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Scientific article
English

Circulating 1,5-anhydroglucitol as a biomarker of ß-cell mass independent of a diabetes phenotype in human subjects

Published inJournal of clinical endocrinology & metabolism, vol. 107, no. 10, p. 2833-2843
Publication date2022-10
First online date2022-07-22
Abstract

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.

eng
Keywords
  • 1,5-anhydroglucitol
  • Biomarker
  • Diabetes
  • Glycemic control
  • Prediabetes
  • ß-cell mass
Funding
  • Swiss National Science Fondation - Glutamate pathways and metabolic stresses in energy homeostasis [31003A_166625]
  • Swiss National Science Fondation - Roles of the pancreatic islet cell-specific circadian oscillators in metabolic regulation in physiology and type 2 diabetes [310030_184708]
  • Swiss National Science Fondation - Interactions between the human circadian clock, diabetes, and metabolic syndrome [CRSII3_160741]
  • Italian Ministry of Education, University and Research - [GR- 2018-12365577]
  • Italian Ministry of Education, University and Research - [RF-2019-12369293]
  • Italian Ministry of University and Research - [PRIN 2020SH2ZZA]
Citation (ISO format)
JIMÉNEZ-SÁNCHEZ, Cecilia et al. Circulating 1,5-anhydroglucitol as a biomarker of ß-cell mass independent of a diabetes phenotype in human subjects. In: Journal of clinical endocrinology & metabolism, 2022, vol. 107, n° 10, p. 2833–2843. doi: 10.1210/clinem/dgac444
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Article (Published version)
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ISSN of the journal0021-972X
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Creation08/24/2022 1:18:00 PM
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