Introduction
The evolution of insulin therapy
Innovative technological advancements for diabetes management
Discovering the role of new genes in diabetes
Breakthroughs in alternative therapies
Towards a cure: promising research in 2023
Conclusion
References
Further reading
Recent diabetes research includes advances in insulin therapy, cutting-edge diabetes management devices and promising therapies such as immunotherapy and β-cell regeneration.
Introduction
By 2050, it is estimated that over 1.31 billion individuals worldwide may have diabetes, a disease linked to substantial morbidity, mortality, and comorbidities. The Lancet has reported that the increase in prevalence, up from 529 million in 2021, is predominantly due to the surge of type 2 diabetes, which is influenced by factors such as obesity and demographic changes.
Type 2 diabetes accounts for 90% of all diabetes cases, with social risk factors such as high BMI, poor diet, environmental hazards, and low physical activity contributing to the burden.
Ongoing research and innovation in diabetes aims to enhance management, treatment, and potentially, discover a cure for this disease.
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The evolution of insulin therapy
Insulin therapy has a rich history that has evolved over time. The discovery of insulin in the early 1920s revolutionized the treatment of diabetes, allowing individuals with the condition to manage their blood sugar levels effectively. Initially, insulin was derived from animal sources (pigs and cows). However, advancements in technology and research have led to the development of recombinant and synthetic human insulin, closely mimicking the insulin produced by the human body.
Over the years, there have been significant improvements in insulin formulations and modes of delivery. These include rapid-acting insulin, short-acting insulin, intermediate-acting insulin, and long-acting insulin. Each type has unique pharmacokinetics and pharmacodynamics, determining the timing and duration of its effect on blood glucose levels.
In recent years, there have been notable advancements in insulin therapy. One area of focus has been the development of insulin pumps. Additionally, research has explored novel approaches to insulin delivery, such as the use of nanomaterials for oral administration.
In 2023, there have been advancements in insulin formulations and affordability. New biosimilars have been approved, providing more affordable options for patients (e.g. Admelog (insulin lispro), an approved biosimilar of Humalog).
Innovative technological advancements for diabetes management
Wearable and implantable devices for insulin release have emerged as promising advancements in diabetes management, offering convenience and improved control for individuals with the condition.
One notable example is the insulin pump. These are small devices that deliver a continuous supply of rapid-acting insulin through a catheter placed under the skin. The pump is programmed to administer precise doses of insulin throughout the day, mimicking the natural insulin release of a healthy pancreas. Some insulin pumps also offer additional features like continuous glucose monitoring (CGM), which provides real-time data on blood glucose levels.
Implantable devices, such as the closed-loop insulin delivery systems are designed to automate insulin delivery based on glucose levels. These devices combine a CGM sensor, an insulin pump, and a control algorithm to continuously monitor blood sugar levels and adjust insulin delivery accordingly.
Some of the algorithms developed for these devices are: the PID algorithm, the Model Predictive Controller (MPC) algorithm, the Hypoglycemic Predictive Algorithms (HPA), the Fuzzy Logic algorithm used by DreaMed (MD logic) and neural networks.
By analyzing trends and patterns, some these algorithms can predict future blood sugar levels and provide personalized recommendations for insulin dosing adjustments or lifestyle modifications.
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Discovering the role of new genes in diabetes
In recent studies, specific genetic variants have been identified in genes related to diabetes development. For instance, in Wolfram syndrome, a rare neurodegenerative disorder that can present diabetes mellitus, an patient carrying the maternally inherited c.1369A > G; p.Arg457Gly variant of the WSF1 gene was found, expanding the spectrum of genetic variants associated with these diseases.
The missense rs2234970 SNP in SCD1 has been shown to contribute to the onset of obesity-related metabolic disorders, such as Type 2 diabetes. Additionally, Massarenti et al. (2022) found associations between SNPs in insulin and insulin receptor genes and the reduced synthesis of anti-insulin antibodies, but poor glycemic control.
Although the identification of recent genetic variants associated with diabetes can contribute to predicting an individual's risk of developing the disease, it is important to note that these associations are often specific to certain populations. Therefore, these criteria cannot be universally applied.
Breakthroughs in alternative therapies
Two new insulin-independent therapies have shown promise in treating diabetes. The first therapy involves targeting the hepatic S100A9-TLR4-mTORC1 axis in non-parenchymal cells to suppress ketogenesis, a process that can lead to life-threatening ketoacidosis in diabetic patients. By administering recombinant S100A9, ketogenesis can be restrained, improving hyperglycemia without causing hypoglycemia in diabetic mice. This pathway presents a potential therapeutic target for managing diabetic ketogenesis.
The second therapy is teplizumab, a humanized monoclonal antibody that delays the onset of type 1 diabetes. Teplizumab targets T cells by binding to CD3. Although the exact mechanism of action is not fully understood, teplizumab may partially activate signaling and deactivate autoreactive T lymphocytes that target pancreatic beta cells. In November 2022, teplizumab became the first FDA-approved drug for delaying the progress of type 1 diabetes.
Towards a cure: promising research in 2023
β cell regeneration and Immunotherapy are the most promising treatments for diabetes.
Restoring both the number and function of beta cells is critical for effective treatment of the disease. While self-duplication and regeneration from stem cells have shown potential for beta cell regeneration, significant progress has been made in developing in vitro strategies for the proliferation and differentiation of functional beta cells. However, there are still obstacles that hinder the translation of β cell regeneration into clinical practice.
On the other hand, immunotherapy aims to regulate the immune response and prevent the β cell destruction that is commonly seen in Type 1 diabetes. Through the inhibition of autoimmunity and the enhancement of tolerance towards β cells, immunotherapy offers great potential in the pursuit of a solution for diabetes.
Conclusion
Staying informed about novel diabetes treatments and risk factors, as well as modifying lifestyle to minimize the chance of developing the disease is essential. Currently, the predominant treatments revolve around managing blood glucose levels and preventing complications utilizing insulin therapy and alternative solutions.
Ongoing research is investigating potential treatments, such as beta cell transplantation, immunotherapy, and regenerative medicine. These groundbreaking prospects generate optimism for future cures, although a conclusive cure is yet to be discovered.
References
- Delvecchio M, et al. (2021). Clinical spectrum associated with Wolfram Syndrome Type 1 and type 2: A review on genotype–phenotype correlations. International Journal of Environmental Research and Public Health, 18(9), 4796. https://doi.org/10.3390/ijerph18094796
- Hirsch I. B, et al.(2020). The evolution of insulin and how it informs therapy and treatment choices. Endocrine Reviews, 41(5), 733–755. https://doi.org/10.1210/endrev/bnaa015
- Ji Z, et al.(2022). Β cell regeneration and novel strategies for treatment of diabetes (review). Biomedical Reports, 17(3). https://doi.org/10.3892/br.2022.1555
- Karmakar S, et al. (2023). Recent advancements on novel approaches of insulin delivery. Medicine in Novel Technology and Devices, 19, 100253. https://doi.org/10.1016/j.medntd.2023.100253
- The Lancet. (2023). Diabetes: A defining disease of the 21st Century. The Lancet, 401(10394), 2087. https://doi.org/10.1016/s0140-6736(23)01296-5
- Massarenti L, et al. (2022). Influence of insulin receptor single nucleotide polymorphisms on glycaemic control and formation of anti-insulin antibodies in diabetes mellitus. International Journal of Molecular Sciences, 23(12), 6481. https://doi.org/10.3390/ijms23126481
- Teplizumab. Uses, Interactions, Mechanism of Action | DrugBank Online. (n.d.). https://go.drugbank.com/drugs/DB06606
- Thomas A, et al. (2021). Algorithms for automated insulin delivery: An overview. Journal of Diabetes Science and Technology, 16(5), 1228–1238. https://doi.org/10.1177/19322968211008442
- Tibori K, et al. (2022). Molecular mechanisms underlying the elevated expression of a potentially type 2 diabetes mellitus associated SCD1 variant. International Journal of Molecular Sciences, 23(11), 6221. https://doi.org/10.3390/ijms23116221
- Ursino G, et al. (2022). Hepatic non-parenchymal S100A9-TLR4-mtorc1 axis normalizes diabetic ketogenesis. Nature Communications, 13(1). https://doi.org/10.1038/s41467-022-31803-5
- How much does insulin cost? here’s how 32 brands and Generics Compare. GoodRx. (n.d.). [online] https://www.goodrx.com/healthcare-access/research/how-much-does-insulin-cost-compare-brands.
Further reading
Metabolomic biomarkers improve diabetes risk prediction accuracy