3/9/18

Consequences of Insulin Resistance (IR)

A review of the role of excess  fructose: Insulin resistance starts with the Western high fructose diet.  About 20% of glucose and all of fructose is transported into the liver.  Fructose—a net 20 times more reactive than glucose[1]--is metabolized only in the liver.  Our high fructose diet overloads the systems that repair glycated proteins and their oxidized end products.[2]  Glucose alone being less reactive can’t cause insulin resistance.  With a high carb meal, the excess glucose causes fructose to be converted to fat in the liver by de novo lipogenesis.  Insulin also signals fat storage to promote glucose metabolism; this gradually leads to a fatty liver (similar to that caused by ethanol).  There is very strong evidence supporting the role of fructose; for example, in a trial in which young-healthy volunteers were fed 40% of calories from fructose; within 2 weeks they developed insulin resistance and fatty liver.  Prof. Robert Lustig has done a sophisticated population study of over 100 populations; they controlled for confounding variables.  His team found that only for the disaccharide sucrose is there a strong association with metabolic syndrome—the same type of population study done to prove that cigarettes cause lung cancer. This one two punches of glycation and fatty liver cells causes functional problems in the liver that leads to IR in the hepatocytes.  The liver plays a major role in controlling serum glucose which is down regulated, and eventually this will lead to IR in the myocytes and adipocytes as they resist excess glucose uptake and thus become IR.  Insulin also regulates other hormones that are part of the weight-regulatory system, and insulin resistance is the major cause for weight gain.[3]  The excess fructose[4] and the resulting IR are the main causes for nearly all the CAWD.  Those conditions, but cancer, are rare to extremely rare among the elderly aboriginal and preindustrial peoples who consume their traditional diet.  Wild fruits--with few exceptions--are both low in sugar and seasonal, thus their consumption of fructose is limited.  A second major healthful practice is their not eating.  While sleeping or not eating, autophagy is turned on, and when insulin remains low by not eating is extended.  The conditions that are extremely rare among the elderly aboriginals:[5]  insulin resistance, obesity, osteoarthritis, dementia, and atherosclerosis with its comorbidities—cancer is about 90% lower.   Their major causes of death are infections, infectious diseases, parasites, trauma, and pregnancy.  The case for our dietary fructose as the starting cause for CAWD is strong--SEE LIST OF CONDITIIONS ON PREVIOUS PAGE. 

Metabolic Syndrome

Originally called syndrome X is a collection of conditions associated with

the western diet (CAWD) that manifest as a cluster.  Most conspicuous

was the dysregulation of the system that regulates adipose tissue and

appetite.  We have progressed from a population in which only the

affluent would gain weight to now over 70% of adults are overweight,

and over half are obese[1], and with that weight gain comes CAWD.

Insulin resistance (other than its role in weight gain), it is considered relatively benign; however it is the main cause of the diseases of Western society and these conditions compared to the aborigines are significantly elevated.  I suspect that like those with type-2 diabetes and those people with IR also have defective collagen, but to a lesser extent (diabetics have CAWD at about twice the average).  In the only study I know of that compares an aboriginal people--the Kitavans to a western society--only 5% of the Swedes had insulin level below that of the average Kitavan.[2]  Current standards for IR are thus well above the ideal level of insulin; thus based on Lindeberg’s work I estimate that over 80% of adults and 90% of seniors are IR.  This would explain why those who aren’t diabetic or overweight also have the other CAWD though their serum glucose is normal.  I believe like with diabetes those others with IR have defective collagen and thus t heir CAWD; but my extensive search of the literature has failed to find articles addressing this nexus.  Whatever the path to illness, clearly IR is most significant.  Independent of the defective collagen hypothesis is the causal factors relating to high fructose diet of high levels of insulin, IGF-1,fatty liver, and glycation leading to ROS.  To this I would add as pathogenic:  rancid vegetable oils, sex hormones mimics, sedatives (neuroleptic drugs), statins, and polypharmacy as significant causes; and I left out refined starches, stress, hypertension, and dyslipidemia.  Materials supporting his list are found at healthfully.org/r (the letter “r” for posting after 2010).   

Leptin resistance, elevated leptin; insulin up regulates leptin thus insulin resistance eventually causes leptin resistance.  Leptin is a hormone secreted by adipose tissue which regulates appetite, metabolism & functions to restore fat storage to its set level through reducing the rate of metabolism from 25% to 40% and increasing appetite.  With long-term excess weight, the normal weight is rest; thus making merely eat less and exercise more futile.  If leptin-insulin system is working right, that  person without efforts stays at normal weight—like the aborigines.  Pharma profits from having doctors focusing on lowering serum glucose and treating CODW; thus their ignorance about the weight regulatory system and how to fix it.       

Obesity and weight gain:   Having above established that that are high fructose western diet causes insulin resistance, and that insulin resistance causes fat storage, and with as little as 20 calories a day stored as fat, that is sufficient to bring about obesity in 30 years.  The issue isn’t slough and gluttony, more calories in than out, or other version of this paradigm, but what is causing the imbalance, for which the answer is insulin resistance, and insulin resistance is caused by the high sugar western diet which has brought about the dis-regulation of the control of weight.  Ignoring the system is to blame the victim; biology rules.  Obesity is a sign of the underlying condition, and not all obese are current insulin resistant—some have reversed it. 

 Non-Alcoholic Fatty Liver Disease (NAFLD), gradually in the liver on a high fructose diet glycation and the conversion of fructose to fat (its only path) this causes insulin resistance in the liver (insulin goes from pancreas first to the liver).   With insulin resistance there is a gradual increase in liver fat to become the silent driver for the conditions of metabolic syndrome--a sick liver has many health consequences including an increase in visceral fat--a sign of NAFLD.  In 1999 it was estimated by the NHANES study that 30% of adults including 80% of the obese have NAFLD.  Grossly underestimated; ultrasound is the most reliable test. Cleansing the liver is essential for good health—see below.   

TOFI  -- thin on outside fat on inside People whose weight is within the normal range, yet they have accumulated visceral fat, and in particular a fatty liver and thus insulin resistance.  Even for those who maintain normal weight, they can have IR and fatty liver and thus CAWD, including diabetes.                     

Type-2 Diabetes, Pharma holds diabetes is a lifelong progressive disease and that their comorbidities are caused by high serum glucose through glycation and its subsequent oxidation (ROS), thus ideal treatment is to keep glucose low with drugs. They also hold that eating carbs (glucose) is necessary to avoid low serum glucose caused by the drugs they are taking.  A number of critics[3] hold that it is much better to go on a very low carb diet and lower their need for medication—the opposite of pharma’s recommendation and guidelines. This ignores the facts that most of the treated diabetics have glucose levels below those who are insulin resistant (about 80% of adults), yet the conditions associated with diabetes are much higher than for those are just insulin resistant.  The high glucose with oxidative stress due to glycation theory has several counter examples.  “No major organization recommends universal screening for diabetes as there is no evidence that such a program improve outcomes [by lowering glucose].^[54][55]” Wikipedia.  This treating of symptoms instead of the conditions is a common business practice of pharma, like treating fever instead of infection.  Thy consequence is that pharma frames the understanding of the diabetes and the search for treatments to lower the sign, high glucose, rather than search for what has gone with the weight regulatory system, how best to cleanse the liver and pancreas of excess fat, and thereby cure tye-2 diabetes with diet.  

Defective collagen, an example of the way pharma buries a fix.  It took me 4 years of full-time dietary research before I came across the role of collagen.  Pharma is happy selling drugs to lower glucose than sell more drugs for the comorbidities associated with diabetes and the drugs to treat diabetes.  Type-2 diabetics have a significantly a low level of ascorbate in tissues that store it.[4]  There is an issue with the function of ascorbate in the polyol pathway that produces collagens.  Though the research is incomplete, it is sufficient to support the conclusion that that defective and/or lack of new replacement collagen plays the major role in the comorbidities associated with diabetes.  And this hypothesis is made stronger by the down grading of the role of glucose in glycation;[5] moreover there is some evidence for the benefits from mega dose of ascorbate or myo-inositol.  The extensive amount of research on collagen during the golden era of medicine has dried up in the subsequent years.  And clinical trials of ascorbate supplement are lacking. 

Dietary fix for insulin resistance, type-2 diabetes,  obesity, and fatty liver and TOFI.  Pharma’s and food manufacturer’s fix is to eat less, exercise more, and eat a low fat diet which by default is high carbs, thus high insulin diet.  This approach doesn’t fix the mammalian weight-regulatory system because it doesn’t cure insulin resistance, thus we have the yo-yo diets. On a caloric energy restricted diet, sugars are reduces and carbs thus lowering insulin which lowers leptin, and low leptin through the brain increases appetite, and to conserve ATP reduces the rate of metabolism to conserve fat stores and this makes the person feel that he needs to eat to restore energy—the biology behind the yo-yo diets.  Type-2 diabetes is a dietary disease with a dietary cure as is insulin resistance, and NAFLD.   For example, bariatric surgery is able to cure 80% of the diabetics, and 51% at 12 year follow up.  And it is not because of extensive weight loss (as pharma maintains).   Studies show that most of these patients are off their diabetic medications before significant weight loss, thus indicating that the forced fasting is curative vector—not weight loss.  Other studies have shown that fasting and for some the ketogenic diet the cures through metabolism of excess stored fat in the liver, and for diabetics in the pancreas.  Following surgery they are on an extremely low calorie, low insulin diet; their body metabolizes the excess fat in the liver and pancreas which cures their diabetes and insulin resistance—excess insulin increases fat storage.[1]  The long-term cure rate would be higher if those surgery patients had been warned of the rule of fructose and had a low carb diet in the hospital and afterwards.  A small but growing group of physicians (Dr. Jason Fung is among the best) are now advocating fasting (both intermittent and alternate day) and lowing carbs or a ketogenic diet.  They have been able to cure type-2 diabetes and obesity by curing insulin resistance and fat storage in the liver and pancreas.    

Mediterranean diet is healthy because of the high consumption of olive oil; wrong, it is the low consumption of sugar.  This is part of the mountains of proposed causes and fixes currently circulating.  That which explains what has gone wrong and the fixes are buried within the mountain of social twaddle.  Switching to a Mediterranean diet won’t fix the fatty liver, insulin resistance, and diabetes, thus what is offered as a fix, isn’t: nor prevent the development of IR, because of the failure to warn about sugar.      

Good and bad fats:   “The type of fats in the diet are important, with saturated fats and trans fatty acids increasing the risk, and polyunsaturated and monounsaturated fat decreasing the risk^[26]” Wikipedia (contrary to the mass of evidence, see rancid fats and saturated fats). The only way to sort out the tobacco science is to question everything, and rely upon the modus operandi.  The modus operandi:  Polyunsaturated and to a lesser extent monounsaturated fats because of their double bond(s) have free electrons which is available for attachment to by reactive chemicals, which when in sufficient amounts and occurring within cell walls, it becomes a healthy issue.   Because of oxidation, milk is high in saturated fats. 

The Dietary Fix and in concise:  The question isn’t how can I lower my risk factor for CAWD to that of those who live on Crete (Mediterranean diet),[2] but to lower it to the level of the Kitavans (footnote 5).  This requires undoing the damage done to our complex weight regulatory system, and then not damaging it again by excessive fructose.[3]  The simple answer is fasting made more effective with a low carb diet.   To learn more I highly recommend reading the two books by Dr. Jason Fung and watching his lectures on YouTube.  In a more concise form then his books, you will find my dietary advice and a longer version (my advice was arrived at prior to reading and watching his lectures).  It is easier not to eat than to significantly reduce calories long term.  With reduce calories the body goes into the starvation mode, and through the hormone leptin lowers metabolism from 25 to 40%, and this makes additional weight loss unlikely and creates the feeling that to eat more will make the dieter feel better. With fasting the body burns fats, not conserve it, and increases metabolism to promote searching for foods.   It is as Dr. Fung wrote in Obesity Code, “It is more important not to eat than what you eat.”  In one clinical trial, skipping breakfast resulted in a reduction of 539.  An easy start is to do intermittent fasting (skipping a meal) and progress into alternate day fasting and thereby avoid the metabolic consequences of being in the starvation mode.