Acta Diabetologica

, Volume 56, Issue 2, pp 211–217 | Cite as

Exercise-induced improvements in glucose effectiveness are blunted by a high glycemic diet in adults with prediabetes

  • Adithya Hari
  • Ciaràn Fealy
  • Thomas P. J. Solomon
  • Jacob M. Haus
  • Karen R. Kelly
  • Hope Barkoukis
  • John P. KirwanEmail author
Original Article



Glucose effectiveness (GE) refers to the ability of glucose to influence its own metabolism through insulin-independent mechanisms. Diminished GE is a predictor of progression to type 2 diabetes. Exercise training improves GE, however, little is known about how dietary interventions, such as manipulating the glycemic index of diets, interact with exercise-induced improvements in GE in at-risk populations.


We enrolled 33 adults with obesity and pre-diabetes (17 males, 65.7 ± 4.3 years, 34.9 ± 4.2 kg m−2) into a 12-week exercise training program (1 h day−1 and 5 day week−1 at ~ 85% of maximum heart rate) while being randomized to concurrently receive either a low (EX-LOG: 40 ± 0.3 au) or high (EX-HIG: 80 ± 0.6 au) glycemic index diet. A 75-g oral-glucose-tolerance test (OGTT) was performed before and after the intervention and GE was calculated using the Nagasaka equation. Insulin resistance was estimated using a hyperinsulinemic-euglycemic clamp and cardiorespiratory fitness using a VO2max test.


Both EX-LOG and EX-HIG groups had similar improvements in weight (8.6 ± 5.1 kg, P < 0.001), VO2max (6 ± 3.5 mL kg−1 min−1, P < 0.001) and clamp-measured peripheral insulin resistance (1.7 ± 0.9 mg kg−1 min−1, P < 0.001), relative to baseline data. GE in EX-LOG and EX-HIG was similar at baseline (1.9 ± 0.38 vs. 1.85 ± 0.3 mg dL−1 min−1, respectively; P > 0.05) and increased by ~ 20% post-intervention in the EX-LOG arm (∆GE: 0.07–0.57 mg dL−1 min−1, P < 0.05). Plasma free fatty acid (FFA) concentrations also decreased only in the EX-LOG arm (∆FFA: 0.13 ± 0.23 mmol L−1, P < 0.05).


Our data suggest that a high glycemic index diet may suppress exercise-induced enhancement of GE, and this may be mediated through plasma FFAs.


Aerobic exercise training Glycemic index Diet Glucose effectiveness Hyperinsulinemic-euglycemic clamp Prediabetes 



Glucose effectiveness


Oral surrogate of glucose effectiveness


Glycemic index


Exercise + low glycemic index diet


Exercise + high glycemic index diet


Maximal oxygen consumption capacity


Oral glucose tolerance test


Frequently sampled intra-venous glucose tolerance test


Free fatty acid


Glucose disposal rate


Rate of disposal


Hepatic glucose production


Post-loading plasma glucose


Insulin glucose ratio at 30 min


Glucose transporter


Fatty acid translocase



We thank the research volunteers for their outstanding dedication and effort and the nursing staff of the Clinical Research Unit and the staff and students who helped with the implementation of the study and assisted with data collection. We also thank the dietary staff in the Bionutrition Unit of the CTSC for their assistance with preparing meals for this study. We thank the study participants who volunteered for this study and the nurses and staff of the Cleveland Clinic Clinical Research Unit for their invaluable assistance with data collection.

Author contributions

AH, CF and JPK generated the data and wrote the manuscript. TPJS, JMH, KRK and HB helped generate the data, reviewed/edited the manuscript and approved the final version. JPK is the guarantor of this work and has full access to the all the data in the study.


Supported by the National Institutes of Health (NIH) (Grants RO1 AG12834; to JPK) and the NIH National Center for Research Resources (Cleveland, OH, USA) (Clinical and Translational Science Award 1UL1RR024989).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer-Verlag Italia S.r.l., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PathobiologyLerner Research Institute, Cleveland ClinicClevelandUSA
  2. 2.Case Western Reserve UniversityClevelandUSA
  3. 3.Maastricht UniversityMaastrichtThe Netherlands
  4. 4.University of BirminghamBirminghamUK
  5. 5.University of MichiganAnn ArborUSA
  6. 6.Warfighter Performance DepartmentNaval Health Research CenterSan DiegoUSA
  7. 7.Pennington Biomedical Research CenterBaton RougeUSA

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