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Cited by 58Pancreatic function and diabetesDiabetes Treatment and ManagementAdrenal Hormones and Disorders

Twenty‐four‐hour profiles of plasma glucose, insulin, C‐peptide and free fatty acid in subjects with varying degrees of glucose tolerance following short‐term, medium‐dose prednisone (20 mg/day) treatment: evidence for differing effects on insulin secretion and action

Open access
Yuen, Kevin C. J., McDaniel, Patricia A., Riddle, Matthew C.·2012·Clinical Endocrinology
DOI 10.1111/j.1365-2265.2011.04242.xPMC PMC3700529
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Abstract

Summary: Objective To determine the time course and prandial effects of short‐term, medium‐dose prednisone on 24‐h metabolic patterns under standardized conditions. Context Glucocorticoids (GCs) adversely affect glucose homoeostasis but 24‐h profiles of glucose, insulin, C‐peptide and free fatty acids (FFAs) following short‐term, medium‐dose prednisone treatment in persons with varying degrees of glucose tolerance are not well defined. Design An open‐label cross‐sectional interventional study. Subjects Three groups were prospectively studied: persons with type 2 diabetes (T2DM; n = 7), persons ‘at risk’ for T2DM (AR; n = 8) and persons with normal glucose tolerance (NGT; n = 5). Methods Before and after 3‐day treatment with prednisone 20 mg each morning, subjects underwent 24‐h frequent blood sampling. Eucaloric mixed meals were provided at 08:00, 12:00 and 18:00 h. Insulin/glucose ratio provided an estimate of β‐cell response to meal stimuli. Measurements Plasma glucose, insulin, C‐peptide, haemoglobin A1c and FFA. Results Prednisone induced greater increases in glucose levels from midday (P = 0·001) to midnight (P = 0·02) in the T2DM than the AR and NGT groups. In contrast, insulin (P = 0·03) and C‐peptide (P = 0·04) levels decreased postbreakfast in the T2DM group, whereas no changes in the morning but higher C‐peptide levels (P = 0·03) from midday to midnight were observed in the AR group. In the T2DM group, insulin/glucose ratio decreased postbreakfast (P = 0·04) and increased postdinner (P = 0·03). Fasting glucose, insulin and C‐peptide levels were unchanged in all groups, and FFA levels modestly increased postdinner (P = 0·03) in the NGT group. Conclusion Short‐term, medium‐dose prednisone treatment induces postprandial hyperglycaemia in T2DM and AR predominantly from midday to midnight because of suppression of insulin secretion followed by decreased insulin action that dissipates overnight. Effective treatment of prednisone‐induced hyperglycaemia should target both rapid onset relative insulin deficiency and a less than 24‐h total duration of effect.

AI snapshot

Written from the paper’s full text.

TL;DR

In an open-label study, 3-day prednisone 20 mg each morning worsened daytime postprandial glucose most in type 2 diabetes (T2DM) and at-risk (AR) groups, with minimal effects in normal glucose tolerance (NGT). The hormonal patterns suggested early suppression of insulin secretion followed by later decreased insulin action, with effects dissipating by midnight/next morning.

Key findings

  • Prednisone increased glucose from midday to midnight in T2DM and AR groups; between-group incremental AUC glucose was significantly different postlunch (P = 0.001) and postdinner (P = 0.02), with the greatest increment in T2DM. By 00:00 h, glucose returned to pretreatment levels in all 3 groups.
  • In T2DM, insulin and C-peptide decreased postbreakfast (P = 0.03 and P = 0.04, respectively), and the insulin/glucose ratio decreased by 77% postbreakfast (P = 0.04) and increased by 77% postdinner (P = 0.03).
  • In AR, no morning changes were seen but C-peptide was higher from midday to midnight (P = 0.03); the insulin/glucose ratio decreased by 44% postbreakfast (P = 0.05).
  • In NGT, glucose effects were minimal, FFA modestly increased postdinner (P = 0.03), and the insulin/glucose ratio increased by 66% postlunch (P = 0.03) and by 59% postdinner (P = 0.03).

Methods

  • Open-label cross-sectional interventional study: T2DM (n = 7), AR (n = 8; impaired glucose tolerance n = 2 or prior gestational diabetes plus first-degree relatives with T2DM n = 6), and NGT (n = 5).
  • Before and after 3 days of prednisone 20 mg each morning, subjects underwent 24-hour frequent blood sampling; eucaloric mixed meals were provided at 0800 h, 1200 h, and 1800 h. Plasma glucose, insulin, C-peptide, HbA1c, and FFA were measured; insulin/glucose ratio estimated β-cell response to meal stimuli.
  • Incremental AUCs for glucose, insulin, C-peptide, FFAs, and insulin/glucose ratio were calculated by trapezoidal rule over four time blocks: 08:00–12:00 h, 12:00–18:00 h, 18:00–00:00 h, and 00:00–08:00 h. Within-group comparisons used paired Student’s t-test or Wilcoxon signed-rank test; between-group effects used one-way or two-way ANOVA with post hoc tests.

Limitations

  • Stated: β-cell function and insulin sensitivity were assessed indirectly via 24-hour profiles and insulin/glucose ratio rather than glucose clamps or deconvolution; multiple measurements were analyzed within four major time blocks to reduce false positives; the study was unrandomized and cross-sectional with a small number of subjects; findings are limited to 20 mg prednisone for 3 days and cannot be extrapolated to other doses, other glucocorticoids, or longer treatment durations.
  • Evident: group sizes were very small (n = 7, 8, and 5) and the design was open-label; baseline groups differed in age and HbA1c (AR younger than T2DM, P = 0.005, and NGT, P = 0.04; HbA1c higher in T2DM vs AR, P = 0.03, and NGT, P = 0.01), which may confound between-group comparisons.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1111/j.1365-2265.2011.04242.x

Cites

35 of 35 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 29 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    By 00:00, insulin levels had returned to baseline in all three groups.

    “By 00:00 h, insulin levels had all returned to baseline levels in all 3 groups.”
    Quote in the paperNot a substantial claim
  • Findingown data

    By 00:00, the insulin/glucose ratio had returned to pretreatment levels in all three groups.

    “By 00:00 h, the insulin/glucose ratio had returned to pretreatment levels in all 3 groups.”
    Quote in the paperNot a substantial claim
  • Findingown data

    By 00:00, glucose levels had returned to pretreatment levels in all three groups.

    “However, by 00:00 h, glucose levels had returned to pretreatment levels in all 3 groups.”
    Quote in the paperNot a substantial claim
  • Findingown data

    In the NGT group, prednisone treatment increased glucose levels at 12:00, 13:00, and 18:00.

    “In the NGT group, glucose levels were increased at 12:00 h, 13:00 h and 18:00 h.”
    Quote in the paperSubstantial claim
  • Findingown data

    Short-term medium-dose morning prednisone under controlled conditions caused significant worsening of daytime postprandial hyperglycaemia in T2DM and AR groups, with minimal effects in the NGT group.

    “In summary, short-term, medium-dose (20 mg/day) morning prednisone treatment under controlled conditions resulted in significant worsening of daytime postprandial hyperglycaemia in the T2DM and AR groups, with minimal effects in the NGT group.”
    Quote in the paperSubstantial claim
  • May combine two claims. 36
  • Classified as probably not a substantial claim. 10
  • The quote only partly states this claim. 1

  • May combine two claims.

    Findingown data

    Between-group incremental C-peptide AUC after breakfast was significantly lower in the T2DM group than in the AR and NGT groups, but no between-group differences were observed after lunch or dinner.

    “When compared between groups, the incremental AUCC-pep postbreakfast was significantly lower in the T2DM compared with the AR and NGT groups (ANOVA, P = 0.02), but no between-group differences were observed for the incremental AUCC-pep postlunch and postdinner.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the AR group, prednisone treatment decreased the insulin/glucose ratio at 10:00 and increased it at 16:00 and 20:00.

    “whereas in the AR group, the insulin/glucose ratio decreased at 10:00 h and increased at 16:00 h and 20:00 h.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Prednisone treatment decreased the incremental C-peptide AUC after breakfast in the T2DM group, increased postlunch and postdinner C-peptide AUC in the AR group, and did not alter C-peptide AUC in the NGT group.

    “Finally, prednisone treatment decreased the incremental AUCC-pep postbreakfast in the T2DM group and increased the incremental AUCC-pep postlunch and postdinner in the AR group, but did not alter the incremental AUCC-pep in the NGT group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The incremental insulin/glucose ratio AUC decreased by 77% after breakfast and increased by 77% after dinner in the T2DM group, decreased by 44% after breakfast in the AR group, and increased by 66% after lunch and by 59% after dinner in the NGT group.

    “Additionally, the incremental AUC of insulin/glucose ratio (AUCIG) decreased by 77% postbreakfast (P = 0.04) and increased by 77% postdinner (P = 0.03) in the T2DM group, decreased by 44% postbreakfast (P = 0.05) in the AR group, and increased by 66% postlunch (P = 0.03) and by 59% postdinner (P = 0.03) in the NGT group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Between-group incremental insulin AUC after breakfast was significantly lower in the T2DM group than in the AR and NGT groups, but no between-group differences were observed after lunch or dinner.

    “When compared between groups, the incremental AUCins postbreakfast was significantly lower in the T2DM compared with the AR and NGT groups (ANOVA, P = 0.03), but no between-group differences were observed for the incremental AUCins postlunch and postdinner.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Between-group comparison of incremental FFA AUC was not significantly different, and by 00:00 FFA levels had returned to pretreatment levels in all three groups.

    “However, between-group comparison of the incremental AUCFFA was not significantly different, and by 00:00 h, FFA levels had returned to pretreatment levels in all 3 groups.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In the AR and NGT groups, prednisone treatment increased insulin levels at 14:00, 16:00, 19:00, and 20:00, and at 18:00, 20:00, and 22:00, respectively.

    “In contrast, in the AR and NGT groups, prednisone treatment increased insulin levels at 14:00 h, 16:00 h, 19:00 h and 20:00 h, and at 1800 h, 2000 h and 2200 h, respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Prednisone treatment significantly increased the incremental glucose AUC after breakfast, lunch, and dinner in the T2DM and AR groups, and after lunch and dinner in the NGT group.

    “Prednisone treatment significantly increased the incremental AUCgluc postbreakfast, postlunch and postdinner in the T2DM and AR groups, and postlunch and postdinner in the NGT group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Prednisone treatment decreased the incremental insulin AUC after breakfast but did not alter postlunch or postdinner insulin AUC in the T2DM group, and increased postlunch and postdinner insulin AUC in the AR and NGT groups.

    “In contrast, prednisone treatment decreased the incremental AUCins postbreakfast but did not alter the incremental AUCins postlunch and postdinner in the T2DM group, and increased the incremental AUCins postlunch and postdinner in the AR and NGT groups.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Between-group incremental insulin/glucose ratio AUC after lunch was significantly different, but not after breakfast or dinner.

    “The between-group incremental AUCIG postlunch was significantly different (ANOVA, P = 0.01), but not for postbreakfast and postdinner.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Prednisone treatment decreased C-peptide levels in the T2DM group from 10:00 to 14:00, while C-peptide levels remained unchanged in the AR and NGT groups.

    “For C-peptide levels, prednisone treatment decreased C-peptide levels in the T2DM group from 10:00 h to 14:00 h, whereas in AR and NGT groups C-peptide levels were unchanged.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Prednisone treatment decreased insulin levels in the T2DM group at 09:00, 10:00, and 13:00, but increased them at 16:00 and 18:00.

    “Prednisone treatment decreased insulin levels in the T2DM group at 09:00 h, 10:00 h and 13:00 h, but increased these levels at 16:00 h and 18:00 h.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Prednisone treatment raised glucose levels in the T2DM and AR groups from midday to midnight, with T2DM showing increases from 12:00 to 00:00 and AR from 12:00 to 20:00.

    “Prednisone induced greater increases in glucose levels from midday (P = 0.001) to midnight (P = 0.02) in the T2DM than the AR and NGT groups.”
    • Also stated in: § 24-hour profiles of glucose, FFA, insulin and C-peptide (Figures 2 and 3) · plain
      “Prednisone treatment increased glucose levels in the T2DM and AR groups from 12:00 h to 00:00 h and from 12:00 h to 20:00 h, respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the NGT group, prednisone treatment did not change the insulin/glucose ratio after breakfast or lunch, but increased it at 18:00, 20:00, and 22:00.

    “This contrasts with the NGT group where no changes were observed postbreakfast and postlunch, but was increased at 18:00 h, 20:00 h and 22:00 h.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Prednisone treatment did not significantly change fasting glucose, FFA, insulin, C-peptide, or insulin/glucose ratio in any of the three groups.

    “No significant changes were observed for fasting glucose, FFA, insulin, C-peptide and insulin/glucose ratio before and after prednisone treatment for the 3 groups of subjects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Prednisone treatment increased FFA levels in the T2DM group at 13:00, in the AR group from 10:00 to 14:00 and at 18:00 to 19:00, but did not alter FFA levels in the NGT group at any time point.

    “Prednisone treatment increased FFA levels in the T2DM group at 13:00 h, in the AR group from 10:00 h to 14:00 h and at 18:00 h to 19:00 h, whereas in the NGT group, prednisone treatment did not alter FFA levels at any time point.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Between-group incremental glucose AUC after lunch and dinner differed significantly, with the greatest increase observed in the T2DM group.

    “In addition, the between-group incremental AUCgluc postlunch and postdinner were significantly different (ANOVA, P = 0.001 and P = 0.02, respectively) with the greatest increment observed in the T2DM group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the T2DM group, prednisone treatment decreased the insulin/glucose ratio at 10:00 and 12:00 and increased it at 19:00 and 20:00.

    “In the T2DM group, prednisone treatment decreased the insulin/glucose ratio at 10:00 h and 12:00 h and increased the insulin/glucose ratio at 190:0 h and 20:00 h”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Prednisone treatment did not alter the incremental FFA AUC after breakfast, lunch, or dinner in the T2DM and AR groups, but increased the postdinner FFA AUC in the NGT group.

    “Prednisone treatment did not alter the incremental AUCFFA postbreakfast, postlunch and postdinner in the T2DM and AR groups, and increased the incremental AUCFFA postdinner in the NGT group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Increased hyperglycaemia in T2DM subjects was transitory, most notable at midday and dissipated by midnight.

    “Increased hyperglycaemia in subjects with T2DM was transitory, being most notable at midday and dissipated by midnight.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    The changes in insulin and C-peptide patterns suggest early suppression of insulin secretion in T2DM and later onset of decreased insulin action in all three groups, followed by complete resolution by the next morning.

    “Our data are in line with those recently reported by Burt et al.,20 but further extend their findings by demonstrating that the changes in the patterns of insulin and C-peptide levels strongly suggest early suppression of insulin secretion in the T2DM group and later onset of decreased insulin action in all 3 groups, followed by complete resolution of all metabolic parameters by the next morning.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Burt et al.,20

      Not checked in the free run.

    • Rests on an assumption: The insulin/glucose ratio provides a valid estimate of β-cell response to meal stimuli.
    • Rests on an assumption: Changes in plasma insulin, C-peptide, and insulin/glucose ratio reflect changes in insulin secretion and insulin action.

  • May combine two claims.

    Interpretationown data

    Short-term medium-dose prednisone treatment induces postprandial hyperglycaemia in T2DM and AR predominantly from midday to midnight through suppression of insulin secretion followed by decreased insulin action that dissipates overnight.

    “Short-term, medium-dose prednisone treatment induces postprandial hyperglycaemia in T2DM and AR predominantly from midday to midnight because of suppression of insulin secretion followed by decreased insulin action that dissipates overnight.”
    • Also stated in: § Discussion · hedged
      “the pertinent changes in the hormonal patterns observed were consistent with a rapidly appearing yet transitory reduction in endogenous insulin secretion followed by decreased insulin action later that dissipated overnight.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The insulin/glucose ratio provides a valid estimate of β-cell response to meal stimuli.
    • Rests on an assumption: Changes in plasma insulin, C-peptide, and insulin/glucose ratio reflect changes in insulin secretion and insulin action.

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

    Premisecitation

    Glucocorticoid-induced hyperinsulinaemia is regarded as an adaptation of pancreatic β-cell function to glucocorticoid-induced insulin resistance in liver, muscle, and adipose tissues.

    “Glucocorticoid-induced hyperinsulinaemia is regarded as an adaptation of pancreatic â-cell function to the GC-induced insulin resistance in liver, muscle and adipose tissues, either through hyperglycaemia, by other signalling mechanisms, or most likely a combination of these mechanisms.27,28”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [27] Buren J Lai YC Lundgren M Eriksson JW Jensen J 2008 Insulin action and signalling in fat and muscle from dexamethasone-treated rats Arch Biochem Biophys 474 91 101 18328801 source

      Not checked in the free run.

    • cites [28] Nicod N Giusti V Besse C Tappy L 2003 Metabolic adaptations to dexamethasone-induced insulin resistance in healthy volunteers Obes Res 11 625 631 12740452 source

      Not checked in the free run.

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

    Premisecitation

    Glucocorticoid receptors are present on β-cells.

    “As GC receptors are known to be present on â-cells,29,30 it is possible that GCs may also exert direct stimulatory and inhibitory effects on insulin secretion.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [29] Fischer B Rausch U Wollny P Westphal H Seitz J Aumuller G 1990 Immunohistochemical localization of the glucocorticoid receptor in pancreatic beta-cells of the rat Endocrinology 126 2635 2641 1691702 source

      Not checked in the free run.

    • cites [30] Matthes H Kaiser A Stier U Riecken EO Rosewicz S 1994 Glucocorticoid receptor gene expression in the exocrine and endocrine rat pancreas Endocrinology 135 476 479 8013388 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Prednisone-induced insensitivity to insulin occurs later in the day and may be less well compensated by β-cell adaptation in T2DM and AR subjects.

    “2) prednisone-induced insensitivity to insulin occurs later in the day and may be less well compensated by â-cell adaptation in the T2DM and AR subjects.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The insulin/glucose ratio provides a valid estimate of β-cell response to meal stimuli.
    • Rests on an assumption: Changes in plasma insulin, C-peptide, and insulin/glucose ratio reflect changes in insulin secretion and insulin action.

  • May combine two claims.

    Premisecitation

    Glucocorticoids induce peripheral hyperinsulinemia via prehepatic β-cell insulin hypersecretion partially ameliorated by increased hepatic insulin clearance, but not with C-peptide because glucocorticoids do not affect hepatic extraction of C-peptide and C-peptide clearance is linear.

    “Glucocorticoids have been previously shown to induce peripheral hyperinsulinemia because of prehepatic β-cell insulin hypersecretion that is partially ameliorated by a concomitant increase of hepatic insulin clearance,22,23 but not with C-peptide as GCs do not affect hepatic extraction of C-peptide24, and the clearance kinetics of C-peptide is linear.25”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [22] Kautzky-Willer A Thomaseth K Clodi M Ludvik B Waldhausl W Prager R Pacini G 1996 Beta-cell activity and hepatic insulin extraction following dexamethasone administration in healthy subjects Metabolism 45 486 491 8609836 source

      Not checked in the free run.

    • cites [23] Meier JJ Veldhuis JD Butler PC 2005 Pulsatile insulin secretion dictates systemic insulin delivery by regulating hepatic insulin extraction in humans Diabetes 54 1649 1656 15919785 source

      Not checked in the free run.

    • cites [24] Bruno A Carucci P Cassader M Cavallo-Perin P Gruden G Olivetti C Pagano G 1994 Serum glucose, insulin and C-peptide response to oral glucose after intravenous administration of hydrocortisone and methylprednisolone in man Eur J Clin Pharmacol 46 411 415 7957534 source

      Not checked in the free run.

    • cites [25] Polonsky K Jaspan J Pugh W Cohen D Schneider M Schwartz T Moossa AR Tager H Rubenstein AH 1983 Metabolism of C-peptide in the dog. In vivo demonstration of the absence of hepatic extraction J Clin Invest 72 1114 1123 6350363 PMC1129279 source

      Not checked in the free run.

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

    Study design and conductnone given

    The study was unrandomized and cross-sectional, with a small number of subjects.

    “Other limitations of this study include the unrandomized and cross-sectional study design and the small number of study subjects.”
    Quote in the paperNot a substantial claim

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

    Study design and conductnone given

    All enrolled subjects completed the study.

    “All enrolled subjects completed the study.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Animal studies show direct inhibitory effects of glucocorticoids on insulin secretion, and some human studies show adverse effects on β-cell function.

    “In addition, animal studies8,9 have demonstrated direct inhibitory effects of GCs on insulin secretion and adverse effects on â-cell function in some human studies.10,11”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [8] Lambillotte C Gilon P Henquin JC 1997 Direct glucocorticoid inhibition of insulin secretion. An in vitro study of dexamethasone effects in mouse islets J Clin Invest 99 414 423 9022074 PMC507814 source

      Not checked in the free run.

    • cites [9] Longano CA Fletcher HP 1983 Insulin release after acute hydrocortisone treatment in mice Metabolism 32 603 608 6341775 source

      Not checked in the free run.

    • cites [10] Kalhan SC Adam PA 1975 Inhibitory effect of prednisone on insulin secretion in man: model for duplication of blood glucose concentration J Clin Endocrinol Metab 41 600 610 1159064 source

      Not checked in the free run.

    • cites [11] van Raalte DH Nofrate V Bunck MC van Iersel T Elassaiss Schaap J Nassander UK Heine RJ Mari A Dokter WH Diamant M 2010 Acute and 2-week exposure to prednisolone impair different aspects of beta-cell function in healthy men Eur J Endocrinol 162 729 735 20124412 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Previous studies have generally used high doses of long-acting glucocorticoids and assessed β-cell function with intravenous glucose tests rather than standardized meals.

    “However, previous studies have generally used high doses of long-acting GCs such as dexamethasone or betamethasone that are infrequently utilized for ambulatory treatment in clinical practice, and â-cell function has been assessed by tests using intravenous glucose loads such as the intravenous glucose tolerance test or the hyperglycaemic clamp12–14 rather than standardized meals.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [12] Grill V Pigon J Hartling SG Binder C Efendic S 1990 Effects of dexamethasone on glucose-induced insulin and proinsulin release in low and high insulin responders Metabolism 39 251 258 2407926 source

      Not checked in the free run.

    • cites [13] Larsson H Ahren B 1999 Insulin resistant subjects lack islet adaptation to short-term dexamethasone-induced reduction in insulin sensitivity Diabetologia 42 936 943 10491753 source

      Not checked in the free run.

    • cites [14] Wajngot A Giacca A Grill V Vranic M Efendic S 1992 The diabetogenic effects of glucocorticoids are more pronounced in low- than in high-insulin responders Proc Natl Acad Sci U S A 89 6035 6039 1631088 PMC402133 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    In NGT subjects, prednisone did not suppress insulin secretion, suggesting that the ability to compensate for decreased insulin action may relate to the severity of the underlying β-cell defect and higher prednisolone doses.

    “This contrasts with our findings where our subjects with NGT did not demonstrate any tendency towards prednisone-induced suppression of insulin secretion, suggesting that the ability to compensate for the decrease in insulin action with corresponding increases in insulin secretion may be related to the severity of the underlying â-cell defect and higher doses of prednisolone used.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The insulin/glucose ratio provides a valid estimate of β-cell response to meal stimuli.
    • Rests on an assumption: Changes in plasma insulin, C-peptide, and insulin/glucose ratio reflect changes in insulin secretion and insulin action.

  • May combine two claims.

    Premisecitation

    Other biologic effects of similar doses of oral prednisone peak between 4 and 8 hours and last 12 to 16 hours.

    “This pattern is consistent with evidence that other biologic effects of similar doses of orally administered prednisone reach a peak between 4 and 8 hours and have a duration of action lasting in the range of 12 to 16 hours.26”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] Magee MH Blum RA Lates CD Jusko WJ 2001 Prednisolone pharmacokinetics and pharmacodynamics in relation to sex and race J Clin Pharmacol 41 1180 1194 11697751 PMC4207281 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Prominent hyperglycaemia is most often observed with high-dose glucocorticoids in persons with known diabetes, but may also occur at moderate and low doses in persons not previously known to be at risk.

    “Prominent hyperglycaemia is most often observed when high dosages of GC are taken by persons with known diabetes, but may also occur at moderate and low doses in persons not previously known to be at risk.3,4”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [3] Gulliford MC Charlton J Latinovic R 2006 Risk of diabetes associated with prescribed glucocorticoids in a large population Diabetes Care 29 2728 2729 17130214 source

      Not checked in the free run.

    • cites [4] van Raalte DH Brands M van der Zijl NJ Muskiet MH Pouwels PJ Ackermans MT Sauerwein HP Serlie MJ Diamant M 2011 Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial Diabetologia 54 2103 2112 21562755 PMC3131514 source

      Not checked in the free run.

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

    Study design and conductreasoning

    Analyses within and between groups were performed on four major time blocks to account for potential false positives from 15 measurements.

    “The study design also involved the measurement of variables at 15 time points before and after prednisone; hence, to account for the potential of false positive results with this number of measurements, analyses within-groups and between-groups of the 4 major time blocks were performed.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    The hyperglycaemic effect of glucocorticoids is generally attributed to reduced insulin sensitivity in muscle, liver, and adipose tissue.

    “This unwanted hyperglycaemic effect is generally attributed to the reduction in sensitivity to insulin action in muscle, liver and adipose tissue.5–7”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [5] Besse C Nicod N Tappy L 2005 Changes in insulin secretion and glucose metabolism induced by dexamethasone in lean and obese females Obes Res 13 306 311 15800288 source

      Not checked in the free run.

    • cites [6] Pagano G Cavallo-Perin P Cassader M Bruno A Ozzello A Masciola P Dall’omo AM Imbimbo B 1983 An in vivo and in vitro study of the mechanism of prednisone-induced insulin resistance in healthy subjects J Clin Invest 72 1814 1820 6355186 PMC370470 source

      Not checked in the free run.

    • cites [7] Subramanian S DeRosa MA Bernal-Mizrachi C Laffely N Cade WT Yarasheski KE Cryer PE Semenkovich CF 2006 PPARalpha activation elevates blood pressure and does not correct glucocorticoid-induced insulin resistance in humans Am J Physiol Endocrinol Metab 291 E1365 1371 16868225 PMC4303180 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    Individuals with an inherent β-cell defect may be susceptible to rapid suppression of insulin secretion by medium-dose prednisone, contributing significantly to daytime hyperglycaemia, whereas NGT subjects are not significantly affected.

    “1) individuals with an inherent â-cell defect may be susceptible to rapid suppression of insulin secretion by medium-dose prednisone, an effect which contributes significantly to prednisone-induced daytime hyperglycaemia, whereas this phenomenon does not significantly affect subjects with NGT”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The insulin/glucose ratio provides a valid estimate of β-cell response to meal stimuli.
    • Rests on an assumption: Changes in plasma insulin, C-peptide, and insulin/glucose ratio reflect changes in insulin secretion and insulin action.

  • May combine two claims.

    Interpretationown data

    Rapid suppression of insulin secretion does not appear to persist beyond lunch, by which time the hyperglycaemic effect due to tissue insensitivity becomes more apparent in both T2DM and AR groups.

    “In addition, the rapid suppression of insulin secretion does not appear to persist beyond lunch, by which time the hyperglycaemic effect because of insensitivity of tissues becomes more apparent in both the T2DM and AR groups.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The insulin/glucose ratio provides a valid estimate of β-cell response to meal stimuli.
    • Rests on an assumption: Changes in plasma insulin, C-peptide, and insulin/glucose ratio reflect changes in insulin secretion and insulin action.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    In healthy men, acute prednisolone 75 mg/day had an acute inhibitory effect on the β-cell, while longer exposure to 30 mg/day caused fasting and postprandial hyperglycaemia but relative hypoinsulinemia, thought secondary to insufficient compensatory β-cell response.

    “In a recent study by van Raalte et al.11 in healthy men, acute treatment with 75 mg/day of prednisolone resulted in an acute inhibitory effect of the â-cell, but longer exposure with a prednisolone dose of 30 mg/day resulted in fasting and postprandial hyperglycaemia but relative hypoinsulinemia, which was thought to be secondary to the insufficient compensatory â-cell response.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [11] van Raalte DH Nofrate V Bunck MC van Iersel T Elassaiss Schaap J Nassander UK Heine RJ Mari A Dokter WH Diamant M 2010 Acute and 2-week exposure to prednisolone impair different aspects of beta-cell function in healthy men Eur J Endocrinol 162 729 735 20124412 source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Study design and conductown data

    AR subjects were younger than T2DM and NGT subjects, and HbA1c was higher in T2DM than in AR and NGT groups.

    “The subjects in AR group had either impaired fasting glucose levels or impaired glucose tolerance or both and were younger than the subjects with T2DM (P = 0.005) and NGT (P = 0.04).”
    • Also stated in: § Baseline characteristics (Table 1) · plain
      “The haemoglobin A1c levels were significantly higher in the T2DM group compared with the AR (P = 0.03) and NGT (P = 0.01) groups.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Glucocorticoids adversely affect glucose homeostasis, including insulin resistance, visceral adiposity, dyslipidaemia, and fasting and postprandial hyperglycaemia.

    “their usage is associated with a significant number of metabolic adverse effects, including insulin resistance, visceral adiposity, dyslipidaemia and fasting and postprandial hyperglycaemia.2”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Donihi AC Raval D Saul M Korytkowski MT DeVita MA 2006 Prevalence and predictors of corticosteroid-related hyperglycemia in hospitalized patients Endocr Pract 12 358 362 16901792 source

      Not checked in the free run.

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

    Study design and conductcitation

    Assays for glucose, insulin, C-peptide, FFA, and HbA1c had coefficients of variation below specified thresholds.

    “The coefficient of variation of this reference method was < 3%.”
    • Also stated in: § Assays · plain
      “has a reported average coefficient of variation of less than 10%”
    • Also stated in: § Assays · plain
      “the coefficients of variation for haemoglobin A1c were less than 2.5%”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [16] Wiedmeyer HM Polonsky KS Myers GL Little RR Greenbaum CJ Goldstein DE Palmer JP 2007 International comparison of C-peptide measurements Clin Chem 53 784 787 17332147 source

      Not checked in the free run.

    • cites [17] Meyer KA Conigrave KM Chu NF Rifai N Spiegelman D Stampfer MJ Rimm EB 2003 Alcohol consumption patterns and HbA1c, C-peptide and insulin concentrations in men J Am Coll Nutr 22 185 194 12805244 source

      Not checked in the free run.

    • cites [18] Cole RA Soeldner JS Dunn PJ Bunn HF 1978 A rapid method for the determination of glycosylated hemoglobins using high pressure liquid chromatography Metabolism 27 289 301 628353 source

      Not checked in the free run.

    • cites [19] Davis JE McDonald JM Jarett L 1978 A high-performance liquid chromatography method for hemoglobin A1c Diabetes 27 102 107 624438 source

      Not checked in the free run.

41 of 41

  • The paper relies on this without support.

    The insulin/glucose ratio provides a valid estimate of β-cell response to meal stimuli.

    “Insulin/glucose ratio provided an estimate of â-cell response to meal stimuli.”

  • The paper relies on this without support.

    Between-group differences in prednisone response are attributable to differences in glucose tolerance rather than baseline differences such as age or HbA1c.

    “The subjects in AR group had either impaired fasting glucose levels or impaired glucose tolerance or both and were younger than the subjects with T2DM (P = 0.005) and NGT (P = 0.04).”
    “The haemoglobin A1c levels were significantly higher in the T2DM group compared with the AR (P = 0.03) and NGT (P = 0.01) groups.”

  • The paper relies on this without support.

    Subjects took 20 mg prednisone as instructed for 3 consecutive days.

    “Following the completion of Visit 1, all subjects were instructed to take 20 mg of prednisone orally for 3 consecutive days (Days 1–3) at 08:00 h.”

  • The paper relies on this without support.

    Changes in plasma insulin, C-peptide, and insulin/glucose ratio reflect changes in insulin secretion and insulin action.

    “the changes in the patterns of insulin and C-peptide levels strongly suggest early suppression of insulin secretion in the T2DM group and later onset of decreased insulin action in all 3 groups”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

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.

  • FFA changes in T2DM and AR are both reported and denied

    Minor

    The results report increased FFA levels at specific times in both groups, but the discussion says no changes in circulating FFA levels were observed in either group.

  • Midnight glucose is described as both elevated and back to pretreatment levels

    Minor

    The stated T2DM interval of increased glucose extends to 00:00 h, while the subsequent statement says glucose had returned to pretreatment levels by 00:00 h in all groups.

2 of 2

Cites

Flagged first, then by citations

1 of the 36 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
Yuen, K. C. J., McDaniel, P. A., & Riddle, M. C.
Affiliations
Oregon Health & Science University (US)
Corresponding author
Yuen, Kevin C. J.
ORCID
Venue
Clinical Endocrinology
Publisher
Wiley
Published
2012-07-10
Volume
77
Issue
2
Pages
224-232
ISSN
  • 0300-0664 (ISSN-L)
  • 1365-2265
DOI
10.1111/j.1365-2265.2011.04242.x
PMC
PMC3700529
OpenAlex
W1719124165
Cited by
58
References
36
Citations by year
2026: 2 · 2025: 3 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 8 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 5 · 2014: 8 · 2013: 7 · 2012: 2
FWCI
5.56
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Clinical Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Deutsches Krebsforschungszentrum
  • National Center for Research Resources (UL1RR024140)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
prednisone, glucocorticoids, glucose tolerance, type 2 diabetes, prediabetes, insulin secretion, insulin resistance, C-peptide, free fatty acids, postprandial hyperglycemia, insulin/glucose ratio, beta-cell function, 24-hour glucose profile, insulin sensitivity, glucose homeostasis, HbA1c
MeSH terms
Adult, Aged, Blood Glucose, C-Peptide, Cross-Sectional Studies, Diabetes Mellitus, Type 2, Fatty Acids, Nonesterified, Female, Humans, Insulin, Male, Middle Aged, Prednisone, Prospective Studies

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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 by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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