Editor's note
Type 2 diabetes mellitus (T2DM) is characterized by persistent hyperglycemia and has traditionally been thought to be an irreversible condition that requires lifelong medication to control blood sugar. Several clinical trials in recent years have shown that remission of type 2 diabetes can be achieved in patients who are overweight or obese with sustained weight control through bariatric surgery [1, 2] or lifestyle interventions [3, 4]. In the STAMPEDE study, approximately one-third of obese patients with T2DM had glycosylated hemoglobin (HbA1c) levels below 6 percent one year after bariatric surgery in the absence of glucose-lowering drugs (GLDs) [1]. The DiRECT study also showed that approximately half of patients with T2DM had less than 6.5 percent HbA1c levels in the absence of GLDs after losing an average of 10 kg of body weight over a 12-month period with a weight management intervention [3]. However, due to the short follow-up time of clinical trials, the long-term remission rate, sustainability, and benefit of diabetes are largely unknown. A RECENT STUDY FROM HONG KONG, CHINA, PUBLISHED IN THE JOURNAL PLOS MEDICINE, SEEMS TO GIVE US SOME HINTS.
Data from 37 326 patients with T2DM in Hong Kong, China were included
The research team included patients with newly diagnosed T2DM (self-reported duration of diabetes < 1 year) in the Diabetes Risk Assessment and Management Program (RAMP-DM) from January 1, 2000 ~ December 31, 2017, in which about 60% of diabetes patients in Hong Kong participated. Exclusion criteria include: those under the age of 18 years and over 75 years, extreme body mass index (BMI) (<15 or >50kg/m2), weight change value (%) outside 0.1%~99.9% within 1 year or missing weight change data, patients with previous cardiovascular disease/malignancy or end-stage renal disease, no use of any GLDs but did not achieve HbA1c ≥6.5% (48 mmol/ / mol) or patients with diabetes mellitus in remission and patients taking insulin at baseline. Finally, 37 326 patients with newly diagnosed T2DM were included. During the analysis, the patients were divided into 4 categories according to the change in body weight within 1 year: weight loss ≥10%, weight loss 5%~9.9%, weight loss 0%~4.9%, and weight gain.
Primary Endpoint: To assess the relationship between weight change (%) at 1 year after diabetes diagnosis and long-term incidence of diabetes and sustainability of diabetes remission. Secondary endpoints: (1) recurrence of hyperglycemia, defined as HbA1c ≥6.5% or use of GLDs in patients in remission of diabetes; (2) All-cause mortality in patients in remission and non-remission diabetes and mortality due to malignant tumors, cardiovascular diseases, and lung infections.
Diabetes mellitus remission is defined as two or more consecutive HbA1c <6.5 percent without any documented use of any GLDs for at least three months [5, 6]. The date of the first HbA1c < 6.5% was taken as the date of the diabetes remitting event.
The more weight you lose, the more you benefit
During a median follow-up of 7.9 years, 6.1% (2279 patients, 7.8/1000 person-years) achieved diabetes remission (see Figure 1A). After adjusting for factors such as age at diagnosis of diabetes, gender, year of assessment, BMI, other metabolic indicators, smoking, alcohol consumption, and drug use, compared with those who gained weight≥, the HR=3.28 (95%Cl: 2.75~3.92; P<0.001), HR=2.29 (95%Cl: 2.03~2.59; P<0.001), HR=1.34 (95%Cl: 1.22~1.47; P<0.001) (Figure 2A).
During a median follow-up of 3.1 years, 67.2% (1531) of patients in remission had recurrence of hyperglycemia, with an incidence of 184.8 per 1000 person-years (95% Cl: 175.5, 194.0) (see Figure 1B). Compared with patients with weight gain, patients with weight loss ≥ 10% had the adjusted HR=0.52 (95%Cl: 0.41~0.65; P<0.001), HR=0.78 (95%Cl: 0.68~0.92; P=0.002), HR=0.90 (95%Cl: 0.80~1.01; P=0.073) (Fig. 2B).
Figure 1. Kaplan-Meier curves of the cumulative incidence of diabetes remission (A) and the cumulative incidence of diabetes relapse (B) during the follow-up period
Figure 2. Relationship between changes in body weight and waist circumference and remission of diabetes mellitus (A) and re-elevation of blood glucose (B)
During the median follow-up of 7.9 years, a total of 2163 deaths were reported, and remission of diabetes mellitus reduced the risk of all-cause mortality by 31% (HR=0.69, 95%Cl: 0.52~0.93; P=0.014). In patients with relapsing hyperglycemia after remission of diabetes, HR for all-cause mortality decreases with prolonged remission.
The ideal of "diabetes remission" can also be achieved in a real-world environment
The main limitation of the study is that the reliability of HbA1c used to define remission in diabetes may be affected by other medical conditions. In addition, the research team also said that no data on bariatric surgery were included.
In the real world, remission of T2DM is achievable, but with conventional management, the incidence of diabetic remission and the likelihood of its long-term sustainability are low, so the incidence of re-elevation of blood glucose is high. Patients who lost more weight (%) within 1 year of diabetes diagnosis were more likely to achieve diabetes remission and have a lower risk of recurrence of hyperglycemia than those who gained weight. Therefore, in the face of some external conditions that are difficult to change, such as patients' treatment philosophy, economic status, and social status, the implementation of early weight management interventions can also be regarded as an important measure to alleviate diabetes.
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