Insulin Resistance: The Biggest Silent Threat to Longevity

You go for your yearly check-up, tick off the usual tests, and walk out thinking you’re in the clear. But what if one of the most significant risk factors wasn’t even on your results slip?

Most people worry about their weight, blood pressure, or cholesterol. Whilst these are important, there’s an even bigger health risk that millions live with every day without even knowing it. It’s called insulin resistance, and chances are you’ve never been tested for it.

What is Insulin Resistance?

Insulin resistance is a condition where your body becomes less responsive to insulin. Insulin is a hormone made by the pancreas that helps move glucose (sugar) from the bloodstream into the cells for energy or storage.

When your body is functioning normally, glucose levels rise after eating. The pancreas - sensing the glucose in the blood - releases insulin, which acts like a key, unlocking the gates so glucose can enter the cells. Blood glucose levels return to normal once glucose is taken up by the cells.

In insulin resistance, this process is malfunctioning. Muscle, fat and liver cells in particular are not responding to these signals to unlock the gates. The pancreas detects the glucose remaining in the blood and in response compensates by releasing more insulin to bring the glucose levels down. Over time, this leads to chronically high insulin levels, known as hyperinsulinaemia[1].

Why Insulin Resistance is Dangerous

Hyperinsulinaemia alone causes health problems through a wide variety of mechanisms:

1. Fat accumulation: Persistently high insulin increases fat storage and reduces fat breakdown. This leads to obesity and fat accumulation around abdominal organs (visceral fat)[2].

2. Inflammation: Fat cells release of inflammatory molecules, which worsens insulin resistance and causes oxidative stress and DNA damage. Oxidative stress is where harmful molecules called free radicals build up in the body and overwhelm your natural defences, leading to cell and tissue damage [3].

3. Blood vessel dysfunction: Insulin resistance disrupts nitric oxide production, which is responsible for widening the blood vessels, thereby promoting high blood pressure. Additionally, it increases vascular smooth muscle proliferation and blood vessel inflammation, both of which are important processes in atherosclerosis - the formation fatty plaques that narrow arteries to the heart and brain[4].

4. Cancer: Insulin stimulates insulin-like growth factor 1 (IGF-1), which signals cells to grow and divide more than normal. Along with inflammation, these mechanisms create an environment where cancer cells can thrive[5].

Health Risks of Insulin Resistance

These processes contribute to the development of a large number of conditions across several different body systems, including at least 13 types of cancer[6,7]:

Insulin Resistance vs Other Risk Factors

Many of you know that high blood pressure, high LDL (”bad”) cholesterol and smoking are risk factors for heart disease. But how does insulin resistance compare to these other markers when we talk about risk to your health?

An analysis of over 28,000 women in the Women’s Health Study measured more than 50 clinical and biomarker risk factors to see which ones were most strongly associated with developing coronary artery disease. One of the standout findings was that Lipoprotein Insulin Resistance Index (LP-IR), a biomarker of insulin resistance, was amongst the strongest predictors for heart disease before age 55[8].

This study suggests that insulin resistance is a stronger predictor of early cardiovascular disease than traditional markers, such as HbA1c, LDL and apolipoprotein B (ApoB), and may be one of the best early warning signals we have for heart disease.

Although this study looked only at women, research has shown that other measures of insulin resistance - like the Triglyceride-Glucose (TyG) Index and HOMA-IR - are also strong predictors of heart disease in men[9,10].

You Might Have Insulin Resistance and Not Even Know It

The problem with most blood tests assessing glucose metabolism is they become abnormal once metabolic dysfunction has already progressed to prediabetes or diabetes - not early when insulin sensitivity is already impaired.

During the early stages, the pancreas compensates by producing more insulin to maintain blood glucose within a normal range. Even if blood sugar appears normal, the body is being damaged by chronic exposure to hyperinsulinaemia and insulin resistance. That is why fasting blood glucose, HbA1c and even continuous glucose monitoring (CGM) monitoring all look normal, lulling you into a false sense of security. Fasting insulin similarly cannot be relied upon as it can fluctuate day to day, varies between people, and is affected by stress, sleep and diet - so a single number doesn’t tell the full story.

Not carrying excess body fat does not mean you are immune from insulin resistance - it can occur in those of normal body weight. It is estimated that just over 30% of normal weight individuals may have underlying metabolic dysfunction[11]

Taking The Fight To Insulin Resistance

Fortunately, we now have more accurate tests to detect insulin resistance long before blood glucose or HbA1c start to rise - including LP-IR, TyG Index and HOMA-IR.

The good news? Insulin resistance is highly reversible when caught early and treated with the right interventions.

In my next articles, we’ll be taking a deep dive into how to test for insulin resistance, and the most effective, evidence-based ways to prevent and reverse insulin resistance - so you can take control of your health.

The information provided in this blog is for educational and general informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. No doctor/patient relationship is formed. Always seek the advice of your medical practitioner or another qualified healthcare provider with any questions you may have regarding your health or medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this blog. Reliance on any information provided here is solely at your own risk.

References

1. Lee SH, et al. Insulin Resistance: From Mechanisms to Therapeutic Strategies. Diabetes Metab J. 2022;46(1):15-37

2. Hardy OT, et al. What causes the insulin resistance underlying obesity?. Curr Opin Endocrinol Diabetes Obes. 2012;19(2):81-87

3. Bkaily G, et al. Pathophysiology of Prediabetes Hyperinsulinemia and Insulin Resistance in the Cardiovascular System. Biomedicines. 2025; 13(8):1842

4. Muniyappa R, et al. Role of insulin resistance in endothelial dysfunction. Rev Endocr Metab Disord. 2013;14(1):5-12

5. Zhang AMY, et al. Hyperinsulinemia in Obesity, Inflammation, and Cancer. Diabetes Metab J. 2021;45(3):285-311

6. Ullah MI, et al. Obesity: Clinical Impact, Pathophysiology, Complications, and Modern Innovations in Therapeutic Strategies. Medicines. 2025;12(3):19

7. Szablewski L. Insulin Resistance: The Increased Risk of Cancers. Curr Oncol. 2024;31(2):998-1027.

8. Dugani SB, et al. Association of Lipid, Inflammatory, and Metabolic Biomarkers With Age at Onset for Incident Coronary Heart Disease in Women. JAMA Cardiol. 2021;6(4):437-447

9. Tian X, et al. Association of lipid, inflammatory, and metabolic biomarkers with age at onset for incident cardiovascular disease. BMC Med. 2022;20(1):383

10. Gast KB, et al. Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis. PLoS One. 2012;7(12):e52036

11. Wang B, et al. Prevalence of Metabolically Healthy Obese and Metabolically Obese but Normal Weight in Adults Worldwide: A Meta-Analysis. Horm Metab Res. 2015;47(11):839-845