Immunonutrition as an Emerging Strategy for Type 2 Diabetes
Introduction
Diabetes is a chronic disease that affects a growing number of people across the world. It is one of the leading causes of illness and early death, regardless of gender, age, or country of origin. In 2021, an estimated 536.6 million adults between the ages of 20 and 79 were living with diabetes, and about 96% of those cases were type 2 diabetes, which occurs most often in older adults. More than half of these cases were linked to a high body mass index (BMI), showing how closely diabetes is connected to obesity. Unfortunately, the trend is still climbing. By 2045, projections suggest that more than 783 million adults worldwide will have diabetes. Even more concerning is that nearly one-third of deaths from diabetes and its complications occur in people younger than 60 years old.
Diabetes is not only a medical problem but also a serious economic issue. The cost of treating diabetes and its complications has risen dramatically in recent decades. Between 2007 and 2021, the worldwide economic burden of diabetes among adults rose by more than 360%, reaching nearly one trillion U.S. dollars. If this trend continues, the global cost of diabetes is expected to exceed one trillion dollars by the year 2030. These expenses include not only hospital care and medication, but also the indirect costs of lost productivity and long-term disability.
Complications of Diabetes
A major reason why diabetes has such a heavy impact is its complications, which can be divided into two broad categories: macrovascular and microvascular. Macrovascular complications involve large blood vessels and include serious cardiovascular diseases such as coronary artery disease, stroke, and peripheral artery disease. Microvascular complications affect small blood vessels and include damage to the eyes (diabetic retinopathy), kidneys (diabetic nephropathy), and nerves (diabetic neuropathy). Research shows that about 50% of patients with type 2 diabetes experience macrovascular complications, while 27% suffer from microvascular complications. These complications reduce both quality of life and life expectancy, making prevention and early treatment essential.
Approaches to Treatment
Managing diabetes requires a comprehensive approach. This usually includes regular physical activity, a carefully balanced diet, prescribed medications, patient education, and ongoing motivation. Because diabetes can also affect mental health, psychological support is sometimes necessary. According to Marc Lalonde’s well-known concept of health determinants, modifiable lifestyle factors account for about 70% of human health, with lifestyle choices alone responsible for nearly 50%. This means that how a person eats, moves, and manages stress can make a powerful difference in both the prevention and treatment of diabetes.
A healthy diet plays a central role in diabetes management. However, modern food systems often work against proper nutrition. Highly processed foods, widespread use of chemical additives, and intensive farming methods have reduced the levels of vitamins and minerals in the foods people eat. Multiple studies show that the nutrient content of plant-based foods, which should form the basis of a healthy diet, has declined significantly over time. As a result, even individuals with normal or high body weight may be malnourished at the micronutrient level, lacking the vitamins and bioactive compounds needed for optimal health.
The Role of the Immune System
The immune system is one of the body’s most important defense mechanisms, and its health is closely linked to chronic diseases such as diabetes. For the immune system to function properly, it requires both protein (needed for the production of key enzymes) and non-nutritive bioactive compounds like vitamins, minerals, and antioxidants. When these nutrients are missing, the immune system cannot operate efficiently, leaving the body more vulnerable to disease.
This connection between diet, immunity, and chronic illness is the focus of a growing field called immunonutrition. Immunonutrition studies how nutrients can influence immune function and inflammation. Research shows that targeted nutrition can improve outcomes in conditions such as gastrointestinal cancers and Crohn’s disease. Applying this same principle to diabetes could help reduce inflammation, improve insulin sensitivity, and limit complications.
Pathogenesis of Diabetes and Inflammation
Obesity is one of the strongest risk factors for type 2 diabetes. Excess body fat promotes insulin resistance, a condition in which cells no longer respond properly to insulin. This resistance is linked to chronic low-grade inflammation. For example, obese individuals have higher levels of inflammatory markers such as tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and plasminogen activator inhibitor. These inflammatory molecules interfere with insulin signaling pathways inside cells. As a result, glucose uptake is impaired, and blood sugar levels rise.
Hyperglycemia (high blood sugar) itself also weakens the immune system. Research shows that people with diabetes have reduced activity of certain white blood cells, including monocytes, T lymphocytes, and neutrophils. This means they may not respond to infections as effectively as healthy individuals. Diabetes has also been associated with changes in toll-like receptor (TLR) expression, impaired production of reactive oxygen species, reduced phagocytosis (cellular “eating” of pathogens), and dysfunctional natural killer cells. Together, these defects show how closely immune dysfunction and diabetes are intertwined.
Oxidative Stress and Beta-Cell Dysfunction
One of the damaging processes in diabetes is oxidative stress. This occurs when levels of harmful molecules called reactive oxygen species (ROS) exceed the body’s ability to neutralize them. ROS are produced naturally in mitochondria but can build up in conditions like chronic hyperglycemia. Excess ROS damage DNA, proteins, and lipids, leading to cellular dysfunction. In diabetes, oxidative stress reduces glucose uptake in muscle and fat cells, impairs insulin secretion from pancreatic beta-cells, and can even cause beta-cell death. Over time, this worsens insulin deficiency and pushes blood sugar levels higher.
Inflammation, Adipose Tissue, and Exosomes
Diabetes is often described as a state of chronic low-grade inflammation. High blood sugar stimulates the release of pro-inflammatory cytokines and chemokines, which further disrupt insulin signaling. Adipose tissue, especially in obese individuals, plays a central role. Fat tissue contains immune cells called macrophages, which release inflammatory molecules and even small particles called exosomes. These exosomes can enter the bloodstream and disrupt insulin signaling in other tissues such as muscle, liver, and fat itself. One study found that these exosomes contained high levels of microRNA-155, a molecule that suppresses genes important for fat metabolism, contributing further to insulin resistance.
Nutritional Deficiencies in Diabetes
The modern food environment makes it difficult for patients with diabetes to meet all of their nutritional needs. Even when body weight is normal or high, deficiencies in protein, vitamins, and minerals are common. Laboratory testing can reveal these deficiencies, though routine clinical evaluation often relies on indirect markers. Essential tests for diabetic patients include complete blood counts, protein levels, vitamin and mineral concentrations (such as vitamin B12, vitamin D3, calcium, and iron), and lipid profiles. Additional testing, such as transferrin saturation, may be needed to diagnose conditions like iron deficiency.
Clinical observations support the prevalence of these deficiencies. For example, research in patients with immune disorders has shown high rates of low hemoglobin, low albumin, vitamin D deficiency, folic acid deficiency, and reduced ferritin levels—even among patients who regularly received medical care and supplementation. Since diabetes itself acts as a type of secondary immune deficiency, identifying and correcting nutritional deficiencies is especially important. Supplementation with vitamins, minerals, and compounds like omega-3 fatty acids has been shown to improve both laboratory markers and patient well-being.
Conclusion
Diabetes is more than a disease of blood sugar; it is a complex condition involving inflammation, oxidative stress, immune dysfunction, and nutritional deficiencies. Its prevalence and economic impact are rising at alarming rates, and the complications it causes significantly reduce quality of life. Lifestyle changes, especially dietary improvements, remain a cornerstone of prevention and treatment. However, modern diets often fail to provide the essential nutrients needed to support both metabolism and immunity. Careful evaluation of nutritional status, along with targeted supplementation, should therefore be considered an important part of diabetes management. By addressing diet and immunity together, it may be possible to not only control blood sugar but also reduce complications and improve long-term health outcomes.
Source:
Immunomodulation through Nutrition Should Be a Key Trend in Type 2 Diabetes Treatment
Nutritional management of diabetes mellitus during the pandemic…..
Vitamin C ameliorated cardiac autonomic neuropathy in type 2 diabetic rats
Lysine: Sources, Metabolism, Physiological Importance, and Use as a Supplement
Vitamins, Minerals and Amino Acids
Vitamin C
Vitamin C, or ascorbic acid, is a water-soluble vitamin. Vitamin C is an antioxidant and also has immune-modulating effects through T-cells transformation, interferon production and phagocytic function. It is a compound that cannot be synthesized in the body, so the main source of vitamin C for humans is diet. Due to its solubility in water, it can easily lead to hypovitaminosis, so it is mandatory for humans to supplement it systematically with diet. Vitamin C is found in citrus fruits, such as orange, kiwi, lemon, guava, and grapefruit, and vegetables, such as broccoli, cauliflower, Brussels sprouts, and peppers.
The main feature of vitamin C is its ability to donate electrons; it is a strong antioxidant and additionally acts as a cofactor for biosynthetic and gene-regulating enzymes. It also affects the functioning of the immune system by acting on cell functions of both the innate and adaptive immune systems. Vitamin C supports the epithelial barrier function against pathogens. It supports the removal of oxidants through the skin, protecting it from environmental oxidative stress. Vitamin C accumulates in phagocytic cells, such as neutrophils. Within cells, it promotes chemotaxis, phagocytosis, and the production of reactive oxygen species. Moreover, it reduces necrosis and potential tissue damage by promoting apoptosis and the removal of neutrophils by macrophages from infected sites. Additionally, vitamin C has been documented to increase the differentiation and proliferation of B and T cells. Recent in vitro experiments investigated the inhibitory effect of vitamin C on the expression of pro-inflammatory mediators, including IL-6 and TNF-α, in blood cells. Additionally, the antioxidant function influences the innate and adaptive immune response.
Vitamin C may reduce insulin resistance and cardiovascular complications in patients with T2DM. It plays an inhibitory role in the production of protein oxidation biomarkers, such as advanced oxidation protein products (AOPPs) and advanced glycation end products (AGEs). Due to the similar structure of vitamin C to glucose, it can be replaced by glucose in response to chemical reactions and prevent the non-enzymatic glycosylation of proteins.
Zinc
Zinc is a crucial microelement in metabolism. It is considered to control over 100 enzymes that are responsible for substantial processes, such as protein folding, gene expression, cell signaling, and cellular processes, including cell division and apoptosis. In terms of the immune system, zinc is known to strongly affect factors of an immunological response, such as chemokines, pro-inflammatory cytokines, complement factors, and bacterial wall compounds. This leads to the early activation of polymorphonuclear leukocytes, which together with macrophages, are listed among first responders when infection occurs. Both zinc deficiency and zinc excess are undesirable because they are proven to inhibit nicotinamide adenine dinucleotide phosphate oxidases, whose activity is responsible for killing pathogens. This process takes place after phagocytosis, which is also influenced by the accessibility of zinc. This microelement can positively influence the amount of cytokines and act as an antioxidant.
Due to the various ways in which zinc affects many signal pathways, it is not fully understood how exactly the lack of zinc homeostasis contributes to the development of T2DM. It has been proven that zinc transporter 8 (ZnT8) plays an important part in zinc uptake by insulin secretory granules in beta cells. In a study conducted in vivo on mice, it was demonstrated that ZnT8 is essential for beta-cell zinc influx, glucose-stimulated insulin secretion, and insulin processing, as well as the formation of insulin granules. Another transporter that is considered important in the pathomechanism of the disease is ZIP7. It is a transporter that is involved in the process of endoplasmic reticulum (ER) stress. ER is critical for the correct processing and folding of proteins, and ER stress arises when the folding capacity of the ER is outpaced by the influx of nascent, unfolded polypeptide chains. Cells undergoing this type of stress will activate a UPR (unfolded protein response) pathway, which will decrease the transcription of genes that encode secretory proteins, causing decreasing folding demand on the ER. ZIP7 is a transporter located in an early secretory pathway, including ER controlling the movement of zinc from this subcellular organelle into cytosol. The importance of ZIP7 is emerging as a key transporter implicated in maintaining ER homeostasis. In that way, zinc protects the ER from imbalance and, therefore, it helps avoid the reduced transcription of genes that are responsible for secretory proteins.
Lysine
Lysine (2,6-diaminohexanoic acid, often written as Lys or K) is an essential amino acid. This means our bodies cannot make it, so we must get it from food. Lysine is also considered both protein-building (proteinogenic) and ketogenic, because it can be used to make proteins and can produce energy through fat metabolism.
Over 60 years ago, researchers discovered that lysine is the “first limiting amino acid” in cereals. Grains like wheat and rice do not contain enough lysine to fully support growth. Studies in children using nitrogen balance techniques showed that adding lysine to a basic wheat diet greatly improved nitrogen retention, a sign of better protein use. Because of this, lysine has long been added to foods and supplements, especially in low-income regions where cereal-based diets are common.
In recent years, scientists have become interested in how lysine is modified after proteins are made—this is called post-translational modification (PTM). For example, hydroxylysine is essential for collagen, which gives structure to skin and connective tissue. Another derivative, desmosine, helps link elastin fibers, giving tissues like blood vessels their flexibility. Lysine also plays a role in forming carnitine, a nutrient important for energy production, which is made from trimethyllysine released during protein breakdown.
PTMs of lysine are also tied to the regulation of metabolism and epigenetics—the way gene activity is turned on or off without changing DNA. Researchers are exploring the balance between lysine and another amino acid, arginine, because it seems to influence nitric oxide (NO) production, blood flow, immunity, and even cancer development.
Finally, modified forms of lysine are used medically. Lysine analogues help prevent bleeding disorders and are being studied as potential therapies for viral infections.
Virus
Does not depend upon a personal definition of life because…..
Without a distinction there can be no such thing as biology, the study of living organisms.
All cellular life has both DNA and RNA. Humans, animals, plants, bacteria, fungi and archaea. Viruses are the exception, as they contain either DNA or RNA, but not both. They are not considered living organisms because they are essentially just genetic material wrapped in a protein shell and cannot reproduce without hijacking a host cell’s machinery. The origin of viral DNA or RNA (as in entity/being) is unknown aside from the host. They will never be living unless they have answered riddle of you can’t make DNA without RNA and you can’t make RNA without DNA.
Immune For Life
M. Ferrari
After decades of chronic health conditions and serious gut issues like IBS and SIBO, immune deficiencies and an autoimmune condition discover how I recovered my health thanks to natural oral immune therapeutics (maf and gcmaf). Due to a premature birth and being formula fed, I was a SAM child in real life. My book is a step by step journey you won't want to miss that illustrates how to regain or maintain health for all ages.