Insulin Resistance: Part Three
Inflammation and Fat Accumulation
Inflammation is either directly or indirectly involved in the development of insulin resistance, which I have discussed in depth in Part One and Part Two of this series (1). A key source of inflammation is through a state of “lipotoxicity” or dysfunctional fat storage (2). It is estimated that approximately 80% of type 2 diabetics are overweight or obese (2). However, obesity can occur without insulin resistance, as long as fat is safely stored in healthy fat cells (adipose tissue) and they can communicate with insulin (or are insulin sensitive) (1). Adipose tissue releases inflammatory chemicals called adipokines, which have been linked to insulin resistance (2). The location of fat storage also matters. Intra-abdominal fat (or visceral fat) is associated with insulin resistance, possibly due to its direct delivery to the liver (3). Lipid “overflow” from adipose tissue leads to fat accumulation in tissue that was not designed to store excessive fat – the liver and muscle (1).
Build-up of fat in the liver is called non-alcoholic fatty liver disease (NAFLD) (2). The liver has internal immune cells that are activated and release inflammatory chemicals (2). Liver insulin resistance is only related to the level of liver fat and not to visceral fat – explaining why people with normal BMIs can have high levels of liver insulin resistance (2).
Excessive fat deposition in muscle cells is also a hallmark of insulin resistance (4). This is a significant issue as muscle is a key site for glucose uptake and, therefore, blood sugar regulation (1). Insulin resistance can occur in muscle due to excessive fat accumulation without a triggered inflammatory response (4). This is likely the result of metabolic toxin formation, such as ceramides, which are produced from some saturated fats (4). Further, saturated fats can impair oxidation (burning) of fat stored in muscle, further contributing to insulin resistance as the excessive fat does not go away (1).
There is a lot of research on the impact of saturated fat on insulin resistance and its causative link. Let’s unpack a study!
Saturated Fat: The Unsuspected Culprit
There are three pathways through which fat can build up in the liver: release of fat from adipose tissue, fat produced from carbohydrate or protein in the liver (de novo lipogenesis), and dietary fat (5). Luukonen et al performed an overfeeding experiment on overweight subjects (5). For three weeks, they ate 1000 EXTRA calories daily of high saturated fat (coconut oil, butter, and cheese fat), high unsaturated fat (olive oil, pesto, pecan nuts, and butter), or high refined carbohydrate (orange juice, soft drink, and sweets). Here’s what they found:
Liver fat increased by:
55% in the saturated fat group
15% in the unsaturated fat group; and
33% in the refined carbohydrate group
Fasting insulin only increased significantly in the saturated fat group.
Ceramides increased by 49% in the saturated fat group, but did not increase in the other groups. While muscle fat was not measured in this study, this ceramide increase indicates likely insulin resistance in muscle cells due to inflammation as mentioned above.
Insulin resistance increased significantly in the saturated fat group by 23%. No significant change was seen in unsaturated fat or high carbohydrate groups.
The key take aways from this article are:
A high energy diet leads to NAFLD.
Saturated fat contributes the most to NAFLD and insulin resistance.
Here you might be wondering why an overfeeding study looking at extreme excess calorie consumption matters? What does that have to do with every day life? NAFLD, T2DM, heart disease … all these diseases are diseases of accumulation. You don't just wake up one day and have one of these conditions - it creeps up on you over time. This study occurred over just three weeks and saw saturated fat by far produce more liver fat build-up. But a diet that is higher in saturated fat (and if you eat meat, dairy, and many processed foods yours probably is) will, over time, put you at greater risk of developing this disease.
What also strikes me in this study, is that the foods used in the saturated fat group (coconut oil, butter and cheese) that led to the worse disease outcomes, are often touted as health foods! Obviously, this is not the case – high saturated fat foods are bad for us. You can also check out my heart disease blog to see how saturated fat increases our risk of our number one killer.
Excess carbohydrates lead to production of saturated fat within the liver, explaining why those eating high carbohydrates increased their liver fat. While we definitely should be limiting refined carbohydrates (like the juice, soft drink, and candy included in this paper), we definitely should NOT be limiting healthy whole carbohydrate foods like whole grains (especially intact or unground), fruits, and vegetables. We’ll learn about the effect of these foods on insulin resistance in the next blog!
Diagram One: An analogy of hyperglycaemia, insulin resistance and glucose intolerance in a typical Western diet high in both saturated fat and refined carbohydrates.
A combination of high refined carbohydrate AND high saturated fat is the cornerstone of the Western diet. We can think of how this dietary pattern affects blood sugar like an overflowing sink. This analogy is depicted in Diagram One. Due to a blocked drain, the water cannot move from the sink and into the pipe. The tap is turned up full blast, compounding the blockage and leading to water overflowing very quickly. Here, the blockage in the drain (insulin receptor) is primarily caused by saturated fat. Water cannot get from the sink (blood) into the pipe (the cell). The water is turned up full blast, representing high refined carbohydrates, leading to a rapid influx of glucose into the blood, and causing an overflow (high blood sugar). However, even if the tap is turned down so the water only flows lightly, if the blockage remains, eventually, an overflow will occur. Additionally, to include the production and release of glucose by the liver into the blood, we can imagine that this drain also pushes water from the pipe back up into the sink! Further contributing to the overflow. I know … it’s complicated - and SO misunderstood.
So what can we do?
Remove the blockage: eat less saturated fat (dairy, meat, and coconut and palm oil)
Turn down the tap: eat fewer refined carbohydrates (juices, soft drinks, white flour products, and sweets)
The overflow will stop and the water will begin to run through the pipe like normal.
Devil’s Advocate: When High Fat Looks Good
Several studies have been published that report improvements in diabetic outcomes when dietary fat (including saturated fat) are increased and carbohydrates (including many fruits and vegetables) are kept very low or eliminated (6). This is contradictory to what we have discussed - so what’s going on?
Remember back to the previous blog - diabetes is a condition of compromised carbohydrate metabolism. When you remove carbohydrate, you side step the problem. But do you solve it? Do you fix underlying insulin resistance? No. Sure, by avoiding carbohydrates you’ll see lower blood glucose levels and lower insulin levels that go along with that. High fat diets also can lead to weight loss, which in turn can improve blood sugar management.
However, studies that report benefits of high fat diets for diabetes do not include an important test. This is an oral glucose tolerance test (OGTT). An OGTT provides a “glucose challenge”, which is a direct measure of insulin resistance. It determines how easily your body can metabolise blood sugar. If blood sugar gets too high, and stays high for too long - that’s insulin resistance. This is THE test that illustrates if the compromised carbohydrate metabolism has been corrected. Additionally, these studies’ favourable outcomes were seen with the use of anti-glycemic (glucose-lowering) medication, which would have contributed to observed benefits.
If we go back to our tap analogy from Diagram One, with a low or no carbohydrate diet we are turning off the tap completely to solve the overflow problem - but we have done nothing about the blockage. In this situation, blood glucose levels and blood insulin levels look great on paper, and the disease is considered to have greatly improved or even resolved. But what if you want to turn the tap on? You can’t! The water has no where to go as the sink doesn’t work - the blockage is still there, and has probably even gotten worse. That’s not a solution - it’s a broken sink and a band-aid. And it’s a bandaid that, in the long-term, likely contributes to very poor health outcomes especially when an animal-based low-carb diet is applied (7).
In the next blog we will unpack the research that investigates nutritional interventions to treat insulin resistance. By the end you’ll be asking yourself “why didn’t I know this before?” Stay tuned.
Written by Jessica Zabow
Accredited Practicing Nutritionist (BHSc)
& Yoga Teacher (RYT500)
References:
Sears, B., & Perry, M. (2015). The role of fatty acids in insulin resistance. Lipids in Health and Disease, 14(1), 1-9. https://doi.org/10.1186/s12944-015-0123-1
Meex, R.C.R., Blaak, E.E., & van Loon, L.J.C. (2019). Lipotoxicity plays a key role in the development of both insulin resistance and muscle atrophy in patients with type 2 diabetes. Obesity Reviews, 20(9), 1205-1217. https://doi.org/10.1111/obr.12862
von Frankenberg, A.D., Marina, A., Song, X., Callahan, H.S., Kratz, M., & Utzschneider, K.M. (2017). A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults. European Journal of Nutrition, 56(1), 432-443. https://doi.org/10.1007/s00394-015-1108-6
Wondmkun, Y.T. (2020). Obesity, insulin resistance, and type-2 diabetes: Associations and therapeutic implications. Diabetes, Metabolic Syndrome, and Obesity: Targets and Therapy, 13(), 3611-3616. https://doi.org/10.2147/DMSO.S275898
Luukonen, P.K., Sadevirta, S., Zhou, Y., Kayser, B., Ali, A., Ahonen, L., Lallukka, S., … Yki-Jarvinen. (2018). Saturated fat is more metabolically harmful for the human liver than unsaturated fat or simple sugars. Diabetes Care, 41(8), 1732-1739. https://doi.org/10.2337/dc18-0071
Goldenberg, J.Z., Day, A., Brinkworth, G.D., Sato, J., Yamada, S., Jonsson, T., … Jonston, B.C. (2021). Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: Systematic review and meta-analysis of published and unpublished randomized trial data. British Medical Journal, 372(1), 1-13. https://doi.org/10.1136/bmj.m4743
Siedelmann, S.B., Claggett, B., Cheng, S., Henglin, M., Shah, A., Steffen, L.M., … Solomon, S.D. (2018). Dietary carbohydrate intake and mortality: A prospective cohort study and meta-analysis. Lancet Public Health, 3(9), e419-e428. https://doi.org/10.1016/S2468-2667(18)30135-X