Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes

Matthew C Riddle, William T Cefalu, Philip H Evans, Hertzel C Gerstein, Michael A Nauck, William K Oh, Amy E Rothberg, Carel W le Roux, Francesco Rubino, Philip Schauer, Roy Taylor, Douglas Twenefour, Matthew C Riddle, William T Cefalu, Philip H Evans, Hertzel C Gerstein, Michael A Nauck, William K Oh, Amy E Rothberg, Carel W le Roux, Francesco Rubino, Philip Schauer, Roy Taylor, Douglas Twenefour

Abstract

Improvement of glucose levels into the normal range can occur in some people living with diabetes, either spontaneously or after medical interventions, and in some cases can persist after withdrawal of glucose-lowering pharmacotherapy. Such sustained improvement may now be occurring more often due to newer forms of treatment. However, terminology for describing this process and objective measures for defining it are not well established, and the long-term risks versus benefits of its attainment are not well understood. To update prior discussions of this issue, an international expert group was convened by the American Diabetes Association to propose nomenclature and principles for data collection and analysis, with the goal of establishing a base of information to support future clinical guidance. This group proposed "remission" as the most appropriate descriptive term, and HbA1c <6.5% (48 mmol/mol) measured at least 3 months after cessation of glucose-lowering pharmacotherapy as the usual diagnostic criterion. The group also made suggestions for active observation of individuals experiencing a remission and discussed further questions and unmet needs regarding predictors and outcomes of remission.

© 2021 by the American Diabetes Association.

References

    1. Vounzoulaki E, Khunti K, Abner SC, Tan BK, Davies MJ, Gillies CL. Progression to type 2 diabetes in women with a known history of gestational diabetes: systematic review and meta-analysis. BMJ 2020;369:m1361.
    1. Simmons LR, Molyneaux L, Yue DK, Chua EL. Steroid-induced diabetes: is it just unmasking of type 2 diabetes? ISRN Endocrinol 2012;2012:910905.
    1. Li Z, Cheng Y, Wang D, et al. . Incidence rate of type diabetes mellitus after gestational diabetes mellitus: a systematic review and meta-analysis of 170,139 women. J Diab Res 2020;3076463
    1. Selvin E, Ning Y, Steffes MW, et al. . Glycated hemoglobin and the risk of kidney disease and retinopathy in adults with and without diabetes. Diabetes 2011;60:298–305
    1. Currie CJ, Peters JR, Tynan A, et al. . Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study. Lancet 2010;375:481–489
    1. Carson AP, Fox CS, McGuire DK, et al. . Low hemoglobin A1c and risk of all-cause mortality among US adults without diabetes. Circ Cardiovasc Qual Outcomes 2010;3:661–667
    1. Kramer CK, Zinman B, Retnakaran R. Short-term intensive insulin therapy in type 2 diabetes mellitus: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 2013;1:28–34
    1. Kramer CK, Zinman B, Choi H, Retnakaran R. Predictors of sustained drug-free diabetes remission over 48 weeks following short-term intensive insulin therapy in early type 2 diabetes. BMJ Open Diabetes Res Care 2016;4:e000270
    1. McInnes N, Smith A, Otto R, et al. . Piloting a remission strategy in type 2 diabetes: results of a randomized controlled trial. J Clin Endocrinol Metab 2017;102:1596–1605
    1. Lean MEJ, Leslie WS, Barnes AC, et al. . Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol 2019;7:344–355
    1. Gregg EW, Chen H, Wagenknecht LE, et al. .; Look AHEAD Research Group . Association of an intensive lifestyle intervention with remission of type 2 diabetes. JAMA 2012;308:2489–2496
    1. Mingrone G, Panunzi S, De Gaetano A, et al. . Metabolic surgery versus conventional medical therapy in patients with type 2 diabetes: 10-year follow-up of an open-label, single-centre, randomised controlled trial. Lancet 2021;397:293–304
    1. Rubino F, Nathan DM, Eckel RH, et al. .; Delegates of the 2nd Diabetes Surgery Summit . Metabolic surgery in the treatment algorithm for type 2 diabetes: a joint statement by international diabetes organizations. Diabetes Care 2016;39:861–877
    1. Schauer PR, Bhatt DL, Kirwan JP, et al. .; STAMPEDE Investigators . Bariatric surgery versus intensive medical therapy for diabetes: 5-year outcomes. N Engl J Med 2017;376:641–651
    1. White MG, Shaw JAM, Taylor R. Type 2 diabetes: the pathologic basis of reversible β-cell dysfunction. Diabetes Care 2016;39:2080–2088
    1. Buse JB, Caprio S, Cefalu WT, et al. . How do we define cure of diabetes? Diabetes Care 2009;32:2133–2135
    1. Nagi D, Hambling C, Taylor R. Remission of type 2 diabetes: a position statement from the Association of British Clinical Diabetologists (ABCD) and the Primary Care Diabetes Society (PCDS). Br J Diabetes 2019;19:73–76
    1. Barnes E. Between remission and cure: patients, practitioners and the transformation of leukaemia in the late twentieth century. Chronic Illn 2007;3:253–264
    1. Taylor R, Al-Mrabeh A, Zhyzhneuskaya S, et al. . Remission of human type 2 diabetes requires decrease in liver and pancreas fat content but is dependent upon capacity for β cell recovery. Cell Metab 2018;28:547–556.e3
    1. Lim EL, Hollingsworth KG, Aribisala BS, Chen MJ, Mathers JC, Taylor R. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia 2011;54:2506–2514
    1. Camastra S, Manco M, Mari A, et al. . Beta-cell function in severely obese type 2 diabetic patients: long-term effects of bariatric surgery. Diabetes Care 2007;30:1002–1004
    1. Consensus Committee . Consensus statement on the worldwide standardization of the hemoglobin A1C measurement: the American Diabetes Association, European Association for the Study of Diabetes, International Federation of Clinical Chemistry and Laboratory Medicine, and the International Diabetes Federation. Diabetes Care 2007;30:2399–2400
    1. Jeppsson J-O, Kobold U, Barr J, et al. .; International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) . Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med 2002;40:78–89
    1. EurA1c Trial Group . EurA1c: the European HbA1c trial to investigate the performance of HbA1c assays in 2166 laboratories across 17 countries and 24 manufacturers by use of the IFCC model for quality targets. Clin Chem 2018;64:1183–1192
    1. Danne T, Nimri R, Battelino T, et al. . Inter-national consensus on use of continuous glucose monitoring. Diabetes Care 2017;40:1631–1640
    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. 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. Shah VN, DuBose SN, Li Z, et al. . Continuous glucose monitoring profiles in healthy nondiabetic participants: a multicenter prospective study. J Clin Endocrinol Metab 2019;104:4356–4364
    1. Hundal RS, Inzucchi SE, Metformin: new understandings, new uses. Drugs 2003;63:1879–1894
    1. Herman WH, Ratner RE. Metformin should be used to treat prediabetes in selected individuals. Diabetes Care 2020;43:1988–1990
    1. Davidson MB. Metformin should not be used to treat prediabetes. Diabetes Care 2020;43:1983–1987
    1. Yki-Järvinen H. Glucose toxicity. Endocr Rev 1992;13:415–431
    1. Isaman DJ, Rothberg AE, Herman WH. Reconciliation of type 2 diabetes remission rates in studies of Roux-en-Y gastric bypass. Diabetes Care 2016;39:2247–2253
    1. Ceriello A. The emerging challenge in diabetes: the “metabolic memory.” Vascul Pharmacol 2012;57:133–138
    1. Murphy R, Jiang Y, Booth M, et al. . Progression of diabetic retinopathy after bariatric surgery. Diabet Med 2015;32:1212–1220
    1. Arun CS, Pandit R, Taylor R. Long-term progression of retinopathy after initiation of insulin therapy in Type 2 diabetes: an observational study. Diabetologia 2004;47:1380–1384
    1. The Diabetes Control and Complications Trial Research Group . Early worsening of diabetic retinopathy in the Diabetes Control and Complications Trial. Arch Ophthalmol 1998;116:874–886
    1. Singh RP, Gans R, Kashyap SR, et al. . Effect of bariatric surgery versus intensive medical management on diabetic ophthalmic outcomes. Diabetes Care 2015;38:e32–e33

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