▲Dr. Banting (right) and his assistant Mr. Best with a dog used in the experiments (Image source: NobelPrize.org, Credits: University of Toronto Archives)

▋1965: Histopathological Studies of the Pancreas in Diabetes

Although the discovery of insulin revolutionized the treatment of diabetes, the pathophysiology of the disease remained unclear for several decades. In 1965, a landmark histological study revealed that in patients with early-onset diabetes (what we now call type 1 diabetes), insulin-producing β cells were greatly reduced (to less than 10% of normal levels), and most patients with acute disease showed inflammatory infiltrates around and within the pancreatic islets. This suggested that β cells were under attack by "external factors."

These histological features differed from those of late-onset diabetes (type 2 diabetes), in which β cell volume typically ranged from 40-50% of normal.

These studies of patients with early-onset diabetes helped elucidate the pathological processes occurring in the pancreatic islets of diabetic patients, ultimately leading to new therapies that improved patient outcomes.

▋1978: Pioneering Studies on Diabetic Complications

By the mid-20th century, the association between diabetes and a range of degenerative conditions—including neuropathy, retinopathy, and nephropathy—was already recognized. However, the precise link between these complications and glycemic control had not received sufficient attention. Belgian physician Jean Pirart published a 30-year longitudinal study in 1977 (first in French, translated into English in 1978) analyzing glycemic control and complication status in 4,398 diabetic patients. Over the first 25 years of the study, nearly 21,000 examinations were conducted. The number of patients and the duration of follow-up were unprecedented at the time. Pirart and his colleagues' findings revealed the association between glycemic control and complications, and demonstrated the potential to reduce complication risk through better blood sugar management.

▲The Genentech research team in the laboratory (Image source: Reference [2])

The U.S. FDA approved synthetic human insulin in 1982. It was the first product manufactured using genetic engineering to be approved by the FDA. This was not only a major advance in diabetes treatment but also a breakthrough in biotechnology, laying the groundwork for FDA approval of more therapeutic recombinant proteins. Today, the FDA has approved over 100 recombinant protein therapies.

▋1987: Uncovering the Role of Incretins

In 1986, the first large-scale randomized controlled trial aimed at reducing the incidence of type 2 diabetes through behavioral interventions (including healthy diet and/or exercise) was launched in Da Qing, China. The study enrolled 577 individuals with impaired glucose tolerance, who were randomly assigned to a control group (n=138) or one of three lifestyle intervention groups (n=438): diet, exercise, or diet plus exercise. The intervention period lasted 6 years.

After 6 years, the cumulative incidence of type 2 diabetes was 67.7% in the control group, 43.8% in the diet group, 41.1% in the exercise group, and 46% in the diet-plus-exercise group. This study demonstrated that a healthy diet and/or exercise could reduce the risk of developing type 2 diabetes.

In 2019, the 30-year follow-up results of the Da Qing Diabetes Prevention Study were published in The Lancet Diabetes & Endocrinology. The study showed that compared with the control group, the combined intervention group experienced a median delay in diabetes onset of 3.96 years and a 39% reduction in diabetes risk (HR 0.61, 95% CI 0.45–0.83; p=0.0015).

▋2006: Advancing Stem Cell Therapies for Diabetes

The establishment of the first human embryonic stem cell line in 1998 opened the door to using stem cell therapies for a variety of diseases. Type 1 diabetes is particularly well-suited for this strategy, as transplanting insulin-producing pancreatic β cells into patients could provide a long-term therapeutic effect, and even the possibility of a cure.

In 2006, a research team from Novocell (now Viacyte) published a paper in Nature Biotechnology describing the differentiation of human embryonic stem cells into endocrine pancreatic cells capable of secreting multiple hormones, including insulin and glucagon.

In 2008, the same team demonstrated that transplanting pancreatic endoderm derived from human embryonic stem cells into mice led to the differentiation of glucose-responsive endocrine cells in vivo, and showed that these cells could help protect the mice from hyperglycemia.

▋2014: "Artificial Pancreas" Systems Transform Patients' Lives

For patients with type 1 diabetes, maintaining blood glucose levels within the normal range can delay or prevent complications. However, the burden of having to monitor blood glucose multiple times a day and calculate insulin doses accordingly is significant.

Advances in continuous glucose monitoring systems and insulin delivery devices have finally enabled the development of "artificial pancreas" systems that combine glucose monitoring with insulin delivery. These systems use algorithms to calculate insulin doses and automatically administer the drug, greatly reducing the burden on patients.