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6:3 Diet basics: Energy restriction, keto, and fasting diets

6-4-Diet basics and t2d treatments    12/23/19

1. Mediterranean diet   2. Why the Mediterranean diet works    3. Weight regulatory system (WRS), Biggest Loser & Angus Barbieri   4. Calorie restriction, low carbs, and Atkins-keto14 diet   5. Fasting, can reset the weight regulatory system   6. Type 2 diabetes diet   7. Before the drugs for t2d   8. Dietary management of t2d, 1950-61   9. A modern update on diet    10. Metformin, bad meds   11. The new 2019 guidelines   12. Bariatric surgery for t2d   13. What causes type 1 diabetes    14. Amino acids and insulin  15.  Listing of what is best for dieting

 


1.    Mediterranean Diet:  There is a continuity between MTDD, MTD, fructosylation and analysis of diet.  However, for those without this foundation, there is no shortage of theory and articles in support of them.  Every good thing isn’t in sufficient amounts to make a difference, and cumulatively they don’t.  The list of miracle foods in the media is long, and even longer is the list of good molecules in the journals.  Then industry steps in and the media gives us a generous serving, often ghost written by CROs (contract research organizations).  Not knowing the nature of what is bad, the Mediterranean diet is more crapolla.  Why does those countries have much lower rate of cardiovascular disease and CAWD a topic buried by corporate media.  The Mediterranean diet has a special place in the literature based on studies that show those countries such as Spain, Italy and Greece have a much lower rate of CVD.

          Even a person who has built upon basics, teaches about health, has a very good grasp of processes, and understands the role of the mitochondria and ATP, both of which are at the center of his explanation of C AWD, he falls short because he has missed the role of glycation, sugar, and fructose.[1]  There is a social trait whereby our analytic part of the brain creates explanations of phenomena when there is a need to.  Know, for example, believes the fats a toxic and free fatty acids the most toxic.[2]  Other claim that the phenols is one are cardio-protective.  And given what is at stake, industry is protecting their sugary goose.  In his Mitochondria in Health and Disease, 2018, Ray Griffiths explains (pgs. 136-37) with journal references as proof states what is good about the Mediterranean diet: 

Many components of the Mediterranean diet support mitochondria in subtle but incredibly important ways.  For example, plant compounds can activate mitochondria-support endogenous antioxidants, protection against aerobic-glycolysis (Ferramosca & Zara 2014a) and can help block mitochondria reactive oxygen species (ROS) induction by pathogen-associated molecular patterns (PAMPs) from gut microbiota (Morris et al. 2015a).  Additionally, the low glycemic index of plant fiber, whole grains and nuts can help protect mitochondria from extremely damaging-effects of high blood sugar (Rodriguez-Rejon et al. 2014; Yan 2014). 

 Olive oil polyphenols can also protect against neurodegeneration and depression by increasing the expression of neurotrophins such as nerve growth fact (NGF) (Carito et al. 2016).  This neurotrophin helps to concentrate mitochondria at sites for axon growth in neurons.  Without mitochondrial ATP, axon growth is inhibited (Hroudova and Fisar 2011). . . . Interestingly, social enrichment is another potential source of the neuotrophin NGF (Brachi et al. 2006) found to support mitochondria-dependent axon growth within neurons (Hrodova & Fisar, 2011).

Impressive evidence, but as I said the standards for science are compromised.  High blood glucose is not the problem, its fructose, and it is not in the blood but cytosol. Next, the claim supporting the Mediterranean diet is focused on brain functions, but on CVD.  Last Griffiths claim about antioxidants is inflating the mouse to elephant size.  Surprisingly, the single greatest contributor to the total antioxidant intake was coffee” and chocolate came in second at 1/5th that of coffee.[3]  My morning gram of ascorbate as too my 300 mgs of CoQ10, the are many fold more than the coffee I drink.  Need I say more?

I bring this up because I want you to see through my eyes.  I am clearing the playing field so that the science behind what is good in the Mediterranean diet makes sense and the 5 important elements to the fix (of which the first 3 are essential) will be what is practiced.  I am erasing the claims that promote cognitive dissonance. 

Over and over again my students in the health classes on seniors they fail to fix their weight-regulatory system because as a social animal with weak cognitive controls they can’t follow that which science and reason supports.  We are a social animal and simply just can’t lift ourselves up by the boot straps, even though our rational module claims it can.  Though I would like to get into psychology and neuroscience, it is beyond this book and too much of a digression.  I want you to lower your risk for the conditions associated with the western diet, so put on your thinking cap, and now that you have the science behind CAWD, I shall expand it with the addition evidence and science to present the two changes in diet that will fix the weight-regulatory system.  Our body has the systems to heal, all that is needed to get them running at a high level and for a sufficient period of time.    

 

2.  Why the Mediterranean diet works: “The recently published PREDIMED randomised controlled trial was stopped early after it showed that in high risk people the Mediterranean diet achieved a 30% improvement over a “low fat” diet in terms of cardiovascular events”[4]  There is major variation between regions of the Mediterranean.   

The all-embracing term 'Mediterranean diet' should not be used in scientific literature.”  Among errors:  “olive oil consumption is negligible… Mediterranean countries tend to consume relatively high amounts of [saturated] fat, they have far lower rates of cardiovascular disease than in countries like the United States, where similar levels of fat consumption are found…The most popular dietary candidate, olive oil, has been undermined by a body of experimental evidence that diets enriched in monounsaturated fats such as olive oil are not athero-protective when compared to diets enriched in either polyunsaturated or even saturated fats.  A healthy active lifestyle (notable a physically active lifestyle or larbour) is also beneficial… red wine … contains flavonoids with powerful antioxidant properties… The proposed mechanism is solar UVB-induced synthesis [sun] of Vitamin D in the oils of the skin, which has been observed to reduce the incidence of coronary heart disease, and which rapidly diminishes with increasing latitude….  A recent randomized Spanish trial of diet pattern published in The New England Journal of Medicine in 2013 followed almost 7,500 individuals over around 5 years found that individuals on a Mediterranean diet supplemented with mixed nuts and olive oil had a 30 percent reduction in risk of having a major cardiovascular event and a 49 percent decrease in stroke risk.  A 10-year study found that adherence to a Mediterranean diet and healthful lifestyle was associated with more than a 50% lowering of early death rates.[5]

 

Undoubted influenced by pharma’s thought leaders, the Wikipedia article is basically a survey, a kitchen sink full of garbage & no mention of sucrose, fructose, refined carbs, or glycation.  However, the research in this series on CVD place as beneficial low use of sucrose, refined carbs and the healthful replacements of saturated fats and monounsaturated fats, then physically active life, lower consumption of pills, and less smoking.    Moreover, the first study of this diet started in the 50’s based upon Italians who ate a peasant diet.[6]  Other factors include lower rate of obesity, and higher intake of diary product, and they probably smoked less.  Wikipedia’s article on the Mediterranean diet repeats the tobacco science of the food and pharmaceutical industries.    Human evolved a biological system for the hunter-gatherer life, not the modern diet. 

 



[1] Lee Know N.D. Mitochondria and the future of medicine. 

[2] Supra 93

[3] Svilaas, Arne, Amrit Sakhi, et al, March 2004 (Osford) Journal of Nutrition, Intakes of Antioxidants in Coffee, Wine, and Vegetables Are Correlated with Plasma Carotenoids in Humans

[4] Malhotra, Aseem, Oct 2013, Saturated fat is not the major issue

[5] Wiki, Mediterranean diet, Aug 2016

[6]   The village of Pioppi and surrounding area (south of Naples) the source for data on the Mediterranean diet in the 50s. at. 

3.  The weight regulatory system (WRS):  this is at the heart of why calorie restricted diets fail; the system turns on to preserve the adipocytes set level of fats stored through hormonal regulations of which 6 are produced in the adipocytes.  The other barrier is that with IR the adipocytes, depending on degree of IR and social environment, will reset as weight is gained after a period of time (I guess at 1 to 2 years depending on age, hormones, fatty liver, and physical activity). Once reset, the WRS will cause regain of weight for years, and/or the degree of insulin resistance which hasn’t been altered is driving the weight gain.  

Free-living humans are especially vulnerable to the effects of obesogenic environmental and behavioural pressures, which pose a significant barrier for the continued success of weight-loss attempts. This is further compounded by elevations in metabolic efficiency (whereby energy expenditure declines beyond that predicted from the change in metabolic mass) and

appetite which accompany weight-loss, and may ultimately predispose to weight regain.  Moreover, changes in neural activity within brain regions known to be involved in regulatory, emotional and cognitive control of food intake have been observed following weight loss.[1]

          This process of regaining has been called the yo-yo diet.   Calorie restriction has two obstacles, that of increased appetite and reduced metabolic rate See for example the discussion of the study done on The Biggest Losers, a television show in which there is a boot-camp for the obese contestants; they compete for cash.  There were 16 contestants in the 2009 season of which 6 men and 8 women agreed to participate in the follow-up study 6 years later.  These 14 lost an average of 38% of their weight, 127 pounds over the 30-week show. 

In the Journal article and New York Times articles on The Biggest Losers, it showed that they at 6 years the 14 had regained 71% of their weight, and “Weight regain was not significantly correlated with metabolic adaptation at the competition's end (r= −0.1, P = 0.75), but those subjects maintaining greater weight loss at 6 years also experienced greater concurrent metabolic slowing (r = 0.59, P = 0.025).”[2]  The averages at baseline were 35 years, weight 327 lbs., BMI of 49.5, percentage fat 49%,   At end of show, 30 weeks, weight 199 lbs., BMI 30, percentage fat 28%,  Weight gain at 6 years would have been a greater if they excluded the one contestant, Rudy Pauls, who prior to surgery had regained 167 lbs.  Rudy after bariatric surgery, lost 102 pounds, thus at 6 years he was just 65 heavier than at end of show.  His metabolism at the end of the show had dropped by 804 calories, after surgery it was 520 calories less than baseline 6 years before.  Excluding Paul, only one contestant at 6 years their basal metabolism had improved compared to at the end of the show, the other 12 had a further decline in metabolism than week 30.  The contestants 6 years later eat hundreds of calories less than people of a comparable size just to maintain their new size.  All 14 contestants at 6 years had a decline in metabolism.  At 6-years for Mark, his metabolism was 525 calories below at the start of the show.  Only one contestant, Erinn Edbert, kept the weight off (and afterwards lost 25 pounds more), but her metabolism dropped at end of show just 30 calories, but at 6 years it was 570 calories lower than baseline.  This is about 30% less calories to maintain her weight loss.  She was the only contestant to continue to lose weight.   Danny Cahill, the biggest lost 235 pounds of which he restored 105 pounds by the 6th year.  All the contestant experienced a very significant reduction in metabolism at the 6-year mark, their WRSs were still functioning to cause weight gain. 

          Prior to bariatric surgery, the most successful treatment for the morbidly obese was a water fast in a metabolic ward of a hospital, or as an out patients.  A male thin (normal weight) male during starvation can go over 4 weeks before metabolizing muscle during starvation—autophagy of skin and adipose tissue supplies the needed amino acids. The fit, thin male is about 13% fat, while the fit woman is about 23%.  A thin woman has near twice the store fat, and thus can last longer. 

This is one of several reasons why I have concluded that the thrifty gene theory as to why we get fat is more crapolla that blames the victim for being fat:  she has thrifty genes, thank god I don’t!   Being able to go without food, assuming that there is scarcity of food, say only 50% of calories, would entail a several month survival.  It is unlikely that the paleo ancestor would have zero food.  These hunter-gatherers have secondary, less-favored sources of food during draughts or other adverse events.  Secondly the known famines affect not paleo peoples, but the areas which depend on farming with a typically 10-fold denser population.  Thirdly there isn’t a mammalian model for thrifty gene that when there is plenty of food causes that specie to become obese.  The mechanism is through insulin resistance,[3] and there is a biological clock.[4]  Weight is so important for survival that the palate doesn’t control it.  A broken system causes obesity.[5]  Obesity is selected against, unless it promotes survival as in cold climates, or sexual selection—the male walrus.  The Rhino, hippo, and elephant have muscle and thick hides. I too have a thick hide that protects me from casuistry of all types.       

https://upload.wikimedia.org/wikipedia/en/thumb/5/57/Angus_Barbieri.jpg/220px-Angus_Barbieri.jpg

An example carefully tracked by physicians and in the Guinness Book of Records is Angus Barbieri, a 456 lbs. Scotsman from Tayport.  Starting in June 1965, he went on a medically supervised water fast lasting 382 days and lost 276 lbs. to obtain his goal of 180 lbs.  He consumed only vitamins, electrolytes, and zero-calorie beverages.[6]  The case study was published 7 years later.  His average blood glucose was 30 mg/dL (1.7 mmol/L),[7] which confirmed that he wasn’t eating—as too his weight loss.  He didn’t need an operation to remove the skin folds because autophagy metabolized the excess skin and adipocytes. Only when fat stores become low, then the body starts metabolizing muscle—that occurs when fat drop below 7%.  On his examination at 7 years, Angus had gained only 16 pounds—much better than the contestants on The Biggest Losers show.[8]   Note: after an hour I gave up on trying to find Angus’s cause of death at the age of 51 and weight at that age. 

Not all are so fortunate, and a friend of mine, a middle-age geriatric physician, had to undergo surgery to remove the folds.  He lost nearly 150 pounds eating 1 meal a day for a year.  With the social support of his wife, a nurse, he kept the weight off, an indication that his insulin resistance was reversed and his social environment improved.  

This brings us back to the question, what is the best way to lose weight and at the same time reset the WRS.    

 

4. Calorie restriction, low carbs and Atkins-keto diet:  As covered above the caloric energy restriction (CER) has few successes because the WRS increases hunger and reduces metabolism. Heads on studies comparing low carbs to high fat diets have shown that fat is better than carbs.  Moreover, compliance is low in the CER diet because of leptin increasing hunger and making the dieter feeling crappy and moody because of the reduction in the rate of metabolism.  Life-long changes in diet is an issue with both diets.

While the ketogenic diet has taken off like the Atkins diet of 20 years ago, They are brothers in that both are very low carbs (5% for the keto diet).  The new Atkins diet is the Atkins with limited protein.  I have failed to find the biological necessity for low protein.  Allow, me to explain.  It is widely circulated that certain amino acids raise inulin, the combination of essential amino acids raise insulin the most (see #14).    

 

 

That is true, but for one detail.  The insulin rise is because of the need to utilize the amino acids which cant be stored.   This rise turns on protein building through the two IGF hormones which are androgenic.  I suspect that this doesn’t through the Randle cycle into glucose metabolism unless there is significant amount of carbs,  do it when in a meal there are sufficient carbs.  Thus on an Atkins diet a modest amount of carbs won’t increase excessively insulin.  For example ,in the insulin index, a measure of the response of insulin to foods, pasta has a slightly lower insulin index that meat.  I have failed, based on the biology and various trial protocols to believe that the extreme low carbs is necessary for sustained weight loss—see #4.  Moreover, the keto diet reminds me of niacin to lower cholesterol, it is being promoted by those who don’t know the science behind it, and it isn’t a sustainable diet for 95%.  I think the food gurus know this, and possible realize that keto deflects interest in fasting.  This pattern reminds me of the niacin story for lowering cholesterol.  The official recommendation is a high dose, 1,500 to 3,000 mgs which causes unpleasant flushing for about 10 minutes, and peak level is half hour, with half-life under one hour.  Moreover, cholesterol is made by the liver at night, and over 70% of cholesterol is produced by the body.  A low dose, slow release at night would be more effective than a high dose in the daytime.  See http://healthfully.org/rc/id4.html for my extensive research on niacin.[9]  Back to the question I suspect though for want of better evidence, I am not sure that a diet of 75% of calories from fat is inferior to the ketogenic diet.  One reason is that being mostly in fat metabolism with carbs might not through the Randle cycle switch to fat storage, if the crab portions are small, because the insulin response is low. This combination has a much higher long-term compliance than a ketogenic diet.  More research is needed on the level of insulin that operates the Randle switch.  

In fact, I find Atkins works, with its maintenance phase effective.  The New Atkins diet claims that moderate protein produces superior results, a change that I find the evidence weak.  Atkins is high protein and high fats.  Atkins recommended that once the lean weight is obtained, that carbs should gradually be reintroduced to the point where weight is gained.  At that amount of carbs (say 25% of calories, then back off about 5% so as to not gain weight. 

I have seen over and over again those who haven’t followed the maintenance level recommendation and have gained most of their lost weight.  I have seen the same with the Medfast diet, once off the WRS restores gradually the previous level of obesity.  Medfast is an extreme low calorie, low fat diet, with prepared foods and weekly counseling.  There is need is research as to when the leptin and other hormones stop operating for gain weight.  It seems that prolonged water fasting and bariatric surgery work, but the pathway through the liver to IR and weight gain is easy to go down again, especially for the mature and elder as their ATP production declines, their MTDD increases, and their sex hormones decline. 

 

5. Fasting, can reset the weight regulatory system and much more:  The success of Angus Barbieri proves that fasting can cure obesity, and the impact of bariatric surgery show that an extreme low-calorie diet (averaging 500 calories from carbs through an IV following bariatric surgery) is more evidence that obesity and t2d can be reversed, and that some carbs following surgery doesn’t stop at that low level the metabolism of lipid droplets in the pancreas and liver.[10]  I wonder if instead of carbs in the IV, there were free fatty acids bound to a transport protein such as albumin, both in promoting metabolism of fats and in extending autophagy by keeping insulin low; would that promote better results?  Better long-term results require better dietary counseling.       

          As repeatedly said the hormonal processes are what causes weight gain, and the processes must be reversed for weight loss, and the regulatory system that establishes the level of fat must be reset.  Adipose tissue functions not only as an important buffer for fatty acids but also as a highly active secretory organ, capable of influencing whole-body physiology through the production of an array of bioactive Adipokines.” [11]  The complexity of system has thus far prevented the detailed diagramming of the process with sufficient basic research to take such a putative chart to the level of established science.  Thus the lower standard of practical experience is used to fill the gap with claims being made for its mechanisms.  The role of insulin in weight gain is beyond questioning both at the laboratory level and observational level.  The success of fasting is beyond questioning, and the combination of high fat thus low carb diet with fasting entails the Randle switch staying in the fat metabolizing setting. 

This combo also turns up autophagy and thus goes far beyond curing t2d: 

There is large empirical and observational evidence that medically supervised modified fasting (fasting cure, 200-500 kcal nutritional intake per day) with periods of 7-21 days is efficacious in the treatment of rheumatic diseases, chronic pain syndromes, hypertension, and metabolic syndrome. The beneficial effects of fasting followed by vegetarian diet in rheumatoid arthritis are confirmed by randomized controlled trials. Further beneficial effects of fasting are supported by observational data and abundant evidence from experimental research which found caloric restriction and intermittent fasting being associated with deceleration or prevention of most chronic degenerative and chronic inflammatory diseases. Intermittent fasting may also be useful as an accompanying treatment during chemotherapy of cancer. . . . Various identified mechanisms of fasting point to its potential health-promoting effects, e.g., fasting-induced neuroendocrine activation and hormetic stress response, increased production of neurotrophic factors, reduced mitochondrial oxidative stress, general decrease of signals associated with aging, and promotion of autophagy.[12]

          Fasting is easier than caloric restriction.  It is easier to stay out of the kitchen, to be away from food, than to be around it and limit the portions:

Persistent hunger and irritability noted in non-obese men and women in earlier IER trials, where food was completely restricted on alternate days, suggest that some individuals are unlikely to be able to comply for extended periods of time.  Compliance with IER [intermittent fasting] protocols which allow some intake on restricted days have been promisingly high. . .  Findings from rodent trials suggest that IER (50-100% ER/alternate days) is capable of modulating adipose physiology, independently of changes to fat-mass. [13] [IER/alternate days is alternate day fasting, ER is energy restriction, the 50-100% is the amount of restriction from 50% of rat chow to 0 rat chow on fasting days.]

The first part is evidence that intermittent fasting compliance. This is consistent with my observation, and an improvement thereon is to limit the intake to proteins and fats. Viz., no carbs.  For example, I use now cheese with butter for snack during the fast, and for 4 years before bell peppers and homemade Russian dressing.[14]  The second section quoted above states that through IER (alternate day fasting) the adipose tissue hormones don’t kick in, in particular leptin, to cause increased hunger and lower metabolism, a metabolic response to preserve adipose tissue and restore its fat to prior level.[15]  Thus alternate day fasting or the short intermittent version are a way to lose weight and cure t2d without the typical at 2 months when the adipose tissues will oppose weight loss by increased appetite and reduced metabolism— of the 6 produced, the main hormone for this change is Leptin.

          The benefit of IER is improved insulin response with those the most IR, namely with t2d showing the greatest improvement.  The article points out that only with sufficient carbohydrate does the glucose level rise to abnormal levels, and thus with low carbs the production of insulin is sufficient to keep the serum glucose at a normal level.  Clearly the low carb diet is the way to manage t2d.

Hepatic IR ensues, increasing endogenous glucose production, hence elevating plasma glucose levels and stimulating further insulin secretion.  Within pancreatic β cells, excessive lipid deposition causes the metabolic inhibition of postprandial insulin secretion which, above an individual threshold, will herald the onset of hyperglycaemia.  Within pancreatic β cells, excessive lipid deposition causes the metabolic inhibition of postprandial insulin secretion which, above an individual threshold, will herald the onset of hyperglycaemia.[16]

It isn’t rocket science that the low carb diet is the way to keep serum glucose within the normal level, and with IER is the most effective of the many types of diet. 

 

6.  Type-2 Diabetic diet:  This is what I would do based on a long hard look at the evidence and history of treating t2d.  I had in 2016 posted Evidence for alternate day fasting—cures diabetes  at http://healthfully.org/rh/id13.html.   In that article I explained that excess fat in the pancreas cause inflammation that results in a reduction in the production of insulin by the beta cells.  Metabolizing the excess fat (lipid droplets) in the pancreas cures t2d, and this occurs for 80% of the diabetics following bariatric sugary.  Other studies placed the figure using diet at between 50 and 70%, and that is for long-term diabetics.  The articles (rh/id13) posted explains why weight loss through a keto diet with alternate day fasting or extended water fasts cures t2d.  Dr. Jason Fung in his large clinic in Toronto does with success.  The evidence is supported by both animals and small human trials using a variety of protocols.[17]  Of course pharma denies all this and claims that t2d can’t be cured, that t2d is a chronic, progressive disease.  The KOLs state that weight loss can at best result only in a reduction in medications.  Then recommend a calorie restricted diet low in fats, and with carb snacks so that the blood glucose doesn’t dip into hypoglycemia.  It is a program with under 5% long-term success, yet for the last 50 years are more that is what the ADA and physicians recommend.  They go on to inform the patients and public that t2d is a progressive condition, and can’t be cured with diet.  Which is right?

There is a chorus pointing out the old wisdom, going back in Western medical literature to the 1797.  Type 2 diabetes can be controlled and reversed by diet.  Of course the ADA, KOLs, and media dominate the belief production and that production includes 6 crapolla tobacco science myths.  In the videos series by What I’ve learned, the first of two links below, the scientific fraud is rebutted.  The second video which explains the process and exposes more KOL crapolla.  This series of over 50 videos sets the standards high for research, video support, and content— of course a few or in error.  Give them a try you will be pleased.   

*****Can you cure diabetes/does fat cause diabetes, 18 min, 217,000,  covers 6 myths about diabetes, what you need to know that is contrary to the myths that media, dieticians, and doctors promote insulin resistance https://www.youtube.com/watch?v=b7zWNabebxs His best at debunking bad science

***** Obesity and diabetes explained: the overflow pheno0menon 16 min, 517,000 views, Oct 2018, What I’ve Learned, lots of good basics such as insulin causes fat storage, and rebuttal of bad studies, but failed to mention industry funding or going into the biology behind ketogenic diet—covered elsewhere.  He shows how a KOL lie to the public & physicians by using very low-quality studies and ignoring the better ones.   https://www.sciencedirect.com/science/article/pii/S1568163713000640 Excellent Part II of Can you cure diabetes/does fat cause diabetes

Again I must steer you to my video web page for the evidence that diet can cure t2d.  This is about a system which is breaking the bank with t2d, destroying quality of life, and burying a treatment that is free, cures IR, and prevents the deterioration of quality of life that accompanies t2d.  A system that is about lives needs to put people before marketing. 

 

7. Before the drugs for t2d:  So what about my aunt Bertha?  She lived a full life without drugs, she was obese and diabetic from the late 1940s until her sudden death from arrhythmia around 1965 in her 6th decade.  And what about the fatsoes of the past, surely many who had the conditions of the affluence and were obese were also diabetic, yet the literature doesn’t have much to say about adult onset diabetes.  It is as though such people weren’t under the care of physicians.  Well, there weren’t drugs for them, could that be why?  Did they die in a few years from associated conditions of the progressive t2d?, or were they like William Banting[18] and my aunt Berth and lived a full life. 

Why is what I know of the past so different than the last 2 generations with t2d?  UK has 70,000 amputation of legs a year.  My brother-in-law’s leg wouldn’t heal and was scheduled for amputation when he died of heart failure in the hospital at the age of 53 in 2006.  Similar to what happened to Jerry Garcia of the Grateful Dead, found dead in 1995 in a care facility also age 53 and 8 days from a heart attack.  My neighbor 3 months ago died from kidney failure, for the last 2 years she was on dialysis.  Tracy, my former officer manger, now managing for my lead installer who took over the business.  She is nearly blind; she has been diabetic for about 30 years.  My real estate agent of 3 years ago, a wonderful lady, has end stage diabetes—extreme IR.  Both ladies are on over 100 units of insulin.  End-stage diabetes is really end-stage insulin resistance.  This didn’t occur, as I recall, before pharma took over the standard of care.  You too should have a list of failures of treatment, that this is avoidable following the older treatment of just diet, this is indeed tragic!  So what was the standard of care for aunt Bertha?

          I picked up my 1950, Eight Edition of the Merck Manual and read their diabetes section.  In the 1950s there was one diabetes in two forms:  either juvenile or latent adult:    

One of the earliest decision the physician must make is whether diet alone will suffice or whether insulin is needed in addition.  Often the obese elderly patient after weight reduction can get along with dietary supervision alone. . . .  Dietary measures:  The diabetic diet is a regularly ingested  “normal diet” with the exception that the more rapidly absorbed carbohydrates[19] and food containing them in large amounts must be eaten sparingly (see Diets). . .  regularlity helps prevent overloading of carbohydrate-disposal mechanisms and consequent hyperglycemia. . . . There now seems to be no reason to believe that adult diabetics cannot under proper care, live as long as nondiabetics and carry on relatively normal activities. . . .  In well controlled cases (i.e., blood sugar normal or nearly so), there are fewer complications.[20]    

So have modern miracle medicines and the guideline-generated standard of care improved the lot of diabetics?  If you were diabetic, would you want diet or drugs? 

 

8,  Dietary management of t2d, 1950-61:  Since the 1950 Merck Manual, Eight Edition, the science behind dietary management has made a big step forward both as how best to lose weight, keep it off, and how to cure with diet and fasting t2d.  The harm associated with t2d (not counting drug side effects) is from insulin resistance which slowly increases with medication, and the increased frequency of turning on the polyol pathway that produces fructose.[21]  These both can be avoided by the low carb diet.  As for carbohydrates, the combination of foods in a meal has major influence on the insulin response because of the rate of absorption of the carbs depends upon the proteins and fats in the meal, and they slow their absorption.  By limiting the rapidly absorbed carbs to small portions taken with a large portion of proteins and fats, the insulin response will be much less and over a longer period of time.  The spike is of concern since it increases the likelihood that the polyol pathway will be turned on to lower cellular glucose and thereby convert some of the glucose to fructose.  The spike in insulin stimulates the uptake of glucose from the blood to cells which are overstuffed with glucose.  Being overstuffed through a cellular signalling system it down regulates the glucose receptors, thereby slowing the absorption of more glucose.  Increasing the insulin overrides this cellular protective system.  The damage by overstuffing cells and the high level of insulin, they are causal for most of the harm associated with t2d.  Insulin which has many regulatory functions (3:5) that are affected.  The longer it takes to clear the carbs from the digestive system, the longer it will take to switch to fat metabolism and turn on autophagy.  Best is a very low carbs diet, and if the goal is ketosis then this includes low fiber, which through the action of intestinal bacteria, hours later the fiber will be converted to glucose and about 50% will be so absorbed, the remaindered being utilized by the bacteria that break it down.  The food topic is too complex for here; much of what I have uncovered is at http://healthfully.org/rh/id8.html.  For t2d, simply keep carbs very low, and prefer slowly digested carbs and eliminate the fast ones, sugars, potatoes, rice, wheat and other grains products, corn, etc.  Another reason to keep carbs low is the insulin response to proteins (certain amino acids) occurs when carbs are included, but on a meal of fats and proteins, the insulin response remain much lower.  Details make a big difference for the diabetic.

The trail for dietary management gets thin.  The 10th edition moves away from dietary control.  Recommended is a normal diet for both t1t and t2d, with the avoidance of large portions of food that rapidly raise glucose.  For t2d there is a section on oral hypoglycemic agents (P. 312-3).  For t2d the obese are advised to lose weight (which almost always fails), and below that is heading 2. “Mild nonobese diabetics usually can be controlled without insulin.  If this is not possible on the adequate diet which maintains ideal weight, insulin or one of the oral agents may be given”-- end of section, P 313.  This is a major revision from the previous 2 editions which clearly recommend diet as first choice.  Moreover, in all 3 editions it is a normal high carb diet with 2 restrictions: to limit fats and large portions of rapidly digested carbs.  This is hardly a suitable diet, since low fat entails more carbs.  The diet is not designed to cure t2d,  Since  up to 90% of t2d are overweight;[22] there by limiting diet treatment in the 10th Edition to at most 10%, and that is not clearly stated as in prior editions.  The diet with carbs will increase the use of insulin for both t1d and t2d as well as drugs for both.  “The diabetic diet is a regularly ingested ‘normal diet’ with the exception that the more rapidly absorbed carbohydrates and foods containing them in large amounts must be eaten sparingly . . .  to avoid hyperglycemia (Eight Edition P. 273, and repeated in the 9th Edition, P. 331, but not 10th Edition). 

 

9.  A modern update on diet:  What diet depends upon one’s health, for which I have broken down into 5 diets depending on situation, at http://healthfully.org/rh/id8.html.  Empower the rational module of the brain by watching the YouTube videos listed at http://healthfully.org/rh/id7.html under categories 1, 2 and 3—knowledge effects behavior.  If I was diabetic.  We are a social animal, thus for most people it is necessary to get the support of the significant other.  Having them watch the videos is a start.  Work on them to be supportive by using condition techniques of reward and withholding rewards. It is hard to diet when the other half is an obstacle. 

          If I was overweight or worse, I would start with low sugar and intermittent fasting while gradually lowering carbs and increasing saturated fats.  I wouldn’t count calories.  When not hungry skip a second meal.  Non-carb snacks help.  I snack on cheese with a big wad of butter (zero carbs), sometimes it is salted nuts with butter.  Sex hormones (6:2) play an important role.  I am 76 as of 6/19, have been on this diet since 2014 with intermittent fasting since 2014.   However, I have always been of normal weight so I don’t try to lose more weight.  Haven’t watched my weight since I started testosterone replacement in 2003. 

If I had t2d I would go on a very low carb, high fat diet with extended water fasting to metabolize the lipid droplets in the liver and pancreas.  Once restoring weight and glucose metabolism to normal, I would stay on a high fat diet with intermittent fasting (#5).  I would once ideal weight increase carbs to about what is craved.  I currently get about 20% of ATP from carbs 70% from fats and 10% from excess amino acid.  Let the body be the guide, unless the leptin system is causing weight gain.  Intermittent fasting might be sufficient, otherwise continue with alternate day fasting and lowering carbs. There would be no need to say no to the drugs? 

Water fasting or if too difficult extremely low net carbs[23] is a key part of the cure.  The  fast autophagy with the result marketed increase in mitophagy.  The rate of replacement of the MTD in the liver peaks at 1.25 days; the control at 1.85 days, and there is nearly zero overlap of the 2 bell curves.[24]  The article goes on to warn that using fasting glucose and HBA1c are inferior to that of “changes in circulating insulin concentration, fasting (hepatic) insulin sensitivity, and glucose uptake/clearance. ..”[25] The mitophagy increase is the key part of what gives the superior results.  Moreover, in this seminal review article it noted with references to 6 articles that “Compliance with IER [intermittent fasting] protocols which allow some intake on restricted days have been promisingly high” (supra).  The review article supports both dietary management of t2d but also through fasting with low carb its cure. 



[1] Antoni, Rona, Kelly Johnston, et al, March 2014, The Effects of Intermittent Energy Restriction on Indices of Cardiometabolic Health

[2] Fothergill, Erin, Juen Guo, et al, May 2016, Persistent metabolic adaptation 6 years after “The Biggest Loser” competition

[3] Shi, Shu-qun, Tasneem Ansari, et al March 2013, Circadian disruption leads to insulin resistance and obesity.  They used Bmal-1 knock-out mice to demonstrate the mechanism.  Moreover, clock-disrupted Bmal1-knockout mice are locked into the trough of insulin action and lack rhythmicity in insulin action and activity patterns.”. 

[4] Okamura, Hitoshi, Shun Yamaguchi, et al, July 2002, Molecular machinery of circadian clock in mammals

[5] There are few rare exceptions where social conditioning (status) creates in a select sub-population obesity; e.g.. the Suma wrestler

[6] A case study was published 7 years later, Stewart, W. Laura Fleming, March 1973, Features of a successful therapeutic fast of 382 days' duration

[7] This level is well below that which causes symptomatic hypoglycemia and death.  During extended fasting the liver adjusts to the lack of food by producing glucose, and other adjustments occur.  Medical supervised water fasting was used to reverse obesity prior to bariatric surgery.   Drenick, Ernst, Marion, Swendseid, et al Jan, 1964, Prolonged Starvation as Treatment for Severe Obesity  

[8] See Jason Fung, The complete guide to fasting, 2016, P 104-106, who relied upon the New York Time’s article mostly, which was based upon an article in Obesity, Fothergill, Erin, Juen Guo, et al, May 2016, Persistent metabolic adaptation 6 years after “The Biggest Loser” competition. 

[9] The same would apply to statins, they should be taken at night slow release low does.  There are benefits for niacin, which has many bio-functions, including lowering the mortality rate long term, but for statins it is net harm. 

[10] The droplets in the pancreas cause the t2d, and the liver is an essential step to the accumulation of fat in the pancreas and IR.  Metabolically, the evidence supports that the liver droplets are metabolized prior to or at the same time as the pancreatic droplets. 

[11] Antoni, Rona, Kelly Johnston, et al, March 2014, The Effects of Intermittent Energy Restriction on Indices of Cardiometabolic Health

[12] Michalsen A, C Li, Dec 2013, Fasting Therapy for Treating and Preventing Disease - Current State of Evidence

[13] Antoni, Rona, Kelly Johnston, et al, March 2014, The Effects of Intermittent Energy Restriction on Indices of Cardiometabolic Health

[14] I make my own dressing using the blender mayonase  receipt with half coconut oil and half canola oil.  As for butter I make a butter substitute using the mayonase receipt and this time heat the coconut oil to 150 degrees farinheit and 3/4th coconut oil.  

[15] Antoni, Rona, Kelly Johnston, et al, March 2014, The Effects of Intermittent Energy Restriction on Indices of Cardiometabolic Health

[16] Antoni, Rona, Kelly Johnston, et al, March 2014, The Effects of Intermittent Energy Restriction on Indices of Cardiometabolic Health

[17] The best book as of 2019 on the studies, and piecing together the evidence for fasting for weight loss and for curing t2d is Jason Fung, The complete guide to fasting, 2016, and it is well written for an educated audience.   

[18] At the advice of his physician, who relied on the work of a French physician, William banting (1796 to 1878) followed an early version of the Atkins diet.  He was the funeral director to the Royal Household.  His book on dieting, Letter on Corpulence, addressed to the public, 1863, went through a number of editions and remains in print.  Banting and bant has entered the English, UK, language, and in Swedish banta is a verb for being on a diet.  William is a relative of Sir Fredrick Banting, of insulin fame.   

[19] Those with a high glycemic index.  The insulin index which once I relied upon falls short in that with carbohydrates certain amino acids will significantly raise insulin, but taken without carbohydrates they don’t.   

[20] Merck Manual, eight editions, 1950, pgs. 268-9; the 9th Edition, 1965 essentially repeats that message p. 331.  The 10th Edition, 1961 refers to diet, but with the sulfonylurea drugs entering the market, the dietary approach is just mentioned in passing.  By 1980, the Goodman and Gilman’s the pharmacological Basis of Therapeutics, Sixth Edition makes no mention of the dietary drug free alternative.  Upon finding that KOL stamp on contents, my 38 years of faith in the quality of science has been shattered.

[21] Probably far less significant, only the journal evidence on polyol pathway and fructose is thin, while blaming sorbitol isn’t. 

[22] Cecil essentials of medicine, 1986, P. 488, There are 6 drugs listed for treatment of diabetes.  Like the Merck of 1961, the diet approach is not stressed, and the progressive nature of the disease with   And it gets worse:  To diminish the risk of vascular disease, all diabetic patients should be place on a diet low in fat. . . . and with a low cholesterol content. . . . P. 490.  The benefits of the drugs are “The complications of diabetes usually take 10 to 20 years to develop.” It goes on to state that tight control of glucose should not be instituted for those with longer life expectancy.  P 490.  I wonder if this message is taught in CME classes? P, 490.

[23] Net carbs are total carbs minus the fiber.  A tern used by the group of professors that runs the New Atkins diet. 

[24]  Antoni, Rona, Kelly Johnston, et al, March 2014, The Effects of Intermittent Energy Restriction on Indices of Cardiometabolic Health  https://wol-prod-cdn.literatumonline.com/cms/attachment/496dba0d-bac9-42ef-81c8-8bfc03fef479/acel_426_f2.gif

[25] Antoni, Rona, Kelly Johnston, et al, March 2014, The Effects of Intermittent Energy Restriction on Indices of Cardiometabolic Health

 

10.  Metformin, bad meds,:  The apple is rotten, see Bad medicine:  the way we manage diabetes, BMJ 2013, which I posted at http://healthfully.org/rh/id15.html.  So I first have when possible to relied upon mode of operation in evaluating a drug, but The molecular mechanism of metformin is not completely understood.  Multiple potential mechanisms of action have been proposed.” [1]  Knowing how it works allows me though the journal articles to see if it is possible significantly effective.  The lack of mechanism, greatly increases the likelihood that there isn’t a mechanism, and the claim of effectiveness are all marketing.  Next. I attempted to research the long-term side effects of metformin, and I only came across industry articles on the standard side effects nausea, diarrhea and flatulents.  The normal pharma pattern is to not look for those horrific side effects like stroke and cancer.  I found benefits for cancer and liver cirrhosis survival, lower blood glucose, HBA1c, IR, and a lack of weight gain (but those studies are compared to other drugs that cause weight gain adverse events.  The lower rate of weight gain is because of its negative effects upon the digestive system (nausea and diarrhea).  Serious side effects don’t show up in an ideal, younger population in a short-term trial.  This is the usual pattern for a  blockbuster, journal articles that claim benefits and adverse events not found.[2]  Journal articles weren’t helpful in evaluating metformin.  Article after article found it lowered IR, ROS, reduced the risk for progressing to t2d, cancer, CVD, weight loss, lower fasting glucose.  I will save you from a list of other drugs that follow the journal pattern of marketing. 

          This brings me back to the start, and again to mention that the positive effects are because of its side effects, nausea, diarrhea, and flatulents.  Experiencing those side effects, estimated at over 50% of those taking metformin and probably higher; weight loss would naturally follow, and with that better fasting glucose, etc.  This still leaves with the nagging thought, why metformin, why is it promoted, now off patent, like acetaminophen?  My best guess would be one, the promotion of managing serum glucose.  The patient taking this off-patent drug is likely to request a different drug, one that is easier on the digestive system.  Metformin thus is a gateway drug.  Second, I suspect like with acetaminophen there are major pathogenic consequences (those for acetaminophen are listed at http://healthfully.org/rc/id5.html).  To find out of metformin’s long-term effects would take an opening up of the data banks.    

Metformin deserves special attention with the new standards soon over 30% of adults will be taking diabetic medication, and metformin is the gate way drug.  In 2014 metformin was the 4th most prescribed drug in the U.S. generating 81 million prescriptions.[3]  This is another case like with hypertension, no symptoms, yet a “condition” being treated with drugs.  After a year on the drug and a failure to lower glucose, the physician rolls out a patented diabetic medication to be added for treatment or replace metformin with a drug that has less side effects, and, of course, is more effective.  By then most patients are sufficiently worried about their t2d and have sufficient faith in their physician who gave them an off patent drug, that they will add a second drug to manage blood glucose. 

Metformin, however, has so little effect on fasting glucose and HBA1c that the current blood test is not sufficiently sensitive.[4]  Its mechanism of action might be the reason for its ineffectiveness (a fact not taught in CME classes). 

The molecular mechanism of metformin is not completely understood.  Multiple potential mechanisms of action have been proposed: inhibition of the mitochondrial respiratory chain (complex I), activation of AMP-activated protein kinase (AMPK), inhibition of glucagon-induced elevation of cyclic adenosine monophosphate (cAMP) with reduced activation of protein kinase A (PKA), inhibition of mitochondrial glycerophosphate dehydrogenase, and an effect on gut microbiota

The lack of a known mechanism of action could be because there is none, or none that are significant.  Alternative it has been proposed that:

Biguanides [metformin is the only marketed one of that class of drugs] can lower fasting levels of insulin in plasma. Their therapeutic uses derive from their tendency to reduce gluconeogenesis in the liver, and, as a result, reduce the level of glucose in the blood [thus lower insulin].  Biguanides also tend to make the cells of the body more willing to absorb glucose already present in the blood stream, and there again reducing the level of glucose in the plasma.[5]

This would explain its minor effect on glucose and side-effect, toxicity.  Gluconeogenesis occurs to replace vital stores of glycogen, which among other things is stored for emergencies such as preventing hypoglycemia which can cause a cascade of events due to the lack of glucose for the erythrocytes.  Secondly, the amount of glucose replacing glycogen daily used is a small percentage of the daily amount of dietary glucose.  The average diabetic uses very little glycogen (prolonged exertion reduces stores, and most are sedentary).  So, if the claim of blocking production (not supported by the Wikipedia article) is correct, metformin would have minimal effect on the glucose markers. 

          This brings me back to the question of how good is metformin?  Quoting the lecture of Prof. James McCormack citing Hirst and Farmer footnote blow:   “Metformin monotherapy reduces A1c ~ 1.1%, doubling the dose from 1000 to 2000 mg/day ads 0.25% to 0.3% additional change in A1c.” [6]  

This brings me to the next fact that in a number of trial the tight management of glucose results in a worse outcome.  There are 2 reasons, one is that most treatments increase IR, and it is IR--not its shadow elevated glucose--that is pathogenic.  Secondly that most treatments over time increase IR.  Thus we are back to Joseph Kraft’s work on insulin testing, and looking at the shadow.  Not surprising a review of the many functions of insulin, IGF1, and leptin, compared to glucose, insulin is the gorilla in the room.  Insulin has regulatory functions for IGF-1 and leptin.  As A1c goes up so too does insulin resistance, which is to say, that the clearance from the blood of glucose and thus fructose (which also causes glycation) is slowed. 

From the lecture by James McCormack (supra footnote #19, YouTube) As A1c goes up a digit from 5 to 6, 8 to 9 and so the risk of adverse event goes up about 2% over 10 years.  Those with t2d have a 10-year risk of CVD of ~ 20%.   The risk of dialysis lifetime risk goes up from about 1% to with A1c of 7 or less to about 2%, with 11 A1c and a 6% risk of peripheral neuropathy.  Blindness lifetime risk with diabetes start at near zero for 7 and 4% for A1c of 11.   Fifty-five percent of diabetics are under 7% A1c.  For metformin there is but only the UKPDF study; it found a 7% reduction in cardiovascular endpoints over 11 years; however, a subsequent meta-analysis found no benefits.  And the study compared it to drugs, not placebo.  Sulfonylureas showed only a 3% reduction in retinal photo coagulation, all of the other types of drugs have not been studies in the chart McCormack showed.  Given the sizes of those studies none were statistically significant.  In a meta study of metformin, 12 studies, 9,500 on metformin and 3,500 on conventional drugs, change in Mortality CVD mortality, MIs strokes, heart failure peripheral vascular disease, amputations and microvascular disease all results were insignificant, [and worse if you consider the built in bias for pharma funded studies.][7]  “In 2013, the level of evidence for the clinical efficacy of antidiabetic drugs is disappointing and does not support the millions of prescriptions written for them.” [8] Without dietary management as the placebo group [the best therapy], all results of clinical trials are inconclusive.  

The manufacturer of the drug testing their product against the worst drug, or made worst by being too low a dose, is marketing not science:  this is what we have with few exceptions.  Again, I remind you the strong case concerning clinical trial made by Prof. Ben Goldacre in Bad Pharma.

With the new guidelines the standard of treatment is to drug the prediabetic.  McCormack asked: “why are we taking these drugs that don’t make a difference for the reason of lowering risk of major events? And why are we give 100% of them a drug to prevent at some future date 25% of them receiving a drug of diabetes?”  Remember, that those with t2d are asymptomatic and can be successfully managed with diet.  The benefits of metformin are repeated by physicians as absolutely proven, beyond a doubt.  However, the UKPDS 34 study[9] followed only 134 on metformin followed 11 years, and given the standard 30% industry positive bias (including burying side effects), I certainly would not take this strange, bioactive chemical.  Oh, and don’t forget in the study when metformin was added to sulfonylureas there was a 60% increase in morality (a 6% absolute increase).[10] The use of multiple drugs is the norm after starting out on metformin.  Relying on the physician as expert is sadly an error comparable to the times of William Osler, the legendary Canadian physician who joined John Hopkins in 1889.    

The dismal results for metformin are extended to others in a study which compared glyburide, metformin and rosiglitazone for newly diagnosed patients.[11]  In the comparison they all gained weight (contrary to the claim that metformin causes weight loss), yet it is commonly repeated by physicians that metformin promotes weight loss.  No, it just causes less weight gain that the other drugs, and that is because the drug nauseates—a great way to slow the weight gain.  From 2004 to 2013, none of the 30 new diabetes drugs that came on the market were proven to improve key outcomes, such as reducing heart attacks or strokes, blinds or other complication of the disease.” [12]  Looking at these numbers as a newly diagnosed patient, I would conclude that the help offered isn’t help.

Drugs to treat glucose are like drugs to treat fever, the problem with t2d is insulin resistance, and with colds a bacteria or virus.  Pharma’s maximization of profits entail over and over again they treat signs of a condition, because to cure a condition is less profitable, and to treat t2d with diet is for them the worse-case scenario.  I am not claiming that pharma isn’t looking for a drug to lower insulin resistance, but as far as I known they haven’t found one, one that would be effective in preventing the progression from IR to t2d.  Would they market it? that is another question. 

Earlier I had mentioned that pharma is maximizing the treatment of glucose, so what are the new guidelines that classifies 10s of millions more as diabetic and recommends treating pre-diabetics with metformin, that is 30% of the adults.  My 2 Canadian friends on were put on metformin in the fall of 2019.  I feel morally obligated to devote space to this issue.  This Section is about fixes and dietary management and curing of t2d thus belongs in Section 6.  T2d is not just a major CAWD; but all the conditions whose numbers go up because of its extreme form of insulin and subsequent inflammation of the pancreas with its diminished production of insulin.  By simply limiting carbohydrates to 10% of calories entails that this lower production of insulin is adequate to regulate serum glucose so as not to be significantly pathogenic.  The association Prof. James McCormack found between increase in A1c and pathology is not because of the glucose but because of the degree of medication with its side effects and their exacerbating of the IR.  The new guidelines are treating healthy people with drugs that cause the side effects associated with t2d.  As Dr. Fung in books and lectures points out, most of those medication increase insulin resistance, and it isn’t glucose but the IR that needs to be managed, which he does through diet and fasting.

Over and over again good treatments are replaced with bad ones.  One point, the UBC professor James McCormack (University of British Columbia)[13] lecture provide a rebuttal to the spin generated by KOLs on the benefits of metformin.  This is what I have up on my video page for his 2015 lecture: 

****** Metformin – the case of exaggerating both benefits and harms, 29 min, 150,000 views Prof James McCormack, UBC   No quality evidence that metformin increases lactic acidosis, reduced renal performance, and does NOT have significant benefits, just less harm than some other drugs.  Very minimal lowering of A1c.  He is skeptical of treating glucose.  A study compared it as to quality of life to that of having a mild stroke.  If your physician told you that any of the drugs for diabetes has no benefits but lowers the quality of life comparable to a stroke, would you take it?  https://www.youtube.com/watch?v=pUOC5d0Siws   Excellent

Again and again association is used by KOLs to “prove” causal.  Elevated glucose is guilty by association.  Insulin resistance is a CC, it is a gateway hormone through leptin and other hormones causes weight gain, so unless a drug counteracts IR or the downstream effects, the norm is for weight gain of those who are the most insulin resistant, and are managing their glucose with insulin gain the most.  Obesity is a marker that is associated with the degree of progression of MTDD, RATP, RRA, LR and IR.  The dupes don’t understand this; they focus on lowering glucose with drugs.  They believe as told that the risk of a high fat diet outweighs the risks associated with t2d and its drug management.  It is the cholesterol-statin story, only now it is glucose and glucose lowering drugs. 

If I seem angry, it is not at the dupes, but at a system which rewards profits before people, one that is very good at marketing, and it is not truly anger, but sadness over the quality of the golden years.  Where I live in a gated senior community there are over 200 seniors, and there are just 3 in good health—drug free and normal lean weight.   And now my 2 life-long Canadian friends, brothers, who head south every winter to metro Palm Springs, where each own a home, their physicians have put them on metformin though there A1c and fasting glucose classify them as pre-diabetic.  They are in the 30% of adults now classified as prediabetic—their BMI is under 30.  Of this group in their lifetime, 25% will progress to t2d.  What are the new guidelines; I would certain say no to my physician for metformin, would you? 

 

11.     The new 2019 guidelines:  I keep wondering how stupid can it get?  The problem is the inability to control the level of serum and cellular glucose as per mammalian design.  So instead of avoiding glucose, the recommendations are to eat more glucose and less fats, the other source of energy.  This is given the expert -opinion (KOL) system what is repeated over and over again, justified because the fats are more pathogenic than the carbs for those who are diabetic or prediabetic, and for the general populace.  I guess the Eskimos still on a traditional diet are the sickest people on this planet.  Refined carbs gram-per-gram are as to amount of glucose nearly equal to the unrefined carbs.  A recommendation of avoiding refined carbs has little impact on the sum total of glucose over a 6-hour period between meals.  So what does the ADA recommend?   

Their 2019 update guidelines is over 100 pages, I picked through for what I considered relevant key points: 

Prediabetic A1C 5.7 to 6.4 fasting glucose 100-125 mg/dL (5.6-6.9 mmol/L).   Diabetic 6.5 or greater; fasting glucose 126 mg/dL (7.0 (mmol.L) 

Metformin therapy for prevention of type 2 diabetes should be con­sidered in those with prediabetes, especially for those with BMI ≥35 kg/m2, those aged <60 years, and women with prior GDM [gestational diabetes].  Several pharmacologic agents have been shown to decrease the incidence of diabetes, although none are ap­proved by the U.S. Food and Drug Administration (FDA) specifically for diabetes prevention.  Metformin has the strongest evidence base and demonstrated long-term safety as pharmacologic therapy for diabetes prevention. 

Based on intervention trials, the eating patterns that may be helpful for those with prediabetes include a Mediterranean eating plan and a low-calorie, low-fat eating plan. Additional research is needed regarding whether a low-car­bohydrate eating plan is beneficial for persons with prediabetes.

 

To achieve weight loss of >5%, short-term (3-month) interven­tions that use very low-calorie diets (≤800 kcal/day) and total meal replacements may be prescribed for carefully selected patients by trained practitioners in medical care settings with close medical monitoring.  [Their insurance won’t cover the expense.]  To maintain weight loss, such programs must incor­porate long-term comprehensive weight-maintenance counseling.

 

  1. Metabolic surgery should be rec­ommended as an option to treat type 2 diabetes in appropriate sur­gical candidates with BMI ≥40 kg/m2 (BMI ≥37.5 kg/m2 in Asian Americans) and in adults with BMI 35.0–39.9 kg/m2 (32.5–37.4 kg/m2 in Asian Americans) who do not achieve durable weight loss and improvement in comorbidities (including hyperglycemia) with reasonable nonsurgical methods.

  2. For patients with diabetes aged <40 years with additional ASCVD risk factors, the patient and provider should consider using moderate-intensity statin in addition to life­style therapy.  

  3.  For patients with diabetes aged 40–75 years and >75 years without ASCVD, use moderate-intensity statin in addition to life­style therapy.

Pregabalin [Lyrica], duloxetine [Cymbalta], or gab­apentin [Neurontin] are recommended as initial pharmacologic treatments for neuropathic pain in diabetes. 

  1. Need I point out the dollar trail?  Or again the results from using sedatives for pain?    

    Only the lowest standard trials have justified treating the prediabetic as Prof. McCormack points out.  That the FDA hasn’t as of Dec. 2019 approved drugs for pre-diabetics is evidence that the ADA used the lowest standard clinical trials.  As Prof. James McCormack said: “It is ridiculous to put the prediabetic on a drug that doesn’t lower the risk of type-2 diabetes for the putative reason that it might reduce his 25% risk of needing drugs to manage his diabetes.”  That reduced risk has not been demonstrated in the better of the clinical trials.  In addition, research indi­cates that low-carbohydrate eating plans may result in improved glycemia and have the potential to reduce antihyperglycemic medications for individuals with type 2 diabetes.

          1.          The Cochrane library failed to find significant advantage to treating pre diabetics with metformin.

          2. In general, the reporting of serious side effects was sparse. Few participants died and we did not detect a clear difference between the intervention and comparator groups. We also did not detect an advantage or disadvantage of metformin in relation to health-related quality of life. Our included studies did not report on non-fatal heart attacks, strokes or complications of diabetes such as kidney or eye disease. Few studies estimated the direct medical costs. When compared to diet and exercise, metformin was more expensive. When compared to intensive diet and exercise, metformin was less expensive.

      1. Note that a slight advantage that is not statistically significant is treated as though it is significant.[14] Add to this the failure to receive the raw data and the average of over 30% positive bias, and it is very likely that metformin promotes t2d, not prevents it. 

      2.  

      3. 12.  Bariatric surgery for t2d:       The failure of bariatric surgery to keep the weight of is based on the wrong message, carbs are good, fats bad, and sugars are empty calories.  The opposite should be drummed into those receiving bariatric surgery.  Their weigh regulatory system functions to restore their weight gradually or often permits an initial loss, and no more.  Under 10% make it to normal weight.  The ADA guidance has a long list of science ignored: There is nothing about insulin resistance, fatty liver disease, fatty pancreas, fasting, increasing fat while lowering carbs, the weight regulatory system and the yo-yo diet.  It is more of the same that for the last 50 years, and it fails.  Is the ADA dumb or are they beholding to pharma and food manufacturers?  They recommend bariatric surgery and the Mediterranean diet, yet fail to mention (and the media too) that the Mediterranean peoples eat on an average about half the sugar of Americans, the failure to mention dietary treatment for t2d should start with dietary management.  So what was done when insulin was the only drug, for those with adult onset diabetes? 

  2.  

13. What’s causing Type 1 diabetes:  While it is an autoimmune response with genetics increasing the risk; however, given that LSPs have near zero rates of t1d the western diet and fructose-MTDD is likely the major CC in that it promotes the immune response that destroys the beta cells.     

  1. William Osler reported that of the thirty-five thousand patients under treatment at John Hopkins since its inception, only ten had been diagnosed with diabetes.  In the next eight years, 156 cases were diagnosed [mainly t1d].  Mortality statistics were wrote Osler, suggested an exponential increase in those reported dying from the disease—nearly doubling between 1870 and 1890 and then more than doubling again by 1900.  By the late 1920s, Joslin’s epidemic of diabetes had become the subject of newspaper and magazine articles. . . Emerson and Larimore published an analysis of diabetes mortality statistics in 1924, they reported a 400 percent increase in some American cities since 1900—almost a 1,500 percent since the Civil War.[15]

  2. As the sugar went down in price t1d went up (the t2d was not fatal, it was managed by diet).  And this trend continues in some areas more than others: “There is on the order of a 10-fold difference in occurrence among Caucasians living in different areas of Europe, and people tend to acquire the disease at the rate of their particular country”. [16]

  3.           There is more direct evidence through the use of markers for the development of t1d, the GAD, protein tyrosine phosphatase-like protein, and for IA, autoantibodies to insulin.  2,547 children were at increased genetic risk for t2d.  142 developed IA and 42 progressed to t1d.   Information on intake of fructose, sucrose, total sugars, sugar-sweetened beverages, beverages with non-nutritive sweetener and juice was collected prospectively throughout childhood via food frequency questionnaires.” [17]  They were followed for 10.2 years.  Conclusion:  Total sugar intake was significantly associated with an increased risk of progression to type 1 diabetes in children with IA,” (supra Lamb).   The use of 2 genetic markers in screening for the observational study o produce only a low percentage of t1d at 10.2 years follow up.

  4.                 The role of T cells has been studied but what initiates the process is in need of further research. The challenge for the future is to determine which factors contribute to the loss of tolerance to beta-cell antigens, and to define what measures T-cells can provide to suppress autoreactivity, since it is becoming increasingly evident that T-cells provide a two-edged sword: some T-cells could be pathogenic, but others can regulate the disease process and thus form new targets for immunointervention.” [18]  Among the factors associated with t1d, besides genetic, are vitamin D3 and its receptor, viral infections, cytokines and chemokines, and the western diet.[19]

  5.           Consistent with the observation of William Osler, the incidence of t1d is rising:  “Across Europe, the average annual increase in the incidence in children under 15 years is 3.4%.” [20]  Finding the process is a drug oriented approach, finding the environmental causes is a prevent approach.  Unfortunately, 95% of the research is focused of processes.  The environmental role, why there is a steady increase in t1d remains unknown.

    It doesn’t stop with youths, given the drug management of t2d, about 20% of those with end-stage t2d, those on high dose of insulin are likely to have LADA,, latent autoimmune diabetes in adults.  It is a form of t1d that comes on slowly among those diagnosed with t2d.  It would also explain why for some dietary management of t2d has disappointing results, and the same for those with bariatric surgery.  And like with t1d there is degrees of beta cell destruction, thus a degree of the dependence on insulin to control their serum glucose and mask the symptom of t1d. 

About 80% of all LADA patients initially misdiagnosed with type 2 (and who have GAD antibodies) will become insulin-dependent within 3 to 15 years (according to differing LADA sources). . . .  It is estimated that between 6-50% of all persons, depending on population, diagnosed with type 2 diabetes might actually have LADA.[10] This number accounts for an estimated 5–10% of the total diabetes population in the U.S. or, as many as 3.5 million persons with LADA[21]

          The research and existence of the condition doesn’t get the attention the numbers would justify.  Pharma is happy lowering glucose with drugs, and the more t2d progress the more drugs.  There is a Wikipedia article and some journal articles: 

Latent autoimmune diabetes in adults (LADA) is a disorder in which, despite the presence of islet antibodies at diagnosis of diabetes, the progression of autoimmune β-cell failure is slow. LADA patients are therefore not insulin requiring, at least during the first 6 months after diagnosis of diabetes.  Prospective studies of β-cell function show that LADA patients with multiple islet antibodies develop β-cell failure within 5 years, whereas those with only GAD antibodies (GADAs) or only islet cell antibodies (ICAs) mostly develop β-cell failure after 5 years. .[22]

          Just what drives the destruction of beta cells is not known, but the association with our high fructose diet, increasing IR through drugs, and the lack among the LSPs create a compelling links to our current treatment and the western diet.  What has gone wrong with the immune system, and which cells, this needs to be confirmed.  It is the B4, it flows from the pattern of other conditons.  The message of Dr. Robert Lustig, that sugar is a slow poison like ethanol, finds supports from many sources. 

 

14.  Amino acid and insulin:  It is widely circulated that certain amino acids raise inulin; the combination of essential amino acids raise insulin the most.  It is a topic I have been pondering over since 2015.  Why should insulin go up when amino acids increase in the blood?  I stopped nibble on cheese during my intermittent fast in the morning.  In 2018, I found an article which stated that it only happened when consuming proteins and carbs.  So I started again cheese nibbling.  Then in December of 2019 I searched insulin amino acids and fond that the glucose amino acid combo was wrong, that the essential amino acids (30 grams infusion) would cause for 1 hour an insulin spike significantly greater than any one of the amino acids.[23]  The spike of the 30 was similar to an infusion by glucose.  So why has nature given us an insulin spike for essential amino acids.

That they be essential entails ,that insulin doesn’t respond to the non-essential amino acids which are synthesized as needed, this suggests that the insulin has another function besides stimulating glycogen synthesis, the release of glucose by the liver, and the uptake by cells of glucose.  Insulin also stimulates the product and release of two androgens, IGF1 and IGF-2—insulin like growth factors.  The insulin rise is because of the need to utilize the amino acids which can’t be stored.  The growth factors stimulate skeletal muscle and other targeted tissues growth.  Thus insulin is signalling for the synthesis of proteins as needed.  I suspect that this doesn’t throw the Randle cycle into glucose metabolism unless there is significant amount of carbs—not a common occurrence among paleo peoples.  The modest drop in serum FFA during the insulin spike suggest that fat metabolism continues.  

Unlike the affluent populations, paleo peoples didn’t make a ritual out of meals, but for special occasions.  They didn’t eat a balance meal, but rather often ate just one food.  Thus they would eat meat without starches, or starches such as taro without meat, or just nuts; etc.  Secondly scarcity of meat and other protein sources in some populations supports a set of thrifty genes for construction of proteins.

As for my diet, I am still doing the intermittent fast, and since I am at my ideal weight, I am not on a weight reduction program.  The last time I was in 2003, when after 2 weeks with relatives, I put on 15 pounds, which I promptly took off when returning to California.  Since then with the supplement of testosterone high dose from a compounding pharmacy, I have not attempted to lose weight.  I naturally stay within the around 160 lbs.  The WCS is working as designed.  Prior to that since I was 27, I would watch my weight, and when it creeped up 6 pounds I would cut back on portions.  I believe that the testosterone makes a major difference, and that I was on two 325 mgs of aspirin daily—aspirin lowers serum glucose. 

With my current diet my snacks are small portions of cheese, about 8 grams with about 10 grams of butter, or I eat bell pepper with homemade Russian dressing.  Small portions low in carbs keeps my insulin low and I stay in mainly the fat metabolizing mode.  I have come to believe based on a number of trials with alternate day fasting and calories up to 500 per day women and 600 men that the results aren’t compromised and the compliance is significant.[24] The complexity has promotes efficiency,[25] thus I presume on indirect evidence that proteins with fats in moderate amounts do not overturn the apple cart, that they are an ideal snack in addition or with leafy vegetables.     

I mention this about proteins so that those who wish to try out intermittent fasting, high fat diet or alternate day fasting will have some tips by one who is strong in nutritional science and practical experience. The evidence supporting both long-term water fasting, and also low carb fasting comes from many directions.   

 

15. A listing of what is best for dieting for weight loss, managing diabetes, and lowering risk for CAWD (in approximate order of importance):

SOCIAL FACTORS:  building the will power to behave differently

  1.  Enlist support of roommate, significant other, friends, family, and others

  2. Watch daily the documentary and lectures at http://healthfully.org//rh/id7.html

    ON DIETING:

  1. Intermittent fasting

  2. Extended low carb fasting

  3. Alternate day fasting[26]

  4. Very low digestible carb snacks[27]

  5. Ratio of fats 75% to carbs 25% in calories (not counting proteins)

  6. Hormone replacement after the age of 60 men 50 women (6:2)

  7. On non-fasting days no digestible carbs 3 hours before going to sleep

  8. Strenuous work or exercise including weight training—especially if on HRT



[1] Wiki, metformin, Dec 2019

[2] When examining the use of statins, on the model of how it works, it is a major cause of dementia.  Surprisingly, there are a number of population studies which “show” that statins lower the risk of dementia.  The autopsy studies find to prove it is Alzheimer’s disease in the dead portions of the brain clumps of amyloid and tau plaque (proteins).  (The tau involves abnormal phosphorylation).  I hold that because of the reduction in the production of ATP caused by a 40% reduction in the essential co-enzyme Q10, there is a corresponding reduction in cellular maintenance permitting this accumulation among the elderly.  Odd that pharma would fund studies that conclude a prophylactic effect.  Do they know something, and are doing damage control?  

[3] Wiki, metformin, Dec 2019

[4] Prof. James McCormack, lecture to physicians, YouTube, Metformin—the case of exaggerating both benefits and harms

[5] Wiki, biguanides, Dec. 2019

[6] Hirst, JA, AJ Farmer, et al, Feb 2012 Quantifying the effect of metformin treatment and dose on glycemic control.  ADA article with support of Pharma, there were 21 versions of the article, and the conclusion follows the pattern of positive bias for a patented drug.  Conclusion: “Evidence supports the effectiveness of metformin therapy in a clinically important lowering of HbA1c used as monotherapy and in combination with other therapeutic agents. There is potential for using higher doses of metformin to maximize glycemic control in diabetic patients without increasing gastrointestinal effects.”

[7] PLoS Medicine 2012;9:e1001204

[8] Diabetes Metab, 2014 Feb 3. Pii:S1262-3636

[9] NEJM 2008;359 – Sep 10

[10] And it gets worse, in that the study was unblended thus all non-objective outcomes ae subject to reporting bias, in a number of outcomes during the study multiple points were added to it (pharma’s common way of getting the outcomes they want), there was dropout period, in that 22% of the volunteers dropped out, and as stated before compared to the raw data there always is industry bias in clinical trials and their write-ups.  Finally these findings were never reproduced (thus the difference between these finding and the meta-analysis referred to above.   

[12] Fauber, Hohn, Elbert Chu, Oct, 2014, The slippery slope:  is a surrogate endpoint evidence of efficacy?  And in The slippery slope:  adverse events and runaway diabetes train.    

[13]  I had applied 1967 to go there but ended up in graduate school at the University of Manitoba. in philosophy  

[14] This slight-of-hand reflects the lower standard applied by Cochrane Collaboration, as made public when Peter Gotzsche was removed from their Governing Board, in a 6 to 4 vote of its 13 members. Sept 2018.  In an interview, Gotzsche wrote in a BMJ article Nov. 2018:  "Cochrane no longer lives up to its core values of collaboration, openness, transparency, accountability, democracy and keeping the drug industry at arm’s length."[  Madsen, KS, Y Chi, et al Dec. 3 2019 Metformin for prevention/delay of type 2 diabetes mellitus (T2DM) and associated complications in persons at increased risk for development of T2DM

[15] [15] Gary Taubes, The case against sugar, P. 7-8. What is now called t2d, was adult onset, was maned by diet, and only a few intractable cases would result in hospital admission, of which probably most had progress to LADA (Latant Autoimmune Diabetes Adult), thus the increase in cases were nearly entirely type 1.  Other sources support this conclusion.  Fredrick Madison Allen in his textbook, Studies concerning glysouria and diabetes, and Elliott Joslin (1869-1962) The treatment of diabetes mellitus:  with observations based upon three thousand cases (1923)

[16] Wiki, type_1_diabetes, Dec 2019. Triggers suggested “include dietary agents such as proteins in gluten, time of eeaning, gut microbiota, viral infectioins and bacterial infections like paratuberculosis.” Again the fruits of the wrong trees. 

[17] Lamb, Molly, Brittni Frederiksen, et al June 2015, Sugar intake is associated with progression from islet autoimmunity to type 1 diabetes: the Diabetes Autoimmunity Study in the Young

[18] Roep, Bart, March 2003, The role of T-cells in the pathogenesis of Type 1 diabetes: From cause to cure a seminal article covering attempts to unravel the processes and causes.

[19] Roep, Bart, March 2003, The role of T-cells in the pathogenesis of Type 1 diabetes: From cause to cure.  The article missed the association with dietary sugar, IR, and MTDD. 

[20] Ozougwu, JC, KC Obimba, et al (Nigeria) June 2013, The pathogenesis and pathophysiology of type 1 and type 2 diabetes mellitus

[21] Wiki, latent_autoimmune_diabetes_in _adults, Dec 2019

[22] Stenstrom, Gunnar, Andres Gottsater, et al, Dec. 2005, Latent autoimmune diabetes in adults:  Definition, prevelance beta cell function, and treatment. The complexity of issues covering LADA is covered in Rolandsson, O, JP Palmer, March 2010, Latent autoimmune diabetes in adults (LADA) is dead:  long live autoimmune diabetes!

[23] Floyd, John, Stefan Fajans, et al, sept 1966, Stimulation of insulin secretion by amino acids

[24] One well received case is that of Michael Mosley, whose 5- 2 diet book made it to the best seller list:  The 8-week blood sugar diet:  how to beat diabetes fast (and sty off medications and The fast die t#1 New York Times Bestseller.  His documentary and interviews on YouTube are very good. 

[25] Patti, ME, Brambilla, et al, April 1998, Bidirectional modulation of insulin action by amino acids

[26] Both #s 2 & 3 a limited numbers of calories, 500 for elderly and women, 600 for men with very low carbs will not significantly tak the dieter out of fat metabolism through elevated insulin to cause conversion of free fatty acids to triglycerides or shut down autophagy

[27] This would consist of cheese, meets, fish, oils, green –leafy vegetables, nuts, in small portions so as not to significantly raise insulin and thereby shut down autophagy and causes the conversion of free fatty acids to triglycerides.  These types of snacks should be used to extend diet and make repeating of 1, 2, and 3 more likely.   

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On how daily excessive fructose damages the mitochondria and thus is the main cause for the conditions associated with the Western diet--much, much, more than insulin resistance, type-2 diabetes, and weight gain