2068-P: Alpha Klotho Modulation with Remission of Prediabetes in Human Subjects

Alpha klotho (αK) a protein named for its severe aging effects when under expressed has one of its primary sites of synthesis in the kidneys. Therefore, anything resulting in kidney damage may result in lower αK levels. Diabetes is one of the most common causes of kidney damage; thus, assessing αK levels in relation to glycemic control was the objective of this study. Twelve obese subjects, age 43.1±1.3 years, with prediabetes were studied at baseline and 6 months (mo) after 10% weight loss on a diet consisting of 30% protein, 30% fat, 40% carbohydrates which resulted in 100% remission of their prediabetes to normal glucose. Glucose, insulin and αK levels were determined during a 75 gm glucose tolerance test (OGTT) at baseline and 6 mo. Soluble αK levels increased significantly from baseline to six mo. Although the microalbumin/creatinine ratio was within normal range at baseline indicating normal kidney function, the ratio improved significantly at 6 mo. Levels of soluble αK were determined to positively covary with the glucose (r 2 = 0.83) and insulin levels (r 2 = 0.74) during the OGTT at both baseline and at 6 mo. These results suggest that αK levels may be markers of very early stages of renal damage in prediabetic subjects and that glucose and insulin interact with soluble αK in a significant manner. These results imply that poor glycemic control can have earlier and more systemic effects that previously thought via altering circulating αK levels. Disclosure F.B. Stentz: None. A. Ammons: None. Funding AD Baskin