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Cited by 27Diabetes Treatment and ManagementDiabetes Management and ResearchHyperglycemia and glycemic control in critically ill and hospitalized patients

Management of hyperglycaemia in persons with non-insulin-dependent type 2 diabetes mellitus who are started on systemic glucocorticoid therapy: a systematic review

Open access
Tatalovic, Milos, Lehmann, Roger, Cheetham, Marcus, Nowak, Albina, Battegay, Edouard, Rampini, Silvana K·2019·BMJ Open
DOI 10.1136/bmjopen-2019-028914PMC PMC6549610
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Abstract

Objectives: What is the most effective pharmacological intervention for glycaemic control in known type 2 diabetes mellitus (DM) without prior insulin treatment and newly started on systemic glucocorticoid therapy? Design: We conducted a systematic literature review. Data sources: We searched MEDLINE, Embase and Cochrane Library databases and Google for articles from 2002 to July 2018. Eligibility criteria: We combined search terms relating to DM (patients, >16 years of age), systemic glucocorticoids, glycaemic control, randomised controlled trials (RCTs) and observational studies. Data extraction and synthesis: We screened and evaluated articles, extracted data and assessed risk of bias and quality of evidence according to Grading of Recommendations Assessment, Development and Evaluation guidelines. Results: Eight of 2365 articles met full eligibility criteria. Basal-bolus insulin (BBI) strategy for patients under systemic glucocorticoid therapy was comparatively effective but provided insufficient glucose control, depending on time of day. BBI strategy with long-acting insulin and neutral protamin Hagedorn as basal insulin provided similar overall glycaemic control. Addition of various insulin strategies to standard BBI delivered mixed results. Intermediate-acting insulin (IMI) as additional insulin conferred no clear benefits, and glycaemic control with sliding scale insulin was inferior to BBI or IMI. No studies addressed whether anticipatory or compensatory insulin adjustments are better for glycaemic control. Conclusion: The lack of suitably designed RCTs and observational studies, heterogeneity of interventions, target glucose levels and glucose monitoring, poor control of DM subgroups and low to moderate quality of evidence render identification of optimal pharmacological interventions for glycaemic control and insulin management difficult. Even findings on the widely recommended BBI regimen as intensive insulin therapy for patients with DM on glucocorticoids are inconclusive. High-quality evidence from studies with well-defined DM phenotypes, settings and treatment approaches is needed to determine optimal pharmacological intervention for glycaemic control. PROSPERO registration number: CRD42015024739.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review found no conclusive evidence identifying the optimal pharmacological intervention for hyperglycaemia in non-insulin-treated type 2 diabetes patients newly started on systemic glucocorticoids. Available studies were heterogeneous and of low to moderate quality, though they suggested basal-bolus insulin (BBI) is preferable to sliding-scale insulin (SSI), with no clear preference between long-acting and NPH basal insulin.

Key findings

  • Eight of 2365 screened articles met full eligibility criteria, including 481 persons total: 343 with diabetes mellitus and 138 with glucocorticoid-induced hyperglycaemia.
  • BBI was comparatively effective but provided insufficient glucose control depending on time of day; in Burt et al., mean daily blood glucose was significantly higher in prednisolone-treated patients than controls (p<0.001), especially at 17:00 and 21:00.
  • SSI was inferior to BBI or intermediate-acting insulin (IMI): Gosmanov et al. found higher mean daily blood glucose with SSI (p<0.001) and 3/28 (11%) SSI-treated persons were referred to intensive care for hyperglycaemic events; Gerards et al. found IMI gave longer time in target range (p<0.001) and lower mean daily blood glucose (p<0.05) than SSI.
  • BBI with long-acting insulin versus NPH as basal insulin showed similar overall glycaemic control across three studies; addition of NPH or correctional insulin to BBI gave mixed results, and no studies addressed whether anticipatory or compensatory insulin adjustments are better.

Methods

  • Systematic review registered with PROSPERO (CRD42015024739), reported according to PRISMA, using PICOS criteria; searched MEDLINE, Embase, Cochrane Library, and Google for articles from 2002 to July 2018.
  • Included randomised controlled trials and observational studies of non-critically ill inpatients or outpatients >16 years with type 2 diabetes treated with diet or oral hypoglycaemic agents and started on systemic glucocorticoids.
  • Data were extracted on population, glucocorticoid dose/duration, target glucose, insulin strategy, and outcomes; risk of bias assessed with Cochrane tool for RCTs and GRADE criteria for observational studies and overall quality; synthesis was descriptive because heterogeneity precluded meta-analysis.

Limitations

  • The paper states that the lack of suitably designed RCTs and observational studies, heterogeneity of interventions, target glucose levels and glucose monitoring, poor control of diabetes subgroups, and low to moderate quality of evidence made it difficult to identify optimal pharmacological interventions or provide formal recommendations.
  • The paper states it included mixed populations—persons with type 2 diabetes with or without prior insulin treatment and type 1 diabetes—because there were insufficient articles with the specific subgroup of interest, which is not standard practice in systematic reviews.
  • Evident from the text: included studies were small (total 481 persons), all RCTs were unblinded, observational studies had confounding risks, and the overall quality of evidence for individual interventions was classified as moderate, low, or very low.

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

Integrity signals

Registry

Crossref · 10.1136/bmjopen-2019-028914

Cites

55 of 55 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 80 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    Glycaemic control with sliding scale insulin was inferior to BBI or IMI.

    “glycaemic control with sliding scale insulin was inferior to BBI or IMI.”
    Quote in the paperSubstantial claim
  • Findingnone given

    Basal-bolus insulin (BBI) strategy for patients under systemic glucocorticoid therapy was comparatively effective.

    “Basal-bolus insulin (BBI) strategy for patients under systemic glucocorticoid therapy was comparatively effective”
    Quote in the paperSubstantial claim
  • Findingnone given

    Intermediate-acting insulin (IMI) as additional insulin conferred no clear benefits.

    “Intermediate-acting insulin (IMI) as additional insulin conferred no clear benefits”
    Quote in the paperSubstantial claim
  • Findingnone given

    Addition of various insulin strategies to standard BBI delivered mixed results.

    “Addition of various insulin strategies to standard BBI delivered mixed results.”
    Quote in the paperSubstantial claim
  • Findingown data

    No studies addressed whether anticipatory or compensatory insulin adjustments are better for glycaemic control.

    “No studies addressed whether anticipatory or compensatory insulin adjustments are better for glycaemic control.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 22
  • May combine two claims. 26
  • The quote only partly states this claim. 3

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

    Findingown data

    Eight of 2365 articles met full eligibility criteria.

    “Eight of 2365 articles met full eligibility criteria.”
    • Also stated in: § Study inclusion · plain
      “Eight articles met full eligibility criteria”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    BGL was significantly higher at 17:00 and 21:00, but not significantly higher at 07:00 and 12:00.

    “More specifically, BGL was significantly higher at 17:00 and 21:00, but not significantly higher at 07:00 and 12:00”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [38] Burt, 2015, Efficacy of a basal bolus insulin protocol to treat prednisolone-induced hyperglycaemia in hospitalised patients, Intern Med J source

      Not checked in the free run.

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

    Findingcitation

    At least 85/481 persons had prior treatment with insulin; three studies did not provide this information.

    “At least 85/481 persons had prior treatment with insulin; three studies did not provide this information.33 34 39”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites 33 34 39

      Not checked in the free run.

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

    Findingcitation

    Seven studies included inpatients only, and one study included both inpatients and outpatients.

    “Seven studies included inpatients only,33–36 38–40 and one study included both inpatients and outpatients.37”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites 33–36 38–40

      Not checked in the free run.

    • cites [37] Gerards, 2016, Add-on treatment with intermediate-acting insulin versus sliding-scale insulin for patients with type 2 diabetes or insulin resistance during cyclic glucocorticoid-containing antineoplastic chemotherapy: a randomized crossover study, Diabetes Obes Metab source

      Not checked in the free run.

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

    Findingcitation

    In persons with or without type 2 diabetes mellitus, addition of correctional insulin matched to the glycaemic profile of the administered glucocorticoid to a basal-bolus insulin regimen significantly improved time in target premeal glucose range (5.6-10 mmol/L) and mean daily blood glucose level, but not time in bedtime target glucose range.

    “Correctional insulin significantly improved ‘time in target premeal glucose range’ (defined as 5.6–10 mmol/L (p=0.002) and mean daily BGL (p=0.0001) but not time in ‘bedtime target glucose range’ (p=0.09).”
    • Also stated in: § Discussion · plain
      “This resulted in significantly lower mean daily BGL and premeal time in target glucose range.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [33] Lakhani, 2017, Comparison of Two Protocols in the Management of Glucocorticoid-induced Hyperglycemia among Hospitalized Patients, Indian J Endocrinol Metab source

      Not checked in the free run.

  • May combine two claims.

    Findingcitation

    The daily insulin dose was significantly higher in the prednisolone-treated group than in the control group, especially at 12:00 and 17:00.

    “In addition, the daily insulin dose was significantly higher in the prednisolone-treated group than in the control group, especially at 12:00 and 17:00.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Burt, 2015, Efficacy of a basal bolus insulin protocol to treat prednisolone-induced hyperglycaemia in hospitalised patients, Intern Med J source

      Not checked in the free run.

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

    Findingown data

    The upper limit was a BGL of 10 mmol/L in all studies.

    “The upper limit was a BGL of 10 mmol/L in all studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Three studies compared BBI regimens with long-acting insulins to BBI regimens with intermediate-acting neutral protamin Hagedorn (NPH) insulin, but in one of these studies, NPH was given in three equal prandial doses.

    “Three studies compared BBI regimens with long-acting insulins to BBI regimens with intermediate-acting neutral protamin Hagedorn (NPH) insulin,35 36 39 but in one of these studies, NPH was given in three equal prandial doses.36”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites 35 36 39

      Not checked in the free run.

    • cites [36] Ruiz de Adana, 2015, Randomized clinical trial of the efficacy and safety of insulin glargine vs. NPH insulin as basal insulin for the treatment of glucocorticoid induced hyperglycemia using continuous glucose monitoring in hospitalized patients with type 2 diabetes and respiratory disease, Diabetes Res Clin Pract source

      Not checked in the free run.

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

    Findingcitation

    In patients with type 2 diabetes mellitus or insulin resistance during cyclic glucocorticoid-containing antineoplastic chemotherapy, addition of intermediate-acting insulin to established diabetes medication resulted in significantly longer time in target glucose range and lower mean daily blood glucose level compared with sliding-scale insulin, and this was achieved with an increased insulinrequi

    “The addition of IMI resulted in significantly longer time in target glucose range (p<0.001) and lower mean daily BGL (p<0.05).”
    • Also stated in: § Discussion · plain
      “Gerards et al 37 corroborates that SSI delivers poorer control compared with IMI when used as an addition to the routine DM regimen.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [37] Gerards, 2016, Add-on treatment with intermediate-acting insulin versus sliding-scale insulin for patients with type 2 diabetes or insulin resistance during cyclic glucocorticoid-containing antineoplastic chemotherapy: a randomized crossover study, Diabetes Obes Metab source

      Not checked in the free run.

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

    Findingcitation

    The lower BGL limit was 3.9-4.5 mmol/L in all but two studies in which it was 5.6 mmol/L.

    “The lower BGL limit was 3.9–4.5 mmol/L in all but two studies in which it was 5.6 mmol/L33 40 (table 2).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites 33 40

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    In the same population, the mean daily blood glucose level and the number of mild hypoglycaemic episodes per day are similar between NPH and glargine groups.

    “More specifically, the mean daily BGL and the number of mild hypoglycaemic episodes per day were similar (table 2).”
    Quote in the paperSubstantial claim

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

    Findingcitation

    In persons with or without type 2 diabetes mellitus, addition of NPH insulin together with a glucocorticoid to a basal-bolus insulin regimen showed no advantage for glycaemic control, mean total daily insulin dose, or hypoglycaemia and hyperglycaemia.

    “The study showed that there was no advantage in this for glycaemic control, mean total daily insulin dose, or hypoglycaemia and hyperglycaemia (table 2).”
    • Also stated in: § Discussion · plain
      “The addition of NPH together with the glucocorticoid in the BBI treatment also failed to improve glycaemic control.34”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [34] Grommesh, 2016, Hospital insulin protocol aims for glucose control in glucocorticoid-induced hyperglycemia, Endocr Pract source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    The eight included articles comprised four RCTs with open-label parallel group designs, one RCT with open-label cross-over design, and three retrospective cohort observational studies.

    “Eight articles met full eligibility criteria, namely, four RCTs33–36 with open-label and parallel group designs, one RCT with open-label and cross-over design37 and three observational studies38–40 with a retrospective cohort design (figure 1 and table 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The eight articles reported studies that included a total of 481 persons, 343/481 persons with DM and 138/481 persons with glucocorticoid-induced hyperglycaemia.

    “The eight articles reported studies that included a total of 481 persons, 343/481 persons with DM and 138/481 persons with glucocorticoid-induced hyperglycaemia.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    In six studies, authors treated control groups with a basal-bolus insulin (BBI) regimen using insulin glargine as basal insulin, in one study with a BBI regimen using twice-daily insulin detemir, and one study using sliding-scale insulin (SSI) in addition to established DM medication.

    “In six studies, authors treated control groups with a basal-bolus insulin (BBI) regimen using insulin glargine as basal insulin,33–36 38 39 in one study with a BBI regimen using twice-daily insulin detemir,40 and one study using sliding-scale insulin (SSI) in addition to established DM medication.37”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites 33–36 38 39

      Not checked in the free run.

    • cites [40] source

      Not checked in the free run.

    • cites [37] Gerards, 2016, Add-on treatment with intermediate-acting insulin versus sliding-scale insulin for patients with type 2 diabetes or insulin resistance during cyclic glucocorticoid-containing antineoplastic chemotherapy: a randomized crossover study, Diabetes Obes Metab source

      Not checked in the free run.

  • May combine two claims.

    Findingreasoning

    The lack of relevant randomised controlled trials and observational studies, heterogeneity of populations, interventions, target glucose levels and glucose monitoring in available studies, and low to moderate quality of available evidence make it difficult to identify pharmacological interventions for effective glycaemic control.

    “The lack of relevant RCTs and observational studies, heterogeneity of populations, interventions, target glucose levels and glucose monitoring in available studies, and low to moderate quality of available evidence make it difficult to identify pharmacological interventions for effective glycaemic control.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    The reviewed studies speak in favour of the use of a basal-bolus insulin regimen without a specific preference for long-acting or intermediate-acting insulin as basal insulin.

    “Second, the reviewed studies speak in favour of the use of BBI without a specific preference for long-acting or IMI as basal insulin”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingcitation

    Insulin requirement was higher in basal-bolus insulin with long-acting insulin compared with NPH as basal insulin in two studies, but it was similar in the other.

    “Insulin requirement, however, was higher in BBI with long-acting insulin compared with NPH as basal insulin in two of the studies,36 39 but it was similar in the other.35”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [36] Ruiz de Adana, 2015, Randomized clinical trial of the efficacy and safety of insulin glargine vs. NPH insulin as basal insulin for the treatment of glucocorticoid induced hyperglycemia using continuous glucose monitoring in hospitalized patients with type 2 diabetes and respiratory disease, Diabetes Res Clin Pract source

      Not checked in the free run.

    • cites [39] Dhital, 2012, A retrospective study comparing neutral protamine hagedorn insulin with glargine as basal therapy in prednisone-associated diabetes mellitus in hospitalized patients, Endocr Pract source

      Not checked in the free run.

    • cites [35] Radhakutty, 2017, Treatment of prednisolone-induced hyperglycaemia in hospitalized patients: Insights from a randomized, controlled study, Diabetes Obes Metab source

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    No screened or included study addressed whether anticipatory or compensatory adjustments are better for glycaemic control, and the reviewed studies do not clarify whether one should initiate anticipatory or compensatory insulin treatment.

    “No screened or included study addressed this issue.”
    • Also stated in: § Discussion · plain
      “Finally, the reviewed studies do not clarify whether one should initiate anticipatory or compensatory insulin treatment.”
    Quote in the paperSubstantial claim

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

    Findingcitation

    No data were provided on subgroups without diabetes mellitus or with type 1 diabetes mellitus and on daily insulin doses in the Lakhani et al study.

    “No data were provided on subgroups without DM or with type 1 DM and on daily insulin doses.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Lakhani, 2017, Comparison of Two Protocols in the Management of Glucocorticoid-induced Hyperglycemia among Hospitalized Patients, Indian J Endocrinol Metab source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Findingreasoning

    The lack of studies reporting high-quality evidence makes it difficult to provide formal and final recommendations.

    “The lack of studies reporting high-quality evidence makes it difficult to provide formal and final recommendations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    There is heterogeneity of experimental designs and a lack of well-powered, high-quality studies.

    “In fact, this review draws attention to the heterogeneity of the experimental designs and the lack of well-powered, high-quality studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Lack of comparability between studied populations and interventions and low to moderate quality of evidence does not permit full quantitative analysis and provision of formal recommendations on specific insulin regimens.

    “Lack of comparability between studied populations and interventions and low to moderate quality of evidence does not permit full quantitative analysis and provision of formal recommendations on specific insulin regimens.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    BBI strategy for patients under systemic glucocorticoid therapy provided insufficient glucose control, depending on time of day (most notably in the afternoon and evening).

    “provided insufficient glucose control, depending on time of day.”
    • Also stated in: § BBI strategy in persons under systemic glucocorticoid therapy · plain
      “Thus, BBI treatment provided insufficient glucose control, most notably in the afternoon and evening.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Steroids increase basal endogenous glucose production and lower insulin sensitivity.

    “due to their effect of increasing basal endogenous glucose production and lowering insulin sensitivity.7–9”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [7] source

      Not checked in the free run.

    • cites [8] source

      Not checked in the free run.

    • cites [9] source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Steroids enhance the likelihood of complications, length of stay and mortality in patients with pre-existing DM.

    “and enhance the likelihood of complications, length of stay and mortality in these patients.3 13–18”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites 3 13–18

      Not checked in the free run.

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

    Study design and conductnone given

    Disagreements between reviewers were resolved by consensus.

    “Disagreements between reviewers 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 conductcitation

    The overall quality of evidence was assessed using the GRADE criteria.

    “The overall quality of evidence was assessed using the GRADE criteria.32”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] source

      Not checked in the free run.

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

    Study design and conductnone given

    MT and SRK independently performed a full-text review of all eligible papers for inclusion, considering the PICOS criteria.

    “MT and SRK independently performed a full-text review of all eligible papers for inclusion, considering the PICOS criteria.”
    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 conductcitation

    The review methods and eligibility criteria were specified in advance, documented in a study protocol, registered online with PROSPERO, and recorded with a PRISMA statement.

    “The review methods and eligibility criteria were specified in advance, documented in a study protocol, registered online with the International Prospective Register of Systematic Reviews, 31 May 2016, and recorded with a Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.28”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [28] source

      Not checked in the free run.

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

    Study design and conductown data

    MT and SKR independently screened a sample of 100 papers by studying titles and abstracts according to selection criteria.

    “MT and SKR independently screened a sample of 100 papers by studying the titles and abstracts according to the selection criteria ‘adult persons with pre-existing DM who received a glucocorticoid therapy’.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    We applied the key criteria of the GRADE guidelines for observational studies to assess the methodological quality of nonrandomised studies.

    “applied the key criteria of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines for observational studies to assess the methodological quality of nonrandomised studies.31”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] 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

    MT performed the screening of all papers and SKR independently double screened a random sample of 10% of all articles.

    “MT performed the screening of all papers and SKR independently double screened a random sample of 10% of all articles.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    We used the Cochrane risk of bias tool to evaluate the risk of bias in RCTs.

    “We used the Cochrane risk of bias tool30 to evaluate the risk of bias in RCTs”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [30] Higgins JP , Altman D . Assessing the risk of bias in included studies. In: Higgins JPT , Green S , eds. Cochrane Handbook for Systematic Reviews of Interventions Version 510 [updated March 2011]: The Cochrane Collaboration 2011 33–49.

      Not checked in the free run.

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

    Premisecitation

    The Canadian Diabetes Association guideline recommends that glycemic monitoring for 48 hours after initiation of steroids may be considered.

    “The Canadian Diabetes Association guideline45 recommends that ‘glycemic monitoring for 48 hours after initiation of steroids may be considered’.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [45] Malcolm, 2018, In-Hospital Management of Diabetes, Can J Diabetes source

      Not checked in the free run.

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

    Premisecitation

    The Joint British Diabetes Societies for inpatient care guideline and the Imperial College Clinical Guidance recommend up-titration of oral hypoglycaemic agents first, and adding or switching to insulin if blood glucose level remains above 10 mmol/L.

    “In contrast, the Joint British Diabetes Societies for inpatient care guideline,19 and the Imperial College Clinical Guidance58 recommend the up-titration of OHA first. They recommend adding19 or switching58 to insulin if BGL remains above 10 mmol/L.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Roberts, 2018, Management of hyperglycaemia and steroid (glucocorticoid) therapy: a guideline from the Joint British Diabetes Societies (JBDS) for Inpatient Care group, Diabet Med source

      Not checked in the free run.

    • cites [58] Jairam C , Oliver N . Steroid Therapy and Management of Hyperglycaemia. Imperial College Clinical Guidance NHS Trust 2010 http://www.imperialendo.co.uk/Steroids.

      Not checked in the free run.

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

    Study design and conductreasoning

    An overall risk of bias of an outcome for all five randomised controlled trials is not so informative because the treatment interventions were not comparable.

    “Notably, an overall risk of bias of an outcome for all five RCTs is not so informative because the treatment interventions were not comparable.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    Unblinding may have affected the attention of staff, and this might be the most relevant risk for bias in these studies.

    “Although placebo effects are very unlikely, unblinding may have affected the attention of staff. This might be the most relevant risk for bias in these studies.”
    Quote in the paperNot a substantial claim

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

    Interpretationreasoning

    Such a protocol may not be flexible enough because it does not give sufficient consideration to the night-time fasting period and the associated risk of nocturnal hypoglycaemia.

    “Such a protocol may not be flexible enough in that it does not give sufficient consideration to the night-time fasting period and the associated risk of nocturnal hypoglycaemia.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Basal-bolus insulin is widely accepted and recommended as intensive insulin therapy in diabetes mellitus.

    “BBI is widely accepted and recommended as intensive insulin therapy in DM.42 51 52”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [42] source

      Not checked in the free run.

    • cites [51] source

      Not checked in the free run.

    • cites [52] source

      Not checked in the free run.

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

    Study design and conductnone given

    The lack of random sequence generation and allocation concealment might be another common bias.

    “The lack of random sequence generation and allocation concealment might be another common bias.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The American Endocrine Society Clinical Practice Guidelines recommends an anticipatory approach with discontinuation of oral hypoglycaemic agents at the time of hospital admission and initiation of insulin with persistent hyperglycaemia.

    “The American Endocrine Society Clinical Practice Guidelines41 recommends an anticipatory approach with discontinuation of OHA at the time of hospital admission and initiation of insulin with persistent hyperglycaemia.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [41] source

      Not checked in the free run.

42 of 42

  • The paper relies on this without support.

    BBI regimen is widely recommended as intensive insulin therapy for patients with DM on glucocorticoids.

    “Even findings on the widely recommended BBI regimen as intensive insulin therapy for patients with DM on glucocorticoids are inconclusive.”

  • The paper relies on this without support.

    Glucocorticoid therapy causes or exacerbates hyperglycaemia in patients with pre-existing type 2 diabetes mellitus.

    “Glucocorticoid treatment inevitably leads to hyperglycaemia in persons with type 2 DM.”
    “Glucocorticoid therapy exacerbates hyperglycaemia in patients with pre-existing DM.”
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.

  • Gerards glucose values are not higher than those in every other study

    Minor

    The claim includes both Gerards groups, but Table 2 reports a mean daily BGL of 16.7 mmol/L for Gosmanov's experimental group, higher than either Gerards value.

  • Ruiz de Adana study year differs from its reference

    Minor

    Table 1 dates the Ruiz de Adana study to 2016, while reference 36 lists its publication year as 2015.

  • Lakhani study year differs from its reference

    Minor

    Table 1 dates the Lakhani study to 2018, while reference 33 lists its publication year as 2017.

  • Burt measurement time differs between text and table

    Minor

    The text identifies 07:00 as a time when BGL was not significantly higher; Table 2 identifies 06:00 instead.

4 of 4

Cites

Flagged first, then by citations

7 of the 62 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. 10.1210/jc.2011-2098 · DOI · Paper page

Cited by

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Related

Authors
Tatalovic, M., Lehmann, R., Cheetham, M., Nowak, A., Battegay, E., & Rampini, S. K.
Affiliations
  • University Hospital Zurich (CH)
  • University of Zurich (CH)
Corresponding author
Rampini, Silvana K
ORCID
Venue
BMJ Open
Publisher
BMJ
Published
2019-05
Volume
9
Issue
5
Pages
e028914
ISSN
2044-6055 (ISSN-L)
DOI
10.1136/bmjopen-2019-028914
PMC
PMC6549610
OpenAlex
W2954309501
Semantic Scholar
374ae0afa680c6813cdb6586084cce4ce34e6d6a
Cited by
27
References
62
Citations by year
2026: 2 · 2025: 3 · 2024: 5 · 2023: 2 · 2022: 6 · 2021: 7 · 2020: 2
FWCI
0.58
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • BMJ Open (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by-nc)
  • HighWire Press Open Archive (submittedVersion)
  • Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by-nc)
  • Zurich Open Repository and Archive (University of Zurich)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hyperglycemia and glycemic control in critically ill and hospitalized patients
Keywords
hyperglycemia, type 2 diabetes, glucocorticoid therapy, glycemic control, multiple daily insulin injections, long-acting insulin, intermediate-acting insulin, sliding scale insulin, insulin management
MeSH terms
Aged, Blood Glucose, Diabetes Mellitus, Type 2, Female, Glucocorticoids, Humans, Hyperglycemia, Hypoglycemic Agents, Male, Middle Aged, Randomized Controlled Trials as Topic, Insulin, Long-Acting

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 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.

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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