GIP Affects Hepatic Fat and Brown Adipose Tissue Thermogenesis but Not White Adipose Tissue Transcriptome in Type 1 Diabetes

Sebastian Møller Nguyen Heimbürger, Bjørn Hoe, Chris Neumann Nielsen, Natasha Chidekel Bergman, Kirsa Skov-Jeppesen, Bolette Hartmann, Jens Juul Holst, Flemming Dela, Julie Overgaard, Joachim Størling, Tina Vilsbøll, Thomas Fremming Dejgaard, Jesper Foged Havelund, Vladimir Gorshkov, Frank Kjeldsen, Nils Joakim Kaas Færgeman, Martin Rønn Madsen, Mikkel B Christensen, Filip Krag Knop

Abstrakt

CONTEXT: Glucose-dependent insulinotropic polypeptide (GIP) has been proposed to exert insulin-independent effects on lipid and bone metabolism.

OBJECTIVE: We investigated the effects of a 6-day subcutaneous GIP infusion on circulating lipids, white adipose tissue (WAT), brown adipose tissue (BAT), hepatic fat content, inflammatory markers, respiratory exchange ratio (RER), and bone homeostasis in patients with type 1 diabetes.

METHODS: In a randomized, placebo-controlled, double-blind, crossover study, 20 men with type 1 diabetes underwent a 6-day continuous subcutaneous infusion with GIP (6 pmol/kg/min) and placebo (saline), with an interposed 7-day washout period.

RESULTS: During GIP infusion, participants (26 ± 8 years [mean ± SD]; BMI 23.8 ± 1.8 kg/m2; glycated hemoglobin A1c 51 ± 10 mmol/mol [6.8 ± 3.1%]) experienced transiently increased circulating concentrations of nonesterified fatty acid (NEFA) (P = 0.0005), decreased RER (P = 0.009), indication of increased fatty acid β-oxidation, and decreased levels of the bone resorption marker C-terminal telopeptide (P = 0.000072) compared with placebo. After 6 days of GIP infusion, hepatic fat content was increased by 12.6% (P = 0.007) and supraclavicular skin temperature, a surrogate indicator of BAT activity, was increased by 0.29 °C (P < 0.000001) compared with placebo infusion. WAT transcriptomic profile as well as circulating lipid species, proteome, markers of inflammation, and bone homeostasis were unaffected.

CONCLUSION: Six days of subcutaneous GIP infusion in men with type 1 diabetes transiently decreased bone resorption and increased NEFA and β-oxidation. Further, hepatic fat content, and supraclavicular skin temperature were increased without affecting WAT transcriptomics, the circulating proteome, lipids, or inflammatory markers.

OriginalsprogEngelsk
TidsskriftThe Journal of clinical endocrinology and metabolism
Vol/bind107
Udgave nummer12
Sider (fra-til)3261-3274
Antal sider14
ISSN0021-972X
DOI
StatusUdgivet - 25 nov. 2022

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