8 replies to this topic

[InquilineKea]

Well, those *and* time-integrated insulin.

It's said that the body only secretes insulin when blood glucose levels are higher than 83. That being said, the question is: what is the rate of insulin secretion? Is it constant beyond 83, or does it increase faster when glucose levels at at 135 rather than 115? [1]

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Okay, I'll try to find a bunch of articles off google scholar, but i'm not sure if i'll ever be successful. maybe library.nu has some good books

Fundamentally, here's the issue. What is the effect of intermittent fasting on time-integrated blood glucose, really? Intermittent fasting is almost always going to result in huge levels of postprandial blood glucose. As for its effects on insulin, maybe it might result in less insulin MOST of the time, but it's possible that there might be an insulin spike or not. We would have to answer question [1] to find out.

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And here's the problem: the articles contradict each other!

http://care.diabetes.../29/2/352.short

"Mean Blood Glucose and Biological Variation Have Greater Influence on HbA1c Levels Than Glucose Instability"

vs

http://www.jdcjourna...e/S1056-8727(04)00114-X/abstract

The Diabetes Complications and Control Trial (DCCT) established glycosylated hemoglobin (A1C) as the gold standard of glycemic control, with levels ≤7% deemed appropriate for reducing the risk of vascular complications. Yet, even when A1Cs were comparable between intensively treated subjects and their conventionally treated counterparts, the latter group experienced a markedly higher risk of progression to retinopathy over time. Our speculative explanation, based on the discovery that hyperglycemia-induced oxidative stress is the chief underlying mechanism of glucose-mediated vascular damage, was that glycemic excursions were of greater frequency and magnitude among conventionally treated patients, who received fewer insulin injections. Subsequent studies correlating the magnitude of oxidative stress with fluctuating levels of glycemia support the hypothesis that glucose variability, considered in combination with A1C, may be a more reliable indicator of blood glucose control and the risk for long-term complications than mean A1C alone.

[InquilineKea]

http://www.jpatholog... Mellitus .pdf suggests linear relationship. But it's a foreign study, so I'm not sure if we can trust results. Paper also seems math-phobic

http://www.springerl...764j6548k56266/ suggests that calorie restriction isn't going to change glycation much in primates

CR in birds and rodents decrease collagen
glycation, glucose autoxidation and tendon collagen cross-linking (Cefalu et al. 1995; Sell et al.
2000). In primates, CR decreases glycemia but
glycated hemoglobin is only marginally decreased.
It is found that the magnitude and onset of these
effects are in part species dependent (Kemnitz
et al. 1994). In primates CR possibly acts by
decreasing glycemia and lipidemia (Edwards et al.
1998; Campisi 2000), the results of which are decreased oxidant stress (Gredilla et al. 2001) and
carbonyl stress, respectively.

[InquilineKea]

http://care.diabetes...2/1830.full.pdf

See table 2 for the powerful results here.

To observe the relationship of fasting plasma glucose (FPG), postchallenge
plasma glucose (PG) (30, 60, 90, and 120 min during an oral glucose tolerance test [OGTT],
as well as maximal PG during an OGTT, postchallenge glucose spikes [PGS], and glucose
under the OGTT curve), and HbA
1c
to intima-media thickness (IMT) as a marker of atherosclerosis.

The key question here - is this: is IMT caused by glycation? Or by something else? It's interesting that postchallenge glucose *and* postchallenge glucose spikes are more important for thickening the IMT than average glucose levels as measured by HbA (odds ratio maxing out at 1.88, as compared to 1.24 for Hba1c and 1.30 for free plasma glucose). So it's possible [1] that hemoglobin glycation is a linear function of glucose level, but IMT thickening is definitely a nonlinear function of glucose level, implying that minimizing peaks is more important (for preventing IMT) than minimizing the time-integrated glucose concentration.

With that being said, that's just the IMT here. It could be different for something else (and especially for CRONites, since CRONites generally don't have to worry about heart disease, but they have more to worry about glycation-induced neuron damage and other things).

This study is the most relevant for us, since it's conducted on non-diabetics.

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We also have http://care.diabetes...9/1236.full.pdf , but this study is conducted on diabetics, so it doesn't really apply to us as much

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[1] Well, actually, maybe not: http://care.diabetes...t/25/2/275.long (2002). The new study I cited shows that Hemoglobin A1c correlates more with PG at certain times of day than others. It also shows that it's affected MOST by glucose levels in the past month (although the last point here is irrelevant to my objective of finding whether or not hemoglobin A1c is really a linear function of average glucose levels)

Edited by InquilineKea, 22 June 2011 - 10:06 AM.

[InquilineKea]

From Wright, E., Scism-Bacon, J. L. and Glass, L. C. (2006), Oxidative stress in type 2 diabetes: the role of fasting and postprandial glycaemia. International Journal of Clinical Practice, 60: 308–314. doi: 10.1111/j.1368-5031.2006.00825.x

It appears that VARIABLE glucose is MORE important than time-integrated glucose when it comes to oxidative stress. Oxidative stress is not glycation, however. As for what contributes more to aging - we don't know yet - it may depend. Do keep in mind that this study was done on diabetics.

Variable Glucose: Effects on Markers of Oxidative Stress and Inflammation
Several in vitro studies have demonstrated increased expression of markers of oxidative stress in cells exposed to fluctuating glucose concentrations (8–10). One such study examined the effects of variable glucose concentrations vs. constant high or normal glucose conditions on cultured human umbilical vein endothelial cells (8). The investigators monitored the generation of ROS by measuring levels of nitrotyrosine and showed higher levels of nitrotyrosine in cells exposed to variable glucose concentrations than for cells exposed to either constant normal or elevated glucose concentrations (8).

Owing to the ability to monitor ROS production via measurement of nitrotyrosine, there are now data in patients with T2DM that make evident the existence of increased oxidative stress in response to postprandial hyperglycaemia (11). In a study comparing T2DM patients with matched healthy controls, nitrotyrosine levels were significantly higher in diabetic individuals in the fasting state and were further elevated in the postprandial state. No such postprandial elevation in nitrotyrosine was observed in healthy control patients (11).

Markers of inflammation, a well-recognised manifestation of oxidative stress, have also been observed to increase in response to intermittent elevated glucose levels (10). In a study comparing the effects of inconsistent vs. constant glycaemic conditions on cultured human kidney cells, the authors noted that production of the inflammatory cytokines, transforming growth factor β (TGF-β) and insulin-like growth factor binding protein (IGFBP)-3, increased to a greater extent when exposed to variable glucose concentrations compared with constant hyperglycaemic conditions. The authors concluded that while maintenance of normal blood glucose levels would result in the smallest degree of oxidative stress and inflammation in the tubulointerstitium, variable glycaemic control would likely be even more damaging than constant hyperglycaemia (10).

Edited by InquilineKea, 22 June 2011 - 10:11 AM.

[InquilineKea]

Other possibly relevant articles: (it's 3:12 AM now and I'm tired so I'll quit for now)

http://www.nature.co...ll/414813a.html

http://onlinelibrary...2/dmrr.517/full

http://www.ajcn.org/...87/1/217S.short

[InquilineKea]

Are pharmacodynamics and pharmacokinetics the right words to look for? I tried searching for them + glucose/insulin but they didn't return anything useful :( there might be related words that are more relevant

[niner]

IK, I don't remember where I read this, but in people with normal glucose control, post-prandial glucose spikes are the largest contributor to HbA1C. I take this to mean that in diabetics, the time-averaged glucose level is higher. I suppose that could either mean that the postprandial peaks are a lot more broad, or the fasting blood glucose is higher, or some combination of those.

[InquilineKea]

Oh okay - thanks for the reply! I'll try to find out more about that

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Anyways, the most important question I now want to ask is this: what happens to postchallenge glucose in intermittent fasting? This is an extremely important question since I'd expect high postprandial glucose spikes on the days when one ate huge amounts of food, and if these postprandial spikes are the largest contributor to HbA1C, then it's quite possible that there could be increased hemoglobin glycation during intermittent fasting

I tried various search terms, but all without avail. See http://scholar.googl...s_ylo=&as_vis=0 for example

Edited by InquilineKea, 22 June 2011 - 08:53 PM.

[madanthony]

Oh okay - thanks for the reply! I'll try to find out more about that

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Anyways, the most important question I now want to ask is this: what happens to postchallenge glucose in intermittent fasting? This is an extremely important question since I'd expect high postprandial glucose spikes on the days when one ate huge amounts of food, and if these postprandial spikes are the largest contributor to HbA1C, then it's quite possible that there could be increased hemoglobin glycation during intermittent fasting

I tried various search terms, but all without avail. See http://scholar.googl...s_ylo=&as_vis=0 for example

I'm interested if you find out a way to prevent postpradial glucose spikes. Life Extension foundation says most of their members have fasting blood sugar of over 100 but less than 140 (not officially diabetes but still damaging). I have (except when I was diabetic under stress - divorce) naver had a fasting blood sugar higher than 83 and mu A1C is excellent (forget what but it is sterling). Diabetes runs in my family though and after Easter dinner by diabetic Dad took everyone's glucose -- mine was up there - don't remember - maybe 140 or 150, but my sister's hubby who is not from a diabetic family had a blood glucose in the 90's even after Easter dinner. So I became concerned aout postprandial blood glucose.