Metabolic Health and Insulin Resistance

Introduction

“[T]he ‘invisible epidemic’ of non-communicable diseases (NCDs) represents the world’s leading cause of death”, with more than 41 million dying annually (Piovani et al, 2022). NCDs, or chronic diseases, are non-contagious, have multiple risk factors, remain latent for long periods, are prolonged, cause functional impairment or disability, and may be incurable.

Excluding non-modifiable factors like age, gender, and ethnicity, Piovani et al (2022) note that the modifiable risk factors for developing NCDs are:

• metabolic/biological – excess weight/obesity, hyperglycaemia, hyperlipidaemia, and raised blood pressure
• behavioural – unhealthy diet, tobacco use, physical inactivity, and harmful use of alcohol or other substances
• socioeconomic issues – poverty, low public spending on health, limited access to health services
• environmental – climate change, sunlight, pollution

Most NCD deaths are preventable by eliminating important modifiable factors like:

• poor diet
• smoking
• alcohol misuse
• physical inactivity “which in turn lead to the metabolic/biological risk factors described above” (Piovani et al, 2022).

The nature of poor metabolic health

Unlike the case with many infectious and non-infectious diseases, no single clinical diagnostic or laboratory test can identify an individual with poor metabolic health. Combe Grove’s Dr Campbell Murdoch is a Somerset-based GP working in the NHS and he explains that many of the symptoms his patients consult him for “can be directly attributed to poor metabolic health, including difficulty losing weight and belly fat, feeling tired all the time, brain fog, energy dips throughout the day, always feeling hungry, and feeling fed up and hopeless with a loss of confidence.”

Why can poor metabolic health be difficult to spot?

The symptoms identified by Dr Murdoch tend to be non-specific, and we’ve previously seen that American endocrinologist Prof Gerald M Reaven described “a syndrome comprising a constellation of cardiovascular risk factors characterised by hyperinsulinaemia [excess secretion of insulin], glucose intolerance, dyslipidaemia [unhealthy concentrations of certain lipids] and hypertension [high blood pressure]. These symptoms, which could all be present in a single individual, is now widely referred to as metabolic syndrome (MetS)” (Kajee, 2023).

Insulin resistance, hyperinsulinaemia, and diagnostic challenges

This cluster of MetS symptoms “can all be centrally linked to insulin resistance (IR). There is a clearly defined association between IR and the individual components of MetS” (Kajee, 2023). IR is a reduced response to the hormone insulin, so when a cell stops responding to insulin it becomes insulin resistant: “Ultimately, as more cells throughout the body become insulin resistant, the body is considered insulin resistant” (Bikman, 2020). Further, IR is a state of hyperinsulinaemia: “That means a person with IR has more insulin in the blood than normal” (Bikman, 2020).

An interesting question now arises. If we can diagnose type 2 diabetes (T2D) by measuring blood glucose concentrations, why is it not as easy to diagnose IR?

This is because someone can have IR but still have normal blood glucose concentrations. However, the concentration that will NOT be normal is insulin because IR means having higher than normal concentrations of insulin. As Bikman (2020) notes: “[T]he problem is both finding a consensus value for ‘too much’ blood insulin and actually getting your blood insulin measured clinically; it’s not part of the standard tests most doctors order.”

Given this explanation, we can now envisage a situation where an individual with IR gradually becomes increasingly resistant to the effects of insulin “but the insulin is still working well enough to keep blood glucose in a normal range. This can develop over years, even decades” (Bikman, 2020). So, although glucose concentrations are often considered as the problem “we don’t recognise there’s an issue until the person is so insulin resistant that their insulin, no matter how much they produce, is no longer enough to keep their blood glucose in check” (Bikman, 2020).

Unsurprisingly, therefore, it may take years for T2D and MetS to become apparent.

This is confirmed by studies like that undertaken by Crofts et al (2016) who found that just over half of a cohort of participants with normal glucose tolerance were shown to have hyperinsulinaemia. Crofts et al (2016) explain: “Hyperinsulinaemia in the absence of impaired glucose tolerance may provide the earliest detection for metabolic disease risk and likely occurs in a substantial proportion of an otherwise healthy population.” Further, in their study cohort over “75% of people with hyperinsulinaemia lacked other clinical symptoms, such as impaired glucose tolerance or obesity, therefore suggesting hyperinsulinaemia is a ‘silent disease’” (Crofts et al, 2016).

Insulin resistance and other health conditions

IR is sometimes referred to as “prediabetes” because “every year, 10% of people with IR will progress to T2D if they don’t change course – but T2D is just the tip of the iceberg … IR either instigates or aggravates the following conditions” (Ede, 2024), some of which include:

• Non-alcoholic fatty liver disease (NAFLD). Insulin instructs the liver to convert excess glucose to fat
• Hearing problems. Over 90% of people with inner ear problems like tinnitus, vertigo and hearing loss have high concentrations of insulin
• Coronary artery disease (CAD). High insulin concentrations promote high blood pressure and coronary artery inflammation. At least 75% of those with CAD have IR
• Polycystic ovarian syndrome and infertility (PCOS). High concentrations of insulin raise testosterone concentrations in the ovaries. 70% of women with PCOS have IR
• Erectile dysfunction (ED). Over 50% of men with ED have IR
• Obesity. High concentrations of insulin instruct fat cells to stop burning fat. Over 90% of people with obesity have IR
• Stroke. High concentrations of insulin promote the formation of blood clots, making it more difficult for blood vessels to relax and dilate

Finally

In the context of the substantial contribution of metabolic-related disorders to NCDs being the world’s leading cause of death, Piovani et al (2022) note that health-promotion initiatives encouraging healthy lifestyles, “addressing modifiable risk factors … and initiatives aiming to manage chronic diseases and related complications (so that their progress is slowed or stopped), can play a key role in controlling the ‘invisible epidemic’ of NCDs, on the national and the global level.”

Encouragingly, help is available to address – and redress – the often unseen problems caused by poor metabolic health.

References

Bikman Benjamin. What is insulin resistance? In Why We Get Sick. BenBella Books: Dallas; 2020

Crofts C, Schofield G, Zinn C, et al. Identifying hyperinsulinaemia in the absence of impaired glucose tolerance: An examination of the Kraft database. Diabetes Res Clin Pract. 2016; 118: 50–57. http://doi.org/10.1016/j.diabres.2016.06.007

Ede Georgia. Insulin Resistance: Your brain’s silent enemy. In Change Your Diet, Change Your Mind. Yellow Kite: London; 2024

Kajee H. Metabolic syndrome. In Ketogenic: the science of therapeutic carbohydrate restriction in human health. Ed. Nutrition Network. Elsevier: London; 2023

Piovani D, Nikolopoulos GK, Bonovas S. Non-Communicable Diseases: The Invisible Epidemic. J Clin Med. 2022; 11: 5939. https://doi.org/10.3390/jcm11195939