Can Insulin Resistance Be Resolved? - What Are the Causes?

Over 90% of the population today has health disorders linked to insulin resistance.

Can Insulin Resistance Be Resolved? - What Are the Causes?

Are you struggling with insulin resistance? The good news is that there may be a solution.

If you constantly feel tired, have thyroid issues, increased visceral fat, low energy levels, and a predisposition to inflammation, you likely have insulin resistance.

Many patients with one or more of these issues struggle with insulin resistance despite following medication and dietary recommendations.

The development of insulin resistance is difficult to resolve due to deficiencies and metabolic disorders that are hard to detect with standard lab tests.

Mitochondrial dysfunction is the primary metabolic disorder leading to its development. Mitochondria are organelles inside cells that produce 90% of the body's energy.

Problems caused by Insulin Resistance

Insulin resistance can lead to several health issues, including dysfunction of the thyroid gland, fat accumulation in the abdominal area, fatty liver, low energy levels, increased blood pressure, predisposition to inflammation, borderline high blood glucose levels (above 100 mg/dl), low HDL “good cholesterol”, and increased triglycerides.

Over 93% of the adult population today has one or more of the above disorders linked to insulin resistance[1,2].

Insulin resistance is a primary risk factor for cardiovascular disease, autoimmune conditions, diabetes, and cancer.

Insulin resistance increases the risk of coronary artery disease over 13 times compared to high cholesterol levels.

A 21-year clinical study conducted by the department of Metabolomics at Harvard Medical School followed 28,000 patients to identify risk factors that can lead to coronary artery disease [3].

The Harvard study found that individuals under 55 years old face an increased risk of developing coronary artery disease due to certain factors.
These include a:

39% increase with higher total cholesterol
290% increase due to smoking
540% increase with insulin resistance

Image 1: Cardiovascular risk and nnsuline resistance. Harvard department of Metabolomics study 2021 [1].

Insulin resistance is also linked to an increased risk of cancer development and autoimmune diseases [4-7].

What is Insulin Resistance?

Insulin resistance is a condition in which the body's cells become unresponsive to the signals sent by the hormone insulin.

Cells stop responding to insulin after reaching their glucose-burning limit.

Image 2: Insulin allows the entry of glucose into the cells and its conversion into energy in the mitochondria. Adapted from NEJM 2022.

When there is an excess of glucose in the body, it triggers the secretion of more insulin, which converts the glucose into fat.

High insulin levels can increase the risk of various diseases, such as cardiovascular diseases, diabetes, and obesity, by elevating visceral fat.

Causes of Insulin Resistance

When glucose enters cells, it undergoes a series of reactions in the mitochondria to produce energy.

The amount of glucose that cells take in depends on the capability of their mitochondria to utilize it.

When mitochondria malfunction, they metabolize less glucose, causing cells to stop responding to insulin and leading to insulin resistance [8].

The ability of cells to take in glucose depends on their mitochondria's capability to use it.

Resolving Insulin Resistance

Treatment can involve:

Pharmaceutical interventions
Medical interventions targeting deficiencies and metabolic disorders that disrupt the function of mitochondria and glucose metabolism.

Pharmaceutical interventions: Insulin resistance can be addressed with pharmaceuticals such as metformin and, more recently, semaglutide injections (marketed as Ozempic and Wegovy).

Metformin's positive metabolic effects are often offset by gastrointestinal side effects that limit tolerability.

Semaglutide's use is associated with some severe side effects, including significant loss of muscle and bone mass, suicidal ideation, and thyroid cancer [9,10].

Metabolic interventions: Assessing mitochondrial function and detecting metabolic disorders leading to insulin resistance was not feasible in clinical practice until recently.

Efforts to improve glucose metabolism and mitochondrial function were based on general guidelines and had limited efficacy.

In recent years, metabolomics analyses have been used to measure small molecules involved in mitochondrial chemical reactions, which detect the causes of their dysfunction. These tests guide medical interventions that resolve mitochondrial dysfunction and insulin resistance.

Metabolomics-guided interventions correct insulin resistance through lifestyle, dietary, and deficiency corrections.

The advantage of metabolomics analysis is that it detects precise deficiencies and leads to formulating a comprehensive treatment plan to improve patient health, targeting insulin resistance.

They detect over 80 markers directly related to an individual's health status[11-15]:

Micronutrient deficiencies
Mitochondrial function and energy production
Insulin resistance
Sugars metabolism
Lipid metabolism
Inflammation management
Gut microbiome health, which links to mitochondrial dysfunction and insulin resistance
Immune system function
Neurotransmitter metabolism: dopamine, adrenaline, serotonin, GABA

The results come with a tailor-made treatment plan for each patient; consistent physician monitoring is essential.

The treatment includes vitamins and micronutrients, diet, and lifestyle recommendations based on the test results.

As marginal deficiencies in micronutrients accumulate over time and lead to disease, time and effort are needed for their correction.

The first step in treating insulin resistance is to perform the analysis. Based on the results of these tests, the physician will design a customized treatment plan for each patient. As the patient applies the treatment the medical team prescribes, consistent monitoring by the medical team is necessary to monitor progress and make any necessary adjustments to the treatment plan.

Typically, 6-8 months are required to achieve significant change and a year to stabilize the body at a better functioning level.

Based on our clinical experience with over 25,000 patients, we have found that improving insulin resistance and mitochondrial function through medical interventions, dietary changes, and addressing nutrient deficiencies significantly improves health:

Increases energy levels and reduces fatigue
Improves metabolism, reduces body weight
Reduces visceral fat
Significantly improves the quality of life of individuals with chronic inflammatory diseases like Hashimoto's, psoriasis, rheumatoid arthritis, ulcerative colitis
Reduces the risk of cardiovascular disease and diabetes
Improves sugar and lipid metabolism
Significantly reduces chronic inflammation

We have seen that correcting deficiencies in vitamins and other elements, restoring metabolism, and regulating weight to healthy levels radically changes the health course of individuals with insulin resistance for the better and improves the quality of life from a stable deterioration to stable improvement [11-14].

Timely intervention is crucial to restore the health and prevent it from deteriorating further.

Bibliographic References

[1] Trends and Disparities in Cardiometabolic Health Among U.S. Adults, 1999-2018 Author links open overlay panelMeghan O’Hearn MS et al. Journal of the American College of Cardiology, 12 July 2022. 10.1016/j.jacc.2022.04.046

[2] The Global Epidemic of the Metabolic Syndrome Mohammad G. Saklayen Curr Hypertens Rep. 2018

[3] Sagar B. Dugani, M. Vinayaga Moorthy, Chunying Li, Olga V. Demler, Alawi A. Alsheikh-Ali, Paul M Ridker, Robert J. Glynn, Samia Mora. Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women. JAMA Cardiology, 2021; DOI: 10.1001/jamacardio.2020.7073

[4] Insulin resistance and breast cancer incidence and mortality in postmenopausal women in the Women’s Health Initiative Correction(s) for this article Kathy Pan MD et al. Cancer 2020. https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.33002

[5] Insulin Resistance and Cancer-Specific and All-Cause Mortality in Postmenopausal Women: The Women's Health Initiative Kathy Pan et al. J Natl Cancer Inst . 2020 Feb https://pubmed.ncbi.nlm.nih.gov/31184362/

[6] Metabolic syndrome, autoimmunity and rheumatic diseases Gabriela Medina et al. Pharmacol Res . 2018. https://pubmed.ncbi.nlm.nih.gov/29382608/

[7] Metabolic pressure and the breach of immunological self-tolerance Veronica De Rosa, Antonio La Cava & Giuseppe Matarese.18 October 2017.
[8] Mitochondrial (Dys)function and Insulin Resistance: From Pathophysiological Molecular Mechanisms to the Impact of Diet Domenico Sergi et al. Front. Physiol., 03 May 2019 https://www.frontiersin.org/articles/10.3389/fphys.2019.00532/full

[9] Prof Keith Frayn, Emeritus Professor of Human Metabolism, University of Oxford https://www.sciencemediacentre.org/expert-reaction-to-study-looking-at-drug-for-treating-obesity-semaglutide/

[10] EU investigates Ozempic. https://www.reuters.com/business/healthcare-pharmaceuticals/eu-probes-novos-weight-loss-drugs-reports-suicide-risks-bloomberg-news-2023-07-10/

[11] Targeted Metabolomic Analysis of Serum Fatty Acids for the Prediction of Autoimmune Diseases. Dimitris Tsoukalas, Vassileios Fragoulakis, Evangelia Sarandi et. al. Frontiers in Molecular Biosciences, Metabolomics, 2019.

[12] Prediction of Autoimmune Diseases by Targeted Metabolomic Assay of Urinary Organic Acids. Dimitris Tsoukalas et al. Metabolites. 2020 Dec 8.

[13] Non-communicable Diseases in the Era of Precision Medicine: An Overview of the Causing Factors and Prospects. Dimitris Tsoukalas et al. Bio#Futures. Springer, Cham. May 2021.

[14] Micronutrient deficiencies in patients with COVID-19: how metabolomics can contribute to their prevention and replenishment. Dimitris Tsoukalas^1,2and Evangelia Sarandi^2,3BMJ Nutri Prev Heal. Nov. 2020; bmjnph-2020-000169

[15] Bacterial metabolism influences insulin resistance. Ashley York. Nature Reviews Microbiology 2023 https://www.nature.com/articles/s41579-023-00977-0

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