title: Circulating mesencephalic astrocyte-derived neurotrophic factor is increased in newly diagnosed prediabetic and diabetic patients, and is associated with insulin resistance.
abstract: Evidence has shown that endoplasmic reticulum (ER) stress was involved in the progression to type 2 diabetes mellitus (T2DM) and development of insulin resistance. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a novel secreted protein upregulated by ER stress. This study aimed to assess serum level of MANF in normal glucose tolerance (NGT) participants and newly diagnosed prediabetic and T2DM patients. A total of 257 participants with NGT, newly diagnosed prediabetes or T2DM were recruited from Yinchao and Hangtian communities of Chengdu, Sichuan, China. Serum MANF level was quantified by enzyme-linked immunosorbent assay (ELISA). The mean age for the 257 participants (147 females) was 62±8 years (range 44-78): 71 with NGT, 115 with newly diagnosed prediabetes and 71 with T2DM. Mean serum MANF level was significantly higher with newly diagnosed prediabetes and T2DM than NGT (2.89±1.09 and 3.03±1.73 vs 2.13±1.37 ng/mL, both p<0.001). MANF level was not correlated with insulin sensitivity indexes (homeostasis model assessment for insulin resistance [HOMA-IR], Matsuda Index and quantitative insulin sensitivity check index [QUICKI]) for NGT and T2DM participants but was correlated with such indexes for prediabetes patients. We concluded that serum MANF level was higher in patients with newly diagnosed prediabetes and T2DM than in NGT controls. MANF appears to be associated with Matsuda Index, QUICKI and HOMA-IR in prediabetes patients.
authors.affiliation: Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.|Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.affiliation: Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Division of Endocrinology and Metabolism, The fifth Hospital of Chengdu, Chengdu, Sichuan 610041, China.
authors.forename: Qiu
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Qinhui
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Molecular Medicine Research Center, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Division of Endocrinology and Metabolism, The fifth Hospital of Chengdu, Chengdu, Sichuan 610041, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Cao
authors.affiliation: The Yinchao Community Hospital of Chengdu, Chengdu, Sichuan 610041, China.
authors.forename: Daigang
authors.initials: D
authors.lastname: Li
authors.affiliation: Chengdu Aerospace Hospital, Chengdu, Sichuan 610041, China.
authors.forename: Shugui
authors.initials: S
authors.lastname: Xie
authors.affiliation: Division of Endocrinology and Metabolism, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Nanwei
authors.initials: N
authors.lastname: Tong
authors.affiliation: Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.|Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital of Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan 610041, China.
authors.forename: Jinhan
authors.initials: J
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis; D005260:Female; D018149:Glucose Intolerance / Q000097:blood; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009414:Nerve Growth Factors / Q000097:blood*; D011236:Prediabetic State / Q000097:blood* / Q000175:diagnosis
chemical_list: D001786:Blood Glucose; C099695:MANF protein, human; D009414:Nerve Growth Factors
keywords: Endoplasmic reticulum stress; Insulin resistance; Mesencephalic astrocyte-derived neurotrophic factor; Type 2 diabetes