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Cited by 16Diabetes, Cardiovascular Risks, and LipoproteinsPhysical Activity and HealthCardiovascular and exercise physiology

Effect of exercise training on insulin-stimulated glucose disposal: A systematic review and meta-analysis of randomized controlled trials

Open access
Rebello, Candida J., Zhang, Dachuan, Kirwan, John P., Lowe, Adam C., Emerson, Carlante J., Kracht, Chelsea L., Steib, Lori C., Greenway, Frank L. +2 more·2023·International Journal of Obesity
DOI 10.1038/s41366-023-01283-8PMC PMC10148910
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Abstract

Background and objective The effect of exercise training on whole-body insulin sensitivity has not been systematically summarized. We aimed to summarize the data from randomized controlled trials evaluating the effect of exercise training on insulin action, in adults. Subjects MEDLINE, EMBASE, and CENTRAL databases were searched until January 2021. Randomized controlled trials lasting ≥4 weeks, including adults, and evaluating the effect of exercise on insulin-stimulated glucose disposal measured using the hyperinsulinemic euglycemic clamp, were included. Methods Three reviewers extracted summary data from published trials. The primary outcome was insulin-stimulated glucose disposal. Standardized weighted mean differences (SMD) in glucose disposal between intervention and control were compared. The PEDro scale was used to assess risk of bias. Results We included 25 trials (36 interventions, N = 851). Exercise increased insulin-stimulated glucose disposal relative to control, SMD = 0.52 (95% confidence interval [CI]: 0.39, 0.65; p < 0.001; I 2 = 47%) without significantly suppressing hepatic glucose production. In trials without isotopic tracers, exercise increased glucose disposal (SMD = 0.63; 95% CI: 0.48, 0.77; p < 0.001, I 2 = 55%). In trials with isotopic tracers, exercise increased glucose disposal only when tracers were added to the exogenous glucose used for clamping (SMD = 0.34; 95% CI: 0.03, 0.66, p = 0.034. I 2 = 0%). In a meta-regression model including aerobic exercise, weight change, and tracer technique, only percent weight change explained between trial heterogeneity (β = 0.069; 95% CI: 0.005, 0.013). The PEDro rating indicated relatively low risk of bias (5.8 ± 0.22). Conclusions Exercise training for at least four weeks significantly increases insulin-stimulated glucose disposal. Weight loss maximizes the effect and may be needed to improve hepatic insulin sensitivity. Differences in tracer methodology contribute to divergent outcomes and should be considered when assessing conclusions from research examining the effect of exercise on insulin action. Registration PROSPERO (CRD42019124381).

Integrity signals

Registry

Crossref · 10.1038/s41366-023-01283-8

Cites

65 of 65 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

12 of 33 cited sources checked · 2 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    People with obesity and type 2 diabetes typically have impaired insulin-stimulated muscle glucose oxidation and glycogen synthesis due to insulin receptor downregulation/degradation and post-receptor signaling defects.

    “People with obesity and type 2 diabetes typically have impaired insulin-stimulated muscle glucose oxidation and glycogen synthesis as a result of downregulation or degradation of insulin receptors and defects in post-receptor insulin signaling 2, 3.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [2] Mitrakou A, Kelley D, Veneman T, Jenssen T, Pangburn T, Reilly J, et al. Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM. Diabetes. 1990;39:1381–90. source
    • cites [3] Petersen MC, Shulman GI. Mechanisms of insulin action and insulin resistance. Physiol Rev. 2018;98:2133–223. source

      Section IV (page unavailable) reports impaired insulin-stimulated muscle glycogen synthesis in type 2 diabetes and says decreased surface insulin-receptor content and signaling defects contribute to typical obesity-associated insulin resistance. Section II (page unavailable) discusses glucose oxidation after insulin stimulation, but the retrieved passages do not establish that muscle glucose oxidation is typically impaired in obesity and type 2 diabetes. They also do not establish receptor degradation as the mechanism. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
  • Premisecitation

    Insulin-mediated glucose disposal in skeletal muscle continues to increase with additional weight loss.

    “Insulin-mediated glucose disposal in skeletal muscle continues to increase with additional weight loss 63.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [63] Magkos F, Fraterrigo G, Yoshino J, Luecking C, Kirbach K, Kelly SC, et al. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab. 2016;23:591–601. source
  • Premisecitation

    Molecular adaptations that regulate insulin sensitivity after one exercise bout lead to sustained elevations in insulin action with regular physical training.

    “The molecular adaptations that regulate insulin sensitivity after one exercise bout lead to sustained elevations in insulin action with regular physical training 57-60.”
    Quote in the paperNot a substantial claim1 of 4 sources checked
    • cites [57] Richter EA, Sylow L, Hargreaves M. Interactions between insulin and exercise. Biochem J. 2021;478:3827–46. source
    • cites [58] Prior SJ, Goldberg AP, Ortmeyer HK, Chin ER, Chen D, Blumenthal JB, et al. Increased skeletal muscle capillarization independently enhances insulin sensitivity in older adults after exercise training and detraining. Diabetes. 2015;64:3386–95. source

      The Discussion reports improved insulin sensitivity after six months of aerobic training, with an 18% improvement remaining after two weeks of detraining. But it attributes most of the lasting improvement to longer-lasting mechanisms, including increased capillary density; the measured intramuscular adaptations reverted toward baseline. The paper does not establish that molecular adaptations after a single exercise bout lead to the sustained improvement. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [59] De Glisezinski I, Crampes F, Harant I, Berlan M, Hejnova J, Langin D, et al. Endurance training changes in lipolytic responsiveness of obese adipose tissue. Am J Physiol. 1998;275:E951–6. source
    • cites [60] Ziogas GG, Thomas TR, Harris WS. Exercise training, postprandial hypertriglyceridemia, and LDL subfraction distribution. Med Sci Sports Exerc. 1997;29:986–91. source
  • Premisecitation

    Following a single exercise bout, improved insulin action involves coordinated effects on vasodilation, capillary perfusion, and GLUT4 translocation to the muscle surface membrane.

    “Following a single exercise bout, the mechanisms underlying improved insulin action involve a coordinated effect of insulin action on vasodilation, augmented capillary perfusion, and increased glucose transporter 4 (GLUT4) translocation to the muscle surface membrane 55, 56.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [55] Sjoberg KA, Frosig C, Kjobsted R, Sylow L, Kleinert M, Betik AC, et al. Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling. Diabetes. 2017;66:1501–10. source

      The Discussion (p. 6) reports that acute exercise augments insulin-stimulated microvascular perfusion and coordinates greater glucose delivery with muscle-cell signaling; the paper also describes insulin as a vasodilator (p. 2). But the Discussion (p. 6) says the cellular response is *likely* at the level of GLUT4 translocation. It does not establish increased GLUT4 translocation as a measured effect. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [56] Miinea CP, Sano H, Kane S, Sano E, Fukuda M, Peranen J, et al. AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain. Biochem J. 2005;391:87–93. source

      The Introduction (page not provided) states that insulin stimulates GLUT4 movement to the cell surface in fat and muscle cells. It does not address improved insulin action following a single exercise bout, vasodilation, or augmented capillary perfusion; searches for exercise and perfusion found no supporting passage. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
  • Findingown data

    Exercise training increased insulin-stimulated glucose disposal relative to control, with SMD 0.52 (95% CI 0.39-0.65; p<0.001; I2=47%).

    “Exercise increased insulin-stimulated glucose disposal relative to control, SMD=0.52 (95% confidence interval [CI]: 0.39, 0.65; p<0.001; I2=47%) without significantly suppressing hepatic glucose production.”
    • Also stated in: § Association of Intervention with End Points · plain
      “Exercise training was related to greater glucose disposal relative to control in both the fixed effects (SMD = 0.52; 95% CI: 0.39, 0.65; p < 0.001; I2 = 47%) and random effects models (SMD = 0.55; 95% CI: 0.37, 0.73; p < 0.001, Figure 2).”
    Quote in the paperSubstantial claim
  • May combine two claims. 26
  • Classified as probably not a substantial claim. 14
  • The quote only partly states this claim. 1

  • May combine two claims.

    Premisecitation

    Skeletal muscle responds to contraction or exercise with a rapid insulin-independent increase in glucose uptake during exercise and a transient insulin-stimulated pathway following exercise.

    “Skeletal muscle responds to contraction or exercise with a rapid insulin-independent increase in glucose uptake during exercise and a transient insulin-stimulated pathway following exercise 7-11.”
    Quote in the paperSubstantial claim3 of 5 sources checked
    • cites [7] DiMenna FJ, Arad AD. Exercise as ‘precision medicine’ for insulin resistance and its progression to type 2 diabetes: a research review. BMC Sports Sci Med Rehabil. 2018;10:21. source

      In the Introduction sections on lipid oxidation during exercise and aerobic training, the review reports increased glucose uptake during exercise and a transient improvement in insulin sensitivity after a single aerobic exercise bout, lasting approximately 38–72 hours. Our copy does not establish that the during-exercise uptake is rapid and insulin-independent, or describe a transient insulin-stimulated pathway following exercise. The indexed passages provide no page numbers. (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [8] Ross R. Does exercise without weight loss improve insulin sensitivity? Diabetes Care. 2003;26:944–5. source

      Section I reports that a single exercise session increases insulin-stimulated glucose uptake and that its benefits generally dissipate within 48–72 hours. It does not describe a rapid, insulin-independent increase in skeletal-muscle glucose uptake during exercise or establish the specific pathways claimed. Page numbers are not provided in our copy. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [9] O’Gorman DJ, Karlsson HK, McQuaid S, Yousif O, Rahman Y, Gasparro D, et al. Exercise training increases insulin-stimulated glucose disposal and GLUT4 (SLC2A4) protein content in patients with type 2 diabetes. Diabetologia. 2006;49:2983–92. source

      The Introduction says muscle contractions during acute exercise enhance glucose transport, and the Discussion reports enhanced insulin-mediated glucose disposal for up to two days after exercise in healthy young subjects. Our copy does not establish that uptake during exercise is rapid and insulin-independent; its explicit discussion of insulin-independent regulation concerns the period after exercise. It also reports no improvement in insulin-mediated disposal 16 hours after acute exercise in the obese and type 2 diabetic subjects studied (Introduction and Discussion; pages unavailable). (LLM, conf=0.84)

      Experimental — accuracy not yet measured
    • cites [10] Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C. Physical activity/exercise and type 2 diabetes. Diabetes Care. 2004;27:2518–39. source
    • cites [11] Maarbjerg SJ, Sylow L, Richter EA. Current understanding of increased insulin sensitivity after exercise - emerging candidates. Acta Physiol (Oxf). 2011;202:323–35. source

  • May combine two claims.

    Premisecitation

    Insulin delivered into the portal vein is a major regulator of hepatic glucose production, and people with obesity, prediabetes, and type 2 diabetes have increased gluconeogenesis and impaired insulin suppression of hepatic glucose production.

    “Furthermore, insulin delivered into the portal vein is a major regulator of hepatic glucose production (HGP) and people with obesity, prediabetes, and type 2 diabetes have increased gluconeogenesis and an impairment in the capacity of insulin to suppress HGP 4, 5.”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites [4] Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, DeFronzo RA. San Antonio metabolisms. Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study. Diabetologia. 2004;47:31–9. source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [5] Smith GI, Polidori DC, Yoshino M, Kearney ML, Patterson BW, Mittendorfer B, et al. Influence of adiposity, insulin resistance, and intrahepatic triglyceride content on insulin kinetics. J Clin Invest. 2020;130:3305–14. source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Weight loss clearly improves insulin sensitivity, but effects in different organ systems vary depending on duration and extent of metabolic dysregulation.

    “Weight loss clearly improves insulin sensitivity but the effects in different organ systems have individual variability depending upon the duration and extent of the metabolic dysregulation.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [63] Magkos F, Fraterrigo G, Yoshino J, Luecking C, Kirbach K, Kelly SC, et al. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab. 2016;23:591–601. source

      The Results and Discussion section reports improved insulin sensitivity after weight loss and different responses in adipose tissue, liver, and skeletal muscle as weight loss progresses (page not available in our copy). It does not establish that those differences depend on the duration or extent of metabolic dysregulation; the measured dose-dependent difference concerns the amount of weight lost. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [64] Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes. 2005;54:603–8. source

  • May combine two claims.

    Premisecitation

    Insulin-mediated suppression of lipolysis in adipose tissue and suppression of hepatic glucose production occur maximally at 5% to 8% weight loss.

    “In general, insulin-mediated suppression of lipolysis in adipose tissue and suppression of HGP occur maximally at 5% to 8% weight loss 63, 64.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [63] Magkos F, Fraterrigo G, Yoshino J, Luecking C, Kirbach K, Kelly SC, et al. Effects of moderate and subsequent progressive weight loss on metabolic function and adipose tissue biology in humans with obesity. Cell Metab. 2016;23:591–601. source
    • cites [64] Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes. 2005;54:603–8. source

  • May combine two claims.

    Findingown data

    Reduction in body weight enhanced the effect of exercise on glucose disposal (significant weight loss SMD=0.89; non-significant SMD=0.32).

    “Although exercise increased glucose disposal regardless of significant (p < 0.05) weight loss compared to control, reduction in body weight enhanced the effect (significant weight loss: SMD = 0.89; 95% CI: 0.69, 1.10; p < 0.001; I2 = 58%; non-significant weight loss: SMD = 0.32; 95% CI: 0.16, 0.48; p < 0.001; I2 = 0.5%).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Findingnone given

    This review is the first to summarize findings on the effect of exercise training on glucose disposal.

    “This review is the first to summarize findings relating to the effect of exercise training on glucose disposal.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Randomized controlled trials examining exercise training effects on glucose disposal and hepatic glucose production had not been systematically summarized before this review.

  • May combine two claims.

    Findingown data

    The review included 25 randomized controlled trials, 36 exercise-versus-control comparisons, and 851 participants.

    “We included 25 trials (36 interventions, N=851).”
    • Also stated in: § Description of Studies · plain
      “25 RCTs including 36 comparisons of exercise versus control (N=851) were eligible for inclusion in our analysis (Table 1).”
    Quote in the paperSubstantial claim

  • The quote only partly states this claim.

    Findingown data

    Aerobic exercise increased glucose disposal compared with other exercise modes (aerobic SMD=0.68; other modes SMD=0.21; p=0.06).

    “trials that administered aerobic exercise (interventions: N = 26 aerobic alone, N = 5 resistance, and N = 5 aerobic and resistance) increased glucose disposal compared to other modes (aerobic, SMD = 0.68; 95% CI: 0.53, 0.84; p < 0.001; I2 = 45%; other modes SMD = 0.21; 95% CI: −0.008, 0.42; p = 0.06; I2 = 2.5%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    In adults, structured exercise training improves glucose disposal compared with control, and the gain extends beyond a single acute exercise bout.

    “This systematic review and meta-analysis demonstrated that in adults structured exercise training improves glucose disposal compared to control, and this gain extends beyond the effect of a single acute bout of exercise.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Distinct methods produce distinct results, which is important for designing and interpreting clamp trials.

    “Distinct methods produce distinct results, which is important for the field to recognize when designing and interpreting trials using the clamp.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Weight loss enhances the effect of exercise, possibly through mechanisms related to hepatic and adipose tissue insulin sensitivity.

    “and weight loss enhances the effect, possibly through induction of mechanisms related to hepatic and adipose tissue insulin sensitivity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductnone given

    There was no evidence of publication bias and overall trials were of high quality, facilitating fair interpretation.

    “However, there was no evidence of publication bias and overall, the trials were of high quality which facilitated a fair interpretation of our results.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationnone given

    Exercise frequency, intensity, duration, or type did not influence insulin action.

    “Exercise frequency, intensity, duration, or type did not influence insulin action”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Skeletal muscle is the principal tissue for insulin-dependent glucose disposal and a primary driver of whole-body glycemic control.

    “Skeletal muscle is the principal tissue for insulin-dependent glucose disposal from the blood, and a primary driver of whole-body glycemic control 1.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [1] DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J, Felber JP.The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization.Diabetes. 1981;30:1000–7. source

  • May combine two claims.

    Premisecitation

    Skeletal muscle is the primary site for insulin resistance in type 2 diabetes, and improving insulin sensitivity in this tissue improves whole-body glucose homeostasis.

    “Skeletal muscle is the primary site for insulin resistance in people with type 2 diabetes and improving insulin sensitivity in this tissue improves whole-body glucose homeostasis 6.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Sylow L, Tokarz VL, Richter EA, Klip A. The many actions of insulin in skeletal muscle, the paramount tissue determining glycemia. Cell Metab. 2021;33:758–80. source

  • May combine two claims.

    Premisecitation

    The cold infusion protocol results in marked underestimation of glucose disposal and biologically implausible negative hepatic glucose production values.

    “The cold infusion protocol results in a marked underestimation of glucose disposal, generating biologically implausible negative values of HGP 17.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Finegood DT, Bergman RN, Vranic M. Modeling error and apparent isotope discrimination confound estimation of endogenous glucose production during euglycemic glucose clamps. Diabetes. 1988;37:1025–34. source

  • May combine two claims.

    Study design and conductnone given

    The literature has consistent methodological weaknesses including small sample sizes, poor reporting of adverse events and compliance, and failure to follow intent-to-treat strategies.

    “Lastly, we noted some consistent methodological weaknesses throughout the literature, such as small sample sizes, poor reporting of both adverse events and compliance with the intervention, and failure to follow intent-to-treat analytic strategies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given

    Variables such as timing of the test after the last exercise bout and insulin infusion rate were not standardized across trials.

    “Furthermore, variables such as the timing of the test following the last exercise bout and insulin infusion rate were not standardized.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The improvement in insulin action occurs regardless of weight loss but is enhanced by reductions in body weight.

    “The improvement in insulin action occurs regardless of weight loss but is enhanced by reductions in body weight.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    While aerobic exercise is an important predictor of improvement in insulin action, duration and intensity do not influence the effect of exercise training on glucose disposal.

    “While aerobic exercise is an important predictor of the improvement in insulin action, the duration and intensity of exercise do not influence the effect of exercise training on glucose disposal.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The mean PEDro score was 5.8, and 64% of trials scored at least 6.0, indicating relatively high quality.

    “The mean PEDro score of the exercise interventions was 5.8 ± 1.08 (mean ± SD, Supplemental Information Table 3). The PEDro score was equal to or greater than 6.0 in 64% of trials indicating relatively high quality 21.”
    • Also stated in: § Results: · hedged
      “The PEDro rating indicated relatively low risk of bias (5.8 ± 0·22).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Trials did not specifically report adverse events, but reasons for withdrawal due to adverse events were reported in seven trials.

    “Trials did not specifically report adverse events but the reasons for withdrawal due to adverse events were reported in seven trials (Supplemental Information Table 4).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The systematic review followed PRISMA reporting guidelines.

    “This systematic review followed the PRISMA reporting guidelines.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    During exercise, muscle glucose uptake increases but the process induced by muscle contractions is not dependent on insulin.

    “During exercise, muscle glucose uptake increases but the process induced by muscle contractions is not dependent on insulin 53.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [53] Richter EA, Garetto LP, Goodman MN, Ruderman NB. Enhanced muscle glucose metabolism after exercise: modulation by local factors. Am J Physiol. 1984;246:E476–82. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    Exploratory sub-analyses were unplanned and should be interpreted as hypothesis-generating.

    “As these analyses were unplanned, data should be interpreted as hypothesis-generating.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    All testing in the intervention and control groups was conducted in a controlled research setting.

    “All testing in the intervention and control groups was conducted in a controlled research setting.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The PEDro scale is validated for reliability of a consensus rating from two or more assessors.

    “This checklist was developed to rate the methodological quality of RCTs and is validated for the reliability of a consensus rating from two or more assessors.21”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Maher CG, Sherrington C, Herbert RD, Moseley AM, Elkins M. Reliability of the PEDro scale for rating quality of randomized controlled trials. Phys Ther. 2003;83:713–21. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    A research librarian searched MEDLINE, EMBASE, and CENTRAL from inception to January 5, 2021.

    “A search of three medical databases, including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted by a research librarian from inception to January 5, 2021”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Few trials reported adherence, and five trials reported more than 20% dropout rates.

    “Few trials reported adherence to the intervention; however, five trials 37, 39, 46, 49, 50 reported more than 20% drop out rates.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The protocol was registered with PROSPERO (CRD42019124381).

    “The protocol was registered with the National Institute for Health Research International Prospective Register of Systematic Reviews (PROSPERO) with registration number, CRD42019124381.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Data were independently assessed by one reviewer and checked by another.

    “Data were independently assessed by one reviewer (ACL or CJE) and checked with another (CJR).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The hyperinsulinemic euglycemic clamp accounts for simultaneous rather than sequential responses to glucose and insulin and is a highly reproducible method for quantifying β-cell sensitivity to glucose and tissue sensitivity to insulin.

    “The hyperinsulinemic euglycemic clamp test (hereinafter referred to as clamp) accounts for the simultaneous rather than sequential responses to glucose and insulin. The clamp offers a highly reproducible physiologic method for quantifying β-cell sensitivity to glucose and tissue sensitivity to insulin 16.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237:E214–23. source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Investigators using isotopic tracer dilution with the hot infusion protocol can measure suppression of hepatic glucose production.

    “Investigators who administer the clamp with isotopic tracer dilution techniques using the hot infusion protocol, which incorporates tracers into the exogenous glucose used for clamping 17, can measure the suppression of HGP.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [17] Finegood DT, Bergman RN, Vranic M. Modeling error and apparent isotope discrimination confound estimation of endogenous glucose production during euglycemic glucose clamps. Diabetes. 1988;37:1025–34. source

  • May combine two claims.

    Premisecitation

    Exercise training leads to sustained increases in insulin sensitivity in healthy subjects and in people with type 2 diabetes.

    “Exercise training leads to sustained increases in insulin sensitivity in healthy subjects and in people with type 2 diabetes.12-14”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [12] Mikines KJ, Sonne B, Farrell PA, Tronier B, Galbo H. Effect of training on the dose-response relationship for insulin action in men. J Appl Physiol (1985). 1989;66:695–703. source
    • cites [13] Boule NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA. 2001;286:1218–27. source
    • cites [14] Fatone C, Guescini M, Balducci S, Battistoni S, Settequattrini A, Pippi R, et al. Two weekly sessions of combined aerobic and resistance exercise are sufficient to provide beneficial effects in subjects with Type 2 diabetes mellitus and metabolic syndrome. J Endocrinol Invest. 2010;33:489–95. source

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Title, abstract, and full-text screening was conducted in duplicate by independent reviewers, with disagreements resolved by consensus.

    “Title, abstract, and full-text screening was conducted in duplicate by independent reviewers (CJR, and ACL or CJE) using Covidence systematic review software (Veritas Health Innovation, Melbourne, Australia). Reasons for exclusion were noted at each stage, and disagreements were resolved by consensus.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Data were independently extracted by one reviewer and checked by another using a pilot-tested form.

    “Data were independently extracted by one reviewer (ACL or CJE) and checked with another (CJR) using a pilot tested form. Disagreements were resolved by consensus or by a third reviewer (JCB).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Risk of bias was assessed using the PEDro scale.

    “A critical appraisal of all trials was conducted using the Physiotherapy Evidence Database scale (PEDro scale).”
    Quote in the paperNot a substantial claim
37 of 37

  • The paper relies on this without support.

    Randomized controlled trials examining exercise training effects on glucose disposal and hepatic glucose production had not been systematically summarized before this review.

    “Randomized controlled trials have examined the impact of exercise training on glucose disposal and suppression of HGP, but these randomized trials have not been systematically summarized.”

  • The paper relies on this without support.

    It was unknown whether exercise mode, duration, intensity, and weight loss influence glucose disposal in response to exercise.

    “Furthermore, it is unknown whether factors such as exercise mode, duration, intensity, and weight loss influence glucose disposal in response to exercise.”
2 of 2

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Cold-infusion estimate is not centered in its confidence interval

    Minor

    The reported confidence limits have a midpoint of 0.19, not the stated SMD of 0.04. This is inconsistent with the symmetric confidence intervals used for the reported SMDs.

    Reported 0.04 · recomputed 0.19

  • Intent-to-treat trial count has only seven citations

    Minor

    The text says eight trials used intent-to-treat analyses but lists only seven trial references.

    Reported 8 · recomputed 7

  • Weight-change estimate falls outside its reported confidence interval

    Minor

    The reported regression coefficient is 0.069, but its 95% confidence interval ends at 0.013. A point estimate cannot lie outside its own reported confidence interval.

  • Intent-to-treat trial and intervention counts conflict with the listed trials

    Minor

    The intent-to-treat statement cites seven trials, not eight. Using the paper's intervention counts for those cited trials gives eleven interventions, not ten.

4 of 4

Cites

Flagged first, then by citations

2 of the 67 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

  1. Lipsey MW, Wilson DB. Practical Meta-Analysis vol. 49. Sage Publications: California, 2001.
  2. Hedges LV, Higgins JPT, Rothstein HR, Borenstein M. Introduction to Meta-Analysis, First edn Wiley: New Jersey, 2009.

Cited by

Sorted by citations

Related

Authors
Rebello, C. J., Zhang, D., Kirwan, J. P., Lowe, A. C., Emerson, C. J., Kracht, C. L., Steib, L. C., Greenway, F. L., Johnson, W. D., & Brown, J. C.
Affiliations
Pennington Biomedical Research Center (US)
Corresponding author
Rebello, Candida J.
ORCID
Venue
International Journal of Obesity
Publisher
Springer Science and Business Media LLC
Published
2023-02-24
Volume
47
Issue
5
Pages
348-357
ISSN
  • 0307-0565 (ISSN-L)
  • 1476-5497
DOI
10.1038/s41366-023-01283-8
PMC
PMC10148910
OpenAlex
W4321781648
Cited by
16
References
67
Citations by year
2026: 8 · 2025: 3 · 2024: 4 · 2023: 1
FWCI
0.57
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Obesity (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • Civil War Book Review (submittedVersion)
Funders
  • Louisiana Clinical and Translational Science Center (U54GM104940, GM104940)
  • National Institutes of Health (GM104940)
  • National Institute on Aging (K99AG065419, R00AG065419)
  • National Cancer Institute (R00CA218603)
  • National Institute of General Medical Sciences (GM104940, U54GM104940)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK064584, T32DK064584, P30DK072476)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
  • Health Sciences › Medicine › Physiology › Physical Activity and Health
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords
exercise training, insulin-stimulated glucose disposal, insulin sensitivity, hepatic glucose production, hyperinsulinemic-euglycemic clamp, aerobic exercise, weight loss, tracer techniques, insulin action
MeSH terms
Adult, Glucose, Humans, Insulin, Insulin Resistance, Exercise, Randomized Controlled Trials as Topic

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read under definition version 3 (extract-v3) on 2026-09-28.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-09-28.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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