Mannose is an insulin-regulated metabolite reflecting whole-body insulin sensitivity in man

• Published in: Metabolism, clinical and experimental clinical and experimental, 2020-01, Vol.102, p.153974-153974, Article 153974
• Main Authors: Ferrannini, E., Bokarewa, M., Brembeck, P., Baboota, R., Hedjazifar, S., Andersson, K., Baldi, S., Campi, B., Muscelli, E., Saba, A., Sterner, I., Wasen, C., Smith, U.
• Format: Article
• Language: English
• Subjects: Aged; Biomarkers - blood; Biomarkers - metabolism; Case-Control Studies; Endocrinology and Diabetes; Endokrinologi och diabetes; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin - blood; Insulin - metabolism; Insulin Resistance - physiology; Male; Mannose - blood; Mannose - metabolism; Middle Aged; Signal Transduction - physiology
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2019.153974

Mannose is a glucose-associated serum metabolite mainly released by the liver. Recent studies have shown several unexpected pleiotropic effects of mannose including increased regulatory T cells (Tregs), prevention of auto-immune disease and ability to reduce growth of human cancer cells. We have previously shown in large cohorts that elevated serum mannose levels are associated with future development of type 2 diabetes (T2D) and cardiovascular disease. However, potential direct effects of mannose on insulin sensitivity in vivo or in vitro are unknown. We here show that administration of mannose (0.1 g/kg BW twice daily) for one week in man did not elicit negative effects on meal-modified glucose tolerance, markers of inflammation or insulin levels. Tregs number and insulin signaling in human liver cells were unchanged. These data suggest that mannose is a marker, and not a mediator, of insulin resistance. To verify this, we examined serum mannose levels during long-term euglycemic hyperinsulinemic clamps in non-diabetic and T2D individuals. Mannose was reduced by insulin infusion in proportion to whole-body insulin sensitivity. Thus, mannose is a biomarker of insulin resistance which may be useful for the early identification of diabetic individuals with insulin resistance and increased risk of its complications. What is known•Mannose administration can prevent auto-immune conditions, increase number of T-regulatory cells and reduce growth of cancer cells•Serum mannose levels are increased in obesity and insulin resistance•Elevated mannose levels are associated with increased risk of developing T2D and CVD New Findings•Administration of mannose to non-diabetic individuals did not increase markers of insulin resistance, inflammation or change number of T-regulatory cells•Mannose did not reduce insulin signaling in human liver cells in vitro•Long-term hyperinsulinemic euglycemic clamps showed that serum mannose levels were reduced in relation to degree of insulin sensitivity in both non-diabetic and T2D individuals Impact on clinical practice•Mannose is an easy biomarker of degree of insulin resistance and can be useful for identifying patients with T2D at high risk of developing diabetic renal complications and CVD