Banting Medal recipient recounts significant discoveries from five decades of impactful diabetes research
The UK Prospective Diabetes Study (UKPDS) conclusively revealed that complications related to type 2 diabetes that were previously considered untreatable could be improved with precise management of blood glucose and blood pressure control.
The landmark randomized, controlled, clinical outcomes trial recruited more than 5,000 participants and collected data over 20 years, from 1977 to 1997, which led to more than 120 subsequently published manuscripts.
Rury R. Holman, MBChB, FRCP(Lond), FMedSci, Emeritus Professor of Diabetic Medicine at the University of Oxford Radcliffe Department of Medicine, United Kingdom, who co-led the UKPDS with his mentor and friend Robert Turner, MD, FRCP, was recognized as the recipient of the 2024 Banting Medal for Scientific Achievement by the American Diabetes Association® (ADA) for his significant and lasting contributions to the understanding, treatments, and prevention of diabetes.
The UKPDS found that progressive hyperglycemia is a key feature of type 2 diabetes driven by the declining function of beta-cells, as opposed to insulin resistance.
• Among the wide-ranging discoveries from this research, hyperglycemia was shown to be a significant independent modifiable risk factor for coronary heart disease, along with the previously acknowledged “deadly quartet” of high LDL cholesterol, low HDL cholesterol, increased systolic blood pressure, and smoking.
“And so, the deadly quartet became the deadly quintet,” Dr. Holman explained.
• The UKPDS also identified the deadly combination of diabetes and hypertension, a condition that was subsequently coined “double jeopardy.”
“Participants with hypertension in addition to type 2 diabetes were at an 82 percent significantly higher risk of diabetes-related death,” Dr. Homan said.
• He spotlighted two more significant findings from the UKPDS research: the glycemic and metformin legacy effects.
The glycemic legacy effect highlights the need to optimize glycemic control after a type 2 diabetes diagnosis to mitigate the impact of early exposure to hyperglycemia.
“I believe the glycemic legacy effect is actually a hyperglycemic legacy effect,” Dr. Holman clarified. “Poor glucose control can induce irreversible pathological changes that permanently increase the risk of diabetic complications and premature death.”
• He emphasized the importance of establishing and maintaining near-normoglycemia as early as possible once a patient is diagnosed with type 2 diabetes to minimize the risks of complications and prolong life.
The metformin legacy effect refers to finding the multitudinous benefits metformin therapy offers patients with type 2 diabetes compared with conventional therapy. These results included a 32 percent relative risk reduction in any diabetes-related endpoint measured in the UKPDS and an enduring risk reduction for all-cause mortality.
• The first UKPDS results were presented in Barcelona in 1998. Five papers from the UKPDS research team were simultaneously published in the September 1998 edition of The Lancet, a record that remains unbroken today. In 1999, Dr. Holman and the UKPDS investigative team were awarded the ADA Charles H. Best Award.
In addition to the UKPDS, Dr. Holman made several key contributions to the field of diabetes management. He invented the Autolet, the first automated lancet that pricked patients’ fingers at the touch of a button and instantly withdrew the needle, making the process much easier and less painful than previous home tests. He also recognized that drawing insulin from vials can be difficult, particularly for elderly patients. In response, he invented the Autopen, the world’s first automated insulin pen.
Dr. Holman is still an active investigator, publishing approximately two papers each month by analyzing data from the many trials he has led and participated in throughout his career. He is also currently co-chairing a three-year Alzheimer’s prevention trial.
“My take-home message for all young researchers is to be sure to follow your vision, be prepared to take risks, and look out for serendipity,” Dr. Holman concluded.
The Banting Medal is given in memory of Sir Frederick Banting, a medical scientist, doctor, and Nobel laureate who is noted as one of the key investigators in the discovery of insulin.
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