A large part of the population suffers from a disorder in the metabolism of energy-rich substances (glucose, fats or proteins), diabetes mellitus (DM). A simple model allows us to understand the aetiology, pathophysiology and basic methods of modern treatment of the disease.
In many cases, the disease is caused by a malfunction of hormones,
especially insulin. More than 10% of
cases of DM are caused by an absolute or relative lack of insulin, mainly due
to an autoimmune process that destroyed insulin-producing cells - type 1
diabetes (DM1) or in the final stages of other types of diabetes due to
terminal failure of regulatory mechanisms. In rare cases, DM is due to a
decrease in all the effects of insulin - real insulin resistance or due to a
real lack of insulin (Mody 2 for example). Metabolism takes place in cells.
Hundreds of different enzymes affect the metabolism of energy-rich substances.
Each of them can be damaged. However, it seems that the main cause of the
disease is an inappropriate lifestyle, which secondarily damages the regulatory
systems. This is the cause of type 2 diabetes (DM2). A high energy input/low
energy expenditure (HEILEE) lifestyle is not compatible with a human genetic
background. Deviations in glucose metabolism initially arise as a feedback,
cellular defence against energy-rich substances overload, and are therefore
reversible. If energy surplus persists for a long time, irreversible
malfunctions occur. Untreated DM1 is characterized by intracellular starvation
and lack of ATP. DM2 is characterized by “cellular overeating”. There gradually
develop serious collision between intracellular regulatory mechanisms (AMPK,
CD36-SR-B2, controlled by the amount of ATP, glycogen, lipid and other
energy-rich substances), and cascades of hormone second messengers. Insulin deficiency and insulin resistance in DM2 are emphasized
above all today. The question, of which of these disorders (or obesity) is the
first, provoking the development of DM2, is discussed in the literature.
Neither of them – both are the consequence of a chronic energy surplus. Chronic
hyperinsulinemia is present in the early stages of the disease. Insulin ensures
a high transfer of glucose from the blood to the tissues in obese people, but
it is unable to maintain an adequate level of glucose in the blood. The disease
is characterized by a special disorder - “Insulin uncoupling", a defect
when there is a simultaneous increase in some effects and a decrease in other
effects of the hormone. The ability of insulin to ensure anabolic processes is
preserved. The ability to form visceral fat stores or the ability to retain
sodium is increased. Hormone synthesis in DM2 gradually decreases, and the
patients may become fully dependent on external insulin administration.
What therapy results from the above-mentioned principles? The goal
of our efforts should be the complete restoration of the metabolism of
energy-rich substances, carbohydrates, fats and other substances. Patients who
are unable to synthesize insulin need this hormone (its analogues), in adequate
amounts depending on needs. Patients who produce insulin but are unable to
release it sufficiently will be optimally treated with sulfonylurea derivatives
(MODY 2, MODY 12). Patients who are unable to release insulin depending on food
intake will be optimally treated with GLP1 analogues, and incretins. The basic
medical treatment for patients suffering from DM 2 reduces energy intake. The
anorexic effect of GLP1 agonists is beneficial.
Metformin reduces the metabolism efficiency. This drug increases the
amount of glucose processed anaerobically. Subsequently, metabolism in the Cori
cycle causes significant energy losses. Currently, there are even drugs
available that allow the removal of unnecessarily received energy by removing
glucose from the body via urine-gliflozins. Insulin administration is
appropriate to restore adequate blood glucose levels. Long-term administration
of high doses of insulin is nevertheless not the optimal therapy for
early-stage DM2. A return to a lifestyle
that corresponds to the conditions under which the human organism evolved -
with limited food intake and relatively high energy expenditure through
physical exercise- could prevent the population from developing diabetes
mellitus.
Author
(s) Details
Kubat K
PN Horni Berkovice, Plesivecka 912/10, 41201 Litomerice, Czech Republic,
Europe.
Please see the book here:- https://doi.org/10.9734/bpi/dhrd/v2/3640
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