How medical advances can help half a billion people living with diabetes

More than half a billion adults are living with diabetes around the world, representing a staggering five-fold surge in the past four decades. The sharp rise in cases represents a ticking healthcare time bomb – but significant advances made in medical treatment are offering hope that the impending crisis can be defused. The World Health Organisation reports the number of people with diabetes around the world rose from 108 million in 1980 to 422 million by 2014. The International Diabetes Federation said this number climbed to 537 million by 2021, and is estimated to reach 643 million by 2030. About 1.5 million deaths annually are blamed on the condition. The explosion in numbers is largely because more people are overweight or obese. But just as diabetes has become much more common, so treatments have moved on significantly. "I think we are in an incredibly fast-moving and transformative period and it’s a great honour to be clinically active in this period," said Dr Victoria Salem, a clinical senior lecturer in diabetes and endocrinology at Imperial College London. The overwhelming majority of people with the condition have Type 2 diabetes, the form that develops later in life and is often the result of lifestyle factors, primarily an unhealthy diet and a lack of exercise, that cause individuals to become overweight or obese, although genetics also play a role. Type 2 diabetes involves glucose levels in the blood climbing too high because the body does not produce enough insulin, the hormone that regulates blood glucose levels, or does not respond properly to it. With Type 1 diabetes, which is not linked to lifestyle, the immune system attacks the insulin-producing beta cells in the pancreas’s islets of Langerhans, so that not enough insulin is produced. Globally, about nine million people, according to 2017 figures, have Type 1 diabetes, with most diagnoses happening in richer nations. A major advance for Type 1 diabetics has been the development of the hybrid closed-loop system or artificial pancreas. This consists of a continuous glucose monitor that communicates with an insulin pump, which releases the required amount of the hormone to regulate glucose levels. Richard Holt, professor in diabetes and endocrinology at the University of Southampton in the UK, describes hybrid closed-loop systems as "a major step forward", helping patients to keep their glucose at appropriate levels and preventing hypoglycaemia, when concentrations fall dangerously low. They also prevent hyperglycaemia, when glucose levels are too high. In December, health regulators in the UK recommended that hybrid closed-loop systems should be introduced to many Type 1 diabetes patients over the following five years. The advent of continuous glucose monitors – small wearable devices that give updates every few minutes on glucose levels – was "truly transformative", Dr Salem said. These, she said, provide granular knowledge, allowing patients to improve blood-glucose control. Current delivery pumps, meanwhile, allow "very, very fine-tuned delivery" of insulin, which is typically synthesised by genetically engineered bacteria, a far cry from when it was taken from pigs or cattle. "What the hybrid closed-loop systems do is they add an AI-driven brain that allows those two technologies to communicate with one another," Dr Salem said. "So now we have an algorithm which is looking at your trends in blood-glucose in real time, is predicting what your blood glucose is about to do and can then feed back and tell the pump what it thinks it needs to do in terms of insulin delivery. "That has the potential to take out of the equation the necessity of a patient having to decide how much insulin to dose themselves with." AI takes away from patients the need to give themselves several insulin injections each day and to work out how much to give according to what they are eating or the exercise they are doing. Although "by far and away the vast majority" of patients are happy with closed-loop systems, Dr Salem said that they do not feel like a cure. "They still have to worry about the pump failing. They have to worry about the sensors falling off or running out. They have to worry about slight inaccuracies sometimes with the sensor," she said. "Some people have argued that the algorithms will never be good enough to produce the really fine level of blood-glucose control the human pancreas has evolved over millions of years to perform." Another step forward is coming from the use of stem cells to create insulin-producing beta cells that can be transplanted into Type 1 diabetics. These are an alternative to the transplantation into the liver of cells from deceased donors, who are in limited supply. It does not cure diabetes and is not suitable for patients, for example, who need large amounts of insulin or who have poor kidney function. Transplant recipients, whether they receive material from deceased donors, or beta cells produced in the laboratory, have to take immunosuppressants to stop their immune system from attacking the cells. This leads to an increased risk of severe infections and cancer, which outweighs the benefits for most patients, usually except those at risk of severe hypoglycaemic episodes. Vertex Pharmaceuticals, based in Boston in the US, is conducting clinical trials with a treatment called VX-880, which consists of islet cells with "standard immunosuppression". Based on what the company describes as "positive data", these trials are being expanded. Vertex is also trialling a treatment that consists of the VX-880 islet cells encapsulated in an immunoprotective device designed to eliminate the need for immunosuppressants. Another approach, still being researched by Vertex, involves gene-editing the islet cells so that they will not be attacked by the immune system. Vertex said "it’s too early to comment" on when its treatments for Type 1 diabetes might be introduced commercially. "We are focused on generating clinical data to support advancement of each therapy as expeditiously as possible for this patient population, who have serious and urgent unmet clinical needs," the company told The National . "Based on the data we’ve seen to date, we are very encouraged that VX-880 may be a potentially transformative therapy for the underlying cause of Type 1 diabetes." Dr Salem, too, is researching ways to eliminate the need for immunosuppression, carrying out laboratory work on materials that could be used as "a scaffold" in which to place cells before transplant to defend them from the immune system. "I think we’re a very long way from that … but what felt like science fiction when I was at medical school now feels like a tangible reality in the medium term," she said. Just as the technology to combat Type 1 diabetes is moving ahead, so efforts to deal with Type 2 are gaining traction, even if more people than ever are presenting with the condition. Type 2 diabetes can already, Dr Salem said, be cured or put into remission with weight loss, which may be aided by bariatric surgery, when the stomach is bypassed or reduced in size. There has been a large increase in the range of drugs to help people with Type 2 diabetes. "Our pharmacological armamentarium for Type 2 diabetes over the past couple of decades has absolutely exploded," Dr Salem said. A common drug used is metformin, which is known by various brand names and is often prescribed when efforts to combat the condition through exercise and diet have proved ineffective. Type 2 is, however, a "very heterogeneous" condition, Dr Salem said, and proves difficult to control in some patients. Patients who do not achieve remission and have an aggressive form of Type 2 diabetes may eventually suffer the failure of their beta cells and require insulin. Some receive islet transplants and also need a kidney transplant. Such patients could, like those with Type 1 diabetes, profit from receiving beta cells that have been derived from stem cells, Dr Salem said. Indeed recent reports claim that a man in China was "cured of Type 2 diabetes" after receiving laboratory-grown insulin-producing cells derived from stem cells. So, with more drugs now available, with stem-cell treatments emerging and with AI-controlled devices to regulate glucose levels being rolled out, treatment options for both forms of diabetes have improved significantly – and could yet take a further leap forward.

How medical advances can help half a billion people living with diabetes

Stem-cell therapies and more sophisticated pumps are emerging to deal with a condition that kills 1.5 million people every year