Book on fructose, mitochondria, and the sickest of mammals

5:4 Diabetes pandemic & its natural cure

6. The tidal wave of diabetes mellitus:  Yes, we have a diabetes epidemic, going back a century and it is for both types of diabetes.  Starting with records from 1867 through to 1910 the admission for diabetes average under 2 a year, from then rocket to 80 in 1938--from diabetes admissions, Pennsylvania Hospital, Philadelphia (the nation’s first hospital, founded in 1751 by Benjamin Franklin and Thomas Bond).  William Osler, considered the father of modern medicine, reported in his seminal textbook, the principles and practice of medicine, 1892, of the 3,500 patients in the first 3 years of Johns Hopkins Hospital only 10 had been diagnosed with diabetes.[1]  “In the next 10 years 156 cases were diagnosed. . .  nearly doubling between 1879 and 1890, and then more than doubling again by 1900.” [2]  

There is over a twenty-year delay in the development of CAWD; cancer is but one example of such delay for CAWD.  In 1870 the US consumption was 70 pounds a year.[3] 

William Osler, 1892, and in all later editions, wrote of managing t2d with low carb diet (#9).  Dr. Richard Thomas Williamson in in Diabetes mellitus and its treatment (1898) wrote of low carbs; as did Fedrick Madison Allen and others. Mortality associated with t2d was limited to those who didn’t limit their carbs.  Today mortality associated with t2d is limited to those who manage the condition with drugs.  Fedrick Madison Allen (1879-1964) in his book[4] wrote of a very low carb diet, 8% of calories.

A diabetes mortality statistic in 1926, they reported a 400 percent increase in some American cities since1900, almost 1,500 percent since the Civil War….  In 2012, one in every seven to eight adults in this country had diabetes—12 to 14 percent, depending on the criteria used to diagnose it.  Another  30 percent are predicted to get diabetes at some point during their lives [this is consistent with the 26% of seniors, before the new lower guidelines (6:5)] …. Among U.S. military veterans, one in every four patients admitted to VA hospitals suffers from diabetes....  perhaps 95% have type 2 diabetes... the market for diabetic drugs and devices in the United States alone is over thirty billion dollars yearly.[5]

The pandemic of t2r, ischemic events, cancer, and Alzheimer’s disease[6] are diseases of the 20^th century along with the conditions of obesity, fatty liver, hypertension, and IR.  Prior to that it was rare, except for the affluent.   

Before 1922, t1d was not treated because there was no treatment; most died in the first year.[7]  The condition was very rare prior to 1900, thus the literature on early-onset diabetes was thin and physicians were concerned with the treating the condition of affluence, t2d.  Diabetes mellitus meant back then type 2 diabetes unless otherwise specified, and I shall follow that usage in this chapter.  

From the fact that it is a recent phenomenon, genes can only be a very minor CC. Allow me to explain, if t2d could be caused by genes, condition would occur among the LSPs.  Evolution has eliminated genes that promote t2d among the LSP.   When LSPs switched in number to the western diet, they were more devastated by the diet. They don’t have several generations of high sugar diet eliminating the early onset t2d group. 

One mystery is the different effects upon 2 populations, the Austrian aborigines and the Orientals (Chinese and Japanese are best documented).  Lacking the 2 centuries of culling the most susceptible coupled with the increased marketing of high sugar foods entails that the Australian aborigines are more effected than most populations who have in the last century adopted the high sugar diet.  Another group is the Pima Indians in Arizona, but not those in Mexico, they are still on a moderate sugar diet.  Though the Chinese Japanese consume less sugar the aborigines, those of normal weight are developing t2d at a higher rate compared to the European who have had 2 centuries of genetic culling.  

Many former LSPs have become heavy drinkers, made severe by the reduction of boredom and by social conditioning. Unfortunate, the high glucose content of beer entails a delayed metabolism of both fructose and ethanol in the liver, thereby increasing their pathogenic consequences.[8]  The combination of sugar and beer explains the very high rate of t2d among aboriginal peoples in Australia and the American Pima Indians.  The literature fails to consider the role of ethanol in addition to sugar.  This too probably affects the rate of fetal alcohol syndrome, and other conditions.  Ethanol also increases malondialdehyde and decreases the protective glutathione.[9]  Ethanol also very significantly lowers the absorption of B vitamins, and thus is causal for major health effects given the B vitamins multiple functions.[10]

I say this because when a person in our society states that t2d runs in their family, the possibility of these three other CCs, ethanol, high carbs, and excessive sugar, they are much more likely the cause than genes.  Chance also could explain familial link.  Take a large population and some will be struck by lightning twice, with a condition that occurs in 26% of seniors, the rate for 3 developing t2d out of 15 close senior relatives is over 50%.[11]  There is also a high concordance with obesity, as too for certain prescription drugs.  All these are variables that increase the risk of developing t2d.  Genes are less a cause than diet, ethanol, and obesity, and studies for genes aren’t considering the contravening variables,  Again, we have blaming the victim for their genes instead of the corporations which manipulate social behavior.  

Sources for B vitamins also include legumes (pulses or beans), whole grains, potatoes, bananas, chili peppers, tempeh, nutritional yeast, brewer's yeast, and molasses. Although the yeast used to make beer results in beers being a source of B vitamins,^[3] their bioavailability ranges from poor to negative as drinking ethanol inhibits absorption of thiamine (B₁),^[4][5] riboflavin (B₂),^[6] niacin (B₃),^[7] biotin (B₇),^[8] and folic acid (B₉).^[9][10] In addition, each of the preceding studies further emphasizes that elevated consumption of beer and other alcoholic beverages results in a net deficit of those B vitamins and the health risks associated with such deficiencies.[12]

Yes, genes are relevant, but age is more relevant with over 50% of the diabetics are over the age of 55.[13]  The concordance of identical twins is 50% for t1d;  However, for t2d a 20% to 40% concordances is not significant given the role of similar environment of siblings and the womb environment,[14] and that 26% of senior have t2d, and overall population.  The concordance for t2d is close to the background frequency of the general population and adjusting for shared environment it is very close.  Genes are not a major cause for t2d.  It is the cancer story all over again, blame the genes and not the diet; a diet which causes MTDD.  

The high concordance of identical twins for t1d, this only shows that the western diet must occur first because t1d is virtually unknown among LSPs.  This is not surprising given the role of fructose and MTDD.  The genetic cause exists only on the western diet.  This occurs with other CAWD such as AD and the APOE4 gene,[15] in that AD is virtually unknown among LSPs. 

7.  Early western history of diabetes:  The diabetes (type 2) is an ancient disease with Aretaeus of Cappadocia is credited with the first description of the condition around 130 AD and the term comes from the Greek.  

Diabetes in Greek means the thing or fluid that runs through, like a water pipe.  “Diabetes [type 1] is a strange affliction, rare among men…. The course is through the kidneys and the bladder; for the patients never stop making water…. The nature of the disease is chronic and takes a long period to form; but the patient is short-lived, if the constitution of the disease be completely established; for the melting is rapid, the death speedy. [16] 

Galen a Greco-Roman a generation later writes on diabetes in several works: 

I am of the opinion that the kidneys too are affected in the rear disease, which some people call chamber-pot dropsy, other again diabetes or violent thirst [type 1].  I have seen now only twice when patients suffered from inextinguishable thirst. (Supra)

Others state that the first complete clinical description of diabetes was made by Aulus Cornelius Celsius (30 BC–50 AD), the Roman encyclopedist whose De medicina volume survived; a reading confirms Aulus’s priority.  And not surprisingly, Hippocrates wrote (or was added to his writings by later Greeks)[17] probably about diabetes mellitus, in that he refers to excessive urination, but the condition wasn’t described.  Gemmill lists 11 Greek and Latin medical authors who mention diabetes or excessive urination.[18]  Some associated diabetes with diet.  Lacking science on metabolism and nutrients, there wasn’t in the literature a recommendation for management of t2d.  The unique symptoms for diagnosis (thirst and urination) creates a bias for reporting the condition.  How common t2d among Romans and Greeks is but a guess.

There are descriptions by the ancient Chinese, Indians, and Egyptian, with the earliest description of diabetes is in the Ebers papyrus (c. 1550 BCE) of the symptom of extreme thirst and urination are for t2d.  In about 400 BC the Indian physician Susruta-smahita described the medical knowledge of his day (with later contributors) in 134 chapters.  Therein are described 1,120 illnesses, 700 medicinal plants, and an extensive description of surgical procedures.  It might have had an effect upon the Greco-Roman understanding of the condition and thus the development of European medicine.  Alexander the Great had invaded India and built several cities.  He gathered information on wild life, plants, customs of people and other matters that might be of interest for his teacher Aristotle who remained in Greece.  Through Alexander and the Greek settlements, there was a conduit for Eastern ideas, similarly for Babylonian scholarship

8. Diabetes care before the drugs for t2d:  The simple fix:  A common-sense analysis to present for those with t2d.  It is followed brief a simplified explanation as how fructose damages tissues and increases risks for CAWD.  An explanation as to the mechanism—not merely association.  A great handout to those in need.   

Consider type-2 diabetes (t2d) like an allergy to glucose.  If it was to peanuts and every time you eat some there was hives, swelling, eczema, abdominal pain, you would avoid eating them.  Consider if every time you ate more than 50 grams of easily digestible carbs you would feel crappy:  have increased thirst, frequent urination, itchiness, fatigue, and reduced cognitive functions, then you would avoid excessive carbohydrates.  (That is what is felt by those with t2d when it becomes symptomatic; their glucose is above 18 mmol/L which is 327 mg/dL). 

Now consider if there was a drug which would hide the unpleasant effects from your peanut allergy, yet the peanuts were still toxic, and eating them regularly would gradually cause end-stage health consequences within an average of 15 years, would you take the drug and continue to eat peanuts?  Then why take the drugs that promote insulin resistance and death from comorbidities of t2d and side effects of the drugs?  Would you if diabetic avoid peanuts, then why not carbs? 

The common warning is that replacing carbs with fats is worse for health then the peanut diet. That argument is supported by tobacco science, profits before health.  There are a pile of journal articles proving the opposite.  Yet the food and drug industries publish in journals crapolla articles repeating the lipid hypothesis that saturated fats and cholesterol are artery clogging. 

Low carbs entail using fats for energy.  The alternative to carbs is fats.  The healthiest are the  saturated fats.  They are stable, don’t become rancid.  Unsaturated fats become rancid, Checkout scholar.google for journal articles on unsaturated fatty acids + rancid fats.   Secondly, in autopsy studies of coronary blood vessels that caused a thrombosis, the percentage of cholesterol is between 7 and 22%  Cholesterol isn’t the main chemical making up plaque.  Yes, we have the history of cigarettes repeated about fats and cholesterol.  The illness care industries and food manufactures use the same rule book as the tobacco and alcohol industries use.  The healthful path is to follow a low carb, high saturated fat diet.  Most type 2 diabetic patients on this strict diet will become drug free, since their blood glucose is normal on a New Atkins (keto) diet.  Moreover, the comorbidity risk factors go way down.  Before drugs since the 1890 the low carb diet was used to managed type 2 diabetes, then drugs were used starting in the 1950s.

END OF FIRST PART   ---   SECOND ON SCIENCE on fructose making us sickest mammals

Pharma taught doctors that elevated glucose is toxic.  Wrong, fructose causes mitochondrial dysfunction which causes insulin resistance (IR)—constant elevated insulin.  The combination of dysfunctional mitochondrial and IR causes increased risk of heart attacks, blindness, kidney failure, cancer dementia, amputation of legs, diabetes, obesity and other conditions associated with the high sugar western diet (CAWDs). 

The role of glucose in CAWD is it causes the use of drugs to stuff cells with glucose.  That harms the cells:  too much glucose causes excess osmotic pressure in the cells.  To lower the osmotic pressure, cells turn on the polyol pathway which converts the extra glucose to fructose to lower the osmic pressure in the cell.  Fructose being 20 times net more reactive than glucose damages the cell, and on a high sugar diet that rate of damage is more than the repair systems can handle.

There are 2 sources for excess fructose, the high sugar diet (sugar  is one half fructose the other half glucose).  The second source is the polyol pathway that converts glucose to fructose in 2 steps.  With repeated excess fructose cells are damaged.  In the U.S. the average sugar consumption all sources including fruits is over 150 pounds a year, with half the population consuming more than 150 pounds.  That is over 10 times the amount consumed by the paleo diet, which is what our biological system evolved for. 

Particularly vulnerable are the mitochondria in the cell.  Mitochondria have their own DNA, and it is not protected like the DNA in the nucleus of the cell.  Damage to the mitochondria DNA is passed on to the next generation of mitochondria in cells, and that error continues as they are replaced in the cell.  Since the mitochondria convert glucose and fats to the energy molecule, and mitochondria provide over 90% of the energy molecules, a reduction in the production of ATP, this entails that every system in the body is not working up to optimal evolutionary levels, for there is a less then optimal amount of ATP to run cellular processes, such as the production of replacement collagen.  That is how damage to the mitochondria increases the risk for all the conditions associated with the western diet.  It is like a battery not having enough voltage to run the various functions in the car.  This damage and reduced production of ATP is why we are the sickest of mammals, the western high sugar diet is the cause. 

When people age there is a natural decline in in the mitochondrial production of ATP, add to this the damaged mitochondria, and we much sicker compared to 1950, especially the aged. 

Now for how this causes insulin resistance.  The slowed metabolism of glucose by the mitochondria causes the pancreas to release more insulin to lower blood sugar.  Insulin has 16 regulatory functions through other hormones it controls.  Insulin resistance (IR) disturbs these regulatory functions.  For example, excess insulin causes excess of the hormone leptin which controls appetite and fat metabolism. The Consequence is a gain in weight. 

The way to avoid excess insulin is to eat a low-carb high-fat diet.  As stated in the first section, type 2 diabetes can will be reversed on a strict low-carb diet, and thus the comorbidities associated with diabetes.  The same applies to those diagnosed as prediabetic.  Since about 90% of Americans have insulin resistance, they too will benefit from a low carb diet.  Their excess insulin is keeping their glucose down, but they too are at risk for CAWDs.  All of us, not just the fat and the diabetic.  Alzheimer’s, cancer, joint replacements, dementia strikes everyone on the western diet, but not the paleo peoples on a traditional diet. 

Now back to the topic of the traditional management of t2d.  Type-2 diabetes and gout because they were conditions of affluence, were easily diagnosed, and because of the deep pockets of patient, they attracted medical history and research.  Climates with year-round fruits, those where fruits are dried, use sources of sugary syrups such as honey and maple syrup, there were some inhabitants who would develop t2d’s. This resulted in early reports of diabetes in the literature of Egypt, Middle East, India and China.  The Arab world, mainly in Byzantium, had a library of Greek and Latin texts including their medical works.[19]  “During the Middle Ages, Arabic was a major vehicle of culture in Europe, especially in science, medicine, mathematics, and philosophy.” [20]  The surviving Greek and Latin writings were translated into Arabic.  This formed a foundation for the flowering of medical science in the Arab world.  The Catholic monasteries bought the Arab texts, including the philosophical and literary writings.  These works were then translated mainly into Latin, and centers of learning acquired the Latin translations.  This laid the foundation for the exit from the Dark Ages, and its replacement with the era now as The Enlightenment. 

Diabetes became more of an issue in Europe due to the popularity of figs, grapes, and dates which are easy to preserve.  The Greek and Romans cultivated these fruits.  Cato the Elder (234 to 149 BC) in c. 160 BC in De Agri Cultura describes four strains of figs.  In the Arab world, diabetes became common, Maimonides (1135 to 1204) claimed to have seen more than 20 cases.  Abd al-Lalif al-Baghdadi (1162-1231 produced a treatise dedicated to diabetes.  

The modern western medical literature on diabetes mellitus goes back to the Swiss Paracelsus.  In the 16th century, Paracelsus (1493–1541) contributed in several areas to the medical revolution and is considered the father of toxicology.  He described diabetes as a constitutional disease affecting many organs.  "Diabetes irritates the kidneys and provokes excessive urination. He reported that evaporating urine from a diabetic patient left an excessive residue, which he called salts." [21]   He advised tasting the urine for sweetness.[22]  

A  classic case is Henry the VIII of England  (1491 to 1547).  He had 4 signs for adult diabetes: obese in his 20s, morbidly obese in this 40s, weighted 392 pounds (28 stones), waist of 54 inches when he died, sores on his legs that wouldn’t heal, and death in his 55^th year from infection.[23]  One observer wrote that you could smell the king when he was 3 rooms away, referring to his infected legs.[24]  His physicians in England were not aware of adult diabetes or the urine testing.  Incongruously, the speculation on his death doesn’t mention t2d, but find the cause a jousting wound in 1536.  He died 11 years later.  The painting showing his face in 1537 is that of a morbidly obese person, made all the more so by a comparison to the 1509 coronation portrait (age 18) of the lean Henry.  A jousting wound to his leg that wouldn’t heal for 11 years is an unlikely cause of death, unless its failure to heal was because of t2d.

Paracelsus wrote of several decades after Henry’s death.  Testing urine entered the English medical literature with Thomas Willis (1621 to 1675),[25] who described the urine of diabetics as “wonderfully sweet as if imbued with honey or sugar.”[26]  Mathew Dodson (1732-1784) an English physician and experimental physiologist in 1776 identified it as sugar.  He collected 2 quarts of urine[27] and evaporated it gradually.  He wrote that the residue smells like brown sugar.  The standard test then was tasting the urines and/or blood for sweetness.

Because of the lag in sugar chemistry, basic distinctions between glucose, sucrose, fructose, lactose, and the alcohol sugars were not recognized in this early period: 

Glucose was first isolated from raisins in 1747 by the German chemist Andreas Marggraf.^[8][9] Glucose was discovered in grapes by Johann Tobias Lowitz in 1792 and recognized as different from cane sugar (sucrose).  Glucose is the term coined by Jean Baptiste Dumas in 1838, which has prevailed in the chemical literature. Friedrich August Kekulé proposed the term dextrose (from Latin dexter = right), because in aqueous solution of glucose, the plane of linearly polarized light is turned to the right....  Since glucose is a basic necessity of many organisms, a correct understanding of its chemical makeup and structure contributed greatly to a general advancement in organic chemistry. This understanding occurred largely as a result of the investigations of Emil Fischer [1852-1919], a German chemist who received the 1902 Nobel Prize in Chemistry for his findings…. For the discovery of the metabolism of glucose Otto Meyerhof received the Nobel Prize in Physiology or Medicine in 1922. In 1947, Bernardo Houssay (for his discovery of the role of the pituitary gland in the metabolism of glucose and the derived carbohydrates) as well as Carl and Gerty Cori (for their discovery of the conversion of glycogen from glucose) received the Nobel Prize in Physiology or Medicine.[28]   

In 1791 Johann Peter Frank, a German physician, developed a yeast test for sugar in the urine; this gradually replaced taste tasting.  In 1788 Thomas Crawley linked the pancreatic dysfunction to diabetes.  Then John Rollo (d. 1809), a Military Surgeon General for the Royal Artillery; he described in 1797 An account of two cases of diabetes mellitus with remarks as they arose during the progress of the cure (in 2 volumes) the low-carb diet.[29]  A second expanded edition appeared in 1806.  Gradually, the high fat-protein, low carbs became the standard treatment. 

A century after to Rollo work--if not early--physicians were determining the severity of adult diabetes by the amount of sugar in the urine over a 24-hour period.  It was crystalized, dried and weighed; under 200 grams was mild, and over 500 grams severe.[30]  Medical science progressed slow for diabetes. 

An excellent resource on the state of science is the 1913 book by the Harvard Professor  and physician Frederick Madison Allen (1879 to 1964), his Glucosuria and diabetes (1,179 page) was published by Harvard University.[31]  We haven’t made that much progress in the last 108 years.  His research on diabetes.  It featured hundreds of animal experiments, and 1200-item bibliography.  For t1d, he set up a clinic for children in 1921 and used an extreme low-carb, starvation diet.[32]  Insulin was discovered in 1922, and became available in significant amounts in 1923.  He went on to research hypertension, and several other health topics. More on the history of diabetes, including the development of insulin and current treatment, is in the next chapter.  

9. The diet in the pre-drugs for t2d era:  The European literatures on LCHF goes back at least to 1797 when Dr. John Rollo (supra) of the UK.  In 1898 Dr. Richard Thomas in his Diabetes mellitus and its treatment wrote, “that all carbs should be cut off”.  He went on to write, “Ever since Rollo published his book on diabetes in 1797, and pointed out the value of restriction of the carbohydrates in the food, it has been acknowledged that of all forms and methods of treatment this dietetic one is the most important.” 

Sugar became inexpensive by 1810 because of selective breeding of sugar beets and sugar cane.  The condition of affluence gradually became common as the diet changed for the bottom 95%, and within a century t2d became common.  With the science not developed as to what causes diabetes mellitus, nor was it realized that the t1d and t2d had different causal foundations; consequently, they were grouped together.  Gradually the use of LCHF became the standard treatment by the 1880s in Europe, and learning from Europe LCHF diet a decade later was the standard treatment in the US. 

“Those managed with low-carb diet lived as long as those without t2d.”  wrote Dr. Elliott  Joslin in 1918.  Joslin had gone to Europe in the late 1890s to learn from the leading German physician; his mother had become diabetic.  The LCHF diet very gradually reduces IR, and thus her moderate the risks for CAWD.  For those like Joslin’s mother who followed the diet, their health remained good and diabetes did not adversely affect life expectancy.  Many had reversed their diabetes—possible his mother on the LCHF diet—records are lacking. 

The importance of treating adult-onset diabetes was rising since the Civil War.  Gary Taubes mentions Dr. William Osler (considered the father of modern medicine), but not his low-carb treatment.[33]  Taubes was writing on the association of increase sugar with the delayed increase in t2d: 

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…. 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.[34]

The leading medical book in sales, The principles and practice of medicine (1892) by Sir William Osler,[35] the most used medical book of that period. Sir William Osler (1849 to 1919) died from the 1918 flu pandemic[36] but it continued in new editions by Dr. Thomas McCrae.  “The text was translated into French, German, Russian, Portuguese, Spanish and Chinese, and for over 40 years it was the world's most significant medical textbook.” [37]  On diabetes mellitus in the 1909 Edition:  “the use of starchy and  saccharine articles should be restricted.... let the patient eat food of easy digestion, such as veal, mutton, and the like and abstain from all sorts of fruit and garden stuff.” (P 420).  There was a major expansion of William Osler’s medical textbook on diabetes from his first publish edition:  in the 1910 edition there are 16 pages on diabetes.  On pages 421-22 he develops the LCHF diet for adult onset (the children didn’t benefit because most died within a few months).  Osler’s section, “Medical Treatment:  This is most unsatisfactory, and no one drug appears to have a directly curative influence [for adult diabetes].  Opium alone stands the test of experience as a remedy capable of limiting the progress of the disease (Supra 423).” [38]  A similar LCHF and praise of Opium is in his first edition, 1892.  Osler was the authority that physicians relied upon.  His early editions listed a number of drugs including alcohol, opioids, arsenic, and potassium bromide.  Osler and Thomas McCrae in the 1921 edition found them ineffective. 

Of the 1,118 pages in 2 volumes in the 1909 Edition (which I have the reprint) there are 11 sections; they are similar to those in the current Merck Manual.[39]   Osler’s section, 1909 edition, is divided into topics:  definition, etiology, morbid anatomy, the pancreas in diabetes, symptoms, complications, course diagnosis, prognosis, treatment [consisting of diet], and medicinal treatment [10^th page].  Of interest is the current science (1909), their knowledge of the condition, and its treatments both dietary and medicinal, on t2d below:   

Definition—a disorder of nutrition, in which sugar accumulates in the blood and is excreted in the urine, the daily amount of which is greatly increased.... and that the excretion of sugar must take place after the ingestion of moderate amounts of carbohydrates.... by functional or organic disease of the islands of Langerhans in the pancreas.  This substance seems necessary for the burn up of carbohydrates.... normally  the carbohydrates of the food are stored in the liver and muscles as glycogen [P 411].... By functional or organic disease of the Island of Langerhans in the pancreas [P 412].... The liver is usually enlarged; fatty degeneralism is common....  Diabetes is secondary to pancreatic lesions.... a considerable percentage of cases diabetes lesions of the pancreas are found; 50 percent show chronic intestinal inflammation [P 413].... the total amount [of glucose in urine] extracted ranged from 320 to 640 grammes and in exceptional cases from 1 to 2 pounds [415]. Complications [listed p 417]:  (a) CUTANEOUS; (b) PULMONARY; (c) RENAL; (d) NERVOUS SYSTEM (1) Diabetic Coma, (2) Peripheral Neuritis, (3) Mental Symptoms, (4) Special Senses--Cataract, (5) Sexual Functions [P 417-19].  Prognosis:  Practically, in cases under forty years of age this outlook is bad;[40] in elderly persons the disease is less serious and much more amenable to treatment.... Treatment:…. Diet: . in the hospital is totally lack of easily digested carbohydrates and includes well-cooked greens, [P 420].... This diet contains about 200 grammes of albumin and about 135 grammes of fat.  The effect of this diet on sugar excretion is remarkable.... In cases in which the urine becomes free of sugar gradually increase quantities of starch up to 20, 50, 100 grammes are added daily.... In patients on a strict diet who continue to excrete from 0.1 to 0.5 percent glucose, he advises a “hungry-day,” during which all foods are cut out for 24-hours [P 421].  [The list of foods forbidden are the same as those for a ketogenic diet of today with the addition of liver and green vegetables, P 421-2].... MEDICINAL TREATMENT –This is most unsatisfactory, and no one drug appears to have directly curative influence.  Opium alone stands the test of experience as a remedy capable of limiting the progress of the disease [P 423].[41]           

This sampling from Osler’s 16 pages is a window on the then current knowledge and treatment of diabetes mellitus.  Have we progressed? 

Among the associated signs of diabetes, Osler found was NAFLD and sclerotic liver, high blood triglycerides, sugar in urine, and blood glucose as high as 0.4% compared to the normal 0.15%,  High triglycerides is caused by insulin resistance causing FFA conversion.

Frederick Madison Allen (1879-1964) at Harvard University was the first of the American doctors to specialize in diabetes and become the leading authority.  He ran a series of experiments, mainly on dogs, in which he removed their pancreas to produce t1d.[42]  He found that feeding them carbs caused glycosuria, while feeding them fats decreased or it disappeared the glycosuria.  Allen published in 1913 Studies Concerning Glycosuria and diabetes, a 1179-page tome covering his several hundred experiments on animal and metabolism related to diabetes and significant space devoted to works of others on diabetes.  Another window on the golden era of medicine.  (The work can be read at Google Books for free, 2019)

Allen published in 1919 Total dietary regulation in the treatment of diabetes.  This book was based on meticulous descriptions of 76 cases--a convincing demonstration of a LCHF diet.  Since those with t2d patients produced some insulin,[43] Fredrick’s patients would be reintroduced to green vegetables until glycosuria reappeared.  “A review of Frederick M. Allen's case histories shows that a 70% fat, 8% carbohydrate diet could eliminate glycosuria among hospitalized patients.  A reconsideration of the role of the high-fat, low-carbohydrate diet for the treatment of diabetes mellitus is in order” [44]    Allen also established a clinic in New Jersey for children with t1d, which only functioned for a couple of years, then insulin became available.  Prior to insulin, his work made him the leading authority on diabetes mellitus in the U.S.  Osler is not counted since he didn’t do research or set up a clinic, nevertheless his influence was the greatest.

By 1927 with the development of insulin in 1922, Allen’s focus changed to hypertension, metabolic disorders, and later cryogenics surgery and cancer. 

10. Dietary low-carb management of t2d, Merck 1950-61:  extreme low carbs go back at least to the 18^th century of adult-onset diabetes for western medicine, and probably 3-thousand years or more based on references to urine and diet in surviving fragments from Greece, India and Egypt.  Choosing practices within my lifetime, 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 decisions 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[45] and food containing them in large amounts must be eaten sparingly (see Diets).... regularity 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., urine free of sugar, tested by a pharmacist or physician through evaporation], there are fewer complications.[46]    

The medical consensus was that elevated blood glucose was relatively benign until it became symptomatic above 11 mmol/L.  Merck manual was following that consensus, but as drugs came to the market, it followed the new, better treatment—new and superior are words attached to the new drugs on the block, and Merck U.S. in 1953 was “the largest US drugmaker.” [47]  Merck & Co. of the U.S. was founded in 1887 as a subsidiary of the German Merck which was founded in 1668.  That connection was broken in WWI when Merck & Co. was confiscated under the Trading with the Enemy Act of 1917.  Its stock was purchased by George Merck in 1919. 

Seemingly, Merck & Co, their The Merck Manual, is supporting the LCHF management.  Pharma loath an effective dietary management of a condition.  A more careful reading and an examination of the entire article reveals otherwise.  Merck favors the recommendation of Elliot Joslin, that of 30% of carbs, but up till and including the 1950 edition, they gave space to the widely used management with LCHF.  The Merck in my 1940 edition recommends:  “QUANTITATIVE DIETS IN DIABETES:  2,400 calories, 300 g carbs, 07 protein, and 89 fat.” [48]  This is similar to Joslin’s recommendation. Merck also mentions the low carb diet. 

The Merck Manual of Diagnosis and Therapy is the world’s best-selling medical reference book.  The manual is similar to Wikipedia medical articles, both follow the consensus of KOLs, but differs in that it focuses on treatment and thus is without the science.  Like Wikipedia the standard KOL generated treatments are praised and unlike Wikipedia it doesn’t have lines criticizing alternatives, they are ignored.    

Merck focuses in its articles on diabetes is the standard treatment.  So, have modern miracle medicines and the guidelines-generated standard-of-care that improved the lot of the diabetics?  Are new drugs better than diet?  Their articles changed from 30% carbs diet for adult diabetes to drugs and over 50% carbs. The next chapter, 5, takes a hard look at the drugs, this chapter is on diet. 

The drug industry doesn’t like a dietary fix, thus they contrary to clinical success pharma adopted Elliot Joslin and others approach to treatment.  Pharma rolled out diabetic ketoacidosis, blamed it on the metabolism of fats, and chose KOLs to spread that message, Eliot Joslin was the best-known expert for nearly 50 years.   Joslin (1869 – 1962) was the leading experts in treatment of diabetes.  He forgot his past and the treatment of his mother, By 1928, Joslin held that fats caused t2d, t1d, and diabetic ketoacidosis (DKA).  In 1924 Edition:  “the diet in health is made up chiefly of carbohydrates; the diet in diabetes is made up chiefly of fats.” [49]

Joslin switch to recommend in the era before drugs for t2d a 30% of carbs for the above reasons.  He forgot his German lesson from the best in Europe, his successful treatment of his mother, and others, all of whom were successful on a LCHF diet.  This Harvard Professor, Eliot Joslin became the leading authority for half a century, and his “Joslin Diabetes Center is the world’s largest research center, diabetes clinic, and provider of diabetes education.” [50]  I am getting ahead of the topic, his switch from LCHF to 30% and on DKA, diabetes ketoacidosis, they are in the next chapter—a detail of chemistry was ignored, DKA is a weak acid; moreover, lowering the pH of the blood is an ineffective treatment.  Merck is a drug manufacturer and their treatment manual follows the consensus of the KOLs. 

By 1940 two schools were mentioned for adult diabetes in The Merck Manual, 7^th Edition, P 343, that of the older dietary management of LCHF, and Joslin’s with carbs. Protamine, long lasting insulin had been on the market for 4 years; its action lasted up to 24 hours. Protamine zinc insulin was marketed for 2 years and last from 24 to 36 hours.   They are recommended for those who after 2-3 days of low-calorie diet still had polyurea (sugar in urine), Supra P 343.  The Joslin two books named above; they then recommended a diet with carbs.  The books warned that fats caused atherosclerosis--laying the ground for medications for treating laying the ground work for lowering cholesterol with drugs.  Insulin instead of diet, two more piece which cause me to conclude that Joslin was a pharma groomed KOL.

          Drugs came on the scene, other than aspirin,[51] with sulfonylureas, discovered in 1942 in France and licensed a few year later. In France but not the US.  When testing sulfonylurea as an antibiotic, it was found in a high dose it induced hypoglycemia in animals by increasing the release of insulin.[52]  Increasing insulin increases weight gain, IR, and the other CAWD (though of course pharma ignores these side effects and blame diabetes).  More on this and other diabetic drugs in the next chapter. 

By 1950 much of the major pieces for t2d were known and covered by Merck: 

Damage to the insulin producing cells of the islets of Langerhans, by causes as yet unknown, is responsible for most cases of diabetes mellitus.... In certain cases, the diabetic state results from increased insulin requirement [t2d] by the tissue cells to maintain normal carbohydrate metabolism… contributor factors are known.  Excessive consumption of sugar and fat.  [Again, slipping in an assault of fats though there was no quality evidence].  Heredity is apparently important.…  Pancreatitis, hemochromatosis, pancreatic tumors, and trauma….  It is estimated that between 1 and 2% of the U.S. population  are diabetics.  The liver in uncontrolled diabetes mellitus often is enlarged and fatty.  When symptoms do exist, they are so mild that they do not cause the patient to seek medical advice.[53]    

Merck’s 1950 recommends for all types of diabetes a “normal diet with the exception that the more rapidly absorbed carbohydrates and foods containing them in large amounts must be eaten sparingly….  fats 50 to 120 gm./day and carbohydrates from 150 to about 250 gm” P 274.  “The disease is most common in the 5^th and 6^th decades of life and in prosperous individuals” P 268.  Long-term  obesity is mentioned as a cause in the manual’s previous article, P 266.  The treatment section, “One of the earliest decisions the physician must make is whether diet alone will suffice or whether insulin in needed in addition.”  However, this entails not the LCHF diet, but Merck‘s the 150 to 250 grams daily of carbs entails  drugs.   

By 1961, 10 Edition of the Merck Manual, 4 insulin types had replaced dietary management (drug table P 365)—in Europe sulfonylureas is the treatment of choice.[54]  So what happened to the diet?  I can hear the cash register pounding out the use of HFLC. 

Not surprisingly by the 10^th Edition of the Manual, “In general, the fat in the diet of normal- weight diabetic patients vary from 50 to 120 Gm./day and the carbohydrate from 150 to about 250 Gm” P 331-332.  This diet promotes insulin management of both type of diabetes mellitus. 

Gerald Reaven (1928 to 2018) was an endocrinologist and professor at Stanford University School of Medicine whose work on insulin resistance and diabetes achieved recognition including the annual Banting lecture in 1988 titled Syndrome X, which focused on what we now call metabolic syndrome, the grouping of cardiovascular disease, hypertension, insulin resistance, impaired glucose tolerance, and abdominal obesity.  Gerald Reaven was critical on the focus on carbs and the glycemic index:  “Raven also disparaged the glycemic index for putting the clinical focus on blood sugar whereas he considered insulin resistance the disease [like Dr. Joseph Kraft and others].  Reaven insisted for t2d treatment to restrict all carbohydrates.” [55]  He was marginalized on role of insulin resistance and sugar in the development of diabetes treatment—as too Joseph Kraft.  The natural progression of the business noose has tightened in the last 5 decades, the past has been hanged. 

The low carb diet was for over a century the most recommended diet by physicians.  Moreover, since the 1950 Merck Manual, Eight Edition, the science behind dietary management has made big steps forward both on the science on why the LCHF diet and fasting as to why they are the best way to lose weight, keep it off, and how to cure t2d.  This also applies to bariatric surgery.  But our standard-of-care hasn’t changed, thus the Merck editors don’t mention the dietary alternative over the last 50 years. 

Today it is known that the harm associated with t2d (not counting drug side effects) is from insulin resistance which slowly increases because of the medications and from MTDD, which is significantly greater with t2d than those with only obesity.  Given the many regulatory functions of insulin, its excess is driving the diabetic health disaster along with the MTDD.  Another CC is the higher intracellular glucose and its slowed rate of conversion to pyruvate, this increases frequency of turning on the polyol pathway that produces fructose and delays the conversion of fructose to pyruvate thereby increasing fructation.[56]  IR, MTDD, are the two major causes and as a result there is the increased fructation, along with the rest of the B-5 and S-5. 

11. Dietary management of t2d, and those with undiagnosed t2d:  I know several who have chosen to manage with diet instead of drugs their diabetes, but without going to the extreme of curing their condition through fasting and ketogenic diet.  How did these two groups fare, diet versus drugs?  Not surprisingly, I found not one perspective long-term quality study comparing the two groups long-term.  One study I did find wasn’t quality observational study using national records in Spain.  It found the “undiagnosed diabetes had a lower prevalence of hypertension, peripheral, dyslipidaemia, peripheral vascular disease and previous myocardial infarction than those with clinical diabetes, similar to that of those without diabetes.”[1]  The study of 400 consecutive patients admitted with acute heart failure to a hospital in Barcelona Spain.  Three groups, no diabetes 188 patients, clinical diabetes 149 patients, and undiagnosed diabetes 63 patients  That study only compared the three groups using healthcare records. At 7 years how each group fared was compared.  The undiagnosed group has a similar mortality rate to the diagnosed group. The limitation is the lack of tracking medications, because only a small percentage of the undiagnosed group would have gone untreated.  I want know the long-term health of those who went untreated, and a subgroup thereof who follow the LCHF diet without taking diabetic drugs for longer than 5 years.  I couldn’t find such a study.  Who would fund it and would an ethics committee approve it? 

12. Low carb diet for diabetes mellitus:  Allow me to repeat what is occurring with t2d:  increasing pancreatic release of insulin by dietary carbs, IR, and drugs stimulating production of insulin.  Excess insulin is a very bad thing (3:6).  Excess insulin affects many homeostasis processes.  In addition, since cellular fructose is metabolized last after glucose, with IR there is a slowed uptake of glucose because of MTDD, this entails an even slower uptake of fructose from the blood and delayed cytosol conversion to pyruvate in the ER, this increases fructation of proteins and UFAs transported into the MTD, thus causing a higher rate of MTDD when compared to those without IR.  For these reasons a low-carbs diet for those with IR is a healthful choice.  The damage by overstuffing cells also turns on PP’s production of fructose.  The longer it takes to clear the carbs from the cytosol, the longer it will take to switch to fat metabolism and turn on autophagy, another CC for CAWD.  The high level of insulin given its many regulatory functions is a major CC for the CAWD for those with IR and t2d. 

The management of t2d with drugs before the development of glucose meter (available in the late 70s in physician offices and the first home meter introduced in November of 1981) there was a major risk for hypoglycemia both for those on insulin and the other drugs for diabetes.  Monitoring consisted of urine testing.  But urine testing is only moderately associated with serum glucose.[2]  The low-fat diet was a major CC for hospitalization and death. This dietary problem has a dietary firx.

          The call for the low-carb treatment of t2d resulted in 2015 of a journal article with 29 signatures.  The article has 12 points, evidence that support low carbs, the 12 are compelling:  “It is not known who decides what constitutes evidence-based medicine but we feel that these points are sufficiently strong that the burden of proof rests on critics.” [3]  This is a seminal article concludes with a call for the science to dictate guidelines: 

12 Points of evidence [bold I consider more important] 

Point 1. Hyperglycemia is the most salient feature of diabetes. Dietary carbohydrate restriction has the greatest effect on decreasing blood glucose levels

Point 2. During the epidemics of obesity and type 2 diabetes, caloric increases have been due almost entirely to increased carbohydrates 

Point 3. Benefits of dietary carbohydrate restriction do not require weight loss

Point 4. Although weight loss is not required for benefit, no dietary intervention is better than carbohydrate restriction for weight loss

Point 5. Adherence to low-carbohydrate diets in people with type 2 diabetes is at least as good as adherence to any other dietary interventions and is frequently significantly better.

Point 6. Replacement of carbohydrate with protein is generally beneficial

Point 7. Dietary total and saturated fat do not correlate with risk for cardiovascular disease

Point 8. Plasma saturated fatty acids are controlled by dietary carbohydrate more than by dietary lipids

Point 9. The best predictor of microvascular and, to a lesser extent, macrovascular complications in patients with type 2 diabetes, is glycemic control (HbA_1c)  [Wrong, insulin resistance is the best measure]

Point 10. Dietary carbohydrate restriction is the most effective method (other than starvation) [water fasting] of reducing serum TGs [triglycerides] and increasing high-density lipoprotein [Misses that those with the highest 20% of cholesterol live the longest—Framingham Heart Study, started with 5,209 residents in 1948.  It is still running with the edition of a 3^rd generation.  Also missed  that triglycerides are a better predictor or cardiovascular disease, the best is insulin resistance]. 

Point 11. Patients with type 2 diabetes on carbohydrate-restricted diets reduce and frequently eliminate medication.  People with type 1 usually require lower insulin.

Point 12. Intensive glucose lowering by dietary carbohydrate restriction has no side effects comparable to the effects of intensive pharmacologic treatment [Missed that intensive lowering of glucose dose not lower the risks for the comorbidities of diabetes.].[4]

Each of these 12 points has several paragraphs with citations to published evidence and most of the 12 have appropriate graphs and tables.  This seminal 2015 article is focused on dietary management of t2d.  It should have been published in one of the 5 major English journals, but pharma’s noose has tightened, the BMJ has become the last to be tamed.  As for their criticisms of the ADA guidelines, the ADA and KOLs avoid confronting the evidence and continue to spew out their poisonous cocktail to physician in their CME classes, textbook chapters, and guidelines for the “progressive condition.”  The dieticians and media repeat it

Though the article is focused on diet for t2d, there is much more to understanding the forest.  Topics developed in this book prior on the CC for MTDD: fructation, IR, NAFLD, inflammation of the pancreas, the conversion of glucose to fructose in the polyol pathway thus fructation in biologically active cell, all these support the call for the low insulin thus low carb management and treatment of t2d and t1d (watch on YouTube and read Dr. Richard Bernstein’s book, he has t1d has been managing his t1d with low-carb diet for over 55 years). 

Not surprisingly is the failure of ADA guideline to mention lipid droplets in the liver and pancreas, and there is in those guidelines a total failure to recognize the issue elevated insulin caused by the medications which are the main CC for the conditions associated with t2d and its fatal progression.  It is long overdue to rediscover the past and again treat t2d with a low carb and for some a ketogenic diet and t1d with low carbs and insulin

I think of Ginter, my brother-in-law dead at 53, Ela Fitzgerald who had both her legs amputated below the knees, of Jerry Garcia at 53 and 8-days, dead from a heart attack, and my neighbor across the street below the age of 65, she died in 2021 from kidney failure after 4 years on dialysis.  Yes, I too cry out for low carbs like Bernstein, Westman, Volker, and the 26 others in a seminal article published 37 times since 2015 (different addresses);, but not in the big 5 English language journals. 

We all know friends and relative that have gone down the drug pathway to the lowered quality of life.  Treating glucose as shown by their examples is a failure.  Where is the major movement in the US for prevention of a once rare condition (”Between 1 and 2% of the population of the USA are diabetics”—Merck 1972, P 1186)?  What is the position of our government and the ADA on this dietary condition? 

The crapolla continues, unphased by the dietary fix, and the bad advice is poured out as the illness care industries frame the topic.  I found an 18-minute documentary, which list and refutes 6 of their pillars:

1    Diabetes is a chronic condition

 2   You must count calories and lose weight to improve diabetes[5]

3   A calorie is a calorie

4   The fat you eat is the fat you wear

5   Dietary fat causes insulin resistance and type two diabetes[6]

6   You need to eat carbohydrates to be healthy

It is by What I’ve Learned (his pseudonym) in Can you cure diabetes at https://www.youtube.com/watch?v=hpOP_HKeazU&t=18s  The quality is excellent.

13.  NAFLD, IR, and fatty pancreas leads to t2d:  “Virtually unknown before 1980, nonalcoholic fatty liver disease now affects over 30% of adults according to the 1999 NHAMES study and between 70% and 90% of those who are obese or who have diabetes.” [7]  Based on current obesity figure adjust for data flaws over half the adults have NAFLD.[8]  “While largely unknown in the 2000s, NAFLD, NAFL and NASH are the leading cause of chronic liver disease as of 2017.  People with NAFLD are likely to be asymptomatic − to have no noticeable symptoms, and often have normal laboratory profiles.... The diagnosis of steatosis is made when fat in the liver exceeds 5–10% by weight.” [9]  

Understanding the route from the liver to t2d entails understanding prevention and the best dietary treatment.  Since fructose has minimal effect upon insulin, and thus blood glucose, the measuring of insulin and glucose promoted the assumption—supported by the Sugar Research Institute—that fructose was harmless.  “It only became apparent by looking at the slow accumulation of fat in the liver. . . .  Replacing glucose with fructose increases liver fat by a massive 38 percent within eight day.” [10]  Between 50 and 70% of dietary fructose is utilized by the liver.[11]  Moreover, fructose can increase DNL 5-fold.[12]  Allow me to explain again, given the importance of this topic.   

1.           As prior mentioned (3:4), fructose causes MTDD first in the liver, because the liver is the most exposed organ via the hepatic portal vein from the intestines.  “Insulin signaling in liver is critical in regulating glucose homeostasis and maintaining normal hepatic functions.” [13]  With the development of NFALD, the rate of utilization of glucose decreases, and since the liver utilizes up to 30% of glucose, this diminished rate will significantly raise insulin secretion to lower blood glucose.  Insulin causes conversion of FFA to triglycerides, thus because of MTDD the excess fat is first in the liver, and with IR, fat accumulates throughout the body.[14]   The pancreas is of particular concern since that organ has receptors for fructose.  The net result is the gradual accumulation on the high sugar diet of lipid droplets in the pancreas.  On the basis of the work of Roy Taylor[15] and others it has been shown that the decline in the production of insulin that causes t2d is a result of inflammation of the pancreas brought on by excessive size of lipid droplets in the pancreas. There are other CCs involving the endoplasmic reticulum and oxidative damage in there: 

1. Failure of the ER’s adaptive capacity [endoplasmic reticulum] and further activation of the unfolded protein response may trigger macroautophagy (hereafter referred as autophagy) as a process of self-protection and inflammation.  Many studies have shown that inflammation plays a very important role in the pathogenesis of T2D…. Thus, the combination of oxidative and ER stress, together with autophagy insufficiency, and inflammation, may contribute to β-cell death or dysfunction in T2D.... Antioxidants act at different levels, inhibiting the formation of ROS, scavenging free radicals or increasing their own defense enzyme capabilities.[16] 

   1.            The article goes on to indicated the ER stress causes mitochondrial stress resulting in the release of ROS.  They find that “ER stress-induced apoptosis causes the loss of a large number of β-cells, insulin secretory capacity is impaired, resulting in T2D. role of mitochondrial dysfunction is not merely associated with but a major cause.”  

   2.           In addition to the assault caused by the load of excessive LD, fructose directly damages the cells of the pancreas, and of special concern the beta cells.  “Fructose is indeed metabolized in pancreatic islets, though at a maximal rate roughly 5-fold lower than that of D-glucose.... Fructose phosphorylation in pancreatic islet homogenates is inhibited to an extent of about 90:70 by glucose, mannose or glucose 6-phosphate…. However, for unknown reasons, fructose, if anything, barely stimulates glucose metabolism in islets” [17]  This is consistent with other articles that found fructose is transported into the pancreas.  The longer duration in the pancreas entails a 50-fold increase rate of fructation compared to glucose.  Fructose congeals with Roy Taylor’s work on the cause of t2d.[18]  Again, we have the B-5 and S-5 as CC for t2d. 

1.          

2. 14.  Bariatric surgery cures t2d:  About 80% of those undergoing biliopancreatic diversion are cured of t2d.[19] the remaining 20%, most have progressed from t2d to t1d, known as latent autoimmune diabetes in adults, LADA.[20] The evidence that surgery not only causes a major reduction in weight but also cures t2d is dispositive: “a ten-year remission rate of type 2 diabetes of 36%.” [21]  “Type 2 remission after 2 years was 72% and 36% after 10 years.” [22]  The modus operandi is through reduction in lipid droplets in the liver and pancreas with its reversal of IR entails those organs are functioning normally for the HSPs that have bariatric surgery .[23]  Autophagy directed metabolism of excess fat works to restore the patient’s health, and this is turned up by the low-calorie IV feed of the patient.  The gradual feed doesn’t raise insulin sufficiently to turn off autophagy.

   1.           The failure to remain drug free for over half of the patients is because of the physicians/guideline message: carbs are good, fats bad, and sugars are empty calories.  As their ability to consume more food is restored, most are back on the pathogenic western diet, and if they live long enough most will gain much of the weight and again develop t2d.  Their weigh regulatory system will again function to restore their weight gradually and again they go down the road to IR in the liver, fatty liver, fatty pancreas, and insulin and leptin resistance.  Again, I must gripe about the crapolla of the KOLs and the wrong message given these patients by physicians, dieticians, and corporate media.

   2.           Pharma claims that t2d is a life-long progressive condition; doctors tell this grim prognosis to their diabetic patients.  Their KOLs, when confronted by the reversal brought about by bariatric surgery, they explain that it is only a remission, not a cure; the remission is caused by significant weight loss and through stomach produced regulatory hormones; however, the evidence for those hormones is weak.  The hormones do not cause a reduction in the lipid droplets size in the pancreas (Roy Taylors work).[24]  Those hormones don’t effect fat storage or metabolism.  The KOL explanation ignores the evidence of lipid droplets as causing t2d (it implies a cure through metabolism of pancreatic fat).  The cure is through a  reduction in size of LD to cure t2d. 

   3. 5        The evidence confronts their explanation.  For example, during the first two week following surgery there is a major reduction in medication, that is before the significant weight loss.  The reversal is consistent with the material I have presented and with the chapter on autophagy (6:1).  The rapidity of reversal for t2d following surgery supports the evidence that autophagy promotes the usage of lipid droplets in the pancreas, kidneys, and liver, the most important organs, and I assume that other important organs are on the Autography Express.  The beta cells with the reduction in size of the LD are functioning sufficiently to control of glucose through production of insulin.  The metabolism of excessively large LD to normal size cures t2d.[25] [26] [27]

      Back to stomach hormones:  the KOLs have the wrong theory for the cause and for the “remission”:it lacks a modus operandi.  The KOLs hold that the remission is caused by the dysregulation of hormone secreted in the stomach to which the surgery corrects: “Bariatric surgery is a hormonal surgery in these procedures, for which the alteration in gut hormones develops as a result of the procedure's restriction and malabsorption.”  [28]  This gut-hormonal theory entails remission is temporary because as the stomach gradually grows to adjust to the quantity of food the hormones from the gut increase and the patient develops t2d a second time.  (That is true for many because they go back to their old recommended low-fat diet as mentioned above.)  Secondly in CME classes and textbooks the fatty pancreas evidence is ignored as too remission.  Those with t2d at best only reduce their medication, thereby supporting the claim that t2d is lifelong.  Like the ADA guidelines covered above and the cure t2d with diet, the bariatric surgery is inconvenient evidence that is ignored.  The KOLs of course ignore important facts about the metabolism of excess fat in the pancreas, kidneys, and liver and that half of bariatric patients are cured in the first two months before significant weight loss.  KOLs are soldiers in pharma’s army. 

      Bariatric surgery is associated with a significant reduction in the weighted incidence of a number of histological features of NAFLD including steatosis (50.2 and 95 %CI of 35.5–65.0), fibrosis (11.9 and 95 %CI of 7.4–16.3 %), hepatocyte ballooning (67.7 and 95 %CI of 56.9–78.5) and lobular inflammation (50.7 and 95 %CI of 26.6–74.8 %).[29]

      Similar finding for lipid droplets in the pancreas fat:

      Recent literature suggests that ectopic fat [lipid droplets] deposition in the pancreas may contribute to endocrine and exocrine organ dysfunction, such as type 2 diabetes (T2D), pancreatitis or pancreatic cancer….  PTGC (pancreatic triglyceride content) was significantly higher in type 2 diabetic subjects (23.8±3.2%) compared with obese (14.0±3.3; P=0.03) and lean subjects (7.5±0.9%; P=0.0002).  An improvement in insulin resistance....  Pancreatic fat increased with T2D and drastically decreased after the bariatric surgery. This suggests that decreased PTGC [pancreatic triglyceride content] may contribute to improved beta cell function seen after the bariatric surgery. [30]

      Restoring t2d by pathogenic high-sugar diet does explain why some do and other don’t get t2d for a second time. Unfortunately, I do not know of studies tracking sugar consumption following surgery.  Looking under the wrong tree entails not tracking diet.  The term remission is inappropriate, since they have been cured, and the subsequent acquiring of diabetes a second time is not the reappearance of a dormant condition like herpes, but the travelling down the same dietary pathway that caused the first bout of t2d.  Insulin resistance, sugar, leptin, WRS, fatty pancreas and liver[31] are all ignored.  Again, they have the research community looking under the wrong type of tree, what Prof. Ben Goldacre calls framing the topic.  We got drugs that promote illnesses, and the dietary fix is marginalized.

                Not wishing to covered here on weight reduction, you can visit 6:3.  In that section are two long-term following of patients who had biliopancreatic diversion (Roux-en-Y bypass); that procedure has superior results.  This surgical option which is more expensive and slower recovery from the procedure, that is not being paid for by insurance companies now, and the procedure has been replaced by less expensive, less invasive, and less effective procedures. 

                On the bright side though is a new procedure with affects similar to the biliopancreatic diversion uses a liner and has similar results.[32]  Is it safe long-term; we don’t know.  On the dark side is the lack of oversight for devices with horrendous consequence; e.g., heart valve replacement, J & J’s hip replacements, meshes joining tissues during surgery to name three high profile failures of the 2010 decade, each harmed tens-of-thousands of patients to millions of patients world-wide.  The dissolving of the mesh with its subclinical side effects has not been long-term studied.  The mesh article warned about younger patients and its likely long-term consequences, with seniors the sensitivity because of the B-5 and S-5 is far greater.  The question remains how safe is the stomach liner? 

       

11. Dietary management of t2d, and those with undiagnosed t2d:  I know several who have chosen to manage with diet instead of drugs their diabetes, but without going to the extreme of curing their condition through fasting and ketogenic diet.  How did these two groups fare, diet versus drugs?  Not surprisingly, I found not one perspective long-term quality study comparing the two groups long-term.  One study I did find wasn’t quality observational study using national records in Spain.  It found the “undiagnosed diabetes had a lower prevalence of hypertension, peripheral, dyslipidaemia, peripheral vascular disease and previous myocardial infarction than those with clinical diabetes, similar to that of those without diabetes.”[1]  The study of 400 consecutive patients admitted with acute heart failure to a hospital in Barcelona Spain.  Three groups, no diabetes 188 patients, clinical diabetes 149 patients, and undiagnosed diabetes 63 patients  That study only compared the three groups using healthcare records. At 7 years how each group fared was compared.  The undiagnosed group has a similar mortality rate to the diagnosed group. The limitation is the lack of tracking medications, because only a small percentage of the undiagnosed group would have gone untreated.  I want know the long-term health of those who went untreated, and a subgroup thereof who follow the LCHF diet without taking diabetic drugs for longer than 5 years.  I couldn’t find such a study.  Who would fund it and would an ethics committee approve it? 

12. Low carb diet for diabetes mellitus:  Allow me to repeat what is occurring with t2d:  increasing pancreatic release of insulin by dietary carbs, IR, and drugs stimulating production of insulin.  Excess insulin is a very bad thing (3:6).  Excess insulin affects many homeostasis processes.  In addition, since cellular fructose is metabolized last after glucose, with IR there is a slowed uptake of glucose because of MTDD, this entails an even slower uptake of fructose from the blood and delayed cytosol conversion to pyruvate in the ER, this increases fructation of proteins and UFAs transported into the MTD, thus causing a higher rate of MTDD when compared to those without IR.  For these reasons a low-carbs diet for those with IR is a healthful choice.  The damage by overstuffing cells also turns on PP’s production of fructose.  The longer it takes to clear the carbs from the cytosol, the longer it will take to switch to fat metabolism and turn on autophagy, another CC for CAWD.  The high level of insulin given its many regulatory functions is a major CC for the CAWD for those with IR and t2d. 

The management of t2d with drugs before the development of glucose meter (available in the late 70s in physician offices and the first home meter introduced in November of 1981) there was a major risk for hypoglycemia both for those on insulin and the other drugs for diabetes.  Monitoring consisted of urine testing.  But urine testing is only moderately associated with serum glucose.[2]  The low-fat diet was a major CC for hospitalization and death. This dietary problem has a dietary firx.

          The call for the low-carb treatment of t2d resulted in 2015 of a journal article with 29 signatures.  The article has 12 points, evidence that support low carbs, the 12 are compelling:  “It is not known who decides what constitutes evidence-based medicine but we feel that these points are sufficiently strong that the burden of proof rests on critics.” [3]  This is a seminal article concludes with a call for the science to dictate guidelines: 

12 Points of evidence [bold I consider more important] 

Point 1. Hyperglycemia is the most salient feature of diabetes. Dietary carbohydrate restriction has the greatest effect on decreasing blood glucose levels

Point 2. During the epidemics of obesity and type 2 diabetes, caloric increases have been due almost entirely to increased carbohydrates 

Point 3. Benefits of dietary carbohydrate restriction do not require weight loss

Point 4. Although weight loss is not required for benefit, no dietary intervention is better than carbohydrate restriction for weight loss

Point 5. Adherence to low-carbohydrate diets in people with type 2 diabetes is at least as good as adherence to any other dietary interventions and is frequently significantly better.

Point 6. Replacement of carbohydrate with protein is generally beneficial

Point 7. Dietary total and saturated fat do not correlate with risk for cardiovascular disease

Point 8. Plasma saturated fatty acids are controlled by dietary carbohydrate more than by dietary lipids

Point 9. The best predictor of microvascular and, to a lesser extent, macrovascular complications in patients with type 2 diabetes, is glycemic control (HbA_1c)  [Wrong, insulin resistance is the best measure]

Point 10. Dietary carbohydrate restriction is the most effective method (other than starvation) [water fasting] of reducing serum TGs [triglycerides] and increasing high-density lipoprotein [Misses that those with the highest 20% of cholesterol live the longest—Framingham Heart Study, started with 5,209 residents in 1948.  It is still running with the edition of a 3^rd generation.  Also missed  that triglycerides are a better predictor or cardiovascular disease, the best is insulin resistance]. 

Point 11. Patients with type 2 diabetes on carbohydrate-restricted diets reduce and frequently eliminate medication.  People with type 1 usually require lower insulin.

Point 12. Intensive glucose lowering by dietary carbohydrate restriction has no side effects comparable to the effects of intensive pharmacologic treatment [Missed that intensive lowering of glucose dose not lower the risks for the comorbidities of diabetes.].[4]

Each of these 12 points has several paragraphs with citations to published evidence and most of the 12 have appropriate graphs and tables.  This seminal 2015 article is focused on dietary management of t2d.  It should have been published in one of the 5 major English journals, but pharma’s noose has tightened, the BMJ has become the last to be tamed.  As for their criticisms of the ADA guidelines, the ADA and KOLs avoid confronting the evidence and continue to spew out their poisonous cocktail to physician in their CME classes, textbook chapters, and guidelines for the “progressive condition.”  The dieticians and media repeat it

Though the article is focused on diet for t2d, there is much more to understanding the forest.  Topics developed in this book prior on the CC for MTDD: fructation, IR, NAFLD, inflammation of the pancreas, the conversion of glucose to fructose in the polyol pathway thus fructation in biologically active cell, all these support the call for the low insulin thus low carb management and treatment of t2d and t1d (watch on YouTube and read Dr. Richard Bernstein’s book, he has t1d has been managing his t1d with low-carb diet for over 55 years). 

Not surprisingly is the failure of ADA guideline to mention lipid droplets in the liver and pancreas, and there is in those guidelines a total failure to recognize the issue elevated insulin caused by the medications which are the main CC for the conditions associated with t2d and its fatal progression.  It is long overdue to rediscover the past and again treat t2d with a low carb and for some a ketogenic diet and t1d with low carbs and insulin

I think of Ginter, my brother-in-law dead at 53, Ela Fitzgerald who had both her legs amputated below the knees, of Jerry Garcia at 53 and 8-days, dead from a heart attack, and my neighbor across the street below the age of 65, she died in 2021 from kidney failure after 4 years on dialysis.  Yes, I too cry out for low carbs like Bernstein, Westman, Volker, and the 26 others in a seminal article published 37 times since 2015 (different addresses);, but not in the big 5 English language journals. 

We all know friends and relative that have gone down the drug pathway to the lowered quality of life.  Treating glucose as shown by their examples is a failure.  Where is the major movement in the US for prevention of a once rare condition (”Between 1 and 2% of the population of the USA are diabetics”—Merck 1972, P 1186)?  What is the position of our government and the ADA on this dietary condition? 

The crapolla continues, unphased by the dietary fix, and the bad advice is poured out as the illness care industries frame the topic.  I found an 18-minute documentary, which list and refutes 6 of their pillars:

1    Diabetes is a chronic condition

 2   You must count calories and lose weight to improve diabetes[5]

3   A calorie is a calorie

4   The fat you eat is the fat you wear

5   Dietary fat causes insulin resistance and type two diabetes[6]

6   You need to eat carbohydrates to be healthy

It is by What I’ve Learned (his pseudonym) in Can you cure diabetes at https://www.youtube.com/watch?v=hpOP_HKeazU&t=18s  The quality is excellent.

13.  NAFLD, IR, and fatty pancreas leads to t2d:  “Virtually unknown before 1980, nonalcoholic fatty liver disease now affects over 30% of adults according to the 1999 NHAMES study and between 70% and 90% of those who are obese or who have diabetes.” [7]  Based on current obesity figure adjust for data flaws over half the adults have NAFLD.[8]  “While largely unknown in the 2000s, NAFLD, NAFL and NASH are the leading cause of chronic liver disease as of 2017.  People with NAFLD are likely to be asymptomatic − to have no noticeable symptoms, and often have normal laboratory profiles.... The diagnosis of steatosis is made when fat in the liver exceeds 5–10% by weight.” [9]  

Understanding the route from the liver to t2d entails understanding prevention and the best dietary treatment.  Since fructose has minimal effect upon insulin, and thus blood glucose, the measuring of insulin and glucose promoted the assumption—supported by the Sugar Research Institute—that fructose was harmless.  “It only became apparent by looking at the slow accumulation of fat in the liver. . . .  Replacing glucose with fructose increases liver fat by a massive 38 percent within eight day.” [10]  Between 50 and 70% of dietary fructose is utilized by the liver.[11]  Moreover, fructose can increase DNL 5-fold.[12]  Allow me to explain again, given the importance of this topic.   

1.           As prior mentioned (3:4), fructose causes MTDD first in the liver, because the liver is the most exposed organ via the hepatic portal vein from the intestines.  “Insulin signaling in liver is critical in regulating glucose homeostasis and maintaining normal hepatic functions.” [13]  With the development of NFALD, the rate of utilization of glucose decreases, and since the liver utilizes up to 30% of glucose, this diminished rate will significantly raise insulin secretion to lower blood glucose.  Insulin causes conversion of FFA to triglycerides, thus because of MTDD the excess fat is first in the liver, and with IR, fat accumulates throughout the body.[14]   The pancreas is of particular concern since that organ has receptors for fructose.  The net result is the gradual accumulation on the high sugar diet of lipid droplets in the pancreas.  On the basis of the work of Roy Taylor[15] and others it has been shown that the decline in the production of insulin that causes t2d is a result of inflammation of the pancreas brought on by excessive size of lipid droplets in the pancreas. There are other CCs involving the endoplasmic reticulum and oxidative damage in there: 

1. Failure of the ER’s adaptive capacity [endoplasmic reticulum] and further activation of the unfolded protein response may trigger macroautophagy (hereafter referred as autophagy) as a process of self-protection and inflammation.  Many studies have shown that inflammation plays a very important role in the pathogenesis of T2D…. Thus, the combination of oxidative and ER stress, together with autophagy insufficiency, and inflammation, may contribute to β-cell death or dysfunction in T2D.... Antioxidants act at different levels, inhibiting the formation of ROS, scavenging free radicals or increasing their own defense enzyme capabilities.[16] 

   1.            The article goes on to indicated the ER stress causes mitochondrial stress resulting in the release of ROS.  They find that “ER stress-induced apoptosis causes the loss of a large number of β-cells, insulin secretory capacity is impaired, resulting in T2D. role of mitochondrial dysfunction is not merely associated with but a major cause.”  

   2.           In addition to the assault caused by the load of excessive LD, fructose directly damages the cells of the pancreas, and of special concern the beta cells.  “Fructose is indeed metabolized in pancreatic islets, though at a maximal rate roughly 5-fold lower than that of D-glucose.... Fructose phosphorylation in pancreatic islet homogenates is inhibited to an extent of about 90:70 by glucose, mannose or glucose 6-phosphate…. However, for unknown reasons, fructose, if anything, barely stimulates glucose metabolism in islets” [17]  This is consistent with other articles that found fructose is transported into the pancreas.  The longer duration in the pancreas entails a 50-fold increase rate of fructation compared to glucose.  Fructose congeals with Roy Taylor’s work on the cause of t2d.[18]  Again, we have the B-5 and S-5 as CC for t2d. 

1.          

2. 14.  Bariatric surgery cures t2d:  About 80% of those undergoing biliopancreatic diversion are cured of t2d.[19] the remaining 20%, most have progressed from t2d to t1d, known as latent autoimmune diabetes in adults, LADA.[20] The evidence that surgery not only causes a major reduction in weight but also cures t2d is dispositive: “a ten-year remission rate of type 2 diabetes of 36%.” [21]  “Type 2 remission after 2 years was 72% and 36% after 10 years.” [22]  The modus operandi is through reduction in lipid droplets in the liver and pancreas with its reversal of IR entails those organs are functioning normally for the HSPs that have bariatric surgery .[23]  Autophagy directed metabolism of excess fat works to restore the patient’s health, and this is turned up by the low-calorie IV feed of the patient.  The gradual feed doesn’t raise insulin sufficiently to turn off autophagy.

   1.           The failure to remain drug free for over half of the patients is because of the physicians/guideline message: carbs are good, fats bad, and sugars are empty calories.  As their ability to consume more food is restored, most are back on the pathogenic western diet, and if they live long enough most will gain much of the weight and again develop t2d.  Their weigh regulatory system will again function to restore their weight gradually and again they go down the road to IR in the liver, fatty liver, fatty pancreas, and insulin and leptin resistance.  Again, I must gripe about the crapolla of the KOLs and the wrong message given these patients by physicians, dieticians, and corporate media.

   2.           Pharma claims that t2d is a life-long progressive condition; doctors tell this grim prognosis to their diabetic patients.  Their KOLs, when confronted by the reversal brought about by bariatric surgery, they explain that it is only a remission, not a cure; the remission is caused by significant weight loss and through stomach produced regulatory hormones; however, the evidence for those hormones is weak.  The hormones do not cause a reduction in the lipid droplets size in the pancreas (Roy Taylors work).[24]  Those hormones don’t effect fat storage or metabolism.  The KOL explanation ignores the evidence of lipid droplets as causing t2d (it implies a cure through metabolism of pancreatic fat).  The cure is through a  reduction in size of LD to cure t2d. 

   3. 5        The evidence confronts their explanation.  For example, during the first two week following surgery there is a major reduction in medication, that is before the significant weight loss.  The reversal is consistent with the material I have presented and with the chapter on autophagy (6:1).  The rapidity of reversal for t2d following surgery supports the evidence that autophagy promotes the usage of lipid droplets in the pancreas, kidneys, and liver, the most important organs, and I assume that other important organs are on the Autography Express.  The beta cells with the reduction in size of the LD are functioning sufficiently to control of glucose through production of insulin.  The metabolism of excessively large LD to normal size cures t2d.[25] [26] [27]

      Back to stomach hormones:  the KOLs have the wrong theory for the cause and for the “remission”:it lacks a modus operandi.  The KOLs hold that the remission is caused by the dysregulation of hormone secreted in the stomach to which the surgery corrects: “Bariatric surgery is a hormonal surgery in these procedures, for which the alteration in gut hormones develops as a result of the procedure's restriction and malabsorption.”  [28]  This gut-hormonal theory entails remission is temporary because as the stomach gradually grows to adjust to the quantity of food the hormones from the gut increase and the patient develops t2d a second time.  (That is true for many because they go back to their old recommended low-fat diet as mentioned above.)  Secondly in CME classes and textbooks the fatty pancreas evidence is ignored as too remission.  Those with t2d at best only reduce their medication, thereby supporting the claim that t2d is lifelong.  Like the ADA guidelines covered above and the cure t2d with diet, the bariatric surgery is inconvenient evidence that is ignored.  The KOLs of course ignore important facts about the metabolism of excess fat in the pancreas, kidneys, and liver and that half of bariatric patients are cured in the first two months before significant weight loss.  KOLs are soldiers in pharma’s army. 

      Bariatric surgery is associated with a significant reduction in the weighted incidence of a number of histological features of NAFLD including steatosis (50.2 and 95 %CI of 35.5–65.0), fibrosis (11.9 and 95 %CI of 7.4–16.3 %), hepatocyte ballooning (67.7 and 95 %CI of 56.9–78.5) and lobular inflammation (50.7 and 95 %CI of 26.6–74.8 %).[29]

      Similar finding for lipid droplets in the pancreas fat:

      Recent literature suggests that ectopic fat [lipid droplets] deposition in the pancreas may contribute to endocrine and exocrine organ dysfunction, such as type 2 diabetes (T2D), pancreatitis or pancreatic cancer….  PTGC (pancreatic triglyceride content) was significantly higher in type 2 diabetic subjects (23.8±3.2%) compared with obese (14.0±3.3; P=0.03) and lean subjects (7.5±0.9%; P=0.0002).  An improvement in insulin resistance....  Pancreatic fat increased with T2D and drastically decreased after the bariatric surgery. This suggests that decreased PTGC [pancreatic triglyceride content] may contribute to improved beta cell function seen after the bariatric surgery. [30]

      Restoring t2d by pathogenic high-sugar diet does explain why some do and other don’t get t2d for a second time. Unfortunately, I do not know of studies tracking sugar consumption following surgery.  Looking under the wrong tree entails not tracking diet.  The term remission is inappropriate, since they have been cured, and the subsequent acquiring of diabetes a second time is not the reappearance of a dormant condition like herpes, but the travelling down the same dietary pathway that caused the first bout of t2d.  Insulin resistance, sugar, leptin, WRS, fatty pancreas and liver[31] are all ignored.  Again, they have the research community looking under the wrong type of tree, what Prof. Ben Goldacre calls framing the topic.  We got drugs that promote illnesses, and the dietary fix is marginalized.

                Not wishing to covered here on weight reduction, you can visit 6:3.  In that section are two long-term following of patients who had biliopancreatic diversion (Roux-en-Y bypass); that procedure has superior results.  This surgical option which is more expensive and slower recovery from the procedure, that is not being paid for by insurance companies now, and the procedure has been replaced by less expensive, less invasive, and less effective procedures. 

                On the bright side though is a new procedure with affects similar to the biliopancreatic diversion uses a liner and has similar results.[32]  Is it safe long-term; we don’t know.  On the dark side is the lack of oversight for devices with horrendous consequence; e.g., heart valve replacement, J & J’s hip replacements, meshes joining tissues during surgery to name three high profile failures of the 2010 decade, each harmed tens-of-thousands of patients to millions of patients world-wide.  The dissolving of the mesh with its subclinical side effects has not been long-term studied.  The mesh article warned about younger patients and its likely long-term consequences, with seniors the sensitivity because of the B-5 and S-5 is far greater.  The question remains how safe is the stomach liner? 

       

      15.  Health benefits of bariatric surgery and fasting;  Like with NAFLD, the same process of accumulation of large lipid droplets and increased adipose tissue occur in kidneys and with the pancreas, which can progress to kidney failure and t2d.  The fasting associated with bariatric surgery (under 600 calories from fats and carbs)[33] often reverses those conditions.  Fasting produces the same benefits as bariatric surgy;  thus a table of benefits following bariatric surgy in the main applies to long-tern or regular alternate day fasting.

       

Table 1. Beneficial cardiovascular effects of bariatric surgery[34]

So why is there a remarkable improvement in health following bariatric surgery?  It comes through a period of low insulin which upregulates autophagy.  Turning up autophagy through a low-calorie period of under 600 a day entails that preferentially there is metabolism of the excess fat in organs—by evolutionary design.  Moreover, the IV feeding lacks fructose.  In the healing mode of autophagy, the excess fat in those organs is metabolized, this promotes healing:

Autophagy has been shown to play an important role in regulating normal function of pancreatic β cells and insulin-target tissues, such as skeletal muscle, liver, and adipose tissue. Enhanced autophagy also acts as a protective mechanism against oxidative stress in these tissues. Altered autophagic activity has been implicated in the progression of obesity to type 2 diabetes through impaired β-cell function and development of insulin resistance. In this review, we outline the normal regulation of autophagy in β cells and insulin target tissues and explore the dysregulation of autophagy in diabetic animal models and human subjects with type 2 diabetes. Furthermore, we highlight the role of impaired autophagy in the pathophysiology of diabetic complications, including nephropathy and cardiomyopathy. Finally, we summarize how autophagy might be targeted as a therapeutic option in type 2 diabetes.[35]

The increasing of fat metabolism and upregulating autophagy fixes much more that t2d, IR, NASH and NAFLD.  Given the fragile state of seniors, those with t2d and obesity are lowering the risk for the other CAWD.  Sadly, the dietary subsequent of the operation lacks a fructose warning and the benefits of a LCHF diet with nut oils.  All 3 of my friends within 10 years regained most or all of their weight.

16.  Curing t2d with ketogenic diet or fasting:   Aalternate-day fasting and ketogenic diet avoid the yo-yo diet and maintain their weight loss if the diet/fasting becomes a lifestyle change (6:3).  Could they also like bariatric surgery reverse t2d IR? [36]  Fasting and the ketogenic diets turns on autophagy.  The low insulin level increases the duration of autophagy and from this comes the variety of benefits as the body rights the floundering ship. 

Very-low carbohydrate diets inducing ketosis have shown to be effective in weight loss although superiority over caloric restricted diets continues to be debated [by KOLs and dupes].  Ketosis can improve markers of metabolic syndrome through reduction in serum triglycerides, elevation in high-density lipoprotein as well as increased size and volume of low-density lipoprotein particles. These changes are consistent with an improved lipid profile despite potential increases in total cholesterol level. 

Seizures  Ketosis induced by a ketogenic diet is a long-accepted treatment for refractory epilepsy.  It was first used in the 1920s and is now widely implemented for pediatric and adult patients. 

Neurological diseases: In addition to its use for epilepsy, ketosis is being investigated in other neurological diseases due to its proposed neuroprotective effects including Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), autism, headache, neurotrauma, pain, Parkinson's disease, and sleep disorders.

Cancer: Preclinical studies have indicated ketosis may have anti-tumor effects, however clinical trials have been limited by small sample sizes and not shown conclusive benefit.[37]

Other conditions: There is emerging evidence for the use of ketosis in other conditions such as type 1 diabetes, non-alcoholic fatty liver disease, acne and polycystic ovary syndrome, however evidence quality is limited by small sample sizes.

The safety of ketosis up to two years is supported by studies of people following a strict ketogenic diet for epilepsy or type 2 diabetes without adverse events.  However, literature on longer term effects or intermittent ketosis is lacking.[38]

Clinical trials have shown this dietary format of fasting and/or LCHF reverses for at least half t2d patients.  Along with the are reversals for some of the comorbidities of diabetes.  Diabetic nephropathy can also be reversed with a ketogenic diet high in short chain fatty acid which produce 3-hydroxybutyrate.[39]  The ketogenic diet supplies the fat; while fasting it is the adipose tissue’s that is metabolized.  If the fat is rich in short chain fatty acids (the economical source is coconut oil from Costco) the salubrious effects are greater than fasting (supra Poplowski). Both fasting and keto diet turn up autophagy sufficiently when they become a life-style they significant lower risk for CAWD. 

The above issue of safety in the Wiki article concerning longer ketogenic diets (also fasting) is waved as the standard warning, like that of drug side effects on TV advertisements; however, the risk from ketogenic diet and fasting is very low, even though most of those who try this treatment have extreme IR, weight issue, polypharmacy, and other risks for CAWD.  The Eskimos diet and health were studied in their natural environment before the western diet was introduced, and they lacked the CAWD, proof of the safety of life-long ketogenic diet.  Many of the paleo people regularly go without food when travelling distances and when hunting.  The mammalian examples provide more evidence for life-long ketogenic diet and intermittent fasting.  The treatment of epilepsy with ketogenic diet also confirms its long-term safety. Homeostasis mechanisms through autophagy explains why both ketosis and fasting are recuperative. 

Ketogenic diet reverses t2d:  Given our understanding of the process, the condition of the pancreas, the history of treatment with low carb diet, and the evidence from bariatric surgery, all these supports that a ketogenic diet can reverse t2d. In a trial on point: 

The LCKD [ketogenic diet] improved glycemic control in patients with type 2 diabetes such that diabetes medications were discontinued or reduced in most participants. Because the LCKD can be very effective at lowering blood glucose, patients on diabetes medication who use this diet should be under close medical supervision or capable of adjusting their medication.[40]

Again, the trail is thin as to studies on point, but with the biological basics the path is clear.  Given the evidence for the wide range of benefits of the ketogenic diet, it will manage t2d drug free and gradually reverse t2d and at the same time through the promoting of autophagy and avoiding the side effects of drugs.

Fasting reverses t2d:  Whatever significantly promotes the metabolism of excess fat in the liver, kidneys, and pancreas will reverse t2d and IR.[41]  This is the approach used by Dr. Jason Fung in his clinic in Toronto with repeated success, using both alternate day fasting and low carbs. 

Fasting allows us to naturally empty the sugar from our body (the sugar bowl).  Once empty any incoming sugar will no longer spill out into the blood, and we will no longer meet the criteria for diabetes.  We will have reversed the disease.... In my Intensive Dietary Management program, we often start with a thirty-six-hour fasting period three times per week for type 2 diabetes.  During the eating periods, we prescribe a low-carbohydrate high-fat diet.... Some people will do a classic water-only fast, others a modified-fat fast, and still others a bone broth fast.[42]    

Some of his patients do a much longer on a 36-hour water fast.  Fung being a  nephrologist, many of his patients are end-stage diabetics with kidney failure.

          A personal comment on fasting:  as before mentioned given the risk of cancer at about 50%, I certainly want to reduce my risk.  I do once or twice a year a longer water fast.  Since I am at my youthful weight and in my 7^th decade, I have experienced hitting the wall (lack of energy), which last for hours as the adipose hormone leptin reduces metabolism and other processes as the body undergoes a metabolic switch.  To avoid this, I do a modify fast with fats, cheese, and fish.  I once used bell peppers with fats, but since the bacteria in the small intestines use enzymes extra-cellular to break down fiber, and thereby the gut absorbs 50 to 70% of the glucose, I have switched to proteins and fats. 

In 1916 Elliott Joslin in his case studies reported a lady “who contracted diabetes twenty-six years ago going without food, but for broth for several days in succession, and that she would follow his advice.  Her severe symptoms of diabetes subsided at the end of four years.  Her tolerance on June 1, 1916, reached 116 grams of carbohydrate.” [43]  Not cured but managing her diabetes with diet.  What if she had combined low carbs with intermittent or alternate day fasting? 

The results of fasting are rapid as to its effect upon IR.  In an experiment on 7 untreated t2d who fasted for 3 days their fasting glucose while on a standard diet was 196, at 3 days it was 127mg/dL.[44]  More on point is the treatment of 13-obese diabetics unmedicated who fasted from 17 to 99 days for obesity. “All patients showed improvement in glucose tolerance, with abolition of previous mildly diabetic curves in five patients, irrespective of subsequent weight gain.” [45]   

Dr. Fung commenting on his clinical experience: “How long it takes to reverse the disease depends on the intensity of the fasting regimen and the length of time you’ve had the disease.” [46]  I believe it is determined by a number of factors:  age, degree of insulin resistance, amount of fat in the liver and pancreas, basil metabolism, lifestyle, and overall health, thus as Jason Fung says everyone is different.  

The dawn phenomenon (dawn effect):  A couple of years ago a friend with t2d tried to manage her condition with a low carb diet.  Monitoring her blood glucoses, she was alarmed at the rise in glucose.  I had no answer as to why this occurred and she discontinued her low carb diet.  Since then, she has gained 40 pounds, cognitive decline, and pain in her legs sometimes severe.  She is now stoically stuck in the quick sand of drugs.

On my second reading of The diabetes code, (January 2020) P 203, I found the answer.  Since in the dawn-hours blood sugar is at a low point, the body in preparation for activity releases epinephrine, which causes the liver to breakdown glycogen to release sugar.  Cortisol is also released:  “This effect is amplified in patients with islet β-cell dysfunction such as diabetics.” [47]

In the early  fasting  state, cortisol stimulates gluconeogenesis (the formation of glucose), and activates antistress and anti-inflammatory pathways. Cortisol also plays an important, but indirect, role in liver and muscle  glycogenolysis, the breaking down of glycogen to glucose-1-phosphate and glucose.  This is done through its passive influence on glucagon.  Additionally, cortisol facilitates the activation of glycogen phosphorylase, which is necessary for  epinephrine to have an effect on glycogenolysis.[48]

This effect is frequently noticed for those with t2d because of blood monitoring:

These hormones are secreted in a pulsatile manner, peaking in the early morning then falling to low levels during the day.  In nondiabetic situation where there is no need to manage blood glucose artificially, the DP [dawn phenomenon] is a normal occurrence, but most people miss it because the magnitude of the rise is very small.  In about 75 percent of type 2 diabetics, however it shows up as a noticeable spike in blood glucose levels early in the morning.... Like the overinflated balloon, the liver puts forth prodigious amounts of sugar in order to relieve itself of this toxic sugar burden.  [49] 

To put it another way, evolution is for our health, the release of glucose during a ketogenic diet or fasting supplies erythrocytes with oxygen.  Incongruously, pharma with their toxic glucose theory holds “plasma cortisol possible contributes to the pathogenesis of dawn phenomenon in NIDDM in patients.” [50]  Drugs for blocking the dawn phenomenon are gaining in sales. 

Proteins and insulin:  Using the insulin index, there is a significant rise in insulin with food high in protein such as 45 cheese, 51 meats, white pasta 51, fish 59, apples 59, and white bread 100.  The reason for the rise in insulin is that several of the essential amino acids raise insulin[51] but why?  Given the effects of insulin upon blood glucose (lowered), autophagy (turned off), fat metabolism (turned off), it would seem that proteins should be avoided.  However, there is no association with hypoglycemia, thus, I have come to believe that in a complex signaling process effects of insulin is blocked for some of insulin functions, in particular that autophagy and fat metabolism continue.  Insulin’s effect upon IGF-1 and IGF-2 I believe are still turned on the conversion of amino acids to proteins,  Amino acids are needed in autophagy when insulin is low, which is during fat metabolism.  I have come across a couple of articles that found that the amino acid by itself doesn’t increase the level of insulin, others hold the opposite conclusion.  Thus, I wonder about how those figures in the Index for meet, cheese, and fat were obtained (I wasn’t able to find out)  To repeat, the answer might lie with IGF-1 and 2 which promote the synthesize proteins and polypeptides from amino acids.  What are their levels post-prandial on a keto diet?  If this mechanism didn’t exist, the high insulin caused by the amino acids would cause hypoglycemia.  Nature is very good at maximizing the utilization of amino acids—they can’t be stored. 

By keeping carbs low, I am proposing that other regulatory hormones assure that amino acids without carbs does not shut down autophagy which turns up the synthesis of proteins.  This must be the case for those on a keto diet including the Eskimos.  I started in 2016 snacking on cheese and butter in response to the belief that autophagy and fat metabolism aren’t affected. 

Stimulants such as norepinephrine and amphetamines raise the insulin level for the breakdown of glycogen to provide extra energy for activities I.  Caffeine in sufficient amounts causes the conversion of glycogen to glucose,[52]thus I limit my caffeine on a low carb diet. 

The combination approach:  This is a “no brainer”, like take a water-soluble antioxidant and a fat-soluble antioxidant.  Combining fasting and ketogenic diet improves the degree and rate of management of t2d and its reversal.  It turns up autophagy more either one alone.  This combination permits the patient to sculpture the management of t2d.  The combo also improves MTD functions, which increases the rate of pyruvate metabolism and thus glucose.[53]  Disconcertingly many of the authors of diet books recommend just one or the other.  An exception is Dr. Jason Fung, who recommends both for weight loss, and for treatment of t2d. 

The critics:  This simple and obvious way to reverse t2d and improve the health of those with t1d LCHF diet has its moneyed critics with their tobacco science, tobacco ethics social engineering, guidelines, and marketing.  One of their standard moves is to claim protecting the public.  Thus, the major weight loss programs including Weight Watcher, Medifast and others are just low-calorie diet with the failure because of the leptin and other hormones restoring the fat.   Physician and dieticians recommend those weight loss programs, to which three of my friends have regained two of whom tried it a second time, Medifast.    

For Intermittent fasting and alternate day fasting doesn’t need the aid of a physician to lose weight or reduced medications for diabetes.  The battery-operated glucose monitoring blood testing is adequate for those trying the dietary fix for t2d or the reduction in injections for t1d.  For the fix effects upon non-diabetic medications, the local pharmacist for free can advise.  Moreover, the physician will criticize the dietary fix and thus dissuade some of those who would otherwise have made the best healthful choice.  For long-term water fasting taking supplements of potassium, sodium, magnesium, vitamins are advisable; they are available over-the-counter and through Amazon.  With weight loss the body through autophagy reprocesses the amino acids obtained from apoptosis. Angus Barbieri at the age of 27, weighing 456 lbs. In June of 1965 he went on a water fast for 382 days.  There was weekly blood work to which monitored his health and confirmed his water fasting.  He lost 276 pounds.  The amino acids were supplied by the dismantled adipocytes.  A water fast over 2 weeks should be under medical supervision.  Long term water fasting was done sometimes in that era for the morbidly obese.  To see a well-meaning physician is likely to do more harm than good because his advice likely will come through KOLs.  Just consider what has happened to t2d which once was managed with diet, and the high rate of failure of the low carb diet.   

For those who wish to delve deeper into the processes associated with t2d, I recommend the article by Roy Taylor in the Diabetes Journal, Type 2 Diabetes Etiology and reversibility, April 2013, available in full.  His 2018, June article published in the BMJ, Dietary and nutritional approaches for prevention and management of type 2 diabetes, also available in full at home.  

A personal note, what I preach I practice.  I have very little subcontanious fat (thin like when I was in my teens but with 10 pounds more muscle); therefore, when running in the morning--averaging over 3 miles--I have a moderate amount of carbs in a protein mix to which I add cocoa powder, milk, 2 ounces of canola oil, and yogurts.  I do this so that at my age so I don’t hit the wall (extreme fatigue occurring about half an hour to 1 one after running.  That is caused by my metabolism of glycogen and thus low blood sugar; an issue I didn’t have 10 years ago and before.  When not running in the morning I continue with the morning fast, which I have been doing since 2014.  I like the way I feel.  If hungry during the morning fast, I have about ½ ounce of cheese with an ounce of butter.  That will keep my insulin low.  There is no need for me to lose weight.  I haven’t dieted since 2004, which I attributed to the high dose of topical testosterone and sublingual DHEA (6:2).  Both and estradiol promote health and can prevent weight gain. 

17. Supplements and exercise:  The sex hormones (a supplement for the seniors) among their many salubrious functions is the partial regulation of lipoprotein lipase (LPL) which is essential for the metabolism of fats; and these sex hormones controls fat disposition: 

“One reason men get fatter above the waist as they age is that they secrete less testosterone…, [which] suppresses LPL activity on the abdominal fat cells…. In women the activity of LPL is high on the fat cells below the waist, which is why they tend to fatten around the hips and gut, and low on the fat cells of the gut.  After menopause, the LPL activity in women’s abdominal fat catches up to that of men. [54]

Gary Taubes (Chapter 9) Why we get fat goes on to describe the experiments of George Wade on rats where he removed the ovaries.  It provides an animal model on the importance of estradiol.  The same applies to testosterone.  A senior by taking natural hormone replacement from a compounding pharmacy (6:2) can reduce excess lipodystrophy.  From the physician and pharma, it follows their pattern. 

Estradiol and testosterone differ only by one functional group, moreover, the level of one influence the level of the other through about a 10% rate of conversion.  Both function to increase metabolism and through testosterone’s androgenic effect muscle mass.  Both also function to reduce ROS damage to the MTD.  Thus, these hormones lower serum glucose and thereby reduce the degree of IR.  They also function in the brain as neurosteroids; important enough that the glia cells make small amounts of them.  Yes, the sex hormones are salubrious and thus a target for bad pharma.  I have been taking topical testosterone, high dose since 2004 from a compounding pharmacy.  These hormones also lower moderately serum glucose, or at least prevent it from going up with age.  By the 6^th decade their benefits become significant.  

Among its many benefits, aspirin lowers glucose (see http://healthfully.org/rc/id3.html under diabetes heading).  A very high dose of uncoated aspirin cured t2d in a clinical trial.  The average carbohydrates for the 8 diabetics in the clinical trial was 25% of calories.[55]  The physician was likely following Elliot Joslin’s recommendation.

High dose of uncoated aspirin—typically 3.5-grams ad a day--was the gold standard of rheumatoid arthritis treatment and used for other conditions to lower inflammation.  It had been noted in the literature that “Rheumatic fever and diabetes rarely coexist”[56]

Though I ate the western diet, I had done far better than my associates.  A major part of this I attribute to aspirin.  I had taken on doctor’s advice starting in 1992, 2.5 grams a day of coated aspirin for chronic back pain.  After 3 years I reduced it to uncoated aspirin at 0.65  grams taken daily until 2018.  Abdominal exercise fixed my back pain by 1994, I was taking it after then to lower my risk of cancer.  A decade later I learned of its other benefits.  Aspirin 325 mg lowers the cancer risk by 50%.   The Harvard Nurses’ Study tracking the use of aspirin long-term found that those having breast cancer stages I, II, and III, their rate of relapse with metastatic breast cancer was lowered about 50%.[57]  That article was published twice in the BMJ, years apart.  Recent extensive research in China has uncovered three ways that aspirin reduces cancer risk including the up-regulates the apoptosis system for abnormal cells (see http://healthfully.org/rc/id18.html). A fourth benefit is the lowering of fructose/glucose.  Like with the sex hormones and neurosteroids, aspirin is a target for bad pharma.  The use of low-dose and coated aspirin, and the exaggeration of the risk of stomach bleeding are all part of pharma’s attack.

Vitamin C ought to be added since the diabetics have low ascorbate in their cells.  Vitamin C among its 8-essential factor, includes its role in the folding of collagen.  This could explain a number of risk factors for diabetics.  If diabetic, I would add 3 grams of sodium or calcium ascorbate to the liquids I was drinking throughout the day, not one dose because of its low rate of absorption due to gastric regulation.  

Exercise stimulates an increase in number of MTD thus increases the rate of metabolism of glucose, thereby lowers insulin.  With regular physical excretion, insulin resistance is reduced.  Exercise also increases autophagy.  This is particularly important for senior, given the evidence from articles on senior runners.  Two studies of senior runners, one at Stanford University the other of a New York runners club:  the mortality rate was 1/3 those of the general population and over an 8-year delay for a major health event.[58]  To be a fit senior requires aerobic regular activities. 

The evidence for both hormone replacement and aspirin are beyond refutation.  It is as Prof. Ben Goldacre writes: “It is amazing how quickly a good drug become bad one once off patent.”  We are a social animal and industries exploit that.  Will the new Atkins diet with fasting become the standard for diabetes treatment?