Impaired glucose tolerance now

[tasbin]

Impaired glucose tolerance (IGT) is a pre-diabetic state of hyperglycemia that is associated with insulin resistance

 

Has anyone ever had to deal with a sudden impaired glucose tolerance ?

I am doing some intermittent dry fast(18h per day) during 1 month & maybe it is related .

I am used to control my blood sugar since 6 months so I know that it was not present many months ago.

My BMI is 20.5  & I have lost 10kg (22 lbs) around slowly (a year) so It is not related to any obesity. But my overweight mother is diabetic type 2 (and grand-father too).

 

I have found one study mentionning that very-low-calorie diets may induce insulin resistance and overt diabetes mellitus.
My fasting blood sugar (FBS) is good (82-83mg/dl).

 

But after a meal breaking the fast with also a home-made smoothie with only fruits, it raises above 140mg and <180mg after 2 hours.

 

I have tested again with a simple fruit & oats, milk some honey and again same values.

 

After 2 hours >140mg is defined as IGT or impaired glucose tolerance.I have confirmed those abrnormal values 4 times in 2-3 days.

 

I am not fasting anymore to see if this could be related & will regain 1-2kg.

 

My last  hba1C last year  was 5.2%(maybe different now) so I am not diabetic at least on two definitions (FBS<1g & HBA1C<6%).

 

I have read a long time ago that some cronies (Dean Pomerleau I think but not sure) had those issues as well.
 

[Dean Pomerleau]

Hi Tasbin,

 

Sorry to hear about your glucose troubles, and thanks for pointing to that study [1] that shows at least some obese folks put on a very low calorie diet for weight loss become insulin insensitive. I too used to have trouble with effectively handling a big glucose challenge. In fact, I was among the worst responders to the 2H oral glucose tolerance test (OGTT) administered by Luigi Fontana to a bunch of CR folks and reported in this 2010 paper [2], discussed here and especially here where I go into just how poor my performance was on the OGTT - my glucose as 199 mg/dL the 2h marker after ingesting the 75g of glucose. But I wasn't the only who exhibited this sort of impaired glucose control. In fact, it appeared to Luigi from the data that is was the folks with the most "classic" signs of CR (lower circulating levels of IGF-1, total testosterone, and thyroid hormone) who were the most impaired. And he indicates in that paper that this is fairly common to see if CR'ed rodents as well.

 

We've speculated and fretted for years over this - wondering if it is something to worry about or a sign that CR is working. What it appears to be is that we have a very low fasting insulin, and a muted first insulin response when glucose enters the bloodstream, allowing glucose levels to rise alarmingly. It may be a natural response by the body to simply downregulate it's insulin synthesis pathways because they aren't needed very often, but that obviously can't be the whole explanation when folks like you see scary glucose spikes even when eating their normal, healthy diet (i.e. not an artificial glucose spike like an OGTT induces). Others of us (including Michael and myself) that it could be a sign of atrophy in pancreatic β-cells (those that produce insulin), which wouldn't be a good thing.

 

I think the general consensus has become that this impaired glucose tolerance is likely a bad thing, or at least something to keep an eye on and take steps to mitigate. In fact, whether prompted by this result or not I'm not sure, but Paul McGlothin went on to develop his (and wife Meredith's) The CR Way™ program (www.livingthecrway.com) which focuses a great deal on combining CR with ways of optimizing glucose control. Paul advocates (or used to advocate - not sure these days what his protocol looks like) things like drinking lemon water prior to a meal, and having a small 'tease' meal to stimulate insulin production before the big meal hits the stomach and bloodstream. He also (IIRC) advocates post-meal exercise (e.g. brisk walking).

 

What I've found to be effective (and perhaps the only thing I've found effective, at least until recently) is post-meal exercise. Vigorously exercising for even a few minutes shortly after I eat I've found can greatly attenuate my glucose level. Exercise, and more recently, the combination of exercise and cold exposure as described in that second post, allows me to eat one big meal a day, and have a quite reasonably glucose peak after a meal. I measure this morning ½ hour after my breakfast, after a short walk followed by some light work cleaning up in the kitchen, brushing teeth etc, and my glucose was peaking at 120 mg/dL (I know because previous 'dense' glucose measures tell me that 30min post meal is when my glucose is at its maximum). Gordo has reported even more dramatic beneficial results of cold exposure (and cold exposure alone) on his glucose control, as he discussed in great detail here and here.

 

So those are interventions you might consider trying. Finally, here is a very good thread about Sirtuin's recent quest to get his troubling postprandial glucose spikes under control. It appears exercise was an important part of his solution too, but perhaps he is around to share directly what he thinks made the difference for him.

 

Good luck, and let us know what you try, and how it works.

 

--Dean

 

---------

[1] J Diabetes Complications. 1996 Mar-Apr;10(2):109-12.

 

Starvation diet and very-low-calorie diets may induce insulin resistance and

overt diabetes mellitus.

 

Koffler M(1), Kisch ES.

 

Author information: 

(1)Diabetes Unit, Tel-Aviv University Medical Center, Ichilov Hospital, Israel.

 

We have observed seven initially obese individuals who, during the course of a

strenuous weight-reduction program, developed diabetes mellitus:

non-insulin-dependent diabetes mellitus in five cases and insulin-dependent

diabetes mellitus in two cases. None had any sign of prior diabetic symptoms.

Although weight reduction is encouraged in obesity, crash diets without proper

medical surveillance may have deleterious effects. This sequence of induction of 

diabetes has not previously been reported in the medical literature. The

metabolic situation in extremely low-calorie diets may be comparable to that in

starvation. An attempt is made to explain our observation concerning the

induction of a diabetic state during such diets, on the basis of increased

insulin resistance in states of starvation and anorexia nervosa, with a

concomitant role in stress hormones.

 

DOI: 10.1016/1056-8727(94)00077-8 

PMID: 8777329

 

--------

[2] Age (Dordr). 2010 Mar;32(1):97-108. doi: 10.1007/s11357-009-9118-z. Epub 2009 Nov

11.

 

Effects of long-term calorie restriction and endurance exercise on glucose

tolerance, insulin action, and adipokine production.

 

Fontana L(1), Klein S, Holloszy JO.

 

Author information:

(1)Washington University School of Medicine, St. Louis, MO 63110, USA.

lfontana@dom.wustl.edu

 

Calorie restriction (CR) slows aging and is thought to improve insulin

sensitivity in laboratory animals. In contrast, decreased insulin signaling

and/or mild insulin resistance paradoxically extends maximal lifespan in various

genetic animal models of longevity. Nothing is known regarding the long-term

effects of CR on glucose tolerance and insulin action in lean healthy humans. In

this study we evaluated body composition, glucose, and insulin responses to an

oral glucose tolerance test and serum adipokines levels in 28 volunteers, who had

been eating a CR diet for an average of 6.9 +/- 5.5 years, (mean age 53.0 +/- 11

years), in 28 age-, sex-, and body fat-matched endurance runners (EX), and 28

age- and sex-matched sedentary controls eating Western diets (WD). We found that

the CR and EX volunteers were significantly leaner than the WD volunteers.

Insulin sensitivity, determined according to the HOMA-IR and the Matsuda and

DeFronzo insulin sensitivity indexes, was significantly higher in the CR and EX

groups than in the WD group (P = 0.001). Nonetheless, despite high serum

adiponectin and low inflammation, approximately 40% of CR individuals exhibited

an exaggerated hyperglycemic response to a glucose load. This impaired glucose

tolerance is associated with lower circulating levels of IGF-1, total

testosterone, and triiodothyronine, which are typical adaptations to

life-extending CR in rodents.

 

PMCID: PMC2829643

PMID: 19904628

[tasbin]

Hi Dean,

Thanks for the detailled reponse !

 

According to the mentionned Fontana's study, "our data suggest that severe
chronic CR, in some individuals, may be associated with a relative peripheral insulin resistance mainly due
to a low muscle mass with decreased capacity to take up glucose".

So I need to increase lean mass-> exercice.

 

 

Also "decreased insulin sensitivity and glucose disposal could enhance survival, by preventing hypoglycemia.. Thus, from an
evolutionary point of view, a CR-mediated reduction in insulin signaling could be a protective metabolic
response against hypoglycemia " and "that various strains of long-lived mice are insulin resistant ".

 

According to the mentionned Fontana's study,  cronies with IGT have also:
-lower IGF-1, hsCRP. I am not vegetarian  (vegan have lower igf1 as you know) so it will be a surprise to discover a low one for me. Unfortunately, I cannot confirm that value with a blood test at the present time.

-lower lean mass (kg) & higher body fat(%) despite having a lower BMI.
Well, no surprise for me. I am more a couch potatoe so your advice to increase exercice after meal makes sense.
I will try to increase lean mass & lower body fat to see if it will makes a difference.

 

 

Some interesting & similar findings of the second & already mentionned study :
"A recent study(14) reported that 72 h of fasting reduced receptor autophosphorylation in liver and a decrease in insulin receptor substrate-1 (IRS-1)"
"Russel (15) reported that the mean A blood glu­cose, after a standard glucose-tolerance test in nine anorexia-nervosa patients, was significantly higher than in normal weight controls or in obese subjects"

14. Saad MJA...Kahn CR: Regulation of insulin receptor substrate-1 in liver and muscle of animal models of insulin resis­tance
15. Russel GFM. Metabolic aspects of anorexia nervosa.

 

 

Strangely, I needed that kind of  kick in the butt to do more exercices.  Despite all the benefits of exercice, I always find easier & less time consuming to cut on calories than to increase exercices.  I was waiting for the right "leverage" to set me on.

 

But it will be ironic that I will end up with T2 diabetes by an unexpected way  despite my deep obsession to get away as far as I can from it : I have probably read every major publications and guidelines for professional for the last 10 years on diabetes, many books. I have now a lower waistline, lower %fat, consume no sugar , used to eat a reduced GI meal &  now on calorie restriction)

 

 

Again, thank you Dean for your help. I will update that thread if I have new inputs on my case & find a solution.

[TomBAvoider]

Al Pater has just posted this interesting article:

 

What Causes Type 2 Diabetes?

 

Well worth reading. It seems worthwhile to get your triglycerides as low as possible. Or maybe there are many different ways things can go pear-shaped.  

[tasbin]

Al Pater has just posted this interesting article:

 

What Causes Type 2 Diabetes?

 

Well worth reading. It seems worthwhile to get your triglycerides as low as possible. Or maybe there are many different ways things can go pear-shaped.  

Thanks for the link. My triglycerides is already quite low: 32mg/dl.

 

I have never had a so low lean body mass in kg despited having a slightly lower weight in the past.

So with that information and the hypothesis suggested by Fontana that insulin resistance is mainly due to a low muscle mass, i suspect that I have reached a personal thresold lean mass causing  IGT.

It reminds me how  once a person crosses a personal fat threshold, type 2 diabetes develops, according to Professor Roy Taylor.

I will put that theory into practice.

[sirtuin]

Finally, here is a very good thread about Sirtuin's recent quest to get his troubling postprandial glucose spikes under control. It appears exercise was an important part of his solution too, but perhaps he is around to share directly what he thinks made the difference for him.

I've been experimenting more extensively with this lately.  You know, I'm still not sure which way to go with it over on the long term with chronic disease prevention & longevity vs hormonal balance & performance in mind.

 

I've tried eating fats + protein + fibers before meals.  I've tried tiny snacks before meals.  I've tried several small meals (5-6) over the day compared with 1-3 meals.  I've tried carbs combined with heavy fats and proteins, and carbs in absence of fats.  I've also tried very low-gi vegetable based meals, cold showers, fasting, AMPK activators, insulin mimetics, exercising before and after meals, carbs in the morning vs night, cyclical carbs, etc.  I've measured a lot of blood around different ideas.

 

The easiest and most reliable way for me to pull off consistently low post-prandial glucose numbers is to simply eat a diet that's mostly fruit by calories (fats) with vegetables + nuts + light seafood & eggs for micronutrients & protein topping off around 30-50g net carbohydrates per day divided across 2-3 meals.  This doesn't require much else and the meals are tasty.  This has a side effect of elevating ketones up into the 1-3mmol/L territory, which I find makes fasting pretty effortless and seems to increase focus... although I find exercise performance worsens and body composition loses definition.  I feel like this likely trades post-prandial hyperglycemia for hyperlipidemia.  While eating this sort of diet, my A1C stays under 5%, fasting glucose is low, insulin is low, inflammation is low, energy is high and stable, and post-prandial glucose hums along around the 90-105 mg/dL peak range.  There are no blood sugar spikes, there are no blood sugar dips -- there's just a sort of afternoon mound that brings me up 20 mg/dL points over fasting glucose then sets it back down.  Glucose runs around 70 at night, 75-80 outside of meals, and 80-100 after meals without many surprises.

 

Last night I measured blood glucose right after my meal and it was at 103 mg/dL.  I went for a 30m stroll around the block and re-measured -- 80 mg/dL.

 

I have been playing around with some interruptions to this diet by throwing in a tiny bit of low-glycemic fruit or low-glycemic whole grain (without the fat / protein / fiber that I would usually eat in a meal) and I've seen spikes up around 170-180mg/dL followed by a very sharp crash in blood sugar.  It's like first-phase insulin just isn't always there for me, meanwhile insulin sensitivity is jacked all the way up.  If I continue to increase carbohydrates, this effect seems to reverse to where I can stay under 130-140 mg/dL, if not under 120 mg/dL.  I haven't decided whether to consistently increase carbs across my meals to try to maintain some of this insulin production / insulin stores or to cycle carbohydrates in, or just stay on a very high fat diet where this isn't as issue and insulin secretion is down-regulated and physiological insulin resistance develops ... sort of like a virtual type I diabetic situation.

 

It's somewhat difficult to catch these peaks on a drop of blood -- I can reach peak glucose within 20-30m from the first bite of a meal going from 75 mg/dL to 175 mg/dL and back down to fasting levels over the course of the following 20 minutes, while a meal might take me 45-60m just to finish chewing it up.  So, short of leaving company in the middle of a meal to start bicycling down the road, it's not always very feasible to exercise away peak glucose or even predict the right time to stick my finger for a reading.  With larger fattier meals, I've seen peak glucose postponed over an hour out, and I'm much less likely to want to exercise while stuffed (which tends to be the case with a restricted eating window and a large intake of fiber.)

 

I have figured out a general approach that allows me to ingest a large volume of carbohydrates (~10 to 14 HFLC days worth of carbs in ~30 minutes to 2 hours) regardless of the glycemic index and keep peak glucose around 110-130 mg/dL, but I haven't decided whether it's better for me to remain in uninterrupted high-fat territory and avoid that insulin spike and mound of sugar.  In theory, I think this could allow me to prevent some of the calorie-restriction hormonal side effects and diabetic-like symptoms that occur from the longterm uninterrupted heavy restriction of carbohydrates at a slight caloric deficit, and give me a chance to diversify my polyphenol intake and get some decent intakes of legumes + fruit + whole grains in... but, perhaps it works against me in other ways. It's a weird sort of insulin vs glucose vs triglycerides and hormones + performance vs longevity + disease prevention optimization problem.

[Dean Pomerleau]

Sirtuin,

 

I have figured out a general approach that allows me to ingest a large volume of carbohydrates (~10 days worth of carbs in ~30 minutes) regardless of the glycemic index and keep peak glucose around 110-130 mg/dL, but I haven't decided whether it's better for me to remain in uninterrupted high-fat territory and avoid that insulin spike.  It's a weird sort of insulin vs glucose vs triglycerides optimization problem.

 

Interesting dilemma. As you know, I go for the high carb with peaks ~120 mg/dL, which I figure is not a big deal.

 

Do you do anything special pre- or post-meal to deal with this load of carbs? Or it is just that your body becomes attuned to it? When you are doing "lots of carbs and glucose peak around 110-130" how much fat and protein (i.e. macronutrient ratio) are you eating along with them?

 

--Dean

[sirtuin]

Sirtuin,

 

I have figured out a general approach that allows me to ingest a large volume of carbohydrates (~10 days worth of carbs in ~30 minutes) regardless of the glycemic index and keep peak glucose around 110-130 mg/dL, but I haven't decided whether it's better for me to remain in uninterrupted high-fat territory and avoid that insulin spike.  It's a weird sort of insulin vs glucose vs triglycerides optimization problem.

 

Interesting dilemma. As you know, I go for the high carb with peaks ~120 mg/dL, which I figure is not a big deal.

 

Do you do anything special pre- or post-meal to deal with this load of carbs? Or it is just that your body becomes attuned to it? When you are doing "lots of carbs and glucose peak around 110-130" how much fat and protein (i.e. macronutrient ratio) are you eating along with them?

 

--Dean

Personally, I find pre-meal exercise to be very useful for glucose disposal.  And, not a light cycle on the bike or round of pushups... but heavy compound exercises (deadlift, barbell squat, weighted pullups) and HIIT style kettlebell swings and sprints.  The problem is, I can't do this before every meal.  Really, once or twice a week is about all I can adequately recover from.  I have read the benefits on glucose uptake do last for a few days.  I can throw in some aerobic exercise on other days with some light bodyweight work, cold exposure, and regular walks to keep some of that metabolic flexibility active.

 

Insulinogenic protein is also very useful for me, and I've gotten in the habit of post-workout cold showers.  A 16-20 hour fast, compound resistance exercise (often with amino acids), a cold shower, a quick shot of massively insulinogenic whey with creatine and some sort of insulin mimetic and I'm likely headed straight for hypoglycemia if I don't get some carbohydrates in.  At this point, I'm a sponge for carbs, which seems to spill into my next meal if I avoid fats and keep protein up.  A mix of fruit + starch seems to work better than either one.  It might even work better for me to just hit high-gi low-fiber carbs, since the spike isn't very apparent and I can just get them in where they need to go quickly.  From the dinner table, I can relax and blood sugar does not climb but just infuses into my muscles / liver.  At the next meal, I generally increase fats and decrease carbs a bit (aiming more for low-gi carbs / legumes), as I'm less insulin-sensitive at the point and I can slow the absorption of the meal (which is generally already running a bit slower as I'm stuffed with food / fiber) and add in some post-prandial activity.

 

This approach likely needs work.

[Dean Pomerleau]

Thanks Sirtuin. Really interesting.

 

This approach likely needs work.

 

Sounds to me like you've got it pretty dialed in!

 

--Dean

[sirtuin]

Thanks Sirtuin. Really interesting.

 

This approach likely needs work.

 

Sounds to me like you've got it pretty dialed in!

 

--Dean

So far, so good -- it's easy to go OCD with it and try to continue to optimize.

 

There's sort of 3 paths from here -- staying low carb without interruptions, where insulin / insulin sensitivity doesn't much matter.  Increasing carb in the meals to a sort of moderate-carb "Perfect Health Diet", where I do get some sort of post-prandial rise after meals.  Or staying in that cyclical HFLC / HCLF refeed zone.  Looking at bloodwork (while fasted), the numbers look pretty good in any of these camps -- possibly best in the High Fat diet + High Carb refeed combo, which does seem to keep body composition in decent shape.  (Here's where I'm at with a BMI just under 20.)

 

What concerns me is that I have read that insulin is a contributor towards heart disease / atherosclerosis, where a 300-450g carbohydrate refeed day in the post-exercise window with a higher than usual protein intake seems pretty dang insulinogenic... although without that refeed, I'm basically running on bare minimum full-time toward glucose deficiency and hypoinsulinemia.

 

Just going by feel, I'm pretty good with any of these dietary scenarios.

[tasbin]

I have never had a so low lean body mass in kg despited having a slightly lower weight in the past.

So with that information and the hypothesis suggested by Fontana that insulin resistance is mainly due to a low muscle mass, i suspect that I have reached a personal thresold lean mass causing  IGT.

It reminds me how  once a person crosses a personal fat threshold, type 2 diabetes develops, according to Professor Roy Taylor.

I will put that theory into practice.

 

Problem solved !

 

I confirm that at least for my case.

Before with IGT:

Weight:                  59.9kg

BMI:                        20.2

+2h PP BS [1](mg/dl):  159,170,143,175,163

 

After with normal 1st phase insulin response:

weight:                          60.4kg

BMI:                               20.4

lean mass increased by 60g

+2h PP BS(mg/dl):         96, 99 - tested with very high carbs meals

 

The IGT could have been related to a too low lean mass (I have never been so low) or/and my alternate dry fasting.

 

I do not want to play with hyperglycemia even if it could be under very specific case such as CR a sign of a "better" CR & related benefits.

I could have managed it with low carb diet with post exercice or some complements. Dr bernstein talks about that in very considerable details in his book from head to toes. i have study thoroughly his book for my diabetic mum but I m not willing to eat a animal & protein-based diet to have an almost flat BS before and after.

 

 

[1] PP BS: Postprandial  blood sugar

[Dean Pomerleau]

Tasbin,

 

I'm not sure I understand your 'solution'.  What did you change to improve your glucose tolerance? I can't imaging gaining 1lb of weight (or 60g! of lean mass) would make any difference whatsoever. Do you really think it is that sharp a threshold? Seems very unlikely to me. Heck, your weight and lean mass has got to vary by more than that day-to-day as a result of measurement error, fluid / feces retention, etc.

 

My guess would be improvement you've seem probably resulted from something else you've changed, or simply natural variation in your glucose response.

 

Can you elaborate?

 

--Dean

[Sthira]

Tasbin, I didn't catch your solution, either. Regarding body weight, mine goes up and down all day long -- usually water weight.

 

Also, can you discuss your rationale for dry fasting? I'm curious what interests you about dry fasting, and what evidence you've found for it.

[tasbin]

My lean mass wast never so low but my weight was even lower in the past without IGT(I have data about that). That is the exact moment when I got impaired glucose tolerance.
Indeed, I have lost 2kg during that intermittent dry fasting & more muscle than usual.

This IGT as I wrote before, was therefore probably linked to my too low lean mass or/and bmi.

SO , I decide to only gain some minor weight, in this case 0.5kg because all cronies with IGT have a lower BMI  & lean mass than the others. It could not be a coincidence.
Now, I weigh 60.9kg (+1kg since IGT "period").

I did not change anything in my food excepting eating more calories & more animal-based proteins to gain more lean mass. I only stop fasting. it could be not related but it is how I can more weight.
I have had IGT for 4 days last week in a row and only after stopping fasting and gaining weight it disappear in just around 1 day after eating ad libitum. I will retest it during this week to confim it.
 

 

 @Dean: Do you really think it is that sharp a threshold.
 

I think so at least in my case. I am used to test my BS regularly and my weight was just a bit higher ( from 1 to 3kg above max) compared to now. so i know it was not present during that time.

 

 

To test that hypothesis I should reduce my weight & lean mass to the same degree during my IGT  or below but without fasting period to confirm it.
I can do it if you are really interested for the sake of  experimentation but not now.

 

But it will be more interesting and reliable if others like you or Sirtuin with IGT increase slightly their weight/lean mass to see if it makes a difference intheir PP BS.
You could always go back to your lower BMI after that.
 

 

I could be wrong but i did not change anything expect my weight by eating more meals per day and it confirms Fontana's hypothesis about a too low lean mass creating insulin resistance. I know by experience that after breaking a period of intermitten fast and returning to my usual meal pattern I gan some weight rapidly in 1-2 days.
 

 

 

@Sthira: "Regarding body weight, mine goes up and down all day long -- usually water weight."

During my fast, I weight only just before breaking the dry fast in the night so I know I am a bit dehydrated .

 

 

@Sthira:  can you discuss your rationale for dry fasting? I'm curious what interests you about dry fasting, and what evidence you've found for it.

 

Nothing special that you do not know here already here about improved Crp, BS and so on.I am doing intermittend dry fasting 1 month per year. I did not used the more common word on purpose: it was just ramadan fasting with eating only during a 6 hour window during the night & dry fasting 18h hours.

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

Addendum:

 

Last but not least,

I have probably a naive other hypothesis:it could be related to the relation of the autonomic nervous system & his choice to somehow "shutdown" the pancreas partially.

 

As you know, this one in in some extreme cases may decide to privilege some organs over other parts of the body that are not critical (cold  & blood circulation in the extremity of the member, flight or fight response & the slowed or stooped digestive process ...)

 

IGT may imply that the person has impaired phase I insulin response because the pancreas has not produce enough granules of insulin to release.

 

The mere presence of food in the gut as well as the rise in the blood sugar signal her pancreas to release the granules of insulin it has stored in order to offset a jump in blood sugar:

 

As the pancreas runs out of stored insulin, it manufactures more, but it has to do so from scratch.
 

The insulin released now is known as the phase II insulin response, and it’s secreted much more slowly and cannot  rapidly correct the initial blood sugar generated by the ingested carbohydrate.

Because of the calories restriction , the body may decide that the required production of insulin during the fasting state is not vital & its storage is not necessary or is reduced a lot for better usage of the calories  for another more vital purpose.

 

Also, when glucose enters someone’s blood, some of the blood sugar is transformed to glycogen, a starchy substance stored in the muscles and liver. But since the person has less muscle mass, he has less storage space for glycogen.

[tasbin]

Actual weight: 62kg (+2.1kg). We cannot flag it as result of measurement error, fluid / feces retention.

 

I have eaten many high carb meal the past days, just white stuff: pure, cheap white bread, and another day white couscous.

It is been a while !
My inner voice like a gentle earworm was telling me "The white the bread the sooner you're dead" :D

PP BG +2h always under 1g

 

On the longecity forum on a similar thread, a user have mentionned some studies

how low muscle mass is linked with increased insulin resistance

His findings :

Low Muscle Mass Associated With Type 2 Diabetes Risk

The occurrence of insulin resistance, which leads to development of type 2 diabetes, is on the rise. Low muscle mass is known to increase this risk. The present study analyzes the role of this relationship in diabetes management. The possibility of improved glucose metabolism and sensitivity by improving muscle mass was worked out in this study. Interestingly, every 10 percent increment in the skeletal muscle index corresponded with 11 percent relative fall in insulin resistance and 12 percent dip in diabetes prevalence. A stronger relationship was noted in the nondiabetic population.

The Role of Skeletal Muscle in Glucose Transport, Glucose Homeostasis, and Insulin Resistance: Implications for Physical Therapy

Quote

Skeletal muscle has a fundamentally important role in the maintenance of normal glucose homeostasis and in regulating whole-body carbohydrate metabolism. In this review, we discuss the regulation of skeletal muscle glucose transport by muscular activity and inactivity. A large number of patients routinely seen by physical therapists exhibit some form of skeletal muscle insulin resistance. Therefore, we discuss how skeletal muscle insulin resistance can be localized to a relatively small muscle mass, or in other circumstances can affect a large proportion of the muscle mass leading to disturbances in whole-body glucose homeostasis.

Relative muscle mass inversely linked with insulin resistance and pre-diabetes
 

In this study, researchers examined the association of skeletal muscle mass with insulin resistance and blood glucose metabolism disorders in a nationally representative sample of 13,644 individuals. Participants were older than 20 years, non-pregnant and weighed more than 35 kg. The study demonstrated that higher muscle mass (relative to body size) is associated with better insulin sensitivity and lower risk of pre- or overt diabetes.

Important statements:
"A 3% increment in muscle mass as a fraction of body weight was associated with 3.4% relative reduction in HOMA-IR and 3.7% in
prevalence of transitional/pre- or overt diabetes).
In nondiabetics, the effects were even larger: 4.4% relative reduction in HOMA-IR and 7.5% relative reduction in prediabetes risk."
 

 

 

In

Paul McGlothin mentions that: "We had some of our slimmest CR people, the past couple of years... this is kind of sad. They really limited calories a lot. Fasting glucose levels 200. Both died of pancreatic cancer"

[mikeccolella]

Good post Tasbin Thanks! Of course you nail it and this explains a lot of the problems with BMI research. Muscle matters!

[Dean Pomerleau]

Tasbin,

 

I agree with Mike - good post!  As you suggest, one potential mechanism by which CR might induce impaired glucose tolerance in some folks is because of very low muscle mass. That, coupled with very low fat mass, makes for very few landing spots for glucose to go (i.e. not enough cells to absorb it) - so it cycles around in the bloodstream for far too long. 

 

The only thing I questioned about your explanation in your own case was the apparent step-function you postulated between good and terrible glucose metabolism. If IGT really is a direct function of muscle mass as you suggest, then adding a tiny amount of muscle mass (as you did) should change your glucose metabolism by only a tiny bit. But this doesn't appear to have been the case. Instead you saw a huge improvement in glucose metabolism associated with just a very small amount of weight / muscle gain.

 

So it seems to me like low muscle mass can't be the only explanation for CR-induced IGT. It appears from his new IGT thread that Michael thinks along the same lines.

 

You wrote:

In this video Paul McGlothin mentions that: "We had some of our slimmest CR people, the past couple of years... this is kind of sad. They really limited calories a lot. Fasting glucose levels 200. Both died of pancreatic cancer"

 

Wow. I've watched that video before and never caught that part. Here is a link to the video cued up at the spot (~24min) when Paul talks about glucose, IGF1, dietary protein and your pancreatic cancer quote, so people can hear it from the horse's mouth. I'm not sure if this is hyperbole, but at 25:00, he talks about "passing out glucometers at a recent CR workshop". He says "75% of CR folks had fasting glucose over 100". I'm not sure what workshop he's talking about, but I find that hard to believe. CR folks I know with IGT generally have normal fasting glucose.

 

But the pancreatic cancer deaths of two CR practitioners (if true), is really troubling. Pancreatic cancer strikes about 1 in 10,000 people. I can't imagine Paul has more than 100-200 people in his program. But let's be conservative and assume it's 500. That would give a 500/10,000 = 5% chance he'd see a single pancreatic cancer incident in his group. To see two such cases would be a 1 in 400 probability. And it would be more unlikely that than if he's following less than 500 people.

 

The fact that according to Paul both people cut calories dramatically, were really skinny, had high glucose is very troubling. While most of us CR folks who have (or used to have) IGT don't have high fasting glucose (just postprandially and in response to a glucose challenge) the profile is uncannily parallel to some of us.

 

The fact that pancreas is largely responsible for glucose control (through insulin production), could be comforting or disconcerting, depending on the direction of causality in the case of Paul's two clients. On the positive side (for us - not for them obviously), perhaps they had pancreatic cancer prior to CR, and their sick pancreas was unable to produce enough insulin and that was the cause of their impaired glucose metabolism. This is a possibility, but would seem like a pretty big coincidence particularly since many CR folks show a similar profile and in light of additional evidence discussed below.

 

The obvious worrisome explanation would be that CR somehow induces β-cell dysfunction and aberrations that not only impairs proper insulin production in the pancreas but also may trigger pancreatic cancer.

 

Interestingly, these two reviews [1][2] found there is evidence to support both causal directions among diabetics - i.e. diabetes → β-cell dysfunction → pancreatic cancer and pancreatic cancer → β-cell dysfunction → diabetes, and that the two explanation for the link between diabetes and pancreatic cancer aren't mutually exclusive:

 

About 80% of pancreatic cancer patients have glucose intolerance or frank diabetes. This observation has led to the following two hypotheses: i. pancreatic cancer causes the associated diabetes and ii. the conditions associated with diabetes promote the development of pancreatic cancer. Evidence supporting both hypotheses has been accumulated in previous studies. This article reviews these studies, especially those that have been conducted recently...

 

Conclusion

 

Recent studies indicate that there is no simple answer to the question of which of the two hypotheses stated at the beginning of this review is right. However, it appears that these hypotheses are not mutually exclusive, since there is considerable experimental and epidemiological evidence in support of both of them. Clearly, the relationships between pancreatic cancer and alterations in glucose metabolism are very complex.

 

Obviously CR folks are not diabetics in the traditional sense, and don't generally have (for example) excessive insulin exposure like type 2 diabetics which can damage pancreas cells (as [1] describes). But interestingly, and troublingly, diabetics whose blood sugar was poorly controlled are at a higher risk of pancreatic cancer than those whose diabetes was well controlled [3].

 

The influence of poor glucose control on risk of pancreatic cancer hints that it may be the long-term glucose exposure and not (or perhaps in addition to) the insulin exposure that might do damage to the pancreas. Also a bit worrying is study [4], which found that those who had type 2 diabetes the longest were the ones most at risk (80% higher risk than the general population) for developing pancreatic cancer. While Steve Jobs had a slow growing form of pancreatic cancer, generally it grows very quickly - 80% of pancreatic cancer patients die within one year of diagnosis. So long-term, undiagnosed "latent pancreatic cancer" causing impaired glucose tolerance does not seem like a very plausible explanation for the association between pancreatic cancer and poor glucose control in diabetics (or Paul's clients), at least in the vast majority of cases of this rare disease.

 

But then things get complicated. There are several types of pancreatic cancers. As I said, Jobs had a rare, slow-growing form that does indeed strike islet (beta) cells. But more typically (i.e. 95%), pancreatic cancers are known as adenocarcinomas. From this link:

 

The pancreas itself is essentially two different organs, which means two distinct kinds of tissue—and two very different types of cancer, Saltz points out. The most common kind of pancreatic cancer, the adenocarcinomas, originate in what is known as the exocrine portion of the pancreas. This is the main mass of the organ, which makes digestive enzymes that get shuttled to the gastrointestinal tract via specialized ducts. 

 

"Scattered in that larger organ are thousands of tiny islands," Saltz explains. "These are islands of endocrine tissue," which makes hormones [including insulin - DP] that are secreted into the blood. It was a cancer of these islet cells that Jobs had. 

 

So in conclusion, it seems impossible to say whether the observed impaired glucose tolerance observed in CR folks results from trashing of our pancreas (potentially making us more prone to pancreatic cancer) or something much more benign. For more detailed analysis on the possible link between a CR-induced reduction in GH/IGF1 signalling and pancreatic β-cell dysfunction, see Michael's new thread.

 

But it seems to me that even the hint that CR-induced impaired glucose metabolism might be associated with pancreatic cancer makes it all the more important for CR folks to determine whether they exhibit IGT and then takes steps to manage it if they do.

 

Having had really bad IGT in the past (see my terrible OGTT results from Luigi's study at the bottom of by blood tests - 252 mg/dL at 60min and 199 mg/dL at 2h!), all this discussion makes me nervous.

 

So I tested my blood glucose once again this morning. I ate my usual, huge (~3500kcal) meal over a 2h period from 5am to 7am. Ten minutes after I finished eating, and over 2 hours since I started eating my meal (which BTW is front-loaded with most of the carbs and fruit) my glucose was 106 mg/dL. I then went on a brisk 30min walk. When I got back I tested it again, 45min after finishing my meal. It was 94 mg/dL. Given my history of IGT, It looks like I'm doing something right. My weight today (125lbs) is just a couple pounds heavier than it was at the time of my terrible OGTT with Luigi (123lbs) - so I don't think it is the muscle mass that makes the difference. In fact I know it's not since I've had good glucose control for quite some time now, even when my weight was < 120 lbs, well below my bad OGTT weight.

 

Instead I think it's likely a combination of:

• Time restricted feeding - These days I eat once a day, in the morning when people are most insulin sensitive
• Exercise - I exercise both before and after eating. In fact, I'm exercising (or at least active) for virtually all of the hours I'm awake ☺
• Cold Exposure - CE builds metabolically active brown and beige adipose tissue which sucks up and burns glucose (and triglycerides) like a sponge, stabilizing blood glucose. As a bonus it appears CE may also boost mTOR via a different pathway from the usual one involving Insulin/IGF1, perhaps improving β-cell function and survival. But this idea about the synergy between CR and CE is much more speculative.

--Dean

 

-------

[1] Mol Cancer. 2003; 2: 4.

Published online 2003 Jan 6. doi:  10.1186/1476-4598-2-4

 

The relationship between diabetes and pancreatic cancer

 

Feng Wang,1 Margery Herrington,1,2 Jörgen Larsson,1 and Johan Permert

 

Free full text: http://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-2-4

 

Abstract

 

About 80% of pancreatic cancer patients have glucose intolerance or frank diabetes. This observation has led to the following two hypotheses: i. pancreatic cancer causes the associated diabetes and ii. the conditions associated with diabetes promote the development of pancreatic cancer. Evidence supporting both hypotheses has been accumulated in previous studies. This article reviews these studies, especially those that have been conducted recently.

 

----

[2] Adv Exp Med Biol. 2012;771:229-39.

 

Pancreatic cancer and diabetes.

 

Morrison M(1).

 

Author information: 

(1)Swedish Organ Transplant Division, Swedish Medical Center, Seattle,

Washington, USA. maureen.morrison@swedish.org

 

Diabetes studies have increasingly been associated with several types of cancer. 

Diabetes and pancreatic cancer have a unique relationship. Genetic mutations,

such as activation of the KRAS2 oncogene, inactivation of the tumor-suppressor

gene CDKN2A, inactivation of the tumor-suppressor gene TP53 and deleted in

pancreatic cancer 4 (DPC4) gene defects are seen in those with pancreatic cancer.

Approximately 80% of those patients, diagnosed with pancreatic cancer, are

identified as having concomitant diabetes with a poor prognostic factor. Damaged 

pancreatic tissue, secondary to pancreatic cancer, leads to diabetes as islet

cells and beta cells are taken over by malignancy. Additionally, those on certain

anti-diabetic regimens are shown to be at a higher risk of developing pancreatic 

cancer due to the effect of stimulation on the pancreatic beta and islet cells.

Therefore, diabetes is thought to be both a potential cause and effect of

pancreatic cancer. Diabetes has become a pandemic, and pancreatic cancer is one

of the most lethal forms of malignancy known. In order to better understand these

diseases and how they are associated, more research needs to be done.

Particularly, research focusing on different types of diabetes in the setting of 

pancreatic cancer will be an important issue for further understanding of the

link between diabetes and pancreatic cancer.

 

PMID: 23393682

 

----------

[3] Medicine (Baltimore). 2016 Jun;95(24):e3921. doi: 10.1097/MD.0000000000003921.

 

Effect of glycemic control on the risk of pancreatic cancer: A nationwide cohort 

study.

 

Er KC(1), Hsu CY, Lee YK, Huang MY, Su YC.

 

Author information: 

(1)aSchool of Medicine, Tzu Chi University, Hualien, Taiwan bEmergency

Department, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, 

Taiwan cDepartment of Public Heath, National Taiwan University, Taipei, Taiwan

dDepartment of Emergency Medicine, Mackay Memorial Hospital, Taipei, Taiwan.

 

Although the relationship between diabetes and pancreatic cancer has been

studied, the effects of glycemic control on pancreatic cancer have never been

evaluated. This study investigates the relationship between glycemic control and 

pancreatic cancer.Data from 1 million National Health Insurance beneficiaries

were screened. The study cohort consisted of 46,973 diabetic patients and 652,142

nondiabetic subjects. Of the patients with diabetes, 1114 who had been admitted

for hyperglycemic crisis episodes were defined as having poorly controlled

diabetes. All adult beneficiaries were followed from January 1, 2005 to December 

31, 2013, to determine whether pancreatic cancer was diagnosed. The Cox

regression model was applied to compare the adjusted hazards for potential

confounders.After controlling for age, sex, urbanization level, socioeconomic

status, chronic liver disease, hypertension, coronary artery disease,

hyperlipidemia, malignancies, smoking, chronic obstructive pulmonary disease,

obesity, history of alcohol intoxication, chronic renal insufficiency, biliary

tract disease, chronic pancreatitis, Charlson Comorbidity Index score, and

high-dimensional propensity score, the adjusted hazard ratio of pancreatic cancer

was 2.53 (95% confidence interval 1.96-3.26) in patients with diabetes. In

diabetic patients with poor glycemic control, the hazard ratio of pancreatic

cancer was significantly higher (hazard ratio 3.61, 95% confidence interval

1.34-9.78).This cohort study reveals a possible relationship between diabetes and

pancreatic cancer. Moreover, poorly controlled diabetes may be associated with a 

higher possibility of pancreatic cancer.

 

DOI: 10.1097/MD.0000000000003921 

PMID: 27311001

[TomBAvoider]

[Admin note: I added the Dean quote below and moved this post (with Tom's permission) along with Randyf's post from Michael's Mechanisms of CR-Associated Impaired Glucose Tolerance thread to this one where it seems more germane.]

 

 

Dean wrote:

 

Saul, while an OGTT would be very interesting. Why don't you just (or also) pick up a glucometer? They are a cheap and useful tool.  

 

Not to go too much OT, but how do you solve the issue of reliability and veracity of glucometers? I asked my PC for a variety of glucose-related tests, and she offered to prescribe to me a glucometer, so I wouldn't even have to pay for it as insurance would cover it, however I declined it. The reason is that when I looked into glucometers a few years ago, I reached the conclusion that it was more hassle than benefit. First, there is a wide variability in results from various glucometers made by different manufacturers. Furthermore, there is only a very loose relationship between your actual glucose numbers as can be ascertained by a blood test (when blood is taken from your vein). For the ones with the "best" reputation, I've seen the glucometers claim that anything within 20% of the vein blood test is "within parameters of norm" for a glucometer - so an approximation of up to 20%... that is frankly INSANE. I mean, 20% can push your numbers into or out of diabetic readings! Wow. Is that worthless! Throw it against the wall. Worse, even testing is screwed up, because drawing blood is not a simple matter - you might get interstitial fluid mixed in with the blood (unlike when taken from the vein), you have to get it from just the right place in your fingertip and get a goodly deep cut so there are no admixtures of other fluids... and the list goes on, affected by everything including the ambient temperature. Having read that, if I had a glucometer, I'd have smashed it on the ground, then picked up the parts and put them in a blender and then taken the refuse and buried it in a landfill. Comprehensively worthless. I suppose there may be some value in simply consistently testing in the same way to see how foods affect the glucometer numbers, to see "lower" and "higher" without expecting the actual numbers to correspond to any kind of reality of a vein test - strictly for relative elevation or decrease of BG, at least perhaps the glucometer would be good for that. But then, that has nothing to do with the kind of precision in numbers discussed in these papers - for that, a glucometer strikes me as platonically worthless. However, that was a few years ago - has technology progressed from that state, or are we still at the stone age level of home BG measuring devices? 

[Saul]

How do you measure lean body mass?

 

(I would guess mine is reasonable, as I exercise vigorously for one hour 6 days every week (latest model of Precor Elliptical Cross Trainer with hand motion:  60 minutes, at maximum resistance, completing about 5.2 miles [in foot motion].)

 

But again, how do you guys measure your lean body mass (without a Dexa scan, and someone expert to interpret it)?

 

  -- Saul

[randyf]

Not to go too much OT, but how do you solve the issue of reliability and veracity of glucometers? ... First, there is a wide variability in results from various glucometers made by different manufacturers. Furthermore, there is only a very loose relationship between your actual glucose numbers as can be ascertained by a blood test (when blood is taken from your vein). For the ones with the "best" reputation, I've seen the glucometers claim that anything within 20% of the vein blood test is "within parameters of norm" for a glucometer - so an approximation of up to 20%... that is frankly INSANE.

 

I think glucose meters are much more accurate than you think. It's true that the FDA requires an error range of +-15%, but most meters today are  better than that. Consumer Reports tested a number of meters for both accuracy and consistency (using a lab test for comparison) and found many brands both accurate and consistent.

http://www.consumerreports.org/cro/blood-glucose-meters/buying-guide.htm

 

Randy

[tasbin]

 

@Dean wrote :"The only thing I questioned about your explanation in your own case was the apparent step-function you postulated between good and terrible glucose metabolism. If IGT really is a direct function of muscle mass as you suggest, then adding a tiny amount of muscle mass (as you did) should change your glucose metabolism by only a tiny bit. But this doesn't appear to have been the case. Instead you saw a huge improvement in glucose metabolism associated with just a very small amount of weight / muscle gain So it seems to me like low muscle mass can't be the only explanation for CR-induced IGT"

 

 

 

Hi Dean, my lean mass calculation & related increase as a result was obviously underestimated.Sorry. The fondana's study about CR & IGT mentionned 47.8kg on average for cronies with IGT when I computed mine around 29kg but I am not a dwarf !

My homemade formula was wrong. Based on various Lean Body Mass Formula for Adults, my lean mass is around 50kg. Huge difference.

 

 

But i am sure i increased my weight anyway & lean mass.

Also, I have posted another naive hypothesis (I am from the IT field) on a edited post that  you have probably not read it (search for the word addendum on this page). But I am not done apparently with my blood sugar. I will post more details when I have collected enough data.

 

 

@Dean wrote "So I tested my blood glucose once again this morning...... I then went on a brisk 30min walk. When I got back I tested it again, 45min after finishing my meal. It was 94 mg/dL. Given my history of IGT, It looks like I'm doing something right."

But you are cheating .  What would be your PP BS without exercice before & after the meal? Do you still have a IGT  and only manage it with exercice?

[AlPater]

Dean, You said:

 

Having had really bad IGT in the past (see my terrible OGTT results from Luigi's study at the bottom of by blood tests - 252 mg/dL at 60min and 199 mg/dL at 2h!), all this discussion makes me nervous.

 

So I tested my blood glucose once again this morning. I ate my usual, huge (~3500kcal) meal over a 2h period from 5am to 7am. Ten minutes after I finished eating, and over 2 hours since I started eating my meal (which BTW is front-loaded with most of the carbs and fruit) my glucose was 106 mg/dL. I then went on a brisk 30min walk. When I got back I tested it again, 45min after finishing my meal. It was 94 mg/dL. Given my history of IGT, It looks like I'm doing something right. My weight today (125lbs) is just a couple pounds heavier than it was at the time of my terrible OGTT with Luigi (123lbs) - so I don't think it is the muscle mass that makes the difference. In fact I know it's not since I've had good glucose control for quite some time now, even when my weight was < 120 lbs, well below my bad OGTT weight.

 

But, why are your fasting glucose levels no different than when you were tested at WUStL and your HbA1c levels higher now than in the months before and after your OGTT at WUStL?

[Saul]

Hi Al!

 

I'm sure that Dean will respond -- but remember, Dean eats more than twice the calories daily than he did when tested at WUSTL -- and has become a very vigorous exerciser, which is why his weight is similar.

 

You expect different numbers.

 

 -- Saul

[Dean Pomerleau]

Nice to hear from you Al,

 

You wrote:

But, why are your fasting glucose levels no different than when you were tested at WUStL and your HbA1c levels higher now than in the months before and after your OGTT at WUStL?

 

I too was puzzled by that. In fact, that's one reason I've been testing my glucose lately. But then I discovered how HbA1c is a really crappy metric for glucose control in healthy people. Apparently you didn't get the memo.

 

Regarding my numbers back in 2002 around the time of my visit to Luigi at WUSTL for testing. Given my demonstrated IGT at the time of my visit to WUSTL and a fasting glucose of 88 on 10/3/02 (one month before my visit to WUSTL), you really think my HbA1c measurement of 4.1 (RR 4.8-5.6) at that time accurately reflected my average exposure to glucose? I think not.

 

And if it did I'd be worried, because people with that low HbA1c have about a 200-300% increased risk of mortality relative to HbA1c in the normal range I have now.

 

And Saul, I'm not eating twice as many calories as I did at WUSTL. On paper I was eating around 2400 kcal/day then (although I estimated it to be lower due to fiber), and I'm eating ~3500 kcal/day now (also likely an overestimate due to fiber - and especially the preponderance of nuts in my current diet). That's only a 45% increase, not a 100% increase. 

 

--Dean

[tasbin]

I really think that this page on the risks of CR should be updated & add IGT at least as a major risk (40% in the fontana's study) even if the implications on health/longevity are not clear.

Concerning the link with lower circulating levels of IGF-1 & CR IGT, if low IGF-1 is linked with (expect genetic defect) low protein consumption , I do not think it is my case.
Indeed, I am eating more than 1g/kg of protein per day (100-110g per day - I have recorded 2-3 usual days on cronometer. Why monitoring? Because I was recently  a bit concerned with the relation of elevated protein consumption & IGF-1 & increased cancer rate & the reduced longevity in animal & one study published by Pr valter Longo & Pr L. Fontana). But I am neither vegan nor vegetarian.
Again, it is only an hypothesis (no lab value).

 

 

Edit: could it be that my intermittent dry  fasting reduced my IGF-1 level ? probably not/ Two studies (1 & 2) concluded that Ramadan fasting has no effect on plasma IGF-1.