Remission of type 2 diabetes mellitus: Emerging concepts and proposed diagnostic criteria

Table 1 Various terminologies used

Terminology	Word meaning	Blood sugar target for remission	Pathophysiological status	Follow-up
Resolution	The subsidence of a pathological state	Attained	Permanent normalization	No
Cure	A complete or permanent solution	Attained	Permanent normalization	No
Reversal	A change from one state to the opposite state	Attained	Permanent normalization	No
Remission	An abatement or reduction in intensity or degree (as in the manifestations of a disease)	Attained	Improvement	Yes

Table 2 Diagnostic criteria for remission of type 2 diabetes mellitus

A: Establishing the diagnosis of T2DM/pre-diabetes
Documented evidence of T2DM based on established criteria like ADA criteria
Diagnosis		HbA1c	FPG	2-h PG
T2DM		≥ 6.5%; ≥ 48 mmol/mol	≥ 126 mg/dL; ≥ 7 mmol/L	≥ 200 mg/dL; ≥ 11.1 mmol/L
Pre-diabetes		5.7% to 6.4%; 39 to 47 mmol/mol	100 to 125 mg/dL; 5.6 to 6.9 mmol/L	140 to 199 mg/dL; 7.8 to 11.0 mmol/L
B: Evidence of maintenance of blood sugar below the threshold for T2DM or normal range (biochemical remission) in people with established T2DM even after the withdrawal of pharmacotherapy/active intervention
Remission		HbA1c	FPG	2-h PG
Partial		5.7% to 6.4%; 39 to 47 mmol/mol	100 to 125 mg/dL; 5.6 to 6.9 mmol/L	140 to 199 mg/dL; 7.8 to 11.0 mmol/L
Complete		< 5.7%; < 39 mmol/mol	< 100 mg/dL; < 5.6 mmol/L	< 140 mg/dL; < 7.8 mmol/L
One or more components needed to establish remission
C: Duration criteria for the intervention and for the test
Normoglycemia persists even after the withdrawal of glucose-lowering intervention (pharmacotherapy/active intervention), which is documented after a reasonable washout period
	Glucose-lowering intervention can be non-pharmacological (medical nutrition therapy or physical activity) or pharmacological intervention (medication or surgical intervention)
	No ongoing pharmacological or surgical procedure (ongoing procedures like repeated placement of endoluminal devices or intragastric balloon)
	If any medication that can reduce blood sugar is continued for non-glycemic indication, it is considered incomplete remission
Duration criteria for the intervention
	Drugs after washout period (after five t ½ of the drug)
	Lifestyle modification takes 3-6 mo to stabilize its effect
Duration criteria for the tests
	HbA1c after 3 mo of washout period of intervention
	FBS/PPBS/RBS/CGM after 24 h of washout period of intervention
Duration of remission is a retrospective assessment. Depending upon the duration of remission
Normoglycemia persisting
	3-6 mo: Transient remission
	6 mo-1 yr: Short-term remission
	1-5 yr: Long-term remission
More than 5 yr: Prolonged remission
D: Evidence of improvement of the pathophysiological mechanism
Improvement in insulin resistance and β cell function
Indirect evidence of this is significant weight loss, about 15 kg
E: Satisfy exclusion criteria
Normalization of blood sugar value in people with T2DM is not due to any complications (e.g., nephropathy or hepatic dysfunction) or comorbid disease that causes reduced appetite, weight loss, or hypoglycemia (e.g., sepsis, adrenal or pituitary disease, malignancy)
Exclusion of stress hyperglycemia, gestational diabetes, or transient hyperglycemia
Exclusion of hyperglycemia due to any medications: Drug-induced diabetes (e.g., steroid, anti-malarial drugs, atypical antipsychotics, protease inhibitors)

ADA: American Diabetes Association; CGM: Continuous glucose monitoring; FBS: Fasting blood sugar; FPG: Fasting plasma glucose; HbA1c: Glycated hemoglobin; PG: Post glucose; PPBS: Post prandial blood sugar; RBS: Random blood sugar; T2DM: Type 2 diabetes mellitus; t ½: Half-life.

Table 3 Interpretation of proposed criteria for remission of type 2 diabetes mellitus

Diagnosis of T2DM/pre-diabetes	Evidence of biochemical remission	Antidiabetic treatment/ongoing intervention	Duration criteria	Reversal of pathophysiologic mechanism	Exclusion criteria	Interpretation
Yes	Complete	No	+	+	+	Complete remission
	Partial					Partial remission
Yes	Complete	Yes, but for non-glycemic indication	+	+	+	Incomplete remission
	Partial					Incomplete partial remission
No	Complete/partial	No	+/-	+/-	+/-	Transient hyperglycemia. No remission. Improvement in risk factors
Yes	Complete/partial	No	+	-	+	State of mitigation/T2DM mitigation

T2DM: Type 2 diabetes mellitus.