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

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.

Changes in cortical volumetric bone mineral density and thickness, and trabecular thickness in lactating women postpartum.

CONTEXT: Lactation is associated with decreased areal bone mineral density (aBMD). Replenishment occurs especially after ceased lactation. Changes in volumetric bone mineral density (vBMD), microstructure, and dimensional parameters are unknown and may clarify the role of lactation for skeletal health. OBJECTIVE AND MAIN OUTCOMES: The objective of the study was to test the hypothesis that lactation is associated with changes in aBMD, vBMD, microstructure, and dimensional parameters. DESIGN: At baseline (0.5 mo after delivery) and 4, 12, and 18 months thereafter, bone was assessed using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. PARTICIPANTS AND SETTING: Eighty-one fair-skinned postpartum women and 21 controls aged 25-40 years were recruited. The completion ratio was 73%. Postpartum women were categorized depending on duration of lactation: 0-3.9, 4-8.9, and 9 months or longer. RESULTS: During the first 4 months, aBMD decreased at several sites (geometric mean ± SE; -0.73% ± 0.21% to -3.98% ± 0.76%) in women lactating at least 4 months. During the same time, cortical vBMD at the ultradistal tibia decreased in women lactating 4-8.9 months (-0.26% ± 0.08%) and 9 months or longer (-0.49% ± 0.10%). At 12 months postpartum, cortical thickness (≥ 9 mo, -2.48% ± 0.41%) and trabecular thickness (4-8.9 mo, -2.14% ± 0.92%; ≥ 9 mo, -2.56% ± 1.21%) also were lower than baseline. No decreases were found in women lactating less than 4 months or in controls in these parameters. At 18 months postpartum, both cortical vBMD (≥ 9 mo, -0.77% ± 0.17%) and trabecular thickness (4-8.9 mo, -2.25% ± 1.25%; ≥ 9 mo, -3.21% ± 1.41%) were lower in women with long lactation. CONCLUSIONS: Decreases in cortical vBMD, thickness, and trabecular thickness at the ultradistal tibia were found in women lactating 4 months or longer. Longer follow-up is needed to confirm whether women with extended lactation recover fully or whether the changes could potentially lead to an increased risk of fracture in later life.