Chronic low-grade inflammation is found in type 2 diabetes mellitus (T2DM), and this contributes to the development of T2DM and the associated complications of nerve, kidney, heart, brain, liver, and eye damage. Interestingly, this inflammation is similar clinically and molecularly to the low-grade inflammation that comes with the ageing process. This process is sometimes referred to as inflammageing. This whole process of inflammation in T2DM is characterised by 4 components: long-term immune system activation, build-up of senescent cells, epigenetic changes, and changes in the intestinal microbiota.
Chronically high BG also leads to increased cellular senescence. This is basically a state in which the cells are no longer undergoing normal cellular cycles and are not really alive and not really dead. Consequently they have more DNA damage and seem to spread their senescence to other cells, almost like an infection. More and more research is associating the accumulation of these cells with chronic and age-related diseases. Fortunately these senescent cells, like many cancer cells, seem to depend on glucose to keep them alive which makes them susceptible to treatment with an appropriate diet and medical therapy.
A healthy immune system deals with challenges as they arise, increasing in activity when there is a foreign invader, and reducing activity when the challenge has been overcome. The high levels of blood glucose (BG), triglycerides, and “unhealthy” cholesterol found in T2DM lead to an inflammatory response by the immune system. This process results in immune cells becoming senescent. This is essentially what happens in the deterioration of the immune system that normally occurs with ageing. This inflammatory reaction seems to be related to the degree of BG overload, which makes it possible to address by controlling the BG level. This is often done with medications but can also be done sustainably with a proper diet. Glucose is not the only culprit though, saturated fatty acids (SFAs) produce pro-inflammatory immune responses which lead to insulin resistance as well.
Epigenetic changes are those in which the DNA sequence doesn’t change, but the expression of the genes coded by the DNA does. DNA methylation is the process that affects the expression of a gene without changing the DNA. This process is influenced by external factors such as the environment, lifestyle, and nutrition. In T2DM the epigenetic changes appear to be mostly pro-inflammatory and the DNA methylation in the pancreas has a negative effect on insulin secretion. Some of these epigenetic changes remain even after blood sugar levels return to normal, but DNA methylation changes may be reversible with diet, exercise, and weight control.
The connection between diet, the gut bacteria, and inflammation has been garnering more attention in recent years and this may have special relevance for individuals with T2DM. Over time the balance of the gut bacteria, the microbiota, undergoes changes. In people who have an imbalance or deficiency of healthy gut bacteria, leakage of bacteria and associated compounds across the gut membrane can occur and lead to chronic low-grade inflammation of the type that is associated with inflammageing. Studies on the microbiota of T2DM patients have found changes in the levels of specific species of bacteria in the gut that contribute to increased inflammation. This balance of gut bacteria can be influenced by factors such as artificial sweeteners, obesity, fiber intake, flavonoids, polyphenols, and supplementation with specific probiotics.
Current medical therapy for diabetes, which consist primarily in oral antihyperglycemic agents such as metformin, does not provide adequate reductions in heart disease and death rates in T2DM patients. Such therapy also does not adequately control the complications of chronically high BG levels. A more effective and balanced approach should include dietary, lifestyle, and medical interventions that reduce inflammation and address the known mechanisms that result in T2DM and its complications. Such an approach would rely on a low-carbohydrate or Mediterranean diet, regular strenuous exercise, and nutritional supplementation to mitigate the damaging effects of chronically high BG and the fluctuations in BG that occur when making diet and lifestyle changes.
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