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Zeta

Elevated fasting glucose

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Hi everyone. I have a broad question, or a series of broad questions, connected with a complicated morass of health problems I've been having for the past few years. I'm still waiting to find the right way to "go public" with a bunch of my health info in order to groupsource my health problems. For now, one question that, without the broader context of everything else that's been happening to me, might be hard to answer, but to put the question in a context-free form:


 


Could 5 g of glycine taken at bedtime, plus 4-5 g more taken in the middle of the night, usually around 3 hours before waking, have a measurable effect on waking fasting glucose?


 


Some of the (complicated) background: I've been on moderate CR, fairly consistently, for over 20 years. I'm in my early 50s. My waking fasting glucose was routinely, with essentially no variation, around 70 mg/dL until a few years ago. Then I noticed, around three years ago, that it was between 75 and 80. Then, a year or so ago, it was routinely 85. Now I've noticed something weird. It's still around 85 when I wake, but then, even though I don't eat for several hours after waking, it goes up to around 90 as the first hour or two of the morning progresses. I've tested many times: the change is robust, even if the absolute numbers on my meter (Accu-Chek Compact Plus) might be off.


 


Again, the very complicated background is probably needed here, but a short version: I think I started going through a very rapid manopause a few years ago (but I don't have a pre-manopause testosterone baseline, so I can't be certain) -- I noticed loss of hair on legs, reduced libido, etc. -- and I'm guessing the increase in morning glucose is related to that, and not to a switch from lowish fat to somewhat high fat (45-50% fat by calories, mostly nuts) diet that I made around that same time. Plus, I'm pretty sure that manopause and glucose changes started before the dietary changes. (I wish I had better records on that....) I also started getting much weaker physically around that time.


 


Anyway, my narrower question: 9-10 g of protein isn't a tiny amount. Could this be contributing to the higher morning glucose, and to the weird continued increase in fasting glucose as the morning wears on? Or might it be fat from the previous evening's meal (even though my last meal is always finished at least 4 hours before going to bed)?? (I'm still learning about the effects of dietary fat on the liver, etc.)


 


Thanks for any help. I'm starting to think I should be on metformin.


 


Oh, another data point. I do my pre-breakfast 7-minute 3- or 4-interval workout a few hours after waking, then measure my fasting glucose, and the workout knocks it down from 90 to 87 or so. That's all! I would expect a bigger decrease.


Edited by Zeta

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From the Laziness Department. Apologies. I should have at least done a quick PubMed search. Turns out, if anything, one would expect the opposite: that glycine would lower blood glucose -- at least that's what's been found in both diabetics and normos (though some studies show little or no effect). So, maybe I just suddenly "got old" (sudden manopause).

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Hi Zeta:

I have Type 2 diabetes. I'm 88 years old and the diabetes became evident a few months ago.  I'm keeping my numbers down by limiting my carbs. 

 

My doctor's concern is not about my fasting glucose but rather my post prandial glucose. Fasting glucose can be influenced by many factors and it might be hard to pin down which factor was responsible.

 

How are your post prandial readings?

 

Pegd

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My postprandial glucose gets into the 140s (mg/dL) if I eat fruit, otherwise it doesn't get above the 120s after dinner, a touch lower after breakfast.

 

I guess for starters I should cut out fruit. Depressing. Two or so years ago my postprandial glucose rarely got to 90. I've gone partially off CR, which might account for some of the change, but something else seems to be at work.

 

Peg, how much do you limit your carbs? I'm up to 55% fat (by calories), 10% protein, and the rest carbs, and am wondering whether cutting even more carbs might be the best idea for me (assuming I can't go back on more severe CR -- which will depend on the results of tests to determine why I have pancytopenia).

 

The low-carb diet notion is starting to seem less faddish to me. Diabetes researchers, for ex., are increasingly taking it seriously. I don't have diabetes, but still.

 

http://www.nutritionjrnl.com/article/S0899-9007(14)00332-3/fulltext

 

 

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The low-carb diet notion is starting to seem less faddish to me. Diabetes researchers, for ex., are increasingly taking it seriously. I don't have diabetes, but still.

 

http://www.nutritionjrnl.com/article/S0899-9007(14)00332-3/fulltext

 

It seems pretty clear that you can control the progression of type 2 diabetes, and perhaps avoid developing it by restricting carbohydrates. But I worry about the long-term health implications of so much fat in the diet, especially when it comes to deficiency in micronutrients & phytochemicals. None of the longest lived populations around the world follow a low carb lifestyle, which makes me wonder about its health / longevity implications.

 

From my reading of studies on the subject, there seem to be two paths to maintaining glucose control and avoiding diabetes - either a low-carb / high-fat diet or a high (good) carb / low-fat diet. Diets in the "no man's land" in the middle - with medium levels of (crappy) carbs and medium levels of (crappy) fats can get you into trouble with insulin sensitivity, particularly if you are sedentary and/or have a genetic disposition towards obesity or T2DM.

 

BTW, a morning rise in glucose isn't all that unusual, but can develop into a problem. Its called the "dawn effect". Here is more about it:

 

http://www.diabetesselfmanagement.com/blog/controlling-the-dawn-phenomenon/

--Dean

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It seems pretty clear that you can control the progression of type 2 diabetes, and perhaps avoid developing it by restricting carbohydrates. But I worry about the long-term health implications of so much fat in the diet, especially when it comes to deficiency in micronutrients & phytochemicals. None of the longest lived populations around the world follow a low carb lifestyle, which makes me wonder about its health / longevity implications.

 

I gather you adopted your "banana strategy" to gaining weight because of such concerns -- that there isn't enough epidemiological evidence for long-term high-fat diets? That's also why (partly inspired by you) I adopted my variation, the "sweet potato strategy" to gaining weight.

 

I just went over my records carefully, and it looks like it's probably the quantity of food I'm now eating that is causing the higher glucose readings. My glucose levels were OK a few months ago (which is after the andropause changes I went through a few years ago). But it might be the quantity that I eat during each meal, because of my IF routine, and not the overall quantity. I'll have to do more testing. It could be both.

 

As I think I noted elsewhere, I'm temporarily keeping my weight up, and eating more protein, ahead of new blood tests to see why I have pancytopenia. It could be that I was on too extreme CR, and I (and the doctors) want to rule that out. I'm having the new round of tests in a few weeks.

 

So my current diet is (all numbers approximate) 3750 calories, 90-100 g vegan protein, or 60 g vegan protein and 20 g protein from fish, for each of two days, followed by a "fasting" day of 750 calories, with 45 g vegan protein. That's an avg. of 2750 calories/day. I started this (in fits and starts) maybe a month or so ago (before that, for two months, I tried 1 day feast, 1 day "fast", but stomach fullness on feast days got to be too much). I'm weight stable at 56.2 kg. A few months ago I was at 54.5 kg. (By the way the reason for the IF approach is that I wanted to get at least some of the benefits of restricted eating without being on CR.)

 

Today is a fasting day. Tomorrow and the next day I'm going to try getting over 70% calories from fat, and do some glucose measurements.

 

By the way, some data from yesterday:

 

Ate dinner from 17:30 to 19:10.

 

19:40. Blood glucose: 157 mg/dL

19:46-20:02. Brisk walk.

20:04. Blood glucose: 94 mg/dL

20:04-21:05: sedentary.

21:05. Blood glucose: 123 mg/dL

21:05-22:22: sedentary.

22:22. Blood glucose: 113 mg/dL

 

That 157 was scary.

 

 

From my reading of studies on the subject, there seem to be two paths to maintaining glucose control and avoiding diabetes - either a low-carb / high-fat diet or a high (good) carb / low-fat diet. Diets in the "no man's land" in the middle - with medium levels of (crappy) carbs and medium levels of (crappy) fats can get you into trouble with insulin sensitivity, particularly if you are sedentary and/or have a genetic disposition towards obesity or T2DM.

 

I've seen similar claims before, also with "crappy" in parentheses. But have medium levels of non-crappy carbs been tested?

 

Zeta

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Zeta,

 

But it [my elevated blood glucose] might be the quantity that I eat during each meal, because of my IF routine, and not the overall quantity. I'll have to do more testing. It could be both.


I suspect your post-prandial glucose might be higher as a result of your calorie intake being more temporally concentrated following an intermittent fasting routine. But your periods of relatively low glucose should be longer as a result of IF as well. So it may be a wash, or even beneficial to concentrate calories via IF despite transiently higher peaks, especially since they appear to be effectively attenuated by your post-meal exercise strategy, which I also employ.

 

 

 

So my current diet is (all numbers approximate) 3750 calories, 90-100 g vegan protein, or 60 g vegan protein and 20 g protein from fish, for each of two days...


That sounds reasonable, as long as the fish is high quality. Dr. Greger has a couple good videos on the link between fish (esp. farm raised salmon), toxins, and diabetes:

 

http://nutritionfacts.org/video/fish-and-diabetes/

 

http://nutritionfacts.org/video/pollutants-in-salmon-and-our-own-fat

 

From my reading of studies on the subject, there seem to be two paths to maintaining glucose control and avoiding diabetes - either a low-carb / high-fat diet or a high (good) carb / low-fat diet. Diets in the "no man's land" in the middle - with medium levels of (crappy) carbs and medium levels of (crappy) fats can get you into trouble with insulin sensitivity, particularly if you are sedentary and/or have a genetic disposition towards obesity or T2DM.

 

I've seen similar claims before, also with "crappy" in parentheses. But have medium levels of non-crappy carbs been tested?

 


I consider a traditional Mediterranean diet to be a good example of a diet with medium (healthy) fat & medium (good) carbs.  And the results are pretty encouraging for the prevention of type 2 diabetes, as these two meta-analyses from 2014 [1, 2] demonstrate:

 


           "Higher adherence to the Mediterranean diet was associated with 23% reduced risk of developing type 2 diabetes."

 

This meta-analysis [3] of ​dietary patterns (DPs) associated with diabetes is also informative:

 

Compared with the lowest category of Unhealthy/Western DP, those in the highest category had a 41% increased risk of type 2 diabetes (95% CI 1.32 to 1.52; P<0.0001). These results provide evidence that DPs are consistently associated with risk of type 2 diabetes even when other lifestyle factors are controlled for. Thus, greater adherence to a DP characterized by high intakes of fruit, vegetables, and complex carbohydrate and low intakes of refined carbohydrate, processed meat, and fried food may be one strategy that could have a positive influence on the global public health burden of type 2 diabetes.

 

This seems to me to reinforce the idea that once you've developed type 2 diabetes, a very low carb diet may help avoid the deleterious health consequences of the disease. But eschewing healthy carbs may not be necessary or advisable for avoiding diabetes in the first place.

 

--Dean

 

-------------------

[1] https://www.ncbi.nlm.nih.gov/pubmed/25145972

 

[2] https://www.ncbi.nlm.nih.gov/pubmed/24931280

 

[3] https://www.ncbi.nlm.nih.gov/pubmed/25001435

 

 

 

 

 

 


 


 

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Hi Dean!

 

I looked at the two links that you gave us to Dr. Gregor's videos -- and, I must admit, I'm very unimpressed -- IMO Dr. Gregor seems to have a very strong bias to push his Vegan views.

 

I'm only one example -- but I've been eating fish (especially salmon -- often farmed) for all my life -- and as my only animal protein source -- for many years (since my teens, at least -- and I'm 76 now).

 

Yet my bloodwork couldn't be farther from diabetic -- my lipid levels are among the best in the CR Society.

 

I think that one of the blatant fallacies in DR. Gregor's presentation is: grouping all "farmed salmon" into one category.  Obviously, when one buys salmon, farmed or otherwise, one must buy from a reliable source.  There are bad sources -- as there are for every animal, vegetable and mineral source.

 

Similarly, Dr. Gregor groups all "fish" together in his other video -- babbling about the use of Agent Orange in Vietnam.

 

  -- Saul

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From my reading of studies on the subject, there seem to be two paths to maintaining glucose control and avoiding diabetes - either a low-carb / high-fat diet or a high (good) carb / low-fat diet. Diets in the "no man's land" in the middle - with medium levels of (crappy) carbs and medium levels of (crappy) fats can get you into trouble with insulin sensitivity, particularly if you are sedentary and/or have a genetic disposition towards obesity or T2DM.

 

I've seen similar claims before, also with "crappy" in parentheses. But have medium levels of non-crappy carbs been tested?

 

I consider a traditional Mediterranean diet to be a good example of a diet with medium (healthy) fat & medium (good) carbs. And the results are pretty encouraging for the prevention of type 2 diabetes.

 
But then shouldn't your claim be just: "crappy diets can get you into trouble with insulin sensitivity"? I've seen the no-man's land claim about fat levels before. Freakishly low-fat can cure or treat diabetes, and high-fat can treat (and maybe cure it). But not anything in between. Never made sense to me.
 
About fish: yes, I've looked into that extensively. I'm currently eating mostly Wild Planet Wild Sardines in Spring Water (downside: aluminum can -- Wild Planet claims they've tested whether the lining prevents aluminum from leaching into the fish and say it does).
 
Had a 75% fat (by calories) day today (well, most of the day). Glucose never got above 95, without exercise even. But then I had 140 g of orange (with peel) in the afternoon and my glucose got up to 115. Went for a 20-minute bike ride and it was 93 when I got back.
 
So replacing my morning 550 g of sweet potato (al dente and a bit crunchy, but still...) and 150 calories of fruit with more than my normal amount of nuts and avocado obviously makes a huge difference! I think my approach for the time being will be to stick with fairly high-fat -- and up the carbs when I know my day will be structured such that I can exercise when needed to bring my glucose levels down. But I don't think I'll ever return to the massive sweet potato consumption.
 
Oh, and back to glycine: I'm going to stop the middle-of-the-night dose. Not sure it was doing much for my sleep anyway, and it is a glucogenic amino acid.
 
Zeta

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Freakishly low-fat can cure or treat diabetes, and high-fat can treat (and maybe cure it). But not anything in between. Never made sense to me.

 

Mechanistically, the theory is that fat can "gum up the works" when it comes to glucose clearance. So a diet without much glucose (i.e. high-fat) aren't a problem because there isn't much glucose to clear. A diet high in carbs but low in fat allows the glucose in the carbs to be cleared effectively. But when there is significant carbs AND fat, the combination leaves the glucose circulating in the bloodstream unable to be transported into (muscle) cells.

 

There is at least some evidence for this "gumming up" effect. Here are a couple studies [1,2] (unfortunately in type 1 diabetics) comparing meals with the same carbs and protein but different levels of fat (10g vs 60g). In [1], after the high fat meal more insulin was required and still the postprandial glucose AUC was TWICE as large, compared to the low fat meal.

 

From the intro to [1]:

 

Dietary fat and free fatty acids (FFAs) are known to impair insulin sensitivity and to enhance hepatic glucose production (3,4).

 

But then I had 140 g of orange (with peel) in the afternoon and my glucose got up to 115. Went for a 20-minute bike ride and it was 93 when I got back.

 

That doesn't seem all that unreasonable. It isn't surprising your glucose goes up after eating carbs, and from Luigi's human CR study, we CRONies appear to have a somewhat attenuated first-phase insulin response, despite high insulin sensitivity.

 

 

I think my approach for the time being will be to stick with fairly high-fat -- and up the carbs when I know my day will be structured such that I can exercise when needed to bring my glucose levels down. But I don't think I'll ever return to the massive sweet potato consumption.

 

It sounds reasonable to me to curtail you carb intake somewhat if your lifestyle prevents you from being active, and you notice your glucose stays uncomfortably high after a carb-heavy meal. Perhaps the elder Okinawans are (were) so long-lived because they eat (ate) a lot of whole, plant-based carbs (sweet potatoes!) AND are (were) very physically active.

 

--Dean

 

-----------------

[1] Diabetes Care. 2013 Apr;36(4):810-6. doi: 10.2337/dc12-0092. Epub 2012 Nov 27.

 

Dietary fat acutely increases glucose concentrations and insulin requirements in

patients with type 1 diabetes: implications for carbohydrate-based bolus dose

calculation and intensive diabetes management.

 

Wolpert HA(1), Atakov-Castillo A, Smith SA, Steil GM.

 

Author information:

(1)Joslin Diabetes Center, Boston, Massachusetts, USA.

howard.wolpert@joslin.harvard.edu

 

 

OBJECTIVE: Current guidelines for intensive treatment of type 1 diabetes base the

mealtime insulin bolus calculation exclusively on carbohydrate counting. There is

strong evidence that free fatty acids impair insulin sensitivity. We hypothesized

that patients with type 1 diabetes would require more insulin coverage for

higher-fat meals than lower-fat meals with identical carbohydrate content.

RESEARCH DESIGN AND METHODS: We used a crossover design comparing two 18-h

periods of closed-loop glucose control after high-fat (HF) dinner compared with

low-fat (LF) dinner. Each dinner had identical carbohydrate and protein content,

but different fat content (60 vs. 10 g).

RESULTS: Seven patients with type 1 diabetes (age, 55 ± 12 years; A1C 7.2 ± 0.8%)

successfully completed the protocol. HF dinner required more insulin than LF

dinner (12.6 ± 1.9 units vs. 9.0 ± 1.3 units; P = 0.01) and, despite the

additional insulin, caused more hyperglycemia (area under the curve >120 mg/dL =

16,967 ± 2,778 vs. 8,350 ± 1,907 mg/dL⋅min; P < 0001). Carbohydrate-to-insulin

ratio for HF dinner was significantly lower (9 ± 2 vs. 13 ± 3 g/unit; P = 0.01).

There were marked interindividual differences in the effect of dietary fat on

insulin requirements (percent increase significantly correlated with daily

insulin requirement; R(2) = 0.64; P = 0.03).

CONCLUSIONS: This evidence that dietary fat increases glucose levels and insulin

requirements highlights the limitations of the current carbohydrate-based

approach to bolus dose calculation. These findings point to the need for

alternative insulin dosing algorithms for higher-fat meals and suggest that

dietary fat intake is an important nutritional consideration for glycemic control

in individuals with type 1 diabetes.

 

PMID: 23193216

 

 

-------------------

[2] Diabetes Care. 2015 Jun;38(6):1008-15. doi: 10.2337/dc15-0100.

 

Impact of fat, protein, and glycemic index on postprandial glucose control in

type 1 diabetes: implications for intensive diabetes management in the continuous

glucose monitoring era.

 

Bell KJ(1), Smart CE(2), Steil GM(3), Brand-Miller JC(4), King B(2), Wolpert

HA(5).

 

 

BACKGROUND: Continuous glucose monitoring highlights the complexity of

postprandial glucose patterns present in type 1 diabetes and points to the

limitations of current approaches to mealtime insulin dosing based primarily on

carbohydrate counting.

METHODS: A systematic review of all relevant biomedical databases, including

MEDLINE, Embase, CINAHL, and the Cochrane Central Register of Controlled Trials,

was conducted to identify research on the effects of dietary fat, protein, and

glycemic index (GI) on acute postprandial glucose control in type 1 diabetes and

prandial insulin dosing strategies for these dietary factors.

RESULTS: All studies examining the effect of fat (n = 7), protein (n = 7), and GI

(n = 7) indicated that these dietary factors modify postprandial glycemia. Late

postprandial hyperglycemia was the predominant effect of dietary fat; however, in

some studies, glucose concentrations were reduced in the first 2-3 h, possibly

due to delayed gastric emptying. Ten studies examining insulin bolus dose and

delivery patterns required for high-fat and/or high-protein meals were

identified. Because of methodological differences and limitations in experimental

design, study findings were inconsistent regarding optimal bolus delivery

pattern; however, the studies indicated that high-fat/protein meals require more

insulin than lower-fat/protein meals with identical carbohydrate content.

CONCLUSIONS: These studies have important implications for clinical practice and

patient education and point to the need for research focused on the development

of new insulin dosing algorithms based on meal composition rather than on

carbohydrate content alone.

PMID: 25998293

Edited by Dean Pomerleau

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Dean, thanks for the comments and references.

 

Perhaps the elder Okinawans are (were) so long-lived because they eat (ate) a lot of whole, plant-based carbs (sweet potatoes!) AND are (were) very physically active.

 

I think that's right. There's some evidence -- despite the studies showing the merits of the Mediterranean diet -- that even MUFA might be harmful in some ways. People in most (all?) long-lived cultures don't actually eat a lot of fat, but they are highly non-sedentary (which doesn't mean they're out jogging; they're just very often in motion).

 

 

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Dean, thanks for the comments and references.

 

Perhaps the elder Okinawans are (were) so long-lived because they eat (ate) a lot of whole, plant-based carbs (sweet potatoes!) AND are (were) very physically active.

 

I think that's right. There's some evidence -- despite the studies showing the merits of the Mediterranean diet -- that even MUFA might be harmful in some ways. People in most (all?) long-lived cultures don't actually eat a lot of fat, but they are highly non-sedentary (which doesn't mean they're out jogging; they're just very often in motion).

 

 

 Be wary of Buettner's BS line about how they don't do intense exercise.

 

As an over-privileged, soft-living first-worlder, he's evidently never chopped wood or cleared brush with a machete.  He also seems to think that the fact that he lost an arm wrestling contest with a guy who's over 90 is just evidence of high levels of "constantly moving around."  NOPE.  It's vigorous activity and heavy lifting.

 

Okinawans do formal martial arts.  Seventh Day Adventists go to the gym.  Ikarians, Sardinians, and Costa Ricans ALL chopped wood daily for wood fires IN HIS ACTUAL BOOK.

 

Watch carefully what he describes versus the lessons he takes from them.  They are often quite different.

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Hi Zeta,

First, on the glycine: in (1), "normal young subjects ingested in random order: water, 25 g glucose, an amino acid (1 mmol/kg lean body mass; range from ≈6.2 to ≈12.7 g), and an amino acid + glucose ... given at ≈0800 h following an overnight fast." When given alon, glycine was in the top 2 for increasing both insulin and glucagon; its incremental effect on these was not as strong as other aminos when combined with glucose, but it still led to one of the strongest blunting effects on the OGTT. It seems quite plausible that some combo of high insulin leading to hypoglycemia (and a reactive cortisol burst) plus elevated glucagon would lead to an overall rise in AM glucose.

An additional factor:
 

I think I started going through a very rapid manopause a few years ago (but I don't have a pre-manopause testosterone baseline, so I can't be certain) -- I noticed loss of hair on legs, reduced libido, etc. -- and I'm guessing the increase in morning glucose is related to that, and not to a switch from lowish fat to somewhat high fat (45-50% fat by calories, mostly nuts) diet that I made around that same time. Plus, I'm pretty sure that manopause and glucose changes started before the dietary changes. (I wish I had better records on that....) I also started getting much weaker physically around that time.


Separately, I see you're also having a problem with CR-induced elevated cortisol and sleep. Now, right on its face, it seems intuitive that a quite low-carb diet, particularly when combined with fasting, is more likely to lead to hypoglycemia overnight as a result of failing to lay down much glycogen and then drawing it down for a longer period, resulting in a reactive surge or cortisol and reactive hyperglycemia. Moreover, you've mentioned in the past that you have followed a regimen of intense daily aerobic exercise, which obviously further depletes glycogen stores. And there's a fair amount of evidence that low-carb diets, when combined with (usually intensive) exercise, both low total and free T and elevated cortisol (2-7). ((7) ostensibly reports no significant effect on cortisol, but the nominal effect was a ≈23% increase in AM cortisol when subjects switched from a
15:45:40 to a 25:15:60 PCF. (8) also ostensibly found no effect, but this was from just adding more fat into the diet with no reduction in P or C).

If you just Google:
carbohydrates cortisol bed OR bedtime
... you'll get plenty of anecdotal accounts and/or advice from low-carb and Paleo dieters saying that they got elevated cortisol in response to going too low on carbs. One of them quotes a diagnostic questionnaire from Rob Wolff on this subject.

Your memory on the timing of your low T, high-AM-cortisol-associated morning insomnia, and waking hyperglycemia vs. your diet change may be slightly mistaken, or you may have undergone an initial shift for other reasons that is being exacerbated by the low-carb diet, exercise, and fasting.

So, while I certainly wouldn't advise this as a general rule, you might try a moderate-GI, fairly high-carb snack before bed. This should also aid endogenous melatonin synthesis. This is a Bad Idea on several fronts in the general population, but quite plausibly not in the context of a CRed, intensely-exercising, otherwise-low-carb-eating person with your endocrinology and symptomatology.
 

Anyway, my narrower question: 9-10 g of protein isn't a tiny amount. Could this be contributing to the higher morning glucose, and to the weird continued increase in fasting glucose as the morning wears on? Or might it be fat from the previous evening's meal (even though my last meal is always finished at least 4 hours before going to bed)?? (I'm still learning about the effects of dietary fat on the liver, etc.)


In this and a couple of other posts, you've conflated increased amino acid intake with increased protein intake: they aren't the same thing, either at an obvious scientific level or at a nutritional or metabolic level, and I suggest/request that you should exercise more precision on this point.

Dean, I did a very deep dig on the question of whether high fat intake impairs insulin sensitivity in humans, and (while you may reasonably think that I am predisposed to this conclusion) I really couldn't find anything convincing. I decided some time ago to limit my own fat intake to 38% was because of the KANWU study (9), which we discussed many years ago (as the List Archives would doubtless attest, if they were up). It found that while substituting MUFA (not even EVOO!) for SaFA improves insulin sensitivity, but in a post hoc analysis they also found that the advantage is lost and insulin sensitivity declines as MUFA exceeds 38% of Calories. They later found a similar effect for BP.(10)

However, my more recent rabbit-hole dig for supporting or refuting evidence found very little, either way. There is a not-terribly-well-documented but consistent effect of very-low-carb diets impairing postprandial glucose as measured on OGTT, but it seems to be rapidly reversible (the caveat being that these studies last for a month or two at most and don't tell you anything about an effect of a lifetime on Atkins). This makes sense, as the body is adapting to a very-low-carb regime and isn't used to dealing with an incoming carb bomb. But not much evidence for high fat as such, or for a Zonish macronutrient ratio (which consistently lowers glucose and lowers postprandial glucose after a meal of the same kind of macronutrient ratio).

I also found next to nothing in humans even really supporting the main KANWU finding that substituting SaFA with MUFA or PUFA improves insulin sensitivity in humans (it certainly does in rodents). As it happens, this is also basically what a 2008 review on this subject (11) found, tho' their conclusion was more scientifically cautious (ie, they're therefore more willing to reserve judgement, whereas I decided that I do, after all, have to eat!). They do say that " In contrast, one of the better designed studies found that consumption of a high-saturated-fat diet decreased insulin sensitivity in comparison to a high-monounsaturated-fat diet"; this turns out to be (surprise!) the KANWU study.

This study:

http://link.springer.com/article/10.1007/s00125-001-0768-3

Initially seems relevant, until you dig in and see that there was a statistically non-significant, but suspicious, 1.7 MJ (406 Calorie!) difference between the PUFA and the SaFA diet.

Here are some of the weeds I was digging in. I'd invite anyone to whack hir way into them and report back .

http://scholar.google.com/scholar?q=monounsaturated+insulin+sensitivity+kanwu&btnG=&hl=en&as_sdt=5%2C31&sciodt=0%2C31&cites=11526430237464658623&scipsc=1
http://link.springer.com/article/10.1007/s00125-001-0768-3
http://www.sciencedirect.com/science/article/pii/S0939475309001306
http://scholar.google.com/scholar?cluster=12272451590766159678&hl=en&as_sdt=5,31&sciodt=0,31
http://www.ncbi.nlm.nih.gov/pubmed/18065577
http://press.endocrine.org/doi/full/10.1210/jc.2004-1489
http://press.endocrine.org/na101/home/literatum/publisher/endo/journals/content/jcem/2005/jcem.2005.90.issue-4/jc.2004-1489/production/images/large/zeg0040532840001.jpeg
http://ajcn.nutrition.org/content/84/3/540.long
http://link.springer.com/article/10.1007/s00125-009-1282-2
http://ajcn.nutrition.org/content/87/4/855.full
http://ajcn.nutrition.org/content/82/1/196.full
http://link.springer.com/article/10.1007/s00125-006-0211-x
http://ajcn.nutrition.org/content/83/2/221.full
http://care.diabetesjournals.org/content/25/8/1283.long
http://jn.nutrition.org/content/142/5/824.long
http://ajcn.nutrition.org/content/95/4/825.full
http://www.pnas.org/content/early/2013/10/31/1309469110.abstract

References
1: Gannon MC, Nuttall FQ. Amino acid ingestion and glucose metabolism--a review. IUBMB Life. 2010 Sep;62(9):660-8. doi: 10.1002/iub.375. Review. PubMed PMID: 20882645.

2: Lane AR, Duke JW, Hackney AC. Influence of dietary carbohydrate intake on the free testosterone: cortisol ratio responses to short-term intensive exercise training. Eur J Appl Physiol. 2010 Apr;108(6):1125-31. doi: 10.1007/s00421-009-1220-5. Epub 2009 Dec 20. PubMed PMID: 20091182.

3: Gleeson M, Bishop NC. Special feature for the Olympics: effects of exercise on the immune system: modification of immune responses to exercise by carbohydrate, glutamine and anti-oxidant supplements. Immunol Cell Biol. 2000 Oct;78(5):554-61. Review. PubMed PMID: 11050539.

5: Tegelman R, Aberg T, Pousette A, Carlström K. Effects of a diet regimen on pituitary and steroid hormones in male ice hockey players. Int J Sports Med. 1992 Jul;13(5):424-30. PubMed PMID: 1387870.

6: Anderson KE, Rosner W, Khan MS, New MI, Pang SY, Wissel PS, Kappas A. Diet-hormone interactions: protein/carbohydrate ratio alters reciprocally the plasma levels of testosterone and cortisol and their respective binding globulins in man. Life Sci. 1987 May 4;40(18):1761-8. PubMed PMID: 3573976.

7: Tsai L, Karpakka J, Aginger C, Johansson C, Pousette A, Carlström K. Basal concentrations of anabolic and catabolic hormones in relation to endurance exercise after short-term changes in diet. Eur J Appl Physiol Occup Physiol. 1993;66(4):304-8. PubMed PMID: 8495690.

8:Christ ER, Zehnder M, Boesch C, Trepp R, Mullis PE, Diem P, Décombaz J. The effect of increased lipid intake on hormonal responses during aerobic exercise in endurance-trained men. Eur J Endocrinol. 2006 Mar;154(3):397-403. PubMed PMID: 16498052.

9: Vessby B, Uusitupa M, Hermansen K, Riccardi G, Rivellese AA, Tapsell LC, Nälsén C, Berglund L, Louheranta A, Rasmussen BM, Calvert GD, Maffetone A, Pedersen E, Gustafsson IB, Storlien LH; KANWU Study. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. Diabetologia. 2001 Mar;44(3):312-9. PubMed PMID: 11317662.

10: Rasmussen BM, Vessby B, Uusitupa M, Berglund L, Pedersen E, Riccardi G, Rivellese AA, Tapsell L, Hermansen K; KANWU Study Group. Effects of dietary saturated, monounsaturated, and n-3 fatty acids on blood pressure in healthy subjects. Am J Clin Nutr. 2006 Feb;83(2):221-6. PubMed PMID: 16469978.

11: Galgani JE, Uauy RD, Aguirre CA, Díaz EO. Effect of the dietary fat quality on insulin sensitivity. Br J Nutr. 2008 Sep;100(3):471-9. doi: 10.1017/S0007114508894408. Epub 2008 Apr 8. Review. PubMed PMID: 18394213.

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Michael Rae wrote:

 

   > Here are some of the weeds I was digging in [on the connection between dietary fat type and insulin sensitivity]. I'd invite anyone to
   > whack hir way into them and report back.
 
It does appear hard to pin down the influence of different dietary fats on insulin sensitivity. But I'm interested in the link between dietary fat per se (independent of fat type) on insulin sensitivity - and therefore the implications for the optimal macronutrient ratios.
 
Dr. Greger recently had an interesting video on fat and insulin sensitivity:
 
 
He highlights pretty strong evidence that plasma free fatty acids (either from diet or introduced intravenously) are absorbed by muscle cells, which impairs glucose uptake by those same muscle cells. From one of those studies [1]:
 

 

In healthy adolescents, an acute elevation in plasma FFA with IL (intravenous lipid) infusion is accompanied by significant increases in IMCL [intramyocellular lipid content - i.e. fat inside muscle cells] and reductions in insulin sensitivity with no race differential.

 

The ability to metabolize blood glucose was reduced by 40% in the adolescent boys when their blood was infused with fat. Study [2] found the same thing in adults. Study [3] found fat in muscle cells strongly correlates with insulin resistance in non-diabetic, non-obese humans.
 
This recent review article [4] on the link between intramyocellular lipid content and insulin resistance says (not surprisingly) that the mechanism is more complicated than originally thought (the "gumming up" hypothesis I alluded to is obviously too simple), but emphasizes that the link between lipids and insulin resistance remains unequivocal. 
 
So it seems plausible that a low-carb meal (or diet) with lots of fat can skirt the impaired insulin sensitivity issue by avoiding the challenges of substantial glucose in the blood. And it also seems plausible that a high-carb meal (or diet) with little fat can maintain high insulin sensitivity and not have a problem with metabolizing glucose. But meals (or diets) with relatively high amounts of both carbs and fat can run into the problem of having substantial glucose in the blood and no effective way to clear it due to impaired glucose metabolism from the fat, leading to elevated glucose and insulin levels, and eventual type 2 diabetes.
 
--Dean
 
----------------
[1] Metabolism. 2013 Mar;62(3):417-23. doi: 10.1016/j.metabol.2012.09.007. Epub 2012 Nov 1.

 

Effects of an overnight intravenous lipid infusion on intramyocellular lipid content and insulin sensitivity in African-American versus Caucasian adolescents.

Abstract
OBJECTIVE:

To explain the predisposition for insulin resistance among African American (AA) adolescents, this study aimed to: 1) examine changes in intramyocellular lipid content (IMCL), and insulin sensitivity with intralipid (IL) infusion; and 2) determine whether the increase in IMCL is comparable between AA and Caucasian adolescents.

MATERIALS AND METHODS:

Thirteen AA and 15 Caucasian normal-weight adolescents (BMI <85th) underwent a 3-h hyperinsulinemic-euglycemic clamp, on two occasions in random order, after an overnight 12-h infusion of: 1) 20% IL and 2) normal saline (NS). IMCL was quantified by (1)H magnetic resonance spectroscopy in tibialis anterior muscle before and after IL infusion.

RESULTS:

During IL infusion, plasma TG, glycerol, FFA and fat oxidation increased significantly, with no race differences. Hepatic insulin sensitivity decreased with IL infusion with no difference between the groups. IL infusion was associated with a significant increase in IMCL, which was comparable between AA (Δ 105%; NS: 1.9±0.8 vs. IL: 3.9±1.6 mmol/kg wet weight) and Caucasian (Δ 86%; NS: 2.8±2.1 vs. IL: 5.2±2.4 mmol/kg wet weight), with similar reductions (P<0.01) in insulin sensitivity between the groups (Δ -44%: NS: 9.1±3.3 vs. IL: 5.1±1.8 mg/kg/min per μU/ml in AA) and (Δ -39%: NS: 12.9±6.0 vs. IL: 7.9±3.8 mg/kg/min per μU/ml in Caucasian) adolescents.

CONCLUSIONS:

In healthy adolescents, an acute elevation in plasma FFA with IL infusion is accompanied by significant increases in IMCL and reductions in insulin sensitivity with no race differential. Our findings suggest that AA normal-weight adolescents are not more susceptible than Caucasians to FFA-induced IMCL accumulation and insulin resistance.

 

--------------

[2] Diabetes. 1999 Feb;48(2):358-64.

Rapid impairment of skeletal muscle glucose transport/phosphorylation by free fatty acids in humans.

Abstract

The initial effects of free fatty acids (FFAs) on glucose transport/phosphorylation were studied in seven healthy men in the presence of elevated (1.44 +/- 0.16 mmol/l), basal (0.35 +/- 0.06 mmol/l), and low (<0.01 mmol/l; control) plasma FFA concentrations (P < 0.05 between all groups) during euglycemic-hyperinsulinemic clamps. Concentrations of glucose-6-phosphate (G-6-P), inorganic phosphate (Pi), phosphocreatine, ADP, and pH in calf muscle were measured every 3.2 min for 180 min by using 31P nuclear magnetic resonance spectroscopy. Rates of whole-body glucose uptake increased similarly until 140 min but thereafter declined by approximately 20% in the presence of basal and high FFAs (42.8 +/- 3.6 and 41.6 +/- 3.3 vs. control: 52.7 +/- 3.3 micromol x kg(-1) x min(-1), P < 0.05). The rise of intramuscular G-6-P concentrations was already blunted at 45 min of high FFA exposure (184 +/- 17 vs. control: 238 +/- 17 micromol/l, P = 0.008). At 180 min, G-6-P was lower in the presence of both high and basal FFAs (197 +/- 21 and 213 +/- 18 vs. control: 286 +/- 19 micromol/l, P < 0.05). Intramuscular pH decreased by -0.013 +/- 0.001 (P < 0.005) during control but increased by +0.008 +/- 0.002 (P < 0.05) during high FFA exposure, while Pi rose by approximately 0.39 mmol/l (P < 0.005) within 70 min and then slowly decreased in all studies. In conclusion, the lack of an initial peak and the early decline of muscle G-6-P concentrations suggest that even at physiological concentrations, FFAs primarily inhibit glucose transport/phosphorylation, preceding the reduction of whole-body glucose disposal by up to 120 min in humans.

PMID: 10334314

 

------------------

[3] Diabetologia. 1999 Jan;42(1):113-6.

Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study.

Erratum in
  • Diabetologia 1999 Oct;42(10):1269.
  • Diabetologia 1999 Mar;42(3):386.
Abstract

Recent muscle biopsy studies have shown a relation between intramuscular lipid content and insulin resistance. The aim of this study was to test this relation in humans by using a novel proton nuclear magnetic resonance (1H NMR) spectroscopy technique, which enables non-invasive and rapid (approximately 45 min) determination of intramyocellular lipid (IMCL) content. Normal weight non-diabetic adults (n = 23, age 29+/-2 years. BMI = 24.1+/-0.5 kg/m2) were studied using cross-sectional analysis. Insulin sensitivity was assessed by a 2-h hyperinsulinaemic (approximately 450 pmol/l)-euglycaemic (approximately 5 mmol/l) clamp test. Intramyocellular lipid concentrations were determined by using localized 1H NMR spectroscopy of soleus muscle. Simple linear regression analysis showed an inverse correlation (r = -0.579, p = 0.0037) [corrected] between intramyocellular lipid content and M-value (100-120 min of clamp) as well as between fasting plasma non-esterified fatty acid concentration and M-value (r = -0.54, p = 0.0267). Intramyocellular lipid content was not related to BMI, age and fasting plasma concentrations of triglycerides, non-esterified fatty acids, glucose or insulin. These results show that intramyocellular lipid concentration, as assessed non invasively by localized 1H NMR spectroscopy, is a good indicator of whole body insulin sensitivity in non-diabetic, non-obese humans.

 

-----------------

[4] Diabetologia

Clinical and Experimental Diabetes and Metabolism201255:2597

DOI: 10.1007/s00125-012-2597-y

Then and Now
Revisiting the connection between intramyocellular lipids and insulin resistance: a long and winding road
D. M. Muoio1, 2, 3  
(1)
Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27710, USA
(2)
Department of Medicine, Duke University, Durham, NC, USA
(3)
Department of Pharmacology & Cancer Biology, Duke University, Durham, NC, USA
 
 
D. M. Muoio
Email: muoio@duke.edu
Published online: 3 June 2012
 
 
ABSTRACT

In the mid-1990s, researchers began to re-examine type 2 diabetes from a more ‘lipocentric’ perspective; giving strong consideration to the idea that systemic lipid imbalances give rise to glucose dysregulation, rather than vice versa. At the forefront of this paradigm shift was a report by Krssak and colleagues (Diabetologia 1999; 42:113–116) showing that intramyocellular lipid content, measured via the (then) novel application of proton nuclear magnetic resonance spectroscopy, served as a robust indicator of muscle insulin sensitivity in healthy individuals. A subsequent wave of investigations produced compelling correlative evidence linking ectopic lipid deposition within skeletal myocytes to the development of obesity-associated insulin resistance. But this relationship has proven much more complex than originally imagined, and scientists today are still left wondering if and how the intramyocellular accumulation of lipid droplets has a direct bearing on insulin action. Originally viewed as a simple storage depot, the lipid droplet is now recognised as an essential and sophisticated organelle that actively participates in numerous cellular processes. This edition of ‘Then and now’ revisits the connection between intramuscular lipids and insulin resistance and looks to future research aimed at understanding the dynamic interplay between lipid droplet biology and metabolic health.

Edited by Dean Pomerleau

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Just a quick thanks to Dean and Michael for the extremely useful and interesting posts. I am currently digging into the referenced studies and will report back when I have something useful to say. (But either way probably not in the next week -- have some big and scary medical appointments next week where I might be getting some bad news.)

 

Also wanted to note an interesting post by Al Pater, which adds to my concerns about my high fat diet (but high protein is the more serious problem) (1):

 

----------------------
Subject: [CR] Carbs earn their place at the table
Date: Mon, 17 Aug 2015 16:12:30 -0600 (MDT)

 

Carbs earn their place at the table


[...]
 

Forget protein. New evidence suggests bread and potatoes have been unfairly demonised. By Norman Swan.

[...]
 
The longest-lived mice in the best metabolic health – their heart doctors would have been happy with their blood lipid profiles, sugar, and insulin levels – were the ones eating more carbohydrates and less fat and protein. A low ratio of protein to carbs appeared to be key. The shortest-lived mice were either on a low protein, low carb, high fat diet or a high protein, high fat, low-carb diet, similar to the original Atkins diet. The mice on the Atkins-type regime were leaner, but the plumper, higher carb eating mice lived 30% longer. [emph. mine]

[...]
 
The Sydney group then decided to compare, head to head, the higher carbohydrate, lower fat and protein diet to calorie restriction, again in mice, and to test their longevity and metabolic health.

The results showed that the free eating, higher carb mice lived as long as those on 40% calorie restriction, and were presumably happier too, even if they were a bit chunkier.

 



 

Zeta

 

(1) The study:

 

The Ratio of Macronutrients, Not Caloric Intake, Dictates Cardiometabolic Health, Aging, and Longevity in Ad Libitum-Fed Mice

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Very interesting.  Of course,

(1)  It's only onestudy, and

(2)  It's with rodents.

But, IMO, the main difference between a human and a rat is human arrogance.

:)

Anyway, I'm happy to say that my diet is, and has been for a very long time, primarily high fibre carbs (raw vegetables), with low protein and very low fat.

  -- Saul

 

P.S.:  My last OGTT was when I was tested by Luigi, I think in 2007 or so.  At the time, my diet was mostly similar -- but somewhat higher in protein (still low protein -- since starting CR, about 16 years ago, I have been a "Walfordian" (as opposed to a "Zonian") -- meaning high complex carbs. low fat and protein.

 

When Luigi gave me my glucose bolus, my serum glucose recovered to normal within a few minutes.  I did not show any trace of the OGTT problem, that many of our most prominent and strict CR practitioners have experienced.

 

:unsure:

 

  -- Saul

Edited by Saul

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On your noticing loss of hair on legs, that seems common among many CR'rs including this author.  

I have lost body hair on many regions below the earlobes and today, after practicing CR 11+ yrs, noticed the outwardly facing surfaces of my fingers are completely bald--it's an astonishingly peculiar appearance!  Kenton

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Hi Kenton!

 

I'm totally revising the message that I left yesterday:

 

I began CR in April, 1996 -- so it's been over 19 years.

 

I had a haircut yesterday -- and the hair stylist noticed that the hair on the middle part of my left cheek was virtually bald; not so on the right side.  I had her cut the relevant parts of both sideburns to symmetry.

 

This made me think:  Actually, I DO remember having fine hair on the back of my fingers and toes, when I was a child and later -- there's none now; my wife doesn't remember it, either.

 

I still have fine hair on the sides of my arms -- but my legs are totally bald (but I do remember having had fine hair there, a long time ago, as well).

 

I also do remember -- as a child -- having some ear lobe hair -- this also has been totally gone, for a very long time.

 

So, I totally take back what I said yesterday.  (Being on CR for over 19 years, it's easy to forget details like that from ad-lib days.)

 

 

  -- Saul

Edited by Saul

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I think a particular pattern of hair-loss in men is to be expected with CR because of the lowered testosterone. In my case, though, it was very sudden.

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I have very low free testosterone -- but no hair loss (but then again, I never had much hair, except on my head  -- you can't lose hair on your fingers if you never had any).  I have some fine hair on my arms. 

 

What little there is hasn't been falling out.

 

I've never had hair on my legs - my wife says that I've always been a pretty hairless man.  (She has more arm hair than I do.)

 

But of course, there's a lot of individual variation.

 

Michael Rae seems to have more than adequate hair, but we'd have to ask him (or April :)).

 

  -- Saul

 

 

 

 

 

 

 

 

 

 

0

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I think I know when my testosterone levels collapsed.

 

From youth until after a certain precise point (unfortunately,I didn't record the time -- but I think it was after a few months of CR, 16 years ago) - I had an intense desire to have sex with girls. 

 

Then, suddenly, the desire collapsed.

 

Since then, it continues to be easy to have sex -- there is just virtually no desire.

 

But I don't recall any change in hair patterns (but, as noted, I always have had almost no body hair).

 

I suspect the collapse of the male sex drive is probably the second best way of testing for reduced free testosterone -- the best way is a blood test.

 

  -- Saul

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I thought this study might be of relevance:

 

1. Metabolism. 2007 Dec;56(12):1729-34.

 

Impact of reduced meal frequency without caloric restriction on glucose

regulation in healthy, normal-weight middle-aged men and women.

 

Carlson O(1), Martin B, Stote KS, Golden E, Maudsley S, Najjar SS, Ferrucci L,

Ingram DK, Longo DL, Rumpler WV, Baer DJ, Egan J, Mattson MP.

 

Author information:

(1)Diabetes Section, Laboratory of Clinical Investigation, National Institute on

Aging Intramural Research Program, Baltimore, MD, USA.

 

An unresolved issue in the field of diet and health is if and how changes in meal

frequency affect energy metabolism in humans. We therefore evaluated the

influence of reduced meal frequency without a reduction in energy intake on

glucose metabolism in normal-weight, healthy male and female subjects. The study

was a randomized crossover design, with two 8-week treatment periods (with an

intervening 11-week off-diet period) in which subjects consumed all of their

calories for weight maintenance distributed in either 3 meals or 1 meal per day

(consumed between 4:00 pm and 8:00 pm). Energy metabolism was evaluated at

designated time points throughout the study by performing morning oral glucose

tolerance tests and measuring levels of glucose, insulin, glucagon, leptin,

ghrelin, adiponectin, resistin, and brain-derived neurotrophic factor (BDNF).

Subjects consuming 1 meal per day exhibited higher morning fasting plasma glucose

levels, greater and more sustained elevations of plasma glucose concentrations,

and a delayed insulin response in the oral glucose tolerance test compared with

subjects consuming 3 meals per day. Levels of ghrelin were elevated in response

to the 1-meal-per-day regimen. Fasting levels of insulin, leptin, ghrelin,

adiponectin, resistin, and BDNF were not significantly affected by meal

frequency. Subjects consuming a single large daily meal exhibit elevated fasting

glucose levels and impaired morning glucose tolerance associated with a delayed

insulin response during a 2-month diet period compared with those consuming 3

meals per day. The impaired glucose tolerance was reversible and was not

associated with alterations in the levels of adipokines or BDNF.

 

PMCID: PMC2121099

PMID: 17998028 [PubMed - indexed for MEDLINE]

Edited by Brett Black

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