Journal article
Processes Underlying Glycemic Deterioration in Type 2 Diabetes: An IMI DIRECT Study
National Research Council of Italy1
Newcastle University2
Royal Victoria Hospital3
Amsterdam Public Health4
Sanofi Aventis Deutschland GmbH5
Novo Nordisk Foundation6
University of Copenhagen7
Bioinformatics, Department of Health Technology, Technical University of Denmark8
Department of Health Technology, Technical University of Denmark9
Copenhagen University Hospital Herlev and Gentofte10
University of Eastern Finland11
University of Bath12
University of Dundee13
Eli Lilly GmbH14
Université de Genève15
KTH Royal Institute of Technology16
Helmholtz Zentrum München - German Research Center for Environmental Health17
University of Exeter18
Lund University19
Ninewells Hospital20
University of Westminster21
Imperial College London22
University of Cambridge23
University of Oxford24
...and 14 moreWe investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D). A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI.
The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression. Faster HbA1c progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R 2 = 0.38).
A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09).
T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role. Deteriorating insulin sensitivity and β-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease.
Stabilization of a single trait among insulin sensitivity, β-cell function, and insulin clearance may be relevant to prevent progression.
Language: | English |
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Publisher: | American Diabetes Association |
Year: | 2021 |
Pages: | 511-518 |
ISSN: | 19355548 and 01495992 |
Types: | Journal article |
DOI: | 10.2337/dc20-1567 |
ORCIDs: | 0000-0002-8251-1730 , 0000-0002-0883-7599 , 0000-0003-0529-6325 , 0000-0002-1646-4163 , 0000-0001-5620-473X , 0000-0002-4181-0937 , 0000-0002-3270-9167 , 0000-0002-6880-5759 , 0000-0001-8748-3831 , 0000-0001-5585-3420 , 0000-0003-3559-6660 , 0000-0002-0520-7604 , 0000-0001-9237-8585 , 0000-0002-1436-5591 , De Masi, Federico , Tsirigos, Konstantinos D. , 0000-0001-5948-8993 , 0000-0003-3090-269X , 0000-0001-7447-6560 , 0000-0003-0316-5866 and 0000-0002-3321-3972 |