Short-term Intensive Insulin Therapy: Don't Miss the Chance for Reversal in Early Diabetes

Wang is the deputy director of the editorial department of a certain media company. A year ago, a physical examination revealed that his fasting blood sugar was 11.0 mmol/L, and the blood sugar two hours after a meal was 17.0 mmol/L. The endocrinologist advised him to measure glycated hemoglobin, and the result was 10.9%. The doctor immediately hospitalized him for intensive insulin therapy for a week. Upon discharge, both his fasting blood sugar and postprandial blood sugar had returned to normal, and the secretion of insulin and C-peptide had also significantly improved compared to before. After discharge, the doctor changed Wang's insulin plan to a long-acting insulin plus oral medication. Three months later, all medications were stopped.

During this year, Wang frequently monitored his blood sugar and tried not to attend social events outside. He adhered to a strict diet and exercised regularly, without the need for injections or medication. One year later, a re-examination of the oral glucose tolerance test and insulin release test showed that both had returned to normal. The doctor told him, "It is not uncommon for diabetes to be alleviated after intensive treatment. Depending on individual circumstances, some patients can be alleviated for half a year, while others can be alleviated for 1 to 5 years."

Short-term intensive insulin therapy can "reverse" diabetes, and there are many such cases in clinical practice, which also adds confidence to diabetic patients for "reversal."

Why can diabetes be reversed?

In 2012, Professor Accil from Columbia University in the United States published a significant research finding: "B-cell dedifferentiation" is an important pathogenic mechanism of type 2 diabetes. The experiment found that in the early stages of diabetes, some islet B-cells did not die but were in a self-protective "dedifferentiated state." What is "dedifferentiation"? It can be imagined as a state similar to feigning death or fainting. Originally, B-cells underwent a differentiation after being hit by the external environment (such as a state of high blood sugar): some "perished"; some "defected" and joined the α-cell team that raises blood sugar; and some smart B-cells pretended to "faint" and escaped. These "fainting" B-cells are the body's reserve force. If we can seize the opportunity and adjust the external environment to a normal state through some means, these "fainting" B-cells can rejoin the main force and become a powerful reserve army to restore islet function.

Who has the most hope of reversal? Those in the prediabetes stage are definitely the best candidates. Because blood sugar has not yet reached the diagnostic criteria for diabetes, and the impact on their own B-cells is not very great. At this stage, intervention to keep blood sugar and blood lipids normal is the most cost-effective. Among patients diagnosed with type 2 diabetes, if you are obese and have a disease course of less than two years, the probability of reversal is 80%. There are also studies showing that even patients with a disease course of 5-10 years can have a reversal rate of 50%, and even patients with a disease course of about 10 years have a 20% chance of reversal. As long as you have a strong desire to reverse diabetes, even if you have been diagnosed with diabetes for many years, you can still try under the guidance of a doctor.

Chinese experts recommend a consensus on reversing type 2 diabetes

Reversing diabetes is not only about improving blood sugar but also about improving the thoughts, life attitudes, and family relationships of diabetic patients, and reducing the occurrence of cardiovascular and cerebrovascular diseases, fatty liver, tumors, hypertension, sleep apnea syndrome, arthritis, and other diseases.

The "Expert Consensus on Reversing Type 2 Diabetes with Short-term Intensive Insulin Therapy" released in 2021 clearly states that short-term intensive insulin therapy can significantly improve islet B-cell function and insulin sensitivity, and is an effective means of reversing type 2 diabetes. The consensus also provides definitions of diabetes remission and hyperglycemia reversal, recommends the use of short-term intensive insulin therapy to reverse treatment for newly diagnosed type 2 diabetic patients or those whose original treatment plans cannot achieve blood sugar standards; during the short-term intensive insulin therapy to reverse treatment period, the goal should be to normalize blood sugar; the course of intensive treatment should be at least two weeks after blood sugar reaches the standard; after intensive treatment, the efficacy should be predicted based on existing clinical evidence, and then an individualized follow-up management plan should be formulated and other guidance.

At present, reversal treatment mainly includes short-term intensive insulin therapy, lifestyle weight loss (low-energy diet + exercise), and metabolic surgery. The core mechanism of metabolic surgery and lifestyle intervention to reverse type 2 diabetes is the significant reduction in body weight and negative energy balance, with evidence mostly coming from people with a shorter disease course, mild to moderate blood sugar increase, and significant obesity.

Interpretation of Reversal and Remission

The essence of diabetes reversal is the recovery of the function of islet B-cells and insulin sensitivity in patients, which is manifested as the ability to maintain good blood sugar control for a period of time even after the intensity of blood sugar-lowering treatment is reduced.

For newly diagnosed or patients with a short disease course of type 2 diabetes, reversal is to be free from oral hypoglycemic drugs, that is, drug-free remission. Given that the Chinese diabetic population is more common with postprandial blood sugar increase, the "Expert Consensus on Reversing Type 2 Diabetes with Short-term Intensive Insulin Therapy" has proposed a stratified definition of the reversal state.

The consensus emphasizes that clinical remission belongs to a higher level of reversal; although patients who have achieved diabetes remission can be free from hypoglycemic drugs and other medical interventions, it does not mean "cure." Even if drug-free remission has been achieved, diabetic patients still need to continue lifestyle management and regular monitoring to detect and intervene hyperglycemia as early as possible.

Why can short-term intensive insulin therapy reverse type 2 diabetes?

The goal of short-term intensive insulin therapy is to improve the function of islet B-cells and increase the sensitivity of insulin.

Comprehensive clinical evidence shows that short-term intensive insulin therapy can significantly improve acute insulin response, that is, the first-phase secretion, early-phase insulin secretion, and can also improve the ratio of insulin area under the curve to glucose area under the curve in the oral glucose tolerance test, C-peptide response, insulin secretion sensitivity index-2 and other B-cell function indicators, and significantly improve the insulin resistance index, thereby enhancing the body's glucose disposal capacity.

Research suggests that this short-term intensive treatment may eliminate the toxicity of hyperglycemia, reduce the demand for endogenous insulin secretion, reduce the metabolic load on islet B-cells, and restore the glycemic sensitivity of B-cells, thereby playing a role in promoting the repair of B-cells.

Research has also found that during the intensive treatment process, patients with lower average blood sugar control levels have higher long-term remission rates; patients with more significant suppression of C-peptide levels also have better recovery of islet function. This indicates that the full substitution of insulin during the treatment period provides an environment for the further repair of residual islet B-cells, which is of vital importance.

In recent years, it has been found that islet B-cells can undergo dedifferentiation changes when damaged. Dedifferentiation is considered an important mechanism for the failure of insulin secretion function in type 2 diabetes. This also provides a powerful way for insulin therapy to induce redifferentiation of dedifferentiated B-cells and significantly improve insulin secretion function.

Which groups are suitable for intensive treatment?

The "Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2020 Edition)" suggests that intensive treatment can be implemented when newly diagnosed type 2 diabetic patients have a glycated hemoglobin ≥9.0% or fasting blood sugar ≥11.1 mmol/L, accompanied by obvious hyperglycemic symptoms.

For newly diagnosed type 2 diabetic patients, glycated hemoglobin is 7.5%-8.9% or fasting blood sugar is 8.0-11.0 mmol/L, and intensive treatment should be implemented cautiously.

For type 2 diabetic patients with a certain course, combined oral hypoglycemic drugs or starting insulin treatment for more than 3 months, glycated hemoglobin ≥7.5%, if the course is less than 15 years, and fasting C-peptide ≥0.4 mmol/L, insulin intensive treatment can be considered according to the patient's wishes.

Intensive treatment is not recommended for newly diagnosed patients with fasting blood sugar less than 8.0 mmol/L or glycated hemoglobin less than 7.5%, and conventional treatment can be used to achieve blood sugar normalization. Patients with a course of more than 15 years have poor reversibility and often have more complications, and such patients are not recommended to undergo reversal