“In the last few years, new insights have made it possible to visualize the manner in which upper-body obesity connects to glucose intolerance, hypertriglyceridemia and hypertension, with hyperinsulinemia being the key intermediary. … This article examines these insights and propose (sic) an overall hypothesis for their interrelationships, with the hope that greater awareness of the critical role of upper-body obesity will increase attention to the need to prevent it or, failing that, to correct it.” (1)
In this paradigm-shifting 1989 paper, Dr. Norman Kaplan argues that the frequent coexistence of obesity, hypertension, glucose intolerance (predecessor to diabetes) and hypertriglyceridemia (predecessor to heart disease) suggests a shared pathogenesis, specifically “insulin resistance with hyperinsulinemia, long recognized as a metabolic derangement of obesity.”
From “The Deadly Quartet: Upper-Body Obesity, Glucose Intolerance, Hypertriglyceridemia, and Hypertension” by Norman Kaplan.
Kaplan notes that upper-body obesity (abdominal obesity) is more closely related to metabolic disorders than general obesity. He further illustrates how abdominal fat leads to hyperinsulinemia as the pancreas secretes greater amounts of insulin to regulate glucose levels as insulin resistance develops. The resulting hyperinsulinemia subsequently induces hypertension through its effects on the kidneys, nervous system and vasculature. Finally, larger abdominal fat stores release free fatty acids that lead to hypertriglyceridemia while further worsening hyperinsulinemia through effects on the liver.
Kaplan thus presents this “Deadly Quartet” as a single metabolic pathway that begins with increased upper-body obesity and peripheral insulin resistance and leads to heart disease, diabetes and hypertension. He notes, in conclusion, that interventions which improve insulin sensitivity—including weight loss via certain diets (high-carbohydrate diets are specifically argued against) and exercise—might be the most effective tools to manage and prevent each and all of these conditions.
References
1. Kaplan NM. The deadly quartet: Upper-body obesity, glucose intolerance, hypertriglyceridemia, and hypertension. Archives of Internal Medicine 149(7): 1,514-1,520, 1989.
Comments on Dr. Kaplan and the Deadly Quartet
I love that stuff, and of course I agree mostly. Also, I’m no expert. But in those articles, I often miss the role of muscles. Both muscle mass (glycose storage) and training (use of glycose as fuel). Are there any bodybuilders or endurance athletes with diabetes? Because most of them life of high carb low fat diets. So, carb intake should not be demonized but rather set in relation to activity. Your body needs proteins, your body needs (some) fats, your body needs calories no matter if it comes from carbs or fats, but you only “need” carbs for when you’re active. Right or wrong?
Like most things, the devils in the details. Carbs are not bad - depending on quantity, quality, and timing. Eating a protein heavy breakfast and a carb heavy lunch (watch HS students eat) would not be a good choice - you’re getting all/most of your protein in one setting and likewise for carbs at lunch. So even though the daily macro count would look balanced, this person would be receiving a huge dosing of sugar and insulin at one time, and having to release glucose via the liver and glucagon at another time.
I can't believe this was published in 1989 and we still need to push this like "news" to most.
I agree Matt.
This also helps explain outliers in the population that are insulin resistant but are not obese.
We are also starting to see an accumulation of evidence (anecdotal and scientific) that points to lowering refined carbohydrate intake (as opposed to lowering fat intake or exclusively reducing caloric intake) as a key contributor to increasing insulin sensitivity leading to weight loss.
I would like to add (for the sake of scientific accuracy and scientific context) that Dr. Kaplan himself recognised that there were other investigators who had introduced these ideas before him and that he disliked the term "Deadly Quartet".
"... Actually other people, Gerald Reaven at Stanford and others, had talked about this syndrome, the insulin resistance syndrome [and hypertension], but in 1989 I gave grand rounds here [at UT Southwestern Medical Center] because of increasing awareness that hypertension was related to insulin resistance. I did extend the work of other people and I used that term first. I am not particularly proud of the “deadly quartet” as a term. Again, I don’t think I made any original contributions to our understanding of this."
Am J Cardiol. 1998 Aug 15;82(4):490-504.
An experiment of 1...this is the underlying basis of Crossfit...try it, (the training and the nutrition), and see if it works for you. And invariably it does, doesn't it!
The 2 figures in Kaplan’s Quartet are significantly different. The replacement of obesity with hyperinsulinemia in the center of figure 2 has drastic differences in respect to pathophysiology and treatment.
As Kaplan points out, weight loss is the obvious way to correct the obesity.....Even minimal amounts of weight loss may be helpful....However, the use of a low-fat high carbohydrate diet has been found to accentuate the hyperglycemia and hyperinsulinemia. We cannot correct the crisis of chronic disease (diabetes, hypertension, cardiovascular disease) with a low-fat high carbohydrate diet.
Kaplan also recognizes the alarming rate of risk factors in children. Prevention starts with parent education, parents as role models, and reducing exposures and risk factors in children.
Shaka, you got at what might be the most important point in this article. Yes, it may be true that weight loss reduces risk and/or progression of metabolic disease. But if the direct cause of those diseases is not excess weight but hyperinsulinemia, weight loss is neither the simplest nor the most effective tool.
For example, I was recently reading this analysis of a 2006 paper showing weight loss is, at the very least, not required for improvements in the lipid profile:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1488852/
And there is lots of literature around gastric bypass showing it improves diabetes well before the weight starts falling off:
http://care.diabetesjournals.org/content/39/6/893
Much of this research has remained niche, but you can find consistent results across the diabetes and heart disease literature - interventions that substantially improve hyperinsulinemia simultaneously improve these disease states.
The negative interpretation you gave is important - losing weight on the WRONG sort of diet could mitigate the impact of weight loss on metabolic disease. But I think the positive interpretation is even more crucial - if you believe Kaplan's argument that the primary driver of these diseases is hyperinsulinemia, interventions (specific forms of diet, exercise & other changes) that target hyperinsulinemia directly could lead to more faster and more meaningful improvements.
Hyperinsulinemia is the root cause of metabolic syndrome and it is present long before abdominal obesity, dyslipidememia, hypertension, elevated glucose/diabetes and inflammation appear.
The current medical system uses medications to treat many of the above symptoms with patients ending up on blood pressure medication, cholesterol lowering medication, and diabetes medication. All of these medications have side effects and can be expensive. None of them address the root cause of the problem. Obesity is often felt to be a reason for diabetes, hypertension, and dylipidemia. The truth is that it is caused by hyperinsulinememia just like the rest of metabolic syndrome.
So the solution to the problem lies in treating hyperinsulinemia. Since most people do not have an insulin secreting tumor, it is very easy to lower insulin. Carbohydrates and especially sugar cause the release of insulin from the pancreas. By limiting the amount of carbohydrates consumed, the amount of insulin secreted can be decreased. Physical activity increases the sensitivity of insulin receptors making the body more responsive to the effects of insulin. This increased sensitivity causes less insulin to be released when carbohydrates are consumed.
Thus the “cure” for metabolic syndrome involves no medication. Simply eating properly and exercise are all that are required.
Exactly! Medications are like bandaids on an active bleed. Have to fix the bleed, not keep adding more bandaids.
Great insights. I have been doing CrossFit for little over a year and with the combination of following the Zone Diet and fitness 5-6 times per week, have lost 110 pounds. I have however gained more that I've lost in the fact that I have gained my health and freedom from the prison I carried with me on a daily basis. Not only this, but I just found out that I was Glucose intolerant, and the doctor never told me, when it was vital for me to have this information. My A1C was 123, which apparently if you score 126 on two test consecutively... congratulations you have diabetes. Luckily I took my health in my own hands and started doing Crossfit, following all the advise I could find on the Journal, and I can now say that my A1C is in optimal range. So much so that when I went to have my Life insurance reassessed, I received preferred plus ratings. I am now a Level 1 CrossFit coach, and am trying to help anyone I can to have the change that I have been blessed with. Thank you Greg Glassman and CrossFit HQ for being the advocate true health and fitness and the direction you are taking Crossfit in the Health Space and targeting those who need your help the most!
David, you are an excellent example of what is possible. We provided the information and you put forth the time to read/learn it. You also did the hardest part...you ACTED on that knowledge. Well done and please keep up the great work.
Congratulations, David, that's an amazing success story. It's a crazy time that we live in where you can find the information necessary to be your own agent of change, for free, (in most cases) from a mobile device.
On the other hand, I'm disappointed to hear about the lack of diligence on the part of your doctor. I'm guessing for every one success story like yours, there are a hundred in which the patient is not savvy or motivated enough to do their own research.
I'm glad to hear that you have your Level 1 and are going to pay it forward.
Awesome work David! Keep it up!
Dr. Kaplan and the Deadly Quartet
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