Circulating mesencephalic astrocyte-derived neurotrophic factor is increased in newly diagnosed prediabetic and diabetic patients, and is associated with insulin resistance

Endocr J. 2017 Apr 29;64(4):403-410. doi: 10.1507/endocrj.EJ16-0472. Epub 2017 Feb 17.


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.

Keywords: Endoplasmic reticulum stress; Insulin resistance; Mesencephalic astrocyte-derived neurotrophic factor; Type 2 diabetes.

MeSH terms

  • Adult
  • Aged
  • Asian Continental Ancestry Group
  • Blood Glucose / metabolism
  • Case-Control Studies
  • China
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Female
  • Glucose Intolerance / blood
  • Humans
  • Insulin Resistance*
  • Male
  • Middle Aged
  • Nerve Growth Factors / blood*
  • Prediabetic State / blood*
  • Prediabetic State / diagnosis


  • Blood Glucose
  • MANF protein, human
  • Nerve Growth Factors