Showing posts with label Impaired Glucose Tolerance (IGT). Show all posts
Showing posts with label Impaired Glucose Tolerance (IGT). Show all posts

Monday, March 11, 2013

Insulin/Proinsulin/etc. in Normal, IGT and T2 Diabetics

One more on the measurement side of things since these type posts are easier to put the finishing touches on to get out the door.  This is another older paper, and I'm trying to track down more info on newer/current analyses and their specificity.  Unlike the last discussion here, I want to focus on the secretory capacity of the  β-cell through the progression of diabetes.  

  • 40 newly diagnosed with T2 diabetes + 21 IGT -- No medications or special diet
  • BMI < 27 in men, < 25 in women
  • Controls were weight matched to study group participants.
Read more »

Friday, October 19, 2012

Blood Sugar 140: Context is Everything II: The OGTT

In the last installment, I discussed the context of blood glucose readings over 140 mg/dL in diabetics vs. non-diabetics.  In this installment I'm going to discuss it in the context of an Oral Glucose Tolerance Test, OGTT.   The crux of this post is that the results of this study do not justify the Ruhl/Jaminet/(and I'll add Kresser) takeaway message vis a vis diabetes complications and "spikes" in blood glucose.   The fact that 50% of the neuropathy subjects to whom OGTT's were administered had 2 hr. glucose levels over 140 (e.g. diagnosed as Impaired Glucose Tolerance, IGT) simply does not support:  Nerve Damage Occurs when Blood Sugars Rise Over 140 mg/dl (7.8 mmol/L) After Meals as stated on Ruhl's site and in Perfect Health Diet (Kindle Locations 712-716).  (This seems to have been repeated by Chris Kresser as well).

What is an OGTT?  The most common form is conducted in the fasted state, at least 8 hrs, studies seem to favor 10 or 12 hrs.  It involves ingesting 75g of liquid glucose solution in a short period of time.  Glucose (and often insulin) levels are sampled at 30 min (sometimes shorter at early time periods)  intervals for 2 to 3 hours.  There are two values that are assessed:
  • 1 hour and/or peak BG:  under 200 mg/dL = normal , 200 mg/dL or over = IGT or diabetic
  • 2 hour BG:  under 140 mg/dL = normal, 140-199 mg/dL = IGT, 200 mg/dL or over = diabetic
Read more »

Wednesday, October 3, 2012

Abnormal OGTT Results - The many causes

direct image link
As often happens, when looking for something a bit more specific, I came across this image at right, which led me to this webpage:  Laboratory Testing for Diabetes Mellitus.

Curve 1 is a normal OGTT, Curve 6 is a diabetic.  The other causes are listed:

  • Hypercorticism - curve 5.
  • Acromegaly - between curves 4 and 5
  • Hyperthyroidism - curve 4.
  • Pheochromacytoma (or "emotional hyperglycemia") - between curves 4 and 5

Read more »

Tuesday, October 2, 2012

Blood Sugar 140: Where did the 140 mg/dL threshold come from?

This post (that is going to be a series to keep post lengths manageable) has been brewing for quite a while, but I was reminded of it because Jenny Ruhl came out with a diet book recently, and appeared recently as an "expert" on Jimmy Moore's Ask the Low Carb Experts podcast.  After listening to her previous podcast with Jimmy, I had some mixed reviews.  Jenny is certainly articulate, well-read (though I disagree with many of her interpretations) on the topic, and quite a bit more moderate/measured about controlling diabetes and the efficacy of low carb.   But she also seems to view all diabetes through her own MODY eyes.  MODY (Mature Onset Diabetes of the Young) is a rare genetic form (there are actually several rare genetic forms classified as MODY) that is lumped quite often under the category of Type 1.5.  One of these days I need to address some other things on Jenny's website, as it (and her book) is one of the more definitive internet sources for diabetes info in LC circles.    Her book, Blood Sugar 101, more specifically this Amazon review , as well as this page on her website, is where I took the title of this post from.  On the website she writes:
Read more »

Wednesday, May 23, 2012

Insulin Resistance II ~ The Complexity of "Hormone Resistance" Phenomena

It's been a while since Part I of this series ... too many irons in too many fires and all that jazz.  But one research track I went down recently reminded me of this lingering series and I thought I'd finish up this second installment. We hear all the time truisms such as that the acute effects of a hormone differ from the chronic effects, and whenever a hormone is present in excess of normal levels, the term "fill in hormone here resistance" is sure to be close behind.  Now there is no doubt that hormone resistance is a very real phenomenon, but what does it mean, specifically?

The concept of insulin resistance, IR, is highly complicated by the fact that insulin has varying actions in various tissues and organs.  I do intend to discuss tissue-specific IR in more depth as this series unfolds.  But for today, I am going to limit the discussion to insulin and the muscle cell.  After all, when general IR is discussed, it is usually systemic or skeletal muscle insulin resistance.   
Read more »

Sunday, June 5, 2011

Protein, Insulin-like Growth Factor-1 (IGF-1) and Glucose Homeostasis

I've blogged previously on the LoBAG diets for treatment of diabetes.  These diets are higher in protein that standard recommendations - 30% vs. 15% - with varying carb content (20,30 & 40% have been studied).  With both of the lower carb diets, this group has achieved good improvements in HbA1c levels in relatively short time (5-10 weeks).  In comparing their diets  they observed:
Increasing the protein content of the diet from 15 to 30% resulted in an 35% increase in IGF-I regardless of whether the carbohydrate content was 40%, 20%, or 30% as in the present study. Thus the dietary protein-induced increase in IGF-I is independent of the amount of dietary carbohydrate and fat.
I believe the near-OCD obsession with insulin in the LC community overshadows the vast body of research on other hormones and peptides that's out there and their role in metabolism.
Read more »

Saturday, May 28, 2011

Elevated Free Fatty Acids Further Impair Glucose Tolerance in IGT but not NGT

High concentrations of nonesterified fatty acids (NEFA) are a risk factor for developing type 2 diabetes in Pima Indians. In vitro and in vivo, chronic elevation of NEFA decreases glucose-stimulated insulin secretion. We hypothesized that high fasting plasma NEFA would increase the risk of type 2 diabetes by inducing a worsening of glucose-stimulated insulin secretion in Pima Indians.
The subjects were 151 Pima - 107 with normal glucose tolerance (NGT) and 44 with impaired glucose tolerance (IGT) at the outset of the study.  At the outset none of the subjects had been diagnosed with frank diabetes.  These subjects were part of a study on pathogenesis of diabetes in the Pima and returned for annual visits to have various tests performed.  Of note, offspring of diabetic mothers were excluded from the analysis, thus the NGT group did not include this "at risk" group. 
Read more »

Monday, May 2, 2011

Aspirin for Insulin Resistance ~ Revisited

I've previously blogged on the effects of high doses of salicylates, aka aspirin, and insulin resistance.  In summary from that paper/post:
... high doses of salicylates reverse hyperglycemia, hyperinsulinemia, and dyslipidemia in obese rodents by sensitizing insulin signaling.
So I was poking around in my Downloads folder the other day and happened across this paper:


Mechanism by which high-dose aspirin improves glucose metabolism in type 2 diabetes  (I've cleaned up the excerpts from the citation #'s as I find them distracting)

Read more »

Saturday, April 23, 2011

Adiposopathy

Presented without comment on the content per se:

Role of the Adipocyte, Free Fatty Acids, and Ectopic Fat in Pathogenesis of Type 2 Diabetes Mellitus

This is probably the most exhaustively referenced review article I've ever come across on the etiology of MetS and T2 Diabetes and the role of adipose tissue.  Too extensive to quote w/o copying the whole darned thing, although I may revisit it at some point to do a bullet point summary type post.  

Friday, April 1, 2011

Does eating carbohydrates cause diabetes?

Type II that is ...

I've made some posts on this topic about the net, and been taken to task over them by some.  In a nutshell, my answer to this question is:  No.  So I thought I would post a little treatise here for future reference.  

I think it is important to define what we mean by Type II Diabetes, aka NIDDM (non-insulin dependent diabetes mellitus).  A T2 diabetic differs dramatically from a T1 diabetic in many ways, however the correlation with obesity aside, the two conditions lead to much the same metabolic derangement:  high triglycerides, NEFA and LDL, hyperglycemia, CVD risk, etc.  Much of the focus in diabetes is profoundly glucocentric,  moreso in avid low carb circles.  Thus in a word association game if I say diabetes, most would respond with hyperglycemia, or blood sugar problems or something like that.  Essentially diabetes = hyperglycemia.
Read more »

Thursday, December 30, 2010

The Finger Pricking Diet?

Dr. William Davis is touting the success of one of his patients on a No BG Rise After Eating diet.  The post is HERE.

So Jack was overweight and:
Try as he might, Jack could simply not stick to the diet I urged him to follow. Three days, for instance, of avoiding wheat was promptly interrupted by his wife's tempting him with a nice BLT sandwich. This triggered his appetite, with diet spiraling downward in short order. 
Presumably the diet he urged was low carb.  But just going LC and trying to cut wheat lasted only three days.  So the good Dr. Davis told Jack to get a BG meter and strive for 1 hour postprandial glucose levels to be no higher than before eating.  So:
If any food or combination of foods increase blood glucose more than the pre-meal value, then eliminate the culprit food or reduce the portion size. For example, if dinner consists of baked salmon, asparagus, and mashed potatoes, and pre-meal blood glucose is 115 mg/dl, post-meal 155 mg/dl, reduce or eliminate the mashed potatoes. If slow-cooked, stone ground oatmeal causes blood glucose to increase from 115 mg/dl to 185 mg/dl (a typical response to oatmeal), then eliminate it.
Now, I've seen the BG levels in like a gazillion studies and even healthy glucose-tolerant individuals will not see their blood glucose return to what it was before eating any meal containing carbs of any significance.  A person with any degree of insulin resistance or impaired glucose tolerance would have to eat basically zero carb to attain this goal.  Looking at the example dinner, we remove the potatoes and where does that get us?  Pretty much biologically zero carb as Dr. A would have called it in 1972.  

Ironically, isn't it the postprandial hypoglycemia from the hyperinsulinemia that is supposed to trigger the voracious appetite??  But Davis blames the sugar spike and insulin.  But I digress ...

The result?
Having immediate feedback on the effects of various foods finally did it for Jack: It identified foods that were triggering excessive blood sugar rises (and thereby insulin) and foods that did not.... Six months later, Jack came back 37 lbs lighter.
OK, I'm all for the immediate feedback thing and I think it is highly instructive to get a BG meter and know how your body reacts to various foods.  But really, now.  We know what does and doesn't spike BG (except for some of the questionably LC foods like Julian breads IMO.   Still, was not the list of issues Jack faced not scary feedback enough to scare him straight?   So, if several BG readings/day is going to keep you motivated on the VLC straight and narrow I encourage you to go for it!**  Still, I find it hard to believe that someone only lasts 3 days trying to eliminate wheat before a BLT sends him spiraling out of control, but using a BG meter is basically able to cut out all carbs for 6 months.  But then Davis really loses me with his closing words of "wisdom":
...What Jack did not do is limit or restrict calories. In fact, I asked him to eat portion sizes that left him comfortable. There was no need to reduce calories, push the plate away, etc. Just don't allow blood sugars to rise. ...  And he got there without calorie-counting, without regulating portion sizes, without hunger. 
I'm all for ad libitum diets that reduce intake spontaneously, but as my regular readers know well, I can't stand the misrepresentation of such diets as not restricting calories or intake.  If Jack lost 37 pounds it had nothing to do with his insulin and blood glucose levels, it was because he was eating a VLC diet known for rather significant reductions in intake w/o deliberate restriction.  Gosh folks!  This IS the BEAUTY of low carbing!  I long for the day that the "gurus" embrace this rather than trying to convince people that they really do lose weight without eating less.   There are literally thousands of folks out there diligently following a low carb plan and wondering why they aren't losing weight ... or worse, gaining.  

I also have to pipe up a bit about hunger.  It's a NATURAL sensation.  If you are eating a diet that has your body signalling properly, etc., being hungry should not be an issue that sends you face down into a pile of insert-fave-food-here.  Sure, starving yourself so that you get so hungry that you lose control is not the answer, but to expect that your body will be in energy deficit to get you all the way down to an ideal weight without ever experiencing a hunger pang is unrealistic.  I'm sure there's someone out there who can claim that to be the case, but let's talk reasonable expectations for the rest of us.  

** I can see where monitoring ones blood glucose can get as obsessive as counting calories, carbs, weighing daily or even more often, etc.   BG meters just aren't all that accurate down to a few points from what I understand, and although the strips I used were well within expiration date, I noticed distinct differences even for strips within the same lot, and one time a small lot that routinely gave me BG's around 10 pts higher than the other lots.  It's also common knowledge that very low carbing can make you more intolerant to a glucose challenge which is why low carbers are encouraged to "carb up" eating 150g/day for several days prior to an oral glucose tolerance test.  Something about the term "carb cripple" used by Dr. Michael Dansinger in a recent JM interview struck a chord with me.  If you get to a point where your body can't tolerate even 10g carb in a mixed meal this could drive you low omega 6 content nuts!  

Saturday, August 28, 2010

Separating Fats & Carbs

Just some musings on carbohydrates and fats, but with a scientific basis so put it here.

Personally I believe the obesity epidemic can be blamed primarily on two phenomena:
1.  The abundance of high calorie foods high in fats & carbs (I'll call them CF) in ever larger portions, and
2.  Liquid calories loaded with sugar and/or fat

To prevent obesity my solution is simple:  Keep the fats and carbs separate.  If you're going to eat carbohydrate, eat it with lean protein and/or in whole form so you get sufficient fiber.  Go easy on the fat.  If you're going to eat fat, chances are it is attached to protein, forgo the carbs.  If you simply must eat CF foods, rely on portion control/calorie counting and not on satiety to determine how much you eat.  Keep the total caloric load low, perhaps in the 2-300 cal range, to keep the unnatural assault on your metabolism to a minimum.  

My reasons for this are twofold:

1.  Our paleolithic ancestors, from whom we differ very little genetically, did not have access to foods that were rich in both lipid and carb content simultaneously.  I don't envision Paleo dude saved up his tubers to cook in rendered wild boar fat to plate tuber fries with his boar ribs and a side of some veggie also cooked in boar fat.  It seems far more likely that  Paleo dude ate the tubers if in abundance perhaps even delaying the need for a hunt, or saved those tubers for a rainy day when a kill was available for the eating.   Paleo dude was mostly an opportunistic eater in a scarce world.  Obesity was not a problem nor did Paleo chick worry over a little belly roll.  We are programmed to store energy in its most efficient form (lipid) in amounts that are seemingly unlimited.  There would have been no evolutionary advantage to not being able to store energy, or not wanting to partake in this energy source during times of abundance to save for times of scarcity.    There is no physiological reason to limit lipid intake on any given day.  I see no reason to doubt Eaton's work indicating that Paleos ate a relatively low fat diet.  Further underlining the need for taking it while they could get it -- e.g. overconsumption one day if necessary -- and weak signaling at best.  Bottom line, our metabolisms seem designed to switch between fuels depending which was more available, not deal with being bombarded by mixed fuels.


(2) As outlined in Nutrient Fates After Absorption  dietary intake of protein and carbohydrate share the following in common:
(a) they invoke an insulin response
(b) they are on the order in terms of quantity with the body's storage capacity (nitrogen "pool" and glycogen)
(c) their intake stimulates their metabolism (protein synthesis, oxidation)
(d) their absorbed form is as metabolic substrate (amino acid, glucose)

As such, our hormonal signaling is tightly attuned to intake of these macronutrients to maintain levels in a relatively narrow window.  Dietary fat, OTOH, is
(a) once absorbed, packaged as triglycerides in chylomicrons and transported mostly to the adipose tissue for immediate storage.
(b) as chylos, the absorbed form is not the metabolic substrate for lipids, that being free fatty acids (NEFA/FFA).
(c) in quantity, orders of magnitude less than total stored lipid even in the leanest of humans
(d) can virtually be stored without limit thus eliminating any need to limit intake in one feeding

Circulating NEFA levels are controlled indirectly by release from storage.  Dietary fat does not significantly contribute directly to the levels of this energy source.  My take-away message from the post/article is that our appetite/satiety signals are finely attuned to intakes of carb and protein out of necessity to maintain structure and storage/circulating levels within a relatively narrow range.  Our metabolisms change remarkably within 24-48 hrs of deprivation.  Lipid storage, even on a lean person, can last weeks (or more).  Even gorging on fat is a drop in the bucket of the amount of lipid we store (again, even in the lean), so there's no need to limit this in the short term.  Fat mass regulation seems almost independent of dietary fat when you think about it.

-----

So, whenever I hear the query "Why do we overeat", in many cases it is a passive process.  Our bodies were not made to handle the caloric punch of CF foods, so we tend to eat more calories before the stop signals go up were we consuming just carbs (usually with lots of fiber) or fats (usually with lots of protein).

-----

Over on the personal blog ( When to Eat ), Helen wondered about separating carbs and fats on a daily basis -- e.g. alternating high fat day(s) with high carb day(s).  This was actually the impetus for this post because my reply became too lengthy for the comments feature here to handle.  In any case, here are my thoughts on that:

Let's say during the day I have a fatty breakfast and a carby dinner or a carby breakfast and a fatty dinner.  Either way, if I'm consuming basically maintenance-caloric levels of these foods, my metabolism will do a bit of switching up within its normal mode.  After carbs, lipid oxidation will be down-regulated and the carbs burnt off or converted to glycogen (see that Nutrient Fate link), but as the glucose is "cleared", lipid oxidation ramps up again.  After fats, lipid oxidation remains as it was.  If there's no to minimal carb in the meal, insulin is likely low so NEFA are released from the fat cells to replenish the IMCL being "burnt".  The metabolism is "normal".  

It takes a few days, however, for the body to transition to a "fat burning" (low carb) metabolism.  Our bodies are inefficient during this transition -- spilling ketones, etc.  This can probably be used to our advantage to get a little more out of weight loss, but is it healthy?  I don't have the answer to that and I'll try to put it on my "to do list" to look into.  My educated guess is that so long as you're not overdoing it caloriewise this is probably OK as diacylglycerols and ceramides shouldn't build up.  It takes a while for IMCL to accumulate anyway on an HF diet.  I don't know if it will accumulate if one's "average" diet is HF, even if some days are LF.

From a weight loss perspective, I do feel this switching up was probably responsible for the whooshes I would experience upon returning to LC after carb cheats.  Was this healthy?  Who knows.  I look at it as a trade-off in the end.  Whatever I did to get here, I'm way better off for it now.

I worry more, however, over the transition from a HF day to a HC day.   The switch gets flipped back almost immediately.   I've posted that as little as a single high fat meal can induce IR, and impaired glucose tolerance (IGT) the following day.  If one is not efficiently burning lipids in short HF stints, this could potentially turn the HC day into a "diabetic day".  I've played with a glucose meter to see about this for myself.  Perhaps the fact that I don't eat particularly high fat (as a % or on a gram basis) version of LC, I've not had issues with tolerating carbs.   Meters are cheap, and you can get strips relatively inexpensively too.  Rather than guess, or look to studies to see, testing one's own response to this is probably better.    But I do think alternating days like this has a greater potential for creating issues than mixing it up "separately" throughout the day.  If one experiences a degree of IGT, I think a good bout of exercise between the last high fat meal and the first high carb meal might be all that's needed.

Companion post to follow ....

Sunday, August 15, 2010

Diabetes progresses on LC/HF Diet


First the disclaimers:
1.  It's a rat study
2.  The OLETF rats used are a strain that become spontaneously diabetic and mildly obese -- however to the best of my knowledge this strain was not created by genetic manipulation (e.g. it's not a "knockout").  More here.

My excerpts will be from scattered around the article.
The long-term effect of low-carbohydrate/high-fat diets on the development of diabetes mellitus was studied in Otsuka Long-Evans Tokushima Fatty strain (OLETF) rats. Four groups of spontaneously diabetic (type 2) male rats at 10 weeks of age were pair-fed semi-purified powder diets containing different amounts of carbohydrate (80 %, 60 %, 40 %, 20 % of total calories) for 30 weeks. The carbohydrate content was isocalorically substituted for the fat content in the diet. At the onset of experimental feeding (10 weeks of age), an oral glucose tolerance test (OGTT) was normal in each group.

This was a fairly long term study for rats -- 40 weeks total. The first 10 weeks were simply to grow the rats. Although this is a spontaneously diabetic strain, the OGTT done at the start of the dietary intervention showed these rats were all still normal -- had not developed diabetes. 

The rats were divided into four groups, diets contained the same calories, and although not mentioned, protein content was held constant as well. Only the carb/fat proportions were altered from LC (20%) to HC (80%) carbs in 20% increments with fat reduced proportionally. I'll call these LC (20%), MLC (40%), MHC (60%) and HC (80%) 

Some background -- emphasis mine.

Many epidemiological studies have already been performed to evaluate the relationship between dietary modification (low-carbohydrate/high-fat diet, LC/HF) and the development of DM. However, their results are contradictory. Some show negative associations, while others show positive associations [5, 6]. Even in animal experiments, some researchers studied the effect of high-fat feeding on the development of DM [7, 8]. However, the experimental duration of the test diet feeding was too short (less than 2 months) in most studies [9, 10]. Moreover, the experimental animals were allowed free access to the test diets in most of the studies. In general, diabetic animals select LC/HF as opposed to a high-carbohydrate/low-fat diet (HC/LF) [11]. In the previous studies, the animals consumed more LC/HF. Therefore, compared with the animals that were kept on the HC/LF, the calorie intake was higher in those fed LC/HF. From the results of the previous studies, it is difficult to draw any conclusion about the effect of LC/HF on the development of DM.
This is interesting that ad libitum, rats gain MORE weight on LC than LF because they eat more. This is counter to low carb dogma.
After 15 weeks of the test diet feeding there was no significant difference in the glucose tolerance among the 4 groups, although most of the rats were diabetic. The body weight increased with the decrease of the carbohydrate intake and increase of the fat intake (p < 0.05), and the difference increased in proportion to age (p < 0.05). The severity of diabetes mellitus was also increased along with the lower carbohydrate intake and higher fat intake, when the carbohydrate intake was less than 60 % (in energy).
So even with isocaloric intake, THESE rats gained MORE weight on low carb than high carb.
On the other hand, there was a significant increase in the 20 % group in the postload plasma insulin levels as compared with the other 3 groups at 40 weeks of age. Fasting plasma free fatty acid levels were increased in the lower carbohydrate content groups (20 % and 40 %) as compared with the higher carbohydrate content groups (60 % and 80 %) at the end of the experiment.
This is to be expected, and is so often ignored.  Since these rats were only mildly obese, the elevated NEFA is probably an indication of some degree of insulin resistance in the fat cells.
Impairment of insulin secretion may be the cause of glucose intolerance induced by low carbohydrate intake rather than insulin resistance. These findings suggest that low-carbohydrate/high-fat diet aggravates diabetes mellitus in genetically diabetic rats, and that the development of diabetes mellitus is associated with the activation of the glucose-fatty acid cycle.

 25 Weeks (15 Weeks Dietary Intervention)

40 Weeks = End of Study


The authors conclude that IGT is due to impaired insulin response (e.g. compromised beta cell function) and not skeletal muscle IR.  I would have to question this because if you look at the tables above, we see that the LC group has a significantly higher insulin response to the glucose challenge at 30 min vs. all of the other groups.  At 60 min, both the LC and MLC groups have higher insulin than the MHC and HC groups (insulin levels correlate inversely with carb), and at the 2 hour mark, only the LC group seems to have abnormally elevated insulin compared to the other groups.  To me their results are consistent with IR -- in the fat tissue resulting in elevated NEFA, and peripherally resulting in the rats having to produce more insulin.

IF I'M READING THESE RESULTS INCORRECTLY, I WELCOME COMMENTS ON WHERE I'VE GONE WRONG.

Again, we have to remember this is a rat model, and one in which the males of this strain are predisposed to diabetes.  However there is a strong genetic component to the development of T2 diabetes in humans.  This study seems to indicate that while the LC'er may have better glycemic control, this is achieved at the expense of elevating the other circulating compound that results in dysfunction and damage -- NEFA's.  

Bottom line:  This study demonstrated that in genetically predisposed rats, diabetes developed and progressed further in those rats fed a LC diet than those fed a HC diet.  

Tuesday, August 10, 2010

Very Low Carb and Insulin Resistance

In response to my recent post -- Can low carb cause central adiposity? -- James Krieger posted a link to a recent study indicating I may well be on to something.  So I thought I would post this study separately (I don't have access to the full text on this one).

Longitudinal adaptations to very low-carbohydrate weight-reduction diet in obese rats: body composition and glucose tolerance.

Longitudinal effects of a very low-carbohydrate (VLC) and a calorie-matched high-carbohydrate (HC) weight reduction diet were compared in dietary obese Sprague-Dawley rats exhibiting impaired glucose tolerance and insulin resistance. Obese rats were divided into weight-matched groups: 
(i) VLC rats consumed an energy-restricted 5% carbohydrate, 60% fat diet for 8 weeks,
(ii) HC rats consumed an isocaloric 60% carbohydrate, 15% fat diet, and
(iii) HF rats consumed a high-fat diet ad libitum.
HC and VLC rats showed similar reductions in body fat and hepatic lipid at the midpoint of the weight-reduction program, indicating effects due to energy deficit. At the end point, however, HC rats showed greater reductions in total and percent body fat, hepatic lipid and intramuscular lipid than did VLC rats, suggesting that diet composition induced changes in the relative efficiencies of the HC and VLC diets over time.

Yes ... this is a rat study with all the issues inherent in trying to extrapolate to humans, but let's not forget Dr. Eades' favorite c57bl6-mouse that he says provides evidence for the so-called metabolic advantage of low carb diets.  In that study, the growth rate of ketogenic diet fed mice was stunted to that of the calorie restricted diet vs. three other diets.  I'll try to remember to update with a citation, but in one longterm study on epileptic children treated with a ketogenic diet, their growth percentiles (height AIR) declined following treatment.  But I'll leave a dissembling of this study and the conclusions Eades draws from it for another day.  

It is important to note that these were not genetically obese rats, but rather were made obese through diet and then put on weight loss diets.  In this study, the VLC and HC rats lost the same for a period of time but the metabolisms of the VLC rats apparently became more efficient indicating an adaptation.  Anecdotally, most low carbers seem to plateau out well above their goal weight.  The various long term studies of LC diets seem to follow a similar trajectory of rapid initial losses followed by regain that would be consistent with the findings of this study.  My own metabolism is in the tank as I do seem to become very efficient during long strings of low carbing.   It would be an interesting study to recruit a number of long term weight loss success stories and compare the metabolisms of VLC'ers to LF'ers.  

Back to the study:

HC rats showed marked improvement in glucose tolerance at the midpoint and end point, whereas VLC rats showed no improvement. 
This ties in with what I've been saying now in many posts regarding "curing" diabetes with low carb diets.  Whatever the glycemic issues of the VLC rats before diet and weight loss, the underlying metabolic impairment persists.  
 Impaired glucose tolerance in VLC rats at the end point was due to insulin resistance and an attenuated insulin secretory response.
So, again, a VLC diet may not only mask symptoms of IR and impaired insulin production, but could potentially sustain the underlying issues and/or further complicate matters by reducing the insulin response.  
Glucose tolerance in energy-restricted rats correlated negatively with hepatic and intramuscular lipid levels, but not visceral or total fat mass. These findings demonstrate that adaptations to diet composition eventually enabled HC rats to lose more body fat than VLC rats even though energy intakes were equal, and suggest that the elevated levels of hepatic and intramuscular lipid associated with VLC diets might predispose to insulin resistance and impaired glucose tolerance despite weight loss.
This paragraph reads a little vaguely to me b/c they lump the VLC & HC groups into one when they talk about the energy-restricted rats.   It sounds like they are saying that VLC rats had higher hepatic (liver) fat and intramuscular lipid (IMCL) compared to the HC rats and this correlated with impaired glucose tolerance/IR.  But visceral and total fat mass was not associated with IGT so it wasn't just the lesser VAT/SCAT fat loss of the VLC group that was responsible for the observed IGT and IR in these rats.

So, yes, this is a rat study.  But it is adding to concerns over long term low carbing.