Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study

Gretha J. Boersma; Emil Johansson; Maria J. Pereira; Kerstin Heurling; Stanko Skrtic; Joey Lau; Petros Katsogiannos; Grigorios Panagiotou; Mark Lubberink; Joel Kullberg; Håkan Ahlström; Jan W. Eriksson

doi:10.1055/a-0643-4739

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2018; 50(08): 627-639
DOI: 10.1055/a-0643-4739

Endocrine Care

Altered Glucose Uptake in Muscle, Visceral Adipose Tissue, and Brain Predict Whole-Body Insulin Resistance and may Contribute to the Development of Type 2 Diabetes: A Combined PET/MR Study

Authors

Gretha J. Boersma

¹Department of Medical Science, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
Emil Johansson

²Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden
Maria J. Pereira

¹Department of Medical Science, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
Kerstin Heurling

²Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden

⁷Wallenberg Centre for Molecular and Translational Medicine and the Department of Psychiatry and Neurochemistry, University of Gothenburg, Sweden
Stanko Skrtic

³AstraZeneca, R & D, Gothenburg, Sweden

⁴Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Joey Lau

¹Department of Medical Science, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

⁵Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden
Petros Katsogiannos

¹Department of Medical Science, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
Grigorios Panagiotou

¹Department of Medical Science, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden
Mark Lubberink

²Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden
Joel Kullberg

²Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden

⁶Antaros Medical, Mölndal, Sweden
Håkan Ahlström

²Department of Surgical Sciences, Radiology, Uppsala University, Uppsala, Sweden

⁶Antaros Medical, Mölndal, Sweden
Jan W. Eriksson

¹Department of Medical Science, Clinical Diabetes and Metabolism, Uppsala University, Uppsala, Sweden

Abstract

We assessed glucose uptake in different tissues in type 2 diabetes (T2D), prediabetes, and control subjects to elucidate its impact in the development of whole-body insulin resistance and T2D. Thirteen T2D, 12 prediabetes, and 10 control subjects, matched for age and BMI, underwent OGTT and abdominal subcutaneous adipose tissue (SAT) biopsies. Integrated whole-body ¹⁸F-FDG PET and MRI were performed during a hyperinsulinemic euglycemic clamp to asses glucose uptake rate (MRglu) in several tissues. MRglu in skeletal muscle, SAT, visceral adipose tissue (VAT), and liver was significantly reduced in T2D subjects and correlated positively with M-values (r=0.884, r=0.574, r=0.707 and r=0.403, respectively). Brain MRglu was significantly higher in T2D and prediabetes subjects and had a significant inverse correlation with M-values (r=–0.616). Myocardial MRglu did not differ between groups and did not correlate with the M-values. A multivariate model including skeletal muscle, brain and VAT MRglu best predicted the M-values (adjusted r²=0.85). In addition, SAT MRglu correlated with SAT glucose uptake ex vivo (r=0.491). In different stages of the development of T2D, glucose uptake during hyperinsulinemia is elevated in the brain in parallel with an impairment in peripheral organs. Impaired glucose uptake in skeletal muscle and VAT together with elevated glucose uptake in brain were independently associated with whole-body insulin resistance, and these tissue-specific alterations may contribute to T2D development.

Key words

diabetes mellitus type 2 - glucose intolerance - insulin resistance - PET-MRI imaging

Full Text

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