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Diabetes Distilled: Consensus group agrees definition of remission in type 2 diabetes

A joint UK, European and US consensus report defines diabetes remission as an HbA1c <48 mmol/mol (6.5%) measured at least 3 months after cessation of glucose-lowering drug therapy. Recurrence of type 2 diabetes may occur following remission, so ongoing surveillance is needed. The consensus group highlights that complications may continue to progress during remission, so all care processes should continue. Sudden worsening of microvascular complications may occur following rapid decrease in glucose levels after prolonged hyperglycaemia, so those with retinopathy beyond the presence of microaneurysms should avoid rapid reduction in glucose levels and retinal screening should be repeated if rapid decline occurs.

Previous definitions of remission differed in different countries, causing confusion about remission diagnosis and ongoing surveillance. An expert panel, representing the Endocrine Society, the European Association for the Study of Diabetes, Diabetes UK and the American Diabetes Association (ADA), has published a consensus report on the definition and interpretation of remission in type 2 diabetes.

Consensus was reached on the following areas:

  • The panel chose the term “remission” (currently used and coded by UK teams) to demonstrate that type 2 diabetes is not always active or progressive and that improvement may not be permanent. Ongoing review is therefore needed.
  • HbA1c, measured using stringent quality control, remains the preferred method of assessing glycaemia for the majority of people. Remission is defined as an HbA1c <48 mmol/mol (6.5%) off all glucose-lowering medication for at least 3 months. HbA1c is not an accurate measure of glycaemia in everyone and, for those unsuitable, the panel proposed the use of 24-hour mean glucose measured by continuous glucose monitoring. A calculated HbA1c equivalent to the mean 24-hour glucose level is to be used, termed an estimated HbA1c (eA1C) or glucose management indicator (GMI), with <48 mmol/mol (6.5%) confirming remission. Fasting plasma glucose (FPG) <7.0 mmol/L (126 mg/dL) may be used, but 2-hour plasma glucose following a glucose load was not favoured due to collection complexity, variability and possible alteration following metabolic surgery.
  • Remission can be diagnosed after bariatric surgery (at least 3 months after surgery) or while lifestyle interventions are ongoing (at least 6 months after lifestyle changes initiated). In all cases, glucose-lowering therapy must have been stopped for at least 3 months to ensure the effects have waned fully and that HbA1c is measuring a period without drug treatment.
  • Once remission occurs, measurement no sooner than 3 months and at no more than 12-month intervals can be used to confirm ongoing remission.
  • Changes in FBG or eA1C may occur sooner than with HbA1c, but are more variable. Therefore, if these need to be used, they can be undertaken earlier but need to be repeated to confirm remission or loss of remission.
  • Previous hyperglycaemia may have caused ongoing complications (“legacy effect”) and complications may continue to develop during remission, so all care processes should continue. Sudden worsening of microvascular complications may occur with rapid lowering of glucose levels after prolonged hyperglycaemia. The panel recommends that when retinopathy beyond microaneurysms is present with poor control, rapid glucose-lowering should be avoided and, if it does occur, retinopathy screening should be repeated.

The authors identified areas requiring further exploration: Should a different HbA1c value or CGM measure be used to define remission, or CGM measures? What is the optimal timing of repeat testing? Are there benefits in continuing metformin? What happens to gut hormones? Is there variation in the duration of remission depending on how it is achieved? And what are the long-term outcomes, including complications, quality of life and function?

Consensus authors’ notes

A consensus report contains a comprehensive examination of a topic by an expert panel and usually includes analysis, evaluation and opinion. A consensus report is needed when clinicians, scientists, regulators and/or policy makers seek guidance and/or clarity on a medical or scientific issue for which the evidence is contradictory, emerging or incomplete. The expert panel can also identify gaps in evidence and propose areas of future research.

This consensus report, published simultaneously in The Journal of Clinical Endocrinology & Metabolism, Diabetologia, Diabetic Medicine and Diabetes Care, reflects the joint working of the expert representatives of the organisations in preparation of the consensus. The authors highlight that it should not be seen as an ADA Position Statement or as a treatment guideline, but rather it proposes definitions and ways to assess glycaemia, and facilitate collection and analysis of data.

To read the report in full, click here.

Riddle MC, Cefalu WT, Evans PH et al (2021) Consensus report: Definition and interpretation of remission in type 2 diabetes. Diabet Med 30 Aug [Epub ahead of print]

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