Type 2 diabetes mellitus (T2DM) is not yet curable, but it is possible to reverse it! In October 2021, China's first "Expert Consensus on Short-term Intensive Insulin Therapy to Reverse Type 2 Diabetes" (hereinafter referred to as the "New Consensus") was officially published in the Chinese Journal of Diabetes[1], and continuous subcutaneous insulin infusion (CSII), that is, insulin pump, was recommended as the preferred option for reversing T2DM in short-term intensive insulin therapy. With the rapid development of insulin pump technology and the continuous iteration of new products, more and more inpatient and out-of-hospital patients will have more opportunities to practice T2DM reversal therapy.
A quick overview of the new consensus points: Regarding the reversal of T2DM with short-term insulin intensive therapy, there are several basic questions that should be understood first
The concept and significance of T2DM reversal
T2DM has a certain reversibility in the early days. Diabetic reversal is essentially a recovery of patient β cell function and insulin sensitivity, manifested by the ability to maintain good blood glucose control for a period of time after the intensity of hypoglycemic therapy has been reduced. For patients with newly diagnosed or short-term T2DM, the purpose of reversal therapy is often to detach from therapeutic measures such as oral hypoglycemic drugs, that is, no drug remission.
The new consensus proposes a definition of hyperglycemia reversal as the maintenance of HbA1c by reverting to the original regimen or using a lower-intensity hypoglycemic regimen than before treatment[1].
Table 1. The new consensus proposes a definition of the T2DM reversal state
It can be seen that the best effect of T2DM reversal therapy can achieve drug-free remission, or enable patients who did not meet the original glucose control standards to maintain a good sugar control state without increasing the intensity of hypoglycemic therapy. Although reversal is not the same as cure, it is important to minimize hyperglycemia exposure and thus the risk of long-term chronic complications associated with it in order to reverse the disease early [1].
Compared with other reversal methods (lifestyle weight loss, metabolic surgery), short-term intensive insulin therapy has the advantages of short intervention time, no surgical trauma, wide applicability, and good safety, so the new consensus is specifically formulated for this purpose.
People who are suitable for short-term intensive insulin therapy to reverse T2DM
The new consensus recommends that short-term intensive insulin therapy reverse T2DM is mainly suitable for the following three conditions [1]:
Newly diagnosed patients with T2DM, HbA1c ≥ 9.0% or fasting blood glucose ≥ 11.1 mmol/L, or with significant hyperglycemia symptoms, may be initiated for short-term intensive insulin therapy.
Newly diagnosed patients with T2DM, HbA1c7.5% to 8.9% or fasting blood glucose 8.0 to 11.0 mmol/L, may be cautiously administered with short-term intensive insulin therapy.
HbA1c≥7.5% of patients with a certain course of disease, such as the course of the disease, are combined with oral hypoglycemic drugs or initiated insulin therapy for more than 3 months, HbA1c
Predictors of a successful reversal of T2DM
The main predictors of remission in newly diagnosed patients with T2DM include younger age, a baseline BMI of >25 kg/m2 or with insulin resistance, low mean blood glucose during reversal therapy, more than 50% insulin reduction, and low fasting blood glucose the day after cessation of insulin infusion ([1].
The main predictors of disease reversal in patients with T2DM with a certain course of illness include a shorter course of disease ([1].
Reverse therapy flowchart
The new consensus suggests that a flow chart of short-term intensive insulin therapy for newly diagnosed patients with T2DM with a certain course of illness and poor glycemic control is shown below (Figures 1, 2) [1].
Figure 1. Flowchart of short-term intensive insulin therapy reversal therapy in newly diagnosed patients with T2DM
Figure 2. Flow chart of short-term intensive insulin therapy reversal therapy in patients with T2DM with a certain course of disease and poor glycemic control
The new consensus recommends CII as the preferred regimen for reversal therapy: clinical advantages and specific applications
Given that blood glucose normalization requires insulin infusion to mimic physiological secretion patterns as much as possible, CSII is closer to this requirement among various injection methods, blood glucose control is more effective and stable, and the risk of hypoglycemia is lower. Therefore, the new consensus recommends CII as the preferred regimen for short-term intensive insulin therapy reversal therapy [1].
Blood glucose targets: The new consensus recommends reversing blood glucose during treatment with fasting and pre-meal
Course of treatment: In view of the need to maintain a certain period of time after the blood glucose standard is maintained for the β the recovery of cell function, it is recommended that the short-term insulin intensive treatment course be no less than 2 weeks after the blood glucose standard is reached.
Insulin dose: It is recommended to estimate the starting insulin dose based on the patient's weight, blood glucose and other indicators, and the recommended ratio of basal insulin to mealtime insulin is 40% and 60%. The insulin infusion regimen should be closely adjusted to the patient's blood glucose, exercise, and diet to ensure that blood glucose is strictly up to standard. After the blood glucose standard is reached, the insulin dose should be adjusted in time according to the results of blood glucose monitoring to reduce the risk of hypoglycemia.
New insulin pump: more possibilities for reversal of T2DM therapy inside and outside the hospital...
Intensive treatment is the trend of the times when it comes to the community
The new consensus points out that although short-term intensive insulin therapy has been systematically introduced into T2DM management for nearly 20 years and recommended by mainland guidelines for nearly 10 years, there are still some problems that need to be solved in its widespread normative application. For example, intensive treatment needs to be adapted to the current hierarchical diagnosis and treatment system. Short-term intensive insulin therapy after 2 to 3 weeks of hospitalization can no longer fully adapt to the current rhythm of diagnosis and treatment. How to shorten the time of intensive treatment in hospitalization, put part of the intensive management in the community, and establish a flexible intensive treatment model of regional center-community linkage is an important topic for the promotion and application [1].
The new insulin pump helps more patients outside the hospital to implement T2DM reversal therapy
In recent years, various new insulin pumps have been constantly innovating, with more and more perfect functions and more and more humane designs. For example, the Medtronic MiniMed 700 insulin pump (Meiyueda), which will be launched™ in the mainland, has multiple advantages such as fine dose regulation (minimum infusion dose 0.025 U/h), intelligent calculation of active insulin dose and real-time display, intelligent preset multiple modes of easy operation, diversified reminders to increase safety and security, more convenient viewing of large color screens, temporary base rate/ square double wave function to cope with diversified lifestyles, etc. More options will be available for short-term intensive insulin therapy to reverse T2DM in people with diabetes outside of hospital or in the community.
epilogue
T2DM reversal is of great significance for the long-term prognosis of patients, and clinicians should seize the opportunity to use short-term insulin intensive reversal therapy for newly diagnosed patients with T2DM who meet the conditions or T2DM patients whose original treatment regimen does not meet the blood glucose standards. The new consensus recommends CII as the preferred regimen for reversing T2DM with short-term intensive insulin therapy and provides detailed guidance for clinical application. In the future, reversal therapy for patients with T2DM will be carried out in the community, and it is expected that the use of new, more flexible and convenient insulin pumps (such as Medtronic MiniMed™ 700) will play an important role in out-of-hospital reverse T2DM treatment. With the rational use of insulin pumps, diabetes can also be successfully overturned!
References: 1. Chinese Insulin Secretion Research Group. Chinese Journal of Diabetes. 2021; 13(10): 949-959.