Inventory: 24 important milestones in the human fight against diabetes in the past 100 years

Source: Pharmaceutical Guanlan

Today (14 November) is United Nations Diabetes Day

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In 1986, a study published in the journal Science showed that the cytokine IL-1 has a direct role in mediating beta cell death
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This finding heralds a new understanding of the mechanisms associated with insulitis and provides a new approach to targeted therapy
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9.
1987: Revealing the role of incretin

In 1987, two important papers examined the relationship between glucagon-like peptide (GLP) and insulin secretion
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The researchers used synthetic and animal-derived GLP-1 fragments, which were found to stimulate insulin secretion in vitro
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These studies laid the foundation for further exploration of the function of GLP-1 in glucose homeostasis, ultimately driving the application and development of incretin-based therapies in the treatment of type 2 diabetes
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10.
1988: Discovery of glucose transporter 4 (GLUT4)

Research published in the journal Nature in 1988 showed that insulin-stimulated glucose transporters in muscle and adipose tissue are molecularly distinct from previously reported glucose transport systems
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The following year, the gene encoding this unique transporter was cloned and its chromosomal location was mapped by several different laboratories
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To reflect its similarity to the already cloned GLUT1-3 glucose transporter, the protein was named GLUT4
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11.
1992: The discovery of monogenic diabetes

In the early 1990s, genetic linkage analysis studies identified a new form of diabetes, monogenic diabetes, a disease caused by mutations in a single gene that interfere with beta cell function
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This discovery is considered an important milestone in the field, as it has profound implications for the clinical care and prognosis of patients
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12.
1993: TNF blocks insulin receptor signaling

In two papers published in 1993 and 1995, scientists found that the proinflammatory cytokine tumor necrosis factor (TNF) was upregulated in the adipose tissue of obese animals and obese humans, and that blocking TNF improved insulin sensitivity in obese animal models sex
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Following this, a 1996 study also identified the molecular basis of TNF-driven insulin resistance
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13.
1993: Blood sugar control prevents diabetes complications

Complications of type 1 "insulin-dependent" diabetes include microvascular, neurological and macrovascular sequelae
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In 1983, the Diabetes Control and Complications Trial (DCCT) began recruiting patients to examine whether intensive treatment could improve outcomes in patients with type 1 diabetes
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The approach to intensive therapy is to use an external pump or insulin injections 3 or more times a day to keep blood sugar in the non-diabetic range as safely as possible
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In 1993, the results of the Diabetes Control and Complications Trial were published
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The trial showed that intensive treatment significantly reduced diabetes complications
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The publication of the trial results marks the emergence of intensive therapy as the new standard of care for patients with insulin-dependent diabetes
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14.
1995: The role of bariatric surgery in type 2 diabetes

Research published in 1995 showed that a group of obese patients treated with bariatric surgery experienced significant relief of type 2 diabetes symptoms
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Currently, bariatric surgery remains one of the most effective treatment options for this disease
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15.
1997: Daqing study reveals the impact of healthy life>

In 1986, the first large randomized controlled trial aimed at reducing the incidence of type 2 diabetes through behavioral interventions, including healthy diet and/or exercise, was initiated in Daqing, China
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The researchers enrolled 577 individuals with impaired glucose tolerance and randomized them to a control group or to one of three life>
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In 1997, the Daqing study reported that, compared with placebo, individuals with impaired glucose tolerance had a statistically significant reduction in the incidence of type 2 diabetes after 6 years of dietary and/or exercise behavioral interventions
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In 2019, the 30-year follow-up results of the Daqing Diabetes Prevention Study were published in The Lancet
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The study showed that the combined intervention group had a median delay in the onset of diabetes of 3.
96 years and a 39% lower risk of developing diabetes compared with the control group
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16.
2000: Inheritance of type 2 diabetes discovered

In 2000, researchers published a groundbreaking genetic association study that identified PPARG as a susceptibility gene for type 2 diabetes
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At present, research in this field has made great progress, and more than 550 type 2 diabetes risk signals have been identified
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Valuable knowledge gained from these genetic factors has been used in the study of disease mechanisms and treatments, and may form the basis of future precision medicine approaches
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17.
2002: CD3-specific antibody first shown to slow the loss of beta cell function in patients with type 1 diabetes

In 2002, Kevan Herold et al.
published the results of a small clinical trial of patients with recently diagnosed type 1 diabetes who received dose-escalating doses of the CD3-specific monoclonal antibody teplizumab over two weeks
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The study found that patients who received a single short-term treatment with CD3 mAb showed a slower deterioration in beta-cell function over a 12-month period
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In addition, the study also found that relatively low doses of CD3 mAb treatment appeared to have a durable effect on the immune response, suggesting the potential to "rewire" the immune response to a state of tolerance
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In 2005, other investigators conducted a larger phase 2 study using another CD3-specific mAb, otelixizumab, in patients with newly diagnosed type 1 diabetes
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The study also showed that brief CD3 mAb treatment improved preservation of beta cell function during an 18-month follow-up period
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At present, researchers are still conducting research on CD3-specific antibodies in human type 1 diabetes
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18.
2006: Towards stem cell therapy for diabetes

The creation of human embryonic stem cell lines has opened up the possibility of using stem cell therapy to treat a variety of diseases, and type 1 diabetes is particularly well suited for this strategy
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Transplanting insulin-producing islet beta cells into patients may offer therapies with long-term efficacy, and even the possibility of a cure
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In 2006, the research team of Novocell (now Viacyte) published a paper in Nature Biotechnology, describing the process of differentiating human embryonic stem cells into endocrine islet cells that can secrete various hormones such as insulin and glucagon
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In 2008, the team successfully differentiated glucose-sensitive endocrine cells in animals by transplanting islet endoderm differentiated from human embryonic stem cells into mice, and demonstrated that these cells can help mice resist hyperglycemia
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19.
2007: Islet inflammation found in type 2 diabetes

In 2007, a study from Marc Donath and colleagues showed that insulitis is a pathological feature of type 2 diabetes as well as type 1 diabetes, a finding that paved the way for further exploration of inflammasome activation and anti-inflammatory therapy in type 2 diabetes.
road
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20.
2012: Published the first clinical data on Treg cells in the treatment of type 1 diabetes

Marek-Trzonkowska et al.
published the results of the first clinical trial of regulatory T cells (Treg cells) in patients with type 1 diabetes in 2012 and 2014
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In a small pilot study of children with recent-onset type 1 diabetes, treatment with Treg cells was found to be safe and tolerable, and reduced the need for exogenous insulin
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A year later, the researchers further reported that repeated treatment of Treg cells was safe and prolonged beta cell survival
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Moreover, the results of this follow-up also showed that, compared with the control group, patients treated with Treg therapy had statistically lower insulin requirements
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21.
2014: "Artificial Pancreas" System Changes Patients' Lives

In 2014, Russell et al.
reported the first results of a randomized crossover trial using a wearable "artificial pancreas" drug delivery system compared to insulin pump therapy
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The "artificial pancreas" system can automatically deliver insulin or glucagon
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Trial results showed that the "artificial pancreas" system provided better blood sugar control in adolescents and adults with type 1 diabetes than an insulin pump
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Today, several "artificial pancreas" systems have been approved in the U.
S.
and Europe, and more are being tested in large clinical trials, hopefully helping more patients reduce the burden of managing their diabetes on a daily basis
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22.
2016: The role of incretin drugs in controlling blood sugar

Incretin drugs include glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 (DPP-4) inhibitors, which use GLP-1's effect on insulin production.
effect to improve glycemic control
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A systematic review and comparative analysis published in 2016 showed that GLP-1 receptor agonists were well tolerated
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Moreover, multiple clinical trials have shown that GLP-1 receptor agonists can reduce the risk of atherosclerotic cardiovascular disease and the risk of kidney disease in patients with type 2 diabetes compared with placebo
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In addition, clinical studies have shown that GLP-1RA drugs promote weight loss and reduce the risk of atherosclerotic cardiovascular disease and kidneys in people with type 2 diabetes
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23.
2019: Revealing the infectious cause of type 1 diabetes?

In 2002, clinical centers in the United States and Europe began recruiting young children to study the environmental causes of type 1 diabetes (TEDDY study)
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Based on this research, a paper published in 2019 showed that chronic type B enterovirus infection plays a role in the development of type 1 diabetes in young children, which is a major advance in human understanding of the link between the virome and type 1 diabetes.

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24.
2019: The role of next-generation hypoglycemic therapy in reducing cardiovascular disease

A meta-analysis published in 2019 showed that in 3 large clinical trials involving 34,322 patients, different SGLT2 inhibitors reduced the odds of major adverse cardiovascular events by 11%
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In addition, SGLT2 inhibitors have also shown benefits in reducing the risk of chronic kidney disease
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These benefits were subsequently validated in patients with heart failure and chronic kidney disease without type 2 diabetes
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Another meta-analysis published in 2019 found that GLP-1 receptor agonists were also able to reduce the rate of major adverse cardiovascular events by 12% in multiple clinical trials
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These added benefits of a new generation of glucose-lowering therapies are revolutionizing the management of type 2 diabetes
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Today, with the continuous breakthroughs and innovations of scientists, diabetes has changed from a fatal emergency to a manageable chronic disease
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Facing the future, we sincerely look forward to the advent of more updated diabetes therapies, effective treatment or even prevention for patients, and an early elimination of the threat of diabetes to human health
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