Insulin resistance: symptoms, how it is diagnosed and how to reverse it

Insulin resistance is a state in which the liver, muscle and fat respond less well to insulin, so the pancreas has to produce more of it to keep blood glucose in check. It rarely causes symptoms, there is no generally accepted test to diagnose it, and what has been shown to reverse it most is losing weight and moving more: losing around 5% of body weight already improves insulin sensitivity in the liver, muscle and fat. In Spain, no medicine is authorised for insulin resistance as such.

What insulin resistance is

Insulin is the hormone the pancreas makes so that glucose in the blood can enter the cells. Insulin resistance is present when those cells, above all in the liver, muscle and fatty tissue, respond less well to its signal. To compensate, the pancreas produces more insulin, and for a while blood glucose stays normal at the cost of high insulin levels. When the pancreas can no longer keep up, glucose rises: first prediabetes appears and, if it keeps rising, type 2 diabetes.

It is mostly acquired and linked to excess body fat. According to the US National Institutes of Health (NIDDK), it is favoured by overweight or a large waist, being 35 or older, a family history of diabetes, a sedentary lifestyle, smoking, polycystic ovary syndrome, sleep apnoea and some medicines, such as glucocorticoids.

It is not rare. In the Di@bet.es study, almost 30% of Spanish adults had some disorder of carbohydrate metabolism, diabetes included, and roughly half of the diabetes cases had not been diagnosed. If your blood test falls in that in-between zone, it is worth reading what prediabetes is and how it is managed.

Symptoms: why it is almost never noticed

Like prediabetes, it does not usually cause symptoms. It is found through its consequences: glucose or HbA1c starting to rise, high triglycerides or blood pressure, or an ultrasound showing fat in the liver, which deserves its own read: metabolic fatty liver disease, what it is and what can be done.

The sign you can see is acanthosis nigricans: darker, velvety skin in the armpits, groin or neck folds. MedlinePlus links it to the insulin resistance of diabetes and obesity, although it can appear in healthy people and, if it develops quickly and extensively, other causes must be ruled out. It is a reason to see a doctor, not a diagnosis.

You do not need to have obesity to have it, either. Among 283 primary care adults in Valencia, 31.7% of those with a normal waist met the criterion for insulin resistance, compared with 54.6% of those with abdominal obesity; waist size and triglycerides were the best independent indicators, two of the building blocks of metabolic syndrome.

How it is diagnosed and what a high fasting insulin level means

There is no generally accepted insulin resistance test for routine clinical use. The reference method, the hyperinsulinaemic-euglycaemic clamp, is a research technique, and the NIDDK notes that the insulin resistance test is used mainly in studies. In practice, what gets diagnosed are its consequences, prediabetes or diabetes, using fasting glucose, glycated haemoglobin (HbA1c) or an oral glucose tolerance test.

The closest thing to a number is HOMA-IR, calculated from fasting glucose and insulin. Described in 1985, it correlated well with the clamp (0.88), but its authors warned of its low precision: a coefficient of variation of 31%.

And there is no universal cut-off. Several have been published for the Spanish population:

• Ascaso and colleagues (Medicina Clínica, 2001), in non-diabetic adults in Valencia: a HOMA-IR of 3.8 or more, or a fasting insulin of 16.7 mU/l or more, the 90th percentile of a subgroup with no criteria for insulin resistance.
• The EPIRCE study (Gayoso-Diz and colleagues, 2013), with 2,459 adults from a random Spanish sample: 3.46 using the 90th percentile, 2.05 using the value that best flagged metabolic syndrome, and 1.85 in men without diabetes.

On top of that, laboratories do not measure insulin in the same way: a working group of the American Diabetes Association found that seven out of ten commercial methods deviated by more than 15.5% from the reference method in between 36% and 100% of samples.

Applied to your blood test: a high fasting insulin is a clue, not a diagnosis on its own. It makes sense alongside glucose, HbA1c, triglycerides, blood pressure and waist size; in the Valencia study, a fasting glucose of 110 mg/dl or more was associated with an odds ratio of 5.9 for insulin resistance.

«I diet and I don't lose weight»: what role insulin plays

This is the sentence many people arrive with, and the frustration is real. But the evidence does not support the idea that insulin resistance stops you losing weight or that it requires a special diet. In the DIETFITS trial (JAMA, 2018), 609 adults with overweight followed a healthy low-fat or low-carbohydrate diet for a year: they lost 5.3 and 6.0 kg on average, with no significant difference, and baseline insulin secretion did not predict who would do better on each diet.

The StatPearls review adds that weight gain goes hand in hand with high insulin, but may be due more to a sustained excess of calories than to insulin itself. The diet that works is the one you can keep up, and if losing weight through habits alone is very hard, that is not a personal failure: it is a reason to ask for a medical assessment.

How to reverse insulin resistance: what has been shown to work

The NIDDK puts it cautiously: healthy living may help prevent or reverse insulin resistance and prediabetes. These are the levers with data behind them.

Losing weight, even 5%

In a randomised trial (Cell Metabolism, 2016) in people with obesity, losing around 5% of body weight improved insulin sensitivity in fatty tissue, liver and muscle at the same time, as well as the function of the pancreatic cells that make insulin. Reaching around 11% and 16% brought further improvements in muscle and in that pancreatic function.

In the Diabetes Prevention Program (NEJM, 2002), 3,234 people with raised glucose aimed to lose at least 7% of their weight and do 150 minutes of physical activity a week: new cases of diabetes fell by 58% compared with placebo, more than with metformin, which reduced them by 31%. A later analysis calculated that each kilo lost was associated with a 16% lower risk.

Moving counts in its own right

Physical activity improves insulin sensitivity in muscle. In the same trial, among the 495 people who did not reach the weight goal in the first year, those who met the activity target had 44% less diabetes. Even if the scales do not move, exercise adds up.

What to eat: the pattern, more than the forbidden food

No single food reverses insulin resistance on its own. There are Spanish data on the Mediterranean pattern: in a subgroup analysis of the PREDIMED trial, with 3,541 people aged 55 to 80 at high cardiovascular risk, a Mediterranean diet with extra virgin olive oil, without calorie restriction, was associated with 40% less diabetes than a low-fat diet. It is a signal in favour, not a prescription.

Getting enough sleep

In a small trial (Annals of Internal Medicine, 2012), seven healthy adults spent four nights with 4.5 hours in bed: their fatty tissue needed almost three times as much insulin to reach half of its maximum response, and whole-body insulin sensitivity fell. It is only seven people, but the direction is consistent with the link between sleep apnoea and insulin resistance.

Are there medicines for insulin resistance?

In Spain, no medicine is authorised for insulin resistance as a diagnosis. Metformin has a single indication in its summary of product characteristics approved by the AEMPS, type 2 diabetes; using it only because of a high insulin or HOMA would be off-label use, and in the Diabetes Prevention Program it came behind lifestyle change.

Obesity is a different matter. Semaglutide (Wegovy) and tirzepatide (Mounjaro) are authorised in Spain, on medical prescription, for weight management alongside a low-calorie diet and more physical activity, in adults with a body mass index of 30 or more, or of 27 to 30 with a weight-related condition such as prediabetes. What is treated is weight, not an insulin figure.

In the SURMOUNT-1 trial, among 1,032 people with obesity and prediabetes, those who received tirzepatide for three years lost between 12.3% and 19.7% of their weight depending on the dose, compared with 1.3% on placebo, and 1.3% developed type 2 diabetes compared with 13.3%. We explain the mechanism in what GLP-1 medicines are and how they work.

What not to believe

• «With insulin resistance it is impossible to lose weight.» The data do not support it, and losing 5% of your weight is exactly what improves it most.
• «You have to cut out carbohydrates.» In DIETFITS, the low-carbohydrate and low-fat diets led to similar losses; what matters more is that the diet can be kept up.
• «A high insulin result is already the diagnosis.» It is a clue, with cut-offs and measurements that change depending on the study and the laboratory.
• «If your glucose is normal, there is nothing to look at.» At first the pancreas compensates with more insulin and glucose stays normal for a while.

What to take away

Insulin resistance is not a label for life: it is a state that responds, and sustained weight loss, movement, dietary pattern and sleep are the levers with the most evidence. When habits are not enough and weight is part of the problem, what exists in Spain today is medical weight-loss treatment, with a prior assessment, prescription where appropriate by a registered doctor and ongoing follow-up. You can check in a few minutes whether you are eligible.