I wanted to thank Ratzo for a great question and also for tracking down a citation for further discussion. Here is the original question:
Hi Robb,I posted this question on Art Devany’s site, since I am very curious about it.If insulin is the key to body composition, then how are there people in studies who are insulin sensitive yet who are obese?
He then provided this abstract:
Robb,Here is a good review study on the subject where Gerald Reaven (who wrote about Syndrome X) mentions there are a substantial number of overweight/obese people who are insulin sensitive:
Diab Vasc Dis Res. 2005 Oct;2(3):105-12.
All obese individuals are not created equal: insulin resistance is the major determinant of cardiovascular disease in overweight/obese individuals.
Reaven G. Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. [email protected]
The ability of insulin to mediate glucose disposal varies more than six-fold in an apparently healthy population, and approximately one third of the most insulin-resistant of these individuals are at increased risk to develop cardiovascular disease. Differences in degree of adiposity account for approximately 25% of this variability, and another 25% varies as a function of level of physical fitness. The more overweight/obese the person, the more likely they are to be insulin-resistant and at increased risk of cardiovascular disease, but substantial numbers of overweight/obese individuals remain insulin-sensitive, and not all insulin-resistant persons are obese. Of greater clinical relevance is evidence that the metabolic benefit and decrease in risk of cardiovascular disease following weight loss occurs primarily in those overweight/obese individuals that are also insulin-resistant. The relationship between insulin resistance and overall obesity, as assessed by measurement of body mass index, is essentially the same as the relationship between insulin action and abdominal obesity as quantified by determining waist circumference. Finally, there appears to be a comparable relationship between insulin-mediated glucose disposal and amount of visceral fat, subcutaneous fat, and total fat as quantified by various imaging techniques, and the magnitude of these relationships is no greater than that between insulin action and simple measure of body mass index.
There are some really interesting points to be made from that paper, perhaps most significant being: Variables from person to person can be enormous. Another point to be made is that “insulin resistance” or “insulin sensitivity” are relative terms that are constructed by testing and drawing somewhat arbitrary lines as to what constitutes normal and abnormal. Obviously there are some parameters under-which most people function but that does not address what is optimal for a given individual. Reavens work and much of what Taubes discusses in his book deals with these confounding findings. It is natural to paint as simplistic a picture as possible, the media is especially prone to this, but few situations boil down as nicely as “this is good, that is bad”. Lets look at two populations Reavens mentions that appear at odds with the notion of insulin resistance and obesity. Lean individuals who are insulin resistant and obese individuals who are insulin sensitive.
The lean individual who is insulin resistant could result from sleep deprivation, stress or excessive exercise oddly enough. Introduce enough of a stressor and the individual will head towards insulin resistance. I suspect these individuals although technically “lean” show a propensity towards abdominal adiposity and if they revers the insulin resistance the hip/waist ratio will improve. Why are these individuals not obese? Honestly, I’m not sure on that one. These individuals show blood profiles similar to obese insulin resistant individuals but they manifest the condition in a different way. Similar to the obese however, these individuals must reduce the action of whatever is contributing to their insulin resistance, be it food, stress or lack of sleep.
There is likely some differences in tissue insulin resistance levels…and here is an interesting study looking at this very situation. Congenital generalized lipodystrophy (CGL) is a genetic condition in which the individual LACKS virtually all body fat, yet is HIGHLY insulin resistant. These individuals are remarkably muscular and have an athrogenic blood profile typical of the insulin resistant, however the condition progresses at a dramatically accelerated rate. The individuals also, not surprisingly, have very low circulating leptin levels. It’s all a bit chicken and egg but the lack of Leptin due to a nearly absent fat mass may play into the pronounced insulin resistance. Leptin plays a role in energy regulation and usage mainly (it is thought) by monitoring energy storage levels. Caloric restriction can decrease leptin, this will tend to increase appetite and this is part of why it’s so damn hard to stay on a calorie restricted diet. Interestingly a ketogenic diet does not lower leptin levels yet it does emulate other elements of fasting. An interesting observation with these folks is that insulin resistance is obviously not a player in obesity (the folks have virtually no body fat) but it absolutely is a player in a blood lipid profile that is unhealthy and will lead to an early death. Not surprisingly, I have found no indication that a ketogenic diet has been explored as a therapy for this condition. We might sum up this condition as “not insulin resistant in the fat mass, highly resistant in the muscle mass.”
Lets now look at the obese yet insulin sensitive individual. One interesting hallmark with these folks is a hip/waist ratio that is “normal”. Adiposity is generally distributed and not centralized to the midsection. This becomes a bit chicken and egg again but if insulin sensitivity is good then we see glucose disposal (either in the muscles or the adipose) and a consequent lack the conversion of glucose to triglycerides in the liver. In the instance of insulin resistance we see significant fatty liver deposits and a tendency for fat to be deposited in and around the viscera. The obese, insulin sensitive individual is partitioning nutrients into the fat mass and apparently staying ahead of insulin resistance. I think this is just one of the phenotypes possible and it reflects a situation in which insulin levels may not be at a pathological level with regards to athrogenic blood profile, however things are sufficiently buggared to induce fat gain. A decreased inslulin level via glycemic control will fix this situation. The fact the individual is not technically insulin resistant is a bit moot and if that fat mass continues to grow it will derange hormonal function at some point sufficiently such that overt insulin resistance occurs.
It’s complex stuff and it shows quite a spectrum of genetic responses to various environmental cues. Chines medicine is “OK” with the notion that one type of irritant may result in differing pathology from person to person. Our false reductionist approach to many questions leaves little or no ability to see the shades of grey that reflect reality.
“Interestingly a ketogenic diet does not lower leptin levels yet it does emulate other elements of fasting.”
Robb, can you elaborate on the reasoning for this statement or post a reference?
Jeremy-
If you search pubmed or Google for ketosis and leptin you will find some interesting info that looks at this. The statement regarding ketosis and fasting comes from much of the research I’ve put into intermittent fasting, hormesis the ketosis and cancer post. If folks are seriously interested in this I can tie that together but it’s rehashing a lot of material I have written on previously.
Hey Robb,
At the American Society of Bariatric Physician this spring in Nashville TN, Jeff Volek presented a study of low fat diets vs. very low carb ketogenic diets. Leptin levels decreased more with the low carb diet than the low fat diet indicating an increase in leptin sensitivity. If I remember correctly leptin decreased by 40% on low carb and 18% on low fat.
Mary-
When I did some digging on this I found most of the leptin refrences to be in both low carb AND caloric restriction (hypocaloric). The the material I referred to yesterday was for non-caloric restriction scenarios. I’ll give this some thought and research and see if there is a distinction between these two situations or if I’m just full of dookey! Either way Volek and folks associated with him are doing fundamental research showing that low carb diets, whether calorie restricted or not, ameliorate the athrogenic blood profile whereas low fat diets DO NOT. Here is a great resource for much of this work:
http://www.nutritionandmetabolism.com/content/3/1/24
Thanks Marry!
Robb
Robb,
Not completely related to the topic, but take a look at Dr. McCleary’s blog over at drmccleary.com. F’ing fantastic.
Sully
That is a GREAT site! I need to update my links and that is going in for sure. thanks Sully!
Robb
“Jeremy-
If you search pubmed or Google for ketosis and leptin you will find some interesting info that looks at this.”
That’s my fault, Robb. I misread it and assumed that you meant a KD would keep leptin elevated in the presence of weight loss.
Jeremy-
I think this relates to what Mary mentioned regarding Jeff Volek’s research. ketosis without weight loss may not decrease leptin levels, whereas Ketosis with weight loss certainly appears to accomplish this. I’ll do some more poking around on the topic.
Robb,
Not sure if you looked, but the full-text of that study is available online. It shows insulin does correlate with total fat, subcutaneous, and visceral fat, but that it only explains 50% or so of the variance.
Ratzo-
I did find the whole study although he allude to this in the abstract. That other 50% is certainly an interesting place of further investigation.
Robb
Another scenario that could cause some variance is the person that has low calorie, but high glycemic index (and possibly high stimulant i.e. soda/coffee/tobacco) diet. At least where I live, it is easy to find people who are eating poorly but still have a low BMI and have enough fitness to do relatively well on a running/aerobic test.
While there is plenty of room for investigation it seems pretty clear that the “low-hanging fruit” of health is still to adopt a diet that addresses insulin sensitivity, rather than just reducing calories. If the person doesn’t lose weight at least they will take themselves out of the high-risk category of overweight/obese AND insulin resistant or know for sure that they need clinical intervention.
saulj
Saul-
You are right and not everyone with overt insulin resistance is overweight. this is the skinny-fat phenomena and it is still typified by an athrogenic blood profile and inflammatory markers. Good to see you this weekend! How did the Oly meet go?
Robb, My Oly meet, 44th Annual Golden West Open at FIT in Los Altos, CA, went really well. I won my weight class (69 kg). After studying the video from my lifts it is clear that my technique needs some serious help, but my goal of body weight snatch and 100 kg C&J is very doable. I was able to drop weight to 68.9 kg pretty easily. I am not really sure where I started. The last time I officially weighed myself was at Masters Nationals in March and I was 74 Kg. Most of that has come off since I started The Zone near the first of August and then getting help from you around the first of September. The good news is that after a minor eating binge post-contest, I am back to right around 69 Kg with very little effort. Not only that, one of the athletes that I am training and who is following your recommendations in “42 Ways to Skin The Zone” dropped his Fran time over 2 minutes to 4:05. I could go on with other success stories but I’ll stop here.
Robb, thank you for all your help with getting The Zone working for me. Your help has been crucial to my success and to my clients’ as well.
Saul-
thanks Amigo! Send some photos in when you nail the 100kg C&J. I’m glad the Zone tweaks are of benefit!
Dear Robb:
I just saw the listing of your article on hormesis and look forward to receiving it in the very near future. As you may know, I have been researching this area for a long time. I have come to believe that hormesis will define the performance capacity of all biological systems. If you would like me to send you pdfs of my published articles on hormesis I would be pleased to do so.
Ed Calabrese
Ed-
I am absolutely familiar with your work and I’d love anything you might have the time to send. robb at norcalsc dot com
Hormesis and punctuated equilibrium are truly fascinating topics. Coach Greg Glassman has put forward the notion that crossfit is effective as a strength & conditioning program because (in his words) crossfit “Increases work capacity across broad time and modal domains”. To me this is almost an operational definition of life AND is illustrative of the need for punctuated, intense stimuli. Hormesis also explains the seeming contradiction between oxidative stress and the inability of antioxidant supplementation to improve/ameliorate disease states. really interesting stuff!
Robb