Introduction and Objective: Older adults with pre-diabetes or type 2 diabetes experience hospitalization and bed rest more frequently than healthy older adults. However, the impact of physical inactivity induced by bed rest on insulin sensitivity in older adults with pre- or type 2 diabetes is unknown. To address this, we conducted a 10-day bed rest study to characterize changes in muscle, hepatic, and adipose tissue insulin sensitivity in older adults with or without pre- or type 2 diabetes.Methods: Thirty-nine older adults with pre- or type 2 diabetes (p-D/T2D; 14M/13F, 65 ± 5.0 yrs) or who were metabolically healthy (CON, 6M/6F, 68 ± 2.9 yrs) completed a 10-day bed rest intervention. A 2-step hyperinsulinemic euglycemic clamp (2hrs @ 20 and 2hrs @ 90 mU/m2/min insulin infusion) with U-13C glucose tracer was performed on day 1 and 10 of bed rest. Skeletal muscle insulin sensitivity (Rate of disposal, Rd/Insulin) and hepatic insulin sensitivity index (endogenous glucose production, EGP/Insulin) were determined. Plasma free fatty acid (FFA) suppression during the clamp was measured as an index of adipose tissue insulin sensitivity. Analyses were performed using a mixed model.Results: Bed rest decreased Rd/Insulin by ~31% at step 1(100-120min; time p<0.001, group p=0.033) and ~31.4% at step 2 (220-240min; time p<0.001) for both p-D/T2D and CON. There was no effect of bed rest on EGP/Insulin at step 1 (time p=0.136) or step 2 (time p=0.174) for p-D/T2D and CON. The percent suppression of EGP was also not affected by bed rest. Fasting insulin, plasma FFA, and FFA suppression during the clamp for both p-D/T2D and CON was not affected by bed rest.Conclusion: These data indicate that bed rest-induced physical inactivity reduces skeletal muscle insulin sensitivity in older adults either with or without pre- or type 2 diabetes, while hepatic and adipose insulin sensitivity are unaffected.
C. Elliehausen: None. J.M. Mucinski: None. S.V. Ramos: None. J. Hinkley: None. F. Yi: None. R. Pratley: Consultant; Current; Lilly USA LLC. Research Support; Current; National Institutes of Health, Novo Nordisk. Speaker’s Bureau; Current; Novo Nordisk. Other – Consulting: Thru 12/31/2023 payment directed to Dr. Pratley’s employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Novo Nordisk. Consultant; Current; Pfizer Inc., Recordati Rare Diseases Inc., Regeneron Pharmaceuticals Inc., Response Pharmaceuticals, Rona Therapeutics Ltd. Research Support; Current; Sanofi. Consultant; Current; Scholar Rock Inc. Other – Consulting: Thru 12/31/2023 payment directed to Dr. Pratley’s employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Sun Pharmaceutical Industries Ltd. Consultant; Current; Third Rock Ventures, Verdiva Bio Dev Limited. Research Support; Current; AstraZeneca AB, Boehringer Ingelheim International GmbH, Abbott Laboratories. Consultant; Current; Abbott Laboratories, AbbVie Inc. Other – Consulting; stock options; Current; Altanine, Inc. Consultant; Current; Amgen Inc., AstraZeneca Pharmaceuticals LP. Other – Consulting: Thru 12/31/2023 payment directed to Dr. Pratley’s employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Bayer AG, Bayer HealthCare Pharmaceuticals Inc. Research Support; Current; Biomea Fusion. Consultant; Current; Boehringer Ingelheim Pharmaceuticals Inc., Carmot Therapeutics, Inc., Corcept Therapeutics. Research Support; Current; Dompé, Eli Lilly and Company. Other – Consulting: Thru 12/31/2023 payment directed to Dr. Pratley’s employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Eli Lilly and Company. Research Support; Current; Endogenex Inc. Other – Consulting: Thru 12/31/2023 payment directed to Dr. Pratley’s employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Current; Endogenex Inc. Consultant; Current; F. Hoffmann-La Roche Ltd. Research Support; Current; Fractyl Health, Inc. Other – Consulting: Thru 12/31/2023 payment directed to Dr. Pratley’s employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Ended; Gasherbrum Bio Inc., Genprex. Consultant; Current; Hanmi Pharm. Co., Ltd. Other – Consulting: Thru 12/31/2023 payment directed to Dr. Pratley’s employer; as of 1/1/2024 payment directed to Dr. Pratley personally.; Ended; Intas Pharmaceuticals Ltd. Research Support; Current; Lexicon Pharmaceuticals, Inc. Consultant; Current; Lexicon Pharmaceuticals, Inc. Speaker’s Bureau; Current; Lilly USA LLC. B. Goodpaster: Advisory Panel; Ended; AbbVie Inc., Altimmune, Merck & Co., Inc., Novo Nordisk, Regeneron Pharmaceuticals Inc. J.P. DeLany: None. P.M. Coen: None.
National Institutes of Health (R01AG060153 to PMC)
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