A quick look at the highlights of hot research at the 2024 ADA Annual Meeting.
From June 21 to 24, 2024, the 84th Annual Meeting of the American Diabetes Association (ADA) was held in Orlando, USA, bringing together diabetes experts from around the world to discuss the latest developments in the field of diabetes. The conference condenses practical application and clinical innovation, and strives to improve the comprehensive prevention and treatment of diabetes, so as to benefit the health and well-being of all mankind.
As one of the important and indispensable treatments for diabetes, insulin is a topic of great concern in the annual ADA academic event, so what are the latest research on insulin application at this ADA annual meeting? From point to point, what are the cutting-edge research results in the field of diabetes management at the annual meeting? This article selects and sorts out the highlights of the annual meeting for readers.
Accumulating data from China, the CREATE study has added new evidence to the use of insulin
The CREATE study (abstract number: 19-PUB), which debuted at this year's ADA Annual Meeting, is the first real-world study of insulin degludec aspart in China, which fills the gap in the real-world data of insulin degludec aspart in Chinese patients with T2DM, and also provides evidence for clinical medical workers in mainland China to better use insulin degludec aspart.
CREATE is a prospective, non-interventional, open-label study evaluating glycemic control in Chinese adults with type 2 diabetes mellitus (T2DM) initiated or switched to insulin degludec aspart in the treatment of Chinese adults. The study included adult patients with T2DM who had received prior oral hypoglycemic drugs (OADs), basal insulin, basal-meal insulin, premixed insulin, and glucagon-like peptide-1 receptor agonist (GLP-1RA) ± insulin for 20 weeks of continuous follow-up at 50 sites nationwide, and were initiated or switched to insulin degludec aspart to observe its real-world efficacy and safety. The primary endpoint of the study was the change in glycosylated hemoglobin (HbA1c) from baseline to week 20, and the secondary endpoints were the change in fasting blood glucose (FPG) and the change in the rate of hypoglycemic events.
A total of 878 adult patients with T2DM (57.4% male; mean age 59.6 years), once (47.2%) or twice (52.2%) daily with insulin degludec aspart. After initiation or switching to insulin degludec aspart:
● Mean HbA1c was significantly reduced by 1.27% (95% CI -1.36; -1.19, p<0.0001) (Figure 1).
● 平均FPG显著下降1.61mmol/L（95%CI -1.81；-1.41，p<0.0001）。
● Fewer non-serious hypoglycemic events at 20 weeks compared to baseline (45 versus 115).
Fig.1 Change from baseline in HbA1c after initiation or conversion to insulin degludec aspart therapy Note: p<0.0001 compared to the end of the study
Studies have shown that initiation or switching to insulin degludec aspart improves glycemic control in real-world adult T2DM patients in China.
Classical research and scientific and technological innovation complement each other,
The ADA Annual Meeting is full of energy
The prevention, diagnosis, and treatment of diabetes mellitus and its complications are important research topics in the academic community, and some of the landmark studies have greatly promoted the development of diabetes management in the world, such as the famous British Prospective Diabetes Study (UKPDS) [1] and the Daqing study in mainland China [2]. Over the years, these classic studies have not stopped exploring, and the latest follow-up results obtained have received people's attention and attention at this ADA annual meeting. Notably, one of the outstanding contributions of Professor Rury R. Holman, winner of the 2024 Banting Scientific Achievement Award, is co-leading the UKPDS study.
In addition, with the rapid development of science and technology, artificial intelligence technology is also being more and more widely used in the field of diabetes research. Under the collision of classic research and scientific and technological innovation, this ADA annual meeting burst out with extraordinary vitality. Let's take a look at the research!
● Extension of post-trial surveillance from 10 to 24 years in a randomized controlled trial investigating a 1:1:2 randomized controlled trial of intensive glycaemic control in patients with type 2 diabetes (UKPDS 91) (DOI: 10.1016/S0140-6736(24)00537-3)
(Swipe up and down to see all the information)
Background: The 20-year UKPDS study showed significant clinical benefit in patients with newly diagnosed type 2 diabetes randomized to intensive glycaemic control with sulfonylureas, insulin, or metformin compared with conventional glycaemic control. Subsequently, the results of a 10-year follow-up study further confirmed the ongoing benefit and the long-term effects of metformin treatment. The UKPDS 91 study was followed up for an additional 14 years on top of the 10-year follow-up to determine whether these benefits could be sustained.
Methods: Between 1977 and 1991, 5102 patients were enrolled, of whom 4209 (82.5%) were initially randomized to receive intensive glycemic control (sulfonylureas or insulin, or metformin if overweight) or conventional glycemic control (primarily dietary interventions). At the end of the 20-year interventional trial, 3,277 surviving participants entered a 10-year post-trial monitoring period that lasted until 2007-09-30. Eligible participants in this study are all surviving participants at the end of the 10-year post-trial monitoring period. These participants were followed up for an extended period of another 14 years by linking them to the National Health Service (NHS) data they routinely collected. Clinical outcomes were derived from records of deaths, hospitalizations, outpatient visits, accidents, and emergency room visits. Using Kaplan–Meier event occurrence time and log-rank analysis, the research team examined seven prespecified composite clinical outcomes (i.e., any diabetes-related endpoints, diabetes-related death, all-cause death, myocardial infarction, stroke, peripheral vascular disease, and microvascular disease) by randomized glycemic control strategies on an intention-to-treat basis.
Results: Between 01.10.2007 and 30.09.2021, 1489 out of 1525 participants (97.6%) could be associated with routinely collected NHS management data. Their mean age at baseline was 50.2 years (SD 8.0) and 41.3% were female. As of 2021-09-30, the mean age of surviving patients was 79.9 years (SD 8.0). Individual follow-up from baseline ranged from 0 to 42 years, with a median of 17.5 years (IQR 12.3 to 26.8). Overall follow-up increased by 21%, from 66,972-years to 80,724-years. Up to 24 years after the end of the trial, blood glucose and metformin carryover showed no signs of abating. Early intensive glycemic control with sulfonylureas or insulin therapy showed a 10% (95% CI 2-17; p=0.015) reduction in the overall relative risk of all-cause mortality and a 17% reduction in myocardial infarction (6-26; p=0.002), and microvascular disease decreased by 26% (14-36; p<0.0001）。 The corresponding absolute risk reductions were 2.7%, 3.3% and 3.5%, respectively. Early intensive glycemic control with metformin therapy showed a 20% overall relative risk of all-cause mortality and a 31% reduction in the overall relative risk of myocardial infarction compared with conventional glycemic control (95% CI 5-32; p=0.010; p=0.003）。 The corresponding absolute risk reductions were 4.9% and 6.2%, respectively. No significant reduction in the risk of stroke or peripheral vascular disease was observed in the two intensive glycemic control groups, nor was a significant reduction in the risk of microvascular disease treated with metformin during or after the trial.
Conclusions: Early intensive glycaemic control with sulfonylureas or insulin or metformin appears to reduce the risk of death and myocardial infarction almost for life compared with conventional glycaemic control. Controlling blood sugar to near-normal levels immediately after diagnosis is essential to minimize the lifetime risk of diabetes-related complications.
● Study 2: Changes in the incidence of stroke in newly diagnosed patients with diabetes and impaired glucose tolerance during the 34-year follow-up in the Daqing Diabetes and Diabetes Prevention Study from 1986 to 2020 (Abstract No.: 1270-P)
(Swipe up and down to see all the information)
Background: Stroke is the leading cause of death in the Chinese population, however, the incidence and risk of stroke attributable to stroke in adults with diabetes and prediabetes have not been quantified. The aim of this study is to observe the evolution of stroke incidence in adults with diabetes and impaired glucose tolerance over a 34-year follow-up period.
Methods: An observational study was conducted in 1632 participants, including 598 individuals with newly diagnosed diabetes mellitus (NDD), 540 individuals with impaired glucose tolerance (IGT), and 494 individuals with normoglucose tolerance (NGT), who were initially identified in 1986 and followed up to 34 years. Studies compared stroke incidence and risk ratios between these groups and estimated differences in median delay time to stroke onset based on the parametric Weibull distribution model.
Results: At 34 years of follow-up, the cumulative incidence of stroke was 65.4%, 62.8%, 49.8%, and 38.2% in the NDD, IGT, IGT, and NGT groups, respectively. After adjusting for covariance, the risk of stroke at 34 years was significantly higher in the NDD group (HR 1.81; 95% CI 1.47-2.72), the IGT non-intervention group (HR 1.63; 95% CI 1.22-2.18), and the IGT intervention group (HR 1.39; 95% CI 1.11-1.73) compared with the NGT group. The median delay in stroke onset was 16.82 years (95% CI 6.50-15.57) in the NGT group and 7.84 years (95% CI 4.19-11.48) in the IGT intervention group compared with the NDD group. Notably, a subgroup analysis of women showed a significantly lower risk of stroke in the IGT intervention group than in the NDD group (HR 0.64; 95% CI 0.47-0.88) and comparable to that in the NGT control group (HR 0.99; 95% CI 0.69-1.40).
Conclusions: More than half of the newly diagnosed type 2 diabetes and IGT adults in China have a stroke over a 34-year period. Lifestyle interventions for women with IGT may be beneficial in reducing the risk of stroke.
● Study 3: Using a Human Digital Twin to Predict Insulin Duration in Prediabetic Patients (Abstract Number: 1854-LB)
(Swipe up and down to see all the information)
Background: Individuals with early prediabetes often present with mildly elevated or even normal blood glucose levels. However, their insulin profiles are often dysregulated in hyperinsulinemia or hypoinsulinemia, suggesting that insulin is a more sensitive biomarker for prediabetes detection.
Methods: The research team developed a human digital twin model that can predict an individual's insulin duration and blood glucose status based on the oral glucose tolerance test (OGTT) time course. This model combines homeostatic processes in fat and muscle, such as insulin secretion and glucose uptake. The model provides individualized data such as age, body mass index (BMI), and OGTT glucose time course to predict insulin status. Overlays of clinical and simulated glucose and insulin curves are shown in Figure 2.
Fig.2 Clinical and simulated glucose and insulin concentration-time curves
Results: The model accurately predicted the insulin duration, area under the curve (AUC) and Matsuda index of 3 Chinese men, 1 healthy (1 subject), 1 insulin insufficiency (2) and 1 insulin resistance (3). The fold change between the predicted and actual insulin AUC and the Matsuda index was within 1.5 times.
Conclusion: The study demonstrates the high accuracy of the model in predicting hard-to-obtain insulin data using readily available glucose data. The research team hopes to use more validation and use of the model to predict insulin-related indicators in different ethnicities and blood glucose states.
brief summary
The 84th ADA Annual Meeting brings together global diabetes experts and scholars with cutting-edge research from around the world, colliding with profound insights and innovations in the field of diabetes management. The CREATE study has accumulated real-world data on insulin gludecaspart in Chinese T2DM patients, which has brought new enlightenment to the domestic T2DM treatment strategy. In addition, while paying tribute to classic research, the annual meeting closely followed the frontier of science and technology, explored the innovative application of artificial intelligence technology in the field of diabetes, and provided new ideas for the global diabetes prevention and treatment.
参考文献[1]King P, et al. British journal of clinical pharmacology, 1999, 48(5): 643. [2] Pan XR, et al. Diabetes care. 1997; 20(4):537-544.
Source of this article: Endocrinology Channel in the medical community
The content of this video/information/article is not intended to be a substitute for professional medical guidance in any way and should not be construed as medical advice. Yimaitong is a professional online doctor platform, and the mission of the platform is to "sense the pulse of the world's medicine and help China's clinical decision-making". Yimaitong has a series of products such as "Clinical Guidelines", "Medication Reference", "Medical Literature King", "Yizhiyuan", "eYantong" and "ePulse", which fully meet the needs of medical workers in clinical decision-making, obtaining new knowledge and improving scientific research efficiency.