Beta-Cell - Liver Interactions in Situations of Modified Beta-Cell Function

Beta-Cell - Liver Interactions in Situations of Modified Beta-Cell Function: From Mice to Children

The investigators will measure blood levels of 1,5-anhydroglucitol in obese children with or without type 2 diabetes and correlate them with parameters related to functional beta-cell mass and glucose metabolism. The values will be compared to those obtained in healthy volunteers. The aim of the study is to test the validity of 1,5-anhydroglucitol as a novel biomarker of beta-cell mass and function in children with obesity with or without type 2 diabetes.

One-center prospective study performed in collaboration between the Pediatric Endocrine and Diabetology unit of the University Hospitals of Geneva (HUG) and Prof. Pierre Maechler, Diabetes Center of the Faculty of Medicine, University of Geneva Switzerland.

1,5-anhydroglucitol (1,5-AG), a deoxyhexose present in almost all foods and forming a stable pool in human subjects, has recently been found to be correlated with functional beta-cell mass in two different mouse models of beta-cell dysfunction leading to diabetes. The decline of this biomarker precedes the development of hyperglycemia in lean b-Phb2 -/- and obese db/db diabetic mice, where beta-cell loss occurs through two different mechanisms.

Additional studies have shown a correlation of 1,5-AG levels with risk of progression of type 1 diabetes (T1DM) in auto-antibody positive children, as well as with glycaemic control in patients with type 2 diabetes (T2DM).

The present project will analyse the correlation between functional beta-cell mass and the circulating levels of 1,5-AG in children with obesity with or without T2DM. This should contribute to the evaluation of a novel biomarker of beta-cell mass and function in T2DM.

Inclusion Criteria:

• Children aged 12 to 16 years
• Obesity. Defined as a body-mass index above the 97th percentile.
• Ability to give informed consent as documented by signature

Exclusion Criteria:

• Patients with diabetes mellitus and positive autoantibodies against islets, insulin, islet antigen 2, glutamic acid decarboxylase or Zinc transporter 8.
• Patients with known liver disease (other than NAFLD)
• Patients treated with an oral antidiabetic drug, glucagon-like peptide-1 analogues or insulin at the time of or less than 2 weeks prior to inclusion.
• Patients treated with a drug known to affect liver function