Obesity and Insulin Resistance: Symptoms, Diagnosis, and Treatment

Anyone can have insulin resistance. Around one in three Americans develops it, including four in 10 people aged 18-44. However, on the list of risk factors, obesity and overweight are typically at the top. That’s because obesity and insulin share a complicated relationship.

Obesity and insulin resistance are interconnected in a variety of ways. Insulin resistance can raise a red flag that a person is trending toward diabetes. Long before type 2 diabetes and even prediabetes is recognized, insulin resistance is already creeping up. There is considerable overlap between these diseases: 90% of people diagnosed with type 2 diabetes also live with overweight or obesity.

Insulin resistance, defined as fasting blood glucose of 100 mg/dl or higher, is a common factor in other chronic metabolic diseases as well, including fatty liver disease, dyslipidemia, and some cancers.

As medical professionals treating people with obesity, we are painfully aware of this link and in a position to make a difference. According to the Journal of the American Heart Association, reducing the prevalence of obesity may prevent up to half of new type 2 diabetes cases in the U.S. Focusing on insulin resistance lets us tackle this serious issue a little earlier in the timeline.

Understanding the Link Between Obesity and Insulin Resistance

As blood sugar increases, beta cells in the pancreas secrete more insulin in an effort to keep it in the normal range. A tug-of-war ensues between forces attempting to remove and store sugar in the body’s cells, as those cells that are “full” become less sensitive to the actions of insulin. The body struggles to maintain blood sugar at the correct level. Eventually, the body does not produce enough insulin to keep up.

Insulin resistance can happen due to a combination of genetics and lifestyle and is related to inflammation in the body. There are many biological stress factors that can set insulin resistance in motion, including excess caloric intake.

When treating patients with obesity, it is important to check for insulin resistance. The American Heart Association reports that 70% of people with obesity have it.

Insulin resistance can appear 10 to 15 years before the onset of type 2 diabetes. Treating it early can help a person avoid type 2 diabetes and other related health issues. The presence of obesity can worsen the complications arising from type 2 diabetes, such as nephropathy, retinopathy, and neuropathy. Understanding the relationship between these diseases is crucial to developing effective prevention and management strategies for both.

Losing weight with insulin resistance is more difficult because the body stores excess blood sugar as fat. Insulin resistance is linked to other health concerns as well. For example, a 2021 study found that it doubles the risk of major depression. We have our work cut out for us.

Lifestyle Factors Influencing Obesity and Insulin Resistance

Insulin resistance can be acquired, genetic, or a combination of the two. Researchers are still working to understand it, but point to excess body fat—especially around the midsection—as the primary cause. This means that much of what we know about the causes of obesity also affects insulin resistance. For example, people with insulin resistance may consume too many highly processed or nutrient-poor foods.

A number of genes are connected with the condition. For example, research by Joshua Knowles, MD, PhD has linked it to the genes NAT2 and NAT1. He led a study where the expression of NAT1 was suppressed in mice. This interfered with the mice’s mitochondria, leading to weight gain and increased biomarkers for inflammation.

Some medications—such as steroids, and some blood pressure medications, psychiatric medications, and HIV treatments—are also linked with insulin resistance. Age also appears to increase an individual’s proclivity for insulin resistance.

Pathophysiology of Obesity-Induced Insulin Resistance

Suggested underlying culprits include mitochondrial function, as mentioned above, lipotoxicity, and that familiar fiend, inflammation.

Inflammation of adipose tissue leads to hormonal and inflammatory changes. Adipose tissue secretes—among other hormones—adipokines. Adipokines are important mediators of insulin signaling, as well as fatty acid oxidation, de-novo lipogenesis, gluconeogenesis, glucose uptake, and other metabolic processes.

Specifically, subcutaneous white adipose tissue deserves our attention.

It stores excess lipids, but when it exceeds its storage capacity, visceral fat begins to accumulate around organs. Visceral fat contributes to various metabolic pathologies. Excessive accumulation of free fatty acids in insulin-sensitive non-adipose tissues can lead to lipotoxicity.

Inflammation and obesity

Obesity predisposes a person to pro-inflammatory states and oxidative stress. Some describe obesity itself as a state of chronic, low-grade inflammation. Obesity induces cell death and inflammation, leading to metabolic changes, including insulin sensitivity. Adipose tissue macrophages secrete pro-inflammatory cytokines, which can impair insulin signaling.

Rare forms of insulin resistance

There are also rare, severe, typically inherited forms of insulin resistance. For example,

type A insulin resistance syndrome tends to affect adolescent girls, who are not typically overweight. The condition is inherited and results from mutations in the INSR gene.

Clinical Implications and Diagnosis

A person with insulin resistance may not have any symptoms, which makes monitoring those at risk important. There are certain signs or risk factors that can alert you to the increased likelihood of insulin resistance, such as increasing waist circumference, weight gain predominantly in the abdominal region, and rising triglycerides and LDL-C (bad cholesterol).

You may discover it through routine physical examinations or blood work. In addition to monitoring BMI—a common if imperfect marker for obesity—look for:

• Fasting blood glucose at or above 100 mg/dl or blood sugar at or above 140 mg/dl two hours after a meal

• A1C between 5.7% and 6.3%

• Fasting triglycerides over 150 mg/dl

• HDL cholesterol under 40 for men or under 50 for women

• A waistline measurement >40 inches for men or >35 inches for women

• Acanthosis nigricans, velvety dark skin patches that appear in skin folds

• Skin tags

• Blood pressure that exceeds 130 over 80

It is important to help a patient understand what these symptoms mean and the importance of addressing them early. Some may have heard that progression to diabetes is inevitable, but you can guide them to take control of their health now. Early detection and intervention could protect them from serious health complications.

Treatment Options for Obesity and Insulin Resistance

Lifestyle interventions are the first line of defense in insulin resistance. As with obesity, you can approach the treatment of insulin resistance with non-judgemental counseling about nutrition and exercise. Getting a patient to follow through can pose a challenge, but explaining their elevated risk for diabetes may help with motivation. In addition to lifestyle interventions, medications and surgery may offer other possible paths to improved health.

Dietary options

Some trendy diets offer potential to combat insulin resistance. It’s okay for a patient to follow a trend as long as it meets the basic tenets of good nutrition: whole grains, adequate fiber, nutrient-dense foods, and a lack of sugar and processed foods.

One popular choice is the Mediterranean Diet, which U.S. News and World Report consistently ranks as “Best Diet.” The Mediterranean Diet consists mainly of unrefined cereals, grains, vegetables, beans, fresh fruits, and nuts. A person may also eat moderate amounts of fish, poultry, dairy in the form of cheese and yogurt, olive oil, wine, and very little red meat.

Exercise

Exercise is almost universally good for people, providing benefits for all manner of health conditions, including this one. The challenge is for the patient to find a regimen they can adhere to. Tracking devices like smart watches and gamification of exercise helps some folks. Others find greater success when they make an exercise plan with a friend. If a patient reports that they already exercise, explore increasing the amount or intensity, depending on their age and ability.

A related approach is to increase non-exercise activity thermogenesis (NEAT), which may be more realistic for certain lifestyles. It can also complement a regular exercise routine. NEAT refers to daily activities like walking, gardening, household chores, and even fidgeting. Research shows it can affect basal metabolic rate and possibly play a bigger role in burning calories than traditional exercise.

Medications

Although most weight loss medications are not expressly indicated for treating insulin resistance (yet), many of them can help when prescribed for obesity.

Current research focuses mainly on GLP-1 receptor agonists, such as semaglutide, to understand their effects on insulin resistance. These medications slow metabolism and improve insulin secretion. As they have been trialed for their effects on obesity and type 2 diabetes, data has been collected on how they affect insulin production, too.

A study in Diabetes from October 2023, showed that a GLP-1 drug could rapidly improve insulin sensitivity. That study looked at 88 individuals with t2d or pre-diabetes. Other classes of weight loss drugs have also shown promise for mitigating insulin resistance.

Bariatric surgery

Surgery is one of OMA’s four pillars of obesity treatment. For some individuals, bariatric, or metabolic, surgery can be an effective intervention for obesity which, in turn, can help treat insulin resistance. Bariatric surgery shrinks the gastrointestinal tract, reducing appetite. It also alters the hormones that regulate energy intake and control blood sugar and the microbiota that impact obesity and weight gain.

Bariatric surgery is recommended for type 2 diabetes with a BMI of 40 or more (class III obesity), regardless of glycemic control. Primary Indications

• BMI ≥ 40 kg/m² (regardless of glycemic control)
• BMI 35-39.9 kg/m² with inadequately controlled type 2 diabetes despite optimal medical therapy
• BMI 30-34.9 kg/m² may be considered for Asian populations or patients with poorly controlled type 2 diabetes despite maximal medical therapy

It can lead to significant weight loss and diabetes remission and increases GLP-1. GLP-1 produced by the intestines causes the pancreas to produce more insulin and delays gastric emptying, therefore playing a major role in blood sugar control.

Increasing insulin sensitivity

There are a number of ways to improve one’s sensitivity to insulin, thereby helping to break the cycle of ever-increasing insulin levels.

• Try to decrease chronic stress

• Get a good night’s sleep

• Avoid sugar-sweetened beverages and added sugars

• Moderate your processed carbohydrate intake (all carbohydrates are NOT created equal)

• Move or get NEAT (non-exercise activity time)

Many studies now show that decreasing chronic stress can decrease cortisol hormone levels, thereby lowering blood sugar. A good night’s sleep leaves more energy to exercise, and also decreases the hunger hormone, ghrelin. Movement sensitizes muscle to insulin, thereby decreasing insulin resistance. Finally, taking care to limit processed foods lessens blood sugar and insulin spikes that can occur with sugar-sweetened beverages and sugars added to foods.

A Developing Area of Medical Knowledge

Insulin resistance, with its many interconnected metabolic functions, presents an exciting area for potential new findings. An analysis of randomized clinical trials identified 24,932 related articles from 2003 to 2022, noting a significant increase from 2008 onward. The authors concluded: “Research on lipid profile, impact on food and insulin resistance in patients with polycystic ovary syndrome will continue to be a hotspot. The findings offer valuable information on research priorities, international collaborations, and impactful publications.”

To keep current with research related to this and other obesity topics, consider becoming a member of the Obesity Medicine Association.

If you are seeking a provider with specialized knowledge of obesity and related conditions, try our tool for finding a healthcare provider.