A Review of the Latest Research on Diabetes

Diabetes is a chronic condition that affects the way the body regulates blood sugar (glucose). Glucose is the main source of energy for the cells, but it needs insulin, a hormone produced by the pancreas, to enter the cells. In diabetes, either the pancreas does not produce enough insulin, or the cells do not respond well to insulin, or both. This causes high blood glucose levels, which can lead to various complications, such as heart disease, kidney disease, nerve damage, eye damage, and foot problems¹

According to the World Health Organization (WHO), the number of people with diabetes rose from 108 million in 1980 to 422 million in 2014. The prevalence of diabetes has been rising more rapidly in low- and middle-income countries than in high-income countries. Diabetes is a major cause of blindness, kidney failure, heart attacks, stroke and lower limb amputation. In 2016, an estimated 1.6 million deaths were directly caused by diabetes, and another 2.2 million deaths were attributable to high blood glucose²

There are two main types of diabetes: type 1 and type 2. Type 1 diabetes is an autoimmune disease, in which the immune system mistakenly attacks and destroys the insulin-producing beta cells in the pancreas. Type 1 diabetes usually occurs in childhood or adolescence, and requires lifelong insulin therapy. Type 2 diabetes is more common and accounts for about 90% of all cases of diabetes. Type 2 diabetes is caused by a combination of genetic and environmental factors, such as obesity, physical inactivity, poor diet, and aging. Type 2 diabetes can be prevented or delayed by adopting a healthy lifestyle, and can be managed by oral medications, insulin, or both¹

In addition to type 1 and type 2 diabetes, there are other specific types of diabetes, such as gestational diabetes, which occurs during pregnancy and may increase the risk of complications for both mother and child; and monogenic diabetes, which is caused by mutations in a single gene and affects about 1-2% of all cases of diabetes¹

Diabetes is a complex and challenging disease that requires constant monitoring and management. However, there is hope for better prevention, diagnosis, treatment, and cure of diabetes, thanks to the advances in scientific research. In this article, we will review some of the latest and most promising research findings on diabetes, covering topics such as the causes and mechanisms of diabetes, the development of new therapies and technologies, and the identification of new biomarkers and risk factors.

Causes and Mechanisms of Diabetes

One of the key questions in diabetes research is what causes the dysfunction or destruction of the beta cells, and how this can be prevented or reversed. Understanding the molecular and cellular mechanisms of beta cell biology is essential for developing novel strategies to preserve or restore beta cell function and mass.

Type 1 Diabetes

Type 1 diabetes is caused by an autoimmune attack of the beta cells, mediated by immune cells called T cells. However, the exact triggers and pathways of this attack are not fully understood. One of the recent discoveries in this field is the identification of a new type of molecule that may explain why the immune system mistakenly recognizes the beta cells as foreign. These molecules are called hybrid insulin peptides (HIPs), and they are formed by the fusion of insulin fragments with other proteins in the beta cells. Dr. Delong and his colleagues found that HIPs are present on the surface of the beta cells of people with type 1 diabetes, and that they are recognized as foreign by their T cells. Moreover, they found that even after the onset of diabetes, T cells that react to HIPs are still present in the blood, suggesting that they may contribute to the progression of the disease. The researchers hope that HIPs can serve as a biomarker or a therapeutic target for type 1 diabetes³

Another important aspect of type 1 diabetes research is the role of environmental factors, such as viruses, toxins, diet, and stress, in triggering or modulating the autoimmune response. One of the hypotheses is that certain viruses, such as enteroviruses, can infect the beta cells and induce inflammation and cell death, or mimic the beta cell antigens and induce cross-reactivity with the immune system. Dr. Richardson and his colleagues tested this hypothesis by analyzing the viral RNA in the pancreas of people who died of type 1 diabetes or other causes. They found that enteroviruses were more prevalent and abundant in the pancreas of people with type 1 diabetes, and that they were associated with increased inflammation and reduced insulin expression. They also found that enteroviruses could infect human beta cells in vitro and impair their function and survival. These findings suggest that enteroviruses may play a causal role in type 1 diabetes, and that antiviral therapies may be beneficial for preventing or treating the disease.

Type 2 Diabetes

Type 2 diabetes is caused by a combination of insulin resistance and beta cell failure. Insulin resistance is a condition in which the cells do not respond well to insulin, and require more insulin to maintain normal blood glucose levels. Beta cell failure is a condition in which the beta cells cannot produce enough insulin to overcome the insulin resistance, and gradually lose their function and mass. The mechanisms of insulin resistance and beta cell failure are complex and multifactorial, involving genetic, epigenetic, metabolic, inflammatory, oxidative, and hormonal factors.

One of the recent advances in understanding the causes of insulin resistance is the discovery of a new type of fat cell that may contribute to the development of metabolic disorders. These fat cells are called adipose progenitor cells (APCs), and they are immature fat cells that can differentiate into mature fat cells (adipocytes) or other cell types. Dr. Rodeheffer and his colleagues found that APCs are increased in the fat tissue of obese mice and humans, and that they secrete a protein called WISP1, which can impair the insulin signaling and glucose uptake in muscle cells. They also found that blocking WISP1 or reducing APCs can improve the insulin sensitivity and glucose tolerance in obese mice. These findings suggest that APCs and WISP1 may be novel targets for treating insulin resistance and type 2 diabetes.

Another recent advance in understanding the causes of beta cell failure is the discovery of a new mechanism that may explain how high blood glucose levels can damage the beta cells. This mechanism is called the thioredoxin-interacting protein (TXNIP) pathway, and it involves a protein that can sense the glucose levels and activate a stress response in the beta cells. Dr. Shalev and his colleagues found that TXNIP is increased in the beta cells of diabetic mice and humans, and that it can induce the expression of a gene called NLRP3, which can trigger inflammation and cell death in the beta cells. They also found that blocking TXNIP or NLRP3 can protect the beta cells from high glucose-induced damage and improve the glucose control in diabetic mice. These findings suggest that TXNIP and NLRP3 may be potential targets for preventing or treating beta cell failure and type 2 diabetes.

Development of New Therapies and Technologies

Another key goal of diabetes research is to develop new and better therapies and technologies to help people with diabetes manage their condition and improve their quality of life. These therapies and technologies include new drugs, devices, cell therapies, gene therapies, and artificial pancreas systems.

New Drugs

One of the challenges of diabetes treatment is to find drugs that can lower the blood glucose levels without causing hypoglycemia (low blood glucose levels) or weight gain, which are common side effects of some of the current drugs. One of the promising classes of drugs that can achieve this goal is the glucagon-like peptide-1 receptor (GLP-1R) agonists. GLP-1R agonists are synthetic molecules that mimic the action of a natural hormone called GLP-1, which is secreted by the gut in response to food intake. GLP-1 can stimulate the beta cells to produce more insulin, inhibit the liver from producing more glucose, and reduce the appetite and food intake. GLP-1R agonists have been shown to lower the blood glucose levels, reduce the risk of cardiovascular events, and promote weight loss in people with type 2 diabetes. However, GLP-1R agonists have some limitations, such as the need for injection, the short duration of action, and the gastrointestinal side effects. Therefore, researchers are trying to develop new and improved GLP-1R agonists that can overcome these limitations.

One of the recent examples of such efforts is the development of a new GLP-1R agonist called semaglutide, which can be taken orally once a day. Dr. Davies and his colleagues conducted a large clinical trial to compare the efficacy and safety of oral semaglutide with placebo or another oral drug called empagliflozin in people with type 2 diabetes. They found that oral semaglutide was superior to placebo and empagliflozin in lowering the blood glucose levels and the hemoglobin A1c (HbA1c), which is a measure of the average blood glucose levels over the past three months. They also found that oral semaglutide was superior to placebo and empagliflozin in reducing the body weight and the systolic blood pressure. The most common side effects of oral semaglutide were mild to moderate nausea and diarrhea, which decreased over time. These findings suggest that oral