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Obesity, Insulin Resistance, And The Development Of Dyslipidaemia
Published on: September 24, 2025
Obesity, Insulin Resistance, And The Development Of Dyslipidaemia
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Natalia Fitas

Introduction

Obesity is on the rise, affecting quality of life and management for many individuals in the 21st century, with the World Health Organisation estimating that the global prevalence of obesity has doubled from 1990 to today.1 Obesity is defined as the excessive accumulation of body fat. Alongside growing risk factors for obesity, such as high blood pressure, poor sleep, and cardiovascular disease, other factors contribute to the development of obesity, including social, economic, and lifestyle factors.3 However, amongst the complications caused by obesity, metabolic syndromes correlate with insulin resistance, commonly observed in patients with type 2 diabetes. This early metabolic disorder is a state in which the body’s tissues respond poorly to insulin, and the excess BMI explains a 16% variance in insulin resistance.4 

The development of dyslipidaemia is also a concern of obesity; this lipid disease is characterised by abnormal serum levels of low-density lipoprotein (LDL) cholesterol (“bad”), triglycerides, and lipoproteins. These small molecules can cluster together to aid in the development of cardiovascular disease and type 2 diabetes.5 

The purpose of this article is to explore and translate the interlinked relationships between these three syndromes and how they foster each other to form implications. 

Obesity and its metabolic consequences

The severity of obesity isn’t solely based on the BMI, but on the location where the fat primarily deposits in the body. Central obesity, defined as excess fat deposition in the visceral (soft) tissues of the organs of the body, including the lungs, the heart, and the organs of the digestive system, poses a far greater threat to the individual than if the fat is distributed peripherally around the lower limbs, such as the hips and thighs.6 The threat comes from central obesity, carrying more problematic risks of diabetes, high blood pressure (hypertension), atherosclerosis, dyslipidaemia, and cancers.7

The principle of how the fat is stored in these visceral adipose tissues can have numerous effects on their immunological and protective roles.8 Due to the overproduction and dysfunction of fat, it causes inflammation from the interaction of the released bacteria with the high local concentrations of fatty acids, encouraging infection.6 This chronic low-grade inflammation disrupts the insulin signalling pathway and increases the level of free fatty acids released into circulation. The influx of these fatty acids into the liver triggers the production of triglyceride-rich lipoproteins, like LDLs, setting the stage for insulin resistance and dyslipidaemia.9,10

Insulin resistance: definition, mechanisms, and measurement

Insulin is a hormone produced by the β-cells in the pancreas, which helps to move digested blood sugars (glucose) from the bloodstream into cells, where it can be processed into energy and involved in anabolic processes, including tissue growth and development. In addition to processing blood sugars, insulin also controls lipid metabolism by promoting lipid synthesis in the liver and fat cells by breaking down triglycerides into small fatty acids.11

In an individual with insulin resistance, the pancreas doesn’t respond normally to insulin. By not recognising it, the β-cells in the pancreas produce extra insulin, so that blood sugar stays within the normal range (between 4.0 to 5.4 mmol/L). After eating, food causes a rapid rise in blood sugar (hyperglycaemia), which exceeds the normal range, causing glucose intolerance and later type 2 diabetes.11 A key problem of hyperglycaemia can induce an overload of harmful reactive oxygen species (ROS) and advanced glycation end products (AGEs); these unstable molecules can damage cells by causing inflammation and a drop in nitric oxide levels. In the long term, it sets off an inflammatory cascade contributing to endothelial dysfunctions in the narrowing of blood vessels and arteries in the heart, which are both early steps in the development of atherosclerosis.12,13

Insulin resistance and dyslipidaemia

Insulin effects on metabolism are critical for the normal function of cellular body functions (e.g. body temperature regulation). It’s critically important for the control of adequate fat metabolism by clearing the flowing fatty acids and glycerol (sugar molecule) from the bloodstream back into the liver and maintaining healthy (“good”) high-density lipoproteins (HDL) cholesterol levels.14

However, when insulin resistance occurs, these processes are disrupted, leading to: 

  • Increased levels of  “bad” cholesterol in the blood: insulin resistance upregulates LDL-cholesterol activity, leading to the condition of atherosclerosis
  • Decreased levels of “good” cholesterol: HDL cholesterol levels are lower in individuals with insulin resistance, making it harder for the body to clear cholesterol out of the arteries15
  • Vital organs (visceral) are covered with dense fat: by removing fatty acids and triglycerides from the bloodstream, they build up around organs instead, increasing the risk of high blood pressure, heart diseases, and breathing difficulties16

This histological pattern of low HDL-cholesterol, higher LDL-cholesterol, and increased triglyceride levels is known as dyslipidaemia, and it’s a key driver for heart disease in people with obesity and insulin resistance.

Obesity as the driver of insulin resistance

As previously discussed, the most critical category of obesity is the deposition of fat in the visceral areas of the body (heart, lungs, digestive tract).6 The adipose (fat) tissues in these areas release several free fatty acids, which are transported to the liver, resulting in an increase in LDL and glucose secretion as well as a decrease in those “good” HDLs. This burden of circulating glucose troubles the pancreas in over-stimulating the β-cells in such a way that they become immune, leading to insulin resistance.11

Too many free fatty acids can also cause oxidative stress, consequently causing damage to cells by ROS. These ROS can trigger direct changes inside cells that can cause insulin resistance to worsen.17

The encouraging news is that research shows weight loss is proven to be beneficial for lowering the impact of insulin resistance by 10%, with or without physical activity. It yielded metabolic health benefits from the decrease of waist circumference and adipose fat tissue to bettering insulin sensitivity, even in the absence of cardiovascular risk factors (LDL-cholesterol).18

Management strategies

Lifestyle actions

  • Diet: A focus on calorie-deficient balanced meals rich in vegetables, whole grains, lean proteins (low-fat, seafood, fish, fat-free dairy), fruit, with the reduction in sugary drinks and refined carbohydrates helps lower cardiovascular risk patterns and type 2 diabetes19
  • Regular physical activity: Aerobic exercise (e.g. running, walking) improves insulin sensitivity, glucose tolerance, and reduces visceral body fat. This sustainable weight-loss achievement effectively controls metabolism20 
  • Sleep: Proper sleep of 7-8 hours/night, also known as the circadian rhythm, is likewise linked to controlling obesity, nutritional fluxes and insulin resistance21

Drug interventions

For further support and tailored treatment, your doctor and health service provider may recommend:

  • Fibrates or omega-3 supplements: Regulate steps in lipid and lipoprotein metabolism, aiding the prevention of dyslipidaemia22
  • Statins: Aid the regulation of LDL cholesterol, helping to reduce any cardiovascular risks that fibrates are unable to control23
  • Semaglutide: a GLP-1 agonist drug that offers cardiovascular benefits for overweight or obese individuals24
  • Metformin: a clinically approved drug for patients with insulin resistance, type 2 diabetes, polycystic ovary syndrome (PCOS), and obesity25

Surgery

Metabolic surgery, also known as bariatric surgery, is a safe and effective route in resolving complications in severely obese patients. It leads to significant improvements in cardiovascular health by lowering lipid profiles, lowering blood pressure, and enhancing insulin control.26

Summary

Obesity is a growing global health challenge, with rates doubling since 1990. It is defined as excessive body fat, quantified by a BMI >30 kg/m2. It is linked to serious health problems with risks, including high blood pressure, sleep disturbances, heart disease, and metabolic disorders. One condition that correlates with obesity is insulin resistance, a condition where the body’s cells respond poorly to insulin, forcing the pancreas to produce more to keep blood sugar stable. If not managed or treated early, it can often lead to type 2 diabetes and damage to blood vessels through inflammation and oxidative stress. 

In particular, central obesity, where fat is deposited around organs including the heart, lungs, and the abdomen, causes the biggest threat as it promotes dyslipidaemia. Dyslipidaemia is classified by the individual carrying high LDL (“bad”) cholesterol, low HDL (“good”) cholesterol, and raised triglycerides. Together, insulin resistance and dyslipidaemia increase the risk of cardiovascular complications.

Lifestyle choices, such as balanced eating, regular aerobic exercise, and good sleep, can significantly improve these conditions by controlling lipid levels and fat deposits. In some cases, oral medications (e.g. statins, metformin, GLP-1 agonists) or bariatric surgery may be recommended.

References

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Natalia Fitas

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