Plasma follistatin is elevated in patients with type 2 diabetes: Relationship to hyperglycemia, hyperinsulinemia, and systemic low-grade inflammation

摘要

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], p0.001 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, p0.0001), 2h glucose (r=0.48, p0.0001), HbA1c (r=0.41, p0.0001), 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.