Plasma follistatin is elevated in patients with type 2 diabetes: Relationship to hyperglycemia, hyperinsulinemia, and systemic low-grade inflammation
Abstract
BACKGROUND: Plasma follistatin is elevated in patients with low-grade inflammation and insulin resistance as observed with polycystic ovary syndrome. In the present study, we evaluated plasma follistatin in patients with type 2 diabetes characterised by low-grade inflammation and assessed the acute effects of hyperglycemia, hyperinsulinemia and LPS on plasma follistatin. METHODS: Baseline plasma follistatin and inflammatory biomarkers were measured in a cross-sectional study that involved 95 patients with type 2 diabetes and 103 matched controls. To determine the acute effect of hyperglycemia and hyperinsulinemia on follistatin, hyperglycemic and hyperinsulinemic-euglycemic clamps were performed in five healthy males. Furthermore, 15 patients with type 2 diabetes and 22 healthy controls were challenged with low-dose LPS to determine the effect on follistatin. RESULTS: Patients with type 2 diabetes have higher HOMA2-IR values mean [95% CI] 1.64 [1.40-1.93] versus mean 0.86 [0.75-0.99], p < 0.001 and inflammatory markers compared with controls. Baseline plasma follistatin is elevated in patients with type 2 diabetes compared with controls mean 1564 [1456-1680] versus mean 1328 [1225-1440] ng/L, p = 0.003 and correlates with fasting glucose levels (r = 0.44, p < 0.0001), 2 h glucose (r = 0.48, p < 0.0001), HbA1c (r = 0.41, p < 0.0001), triacylglycerol (r = 0.28, p = 0.008) and total cholesterol (r = 0.33, p = 0.004) in patients but not in controls. No correlation exists between plasma follistatin and inflammatory biomarkers in either of the groups. Neither hyperglycemia, hyperinsulinemia nor LPS increase plasma follistatin. CONCLUSIONS: Plasma follistatin is moderately elevated in patients with type 2 diabetes. Our findings suggest that this is not likely caused by hyperglycemia, hyperinsulinemia or systemic low-grade inflammation.
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Patients with obesity-related insulin resistance present increased basal levels of follistatin, but its exercise-induced release by the liver is blunted.
“Expectedly, like FGF21, patients with obesity-related insulin resistance present increased basal levels of follistatin [157,180], but its exercise-induced release by the liver is blunted [157].”
Patients with type 2 diabetes have slightly elevated levels of circulating FST and plasma levels associated with glycemic parameters.
“Patients with type 2 diabetes have slightly elevated levels of circulating FST and plasma levels associated with glycemic parameters in these patients [188,191,192] (Table 1).”
From Hepatokines and metabolism: Deciphering communication from the liver (2021) · cites this paper as [191]
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- Authors
- Hansen, J., Rinnov, A., Krogh‐Madsen, R., Fischer, C. P., Andreasen, A. S., Berg, R. M. G., Møller, K., Pedersen, B. K., & Plomgaard, P.
- Affiliations
- University of Copenhagen (DK)
- Corresponding author
- Hansen, J.
- ORCID
- Venue
- Diabetes/Metabolism Research and Reviews
- Publisher
- Wiley
- Published
- 2013-09
- Volume
- 29
- Issue
- 6
- Pages
- 463-472
- ISSN
- 1520-7552 (ISSN-L)
- 1520-7560
- OpenAlex
- W1719604068
- Cited by
- 71
- References
- 34
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 2 · 2020: 5 · 2019: 6 · 2018: 7 · 2017: 4 · 2016: 9 · 2015: 4 · 2014: 1
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes/Metabolism Research and Reviews (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Sundhed og Sygdom, Det Frie Forskningsråd
- Danmarks Grundforskningsfond
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- follistatin, type 2 diabetes, hyperinsulinemia, hyperglycemia, low-grade inflammation, insulin resistance, lipopolysaccharide, HOMA-IR, hyperinsulinemic-euglycemic clamp, inflammatory markers, HbA1c, triglycerides, total cholesterol, polycystic ovary syndrome, adiponectin
- MeSH terms
- Adult, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Female, Humans, Hyperglycemia, Hyperinsulinism, Inflammation, Male, Middle Aged, Case-Control Studies, Follistatin, Young Adult
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