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Cited by 113Diabetes Treatment and ManagementDiabetes Management and ResearchDiabetes, Cardiovascular Risks, and Lipoproteins

Targets for Glycemic Control

Open access
Imran, S. Ali, Agarwal, Gina, Bajaj, Harpreet S., Ross, Stuart·2018·Canadian Journal of Diabetes
DOI 10.1016/j.jcjd.2017.10.030
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Crossref · 10.1016/j.jcjd.2017.10.030

Cites

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Statistics

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Claims the paper makes

43 of 78 cited sources checked · 16 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    The ACCORD glycemic control portion was prematurely terminated after 3.5 years due to higher mortality (1.41% vs. 1.14% per year, HR 1.22) associated with assignment to the intensive-treatment arm.

    “The glycemic control portion of the trial was prematurely terminated after 3.5 years due to higher mortality (1.41% vs. 1.14% per year, HR 1.22) associated with assignment to the intensive-treatment arm (19,20).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [19] 19. Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Inter- ventions and Complications (EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular outcomes in type 1 diabetes: The DCCT/EDIC study 30-year follow-up. Diabetes Care 2016;39:686-93. source

      The Abstract and Results describe the DCCT/EDIC study in type 1 diabetes, not the ACCORD trial. Searches for ACCORD and the claimed mortality rates, hazard ratio, and early termination found no passage in our copy addressing those ACCORD claims. (LLM, conf=0.75)

      Experimental — accuracy not yet measured
    • cites [20] 20. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-59. source
  • Premisecitation

    In the ACCORD trial, intensive therapy targeting an A1C <6.0% did not significantly reduce the primary composite major CV outcomes compared with standard therapy targeting an A1C of 7.0% to 7.9% (HR 0.90, p=0.16).

    “The primary composite major CV outcomes (nonfatal MI, nonfatal stroke or death from CV causes) were not reduced significantly in ACCORD (hazard ratio [HR] 0.90, p=0.16).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [20] 20. Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008;358:2545-59. source
    • cites [21] 21. The ACCORD Study Group and ACCORD Eye Study Group. Effects of medical thera- pies on retinopathy progression in type 2 diabetes. New Engl J Med 2010;363:233-44. source

      Methods > The ACCORD Study (page not provided) gives the A1C targets and defines the primary cardiovascular composite as nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The cited paper does not report the claimed nonsignificant result, HR 0.90, or p=0.16 for that outcome; its reported treatment results concern retinopathy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • Premisecitation

    A major challenge in using evidence-based observations to determine the value of tighter PPG control has been the lack of well-designed, long-term outcome studies where assessing PPG values is the major objective.

    “However, a major challenge in attempting to use evidencebased observations to determine the value of tighter PPG control has been the lack of well-designed, long-term outcome studies where assessing PPG values is the major objective of the study.”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [49] 49. Esposito K, Giugliano D, Nappo F, et al. Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus. Circulation 2004;110:214-19. source
    • cites [50] 50. Raz I, Wilson PW, Strojek K, et al. Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: The HEART2D trial. Diabetes Care 2009;32:381-6. source
  • Premisecitation

    In the VADT, during an observational median follow-up of 9.8 years, the intensive-therapy group had a significantly lower risk of the primary outcome (HR 0.83, p=0.04), with an absolute reduction in risk of 8.6 major CV events per 1,000 person-years.

    “However, during an observational median follow up of 9.8 years, the intensive-therapy group had a significantly lower risk of the primary outcome (MI, stroke, new or worsening congestive heart failure [CHF], amputation for ischemic gangrene, or CV-related death) than did the standard therapy group (HR 0.83, p=0.04), with an absolute reduction in risk of 8.6 major CV events per 1,000 personyears (”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [27] 27. Hayward RA, Reaven PD, Wiitala WL, et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. New Engl J Med 2015;372:2197- 206. source
  • Premisecitation

    The frequency of severe hypoglycemia in the intensive therapy groups of the ACCORD, ADVANCE and VADT trials was 2 to 3 times higher than in standard therapy groups.

    “the frequency of severe hypoglycemia in these trials was 2 to 3 times higher in the intensive therapy groups”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [30] 30. Bonds DE, Miller ME, Bergenstal RM, et al. The association between symptom- atic, severe hypoglycaemia and mortality in type 2 diabetes: Retrospective epi- demiological analysis of the ACCORD study. BMJ 2010;340:b4909. source

      The Results report severe hypoglycaemia in about three times as many ACCORD participants in the intensive arm as in the standard arm. This paper does not report corresponding rates for ADVANCE or VADT, so it does not establish the claimed range across all three trials. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [31] 31. Zoungas S, Patel A, Chalmers J, et al. Severe hypoglycemia and risks of vascu- lar events and death. N Engl J Med 2010;363:1410-18. source

      Rates of Hypoglycemia over Time (p. 4) reports severe hypoglycemia in 2.7% of ADVANCE’s intensive group versus 1.5% of its standard group—about 1.8 times as frequent. The Discussion (p. 7) also describes a higher rate with intensive treatment in ACCORD, but our copy does not establish a two- to threefold difference across ACCORD, ADVANCE, and VADT. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [25] 25. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular compli- cations in veterans with type 2 diabetes. N Engl J Med 2009;360:129-39. source

      The Discussion says hypoglycemia rates were higher with intensive therapy in ACCORD, ADVANCE, and VADT, but gives no two- to threefold comparison for ACCORD or ADVANCE. Table 2 reports threefold rates for VADT episodes involving impaired consciousness or complete loss of consciousness (9 versus 3 and 3 versus 1 per 100 patient-years). Page numbers are unavailable in our copy. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • May combine two claims. 23
  • Classified as probably not a substantial claim. 6

  • May combine two claims.

    Premisecitation

    Both fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) are directly correlated to the risk of complications, with some evidence that PPG might be a stronger independent risk factor for CV complications.

    “Similarly, both fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) are directly correlated to the risk of complications, with some evidence that PPG might constitute a stronger independent risk factor for CV complications (4)(5)(6)(7)(8)(9)(10).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [4] 4. Service FJ, O'Brien PC. The relation of glycaemia to the risk of development and progression of retinopathy in the diabetic control and complications trial. Diabetologia 2001;44:1215-20. source

      The Results and Discussion report that preprandial, before-breakfast, and postprandial glucose measures were associated with risk of retinopathy progression. They do not assess cardiovascular complications or show that postprandial glucose is a stronger independent risk factor; the Discussion instead identifies mean blood glucose as the primary determinant of retinopathy risk. Page numbers are unavailable in our copy. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [5] 5. Coutinho M, Gerstein HC, Wang Y, et al. The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. Diabetes Care 1999;22:233-40. source
    • cites [6] 6. Levitan EB, Song Y, Ford ES, et al. Is nondiabetic hyperglycemia a risk factor for cardiovascular disease? A meta-analysis of prospective studies. Arch Intern Med 2004;164:2147-55. source

  • May combine two claims.

    Premisecitation

    In the DCCT cohort, there was a significant reduction in CV outcomes (42%), nonfatal myocardial infarct (MI), stroke and CV death (57%), as well as all-cause mortality (33%) in previously intensively treated participants compared with those who were previously in the standard arm.

    “In the DCCT cohort, there was a significant reduction in CV outcomes (42%), nonfatal myocardial infarct (MI), stroke and CV death (57%), as well as all-cause mortality (33%) in previously intensively treated participants compared with those who were previously in the standard arm (17)(18)(19).”
    Quote in the paperSubstantial claim3 of 3 sources checked
    • cites [17] 17. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and car- diovascular disease in patients with type 1 diabetes. N Engl J Med 2005;353:2643- 53. source

      Split into 2 atoms — 1 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 1 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [18] 18. Writing Group for the DCCT/EDIC Research Group, Orchard TJ, Nathan DM, et al. Association between 7 years of intensive treatment of type 1 diabetes and long- term mortality. JAMA 2015;313:45-53. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [19] 19. Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Inter- ventions and Complications (EDIC) Study Research Group. Intensive diabetes treatment and cardiovascular outcomes in type 1 diabetes: The DCCT/EDIC study 30-year follow-up. Diabetes Care 2016;39:686-93. source

      The Conclusions (page unavailable) mention 42% fewer CVD outcomes and 57% fewer major cardiovascular events, but identify those figures as earlier follow-up results. For the paper’s 30-year follow-up, the Results report reductions of 30% and 32%, respectively; the 32% reduction was not statistically significant (P = 0.07). The passages found do not report a 33% reduction in all-cause mortality. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Subsequent observational data from long-term follow-up after termination of randomization periods of both the DCCT and UKPDS cohorts showed a persistence of significant microvascular benefits and also demonstrated an emergence of beneficial effect on CV outcomes attributed to intensive glycemic control (metabolic memory or legacy effect).

    “Subsequent observational data from long-term follow up after termination of randomization periods of both the DCCT and UKPDS cohorts showed a persistence of significant microvascular benefits and also demonstrated an emergence of beneficial effect on CV outcomes attributed to intensive glycemic control.This has been termed as”
    Quote in the paperSubstantial claim2 of 3 sources checked
    • cites [14] 14. Writing Team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. Effect of inten- sive therapy on the microvascular complications of type 1 diabetes mellitus. JAMA 2002;287:2563-9. 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 [15] 15. Martin CL, Albers J, Herman WH, et al. Neuropathy among the diabetes control and complications trial cohort 8 years after trial completion. Diabetes Care 2006;29:340-4. 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 [16] 16. Holman RR, Paul SK, Bethel MA, et al. 10-Year Follow-up of intensive glucose control in type 2 diabetes. New Engl J Med 2008;359:1577-89. source

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

    Interpretationcitation

    If an A1C target ≤7.0% cannot be achieved with a FPG target of 4.0-7.0 mmol/L and PPG target of 5.0-10.0 mmol/L, further FPG lowering to 4.0 to 5.5 mmol/L and/or PPG lowering to 5.0-8.0 mmol/L may be considered, but must be balanced against the risk of hypoglycemia.

    “If an A1C target ≤7.0%cannot be achieved with a FPG target of 4.0-7.0mmol/L and PPG target of 5.0-10.0mmol/L, further FPG lowering to 4.0 to 5.5 mmol/L and/or PPG lowering to 5.0-8.0 mmol/L may be considered, but must be balanced against the risk of hypoglycemia [Grade D, Level 4 (38) for FPG target for type 2 diabetes; Grade D, Consensus for FPG target for type 1 diabetes; Grade D, Level 4 (38,40”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [38] 38. Woerle HJ, Neumann C, Zschau S, et al. Impact of fasting and postprandial gly- cemia on overall glycemic control in type 2 diabetes Importance of postpran- dial glycemia to achieve target HbA1c levels. Diabetes Res Clin Pract 2007;77:280-5. source
    • cites [40] 40. Monnier L, Colette C, Dunseath GJ, et al. The loss of postprandial glycemic control precedes stepwise deterioration of fasting with worsening diabetes. Diabetes Care 2007;30:263-9. 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

  • May combine two claims.

    Premisecitation

    In the ADVANCE trial, intensive glucose control aimed at reducing A1C ≤6.5% significantly reduced the incidence of major microvascular events, mainly through a 21% relative reduction in nephropathy, but had no beneficial effect on major CV events or all-cause mortality during the trial or subsequent median 5.4-year follow-up.

    “There was significant reduction in the incidence of major microvascular events in the intensive control group, mainly through a 21% relative reduction in nephropathy (23); however, no beneficial effect of intensive glucose lowering was found on major CV events or allcause mortality either during the trial or the subsequent median observational follow up of 5.4 years (24).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [23] 23. ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560-72. source

      Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites [24] 24. Zoungas S, Chalmers J, Neal B, et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. New Engl J Med 2014;371:1392-406. source

  • May combine two claims.

    Premisecitation

    Nontraditional glycemic targets, such as fructosamine and glycated albumin, have been associated with CV outcomes and mortality in a cohort study, but their broader utility and correlation with A1C have not yet been established.

    “Although, nontraditional glycemic targets, such as fructosamine and glycated albumin, have also been associated with CV outcomes and mortality in a cohort study (51), the broader utility of such targets and their correlation with A1C has not yet been established.”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [51] 51. Selvin E, Rawlings AM, Lutsey PL, et al. Fructosamine and glycated albumin and the risk of cardiovascular outcomes and death. Circulation 2015;132:269- 77. source

  • May combine two claims.

    Premisecitation

    In the VADT, during a median follow-up of 5.6 years, there was a nonsignificant reduction in the primary outcome, but progression to albuminuria was significantly reduced in the intensive-treatment participants (9.1% vs. 13.8%).

    “During a median follow up of 5.6 years, there was a nonsignificant reduction in the primary outcome (first occurrence of a major CV event), but the progression to albuminuria was significantly reduced in the intensive-treatment participants, with 9.1% of participants having significantly reduced progression compared to 13.8% in the standard therapy group.”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites [25] 25. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular compli- cations in veterans with type 2 diabetes. N Engl J Med 2009;360:129-39. source
    • cites [26] 26. Moritz T, Duckworth W, Abraira C. Veterans Affairs diabetes trial-corrections. N Engl J Med 2009;361:1024-5. source

  • May combine two claims.

    Premisecitation

    In the 21-year follow-up of the Steno-2 study, multifactorial interventions led to significant microvascular and CV benefits and mortality reduction.

    “Such multifactorial interventions have recently been suggested to lead to not only significant microvascular and CV benefits but also mortality reduction in the 21-year follow up of the Steno-2 study (34).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [34] 34. Gaede P, Oellgaard J, Carstensen B, et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia 2016;59:2298- 307. source

  • Classified as probably not a substantial claim.

    Interpretationcitation

    In people with type 2 diabetes, an A1C ≤6.5% may be targeted to reduce the risk of CKD and retinopathy, if they are assessed to be at low risk of hypoglycemia based on class of antihyperglycemic medication(s) utilized and the person's characteristics.

    “In people with type 2 diabetes, an A1C ≤6.5% may be targeted to reduce the risk of CKD [Grade A, Level 1A (23)] and retinopathy [Grade A, Level 1A (21)], if they are assessed to be at low risk of hypoglycemia based on class of antihyperglycemic medication(s) utilized and the person's characteristics [Grade D, Consensus].”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [23] 23. ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560-72. source
    • cites [21] 21. The ACCORD Study Group and ACCORD Eye Study Group. Effects of medical thera- pies on retinopathy progression in type 2 diabetes. New Engl J Med 2010;363:233-44. source

      The Results report less retinopathy progression with intensive glycemic therapy (7.3% versus 10.4%); the intensive group's median A1C at one year was 6.4%. However, the Methods specify a target below 6.0%, not ≤6.5%, so this study supports intensive control for retinopathy but does not directly test the cited threshold. CKD and the hypoglycemia-risk qualification have separate attributions in the citing sentence. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Several insulin treat-to-target trials have safely used dose titration protocols in individuals not at target A1C to reach lower than traditional FPG and PPG targets, including FPG levels of 4.5 to 5.5 mmol/L in type 2 diabetes, FPG levels of 4.0 to 5.5 mmol/L in type 2 diabetes, FPG levels of 3.9 to 5.0 mmol/L in type 1 diabetes, and protocols targeting both FPG 4.5-5.5 and 2-hour PG 5.0-7.0 in类型

    “In addition, several insulin treat-to-target trials have safely used dose titration protocols in individuals not at target A1C to reach lower than”
    Quote in the paperSubstantial claim4 of 7 sources checked
    • cites [41] 41. Bolli GB, Riddle MC, Bergenstal RM, et al. New insulin glargine 300 U/ml com- pared with glargine 100 U/ml in insulin-naive people with type 2 diabetes on oral glucose-lowering drugs: A randomized controlled trial (EDITION 3). Dia- betes Obes Metab 2015;17:386-94. source

      Study Procedures (page not available) describes dose titration toward fasting self-monitored plasma glucose of 4.4–5.6 mmol/L in insulin-naïve people with type 2 diabetes, and Results > Hypoglycaemia reports that severe events were infrequent. The paper does not support the sentence’s other specified fasting ranges, a type 1 diabetes protocol, or a protocol targeting both fasting and 2-hour postprandial glucose. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [42] 42. Gerstein HC, Yale JF, Harris SB, et al. A randomized trial of adding insulin glargine vs. avoidance of insulin in people with type 2 diabetes on either no oral glucose- lowering agents or submaximal doses of metformin and/or sulphonylureas. The Canadian INSIGHT (Implementing New Strategies with Insulin Glargine for Hyperglycaemia Treatment) study. Diabet Med 2006;23:736-42. source
    • cites [43] 43. Yki-Järvinen H, Juurinen L, Alvarsson M, et al. Initiate insulin by aggressive titra- tion and education (INITIATE): A randomized study to compare initiation of insulin combination therapy in type 2 diabetic patients individually and in groups. Diabetes Care 2007;30:1364-9. source
    • cites [44] 44. Yki-Järvinen H, Kauppinen-Mäkelin R, Tiikkainen M, et al. Insulin glargine or NPH combined with metformin in type 2 diabetes: The LANMET study. Diabetologia 2006;49:442-51. source
    • cites [45] 45. Davies M, Storms F, Shutler S, et al. Improvement of glycemic control in sub- jects with poorly controlled type 2 diabetes: Comparison of two treatment algo- rithms using insulin glargine. Diabetes Care 2005;28:1282-8. 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 [46] 46. Riddle MC, Rosenstock J, Gerich J. The treat-to-target trial: Randomized addi- tion of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003;26:3080-6. source

      The trial summary (p. 1) and Study protocol and treatment (p. 2) support the use of insulin dose titration in people with type 2 diabetes above the A1C goal. Its FPG target was ≤5.5–5.6 mmol/L, not a stated range of 4.5–5.5 mmol/L; mean FPG at the end of the trial was 6.5–6.7 mmol/L. This paper does not establish the other type 1 diabetes or combined FPG/2-hour PG targets listed in the claim. (LLM, conf=0.86)

      Experimental — accuracy not yet measured
    • cites [47] 47. Heller S, Buse J, Fisher M, et al. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): A phase 3, randomised, open- label, treat-to-target non-inferiority trial. Lancet 2012;379:1489-97. source

  • May combine two claims.

    Interpretationcitation

    In most people with type 1 or type 2 diabetes, an A1C ≤7.0% should be targeted to reduce the risk of microvascular complications and, if implemented early in the course of disease, CV complications.

    “In most people with type 1 or type 2 diabetes, an A1C ≤7.0% should be targeted to reduce the risk of microvascular [Grade A, Level 1A (1,2,22,23)] and, if implemented early in the course of disease, CV complications [Grade B, Level 3 (23)].”
    Quote in the paperSubstantial claim2 of 4 sources checked
    • cites [1] 1. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53. source
    • cites [2] 2. The Diabetes Control and Complications Trial Research Group. The relation- ship of glycemic exposure (HbA1c) to the risk of development and progres- sion of retinopathy in the diabetes control and complications trial. Diabetes 1995;44:968-83. source
    • cites [22] 22. Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Eye Study Group and the Action to Control Cardiovascular Risk in Diabetes Follow-On (ACCORDION) Study Group. Persistent effects of intensive glycemic control on retinopathy in type 2 diabetes in the Action to Control Cardiovas- cular Risk in Diabetes (ACCORD) follow-on study. Diabetes Care 2016;39:1089- 100. source

      The Results and Conclusions report that intensive glycemic control reduced retinopathy progression in people with established type 2 diabetes, supporting the microvascular portion of the claim. The Methods specify an intensive A1C target below 6.0%, not a recommended target of ≤7.0% for most people with either type of diabetes. The paper does not report that early implementation reduces cardiovascular complications; its discussion of early treatment concerns the effect on the eyes. (LLM, conf=0.88)

      Experimental — accuracy not yet measured
    • cites [23] 23. ADVANCE Collaborative Group, Patel A, MacMahon S, et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008;358:2560-72. source

      The Results (p. 2) show that intensive glucose control reduced major microvascular events in patients with type 2 diabetes, primarily through fewer cases of nephropathy. The study did not include people with type 1 diabetes, and the Discussion (pp. 11–12) reports no significant reduction in major cardiovascular events. It does not establish a cardiovascular benefit from starting the target early in the disease course. (LLM, conf=0.89)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    The Steno-2 study results include increased survival for a median of 7.9 years; 8.1 years longer median time before first CV event; and reduction in all microvascular complications, except for peripheral neuropathy, for participants in the intensive-therapy group compared to the conventional therapy group.

    “The salient results of this study include: increased survival for a median of 7.9 years; 8.1 years longer median time before first CV event; and reduction in all microvascular complications, except for peripheral neuropathy, for participants in the intensive-therapy group compared to the conventional therapy group.”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [34] 34. Gaede P, Oellgaard J, Carstensen B, et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia 2016;59:2298- 307. source

  • May combine two claims.

    Premisecitation

    Most large outcome trials conducted so far have been mostly based on preprandial glucose and A1C targets, with limited evidence of a long-term benefit of targeting PPG alone.

    “Most of the large outcome trials conducted so far have been mostly based on preprandial glucose and A1C targets, with limited evidence of a long-term benefit of targeting PPG alone (49,50).”
    Quote in the paperSubstantial claim2 of 2 sources checked
    • cites [49] 49. Esposito K, Giugliano D, Nappo F, et al. Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus. Circulation 2004;110:214-19. source

      The Discussion says earlier intervention studies paid no attention to controlling postprandial hyperglycemia, and that this trial’s limited follow-up prevented evaluation of clinical events. That supports the point about limited long-term outcome evidence, but the paper does not establish that most large trials used preprandial glucose and A1C targets. (LLM, conf=0.85)

      Experimental — accuracy not yet measured
    • cites [50] 50. Raz I, Wilson PW, Strojek K, et al. Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: The HEART2D trial. Diabetes Care 2009;32:381-6. source

      The Conclusions (page not specified) call HEART2D the first study to examine whether reducing postprandial glucose affects cardiovascular outcomes and report no difference between prandial and basal strategies. They also discuss large trials using A1C goals, but do not establish that most large outcome trials used preprandial glucose targets. HEART2D targeted A1C in both arms, so it did not test targeting PPG alone. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    When A1C values are higher, the major contribution is the FPG levels, but as the A1C value approaches the target value of ≤7.0%, there is a greater contribution from PPG values.

    “When A1C values are higher, the major contribution is the FPG levels, but as the A1C value approaches the target value of ≤7.0%, there is a greater contribution from PPG values (37-39).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites [37] 37. Monnier L, Lapinski H, Colette C. Contributions of fasting and postprandial plasma glucose increments to the overall diurnal hyperglycemia of type 2 diabetic patients: Variations with increasing levels of HbA(1c). Diabetes Care 2003;26:881-5. source
    • cites [38] 38. Woerle HJ, Neumann C, Zschau S, et al. Impact of fasting and postprandial gly- cemia on overall glycemic control in type 2 diabetes Importance of postpran- dial glycemia to achieve target HbA1c levels. Diabetes Res Clin Pract 2007;77:280-5. source
    • cites [39] 39. Riddle M, Umpierrez G, DiGenio A, et al. Contributions of basal and postpran- dial hyperglycemia over a wide range of A1C levels before and after treatment intensification in type 2 diabetes. Diabetes Care 2011;34:2508-14. source

      The Results (page not available) show that basal hyperglycemia contributed more at higher A1C levels, while the postprandial contribution was relatively greater at lower levels after treatment intensification. But the baseline trend was not statistically significant, and the Conclusions caution that treatment type can matter more than A1C alone. The claim omits those qualifications and extends the pattern toward ≤7.0%, a range not represented at baseline. (LLM, conf=0.86)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Premisecitation

    Evidence supports the use of multifactorial risk-reduction strategies in addition to A1C control for CV prevention, including blood pressure (BP) and lipid targets; CV prevention medications; physical activity and other healthy behaviours; as well as smoking cessation.

    “Evidence also supports the use of multifactorial risk-reduction strategies in addition to A1C control for CV prevention, including blood pressure (BP) and lipid targets; CV prevention medications; physical activity and other healthy behaviours; as well as smoking cessation (see Cardiovascular Protection in People with Diabetes chapter, p. S162).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [34] 34. Gaede P, Oellgaard J, Carstensen B, et al. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia 2016;59:2298- 307. source

      Split into 2 atoms — 1 confirmed, 1 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

    The initial prospective randomized controlled trials (DCCT, Kumamoto, UKPDS) confirmed that improved glycemic control significantly reduced the risk of microvascular complications, but had no significant effect on CV outcomes.

    “These trials-the DCCT in type 1 diabetes (11), the Kumamoto trial (12) and the UKPDS (1,13) in type 2 diabetes-confirmed that improved glycemic control significantly reduced the risk of microvascular complications, but had no significant effect on CV outcomes.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [11] 11. The Diabetes Control and Complications Trial Research Group, Nathan DM, Genuth S, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes melli- tus. N Engl J Med 1993;329:977-86. source
    • cites [12] 12. Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: A randomized prospective 6-year study. Diabetes Res Clin Pract 1995;28:103-17. source
    • cites [1] 1. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53. source
    • cites [13] 13. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabe- tes Study (UKPDS) Group. Lancet 1998;352:854-65. source

  • May combine two claims.

    Premisecitation

    In the UKPDS cohort, there was a significant reduction in MI (15% to 33%) and all-cause mortality (13% to 27%) in participants who had been originally randomized to intensive treatment.

    “Similarly, there was a significant reduction in MI (15% to 33%) and all-cause mortality (13% to 27%) in the UKPDS cohort in participants who had been originally randomized to intensive treatment (16).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] 16. Holman RR, Paul SK, Bethel MA, et al. 10-Year Follow-up of intensive glucose control in type 2 diabetes. New Engl J Med 2008;359:1577-89. source

  • May combine two claims.

    Premisecitation

    The relationship between A1C and diabetes complications is curvilinear, with no apparent threshold of benefit, although the absolute reduction in risk is substantially less at lower A1C levels.

    “The initial data from the Diabetes Control and Complications Trial (DCCT; type 1 diabetes) (2) and the United Kingdom Prospective Diabetes Study (UKPDS; type 2 diabetes) (3) demonstrated a curvilinear relationship between A1C and diabetes complications, with no apparent threshold of benefit, although the absolute reduction in risk was substantially less at lower A1C levels.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [2] 2. The Diabetes Control and Complications Trial Research Group. The relation- ship of glycemic exposure (HbA1c) to the risk of development and progres- sion of retinopathy in the diabetes control and complications trial. Diabetes 1995;44:968-83. source
    • cites [3] 3. Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study. BMJ 2000;321:405-12. source

  • May combine two claims.

    Premisecitation

    Improved glycemic control reduces the risk of both microvascular and CV complications.

    “Evidence indicates that improved glycemic control reduces the risk of both microvascular and CV complications.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [11] 11. The Diabetes Control and Complications Trial Research Group, Nathan DM, Genuth S, et al. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes melli- tus. N Engl J Med 1993;329:977-86. source
    • cites [12] 12. Ohkubo Y, Kishikawa H, Araki E, et al. Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: A randomized prospective 6-year study. Diabetes Res Clin Pract 1995;28:103-17. source
    • cites [1] 1. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53. source
    • cites [13] 13. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabe- tes Study (UKPDS) Group. Lancet 1998;352:854-65. source

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    More intensive glucose control, A1C ≤6.5%, may be sought in people with a shorter duration of diabetes and longer life expectancy, especially in those people who are on treatment with antihyperglycemic agents with a low risk of hypoglycemia.

    “More intensive glucose control, A1C ≤6.5%, may be sought in people with a shorter duration of diabetes and longer life expectancy, especially in those people who are on treatment with antihyperglycemic agents with a low risk of hypoglycemia.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    An A1C target ≤8.5% may be more appropriate in people with type 1 and type 2 diabetes with limited life expectancy, higher level of functional dependency and a history of repeated severe hypoglycemia with hypoglycemia unawareness.

    “An A1C target ≤8.5% may be more appropriate in people with type 1 and type 2 diabetes with limited life expectancy, higher level of functional dependency and a history of repeated severe hypoglycemia with hypoglycemia unawareness.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Intensive glucose control with lowering A1C values to ≤7.0% in both type 1 and type 2 diabetes provides strong benefits for microvascular complications and, if achieved early in the disease with avoidance of hypoglycemia and glucose variability as part of a multifactorial treatment approach, likely provides a significant CV benefit.

    “Intensive glucose control with lowering A1C values to ≤7.0% in both type 1 and type 2 diabetes provides strong benefits for microvascular complications and, if achieved early in the disease with avoidance of hypoglycemia and glucose variability as part of a multifactorial treatment approach, likely provide a significant CV benefit.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    A meta-analysis suggests that people with type 2 diabetes who receive intensive glucose lowering therapy have a reduced risk of the composite major adverse CV events (MACE) and MI, with no significant effect on the risk of total mortality, cardiac death, stroke and CHF.

    “Data from a meta-analysis suggest that people with type 2 diabetes who receive intensive glucose lowering therapy have a reduced risk of the composite major adverse CV events (MACE) and MI, with no significant effect on the risk of total mortality, cardiac death, stroke and CHF (28).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] 28. Fang HJ, Zhou YH, Tian YJ, et al. Effects of intensive glucose lowering in treat- ment of type 2 diabetes mellitus on cardiovascular outcomes: A meta-analysis of data from 58,160 patients in 13 randomized controlled trials. Int J Cardiol 2016;218:50-8. source

  • May combine two claims.

    Interpretationcitation

    In order to achieve an A1C ≤7.0%, people with diabetes should aim for a FPG or preprandial PG target of 4.0 to 7.0 mmol/L and a 2-hour PPG target of 5.0-10.0 mmol/L.

    “In order to achieve an A1C ≤7.0%, people with diabetes should aim for: a. FPG or preprandial PG target of 4.0 to 7.0 mmol/L and a 2-hour PPG target of 5.0-10.0mmol/L [Grade B, Level 2 (2) for type 1; Grade B, Level 2 (1) for type 2 diabetes]”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [2] 2. The Diabetes Control and Complications Trial Research Group. The relation- ship of glycemic exposure (HbA1c) to the risk of development and progres- sion of retinopathy in the diabetes control and complications trial. Diabetes 1995;44:968-83. source
    • cites [1] 1. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837-53. source

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    Management strategies that would minimize glucose variability and their impact on hard clinical outcomes remain to be determined before novel measurement targets of glucose quality can systematically be incorporated into clinical practice guidelines.

    “However, management strategies that would minimize glucose variability and their impact on hard clinical outcomes remain to be determined before these novel measurement targets of glucose quality can systematically be incorporated into clinical practice guidelines.”
    Quote in the paperSubstantial claim

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

    Interpretationreasoning

    Higher glycemic targets are appropriate for functionally dependent adults of any age or individuals with limited life expectancy and little likelihood of benefit from intensive therapy.

    “Higher glycemic targets are also appropriate for functionally dependent adults of any age or individuals with limited life expectancy and little likelihood of benefit from intensive therapy.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisenone given

    Table 1 shows the correlation between A1C and estimated mean glucose values: A1C 5.5-6.5% corresponds to estimated mean glucose 6.2-7.7 mmol/L; A1C 6.5-6.9% to 7.8-8.5 mmol/L; A1C 7.0-7.4% to 8.6-9.3 mmol/L; A1C 7.5-7.9% to 9.4-10.1 mmol/L; A1C 8.0-8.5% to 10.2-10.9 mmol/L.

    “Correlation between A1C and estimated mean glucose values A1C values (%) 5.5-6.5 6.5-6.9 7.0-7.47.5-7.98.0-8.5 Estimated mean glucose (mmol/L) 6.2-7.7 7.8-8.5 8.6-9.3 9.4-10.1 10.2-10.9”
    Quote in the paperNot a substantial claim
27 of 27

  • The paper relies on this without support.

    Optimal glycemic control is fundamental to the management of diabetes.

    “Optimal glycemic control is fundamental to the management of diabetes.”
1 of 1

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Authors
Imran, S. A., Agarwal, G., Bajaj, H. S., & Ross, S.
ORCID
Venue
Canadian Journal of Diabetes
Publisher
Elsevier BV
Published
2018-04
Volume
42
Pages
S42-S46
ISSN
1499-2671 (ISSN-L)
DOI
10.1016/j.jcjd.2017.10.030
OpenAlex
W4236265835
Cited by
113
References
54
Citations by year
2026: 9 · 2025: 17 · 2024: 17 · 2023: 15 · 2022: 15 · 2021: 16 · 2020: 15 · 2019: 7 · 2018: 2
FWCI
8.01
Type
journal article
Language
en
Open access
Licence
Locations
Canadian Journal of Diabetes (publishedVersion)
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 › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
glycemic control, HbA1c, HbA1c targets, diabetes complications, microvascular complications, cardiovascular complications, type 1 diabetes, type 2 diabetes, Diabetes Control and Complications Trial, UKPDS

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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 2026-10-11.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-11.

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