Hyperinsulinemia and Hypertriglyceridemia T2D 29

posted in: Diabetes, Health and Nutrition | 28

The liver lies at the nexus of metabolism and nutrient flow, particularly carbohydrates and proteins. Situated immediately downstream from absorptive surface of the intestines, those nutrients enter the blood in the portal circulation and pass directly to the liver. The major exception is dietary fat, which is absorbed as chylomicrons directly into the lymphatic system where it empties into the bloodstream without first passing the liver.

As the major organ responsible for storing and distributing energy, it is naturally the main site of action of the hormone insulin. When carbohydrates and proteins are absorbed, insulin is released from the pancreas. It travels in the portal vein, heading expressly to the liver. Concentrations of glucose and insulin are often 10 times higher in the blood of portal system and liver compared to the rest of the body and the systemic circulation.

Insulin promotes storage of food energy for later use. This is crucial in the survival of the species, since food is not constantly available. We must be able to store enough food to survive the periods of famine inherent in human history. In the liver, glucose molecules from dietary carbohydrates are strung together in long chains to form the molecule glycogen. For a quick energy boost, glycogen can easily be broken back down into its component glucose molecules.

Dietary protein is broken down into its component amino acids upon intestinal absorption. Some amino acids are required for make new proteins and overall protein turnover. However, any excess cannot be stored directly. These must be transformed into glucose at the liver before being stored as glycogen. Dietary fat, because it does not require liver processing, does not require insulin. In response to ingestion of dietary fat, there is minimal insulin secretion.

Glycogen is the preferred storage form of glucose since it is easily accessible. However, there is limited storage room available inside the liver. Glycogen is analogous to a refrigerator. Food brought into the house is easily placed into and taken out of the refrigerator. However, it can only hold a certain amount of food.

Once full, excess glucose needs a different storage form. The liver transforms this glucose into newly created molecules of triglycerides, also known as body fat. This process is called De Novo Lipogenesis (DNL). ‘De Novo’ means ‘from new’, and ‘lipogenesis’ means fat creation. So, DNL means literally, the making of new fat. It is left unsaid that this newly created fat is made from the substrate glucose, not dietary fat. This distinction is important because fats made from DNL are highly saturated, leading to confusion. Eating excessive carbohydrates can lead to an increase in saturate fat levels in the blood.

When needed, the triglyceride molecule from body fat can be broken into three fatty acids which most of the body is able to use directly for energy. Compared to glycogen, it is a much more cumbersome process of converting fat to energy and back again. However, fat storage provides the unique advantage of unlimited storage space.

This body fat is analogous your basement deep freezer. While it is more difficult to move food into and out of your freezer, you may store larger amounts. There is also room to buy a second or third freezer in the basement if needed. These two forms of storage fulfill different and complementary roles. Glycogen (fridge) is easily accessible, but limited in capacity. Body fat (freezer) is hard to access, but unlimited in capacity.

There are two main activators of DNL. The first is insulin. High dietary intake of carbohydrates, and to a lesser extent, protein stimulates insulin secretion and also provides the substrate for DNL. The second main factor is excessive dietary fructose.

With DNL running at full production, large amounts of new fat are being created. But the liver is not the appropriate place to store this new fat. The liver should normally only contain glycogen. What happens to all this new fat?

First, you could try to burn this fat for energy. However, with all the available glucose around after the meal, there is simply no reason for the body to burn the new fat. Imagine that you have gone to Costco and simply bought waaayyy too much food to store in your refrigerator. One option is to eat it, but there’s simply too much. If you cannot get rid of it, much of the food will be left on the counter where it will rot. So this option is not viable.

The only option left is to transfer this new created triglyceride somewhere else. This is known as the endogenous pathway of lipid transport. Triglycerides are packaged together with special proteins called very low-density lipoproteins (VLDL). These packages can now be exported out to help decompress the congested liver.

The amount of VLDL produced mostly depends upon the availability of hepatic triglycerides. Lots of newly created fat triggers production of more of these triglyceride filled VLDL packages. Insulin plays a key facilitating role in the production of VLDL, by increasing the genes needed for DNL. Experimental infusion of large amounts of carbohydrates increases the release of VLDL from the liver by a massive 3.4 fold. This massive increase in triglyceride rich VLDL particles is the major reason for an increased plasma triglyceride level, detectable in all standard blood test for cholesterol.

Excessive DNL can overwhelm this export mechanism resulting in the abnormal retention of this new fat in the liver. As you stuff more and more fat into that liver, it becomes noticeably engorged and can be diagnosed on ultrasound as fatty liver.

Once released from the liver, the VLDL particles circulate through the bloodstream. The hormone lipoprotein lipase (LPL), found in the small blood vessels of muscles, adipocytes and heart, breaks down the VLDL. This releases the triglycerides and breaks it into fatty acids, which can be used directly for energy. As VLDL releases triglycerides, the particles become smaller and denser, called VLDL remnants. These are reabsorbed by the liver again and released as low-density lipoproteins (LDL). This is measured by standard blood cholesterol panels and is classically considered the ‘bad’ cholesterol.

High carbohydrate diets increase VLDL secretion and raise blood triglyceride levels by 30-40%. This phenomenon is called carbohydrate-induced hypertriglyceridemia and can occur with as little as five days of high intake. Similarly, increased intake of fructose has been linked to hypertriglyceridemia.

Dr. Reaven described hyperinsulinemia’s starring role in causing high blood triglycerides in 1967 accounting for 88% of the variability. Higher insulin levels produce higher blood triglyceride levels.

Therefore, it is no surprise that reducing dietary carbohydrates and fructose effectively lowers blood triglycerides. The landmark DIRECT study showed that the Atkins-styled diet reduced triglycerides by 40%, compared to only an 11% reduction in the low fat group. But why should we care about high triglycerides?

28 Responses

  1. So how why, after 3 years of lchf and into 2nd year of ketogenic are myHDL and LDL still high where triglycerides never were high??? (still overweight but not obese (barely)?

    • Danielle

      8 years HFLC then keto kept me obese too. My solution was to spend time in the fasted state. The higher your insulin, the longer you need to reach the fasted state. Eating one large keto meal every 2-5 days made the difference for me. I am now smaller jeans size than when I was 9yo. Been obese all my life.

      • Thx Danielle. Your message is inspirational as I have experienced the same poor results with HFLC and keto protocols. If you found a good resource (books/website) for developing what worked for you (large keto meal once every 2-5 days), I’d really appreciate it if you could share. Congrats on your success!

      • Lovingthisstuff

        Beautiful. Very inspiring, and sounds doable. Love to hear the details of that large keto meal.

    • BernardP

      You mean HDL and LDL as in cholesterol test results. Cholesterol matters very little, if at all. Studies have shown people with higher cholesterol levels live longer. Recommended reading:


      The author’s blog :


    • Dr Peter Haynes

      The relevance of these lipoproteins for those on a standard western diet is still being debated. Their relevance for someone who is on a LCKD is simply not known. My advice is to Chill and ignore them.

      Judith, how much weight have you lost in 2 years? If it is not much, maybe you need to seek advice and discuss, in detail, about your current diet.

  2. After 3 years of a LCHF/Ketogenic diet you should have higher levels of both HDL and LDL but it is the ratio that determines risk.

    Divide your HDL reading by your LDL reading as per this example –

    “For example, if a person has an HDL cholesterol of 50 mg/dL and an LDL cholesterol of 150 mg/dL, the HDL/LDL ratio would be 0.33. The goal is to keep the ratio above 0.3, with the ideal HDL/LDL ratio being above 0.4.”

    Example taken from here – http://cholesterol.emedtv.com/hdl/hdl-ldl-ratio.html

  3. I’m not a doctor, and don’t play one on the Internet, but here goes:

    A high HDL particle count (on its own) isn’t necessarily bad. What was your Triglyceride/HDL-C ratio from your last lipid panel? Take your TG (in mg/dL) value and divide it by your HDL (in mg/dL) value. That gives you your ratio; anything below 2 is considered ideal.

    As far as your “high” LDL particle value, I wonder if your stored liver fat is still in the process of slowly diminishing, thus a consistently high blood value even three years after dietary intervention. With a constant supply of dietary energy consumption (regardless of macronutrient profile) I would imagine stored liver fat would be preferentially stored, rather than released.

    Do you fast often/at all? If so, how often and for what duration?

    • Dr Peter Haynes

      Stored liver fat (ectopic fat) is usually the first to go and disappears rapidly with a LCKD

  4. Judith, good point, this post is what is “supposed” to happen. It doesn’t always work this way. Large minority of people have high LDL and TG after several years of LCHF. Such people are largely ignored by pundits as they do not fit the paradigm. People whose bodies who do not respond according to LCHF orthodoxy are increasingly blamed/shamed. Outliers unfortunately do not sell books.

  5. This is very confusing. First, I have never had my HDLs move more than a few points in 30 years. They are always in the mid-30s regardless of how I eat, junk food to low-carb keto. My HDLs range from 31 to 37, my LDLs from 76 to 157, triglycerides from 74 to 568

    2004: HDL 37 — LDL 130: ratio of 0.28 … triglycerides 107 cholesterol 104
    2012: HDL 33 — LDL 76: ratio of 0.43 … triglycerides 520 cholesterol 223
    2015: HDL 33 — LDL 157: ratio of 0.21 … triglycerides 353 cholesterol 301
    2016: HDL 34 —LDL 133: ratio of 0.25 … triglycerides 284 cholesterol 202

    In January 2017 Glucose 98, A1C 5.1% fasting insulin 9.2

    I have been low carbing for many years. When the blood test was taken in 2016 I was averaging 23 carbs a day, no alcohol, no sugar, no bread et cetera. More so when the test was taken in the fall I had been for over a year bicycling 70 plus miles a week (fasting 12 hours then cycling 35 miles while fasting for a total of 18 hours fasting, twice a week) lifting weights two days a week — upper, lower — and one full 24-hour fast Saturday night to Sunday night. My weight is 179, I’m 5-foot-9 my body fat is around 15%, BMI 24 and change. Male 66. I am now cycling 100 miles a week and still fasting and still lifting.

    What I also can’t figure out is 2012 with a 0.43 ratio but 520 triglycerides. And in 2004 my lowest triglycerides and cholesterol and the worst HDL LDL ratio, 0.28

    I track virtually everything I eat. In the last eight weeks I have eaten a net of 41 carbs a day (9.1 fructose) 77 grams of protein, 125 grams of fat 5/13 Omega 3 to Omega 6, 493mg cholesterol daily, average calorie expenditure 1681.7.

    Lastly I do carry the gene for High Fructose Intolerance but do not have, as far as I known, the syndrome myself. (When I eat fruit — rare these days — I don’t have symptoms and ate a lot of fruit as a child.)

    I can’t seem to get a good HDL/LDL ratio and low triglycerides at the same time.

    • tuba take niacin – B3 vitamin. Check this http://www.mayoclinic.org/diseases-conditions/high-blood-cholesterol/in-depth/niacin/art-20046208

      • Thanks …Yes… but the problem is B3 can raise uric acid. At the moment I am taking 300mg a day and eating on average 18mg.

    • Tuba, I think what you’re running into is using triglycerides for fuel. If you’re eating very low carb and biking a lot, your body has to have fuel, and that fuel would be (in part) triglycerides. For instance, I had a test taken on Monday after a 12 hour fast (TGs = triglycerides):

      TC: 168; LDL: 103; HDL 52; TGs: 65; TG/HDL: 1.25

      On Friday of the same week after 4.5 days of fasting:

      TC: 188; LDL: 121; HDL 36; TGs: 157; TG/HDL: 4.36

      That’s a 142% increase in TGs in less than a week. My conclusion is that my body was living on TGs, as I was not eating (and I exercised probably 2 times that week, for 1 hour each time). That might be what you’re doing.

      Personally, I don’t think any of these values — with the possible exception of Lp(a) or a CAC score — mean anything. Low HDL is probably a marker for high carb intake/high insulin resistance, and “high” TGs could be the same (except in instances like yours and mine, when our bodies are producing high TGs because we’re living on them).

      If you start researching in this area, you can find studies indicating anything. I think Malcolm Kendrick is most likely closest to the true “cause” of heart disease, and his theory has “nothing” to do with any of these markers (though some markers might limit the cause).

      • If you are fasting and releasing stored body fat, then these will show up on cholesterol bloodwork as elevated triglycerides. Fatty acids with a glycerol backbone which will be split off til they are free fatty acids are exactly what you want to see! That means your body is really burning stored fat for energy.

        While in active fat burning mode I would avoid cholesterol bloodwork work because it just panics the doctor-by-numbers mainstream medical establishment. The aren’t able to understand that to burn body fat it has to be freely available in the bloodstream. To me,low triglycerides is a sign that you are a sugar burner not a fat burner. Body fat is locked up tight in the fat cells and nary a one will be burned for fuel because they aren’t being let loose because of the scare mongering of the antiquated High Cholesterol bugbear everybody is conditioned to fear. Think Pavlov’s dog and the ringing bells.

        • Stephen T

          Abi, I’ve read many times that when people reduce carb intake and go LCHF that triglycerides drop and that this is good.

          I can see the logic of fat burning mode releasing triglycerides, but high triglycerides surely can’t be both good and bad?

    • Dr Peter Haynes

      The standard method of estimating LDL-cholesterol levels using the Friedewald equation underestimates them, particularly when triglyceride levels are high. So I would have been inclined to re-check the lipid profile in 2012. However, as I mentioned elsewhere, the relevance of lipid profiles for an individual like yourself on a LCD who cycles and lifts is not known and so should be thoroughly ignored.

  6. DrugDealer

    Hi Tuba,
    Something to think about as it appears your total daily calorie intake which I think is just above 1600 calories a day mirrors the same intake done by study participants in the Minnesota Starvation Experiment.
    The individuals in the study ate 1570 calories a day for 6 months and walked 22 miles a week. This protocol wrecked havoc on their bodies.

    Also, Dr Fung covers the study in detail in his book “The Obesity Code”

    Exercise more and eat less dosen’t work long-term.

    Also, as far as cholesterol levels go, your liver makes most of the cholesterol in your body about 80%. So you can’t affect it all that much.

    Eat more calories as I think you are in starvation mode everyday, not sure if increasing protein may be something to consider as I believe you are following the Keto diet.

    Hope this helps

  7. J L De Foa, MD

    This isn’t about triglycerides, but you mentioned Dr. Reaven. I stumbled upon this paper of his:

    Reaven GM, Bernstein R, Davis B, Olefsky JM. Nonketotic diabetes mellitus: insulin deficiency or insulin resistance? Am J Med. 1976;60:80–88.

    It appears the existence of hyperinsulinemia in patients with IFG (impaired fasting glucose) & IGT (impaired glucose tolerance) and even those with mild persistent hyperglycemia, while insulin deficiency essentially only occurred in those who’s glycemia exceeded the renal threshold of 11 mmol/L (i.e. even Banting & Best would have said they had “diabetes mellitus”) was known, or should have been, even before the food pyramid was promulgated.

    It seems decades have been lost treating hyperinsulinemics as if they lacked insulin.

  8. Charlene

    Newbie here–trying to make sense of it all. So much of this is over my head. Is there a chart that lists the healthy ranges for, well, everything. HDL, LDL, TG, BGL, fasting BLG, Insulin, Leptin, etc. ??? I go to a variety of what are considered reliable sources, but they give contradictory ranges.

  9. Stephen T

    Charlene, your curiosity is commendable, but I became satisfied some time ago that all heart bio-markers went in the right direction on LCHF. If you scroll up you’ll see a prominent doctor in the UK who made a move in this direction and tested himself.

    I’m a little sceptical about the accuracy of some of these tests and I haven’t had any done. When I go to my doctors I refuse to give blood in case they test and decide I’ve hit some artificial, pharma drawn boundary for, say, statins. They can’t say I’ve refused statins because I won’t give them the option to recommend them. I have no fear of cholesterol. If you look at the attached talk by Professor Jeff Volek at 35.20, he lists thirteen bio-markers and how low carb affects them. Worth a look. It confounds most doctors because they’ve been fed fat and cholesterol dogma and most have swallowed it.


  10. NOVA internist

    Dr. Fung. I’m an internist and became completely convinced after watching one of your videos on youtube and started fasting 8-16. My question to you is if muslims fast a lot why do they have diabetes?

    • Stephen T

      Nova, the Middle-East has some of the highest rates of diabetes in the world and fasting is only for one month. The locals drink extraordinary amounts of sugary drinks and I’d suggest this is leading to fatty liver disease and then diabetes. Fatty liver was discussed a post or two ago.

      It’s been noted that the cities in the UK with Muslim populations have the worst rates of tooth decay. Sugary drinks and food are again the problem. Sugar is very much associated with hospitality and gifts. I’ve been in Muslim houses where it’s very difficult to convince the host that you want tea without heaps of sugar.

      The Western world first encountered sugar during the Crusades in the Middle-East and the Knights loved it and brought it to the west, but its use remained rare outside the aristocracy. This is probably some way short of the full answer, but I think it explains a lot.

      Good luck with your studies. We need people with open minds.

  11. The Chief

    So, please, help me with a couple of things here. Trying to consolidate my understanding and put it in a form that makes sense to me. I read Obesity Code a few months back and trying to digest (ha ha) all of this new learning after being harangued for a lifetime by the traditional dietary approach to weight management.

    Firstly. Dietary fat does not effect body fat. Body fat is the outcome of elevated insulin production stimulated by carbohydrate (and to a lesser extent) protein intake. The insulin response of carb intake is for the liver to take onboard glucose in the form of glycogen for the body’s energy needs. Where there is excess energy, it is transformed into triglyceride and stored (the food in the basement deep-freeze example) through the process of DNL.

    Excessive DNL production leads to over-storage of fat in the liver (obviously leading to fatty liver, potentially prompting the development of insulin resistance) – I think engorgement was the word used! This also leads to the increased creation of LDL – the ‘bad’ cholesterol.

    How am I going?

  12. There is one thing that I am not able to understand. If the liver converts excess glucose into triglycerides (body fat) then it should continue to do so. This means triglycerides should continue to be deposited in the adipose tissues and obesity can keep increasing but fat should not accumulate in the liver. Why does this happen ?

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