Hyperinsulinemia and age-related diseases: interrelations and approaches to treatment

Abstract

Hyperinsulinemia is closely related with insulin resistance, that is the key mechanism for the progression of age-related diseases. A lot of aspects of hyperinsulinemia and interrelations between the mentioned conditions are very scarcely covered in Russian publications.

The present review is designed to fill the gaps in understanding the causal relationships between hyperinsulinemia, insulin resistance, age-related diseases and lifestyle factors.

Material and methods. Based on sources from PubMed and Google Scholar, using the keywords “hyperinsulinemia” + “chronic disease” OR “age-related disease” the authors analyzed the causes of hyperinsulinemia, the mechanisms of its influence on various aspects of insulin resistance, and the role of hyperinsulinemia in pathogenesis of a wide range of clinical syndromes and age-related diseases. Consideration of the effects that lifestyle factors produce on hyperinsulinemia opens up opportunities for its correction.

Results. The major causes of hyperinslinemia are improper diet and nutrition regime (frequent meals and excess of highly glycemic food, too short fasting window), along with other factors causing hyperreactivity of pancreatic beta-cells (fructose, systemic inflammation, oxidative stress, low vitamin D level, etc.). Hyperinsulinemia affects cellular energy balance (primarily, in liver, muscle, brain and adipose tissue); a major factor is suppression of 5’AMP-activated protein kinase (AMPK) along with stimulation of mitogen-activated protein kinase. Insulin resistance is a consequence of AMPK inhibition, an adaptive response designed to preserve cellular homeostasis.

Conclusion. Obesity, metabolic syndrome, chronic systemic inflammation, age-related syndromes and diseases (including arterial hypertension, atherosclerosis, neurodegenerative diseases, tumors, osteoarthritis, sarcopenia, etc.) can be considered as clinical manifestations of the body’s systemic adaptation to hyperinsulinemia in the form of insulin resistance. Available approach to reduce insulin resistance is correction of lifestyle factors to mitigate hyperinsulinemia and restore AMPK activity. The revealed causal relationships can provide background for personalized strategy of prevention and treatment for age-related diseases through reduction of insulin resistance and correction of energy homeostasis.

Keywords:age-related diseases; hyperinsulinemia; obesity; insulin resistance; inflammaging; metabolic syndrome; AMP-activated protein kinase

Funding. The analytical study was carried out within the framework of the state assignment No. 075-00483-21-01 “Preventive technologies for personalized geroprotection”.

Conflict of interest. The authors declare no conflicts of interest.

Contribution. All authors approved the final version of the article before publication, agreed to be responsible for all aspects of the work, implying the proper study and resolution of issues related to the accuracy or integrity of any part of the work.

For citation: Martyushev-Poklad A.V., Yankevich D.S., Petrova M.V., Savitskaya N.G. Hyperinsulinemia and age-related diseases: interrelations and approaches to treatment. Voprosy pitaniia [Problems of Nutrition]. 2022; 91 (3): 21–31. DOI: https://doi.org/10.33029/0042-8833-2022-91-3-21-31 (in Russian)

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Viktor A. Tutelyan
Full Member of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor, Scientific Director of the Federal Research Centre of Nutrition, Biotechnology and Food Safety (Moscow, Russia)

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