Insulin resistance is arguably the single most important metabolic concept in weight management and it is almost entirely absent from mainstream diet culture. The premise of ‘eat less, move more’ assumes a level physiological playing field. For people with insulin resistance, that field is anything but level.
What Is Insulin and What Does Resistance Mean?
Insulin is a peptide hormone produced by the pancreatic beta cells. Its primary role is to facilitate the uptake of glucose from the bloodstream into cells, where it is used for energy. When cells become resistant to insulin’s signal, the pancreas compensates by producing more insulin, resulting in hyperinsulinaemia (chronically elevated insulin levels).
Chronically elevated insulin is profoundly anti-lipolytic: it actively inhibits the breakdown of stored fat. The body cannot mobilise fat stores while insulin is high, regardless of caloric deficit. This is why patients with significant insulin resistance can adhere rigorously to a calorie-restricted diet and still fail to lose meaningful weight.
How Does Insulin Resistance Develop?
- Chronic caloric excess, particularly from refined carbohydrates and ultra-processed foods
- Visceral adiposity (fat surrounding the organs), which releases inflammatory cytokines that impair insulin signalling
- Physical inactivity: skeletal muscle is the primary site of glucose disposal; sedentary behaviour reduces its capacity
- Chronic stress and elevated cortisol: cortisol raises blood glucose and worsens insulin sensitivity
- Sleep deprivation: even one night of poor sleep measurably impairs insulin sensitivity
- Genetic predisposition: South Asian, Middle Eastern, and certain other ethnicities have higher intrinsic susceptibility
Diagnosis: Why Fasting Glucose Is Not Enough
Standard NHS testing for ‘diabetes risk’ typically involves fasting plasma glucose and HbA1c. These measures identify frank diabetes or pre-diabetes, but insulin resistance can be severe and clinically significant long before glucose levels rise. The pancreas compensates for years by producing ever-greater amounts of insulin, maintaining normal glucose while the insulin environment becomes increasingly pathological.
Fasting insulin, HOMA-IR (Homeostatic Model Assessment of Insulin Resistance), and a glucose-insulin ratio provide far greater sensitivity for identifying early insulin resistance. These are included in our standard diagnostic blood panel.
Treatment: A Multi-Modal Approach
Addressing insulin resistance requires a targeted combination of nutritional intervention (carbohydrate quality and meal timing), physical activity prescription, sleep optimisation, stress management, and where appropriate, pharmacological support. GLP-1 medications are directly insulin-sensitising in addition to their appetite effects, which is one reason they are so effective in this population.
Specific nutritional supplements including berberine, inositol, and alpha-lipoic acid have meaningful evidence for improving insulin sensitivity as adjuncts to dietary change. These are prescribed as part of our integrative approach where clinically indicated.
Written by Dr Saima Ajaz, MBBS, MRCGP
Lead Clinician, Medical Director, Harley Weight Loss Clinic
