T1, T2 and T3) according to tertiles of OCN. Comparison of parameters among three groups was studied. Correlation analysis confirmed the relationship between OCN and pancreatic secretion. Multiple regression analysis showed independent contributors to pancreatic secretion.

MAIN RESULTS

FBG, and PBG2h were the lowest while Δcp0.5h was the highest in the highest tertile group (respectively, p < 0.05). INS3h, area under the curve of insulin (AUC) in T3 Group were significantly lower than T1 Group (respectively, p < 0.05). GLA1h in T3 group was lower than T1 group (p < 0.05), and GLA0.5 h in T3 group was lower than T2 and T1 groups (p < 0.05). Correlation analysis showed OCN was inversely correlated with Homeostatic model of insulin resistance (HOMA-IR), INS3h, AUC (p < 0.05), and was still inversely correlated with FCP, GLA0.5 h, GLA1h, area under the curve of glucagon (AUC) (respectively, p < 0.05) after adjustment for body mass index (BMI) and alanine aminotransferase (ALT). The multiple regression analysis showed that OCN was independent contributor to Δcp0.5h, GLA0.5h and GLA1h (respectively, p < 0.05).

CONCLUSIONS

Higher serum OCN level is closely related to better blood glucose control, higher insulin sensitivity, increased early-phase insulin secretion of islet β cells and appropriate inhibition of postprandial glucagon secretion of islet ɑ cells in adult patients with type 2 diabetes mellitus.

摘要

背景

最近的几项研究发现,骨钙素(OCN)是一种仅由成骨细胞分泌的多功能蛋白质,对葡萄糖代谢和2型糖尿病(T2DM)有益。然而,在以双激素疾病为特征的2型糖尿病患者中,OCN对胰岛功能尤其是胰岛α细胞功能的影响仍不清楚。这项横断面研究的目的是调查中国2型糖尿病患者血清OCN与胰岛β细胞和α细胞分泌之间的关系。

方法

招募204例T2DM患者。在100克标准面包餐负荷后0小时、0.5小时、1小时、2小时和3小时测量血糖(空腹血糖、餐后0.5小时血糖、餐后1小时血糖、餐后2小时血糖、餐后3小时血糖)、胰岛素(空腹胰岛素、餐后0.5小时胰岛素、餐后1小时胰岛素、餐后2小时胰岛素、餐后3小时胰岛素)、C肽(空腹C肽、餐后0.5小时C肽、餐后1小时C肽、餐后2小时C肽、餐后3小时C肽)和胰高血糖素(空腹胰高血糖素、餐后0.5小时胰高血糖素、餐后1小时胰高血糖素、餐后2小时胰高血糖素、餐后3小时胰高血糖素)水平。胰岛β细胞的早期餐后分泌功能计算为Δcp0.5h = CP0.5 - FCP。根据OCN的三分位数将患者分为低、中、高组(T1、T2和T3)。研究三组之间参数的比较。相关性分析确定了OCN与胰腺分泌之间的关系。多元回归分析显示了胰腺分泌的独立影响因素。

主要结果

最高三分位数组的空腹血糖和餐后2小时血糖最低,而Δcp0.5h最高(分别为p < 0.05)。T3组的餐后3小时胰岛素、胰岛素曲线下面积(AUC)显著低于T1组(分别为p < 0.05)。T3组的餐后1小时胰高血糖素低于T1组(p < 0.05),T3组的餐后0.5小时胰高血糖素低于T2组和T1组(p < 0.05)。相关性分析显示OCN与胰岛素抵抗稳态模型(HOMA-IR)、餐后3小时胰岛素、AUC呈负相关(p < 0.05),在调整体重指数(BMI)和丙氨酸转氨酶(ALT)后,仍与空腹C肽、餐后0.5小时胰高血糖素、餐后1小时胰高血糖素、胰高血糖素曲线下面积(AUC)呈负相关(分别为p < 0.05)。多元回归分析显示OCN是Δcp0.5h、餐后0.5小时胰高血糖素和餐后1小时胰高血糖素的独立影响因素(分别为p < 0.05)。

结论

在成年2型糖尿病患者中,较高的血清OCN水平与更好的血糖控制、更高的胰岛素敏感性、胰岛β细胞早期胰岛素分泌增加以及胰岛α细胞餐后胰高血糖素分泌的适当抑制密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1d1d/9615358/b9bd9432bf59/13098_2022_932_Fig1_HTML.jpg

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