Background: Assessing the progression of a disorder from its pre-clinical state is important in the prevention of various diseases. In the present study, we evaluated the role of serum levels of αKlotho (αKl) in the progression of several pre-clinical disorders. Methods: This cohort study included 80 males who underwent their annual health checkup during the entry period between April 2005 and March 2008. Physical and biochemical parameters were obtained from all subjects. The associations of baseline serum levels of soluble αKl (sαKl) with the progression of the disorders were assessed in the study. Results: Baseline serum levels of sαKl were significantly lower in subjects developing a high fasting plasma glucose (FPG) level than in subjects not developing a high FPG level. Logistic multivariable analysis showed that baseline serum levels of sαKl and FPG levels significantly associated with a high FPG level progression. It is suggested that low sαKl levels are associated with the progression of hyperglycemia. Evaluation of serum levels of sαKl in subjects with multiple disorders revealed that those with more pre-clinical disorders progression tended to show lower sαKl levels. Conclusion: A decrease in serum levels of sαKl could be associated with the progression of pre-clinical disorders.