What is the main cause of insulin resistance? Insulin resistance develops when the body's cells become less responsive to insulin, a hormone that regulates blood glucose. Whilst no single cause exists, excess visceral adiposity (particularly abdominal fat) is the most significant modifiable driver in the UK population. Physical inactivity, dietary patterns high in refined carbohydrates and saturated fats, and genetic predisposition also contribute substantially. Understanding these interconnected factors is essential for prevention and early intervention, particularly as insulin resistance often progresses silently for years before symptoms appear.

What Is Insulin Resistance and How Does It Develop?

Insulin resistance is a metabolic condition in which the body's cells become less responsive to the hormone insulin, which is produced by the pancreas. Insulin normally facilitates the uptake of glucose from the bloodstream into cells, where it is used for energy. When cells become less responsive to insulin's effects, the pancreas compensates by producing more insulin to maintain normal blood glucose levels. Over time, this compensatory mechanism can become insufficient, leading to elevated blood glucose and potentially progressing to non-diabetic hyperglycaemia (NDH, also called prediabetes) or type 2 diabetes.

The development of insulin resistance is a gradual process involving complex interactions between genetic predisposition and environmental factors. At the cellular level, insulin resistance involves impaired signalling pathways, particularly affecting the insulin receptor substrate proteins and glucose transporter type 4 (GLUT4) translocation. This may result in reduced glucose uptake by muscle and adipose tissue, whilst the liver continues to produce glucose inappropriately.

Inflammation appears to play an important role in the pathophysiology of insulin resistance. Adipose tissue, particularly visceral fat, secretes pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), which may interfere with insulin signalling. Additionally, the accumulation of lipids in non-adipose tissues (ectopic fat deposition) in the liver and muscle can further impair insulin sensitivity.

Insulin resistance often exists for years before clinical symptoms become apparent. Many individuals remain asymptomatic until blood glucose levels rise significantly. Early detection is important, particularly in high-risk populations. Rather than universal screening, NICE recommends a risk-based approach using validated tools (such as QDiabetes) to identify those at high risk, followed by appropriate blood tests to assess glycaemic status.

Main Causes of Insulin Resistance in the UK

Excess adiposity, especially visceral fat, is a major modifiable driver of insulin resistance in the UK population. Visceral adipose tissue is metabolically active and releases free fatty acids and inflammatory mediators that may impair insulin signalling pathways. According to the Health Survey for England, approximately 64% of adults in England are overweight or obese, making this a significant risk factor for insulin resistance.

Physical inactivity represents another major contributory factor. Sedentary behaviour reduces glucose uptake by skeletal muscle, which is the primary site of insulin-mediated glucose disposal. Regular physical activity enhances insulin sensitivity through multiple mechanisms, including increased GLUT4 expression and improved mitochondrial function. The UK Chief Medical Officers recommend at least 150 minutes of moderate-intensity activity weekly, yet many adults fail to meet these targets.

Dietary patterns prevalent in the UK contribute substantially to insulin resistance. Diets high in refined carbohydrates, added sugars, and saturated fats promote weight gain and metabolic dysfunction. Ultra-processed foods, which constitute a significant proportion of UK dietary intake, are associated with insulin resistance, though this relationship may be partly mediated by their effects on energy intake and body weight. Conversely, diets rich in fibre, whole grains, and unsaturated fats are associated with improved insulin sensitivity.

Genetic predisposition also plays an important role, with certain ethnic groups showing higher susceptibility. South Asian, African-Caribbean, and Middle Eastern populations in the UK demonstrate increased insulin resistance at lower body mass indices compared to white European populations. This genetic vulnerability interacts with environmental factors to determine individual risk, highlighting the multifactorial nature of insulin resistance development.

Risk Factors That Increase Insulin Resistance

Several demographic and physiological factors increase the likelihood of developing insulin resistance. Age is a significant risk factor, with insulin sensitivity declining progressively after the age of 40, partly due to age-related loss of muscle mass and increased adiposity. Family history of type 2 diabetes substantially elevates risk, suggesting strong genetic components involving multiple genes that regulate glucose metabolism and insulin action.

Ethnicity profoundly influences insulin resistance risk. As mentioned, individuals of South Asian, African-Caribbean, Black African, and Chinese descent face higher risk at lower BMI thresholds. NICE guidance (PH46) recommends using lower BMI thresholds (23 kg/m² and 27.5 kg/m² rather than 25 kg/m² and 30 kg/m²) to trigger weight management advice and diabetes risk assessment in these groups. Risk assessment using validated tools like QDiabetes should precede blood testing.

Hormonal factors also contribute to insulin resistance. Polycystic ovary syndrome (PCOS) affects approximately 10% of women of reproductive age in the UK and is characterised by significant insulin resistance, independent of obesity. Women with PCOS should be screened for glucose intolerance or diabetes using HbA1c or oral glucose tolerance tests. Pregnancy induces physiological insulin resistance, which normally resolves postpartum; however, women with gestational diabetes have substantially increased risk of developing permanent insulin resistance and type 2 diabetes later in life.

Medications can induce or worsen insulin resistance. Corticosteroids (such as prednisolone) are well-recognised culprits, promoting hyperglycaemia through multiple mechanisms including increased hepatic glucose production and reduced peripheral glucose uptake. Atypical antipsychotics (particularly olanzapine and clozapine) and some antiretroviral medications used in HIV treatment also impair insulin sensitivity. Patients on long-term therapy with these agents require regular metabolic monitoring as recommended in their Summary of Product Characteristics. Suspected side effects should be reported via the MHRA Yellow Card Scheme (yellowcard.mhra.gov.uk).

How Lifestyle and Diet Contribute to Insulin Resistance

Dietary composition exerts significant effects on insulin sensitivity. Diets high in refined carbohydrates and added sugars cause rapid spikes in blood glucose and insulin levels, which may contribute to progressive insulin resistance. Sugar-sweetened beverages are particularly problematic, providing concentrated calories without satiety signals. The UK Scientific Advisory Committee on Nutrition (SACN) recommends limiting free sugars to less than 5% of total energy intake.

Saturated fat intake may impair insulin signalling through mechanisms including inflammation and lipotoxicity. Conversely, replacing saturated fats with unsaturated fats may be beneficial for metabolic health. Omega-3 fatty acids found in oily fish have been associated with reduced inflammation, though their direct effects on insulin sensitivity are less consistently demonstrated. The Mediterranean dietary pattern, emphasising vegetables, fruits, whole grains, legumes, nuts, and olive oil, has evidence for improving metabolic health and is one of several dietary approaches that may help improve insulin sensitivity.

Dietary fibre plays a protective role against insulin resistance. Soluble fibre slows glucose absorption, reducing postprandial glucose and insulin excursions. It also promotes beneficial gut microbiota, which produce short-chain fatty acids that may enhance insulin sensitivity. SACN recommends UK adults consume 30g of fibre daily, yet average intake falls significantly short at approximately 18g.

Physical activity patterns are equally crucial. Aerobic exercise improves insulin sensitivity by increasing glucose uptake in skeletal muscle during and after activity. Resistance training builds muscle mass, expanding the body's glucose disposal capacity. Even a single bout of exercise can enhance insulin sensitivity for 24–48 hours. Conversely, prolonged sitting is associated with increased insulin resistance, even in individuals who meet physical activity guidelines. Breaking up sedentary time with brief activity breaks every 30 minutes may help mitigate these adverse effects, as supported by emerging research.

Medical Conditions Linked to Insulin Resistance

Type 2 diabetes mellitus represents the most significant clinical consequence of insulin resistance. The condition develops when pancreatic β-cells can no longer produce sufficient insulin to overcome peripheral insulin resistance, resulting in chronic hyperglycaemia. Approximately 90% of people with type 2 diabetes have underlying insulin resistance. In the UK, diabetes is diagnosed when HbA1c is 48 mmol/mol or above; in asymptomatic individuals, a confirmatory test is required. Non-diabetic hyperglycaemia (NDH) is defined as HbA1c 42-47 mmol/mol.

Non-alcoholic fatty liver disease (NAFLD) is both a cause and consequence of insulin resistance, creating a cycle of metabolic dysfunction. Insulin resistance promotes hepatic fat accumulation, whilst fatty liver further impairs hepatic insulin sensitivity and increases glucose production. NAFLD affects approximately 25% of the UK population and can progress to non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. NICE guidance (NG49) recommends case-finding in high-risk individuals using non-invasive fibrosis assessment tools (such as FIB-4 or NAFLD fibrosis score). Liver function tests and ultrasound may be indicated when these scores suggest advanced fibrosis or when liver enzymes are abnormal.

Cardiovascular disease shares common pathophysiological pathways with insulin resistance. Insulin resistance promotes atherogenic dyslipidaemia (elevated triglycerides, low HDL cholesterol, small dense LDL particles), hypertension, and endothelial dysfunction. These factors substantially increase the risk of coronary artery disease, stroke, and peripheral vascular disease. The UK cardiovascular risk assessment tools (such as QRISK3) incorporate diabetes status, reflecting this association.

Polycystic ovary syndrome (PCOS) demonstrates bidirectional relationships with insulin resistance. Hyperinsulinaemia stimulates ovarian androgen production, contributing to the hormonal imbalances characteristic of PCOS. Women with PCOS should be screened for glucose intolerance or diabetes using HbA1c or oral glucose tolerance tests at diagnosis and periodically thereafter. Obstructive sleep apnoea also associates strongly with insulin resistance, partly through intermittent hypoxia and sleep fragmentation, which activate stress pathways and promote metabolic dysfunction.

Preventing and Managing Insulin Resistance

Lifestyle modification represents the cornerstone of both preventing and managing insulin resistance. Weight loss of just 5–10% of body weight significantly improves insulin sensitivity and reduces progression to type 2 diabetes. The NHS Diabetes Prevention Programme offers structured lifestyle interventions for individuals identified with non-diabetic hyperglycaemia (HbA1c 42–47 mmol/mol), providing education, dietary advice, and physical activity support over nine to twelve months.

Dietary interventions should focus on sustainable, evidence-based approaches. Reducing refined carbohydrates and added sugars whilst increasing fibre intake forms the foundation. Portion control and regular meal patterns can help regulate energy intake. Mediterranean and low-glycaemic-index diets have evidence supporting their benefits. NICE guidance (PH38) emphasises energy balance, reduced saturated fat intake, and lower glycaemic load approaches. Referral to NHS dietetic services may be appropriate for individuals requiring structured support.

Physical activity recommendations should be individualised and progressive. The UK Chief Medical Officers recommend 150 minutes of moderate-intensity aerobic activity weekly, combined with resistance training on two or more days, which improves insulin sensitivity substantially. For sedentary individuals, starting with achievable goals (such as 10-minute walks) and gradually increasing intensity and duration promotes adherence. Reducing sedentary time is equally important.

Pharmacological interventions may be considered in specific circumstances. Metformin is recommended by NICE (PH38) for adults at high risk of type 2 diabetes (with NDH) whose HbA1c or fasting glucose continues to rise despite lifestyle measures, particularly if BMI ≥35 kg/m², and for women with a history of gestational diabetes who are not responding to lifestyle interventions.

Monitoring and follow-up are essential. Individuals with NDH should undergo HbA1c testing at least annually (consider 6-monthly if values are rising or near diagnostic thresholds). When to contact your GP: seek medical advice if you experience symptoms of hyperglycaemia (excessive thirst, frequent urination, unexplained weight loss, fatigue, blurred vision), have risk factors for insulin resistance, or have been diagnosed with non-diabetic hyperglycaemia and need support with lifestyle modification. Early intervention significantly reduces the risk of progression to type 2 diabetes and associated complications.

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