TY - JOUR
T1 - Circulating 1,5-anhydroglucitol as a biomarker of ß-cell mass independent of a diabetes phenotype in human subjects
AU - Jiménez-Sánchez, Cecilia
AU - Mezza, Teresa
AU - Sinturel, Flore
AU - Li, Lingzi
AU - Di Giuseppe, Gianfranco
AU - Quero, Giuseppe
AU - Jornayvaz, François R
AU - Guessous, Idris
AU - Dibner, Charna
AU - Schrauwen, Patrick
AU - Alfieri, Sergio
AU - Giaccari, Andrea
AU - Maechler, Pierre
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].
PY - 2022/9/28
Y1 - 2022/9/28
N2 - CONTEXT: During an asymptomatic pre-diabetic state, the functional ß-cell mass decreases up to a critical threshold triggering diabetes and related symptoms. To date, there are no reliable readouts able to capture in vivo a potential drop of the ß-cell mass.OBJECTIVE: Beside its use as a short-term marker of glycemic control, the deoxyhexose 1,5-anhydroglucitol was identified in rodents as a circulating biomarker of the functional ß-cell mass already in the asymptomatic prediabetic stage. The present study investigated the putative corresponding relevance of circulating 1,5-anhydroglucitol in different human cohorts.METHODS: We analyzed clinical and blood parameters in patients with established type 2 diabetes and subjects considered at high risk of developing diabetes, as well as patients with no history of diabetes scheduled for pancreaticoduodenectomy.RESULTS: Circulating 1,5-anhydroglucitol was reduced in type 2 diabetic patients, negatively correlating with fasting plasma glucose (p<0.0001) and HbA1c (p<0.0001). In healthy subjects, 1,5-AG levels positively correlated with body mass index (p=0.004) and HOMA%S (p<0.03) and was particularly high in nondiabetic obese individuals, potential accounting for compensatory ß-cell expansion. Patients with no history of diabetes undergoing pancreaticoduodenectomy exhibited a 50% reduction of circulating 1,5-anhydroglucitol levels following surgery leading to an acute loss of their ß-cell mass (p=0.002), regardless their glucose tolerance status.CONCLUSION: In summary, plasma concentration of 1,5-anhydroglucitol follows the ß-cell mass and its non-invasive monitoring may alert about the loss of ß-cells in subjects at risk for diabetes, an event that cannot be captured by other clinical parameters of glycemic control.
AB - CONTEXT: During an asymptomatic pre-diabetic state, the functional ß-cell mass decreases up to a critical threshold triggering diabetes and related symptoms. To date, there are no reliable readouts able to capture in vivo a potential drop of the ß-cell mass.OBJECTIVE: Beside its use as a short-term marker of glycemic control, the deoxyhexose 1,5-anhydroglucitol was identified in rodents as a circulating biomarker of the functional ß-cell mass already in the asymptomatic prediabetic stage. The present study investigated the putative corresponding relevance of circulating 1,5-anhydroglucitol in different human cohorts.METHODS: We analyzed clinical and blood parameters in patients with established type 2 diabetes and subjects considered at high risk of developing diabetes, as well as patients with no history of diabetes scheduled for pancreaticoduodenectomy.RESULTS: Circulating 1,5-anhydroglucitol was reduced in type 2 diabetic patients, negatively correlating with fasting plasma glucose (p<0.0001) and HbA1c (p<0.0001). In healthy subjects, 1,5-AG levels positively correlated with body mass index (p=0.004) and HOMA%S (p<0.03) and was particularly high in nondiabetic obese individuals, potential accounting for compensatory ß-cell expansion. Patients with no history of diabetes undergoing pancreaticoduodenectomy exhibited a 50% reduction of circulating 1,5-anhydroglucitol levels following surgery leading to an acute loss of their ß-cell mass (p=0.002), regardless their glucose tolerance status.CONCLUSION: In summary, plasma concentration of 1,5-anhydroglucitol follows the ß-cell mass and its non-invasive monitoring may alert about the loss of ß-cells in subjects at risk for diabetes, an event that cannot be captured by other clinical parameters of glycemic control.
KW - 1
KW - 1,5-ANHYDRO-D-GLUCITOL
KW - 5-anhydroglucitol
KW - CLINICAL MARKER
KW - IMPAIRED GLUCOSE-TOLERANCE
KW - INSULIN SENSITIVITY
KW - LEVEL
KW - PATHOGENESIS
KW - PLASMA 1,5-ANHYDROGLUCITOL
KW - PREVENTION
KW - RESISTANCE
KW - SERUM 1,5-ANHYDROGLUCITOL
KW - biomarker
KW - diabetes
KW - glycemic control
KW - prediabetes
KW - ss-cell mass
U2 - 10.1210/clinem/dgac444
DO - 10.1210/clinem/dgac444
M3 - Article
C2 - 35867405
SN - 0021-972X
VL - 107
SP - 2833
EP - 2843
JO - Journal of Clinical Endocrinology & Metabolism
JF - Journal of Clinical Endocrinology & Metabolism
IS - 10
ER -