Novel deuterium metabolic imaging technique reveals distinct patterns of postprandial hepatic glucose homeostasis in individuals with type 1 diabetes and healthy control individuals: a case-control study.
Description
Alessandro Brunasso, Naomi F. Lange and Simone Poli share first
authorship. Roland Kreis and Lia Bally share last authorship.
authorship. Roland Kreis and Lia Bally share last authorship.
Publisher DOI
PubMed ID
41686194
Abstract
Aims/hypothesis
Subcutaneous insulin delivery in individuals with insulin-deficient type 1 diabetes bypasses the portal circulation, disrupting the physiological porto-systemic insulin gradient and affecting postprandial hepatic glucose regulation. However, direct, non-invasive measurement of these liver-specific dynamics and their deviation from normal physiology in individuals with type 1 diabetes is challenging. To address this, we integrated metabolic imaging with whole-body tracer dilution to map postprandial glucose metabolism in both the liver and systemically in adults with type 1 diabetes and healthy control individuals.Methods
In this cross-sectional study, ten adults with type 1 diabetes and ten healthy control individuals with similar age, BMI and gender distributions were enrolled. After an overnight fast, participants ingested 60 g [6,6'-2H2]-glucose (D-Glc); subcutaneous insulin was administered to type 1 diabetes participants according to their carbohydrate-to-insulin ratio. Interleaved deuterium metabolic imaging (DMI) and 13C-magnetic resonance spectroscopy (13C-MRS) at 7 T were performed from pre-ingestion to 150 min post-ingestion to quantify hepatic D-Glc and glycogen concentrations. Blood samples were collected to measure plasma glucose, insulin and glucagon. Postprandial glucose-insulin dynamics were quantified using the single tracer oral minimal model, accounting for non-steady-state insulin exposure.Results
At baseline, individuals with type 1 diabetes had significantly higher plasma glucose concentrations than control individuals (10.7±2.3 and 5.2±0.4 mmol/l, respectively; p<0.001), while preprandial glycogen levels did not differ significantly. Following D-Glc administration, hepatic D-Glc increased more markedly in the individuals with type 1 diabetes compared with the control group (peak values 4.7±2.0 and 3.0±0.8 mmol/l, respectively; p=0.02). In the postprandial period, glycogen levels did not significantly rise at 150 min in type 1 diabetes, whereas a clear increase was observed in control individuals (iAUC0-180=2.4 mol/l × min). Despite similar systemic insulin exposure and no significant differences in postprandial glucagon concentrations between groups, individuals with type 1 diabetes demonstrated significantly reduced suppression of endogenous glucose production (p=0.001) but similar insulin-dependent glucose disposal. Hierarchical clustering identified two distinct type 1 diabetes subgroups: Subgroup 1 exhibited a steeper increase in both hepatic and systemic D-Glc profiles, while subgroup 2 showed a divergent D-Glc trajectory and net glycogen depletion relative to accumulation in subgroup 1 (iAUC0-180=-3.0 vs 2.5 mol/l × min, p=0.04), despite no overt clinical differences between subgroups.Conclusions/interpretation
By integrating DMI/13C-MRS liver imaging with systemic stable-isotope modelling, this comparative study demonstrates significantly altered hepatic glucose metabolism in adults with well-managed type 1 diabetes vs control individuals, together with substantial phenotypic heterogeneity within the type 1 diabetes cohort. These findings highlight the potential of non-invasive metabolic phenotyping to resolve metabolic alterations and inter-individual variation in type 1 diabetes, which are essential steps towards the provision of precision medicine.
Subcutaneous insulin delivery in individuals with insulin-deficient type 1 diabetes bypasses the portal circulation, disrupting the physiological porto-systemic insulin gradient and affecting postprandial hepatic glucose regulation. However, direct, non-invasive measurement of these liver-specific dynamics and their deviation from normal physiology in individuals with type 1 diabetes is challenging. To address this, we integrated metabolic imaging with whole-body tracer dilution to map postprandial glucose metabolism in both the liver and systemically in adults with type 1 diabetes and healthy control individuals.Methods
In this cross-sectional study, ten adults with type 1 diabetes and ten healthy control individuals with similar age, BMI and gender distributions were enrolled. After an overnight fast, participants ingested 60 g [6,6'-2H2]-glucose (D-Glc); subcutaneous insulin was administered to type 1 diabetes participants according to their carbohydrate-to-insulin ratio. Interleaved deuterium metabolic imaging (DMI) and 13C-magnetic resonance spectroscopy (13C-MRS) at 7 T were performed from pre-ingestion to 150 min post-ingestion to quantify hepatic D-Glc and glycogen concentrations. Blood samples were collected to measure plasma glucose, insulin and glucagon. Postprandial glucose-insulin dynamics were quantified using the single tracer oral minimal model, accounting for non-steady-state insulin exposure.Results
At baseline, individuals with type 1 diabetes had significantly higher plasma glucose concentrations than control individuals (10.7±2.3 and 5.2±0.4 mmol/l, respectively; p<0.001), while preprandial glycogen levels did not differ significantly. Following D-Glc administration, hepatic D-Glc increased more markedly in the individuals with type 1 diabetes compared with the control group (peak values 4.7±2.0 and 3.0±0.8 mmol/l, respectively; p=0.02). In the postprandial period, glycogen levels did not significantly rise at 150 min in type 1 diabetes, whereas a clear increase was observed in control individuals (iAUC0-180=2.4 mol/l × min). Despite similar systemic insulin exposure and no significant differences in postprandial glucagon concentrations between groups, individuals with type 1 diabetes demonstrated significantly reduced suppression of endogenous glucose production (p=0.001) but similar insulin-dependent glucose disposal. Hierarchical clustering identified two distinct type 1 diabetes subgroups: Subgroup 1 exhibited a steeper increase in both hepatic and systemic D-Glc profiles, while subgroup 2 showed a divergent D-Glc trajectory and net glycogen depletion relative to accumulation in subgroup 1 (iAUC0-180=-3.0 vs 2.5 mol/l × min, p=0.04), despite no overt clinical differences between subgroups.Conclusions/interpretation
By integrating DMI/13C-MRS liver imaging with systemic stable-isotope modelling, this comparative study demonstrates significantly altered hepatic glucose metabolism in adults with well-managed type 1 diabetes vs control individuals, together with substantial phenotypic heterogeneity within the type 1 diabetes cohort. These findings highlight the potential of non-invasive metabolic phenotyping to resolve metabolic alterations and inter-individual variation in type 1 diabetes, which are essential steps towards the provision of precision medicine.
Date Issued
2026-05
Publication Type
Article
Subject(s)
Subjects
Deuterium metabolic imaging
•
Endogenous glucose production
•
Glucose fluxes
•
Glucose metabolism
•
Glycogen
•
Insulin sensitivity
•
Liver glucose metabolism
•
Magnetic resonance spectroscopy
•
Stable isotopes
•
Type 1 diabetes
Language(s)
en
Author(s)
Brunasso, Alessandro | |
Schiavon, Michele | |
Dalla Man, Chiara | |
Additional Credits
Journal
Diabetologia
Publisher
Springer
ISSN
1432-0428
0012-186X
Access(Rights)
open.access