In recent years, the incidence of newly diagnosed type 2 diabetes has increased significantly in China. 1999-2005, the incidence of new type 2 diabetes in the Harbin area increased at an annual rate of 12%; a 2007 study in the Shanghai area found that the annual incidence of new diabetes far exceeded that of the United States during the same period. Although there is a lack of data on the incidence of diabetes in China over the years, the number of new cases in China is projected to be between 6.8 and 7.4 million per year by referring to the incidence of newly diagnosed patients in the United States in recent years. The latest data from the nationwide HbAlc screening network shows that the proportion of newly diagnosed type 2 diabetes patients with HbAlc over 9% in China is 28.8%. This shows that there are two major clinical characteristics of the new type 2 diabetes population in China – the huge number and the high blood glucose level at the time of diagnosis.
Feasibility of short-term insulin intensive therapy
In recent years, there has been an increasing amount of clinical evidence regarding the benefit of short-term insulin intensive therapy in patients with newly diagnosed type 2 diabetes. In fact, as early as 1997, a study found a 70% remission rate in newly diagnosed type 2 diabetic patients after short-term intensive insulin therapy (two-week insulin pump therapy) (i.e., no medication required and blood glucose maintained at normal levels through medical nutrition therapy and exercise therapy alone). Several clinical studies from Canada and China have since confirmed the unique benefits of short-term intensive insulin therapy in patients with newly diagnosed type 2 diabetes, particularly its positive effects on the restoration and improvement of islet cell function. For example, a Canadian study was selected in which patients with newly diagnosed type 2 diabetes were treated with multiple daily insulin injections (MDI) for 2 to 3 weeks, and the area under the insulin curve in the oral glucose tolerance test improved significantly both after treatment and at 1 year of follow-up. A study using insulin pump therapy showed that diabetes remission rates were 47.1% and 42.3% at 12 and 24 months after short-term intensive treatment, respectively, and that islet beta-cell function index (HOMA-β) as assessed by the homeostatic model was significantly higher in the remission group. However, these clinical studies were observational (level C of evidence in evidence-based medicine) and only suggest that we may induce remission with short-term intensive insulin therapy early in type 2 diabetes.
Superior to oral hypoglycemic intensification
In 2008, a multicenter, randomized, controlled trial conducted by Prof. Weng Jianping et al. found that short-term intensive treatment had good clinical efficacy, with higher 1-year glucose remission rates in the insulin group compared to the oral hypoglycemic group – 51.1% in the insulin pump group, 44.9% in the MDI group, and 26.7% in the oral hypoglycemic group. In addition, first-phase insulin secretion was significantly improved in the insulin-treated group. This study provides further evidence that short-term intensive insulin therapy improves pancreatic β-cell function in patients and leads to remission in some patients with newly diagnosed type 2 diabetes (level B of evidence-based medicine).
Inducing long-term glycemic remission
A 2013 meta-analysis demonstrated that short-term intensive insulin therapy induced longer-term glycemic remission in some patients with newly diagnosed type 2 diabetes and improved key pathophysiological mechanisms of type 2 diabetes, as evidenced by significant improvements in insulin resistance index (HOMA-IR) as assessed by HOMA-β and homeostatic models (Level A of evidence-based medicine).
Better patient adherence
Two other studies showed that patients with newly diagnosed type 2 diabetes had much higher treatment satisfaction and quality of life scores after short-term intensive insulin therapy than before treatment, suggesting that patients are well tolerating short-term intensive insulin therapy as a treatment modality.
Long-term application still needs to be studied
The Initial Interventional Regression Study with Glargine Insulin (ORIGIN), published in 2012, looked at whether early long-term insulin use would provide long-term cardiovascular benefit. The results found that early basal insulin long-term treatment failed to reduce the risk of cardiovascular disease in patients with prediabetes and diabetes. Therefore, more evidence from clinical studies is needed on the benefits of early long-term insulin use in patients with type 2 diabetes.
What conditions may be considered
The AACE guidelines suggest that insulin therapy can be given for HbAlc >9% in patients with first-episode type 2 diabetes. In numerous studies of short-term intensive insulin therapy, the subjects included were all with fasting glucose above 7 mmoL/L, and the majority of these studies with 1 year or more follow-up demonstrated that the use of short-term intensive insulin therapy in patients with fasting glucose >11.1 mmol/L can lead to improvements in β-cell function, and some patients can achieve long-term glycemic remission. Therefore, the Expert Consensus on Short-term Intensive Insulin Therapy for Newly Diagnosed Type 2 Diabetes Mellitus (hereinafter referred to as “Consensus”) recommends the use of short-term intensive insulin therapy for newly diagnosed type 2 diabetes mellitus patients with HbAlc>9% or fasting glucose>11.1mmol/L.
Thus, this case meets the clinical indications for short-term insulin intensive therapy and is expected to achieve long-term glycemic remission with this therapy. So how exactly does it work?
How to perform short-term insulin intensive therapy
Although many physicians have embraced the concept of short-term intensive insulin therapy for patients with newly diagnosed type 2 diabetes and are ready to practice it, the actual practice can feel overwhelming. Which insulin regimen should I choose? What is the duration of short-term therapy? What is the appropriate level of blood glucose control? What should I do after intensive therapy? These questions can be answered by referring to the “consensus” recommendations.
Duration of treatment
The majority of studies have used a 2-3 week treatment course for short-term treatment, with a few studies extending it to 3 months. In the light of the clinical situation, the recommendation of the “guideline” is 2 weeks to 3 months, and the treatment goal is to achieve the fasting and 2 hours postprandial glucose standard, but not to achieve the HbAlc standard as the treatment goal.
Program selection
It can be seen from a number of domestic and international clinical studies that although there are many regimens that can be used for insulin intensive therapy, including CSII, MDI and premixed insulin 2 or 3 times a day regimens, there are fewer studies comparing the efficacy of different insulin intensive regimens. 2008 study by Prof. Weng Jianping et al. reported that there was no significant difference in glycemic control and diabetes remission rate between CSII and MDI compared to MDI. A retrospective analysis published in Korea in 2010 showed that there was also no significant difference in glycemic control and diabetes remission rates between premixed insulin and MDI. In a study conducted by Prof. Yang Jie et al. on patients with primary type 2 diabetes who were intensively treated with menadione insulin 30 (Novolac 30) three times a day, the patients’ serum insulin and C-peptide first-phase secretion increased significantly and HOMA-IR decreased significantly after 2 weeks of treatment.
Therefore, the Consensus believes that in the choice of insulin intensive treatment regimen, CSII, MDI or premixed insulin injections 2 or 3 times a day can be used according to the actual situation, and the specific adjustment of insulin dose can be referred to the Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes (2010 Edition) (see Table 1). 1). “The Consensus also states that the short-term insulin intensive treatment regimen for newly diagnosed type 2 diabetes is applicable to adults with type 2 diabetes. For patients with acute complications (e.g., ketoacidosis or severe chronic complications), the insulin regimen and duration of treatment should refer to the relevant guidelines.
Control target
Fasting blood glucose control is 3.9-7.2mmol/L (70-130mg/d1) and non-fasting blood glucose control is ≤10.0mmol/L (180mg/d1). “The consensus also pointed out that patients should be given medical nutrition therapy and exercise therapy at the same time as intensive insulin therapy. Follow-up treatment A large number of clinical studies have confirmed that short-term intensive insulin therapy can lead to clinical remission in some patients with newly diagnosed type 2 diabetes, with a remission period of 3-59 months. Therefore, the Consensus recommends that for patients who fail to induce remission with short-term intensive insulin therapy, whether to continue insulin therapy or switch to other medications should be determined by an endocrinologist based on the patient’s specific situation. For patients who have reached the standard of treatment and are in clinical remission, regular (e.g., 3 months) follow-up monitoring is allowed; when blood glucose rises again, patients with fasting blood glucose >7.0 mmol/L or 2-hour postprandial blood glucose >10.0 mmol/L should restart drug therapy.
Blood glucose monitoring
During the course of intensive insulin therapy, close monitoring of blood glucose is required. During the intensive treatment phase, blood glucose monitoring needs to be performed at least 3 days a week, monitoring blood glucose at 5-7 time points a day to guide the adjustment of insulin dose and regimen. For patients who only need medical nutrition therapy and exercise to maintain normal blood glucose level after the end of intensive insulin therapy, the Consensus recommends monthly blood glucose monitoring for the first 3 months to observe the changes of fasting blood glucose and 2-hour postprandial blood glucose; then blood glucose testing can be performed once every 3 months. For patients who need oral medication, the protocol recommended in the “China Clinical Application Guidelines for Blood Glucose Monitoring (2011 Edition)” should be followed.
Patient education
Patient education on diabetes should be enhanced for patients undergoing short-term insulin intensive therapy. Some studies have shown that after short-term insulin intensive therapy, patients with newly diagnosed type 2 diabetes in remission group (those who have been in glycemic remission for more than 1 year) showed more positive attitudes and better self-management ability in the pre-treatment and follow-up phases compared with the non-remission group (those who have been in glycemic remission for less than 1 year). Therefore, before newly diagnosed type 2 diabetes patients receive short-term intensive insulin therapy, clinicians and educational nurses should provide patients with detailed and adequate knowledge about diabetes and insulin application, as well as monitoring at the end of the program and guidance on subsequent treatment regimens, in order to strengthen patients’ confidence and ability to manage their disease with a view to improving the effectiveness of short-term intensive insulin therapy.
Type 2 diabetes management to win at the starting line
The starting treatment regimen for newly diagnosed type 2 diabetic patients is closely related to their prognosis, and short-term intensive insulin therapy has significant benefits for some newly diagnosed type 2 diabetic patients with high blood glucose (fasting glucose >11.1 mmol/L). Although more studies are still needed clinically to understand whether there are differences between different treatment regimens and courses, factors that affect patients’ remission rates and how to predict which patients are likely to achieve remission, they are now being carried out more widely in the clinic, and clinicians need to standardize the relevant clinical use so as to obtain the desired results.
In addition, the field of type 2 diabetes treatment has further expanded in recent years, with enteral hypoglycemia-based diabetes medications as well as surgical treatments being widely available. These treatment modalities have not only achieved excellent clinical efficacy, but also suggest the reversibility of the type 2 diabetes condition from several perspectives. Therefore, in order to develop better individualized treatment plans when dealing with newly diagnosed type 2 diabetic patients, we have to consider more needs beyond glycemic attainment, especially the possibility of clinical remission.