The Overlooked Starting Point of Chronic Disease
What is Insulin Resistance?
Insulin resistance is a condition in which the body’s cells become less responsive to the hormone insulin, reducing its effectiveness. As a result, the body must produce more insulin to maintain normal blood glucose levels.
In the early stages, blood glucose levels may still appear normal, but insulin levels gradually rise. Once the body can no longer compensate, this may lead to prediabetes and eventually Type 2 diabetes mellitus.
Current evidence suggests that insulin resistance is not solely related to blood sugar regulation. It is also associated with chronic low-grade inflammation, an important mechanism linked to many chronic diseases.
What is Chronic Inflammation?
Inflammation is the body’s natural defence mechanism. When the body experiences injury, infection, or other stimuli, the immune system responds to protect and repair tissues.
However, when low-level inflammation persists over a prolonged period, it can lead to damage to cells, tissues, and blood vessels. This condition often produces no obvious symptoms in its early stages but may be detected through certain inflammatory markers, including:
- High-sensitivity C-reactive Protein (hs-CRP)
- Interleukin-6 (IL-6)
- Tumour Necrosis Factor-alpha (TNF-α)
How are Insulin Resistance and Chronic Inflammation Related?
Insulin resistance and chronic inflammation are closely interconnected. Each condition can promote the other, creating a vicious cycle that progressively impairs metabolic health and overall wellbeing.
1. Chronic inflammation may contribute to insulin resistance
When chronic inflammation occurs, the body releases increased amounts of inflammatory cytokines, including:
- CRP (C-Reactive Protein)
- TNF-α (Tumour Necrosis Factor-alpha)
- IL-6 (Interleukin-6)
These inflammatory substances can interfere with the function of insulin receptors, reducing cellular responsiveness to insulin. As a result, the body must produce more insulin to regulate blood glucose levels.
2. Insulin resistance may increase inflammation
Insulin resistance can lead to several metabolic abnormalities, including:
- Elevated blood glucose levels
- Chronically elevated insulin levels (hyperinsulinaemia)
- Increased abdominal fat accumulation (visceral fat)
Visceral fat is not merely an energy store. It also acts like an endocrine organ, releasing inflammatory substances such as TNF-α, IL-6, and MCP-1.
These inflammatory mediators further impair insulin signalling, causing cells to become increasingly resistant to insulin. Consequently, the body produces more insulin, leading to chronic hyperinsulinaemia and oxidative stress.
Persistent oxidative stress may impair mitochondrial function, damage blood vessels, and disrupt overall metabolism, thereby worsening insulin resistance and further promoting inflammation.
Additionally, prolonged high blood glucose levels can lead to the formation of Advanced Glycation End Products (AGEs). AGEs stimulate the immune system to release more inflammatory substances and accelerate the degeneration of various organs.
Chronic Diseases Associated with Insulin Resistance and Chronic Inflammation
When insulin resistance occurs alongside chronic inflammation, it may become a key underlying factor in several chronic diseases, including:
- Type 2 diabetes mellitus
- Cardiovascular disease
- Atherosclerosis
- Non-Alcoholic Fatty Liver Disease (NAFLD)
- Dementia
- Metabolic dysfunction
- Accelerated ageing associated with chronic inflammation (Inflammaging)
- Hormonal disorders, including:
- Polycystic Ovary Syndrome (PCOS) in women
- Low testosterone levels in men
- Fertility problems
Strategies to Reduce Insulin Resistance and Inflammation
Improving lifestyle habits plays a crucial role in reducing insulin resistance and chronic inflammation:
- Lose excess weight, particularly abdominal fat
- Exercise regularly, including both cardiovascular exercise and resistance training
- Aim for 7–8 hours of sleep each night
- Manage stress to help reduce cortisol levels
- Consume an anti-inflammatory diet, rich in vegetables, fruit, nuts, fish, and omega-3 fatty acids
- Reduce intake of sugar, refined carbohydrates, processed foods, and sugar-sweetened beverages
Summary
Insulin resistance is not only an early stage in the development of diabetes but also an important mechanism linking chronic inflammation throughout the body.
When insulin resistance and chronic inflammation occur together, they significantly increase the risk of chronic diseases such as cardiovascular disease, fatty liver disease, dementia, hormonal disorders, and accelerated ageing (inflammaging).
Early risk assessment, together with appropriate lifestyle modifications, is therefore essential for the long-term prevention of chronic disease.
Insulin Resistance Screening Programme
- Fasting Blood Sugar
- Fasting Insulin
- HOMA-IR
- HbA1c
- Lipid Profile
- hs-CRP
Note: Please fast from food and beverages for approximately 10–12 hours before testing. Plain water may be consumed.
References
- American Diabetes Association. (2025). Standards of care in diabetes—2025. Diabetes Care, 48(Supplement_1), S1–S350.
- DeFronzo, Ralph A., Ferrannini, Ele, & Grodsky, Gerald M. (2015). Type 2 diabetes mellitus. Nature Reviews Disease Primers, 1(1), 15019.
- Hotamisligil, Gökhan S. (2006). Inflammation and metabolic disorders. Nature, 444(7121), 860–867.
- Lumeng, Carey N., & Saltiel, Alan R. (2011). Inflammatory links between obesity and metabolic disease. The Journal of Clinical Investigation, 121(6), 2111–2117.
- Saltiel, Alan R., & Olefsky, Jerrold M. (2017). Inflammatory mechanisms linking obesity and metabolic disease. The Journal of Clinical Investigation, 127(1), 1–4.
- Shoelson, Steven E., Lee, Jongsoon, & Goldfine, Allison B. (2006). Inflammation and insulin resistance. The Journal of Clinical Investigation, 116(7), 1793–1801.
- Tilg, Herbert, & Moschen, Alexander R. (2008). Inflammatory mechanisms in the regulation of insulin resistance. Molecular Medicine, 14(3–4), 222–231.
- World Health Organization. (2024). Obesity and overweight. Geneva, Switzerland: Author.
