Glucose Metabolism and Metabolomic Changes in Response to Prolonged Fasting in Individuals with Obesity, Type 2 Diabetes and Non-Obese People—A Cohort Trial

Norbert J. Tripolt, Sebastian J. Hofer, Peter N. Pferschy, Faisal Aziz, Sylvère Durand, Fanny Aprahamian, Nitharsshini Nirmalathasan, Mara Waltenstorfer, Tobias Eisenberg, Anna M.A. Obermayer, Regina Riedl, Harald Kojzar, Othmar Moser, Caren Sourij, Heiko Bugger, Abderrahim Oulhaj, Thomas R. Pieber, Matthias Zanker, Guido Kroemer, Frank MadeoHarald Sourij

    Research output: Contribution to journalArticlepeer-review

    2 Scopus citations

    Abstract

    Metabolic regulation of glucose can be altered by fasting periods. We examined glucose metabolism and metabolomics profiles after 12 h and 36 h fasting in non-obese and obese participants and people with type 2 diabetes using oral glucose tolerance (OGTT) and intravenous glucose tolerance testing (IVGTT). Insulin sensitivity was estimated by established indices and mass spectrometric metabolomics was performed on fasting serum samples. Participants had a mean age of 43 ± 16 years (62% women). Fasting levels of glucose, insulin and C-peptide were significantly lower in all cohorts after 36 h compared to 12 h fasting (p < 0.05). In non-obese participants, glucose levels were significantly higher after 36 h compared to 12 h fasting at 120 min of OGTT (109 ± 31 mg/dL vs. 79 ± 18 mg/dL; p = 0.001) but insulin levels were lower after 36 h of fasting at 30 min of OGTT (41.2 ± 34.1 mU/L after 36 h vs. 56.1 ± 29.7 mU/L; p < 0.05). In contrast, no significant differences were observed in obese participants or people with diabetes. Insulin sensitivity improved in all cohorts after 36 h fasting. In line, metabolomics revealed subtle baseline differences and an attenuated metabolic response to fasting in obese participants and people with diabetes. Our data demonstrate an improved insulin sensitivity after 36 h of fasting with higher glucose variations and reduced early insulin response in non-obese people only.

    Original languageBritish English
    Article number511
    JournalNutrients
    Volume15
    Issue number3
    DOIs
    StatePublished - Feb 2023

    Keywords

    • fasting
    • glucose metabolism
    • IVGTT
    • metabolic flexibility
    • obesity
    • OGTT
    • type 2 diabetes

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