Clinical Targets for Continuous Glucose Monitoring Data Interpretation: Recommendations From the International Consensus on Time in Range

Tadej Battelino, Thomas Danne, Richard M Bergenstal, Stephanie A Amiel, Roy Beck, Torben Biester, Emanuele Bosi, Bruce A Buckingham, William T Cefalu, Kelly L Close, Claudio Cobelli, Eyal Dassau, J Hans DeVries, Kim C Donaghue, Klemen Dovc, Francis J Doyle 3rd, Satish Garg, George Grunberger, Simon Heller, Lutz Heinemann, Irl B Hirsch, Roman Hovorka, Weiping Jia, Olga Kordonouri, Boris Kovatchev, Aaron Kowalski, Lori Laffel, Brian Levine, Alexander Mayorov, Chantal Mathieu, Helen R Murphy, Revital Nimri, Kirsten Nørgaard, Christopher G Parkin, Eric Renard, David Rodbard, Banshi Saboo, Desmond Schatz, Keaton Stoner, Tatsuiko Urakami, Stuart A Weinzimer, Moshe Phillip, Tadej Battelino, Thomas Danne, Richard M Bergenstal, Stephanie A Amiel, Roy Beck, Torben Biester, Emanuele Bosi, Bruce A Buckingham, William T Cefalu, Kelly L Close, Claudio Cobelli, Eyal Dassau, J Hans DeVries, Kim C Donaghue, Klemen Dovc, Francis J Doyle 3rd, Satish Garg, George Grunberger, Simon Heller, Lutz Heinemann, Irl B Hirsch, Roman Hovorka, Weiping Jia, Olga Kordonouri, Boris Kovatchev, Aaron Kowalski, Lori Laffel, Brian Levine, Alexander Mayorov, Chantal Mathieu, Helen R Murphy, Revital Nimri, Kirsten Nørgaard, Christopher G Parkin, Eric Renard, David Rodbard, Banshi Saboo, Desmond Schatz, Keaton Stoner, Tatsuiko Urakami, Stuart A Weinzimer, Moshe Phillip

Abstract

Improvements in sensor accuracy, greater convenience and ease of use, and expanding reimbursement have led to growing adoption of continuous glucose monitoring (CGM). However, successful utilization of CGM technology in routine clinical practice remains relatively low. This may be due in part to the lack of clear and agreed-upon glycemic targets that both diabetes teams and people with diabetes can work toward. Although unified recommendations for use of key CGM metrics have been established in three separate peer-reviewed articles, formal adoption by diabetes professional organizations and guidance in the practical application of these metrics in clinical practice have been lacking. In February 2019, the Advanced Technologies & Treatments for Diabetes (ATTD) Congress convened an international panel of physicians, researchers, and individuals with diabetes who are expert in CGM technologies to address this issue. This article summarizes the ATTD consensus recommendations for relevant aspects of CGM data utilization and reporting among the various diabetes populations.

© 2019 by the American Diabetes Association.

Figures

Figure 1
Figure 1
CGM-based targets for different diabetes populations.
Figure 2
Figure 2
Ambulatory Glucose Profile.

References

    1. Lind M, Polonsky W, Hirsch IB, et al. . Continuous glucose monitoring vs conventional therapy for glycemic control in adults with type 1 diabetes treated with multiple daily insulin injections: the GOLD randomized clinical trial. JAMA 2017;317:379–387
    1. Aleppo G, Ruedy KJ, Riddlesworth TD, et al. .; REPLACE-BG Study Group . REPLACE-BG: A randomized trial comparing continuous glucose monitoring with and without routine blood glucose monitoring in adults with well-controlled type 1 diabetes. Diabetes Care 2017;40:538–545
    1. Beck RW, Riddlesworth T, Ruedy K, et al. .; DIAMOND Study Group . Effect of continuous glucose monitoring on glycemic control in adults with type 1 diabetes using insulin injections: The DIAMOND randomized clinical trial. JAMA 2017;317:371–378
    1. Beck RW, Riddlesworth TD, Ruedy K, et al. .; DIAMOND Study Group . Continuous glucose monitoring versus usual care in patients with type 2 diabetes receiving multiple daily insulin injections: a randomized trial. Ann Intern Med 2017;167:365–374
    1. Polonsky WH, Hessler D, Ruedy KJ, Beck RW; DIAMOND Study Group . The impact of continuous glucose monitoring on markers of quality of life in adults with type 1 diabetes: further findings from the DIAMOND randomized clinical trial. Diabetes Care 2017;40:736–741
    1. Šoupal J, Petruželková L, Flekač M, et al. . Comparison of different treatment modalities for type 1 diabetes, including sensor-augmented insulin regimens, in 52 weeks of follow-up: a COMISAIR study. Diabetes Technol Ther 2016;18:532–538
    1. van Beers CA, DeVries JH, Kleijer SJ, et al. . Continuous glucose monitoring for patients with type 1 diabetes and impaired awareness of hypoglycaemia (IN CONTROL): a randomised, open-label, crossover trial. Lancet Diabetes Endocrinol 2016;4:893–902
    1. Bolinder J, Antuna R, Geelhoed-Duijvestijn P, Kröger J, Weitgasser R. Novel glucose-sensing technology and hypoglycaemia in type 1 diabetes: a multicentre, non-masked, randomised controlled trial. Lancet 2016;388:2254–2263
    1. Haak T, Hanaire H, Ajjan R, Hermanns N, Riveline JP, Rayman G. Flash glucose-sensing technology as a replacement for blood glucose monitoring for the management of insulin-treated type 2 diabetes: a multicenter, open-label randomized controlled trial. Diabetes Ther 2017;8:55–73
    1. Choudhary P, Olsen BS, Conget I, Welsh JB, Vorrink L, Shin JJ. Hypoglycemia prevention and user acceptance of an insulin pump system with predictive low glucose management. Diabetes Technol Ther 2016;18:288–291
    1. Bergenstal RM, Garg S, Weinzimer SA, et al. . Safety of a hybrid closed-loop insulin delivery system in patients with type 1 diabetes. JAMA 2016;316:1407–1408
    1. Heinemann L, Freckmann G, Erdmann D, et al. . Real-time continuous glucose monitoring use in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): a multicentre, randomised controlled trial. Lancet 2018;391:1367–1377
    1. Reddy M, Jugnee N, El Laboudi A, Spanudakis E, Anantharaja S, Oliver N. A randomised controlled pilot study of continuous glucose monitoring and flash glucose monitoring in people with type 1 diabetes and impaired awareness of hypoglycaemia. Diabet Med 2018;35:483–490
    1. Battelino T, Nimri R, Dovc K, Phillip M, Bratina N. Prevention of hypoglycemia with predictive low glucose insulin suspension in children with type 1 diabetes: a randomized controlled trial. Diabetes Care 2017;40:764–770
    1. Dovc K, Cargnelutti K, Sturm A, Selb J, Bratina N, Battelino T. Continuous glucose monitoring use and glucose variability in pre-school children with type 1 diabetes. Diabetes Res Clin Pract 2019;147:76–80
    1. American Diabetes Association 7. Diabetes technology: Standards of Medical Care in Diabetes—2019. Diabetes Care 2019;42(Suppl. 1):S71–S80
    1. Fonseca VA, Grunberger G, Anhalt H, et al. .; Consensus Conference Writing Committee . Continuous glucose monitoring: a consensus conference of the American Association of Clinical Endocrinologists and American College of Endocrinology. Endocr Pract 2016;22:1008–1021
    1. Danne T, Nimri R, Battelino T, et al. . International consensus on use of continuous glucose monitoring. Diabetes Care 2017;40:1631–1640
    1. Petrie JR, Peters AL, Bergenstal RM, Holl RW, Fleming GA, Heinemann L. Improving the clinical value and utility of CGM Systems: issues and recommendations: a joint statement of the European Association for the Study of Diabetes and the American Diabetes Association Diabetes Technology Working Group. Diabetes Care 2017;40:1614–1621
    1. Agiostratidou G, Anhalt H, Ball D, et al. . Standardizing clinically meaningful outcome measures beyond HbA1c for type 1 diabetes: a consensus report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange. Diabetes Care 2017;40:1622–1630
    1. Sherr JL, Tauschmann M, Battelino T, et al. . ISPAD Clinical Practice Consensus Guidelines 2018: diabetes technologies. Pediatr Diabetes 2018;19(Suppl. 27):302–325
    1. Foster NC, Beck RW, Miller KM, et al. . State of type 1 diabetes management and outcomes from the T1D Exchange in 2016–2018. Diabetes Technol Ther 2019;21:66–72
    1. Foster NC, Miller K, Dimeglio L, et al. . Marked increases in CGM use has not prevented increases in HbA1c levels in participants in the T1D Exchange (T1DX) clinic network (Abstract). Diabetes 2018;67(Suppl. 1):A451
    1. Bergenstal RM, Ahmann AJ, Bailey T, et al. . Recommendations for standardizing glucose reporting and analysis to optimize clinical decision making in diabetes: the Ambulatory Glucose Profile (AGP). Diabetes Technol Ther 2013;15:198–211
    1. American Diabetes Association Introduction: Standards of Medical Care in Diabetes—2017. Diabetes Care 2017;41(Suppl. 1):S1–S2
    1. Beck RW, Bergenstal RM, Cheng P, et al. . The relationships between time in range, hyperglycemia metrics, and HbA1c. J Diabetes Sci Technol. 13 January 2019. [Epub ahead of print]. DOI: 10.1177/1932296818822496
    1. Vigersky RA, McMahon C. The relationship of hemoglobin A1C to time-in-range in patients with diabetes. Diabetes Technol Ther 2019;21:81–85
    1. Brod M, Christensen T, Thomsen TL, Bushnell DM. The impact of non-severe hypoglycemic events on work productivity and diabetes management. Value Health 2011;14:665–671
    1. Brod M, Rana A, Barnett AH. Impact of self-treated hypoglycaemia in type 2 diabetes: a multinational survey in patients and physicians. Curr Med Res Opin 2012;28:1947–1958
    1. Seaquist ER, Anderson J, Childs B, et al. . Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 2013;36:1384–1395
    1. International Hypoglycaemia Study Group Glucose concentrations of less than 3.0 mmol/L (54 mg/dL) should be reported in clinical trials: a joint position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2017;40:155–157
    1. Novodvorsky P, Bernjak A, Chow E, et al. . Diurnal differences in risk of cardiac arrhythmias during spontaneous hypoglycemia in young people with type 1 diabetes. Diabetes Care 2017;40:655–662
    1. Battelino T, Conget I, Olsen B, et al. .; SWITCH Study Group . The use and efficacy of continuous glucose monitoring in type 1 diabetes treated with insulin pump therapy: a randomised controlled trial. Diabetologia 2012;55:3155–3162
    1. Bergenstal RM, Tamborlane WV, Ahmann A, et al. .; STAR 3 Study Group . Sensor-augmented pump therapy for A1C reduction (STAR 3) study: results from the 6-month continuation phase. Diabetes Care 2011;34:2403–2405
    1. Cox DJ, Kovatchev BP, Julian DM, et al. . Frequency of severe hypoglycemia in insulin-dependent diabetes mellitus can be predicted from self-monitoring blood glucose data. J Clin Endocrinol Metab 1994;79:1659–1662
    1. Qu Y, Jacober SJ, Zhang Q, Wolka LL, DeVries JH. Rate of hypoglycemia in insulin-treated patients with type 2 diabetes can be predicted from glycemic variability data. Diabetes Technol Ther 2012;14:1008–1012
    1. National Institute of Diabetes and Digestive and Kidney Diseases Health Information Center. Sickle cell trait & other hemoglobinopathies & diabetes (for providers) [Internet]. Available from . Accessed 12 January 2018
    1. Bry L, Chen PC, Sacks DB. Effects of hemoglobin variants and chemically modified derivatives on assays for glycohemoglobin. Clin Chem 2001;47:153–163
    1. Ford ES, Cowie CC, Li C, Handelsman Y, Bloomgarden ZT. Iron-deficiency anemia, non-iron-deficiency anemia and HbA1c among adults in the US. J Diabetes 2011;3:67–73
    1. Nielsen LR, Ekbom P, Damm P, et al. . HbA1c levels are significantly lower in early and late pregnancy. Diabetes Care 2004;27:1200–1201
    1. Beck RW, Connor CG, Mullen DM, Wesley DM, Bergenstal RM. The fallacy of average: how using HbA1c alone to assess glycemic control can be misleading. Diabetes Care 2017;40:994–999
    1. Xing D, Kollman C, Beck RW, et al. .; Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group . Optimal sampling intervals to assess long-term glycemic control using continuous glucose monitoring. Diabetes Technol Ther 2011;13:351–358
    1. Riddlesworth TD, Beck RW, Gal RL, et al. . Optimal sampling duration for continuous glucose monitoring to determine long-term glycemic control. Diabetes Technol Ther 2018;20:314–316
    1. American Diabetes Association 14. Management of diabetes in pregnancy. Standards of Medical Care in Diabetes—2019. Diabetes Care 2019;42(Suppl. 1):S165–S172
    1. Rama Chandran S, Tay WL, Lye WK, et al. . Beyond HbA1c: comparing glycemic variability and glycemic indices in predicting hypoglycemia in type 1 and type 2 diabetes. Diabetes Technol Ther 2018;20:353–362
    1. Famulla S, Pieber TR, Eilbracht J, et al. . Glucose exposure and variability with empagliflozin as adjunct to insulin in patients with type 1 diabetes: continuous glucose monitoring data from a 4-week, randomized, placebo-controlled trial (EASE-1). Diabetes Technol Ther 2017;19:49–60
    1. Dandona P, Mathieu C, Phillip M, et al. .; DEPICT-1 Investigators . Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: the DEPICT-1 52-week study. Diabetes Care 2018;41:2552–2559
    1. Mathieu C, Dandona P, Phillip M, et al. .; DEPICT-1 and DEPICT-2 Investigators . Glucose variables in type 1 diabetes studies with dapagliflozin: pooled analysis of continuous glucose monitoring data from DEPICT-1 and -2. Diabetes Care 2019;42:1081–1087
    1. Lu J, Ma X, Zhou J, et al. . Association of time in range, as assessed by continuous glucose monitoring, with diabetic retinopathy in type 2 diabetes. Diabetes Care 2018;41:2370–2376
    1. Beck RW, Bergenstal RM, Riddlesworth TD, et al. Validation of time in range as an outcome measure for diabetes clinical trials. Diabetes Care 2019;42:400–405
    1. Weinstock RS, DuBose SN, Bergenstal RM, et al. .; T1D Exchange Severe Hypoglycemia in Older Adults With Type 1 Diabetes Study Group . Risk factors associated with severe hypoglycemia in older adults with type 1 diabetes. Diabetes Care 2016;39:603–610
    1. Bremer JP, Jauch-Chara K, Hallschmid M, Schmid S, Schultes B. Hypoglycemia unawareness in older compared with middle-aged patients with type 2 diabetes. Diabetes Care 2009;32:1513–1517
    1. Punthakee Z, Miller ME, Launer LJ, et al. .; ACCORD Group of Investigators; ACCORD-MIND Investigators . Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial. Diabetes Care 2012;35:787–793
    1. Giorda CB, Ozzello A, Gentile S, et al. .; HYPOS-1 Study Group of AMD . Incidence and risk factors for severe and symptomatic hypoglycemia in type 1 diabetes. Results of the HYPOS-1 study. Acta Diabetol 2015;52:845–853
    1. Cariou B, Fontaine P, Eschwege E, et al. . Frequency and predictors of confirmed hypoglycaemia in type 1 and insulin-treated type 2 diabetes mellitus patients in a real-life setting: results from the DIALOG study. Diabetes Metab 2015;41:116–125
    1. Abdelhafiz AH, Rodríguez-Mañas L, Morley JE, Sinclair AJ. Hypoglycemia in older people – a less well recognized risk factor for frailty. Aging Dis 2015;6:156–167
    1. Beck RW, Bergenstal RM, Riddlesworth TD, Kollman C. The association of biochemical hypoglycemia with the subsequent risk of a severe hypoglycemic event: analysis of the DCCT data set. Diabetes Technol Ther 2019;21:1–5
    1. Murphy HR, Rayman G, Duffield K, et al. . Changes in the glycemic profiles of women with type 1 and type 2 diabetes during pregnancy. Diabetes Care 2007;30:2785–2791
    1. Feig DS, Donovan LE, Corcoy R, et al. .; CONCEPTT Collaborative Group . Continuous glucose monitoring in pregnant women with type 1 diabetes (CONCEPTT): a multicentre international randomised controlled trial. Lancet 2017;390:2347–2359
    1. Kristensen K, Ögge LE, Sengpiel V, et al. . Continuous glucose monitoring in pregnant women with type 1 diabetes: an observational cohort study of 186 pregnancies. Diabetologia. 23 March 2019. [Epub ahead of print]. DOI: 10.1007/s00125-019-4850-0
    1. Stewart ZA, Wilinska ME, Hartnell S, et al. . Closed-loop insulin delivery during pregnancy in women with type 1 diabetes. N Engl J Med 2016;375:644–654
    1. Stewart ZA, Wilinska ME, Hartnell S, et al. . Day-and-night closed-loop insulin delivery in a broad population of pregnant women with type 1 diabetes: a randomized controlled crossover trial. Diabetes Care 2018;41:1391–1399
    1. Law GR, Alnaji A, Alrefaii L, et al. . Suboptimal nocturnal glucose control is associated with large for gestational age in treated gestational diabetes mellitus. Diabetes Care 2019;42:810–815
    1. Murphy HR, Rayman G, Lewis K, et al. . Effectiveness of continuous glucose monitoring in pregnant women with diabetes: randomised clinical trial. BMJ 2008;337:a1680.
    1. Secher AL, Ringholm L, Andersen HU, Damm P, Mathiesen ER. The effect of real-time continuous glucose monitoring in pregnant women with diabetes: a randomized controlled trial. Diabetes Care 2013;36:1877–1883
    1. Paramasivam SS, Chinna K, Singh AKK, et al. . Continuous glucose monitoring results in lower HbA1c in Malaysian women with insulin-treated gestational diabetes: a randomized controlled trial. Diabet Med 2018;35:1118–1129
    1. Mazze RS, Lucido D, Langer O, Hartmann K, Rodbard D. Ambulatory glucose profile: representation of verified self-monitored blood glucose data. Diabetes Care 1987;10:111–117
    1. Fonseca V, Grunberger G. Letter to the editor: standard glucose reporting: follow-up to the February 2016 AACE CGM Consensus Conference. Endocr Pract 2017;23:629–632
    1. Mullen DM, Bergenstal R, Criego A, Arnold KC, Goland R, Richter S. Time savings using a standardized glucose reporting system and ambulatory glucose profile. J Diabetes Sci Technol 2018;12:614–621
    1. Carlson AL, Mullen DM, Bergenstal RM. Clinical use of continuous glucose monitoring in adults with type 2 diabetes. Diabetes Technol Ther 2017;19(Suppl. 2):S4–S11
    1. Hirsch IB, Verderese CA. Professional flash continuous glucose monitoring with ambulatory glucose profile reporting to supplement A1C: rationale and practical implementation. Endocr Pract 2017;23:1333–1344
    1. Kruger DF, Edelman SV, Hinnen DA, Parkin CG. Reference guide for integrating continuous glucose monitoring into clinical practice. Diabetes Educ 2019;45(Suppl. 1):3S–20S
    1. Rodbard D. Continuous glucose monitoring: a review of successes, challenges, and opportunities. Diabetes Technol Ther 2016;18(Suppl. 2):S3–S13
    1. Rodbard D. Glucose variability: a review of clinical applications and research developments. Diabetes Technol Ther 2018;20(Suppl. 2):S25–S215
    1. Bergenstal RM, Beck RW, Close KL, et al. . Glucose management indicator (GMI): a new term for estimating A1C from continuous glucose monitoring. Diabetes Care 2018;41:2275–2280
    1. Cohen RM, Franco RS, Smith EP, Higgins JM. When HbA1c and blood glucose do not match: how much is determined by race, by genetics, by differences in mean red blood cell age? J Clin Endocrinol Metab 2019;104:707–710
    1. Svensson E, Baggesen LM, Johnsen SP, et al. . Early glycemic control and magnitude of HbA1c reduction predict cardiovascular events and mortality: population-based cohort study of 24,752 metformin initiators. Diabetes Care 2017;40:800–807
    1. Safford MM, Shewchuk R, Qu H, et al. . Reasons for not intensifying medications: differentiating “clinical inertia” from appropriate care. J Gen Intern Med 2007;22:1648–1655
    1. Nathan DM, Genuth S, Lachin J, et al. .; Diabetes Control and Complications Trial Research Group . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–986
    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). Lancet 1998;352:837–853
    1. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577–1589
    1. Ismail-Beigi F, Craven T, Banerji MA, et al. .; ACCORD trial group . Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial. Lancet 2010;376:419–430
    1. Hayward RA, Reaven PD, Wiitala WL, et al. .; VADT Investigators . Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2015;372:2197–2206
    1. DeWalt DA, Davis TC, Wallace AS, et al. . Goal setting in diabetes self-management: taking the baby steps to success. Patient Educ Couns 2009;77:218–223
    1. Lawlor KB, Hornyak MJ. SMART goals: how the application of SMART goals can contribute to achievement of student learning outcomes. Developments in Business Simulation and Experiential Learning: Proceedings of the Annual ABSEL Conference 2012;39:259–267
    1. DiMeglio LA, Acerini C, Codner E, et al. ISPAD Clinical Practice Consensus Guidelines 2018: glycemic control targets and glucose monitoring for children, adolescents, and young adults with diabetes. Pediatr Diabetes 2018;19:105–114
    1. Aleppo G, Laffel LM, Ahmann AJ, et al. A practical approach to using trend arrows on the Dexcom G5 CGM system for the management of adults with diabetes. J Endocr Soc 2017;1:1445–1460
    1. Laffel LM, Aleppo G, Buckingham BA, et al. . A practical approach to using trend arrows on the Dexcom G5 CGM system to manage children and adolescents with diabetes. J Endocr Soc 2017;1:1461–1476
    1. Kudva YC, Ahmann AJ, Bergenstal RM, et al. Approach to using trend arrows in the FreeStyle Libre Flash Glucose Monitoring Systems in adults. J Endocr Soc 2018;2:1320–1337
    1. Monnier L, Colette C, Wojtusciszyn A, et al. . Toward defining the threshold between low and high glucose variability in diabetes. Diabetes Care 2017;40:832–838
    1. Rodbard D. Hypo- and hyperglycemia in relation to the mean, standard deviation, coefficient of variation, and nature of the glucose distribution. Diabetes Technol Ther 2012;14:868–876

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