89 replies to this topic

[zorba990]

My thoughts:
I believe that the science definitely shows that people with higher blood sugar levels have higher levels of glycation as is easily measured by an A1C test.. I also believe that elevated glycation leads to accelerated aging as we obviously see in diabetics. I test my blood regularly, fasting, post prandial and A1C to see how various foods and supplements effect the numbers. Mister E is at least partially correct as uncontrolled gluconeogenesis does elevate blood sugar levels. Supplements like green coffee bean extract limit glucoeogenesis and reduce blood sugar levels. I know this because I test often. I also know that high simple high carb foods and starches spike blood sugar levels, the key I guess is how long does it take for insulin to reduce those levels. The variability in each of us individually in terms of insulin sensitivity determines that. I don't need to read a study, my sore fingers have clearly shown me how various foods effect my numbers.
I take Metformin and various gluconeogenesis inhibiting supplements to suppress my glucose levels and hence my levels of glycation. I also take supplements that have been shown to reduce glycation....carnosine, p5p, benfotiamine, ALA, vitamin C etc.
I've been able to reduce my A1C levels from as high as 5.6 to currently 5.0. I'm hoping to break 5.0 the next test. I've begun also taking / testing LEF 's " tri sugar shield " product.
Re: green coffee bean. http://www.lef.org/m...een coffee bean

Thanks for the report, good science. Maybe do spectracell testing to check chromium and magnesium levels as well as adding unmodified (resistant) potato starch. Ursolic acid would be a more exotic try.

Arginine seems worth a look as well
http://www.ncbi.nlm....pubmed/11347747

Edited by zorba990, 27 February 2014 - 01:57 AM.

[eon]

Been using arginine for workouts. I read something about it being good for something related to glucose but i'm more familiar with it as pre-workout supplement as well as its potential growth hormone production, etc.

[albedo]

My thoughts:
I believe that the science definitely shows that people with higher blood sugar levels have higher levels of glycation as is easily measured by an A1C test.. I also believe that elevated glycation leads to accelerated aging as we obviously see in diabetics. I test my blood regularly, fasting, post prandial and A1C to see how various foods and supplements effect the numbers. Mister E is at least partially correct as uncontrolled gluconeogenesis does elevate blood sugar levels. Supplements like green coffee bean extract limit glucoeogenesis and reduce blood sugar levels. I know this because I test often. I also know that high simple high carb foods and starches spike blood sugar levels, the key I guess is how long does it take for insulin to reduce those levels. The variability in each of us individually in terms of insulin sensitivity determines that. I don't need to read a study, my sore fingers have clearly shown me how various foods effect my numbers.
I take Metformin and various gluconeogenesis inhibiting supplements to suppress my glucose levels and hence my levels of glycation. I also take supplements that have been shown to reduce glycation....carnosine, p5p, benfotiamine, ALA, vitamin C etc.
I've been able to reduce my A1C levels from as high as 5.6 to currently 5.0. I'm hoping to break 5.0 the next test. I've begun also taking / testing LEF 's " tri sugar shield " product.
Re: green coffee bean. http://www.lef.org/m...een coffee bean

I fully stand with you with the sad difference I cannot get access to metformin I would like to try. Anyway I decided I will make a try with the green coffe bean formula from LEF for 4 months. I was also tempted by the "tri sugar shield" but did not want to mix and confound results. I take some of the supplements you mention too but so far only got to 5.4 last month. The only case when I got it under 5 was when strictly followed the Zone diet but found it hard to continue.

Let us know and good luck!

[Darryl]

Kindly forgive this digression, as I take a brief rest from garden tilling.

The excessive blood-sugar from diabetes is caused by excessive gluconeogenesis.

This oversimplification doesn't get to the heart of the matter, which is skeletal muscle and adipose tissue insulin resistance. Here's a thing I wrote elsewhere that may clarify matters:

Its important to distinguish between the high-saturated fat, sugar, and protein diets that lead to insulin resistance and type 2 diabetes, and high glycemic index carbohydrates which, while not independently causing insulin resistance, may contribute to diabetic progression in the context of insulin resistance, obesity and high dietary fat.

When consuming their traditional high glycemic index staples, rural Chinese and Indians (short-grain white rice), rural Africans (cassava & yam flours), rural New Guineans (sweet potatoes), and Native Americans (corn flour), all have extremely low diabetes incidence, so starches alone cannot account for the higher incidence of diabetes among the same people when adopting Western diets. Their traditional diets are also low in saturated fat, refined sugars, and animal protein, and the past two decades have revealed how these later components cause insulin resistance and progressively kill pancreatic β-cells.

Saturated fats worsen insulin resistance by a number of mechanisms. Their metabolites accumulate in muscle and fat cells, activate proinflammatory signalling cascades, cause mitochondrial dysfunction, and interfere with insulin-stimulated glucose transport. After muscle and fat tissue have become insulin resistant in metabolic syndrome/early type 2 diabetes, saturated fats in concert with high blood glucose cause pancreatic β-cell glucolipotoxicity, which progressively kill these insulin producing cells till most are gone in late type 2 diabetes. High sugar intake, and in particular fructose (which, shockingly, is sometimes recommended for diabetics due its low glycemic index), is also implicated in insulin resistance and metabolic syndrome via impaired satiety, dyslipidemia, increased hepatic lipid deposition, and inflammation, amongst other mechanisms. Meanwhile, high dietary protein (especially animal protein) independently elicits insulin response, and potentiates the response to co-ingested carbohydrates, contributing to resistance.

While saturated fats, sugars, and protein may contribute to insulin resistance, it doesn't necessarily follow that a low-fat, high-carb diet would reverse the pathology. After all, aren't glycemic spikes central to β-cell toxicity and diabetic complications? And yet, low-fat, high complex-carbohydrate diets may be the best dietary interventions for insulin resistance and diabetes. Some important studies include:
• Beneficial effects of a high carbohydrate, high fiber diet on hyperglycemic diabetic men (1976)
• Response of non-insulin-dependent diabetic patients to an intensive program of diet and exercise (1982)
• Diet and exercise in the treatment of NIDDM: The need for early emphasis(1994)
• Toward improved management of NIDDM: A randomized, controlled, pilot intervention using a low fat, vegetarian diet (1999)
• The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity (2005)
• A low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type 2 diabetes (2006)
• A low-fat vegan diet and a conventional diabetes diet in the treatment of type 2 diabetes: a randomized, controlled, 74-wk clinical trial (2009)
• Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes (2011)
• Glycemic and cardiovascular parameters improved in type 2 diabetes with the high nutrient density (HND) diet (2012)
Remove the causes of insulin resistance, and the body begins to heal itself.
If a pill offered the same benefits as low-fat high complex carbohydrate diets in restoring insulin sensitivity, it would be considered miraculous. Yet, because millions aren't aware that insulin resistance is fundamentally a disease of saturated fat toxicity, less effective medications and diets continue to be prescribed.

Back to the topic at hand, I believe that even with lower fat diets, for longevity its important to keep the glycemic indexes moderate. The recent benefit seen with acarbose in mouse life extension suggests that there remains a benefit to moderating glucose spikes (and subsequent insulin activity), even in the absence of differences in lipotoxicity. Personally, I think the key may be cross talk with IGF-1 signalling. Insulin and IGF-1 receptors are commonly hybridized, so peaks of either can cause the same cellular growth signalling cascades all the way to mTOR activation, excess cell proliferation, autophagy inhibition, etc. Reducing transient glucose spikes, and hence the requirement for insulin, would reduce this excess of inadvertent growth signalling.

Edited by Darryl, 02 March 2014 - 11:41 PM.

[misterE]

This oversimplification doesn't get to the heart of the matter, which is skeletal muscle and adipose tissue insulin resistance.

Yes you are right, I was kinda oversimplifying it… the heart of the matter is adipose-tissue insulin-resistance, which thru its outpour of FFA’s, is able to cause insulin-resistance throughout the entire-body (liver, pancreas, muscle, etc). An insulin-resistant (fatty) liver is unable to clear blood-glucose and hepatic gluconeogenesis stays uninhibited due to the lack of the insulin-signal. Both the excessive-gluconeogenesis and the inability of organs to absorb and properly use glucose… causes elevated blood-sugar.

I believe that even with lower fat diets, for longevity its important to keep the glycemic indexes moderate.

I don’t. I think that high-glycemic foods (grains and potatoes) are actually the healthiest foods that humans need to be eating more of. When you eat, blood-sugar naturally rises and the body produces insulin to compensate. The insulin released in response to eating starchy-foods causes a stable regulation of metabolism, it is when there is a lack of insulin (as in type-1 diabetes) or the insulin-signal (as in type-2 diabetes) that causes catabolic-metabolism and leads to diabetes. Even if you restrict all forms of carbohydrate, blood-sugar will still elevate due to an increase in gluconeogenesis. The body has a whole entire counter regulatory system installed.

So restricting high-glycemic starches like rice, potatoes, flours, etc, is a huge mistake that would only make diabetes worse, because, you would in essence have less overall insulin-signaling, if you removed those insulinogenic foods from the diet. The much maligned potato is actually one of the most insulinogenic foods known to man (besides the good-ole’ pinto-bean; a low-glycemic-food).

Personally, I think the key may be cross talk with IGF-1 signalling. Insulin and IGF-1 receptors are commonly hybridized, so peaks of either can cause the same cellular growth signalling cascades all the way to mTOR activation, excess cell proliferation, autophagy inhibition, etc.

mTOR activation is actually decreased in diabetics (this is one of the main reasons why diabetics have such poor wound-healing). mTOR is stimulated by glucose, insulin and IGF-1, and in diabetics their body is unable to utilize glucose, they have insulin-resistance and they have reduced IGF-1 levels. All of those factors is why mTOR activation is decreased in diabetes… opposite is true with cancer patients however.

Reducing mTOR with Rapamycin, will actually induce a state of diabetes.

Reducing transient glucose spikes, and hence the requirement for insulin, would reduce this excess of inadvertent growth signalling.

But you need insulin and IGF-1 siganlling to survive and thrive! Without insulin-signalling you cannot store macronutrients, you have decreased sex-hormones and sex-drive, you have increased atherosclerosis, increased fat-migration and a whole host of other ailments. It has recently been discovered that Alzheimer’s patients have reduced insulin and IGF-1 signaling in their brains and that this reduced the uptake of glucose into the brain, reduced the vascularity of the brain, reduced the rate of brain-cell proliferation and increased brain-cell apoptosis!

…You don’t want to mimic a type-1 diabetic. They need their insulin-shot daily or even hourly to function and survive, you need an insulin-shot daily as well, however your insulin-shot comes in the form of starchy-foods.

Edited by misterE, 04 March 2014 - 02:16 AM.

[Brett Black]

Back to the topic at hand, I believe that even with lower fat diets, for longevity its important to keep the glycemic indexes moderate. The recent benefit seen with acarbose in mouse life extension suggests that there remains a benefit to moderating glucose spikes (and subsequent insulin activity)

Some other experiments with rodents seem to suggest that glycemic index may not impact longevity. Lifelong feeding of mice and rats with equivalent calories in either a single large meal per day or as multiple smaller meals per day (thereby likely producing either a large postprandial glucose spike or multiple moderate glucose excursions) did not affect lifespan:

1. J Nutr. 1986 Nov;116(11):2244-53.

Meal-timing, circadian rhythms and life span of mice.

Nelson W, Halberg F.

The possibility that circadian rhythm alteration may contribute to the
life-prolonging effect of food restriction was investigated in female CD2F1 mice
housed in a room with a 12-h span of fluorescent lighting daily. A control group
was allowed to feed ad libitum throughout life while three other groups began
lifelong restriction to about 75% of ad libitum intake when 6 wk old. The daily
schedule of food accessibility differed among these three groups: a single meal
during early darkness; a single meal during early light; six smaller meals at
about 2-h intervals during darkness. Food restriction as such clearly prolonged
life, but there were no statistically significant differences in overall mean
life span or in 10th-decile life span among the three restricted groups.
Telemetered body temperature data confirmed marked differences in the effects of
these different restricted feeding schedules on circadian rhythms. The effect of
food restriction on survival is probably not due to altered relations among
circadian rhythmic variables. Possible contributing factors suggested by the
results are a lower body temperature, a reduced overall metabolic rate and an
increased circadian amplitude.

PMID: 3794831 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm..../pubmed/3794831

---

1. J Gerontol A Biol Sci Med Sci. 1995 Jan;50A(1):B48-53.

Temporal pattern of food intake not a factor in the retardation of aging
processes by dietary restriction.

Masoro EJ(1), Shimokawa I, Higami Y, McMahan CA, Yu BP.

Author information:
(1)Department of Physiology, University of Texas Health Science Center at San
Antonio.

Long-term dietary restriction programs which retard aging processes in rodents
usually involve meal eating rather than the nibbling pattern of food intake of ad
libitum fed rodents. Thus, the possibility arises that the antiaging action may
at least in part result from an altered temporal pattern of food intake. This
possibility was investigated using male F344 rats maintained on the following
dietary regimens: Group A rats fed ad libitum; Group B rats fed 60% the ad
libitum intake in a single meal at 1500 h; Group B-2 rats fed 60% of the ad
libitum intake in two meals (0700 h and 1500 h). The diurnal pattern of plasma
corticosterone concentration differed among the groups as did that of the plasma
glucose concentration. The median length of life and age of tenth percentile
survivors were similar for Group B and B-2 rats and much greater than those for
Group A rats. Both modes of dietary restriction influenced age-associated disease
processes in a similar fashion. Thus, although the temporal pattern of food
intake influenced circadian rhythms of food-restricted rats, it did not
significantly affect the antiaging action.

PMID: 7814779 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm..../pubmed/7814779

[Kevnzworld]

It isn't high glucose from one meal per se that accelerates aging IMO , it's glycation. There are two obvious ways to lower levels of glycation, the first being to lower overall blood sugar levels. Diabetics have higher rates of blindness, kidney disease etc due to higher A1C levels as a result of higher average daily blood sugar levels. It's the overall average BG level that matters, that's why a fasting reading in the morning doesn't give one a complete picture. Post prandial is somewhat better because it can show one how long it takes for BG levels to normalize after a meal,,, ie level of insulin control or resistance. ( does it take 1, 3 or 6 hours for BG to return to a close to fasting level )
The other way to lower levels of glycation is to take supplements that have shown some efficacy in blocking the cross linking of sugar with protein.
I choose to employ strategies in diet and supplementation that contribute to both the lowering of average daily BG levels, while also mitigating glycation.
( Metformin, p5p, pyridoxamine , carnosine, benfotiamine, vit C, green coffee bean extract, cinnamon etc )
The HbA1C blood test is the best arbiter of effectiveness.

[Kevnzworld]

This study showed that mice fed a low glycemic index diet beginning in old age extended their lifespan by 12%.
Note this is a low glycemic index, NOT a CR diet..
" The present study has identified the potential benefit of a low GI diet to increase lifespan. Compellingly, we were able to extend mouse lifespan from a very late intervention point suggesting that a long-term regime could be a very powerful agent for longer, healthier life. The most direct indication of low GI impact was in markers of oxidative stress that were significantly decreased at 24 months of age in the low GI diet group. "
http://www.longevity...m/content/2/1/4

This correlates with research that's shown that arcobose and Metformin extend mice lifespan.

[Darryl]

@Kevnzworld

Glycemic index wasn't the only thing that differed in those high glycemic and low glycemic mice diets. Likewise metformin's activity as a mild mitochondrial respiratory complex I poison has a lot of off target downstream effects.

That's why I think the study with acarbose, which should have little effect on anything but the speed of carb absorption after a meal, is the animal study on effective glycemic index and longevity with the fewest confounders.

I will, however, be adding barley rather than whole wheat pasta to my soups.

Edited by Darryl, 06 March 2014 - 07:20 PM.

[Brett Black]

That's why I think the study with acarbose, which should have little effect on anything but the speed of carb absorption after a meal, is the animal study on effective glycemic index and longevity with the fewest confounders.

I don't know too much about this subject, but from my very brief reading, it seems that acarbose, by reducing the normal digestion of starches, leads to a higher percent of them being broken down lower in the GI tract (by resident bacteria) into short chain fatty acids.

This also happens to be one of the fates of soluble fibre, and it may be a cause of some of the benefits associated with soluble fiber intake. So it could be that acarbose is essentially making starch mimick the benefits of soluble fiber, rather than lower glycemic index being the source of the benefits.

E.g. acarbose can increase the SCFA butyrate production:
http://www.ncbi.nlm..../pubmed/9164992

Edited by Brett Black, 07 March 2014 - 05:02 AM.

[Brett Black]

Here's an interesting one - genetically engineering mice to have lower glucose levels did not increase their lifespan:

1. J Gerontol A Biol Sci Med Sci. 2007 Oct;62(10):1059-70.

Plasma glucose and the action of calorie restriction on aging.

McCarter R(1), Mejia W, Ikeno Y, Monnier V, Kewitt K, Gibbs M, McMahan A, Strong
R.

Author information:
(1)The Pennsylvania State University, Center for Developmental and Health Genetics,
Gardner House, University Park, PA 16802, USA. rjm28@psu.edu

We tested the hypothesis that retardation of aging by caloric restriction is due
in part to decreased levels of plasma glucose over the life span. Male C57BL/6
mice expressing a human GLUT4 minigene (transgenic [TG] mice) and their
nontransgenic littermates (NTG mice) were maintained under specific pathogen-free
conditions. Mice were fed ad libitum (A mice) or 40% less than ad libitum (R
mice) from age 6 weeks. Over the life span there were three different levels of
plasma glucose, with NTGA mice having the highest daily levels, TGR mice the
lowest daily values, and TGA and NTGR mice having similar levels intermediate
between these values. Despite differences in plasma glucose, the differences
measured in longevity (50% and 10% survival), physiology and tissue pathology
were associated with diet rather than with levels of plasma glucose. We conclude
that decreased plasma glucose over the life span is not an important factor in
the action of calorie restriction on aging processes.

PMID: 17921417 [PubMed - indexed for MEDLINE]

[Darryl]

Brett Black, thanks for that surprising pointer. Along the same lines is this one:

Nelson, James F., et al. "Probing the relationship between insulin sensitivity and longevity using genetically modified mice." The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 67.12 (2012): 1332-1338.

Life span of insulin insensitive IRKO+/ mice was increased (males) or unaffected (females). Life spans of mice with increased insulin sensitivity were shortened overall (PTP-1B−/−mice) or partially (PGC-1αTG: survival at the 25th percentile was reduced). These results show that insulin sensitivity in some murine genotypes is inversely related to longevity.

This is a really baffling result given my expectations (which should be reconsidered).

Edited by Darryl, 07 March 2014 - 06:42 AM.

[niner]

Thanks for those two papers, Brett. Very interesting! We know (or do we?) that high blood glucose causes premature mortality in diabetics humans. Could it be that the mouse experiment was unable to recapitulate the high levels of glucose that a diabetic experiences? Perhaps because mice are uniquely susceptible to oxidative stress, it's the elephant in the room that kills them before glycation has a chance to cause problems?

[Mind]

Brett Black, thanks for that surprising pointer. Along the same lines is this one:

Nelson, James F., et al. "Probing the relationship between insulin sensitivity and longevity using genetically modified mice." The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 67.12 (2012): 1332-1338.

Life span of insulin insensitive IRKO+/ mice was increased (males) or unaffected (females). Life spans of mice with increased insulin sensitivity were shortened overall (PTP-1B−/−mice) or partially (PGC-1αTG: survival at the 25th percentile was reduced). These results show that insulin sensitivity in some murine genotypes is inversely related to longevity.

This is a really baffling result given my expectations (which should be reconsidered).

Don't be too flummoxed. It was a mouse study. Mouse studies rarely translate into anything actionable for humans.

[Brett Black]

Dandona has had published numerous papers that describe insulin favourably, for example:

1. Metab Syndr Relat Disord. 2004 Jun;2(2):137-42. doi: 10.1089/met.2004.2.137.

Insulin Is an Anti-inflammatory and Anti-atherosclerotic Hormone.

Dandona P(1), Aljada A, O'donnell A, Dhindsa S, Garg R.

Author information:
(1)Division of Endocrinology, Diabetes and Metabolism, State University of New York
and Kaleida Health, Buffalo, New York.

Fasting hyperinsulinemia is associated with an increased risk of atherosclerotic
complications of heart attack and stroke. This has resulted in the concept that
insulin may promote atherosclerosis in spite of the absence of any evidence that
insulin is atherogenic either in the human or in experimental models. Recent
evidence shows that insulin exerts vasodilatory, anti-platelet and
anti-inflammatory effects at the cellular level in vitro and in the human in
vivo. Since atherosclerosis is a chronic inflammatory process of the arterial
wall, insulin may be potentially anti-atherosclerotic in the long term. More
recent data on experimental atherosclerosis in the mouse shows that (1) insulin
administration reduces the number and the size of atherosclerotic lesions in apo
E null mice and (2) in IRS-2 null mice, the interruption in insulin signal
transduction results in enhanced atherogenicity. Finally, the use of a low dose
of insulin infusion in patients with acute myocardial infarction has been shown
to markedly improve clinical outcomes, both in diabetic and nondiabetic patients.
Our own most recent data show that a low dose infusion of insulin in patients
with acute myocardial infarction induces a reduction in inflammation (C-reactive
protein and serum amyloid A) and oxidative stress, and promotes fibrinolysis. We
conclude that insulin is anti-inflammatory and potentially antiatherogenic and
may be of use in the treatment of cardiovascular inflammatory conditions.

PMID: 18370645 [PubMed]
http://www.ncbi.nlm....pubmed/18370645

1. Diabetes Care. 2010 Nov;33(11):2416-23. doi: 10.2337/dc10-0929. Epub 2010 Aug 10.

Insulin suppresses endotoxin-induced oxidative, nitrosative, and inflammatory
stress in humans.

Dandona P(1), Ghanim H, Bandyopadhyay A, Korzeniewski K, Ling Sia C, Dhindsa S,
Chaudhuri A.

Author information:
(1)Division of Endocrinology, Diabetes and Metabolism, State University of New York
at Buffalo and Kaleida Health, Buffalo, New York, USA. pdandona@kaleidahealth.org

OBJECTIVE: To investigate whether insulin reduces the magnitude of oxidative,
nitrosative, and inflammatory stress and tissue damage responses induced by
endotoxin (lipopolysaccharide [LPS]).
RESEARCH DESIGN AND METHODS: Nine normal subjects were injected intravenously
with 2 ng/kg LPS prepared from Escherichia coli. Ten others were infused with
insulin (2 units/h) for 6 h in addition to the LPS injection along with 100 ml/h
of 5% dextrose to maintain normoglycemia.
RESULTS: LPS injection induced a rapid increase in plasma concentrations of
nitric oxide metabolites, nitrite and nitrate (NOM), and thiobarbituric
acid-reacting substances (TBARS), an increase in reactive oxygen species (ROS)
generation by polymorphonuclear leukocytes (PMNLs), and marked increases in
plasma free fatty acids, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6),
monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibition
factor (MIF), C-reactive protein, resistin, visfatin, lipopolysaccharide binding
protein (LBP), high mobility group-B1 (HMG-B1), and myoglobin concentrations. The
coinfusion of insulin led to a total elimination of the increase in NOM, free
fatty acids, and TBARS and a significant reduction in ROS generation by PMNLs and
plasma MIF, visfatin, and myoglobin concentrations. Insulin did not affect TNF-α,
MCP-1, IL-6, LBP, resistin, and HMG-B1 increases induced by the LPS.
CONCLUSIONS: Insulin reduces significantly several key mediators of oxidative,
nitrosative, and inflammatory stress and tissue damage induced by LPS. These
effects of insulin require further investigation for its potential use as
anti-inflammatory therapy for endotoxemia.

PMCID: PMC2963505
PMID: 20699433 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm....pubmed/20699433

Edited by Brett Black, 09 March 2014 - 02:25 AM.

[Ukko]

Glucose accelerates aging? LOL. As revolutionary as gravity causing items to fall. Obviously so.

[misterE]

Glucose without insulin causes glycation. But insulin itself has important anti-aging properties, as pointed out above by Brett Black.

Edited by misterE, 09 March 2014 - 04:22 AM.

[Vardarac]

Isn't the Maillard reaction that causes glycation spontaneous? I would think insulin would just decrease its likelihood by quickly tucking it away rather than giving it more chances to glue together proteins.

[Kevnzworld]

Glucose without insulin causes glycation. But insulin itself has important anti-aging properties, as pointed out above by Brett Black.

Higher insulin levels are often the result of insulin resistance and equate with higher blood glucose levels.
" How Good a Marker Is Insulin Level for Insulin Resistance?"
The authors conclude that in population studies, only the fasting insulin level should be used as a marker of insulin resistance, particularly in subjects with abnormal glucose tolerance.
http://aje.oxfordjou...137/9/959.short

High insulin levels are an independent marker for CHD
"Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels. The Paris Prospective Study, ten years later."
(PMID:3908280)
"We conclude that high insulin levels may constitute a more sensitive predictor of CHD than the degree of glucose intolerance, it could be useful to avoid excessive insulin plasma concentration, and even to lower its level."
http://europepmc.org...act/MED/3908280

[misterE]

I would think insulin would just decrease its likelihood by quickly tucking it away rather than giving it more chances to glue together proteins.

Exactly. Insulin also stimulates glutathione synthesis also, which helps decrease the amount of oxidative damage caused by unmetabolized glucose.

[misterE]

Higher insulin levels are often the result of insulin resistance and equate with higher blood glucose levels.


High insulin levels are an independent marker for CHD

Hyperinsulinemia is actually a protective adaptation taken by the body to try and overcome the underlying insulin-resistance… it is not the cause, but rather the result.



Hyperinsulinemia is a good predictor of CHD because insulin has cardio-protective effects, like its ability to stimulate angiogenesis and nitric-oxide and its ability to lower blood-lipids, hypertension, and inflammation. So if a person has insulin-resistance and subsequently hyperinsulinemia, then their chance of dying from heart-disease increases because their body and blood-vessels are starting to become resistant to the beneficial effects of insulin.



This is why type-1 diabetics develop atherosclerosis and heart-disease if they quite taking insulin.

Edited by misterE, 10 March 2014 - 05:40 PM.

[Kevnzworld]

Higher insulin levels are often the result of insulin resistance and equate with higher blood glucose levels.


High insulin levels are an independent marker for CHD

Hyperinsulinemia is actually a protective adaptation taken by the body to try and overcome the underlying insulin-resistance… it is not the cause, but rather the result.



Hyperinsulinemia is a good predictor of CHD because insulin has cardio-protective effects, like its ability to stimulate angiogenesis and nitric-oxide and its ability to lower blood-lipids, hypertension, and inflammation. So if a person has insulin-resistance and subsequently hyperinsulinemia, then their chance of dying from heart-disease increases because their body and blood-vessels are starting to become resistant to the beneficial effects of insulin.



This is why type-1 diabetics develop atherosclerosis and heart-disease if they quite taking insulin.

One wants BOTH, low glucose levels and low insulin levels...elevation of either is a marker of metabolic dysfunction, insulin resistance and or pre diabetes.
" Hyperinsulinemia is a clinically important marker for patients who have a family history of diabetes or who have slightly elevated blood glucose levels without other symptoms of diabetes. Abnormal fasting insulin, especially when combined with other risk factors, identifies patients at significantly higher risk for the development of cardiovascular disease. A continuous hyperinsulinemic state can impact the body's ability to utilize stored energy effectively, thus hampering weight loss."
http://www.bhlinc.co...iptions/Insulin
Diabetics have a higher incidence of CVD than normal individuals even if they take insulin. If they don't control their blood sugar with insulin or other drugs, yes they become even more susceptible to heart disease, mostly due to increased blood sugar levels.
Lower HbA1C levels are associated with lower incidence of CVD and other maladies associated with aging. Elevated glucose, insulin and glycation levels are inversely correlated with longevity and health.

Edited by Kevnzworld, 10 March 2014 - 06:37 PM.

[misterE]

Yeah, but the elevated blood-glucose and hyperinsulinemia observed in insulin-resistant people isn’t caused by eating high-glycemic foods like potatoes or rice… but rather an accumulation of FFA’s within the peripheral-tissues, which is causing the underlying insulin-resistance.



Hyperinsulinemia is not only your body’s way of trying desperately to shove glucose into the cell, but also an attempt to inhibit lipolysis and suppress the flood of FFA’s. Remember that hyperinsulinema is a protective adaptation. Now, as the FFA’s keep pouring out of the insulin-resistant adipocytes, an accumulation of FFA’s on the pancreas occurs and causes the beta-cells (insulin-producing cells) to undergo apoptosis (cell death), when this happens you begin to develop insulin-deficiency and if you don’t receive exogenous insulin, you will eventually die from lipotoxicity.

[Kevnzworld]

Yeah, but the elevated blood-glucose and hyperinsulinemia observed in insulin-resistant people isn’t caused by eating high-glycemic foods like potatoes or rice… but rather an accumulation of FFA’s within the peripheral-tissues, which is causing the underlying insulin-resistance.

High glycemic foods increase blood sugar more than low glycemic foods. I know this because I test my blood 2 hours after eating various foods. My fasting glucose level is 82-86.
Here's a study, not anecdotal .
" To determine the effect of different foods on the blood glucose, 62 commonly eaten foods and sugars were fed individually to groups of 5 to 10 healthy fasting volunteers. Blood glucose levels were measured over 2 h, and expressed as a percentage of the area under the glucose response curve when the same amount of carbohydrate was taken as glucose. The largest rises were seen with vegetables (70 +/- 5%), followed by breakfast cereals (65 +/- 5%), cereals and biscuits (60 +/- 3%), fruit (50 +/- 5%), dairy products (35 +/- 1%), and dried legumes (31 +/- 3%). A significant negative relationship was seen between fat (p less than 0.01) and protein (p less than 0.001) and postprandial glucose rise but not with fiber or sugar content."
http://ajcn.nutritio.../34/3/362.short
" Results Glycemic control was improved on the low-GI diet compared with the high-GI diet (statistically significant findings, P < 0.05). Mean glycosylated hemoglobin at the end of the low-GI diet was 11% lower (7.0 ± 0.3%) than at the end of the high-GI diet (7.9 ± 0.5%), and the 8-h plasma glucose profile was lower (area under the curve above fasting 128 ± 23 vs. 148 ± 22 mmol.h-1.L-1, respectively)."
http://care.diabetes...t/14/2/95.short
This is not to say that high fat/saturated fat diets don't impede glucose control, but to say that high glycemic foods don't contribute to elevated blood glucose and hyperinsulinemia is just not accurate.

Edited by Kevnzworld, 11 March 2014 - 04:53 AM.

[addx]

To the best of my knowledge the liver can not possibly produce enough glucose to overwhelm blood in the long run.

Given that claim, I can never understand why can't diabetics simple remove carbohydrates from their diet instead of using insulin? AFAIK, healthy fats diet reverses insulin insensitivity and fatty liver achieved via fructose diet.

I've also seen it written here that overwhelming FFAs kill insuling producing cells in the final stages of diabetes? I'd guess that insulin producing cells most probably get overstressed due to extra pressue of generating abnormally high insulin levels via some stress map kinase signalling and die IMO.

IMO:

Accumulation of FFAs does cause insulin resistance. The adipose cell is *full*, it can't take any more so it becomes insulin resistant to stop more inflow. But, FFAs don't really accumulate from eating dietary fats alone without carbs because insulin doesnt spike from that. If it did, we would not be able to live off our stored fats either. FFAs accumulate from eating too much carbs which spikes insulin and also forces the liver to churn carbs into fats. Cells that always need glucose to function(retina, nerves, kidneys) can not become insulin resistant so they suffer through the high levels of glucose stuffing caused by high blood sugar and high insulin.
I can't understand why would it benefit a diabetic to repeat this process indefinitely using exogenous insulin until he dies prematurely?

[DukeNukem]

I consider glucose control as a key part of my pro-longevity regimen.

The A1c test is a very good indicator (maybe the best indicator) of success or failure in this area. I've kept mine at or under 4.8 for the last 8+ years. This is done through eating a good carb diet (no gluten grains, no processed foods, no foods/drinks with added sugar), and through taking supplements that aid in glucose control, like Pycnogenol, metformin, resistance starch, and a few others. Certain supplements seem to reduce glycation, too, like carnosine and pyridoxamine.

[zorba990]

I've also seen it written here that overwhelming FFAs kill insuling producing cells in the final stages of diabetes? I'd guess that insulin producing cells most probably get overstressed due to extra pressue of generating abnormally high insulin levels via some stress map kinase signalling and die IMO.

Oxidized FFA, producing free radical damage, as a side effect of chronic inflammation. Excess calories, bad food, no exercise, bad breathing technique, sitting all day = inflammation IMO and the easiest way to cut calories is to first knock off all processed food (especially sugar and white flour) and then cut out high glycemic low volume carbs.

I added 'low volume' because some of the glycemic index is misleading. You are probably not going to eat a pound of carrots or 3 large apples at one sitting. This is because these food are high volume. At the other end of the volume spectrum would be sugar soda. White rice being somewhat in between depending on if it is parboiled or relatively nutritionally bankrupt white sticky rice.

There is an oldie but goodie book called "No sugar no flour gives me the power". It's a great simple starting point for people that eat a lot of processed food.

Having a close relative with Diabetes I can tell you that lowering carbs absolutely works! And it doesn't require very high fat diet either. Just sanity in portion control and balancing protein, fats and minimizing junk carbs (and total carbs to about 100-150 max). Myself I find 100g carb plenty for an active lifestyle at about 1800 cals a day (so 400 cals carbs about 600 cals protein and the rest fats). I don't always feel like eating that much protein so then my calories drop. Lower than 100g protein a day and muscle mass is not maintained for me. Lower than about 80g carbs a day and I still feel fine but I notice some dizziness at the end of workouts.

But really everyone who cares should just measure their blood glucose and see what works for them. Blood sugar spikes are not healthy in the long run and this is why Gestational diabetes is diagnosed with postprandial measurements.

Blood sugar : measure twice and you won't have to cut once. :-)

[addx]

I've also seen it written here that overwhelming FFAs kill insuling producing cells in the final stages of diabetes? I'd guess that insulin producing cells most probably get overstressed due to extra pressue of generating abnormally high insulin levels via some stress map kinase signalling and die IMO.

Oxidized FFA, producing free radical damage, as a side effect of chronic inflammation. Excess calories, bad food, no exercise, bad breathing technique, sitting all day = inflammation IMO and the easiest way to cut calories is to first knock off all processed food (especially sugar and white flour) and then cut out high glycemic low volume carbs.

I dont doubt oxidized FFA cause damage. But I doubt this process causes very targeted damage to insuling producing cells. I'd say insulin producing cells are pushed/stressed to death by ever increasing insulin demands during insulin resistance.

Body kills of all stressed tissues/cells. It's normal.

Oxidizing FFA on a search and destroy against pancreas - I'd have to see it to beleive it.

Having a close relative with Diabetes I can tell you that lowering carbs absolutely works!

Diabetic people feeding on carbs and insulin - I'll never understand why medicine wants it to be so. Why doesnt anyone instruct them to avoid carbs and reduce proteins for a while? Why do they tell them "here's your insulin shot, now go eat that loaf of bread quick or you'll die, come back here when you want to eat more".

Insulin sensitivity is restored by keeping insulin LOW which allows FFAs OUT. Once they're out, the cell can again restore insulin sensitivity. This is only possible with a high fat diet. Even proteins cause an insulin spike easily, perhaps a third or a half of similarly-caloric carb meal but still a spike so they must be kept low. Such diets can rescue non-alcoholic fatty livers (fructose fatty livers).

There is a kind of therapy for epilepsy for kids, a ketogenic diet. It takes a few years of a strict ketogenic diet to CURE epilepsy in as much as 50% of epileptic children. Cure meaning the diet is no longer required and the symptoms stay at bay it seems indefinitely. There isn't a pill that can do that. Fats do it by restarting mitochondria and keeping glucose low which causes too much nervous system agitation. It seems neurons pur much more nicely on ketones.

Most importantly, these kids are fed a very high fat diet and basicly zero carbs in order to reap most benefits and they do it for years. Only thing they observed and is logical is a small reduction in growth from the lack of insulin powered growth.

So, someone explain to me please: Why do doctors tell diabetics to eat carbs instead of a high fat diet? They're worried about their mucosal linings thining from lack of glucose and increasing cancer risk? Seriously?

The repeated exposure to huge quantities of exogenous insulin required for them to overpower their insulin insensitivity is not helping them at anything except acute survival during carb meals. Which got them sick in the first place. Helping acute survival always causes detrimental after effects as does taking cocaine to overpower stagefright. It works, for a while. And then our diabetic dies of kidney failure.

[zorba990]

So, someone explain to me please: Why do doctors tell diabetics to eat carbs instead of a high fat diet? They're worried about their mucosal linings thining from lack of glucose and increasing cancer risk? Seriously?

I don't understand it either. But anyone can find their own truth with the easily obtained and used glucose meter.

BTW if you take high dose vitamin C it can cause some meters to mis-read.

http://www.health.ha...r_100_foods.htm

Try some chickpeas if you want some carbs! Good luck over-eating chickpeas...

[Brett Black]

High glycemic foods increase blood sugar more than low glycemic foods. I know this because I test my blood 2 hours after eating various foods. My fasting glucose level is 82-86.

The total exposure to increased glucose levels is similar between high and low glycemic foods. The difference is that high glycemic foods result in a short duration exposure to a high intensity "spike" of glucose, whilst low glycemic foods result in a long duration exposure to a low intensity "wave" of glucose. Here is an idealized example of the phenomena:



You can see that glucose stays elevated above the baseline for much longer with the low GI food.