What is insulin resistance?

The reason why you can't get rid of your belly fat

Do you know what is the real reason behind your abdominal fat? Have you ever wondered why you accumulate more belly fat as you age?

The primary culprit behind belly fat and weight gain is insulin resistance. This is particularly true when you start to gain abdominal fat while your limbs remain small.

In the other way, visceral fat releases chemicals called adipokines. These chemicals interfere with insulin's ability to regulate blood sugar levels.

What is insulin resistance?

Insulin resistance occurs when cells become less responsive to insulin, a hormone that regulates blood sugar levels.

Graphic credit: Alpha Hormones (12)

When we eat, our blood sugar rises, prompting the pancreas to release insulin. Insulin usually helps cells absorb glucose for energy, but cells don't respond effectively to insulin resistance.

As a result, glucose remains in the bloodstream, and the pancreas produces more insulin to compensate. The excess glucose is then stored as fat, leading to weight gain.

Do you feel tired even after eating?

This cycle can leave individuals feeling tired and hungry due to inefficient energy use, resulting in low energy levels and increased cravings for more food.

Apart from that, you usually can't remain asleep throughout the night without night urination, called nocturia (frequent urination at night), and you often feel thirsty immediately when you wake up and feel the urge to drink water immediately (polydipsia).

1. What does high HOMA-IR mean in insulin resistance?

Insulin resistance can be measured using the HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) technique.

Computing glucose and insulin levels from fasting blood are more accurate before diabetes develops.

The HOMA-IR result would be high when the body's cells decrease sensitivity to the hormone insulin. Therefore, it is an indicator before developing:

Type 2 diabetes
Metabolic syndrome
Cardiovascular disorder
Other conditions involve altered glucose metabolism

What does high HOMA-IR mean in insulin resistance?

A high HOMA-IR value indicates that the pancreas must produce more insulin to maintain blood glucose levels within normal ranges; this might eventually result in beta-cell malfunction in the pancreas and other metabolic problems.

2. How do you interpret the HOMA index?

In clinical practice, HOMA-IR > 2.5-3.0 is often used as an indicator of insulin resistance.
>1.9 indicates early IR, and values between 0.5 and 1.4 are good (1).

If the underlying insulin resistance is not addressed, the pancreas's ability to produce insulin declines further, leading to the transition from prediabetes to type 2 diabetes.

A 6 year follow-up study with 2,399 individuals found that people with high insulin resistance developed diabetes mellitus (2.7%), 5.1% had combined Glucose Intolerance (CGI), 13.2% had Impaired Glucose Tolerance (iIGT), and 18.8% had iIFG (Impaired Fasting Glucose)(2).

CGI (Combined Glucose Intolerance): When an individual exhibits both impaired fasting glucose and impaired glucose tolerance, meaning both higher than normal blood glucose levels when fasting and after consuming glucose, but usually not high enough to be classified as diabetes.

iIGT (Impaired Glucose Tolerance): Blood glucose levels are higher than normal after eating, typically identified through an oral glucose tolerance test (OGTT). Prediabetes iIGT = 2-hour plasma glucose levels between 140 to 199 mg/dL (7.8 - 11.0 mmol/L)

iIFG (Impaired Fasting Glucose): Another prediabetic condition where blood glucose levels are elevated after fasting. Prediabetes iIFG = Fasting Plasma Glucose (FPG) between 100 to 125 mg/dL (5.6 - 6.9 mmol/L).
These are widely recognized and used by major health organizations, including the American Diabetes Association (ADA) and the World Health Organization (WHO) (3):

3. Can Insulin resistance cause high blood pressure?

Let's discover from this study from 10,810 selected Hispanic / Latino adults with a mean age of 37 who did not have diabetes and were not on blood pressure medications to find out the root cause of high blood pressure.

Individuals who took antihypertensive medications and diabetic patients were carefully excluded from the study; all of them went through the HOMA-IR test.

Higher levels of insulin resistance were closely associated with high systolic and diastolic blood pressure. This association is more straightforward in men but varied in women (4):

Graph extracted from AHA Journals: Hypertension

Prediabetes didn't change how insulin resistance affected blood pressure. This is an important finding that suggests that insulin resistance adversely affects the blood vessels during the early stage, even before the development of diabetes, for people experiencing elevated hypertension, particularly in women.

Another important finding is that DBP can increase even in individuals with normal blood glucose. This suggests that DBP happens before hyperinsulinemia and is the reason why DBP is a stronger predictor of coronary heart disease in young to middle-aged adults.

4. Hypertension: To blame the salt or High blood sugar?

Generally, people with hypertension are advised to reduce salt intake, which will worsen their condition, and salt is often blamed as the root cause of hypertension. Is this true?

The answer is yes and no. Firstly, salt sensitivity is a key risk factor for cardiovascular issues. High salt intake worsens insulin sensitivity, particularly in people with hypertension who are salt-sensitive. Hence, salt intake is recommended for people who have already been diagnosed with kidney disease and kidney damage.

However, we need to understand what causes salt sensitivity to increase. High insulin levels can worsen vasoconstriction, inflammation, and sodium retention, leading to higher blood pressure.

In addition, insulin resistance affects blood pressure by increasing sodium reabsorption in the kidneys and boosting sympathetic nerve activity (5). Normal Insulin usually helps relax blood vessels and reduce inflammation, but insulin resistance impairs this effect.

Therefore, the answer is no for individuals who are healthy, particularly kidney function test Estimated GFR (eGFR) >90 and a urine microalbumin/creatine ratio UACR < 30 mg/g (6) recommended by the American Diabetes Association.

Since Insulin regulates sodium reabsorption in the kidneys by affecting key transporters, influencing blood pressure and fluid balance, there is no need to worry about salt intake for a normal individual unless you are suffering from insulin resistance.

5. The linkage between PCOS and Insulin Resistance

Polycystic Ovary Syndrome (PCOS) is a condition characterized by the formation of cysts (small fluid-filled sacs) on the ovaries. This condition can lead to irregular menstrual cycles and is a prevalent cause of infertility, impacting up to 5 million women (7).

Symptoms include:

Irregular menstrual cycles
Excessive hair growth (hirsutism)
Acne
Overweight
Difficulty with sexual function (impotence)

It is important to note that the majority of people with PCOS have, in fact, insulin resistance; hence, these types of women are often overweight individuals with high blood pressure as well.

Here is the possible linkage and reason for this (8):

Inflammation: Long-term, low-grade inflammation plays a major role in PCOS.

Glucose Levels: Elevated glucose levels can cause oxidative stress and affect certain immune cells (mononuclear cells or MNCs).

Impact on Phenotypes: Different forms of PCOS show similar insulin resistance, even if BMI (Body Mass Index) doesn't vary significantly.

MNCs and Macrophages: These cells usually don't rely on fat but are important in producing cytokines (inflammatory signals). They contribute to inflammation in adipose (fat) tissue, producing more cytokine production by fat cells.

The above linkage and mechanisms cause women with PCOS to be often obese with high insulin levels. Hence, doctors usually prescribe Metformin for PCOS patients.

Metformin is a common diabetes medicine that helps regulate insulin and lower blood sugar; it helps with symptoms such as irregular ovulation (9).

6. Reversing PCOS & Insulin Resistance

Since PCOS is highly associated with body fat, metabolism, inflammation, and insulin resistance, what are some alternatives compared to medication treatment?

The answer is fasting to reset the body's metabolism and regulate insulin resistance.

A study was conducted with 18 PCOS patients aged between 18 and 31 (without fasting habits, certain diseases like thyroid, and people with intense exercise habits) using the Time Restricted Feeding (TRF) method (an eating window of 8 hours from 8 a.m. to 4 p.m. daily) for a 6-week duration.

Here are the pre and post-fasting results (10):

Polycystic Ovaries and Inflammation: We know that PCOS have constant inflammation because these cells cause insulin resistance, increase male hormone (androgen) production, and disrupt hormone balance.

In this study, the participant's Hs-CRP level (inflammation marker) dropped tremendously, suggesting a profound effect.

Insulin-Like Growth Factor 1 (IGF-1): IGF-1 is essential for managing glucose. An increased IGF-1 can effectively protect the heart as the increase indicates improved glucose metabolism and insulin sensitivity.

Therefore, increased blood vessel formation leads to better blood flow.

Alanine Aminotransferase (ALT) Levels: A high liver ALT level often indicates poor insulin sensitivity, particularly for women with PCOS, regardless of age and body fat.

In this study, fasting has a significant effect in improving liver health and reversing liver disease.

7. What is the waist-to-hip ratio for heart disease?

We have discussed the possible cause of PCOS linkage with insulin resistance; here is a study focusing on males.

The study recruited 2,891 males (mean age = 58 years old) and used the waist-to-hip ratio* (abdominal fat) to evaluate the potential risk of developing heart disease.

The waist-to-hip ratio (WHR) measures a person's waist/hip size.

For example, if your waist circumference is 90 cm and your hip circumference is 90cm, you get a score of 1.0 (90/90). If your waist is 80cm and your hip is 100cm, you get a score of 0.8 (80/100).

Here are the findings (11):

Participants with the most abdominal fat (>1.01) were 3.2 times more likely to get diabetes, and their HbA1c levels were higher.

Patients with >1.01 WHR had a staggering high of 39.8% possibility of developing hypertension.

Triglyceride levels increase, while HDL decreases when the WHR increases.

With every 0.1 unit increase in WHR, the risk of SC-MI* increases by more than 10%, whereas the CIIS* score is 2.6 times higher when abdominal fat is more obvious.

Note:

*SC-MI = Subclinical myocardial injury, referring to the damage to the heart muscle that is not severe enough to cause noticeable symptoms.

*CIIS = The Cardiac Infarction/Injury Score (CIIS) is a scoring system used to quantify the extent of myocardial damage or injury.

8. Key Takeaways

1. Insulin resistance occurs when cells become less responsive to Insulin. Symptoms include constant low energy, hunger, inability to fast, and night urination.

2. How do you know if you have insulin resistance? Test your HOMA-IR; a value >2.5 is an indicator. So, aim for a score between 0.5 and 1.4.

3. High blood pressure is highly associated with Insulin Resistance; a high DBP (Diastolic blood pressure) is a strong predictor of coronary heart disease.

4. If you have high blood pressure, it's not just about the salt. Insulin resistance could be the culprit. Normal insulin levels are crucial in relaxing blood vessels, but this effect is impaired when Insulin Resistance occurs.

5. The root cause of women suffering from PCOS is insulin resistance, often accompanied by high Hs-CRP levels (inflammation) and high liver ALT levels. Fasting helps to reduce both.

6. Males with a waist-to-hip ratio of more than >1.01 are 3.2 times (320%) more likely to get diabetes and 40% of the possibility to get hypertension.

7. With just every 0.1 unit increase in your waist-to-hip ratio, the damage to your heart muscle increases by 10%, and myocardial damage increases by 260% (2.6 times).