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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

Abstract

Aims

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.

Methods

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.

Results

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).

Conclusions

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

Keywords

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

Abbreviations

GE

Glucose effectiveness

oGE

Oral surrogate of glucose effectiveness

GI

Glycemic index

EX-LOG

Exercise + low glycemic index diet

EX-HIG

Exercise + high glycemic index diet

VO2max

Maximal oxygen consumption capacity

OGTT

Oral glucose tolerance test

FSIVGT

Frequently sampled intra-venous glucose tolerance test

FFA

Free fatty acid

GDR

Glucose disposal rate

Rd

Rate of disposal

HGP

Hepatic glucose production

PPG

Post-loading plasma glucose

IGR30

Insulin glucose ratio at 30 min

GLUT

Glucose transporter

FAT/CD 36

Fatty acid translocase

Notes

Acknowledgements

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.

Funding

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.

References

  1. 1.
    Glechner A, Keuchel L, Affengruber L et al (2018) Effects of lifestyle changes on adults with prediabetes: a systematic review and meta-analysis. Primary Care Diabetes 12:393–408CrossRefGoogle Scholar
  2. 2.
    American Diabetes Association (2017) Standards of Medical Care in Diabetes: lifestyle management. Diabetes Care 40:S33–S43CrossRefGoogle Scholar
  3. 3.
    Solomon TP, Haus JM, Kelly KR et al (2010) A low-glycemic index diet combined with exercise reduces insulin resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese, prediabetic humans. Am J Clin Nutr 92(6):1359–1368CrossRefGoogle Scholar
  4. 4.
    Solomon TP, Haus JM, Cook MA et al (2013) A low-glycemic diet lifestyle intervention improves fat utilization during exercise in older obese humans. Obesity 21(11):2272–2278CrossRefGoogle Scholar
  5. 5.
    Solomon TP, Haus JM, Kelly KR et al (2009) Randomized trial on the effects of a 7-d low-glycemic diet and exercise intervention on insulin resistance in older obese humans. Am J Clin Nutr 90(5):1222–1229CrossRefGoogle Scholar
  6. 6.
    Vranic M, Fono P, Kovacevic N et al (1971) Glucose kinetics and fatty acids in dogs on matched insulin infusion after glucose load. Metab Clin Exp 20(10):954–967CrossRefGoogle Scholar
  7. 7.
    Dube S, Errazuriz-Cruzat I, Basu A et al (2015) The forgotten role of glucose effectiveness in the regulation of glucose tolerance. Curr Diabetes Rep 15(6):1–6CrossRefGoogle Scholar
  8. 8.
    Best JD, Kahn SE, Ader M et al (1996) Role of glucose effectiveness in the determination of glucose tolerance. Diabetes Care 19(9):1018–1030CrossRefGoogle Scholar
  9. 9.
    Edgerton DS, Cardin S, Neal D et al (2004) Effects of hyperglycemia on hepatic gluconeogenic flux during glycogen phosphorylase inhibition in the conscious dog. Am J Physiol Endocrinol Metab 286(4):E510–E522CrossRefGoogle Scholar
  10. 10.
    Davidson MB (1981) Autoregulation by glucose of hepatic glucose balance: permissive effect of insulin. Metab Clin Exp 30(3):279–284CrossRefGoogle Scholar
  11. 11.
    Hawkins M, Tonelli J, Kishore P et al (2003) Contribution of elevated free fatty acid levels to the lack of glucose effectiveness in type 2 diabetes. Diabetes 52(11):2748–2758CrossRefGoogle Scholar
  12. 12.
    Bergman RN (1989) Towards physiological understanding of glucose tolerance: Lilly lecture. Diabetes 38:1512–1527CrossRefGoogle Scholar
  13. 13.
    Nagasaka S, Kusaka YK, Funase Y et al (2012) Index of glucose effectiveness derived from oral glucose tolerance test. Acta Diabetol 49(Suppl 1):S195–S204CrossRefGoogle Scholar
  14. 14.
    Weiss R, Magge SN, Santoro N et al (2015) Glucose effectiveness in obese children: relation to degree of obesity and dysglycemia. Diabetes Care 38(4):689–695PubMedPubMedCentralGoogle Scholar
  15. 15.
    Osei K, Rhinesmith S, Gaillard T et al (2004) Impaired insulin sensitivity, insulin secretion, and glucose effectiveness predict future development of impaired glucose tolerance and type 2 diabetes in pre-diabetic African Americans: implications for primary diabetes prevention. Diabetes Care 27(6):1439–1446CrossRefGoogle Scholar
  16. 16.
    Lorenzo C, Wagenknecht LE, Rewers MJ et al (2010) Disposition index, glucose effectiveness, and conversion to type 2 diabetes: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetes Care 33(9):2098–2103CrossRefGoogle Scholar
  17. 17.
    Higaki Y, Kagawa T, Fujitani J et al (1996) Effects of a single bout of exercise on glucose effectiveness. J Appl Physiol 80(3):754–759CrossRefGoogle Scholar
  18. 18.
    Araujo-Vilar D, Osifo E, Kirk M et al (1997) Influence of moderate physical exercise on insulin-mediated and non-insulin-mediated glucose uptake in healthy subjects. Metab Clin Exp 46(2):203–209CrossRefGoogle Scholar
  19. 19.
    Fujitani J, Higaki Y, Kagawa T et al (1998) Intravenous glucose tolerance test-derived glucose effectiveness in strength-trained humans. Metab Clin Exp 47(7):874–877CrossRefGoogle Scholar
  20. 20.
    Nishida Y, Higaki Y, Tokuyama K et al (2001) Effect of mild exercise training on glucose effectiveness in healthy men. Diabetes Care 24(6):1008–1013CrossRefGoogle Scholar
  21. 21.
    Bordenave S, Brandou F, Manetta J et al (2008) Effects of acute exercise on insulin sensitivity, glucose effectiveness and disposition index in type 2 diabetic patients. Diabetes Metab 34(3):250–257CrossRefGoogle Scholar
  22. 22.
    Taylor HL, Jacobs Jr DR, Schucker B et al (1978) A questionnaire for the assessment of leisure time physical activities. J Chronic Dis 31(12):741–755CrossRefGoogle Scholar
  23. 23.
    O’Leary VB, Marchetti CM, Krishnan RK et al (2006) Exercise-induced reversal of insulin resistance in obese elderly is associated with reduced visceral fat. J Appl Physiol 100(5):1584–1589CrossRefGoogle Scholar
  24. 24.
    Steele R (1959) Influences of glucose loading and of injected insulin on hepatic glucose output. Ann N Y Acad Sci 82(2):420–430CrossRefGoogle Scholar
  25. 25.
    Matthews DR, Hosker JP, Rudenski AS et al (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28(7):412–419CrossRefGoogle Scholar
  26. 26.
    Henderson M, Baillargeon J, Rabasa-Lhoret R et al (2012) Estimating insulin secretion in youth using simple indices derived from the oral glucose tolerance test. Diabetes Metab 38(4):309–315CrossRefGoogle Scholar
  27. 27.
    Team R (2017) RStudio: integrated development environment for R (Version 1.0. 136). RStudio Inc., BostonGoogle Scholar
  28. 28.
    Alford F, Henriksen J, Rantzau C et al (2018) Glucose effectiveness is a critical pathogenic factor leading to glucose intolerance and type 2 diabetes: an ignored hypothesis. Diabetes Metab Res 34(4):e2989CrossRefGoogle Scholar
  29. 29.
    Ahola A, Forsblom C, Groop P (2018) Adherence to special diets and its association with meeting the nutrient recommendations in individuals with type 1 diabetes. Acta Diabetol 2018:1–9Google Scholar
  30. 30.
    Radulian G, Rusu E, Dragomir A et al (2009) Metabolic effects of low glycaemic index diets. Nutr J 8(1):5CrossRefGoogle Scholar
  31. 31.
    Cheng I, Liao S, Liu K et al (2009) Effect of dietary glycemic index on substrate transporter gene expression in human skeletal muscle after exercise. Eur J Clin Nutr 63(12):1404–1410CrossRefGoogle Scholar
  32. 32.
    Nishida Y, Tokuyama K, Nagasaka S et al (2004) Effect of moderate exercise training on peripheral glucose effectiveness, insulin sensitivity, and endogenous glucose production in healthy humans estimated by a two-compartment-labeled minimal model. Diabetes 53(2):315–320CrossRefGoogle Scholar

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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