The Triglyceride/HDL ratio detects insulin resistance and predicts diseases

Anyone who had a blood test called a lipid profile has probably heard of triglycerides and HDL. HDL stands for high-density lipoprotein, commonly called the “good cholesterol.” HDL is a lipoprotein carrier and cleans up the arteries of atherosclerosis.

Metabolic Syndrome

Triglycerides are also good, but they are bad for the body in excess. A high triglyceride (>150mg/dL) and a low HDL (40 mg/dl for men and < 50 for women are two of the five criteria for metabolic syndrome. The rest are high fasting blood sugar (>100 mg/dl), hypertension >135/85) and excess fat inside the abdomen (visceral fat).

Insulin Resistance

Metabolic syndrome is the underlying cause of many diseases like heart attacks, strokes, cancer, diabetes, etc. The root cause of the metabolic syndrome is insulin resistance.

Insulin resistance is when the body’s insulin secretion is insufficient to lower blood sugar adequately. Insulin works like this. Every time we eat, carbohydrates have to be broken down into simple sugars (glucose) and then absorbed into the liver and skeletal muscles to form glycogen, a storage form of energy. Some amino acids from protein are also changed to glucose and become glycogen.

The liver and skeletal muscles are filled with glycogen to full capacity in insulin resistance. Why is that? The most common causes are excess caloric intake combined with an inactive lifestyle.

Next, the pancreas has to produce more insulin to “push” the glucose into the liver and skeletal muscles. But both are already filled with glycogen to capacity. Two bad things happen next.

The first is that visceral fat inside the abdominal cavity increases. Some fat also infiltrates the solid organs to create disease-causing conditions like fatty liver and fatty pancreas.

The second condition is a state of persistently high insulin levels called hyperinsulinemia. Insulin also affects other organs like the bone, brain, kidneys, fatty tissues, and blood vessels. In excess, any hormone (thyroid, adrenal, testosterone, pituitary, or estrogen) leads to disease conditions. Elevated hormones affect multiple organs and need expensive treatment.

That is why it is crucial to detect insulin resistance, and this article will show you how anyone with a lipid profile can quickly know if they have it.

Until now, there is no routine test for insulin resistance. The euglycemic/hyperglycemic clamp is the gold standard test to detect insulin resistance.

Euglycemic/Hyperglycemic Clamp

Insulin is infused intravenously during this test, and the blood sugar is monitored. Blood sugar has to be measured constantly since insulin can drive it down. To prevent that, glucose is also infused intravenously to maintain glucose levels. Based on the rate of insulin that needs to be provided, insulin resistance can be known.

The euglycemic/hyperglycemic clamp is quite complicated, expensive, and may need a doctor to be around because of the risk of hypoglycemia. That is why it is used mainly for research.

The HOMA – IR test

The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) is a test to measure insulin resistance. It is calculated using the formula: Insulin X Glucose = HOMA-IR. [1] The problem with this test is that insulin levels are not routinely done. What more insulin levels can change in minutes.

An ideal test should be inexpensive, accessible, and simple to be available to the public.

The Triglyceride/ HDL ratio

The triglyceride/HDL (TG/HDL ratio) ratio is one test, and both are components of the lipid profile. Lipid profiles are routinely ordered to check for total cholesterol, LDL, HDL, and triglycerides levels.

The triglyceride/HDL ratio is the value of the triglyceride divided by the HDL.

A study compared the Triglyceride/HDL (TG/HDL) ratio among different racial and ethnic groups in the US. The study compared the triglyceride/HDL ratio and fasting insulin. Fasting insulin is another measure of insulin resistance.[2]

In the study [6], TG/HDL ≥ 3.5 correlates with insulin resistance across three BMI (Body Mass Index) categories and three ethnic groups, namely the non-Hispanic whites, non-Hispanic blacks, and Mexican Americans.

The optimal cut-off point of the TG/HDL-C ratio for predicting insulin resistance and hyperinsulinemia was 3.0 (in mg/dL unit) for non-Hispanic whites and Mexican Americans and 2.0 (in mg/dL unit) for non-Hispanic blacks. [6]

The TG/HDL-C ratio with hyperinsulinemia was stronger among people with a BMI <25 kg/m2 than those with a BMI ≥ 30 kg/m2. The significance of that finding is early detection. High triglyceride levels happen first before excess visceral fat or obesity if obvious. Some people with high triglycerides may not even be obese.

The use of that high TG/HDL to dete4c insulin resistance in the non-obese will be duplicated in children and proven with another study below.

Among Asians, the TG/HDL has also been found to correlate with insulin resistance based on studies from China [3], Taiwan [4], and South Korea [5]. The three studies show that the higher the TG/HDL ratio, the more likely the subject is insulin resistant.

The study from China also showed that TG/HDL-C was associated with insulin resistance in newly diagnosed T2DM regardless of BMI, waist circumference, waist to hip ratio, and waist to height ratio. However, the three Asian studies did not provide a cut-off number. For me, I will use the cut-off of 2.0. [3]

Triglyceride/HDL to detect insulin resistance in children

In children 5-18 years old, a study from Turkey found that TG/HDL ratio was significantly higher in patients who had insulin resistance and fatty liver than in those who did not. There was no significant difference in TG/HDL ratio between female-male, prepubertal-pubertal, and overweight/obese patients. There was no correlation between age, body mass index standard deviation score (SDS), and TG/HDL ratio. [7]

Again, this study [7] shows that insulin resistance and fatty liver can be detected in children even before becoming obese.

The next part will show the TG/HDL ratio in predicting diseases.

Uses of Triglyceride/ HDL-C Ratio in Diseases

Cardiovascular Heart Disease Prediction

One thousand seven hundred twenty men aged 50 years, free from diabetes and cardiovascular disease, were evaluated from 1970 to 1974. They were followed for 40 years to see if they would have myocardial infarction or an ischemic stroke (n = 576). [8]

Those with a high TG/HDL-C ratio (>1.8) at baseline (from 1970 to 1974) were more insulin resistant, with a significantly more adverse cardiometabolic risk profile than those with a lower ratio. This group also showed an increased risk of cardiovascular disease.[8]

What is surprising in the study is that 25% of apparently healthy 50-year-old men with the highest TG/HDL-C ratio had a significantly more adverse cardiometabolic profile at baseline and developed more cardiovascular disease over the next 40 years. This is what I referred to earlier about the usefulness of the TG/HDL ratio to predict cardiovascular diseases independent of obesity. [8]

Intracranial Atherosclerosis

In neurologically healthy participants, a study of 851 subjects showed that those with a high TG/HDL (> 2.06) were more likely to have intracranial atherosclerosis [9]

Intracranial atherosclerosis affects the major arteries of the brain. If they are involved in a stroke, the motor and sensory deficits are more pronounced. An example will be paralysis of the whole side of the body when the middle cerebral artery is blocked.

By derivative work: Frank Gaillard (talk)Brain_stem_normal_human.svg: Patrick J. Lynch, medical illustrator – Brain_stem_normal_human.svg, CC BY 2.5,

Type 2 diabetes

Once triglycerides become elevated, diabetes often follows. A study from China followed forty-five thousand nine hundred eleven patients with three triglyceride and HDL measurements between 2006 and 2011. The result showed that the higher the TG/HDL ratio at baseline, the greater the likelihood of having Type 2 diabetes. [10]

In another study about people with Type 2 diabetes in China, the TG/HDL ratio could predict insulin resistance independent of the waist circumference [11].

Worse COVID-19 outcomes

A chart review was done on COVID-19 patients consisting of 244 survivors and 18 non-survivors. The non-survivors of COVID-19 had a significantly higher TG/HDL ratio (1.4 vs. 2.5; P = 0.001) compared with survivors. Statistical analysis showed that the TG/HDL-c ratio could predict the mortality of COVID-19.

Patients with a high TG/HDL-c ratio showed a worse survival than those with a low TG/HDL-c ratio. In addition, the study also showed that the TG/HDL-c ratio was an independent factor in predicting the mortality of COVID-19 patients with no underlying diseases.[12]

Summary

The Triglyceride/ HDL ratio is a simple tool to detect insulin resistance even in people who are not overweight or obese. Since insulin resistance is associated with cardiovascular disease and diabetes in the future, it is essential to know your triglyceride/HDL ratio.

If you haven’t done a lipid profile lately, call your doctor to schedule one.

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References:

Matthews DR, et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28(7):412-9. doi: 10.1007/BF00280883. PMID: 3899825.
Yeni-Komshian H, et al. Relationship between several surrogate estimates of insulin resistance and quantification of insulin-mediated glucose disposal in 490 healthy nondiabetic volunteers. Diabetes Care. 2000 Feb;23(2):171-5. doi: 10.2337/diacare.23.2.171. PMID: 10868826.
En X et al. (2016) Association between Triglyceride to HDL-C Ratio (TG/HDL-C) and Insulin Resistance in Chinese Patients with Newly Diagnosed Type 2 Diabetes Mellitus. PLoS ONE 11(4): e0154345. https://doi.org/10.1371/journal.pone.0154345
Chiang JK, et al. Predicting insulin resistance using the triglyceride-to-high-density lipoprotein cholesterol ratio in Taiwanese adults. Cardiovasc Diabetol. 2011 Oct 17;10:93. doi: 10.1186/1475-2840-10-93. PMID: 22004541; PMCID: PMC3224454.
Kim JS, et al. The association between the triglyceride to high-density lipoprotein cholesterol ratio with insulin resistance (HOMA-IR) in the general Korean population: based on the National Health and Nutrition Examination Survey in 2007-2009. Diabetes Res Clin Pract. 2012 Jul;97(1):132-8. doi: 10.1016/j.diabres.2012.04.022. Epub 2012 May 18. PMID: 22607906.
Li C et al. Does the association of the triglyceride to high-density lipoprotein cholesterol ratio with fasting serum insulin differ by race/ethnicity? Cardiovasc Diabetol. 2008 Feb 28;7:4. doi: 10.1186/1475-2840-7-4. PMID: 18307789; PMCID: PMC2292689.
Demiral M. A novel diagnostic tool in determining insulin resistance in obese children: Triglyceride / HDL ratio. J Surg Med. 2021;5(11):1144-1147.
Lind L, Ingelsson E, Ärnlöv J, Sundström J, Zethelius B, Reaven GM. Can the Plasma Concentration Ratio of Triglyceride/High-Density Lipoprotein Cholesterol Identify Individuals at High Risk of Cardiovascular Disease During 40-Year Follow-Up? Metab Syndr Relat Disord. 2018 Oct;16(8):433-439. doi: 10.1089/met.2018.0058. Epub 2018 Sep 5. PMID: 30183521; PMCID: PMC6913120.
Woo MH, Lee KO, Chung D, Choi JW, Kim SH, Oh SH. Triglyceride/HDL-Cholesterol Ratio as an Index of Intracranial Atherosclerosis in Nonstroke Individuals. Front Neurol. 2021 Jan 18;11:504219. doi: 10.3389/fneur.2020.504219. PMID: 33536991; PMCID: PMC7848285.
Cai, Zefeng et al. “Triglyceride to high-density lipoprotein cholesterol ratio variability and incident diabetes: A 7-year prospective study in a Chinese population.” Journal of diabetes investigation vol. 12,10 (2021): 1864-1871. doi:10.1111/jdi.13536
Ren X, Chen Z, Zheng S, Han T, Li Y, Liu W, et al. (2016) Association between Triglyceride to HDL-C Ratio (TG/HDL-C) and Insulin Resistance in Chinese Patients with Newly Diagnosed Type 2 Diabetes Mellitus. PLoS ONE 11(4): e0154345. https://doi.org/10.1371/journal.pone.0154345
Peng, Fei et al. “Triglyceride/High-Density Lipoprotein Cholesterol Ratio is Associated with the Mortality of COVID-19: A Retrospective Study in China.” International journal of general medicine vol. 15 985-996. 31 Jan. 2022, doi:10.2147/IJGM.S346690

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