Category Archives: Dr. Ali Course on Insulin Toxicity

Dr. Ali’s Insulin Library

Majid Ali, M.D.

My Oxygen Thinking Has Given Me Insights About the Roles of Insulin in Health and Disease which Robustly Challenge the Prevailing Notions of Insulin, Insulin Resistance, and Hyperinsulinism. 


 

Large Claims Require Large Bodies of Information

I offer my free-access library of insulin and hyperinsulinism (links included below) in an attempt to meet my obligation when I choose to challenge the prevailing dogmas of hyperinsulinism and Type 2 diabetes (T2D).

I would be most grateful to visitors to this website who find errors in my materials or disagree with me in other ways to send their disagreements to me at aliacademy7@yahoo.com.  


Dr. Ali’s Insulin Library


Community Texts : Free Books : Free Texts : Download & Streaming …

Majid Ali, M.D. Why I Don’t Recommend Skim Milk Products. – -. by Majid Ali, M.D.. texts … 20 20. 4. IJGMP Metabolic Syndrome. Aug 20, 2016 08/16. by IASET …

Seven Stages of Insulin Toxicity | The Ali Academy Community

Apr 30, 2011 – Majid Ali, M.D. In matters of life span, I summarize the lessons learned from my patients with the following simple words: Keep insulin low …

Insulin Toxicity and Dysfunction videos part 1 | The Ali Academy …

Insulin Literacy Understanding Insulin Dysfunction A1c and Insulin Toxicity from Majid Ali on Vimeo. Cheese Is Good For Reversing Insulin Toxicity Part Two …

The Oxygen Model of Insulin Toxicity – Majid Ali, M.D. | The Ali …

Aug 4, 2012 – I proposed my Oxygen Model of Insulin Toxicity as a unifying model that recognizes disturbances of oxygen functions as the fundamental …

INSULIN TOXICITY – Insulin Club

Insulin Toxicity. Majid Ali, M.D.. Related … Insulin Thinking Videos on YouTube Encyclopedia … Hypoglycemia) Is Nearly Always Caused by Insulin Toxicity.

Seven Stages of Insulin Toxicity – Dr. Ali’s Virtual Medical Library

drali1.org/insulin_seven_stages.htm

Seven Stages of Insulin Toxicity. Majid Ali, M.D. In matters of the life span, I summarize the lessons learned from my patients with the following simple word.

Insulin Toxicity – Dr. Ali’s Virtual Medical Library

drali1.org/insulin-toxicity.htm

Dr. Ali’s nsulin Toxicity Course Majid Ali, M.D.. I divide my Insulin Toxicity Course in the following two parts: Insulin Toxicity Course Part One. Insulin Toxicity …

Majid Ali, M.D. * Insulin Toxicity De-mystifies the Metabolic Syndrome …

Jun 28, 2012 – Uploaded by majid ali

The true mature of the metabolic syndrome is insulin toxicity. The term metabolic syndrome creates creates …

Seven Stages of Insulin Toxicity Seminar Majid Ali MD on Vimeo

https://vimeo.com › Majid Ali › Videos
May 12, 2014

Professor Majid Ali shares information about “Seven Stages of Insulin ToxicitySeminar”

Insulin Toxicity De-mystifies the Metabolic Syndrome Majid Ali MD on …

https://vimeo.com › Majid Ali › Videos
Apr 6, 2014

Professor Majid Ali MD. shares information about Insulin Toxicity De-mystifies the Metabolic Syndrome.

Dr. Ali’s Course on Insulin Toxicity | – Ali Healing Community

Jan 11, 2017 – Majid Ali, M.D. Workable Simplicity to Understand Maddening Complexity of Three Scourges of Our Time Dr. Ali’s Insulin-Diabetes Video and …

Ali Diabetes | Preventing and Reversing Diabetes With Insulin Literacy

5 days ago – Preventing and Reversing Diabetes With Insulin Literacy. … Majid Ali, M.D. ….. Majid Ali, M.D. * Insulin Toxicity De-mystifies the Metabolic …

Insulin Toxicity | Ali Academy

Feb 9, 2015 – Posts about Insulin Toxicity written by Majid Ali MD.

Dr. Ali’s Autism Course | Childrens Health Corps

Sep 20, 2015 – Majid Ali, M.D. Evidence for My Proposed Insulin-Autism Connection … studies of the energetic-molecular of autism, as well as insulin toxicity.

Dr. Ali Course On Insulin Toxicity — Blogs, Pictures, and more on …

ia.wordpress.com/tag/dr-ali-course-on-insulin-toxicity/

Diabetes Is Rooted In Insulin Toxicity – Part Two. Majid Ali, M.D.. Diabetes Begins 15–20 years before it is diagnosed. Text Reproduced From An Important …

Insulin Neuropathy Reversed With Natural Remedies Majid Ali, MD

aliacademy.org/neuropathy1.htm

Majid Ali, M.D.. In my clinical experience, the most common cause of neuropathy is insulin toxicity. Some years ago, I introduced the term “insulin neuropathy” for …

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Sign up for Dr. Ali’s E-Newsletter. Dr. Ali’s … Majid Ali, M.D.’s Seminars … $14.95, Reduction of Insulin,Toxicity of Insulin, and the Management of Insulin. $14.95.

DIABETES – Insulin Toxicity and Reversal of Diabetes Seminar by …

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In this 55-minute video seminar, Professor Majid Ali, M.D. discusses the causes, clinical features, and consequences of insulin toxicity, including pre-diabetes …

Majid Ali MD, Gestational Diabetes Is Insulin Toxicity of the Unborn …

Jan 22, 2017 – It is regrettable that doctor order glucose tolerance for expecting mothers but do not include insulin tests with the same blood tests. Excess …

Dr. Majid Ali, MD discusses the serious impact of insulin toxicity …

http://www.ihealthtube.com Dr. Cal Streeter talks about the dangers of a couple of traditional cancer treatments. He also talks about the body’s own ability to kill …

Two Dimensions of Insulin Dysregulation

Majid Ali, M.D., FRCS (Eng), FCAP (Path)

Type 2 Diabetes (TD2) Is Rooted In the First Dimension of Insulin Dysregulation. Type 2 diabetes does not occur when the first dimension of insulin dysregulation is detected and reversed.


SPECIAL NOTES

Treatment plans for reversing prediabetes (hyperinsulinism) and diabetes are presented at this site under the titles of

Reversing Prediabetes and Diabetes With 3D Plan 

 Links to important related articles are included at the end of this article.


Two Dimensions of Insulin Dysregulation

The author recognizes two primary dimensions of insulin dysregulation: (1) the first dimension is of excess insulin accompanied by a multitude of adverse effects of hyperinsulinism without associated glycemic disruptions characteristic of Type 2 diabetes; and (2) the second dimension of excess insulin accompanied by glycemic disruptions that meet the numerical criteria of Type 2 diabetes (T2D). The first dimension is rooted in the toxicities of food, environment and thought, while the second dimension is rooted in the first dimension. The first dimension is optimally detected by measuring timed blood insulin concentrations following an oral glucose load as shown in Tables used for case studies. The core message of this short article is this: If the first dimension of insulin dysregulation can be reversed, the problem of the second dimension (T2D) simply does not arise.


The Oxygen-Insulin View of Insulin Dysfunction, Diabetes Type 2, and Reversing Diabetes 3D

Oxygen is the organizing principal of biology and governs the aging process. The author began his book Oxygen and Aging (2000) with those words. This simple statement was the essence of his interest and study of molecular biology of oxygen for twenty years.1-4 His interest in molecular biology of insulin5-8 arose from his work in oxygen. The “oxygen-insulin perspective” of the two dimensions of insulin dysfunction and its scientific underpinnings was comprehensively discussed in his book entitled Dr. Ali’s Plan for Reversing Diabetes (2011)9 as well as in a series of follow-up publications.10-18

Life is an injury-repair-injury cycle. Cellular injury is intertwined with cellular repair by diverse mechanisms. Patterns of repair change with varying types of injury and the prevailing tissue condition. The constant in all this is expanded energy requirement of cells in the repair processes. Whether cellular repair is in acne or psoriasis, in polycystic ovarian syndrome in young women or recurrent prostatitis in young men, in chronic GERD-gastritis complex or Crohn’s colitis, inflammatory arthritis or pulmonary interstitial fibrosis, steatosis of the liver or chronic renal failure, systemic lupus erythematosus (see illustrative case study in Table 4) or scleroderma, the core requisite of cellular repair is the same: increased energy demands. Hyperinsulinism, in this context, is pancreatic response to increased energy needs for repair of injured tissues. The author has documented the presence of the first dimension of insulin dysregulation in all of the above-mentioned pathologic entities.


 

Three Crucial Aspects of Two Dimensions of Insuloin Dysregulation

From a clinical standpoint, three other aspects of the two dimensions of insulin dysfunction are:

  1. Epigenetics play greater roles than genetics in both dimensions;
  2. Understanding the pathophysiology, clinical courses, and optimal management of both dimensions of insulin dysregulation calls for a shift of focus from glycemic status to insulin homeostasis;
  3. Since first dimension is not accompanied by glycemic disruptions, the lab tests for glycemic status (fasting and 2-hour postprandial blood sugar levels, and A1c test) are not suitable in the detection and reversal of the first dimension.

 

Neglect of the First Dimension Deepens the Suffering of the Second Dimension

The data in Tables 1 and 2 summarizes the core statistical relationships between the two dimensions of insulin dysfunction. The two columns presenting mean peaks of blood glucose and post-glucose-load insulin concentrations in Table 1 dramatically document how far the prevailing practices of neglecting the first dimension go to deepening the problems caused by the second dimension.

Table 1. Insulin Homeostasis Categories in 506 Study Subjects Without Type 2 Diabetes

Insulin Category* Percentage of Subgroup Mean Peak Glucose mg/dL(mmol/mL) Mean Peak Insulin (uIU/mL)
Exceptional Insulin Homeostasis   N =   12**
1.7% 110.2     (6.12) 14.3
Optimal Insulin Homeostasis         N =   126
24.9 % 121.2     (6.73) 26.7
Hyperinsulinism, Mild                       N = 197
38.9 % 136.5   (7.58) 58.5
Hyperinsulinism, Moderate           N = 134
26.5 % 147.0   (8.16) 109.1
Hyperinsulinism, Severe                 N = 49
9.7 % 150.0   (8.33) 231.0
Correlation coefficient, r value, for means of peak glucose and insulin levels in the five insulin categories is 0.84.

*Criteria for classification: (1) Exceptional insulin homeostasis, with fasting insulin concentration of <2 uIU/mL and mean peak insulin concentration of <20; (2) optimal insulin homeostasis, peak insulin <40 accompanied by unimpaired glucose tolerance; (3) mild hyperinsulinism, peak insulin <80 accompanied by unimpaired glucose tolerance; (4) moderate hyperinsulinism, peak insulin <160 accompanied by unimpaired glucose tolerance; (5) severe hyperinsulinism, peak insulin <160 accompanied by unimpaired glucose tolerance.

** Exceptional insulin homeostasis, a subgroup of optimal insulin homeostasis.


 

Table 2 Insulin Homeostasis Categories in 178 Study Subjects With Type 2 Diabetes
Insulin Category Percentage of Subgroup Mean Peak Glucose, mg/dL

(mmol/mL)
Mean Peak Insulin (uIU/mL)
Diabetic Hyperinsulinism, Mild       N =   53
29.0% 252.0   (14.00) 55.4
Diabetic Hyperinsulinism, Moderat N = 42
24.0% 242.1   (13.45) 112.4
Diabetic Hyperinsulinism, Seve       N =   24
13.9% 224.6   (12.47) 298.0
Diabetic Insulin Deficit                     N = 59
33.1% 294.0   (16.33) 22.9

 

Neglect of the First Dimension By Laboratory Professionals

 The neglect of first dimension by the laboratory professionals is one of the most disturbing aspects of the sordid story of the two dimensions of insulin dysregulation. For instance, the reference range for the 2-hr post challenge blood insulin concentration of laboratory 2 (Table 3) is an astonishingly and utterly clinically unusable 0.0 to 163.5.

Table 3. Insulin Reference Ranges in uIU/mL of Six Laboratories in New York Metropolitan Area*

 

Laboratory Fasting 1 Hr 2 Hr 3 Hr
Laboratory 1 1.9 – 23 8 – 112 5 – 35 Not Reported
Laboratory 2 2.6 – 24.9 0.0 – 121.9 0.0 – 163.5 Not Reported
Laboratory 3 6 – 24.9 8 – 112 5 – 55 3 – 20
Laboratory 4 6 – 27 20 – 120 18 – 56 8 – 22
Laboratory 5 00 – 30 30 – 200 40 – 300 50 – 150
 

Laboratory 6

Does not include insulin ranges in the report. Instead it includes the following note: Insulin analogues may demonstrate non-linear cross-reactivity in this essay. Interpret results accordingly.**

*Upper and lower limits of laboratory reference ranges for blood insulin concentration determined following a Standard 75-gram glucose challenge.

**Personal communications with clinicians revealed that they do not find this laboratory note to be satisfactory in their clinical decision-making.


 

Mechanisms of Insulin Regulation and Two Dimensions of Insulin Dysregulation

 The following is text on the subject from the author’s comments e-published in June, 2017 by the journal Nature. “The work of Zhang and colleagues is important for physicians who treat diabetes because class B G- protein-coupled receptors (GPCRs) are important therapeutic targets. Beyond that, this work invites all physicians to a deeper study of the inner mechanisms of insulin homeostasis, a subject that is seldom duly considered in clinical medicine. Specifically, insulin dysregulation has two distinct dimensions: (1) the first dimension of pathophysiology of hyperinsulinism which predates Type 2 diabetes (T2D) and is not accompanied by glycemic abnormalities detectable by the laboratory tests in current use; and (2) the dimension of T2D accompanied by hyperglycemia and its biochemical consequences. This author has long recognized the need for a shift of clinical focus from glycemic status to insulin homeostasis for detecting and optimally managing adverse metabolic, proinflammatory, endothelial, developmental, and neurologic effects of hyperinsulinism (ref. 2-6).”

Table 4. Severe Hyperinsulinism In A 13-Yr-Old With SLE, ITP, Recurrent Pneumonia, and Optic Neuritis With Right Eye Blindness.

The Peak Insulin Fell from 718 to 238.5 In Four Months of Robust Integrative Treatment.

Fasting ½ Hr 1Hr 2Hr 3Hr
Insulin uIU/mL
27.9 362.5 424.0 718.2 571.7
Glucose mg/mL
      70 140 157 150 111
Insulin and Glucose Profiles Obtained After Four Months of Robust Integrative Therapies
Insulin uIU/mL
7.2 125.1 238.5 208.0 132.0
Glucose mg/mL
81 154 181 130 97
 

Table 5. Control of Hyperinsulinism With Reversal of Type 2 Diabetes In A 75-Yr-Old 5’ 2” Female Weighing 162 Lbs. With Hypertension and Chronic Sinusitis.

4.30.2013 Fasting ½ hr 1 hr 2 Hr 3 Hr
Insulin uIU/mL
16 37 59 113 152
Glucose mg/mL (mmol/L)
112 158 214 241 155
10.17.2014*
Insulin uIU/mL
23.8 19.3 36.9 114.7 75.2
Glucose mg/mL (mmol/L)
116 167 253 297 172
4.14.2015**
Insulin uIU/mL
6.2 22.1 42.9 51.2 39.7
Glucose mg/mL /L)
96 130 193 112 105

* A1c, 6.3%; ** A1c, 5.9%

 

Reversing Prediabetes (Hyperinsulinism) and Diabetes With 3D Plan

The insulin homeostasis protocol (the “Protocol”) evolved as a three-prong approach comprising: (1) diet; (2) detox; and (3) dysoxic comorbidities (oxygen-related coexisting pathologic entities) including disrupted hypothalamic and related neural pathways which regulate the energy economy of the body. The three “diabetes 3D” subjects are vast and clearly beyond the scope of this brief outline. A comprehensive discussion of all above subjects is presented at free access www.alidiabetes.org. Google search words are: majid ali, shifting focus from glycemic status to insulin homeostasis.


 

References

1.   Ali. M. Respiratory-to-Fermentative (RTF) Shift in ATP Production in Chronic Energy Deficit Disorders. Townsend Letter for Doctors and Patients. 2004.

2.   Ali M. Darwin, oxidosis, dysoxygenosis, and integration. J Integrative Medicine. 1999;3:11-16.

3.   Darwin, Dysox, and Disease. Volume 11. The Principles and Practice of Integrative Medicine 11. New York: Canary 21 Press; 2002.

4.   Ali M. The Principles and Practice of Integrative Medicine Volume I: Nature’s Preoccupation With Complementarity and Contrariety. New York. Canary 21 Press. 1998. 2nd edition 2005.

5.   Ali M. Epidemic of Dysoxygenosis and the Metabolic Syndrome. In: The Principles and Practice of Integrative Medicine. Volume 5. Pp 246-256. Canary 21 Press. New York. 2005.

6.   Ali M. Insulin Toxicity, Inflammation, And  the Clinical Benefits of Chelation. Part I. Townsend Letter-The examiner of Alternative Medicine. 2009;315:105-109. October, 2009.

7.   Ali M. Hypothesis: obesity is adipomyocytic dysoxygenosis. J Integrative Medicine. 2004;9:19-38.

8.   Kahn SE, 1, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444, 840-846.

9.   Shoelson, SE, Lee J. Goldfine AB. Inflammation and insulin resistance. J. Clin. Invest. 2006;116: 1793–1801.
2

10.                  Murphy KG, Bloom SR. Gut hormones and the regulation of energy homeostasis. Nature. 2006;444:854-859.

11.                 .Kamada N, Seo S-U, Zhiming C, et al. Role of the gut microbiota in immunity and inflammatory disease. Nature Reviews Immunology. 2013;12:321-335.

12.                 International Diabetes Federation. Diabetes Atlas. 2016. Seventh edition. www.diabetesatlas.org.

13.                 Shulman G. Ectopic Fat in Insulin Resistance, Dyslipidemia, and Cardiometabolic Disease. N Engl J Med. 2014; 371:1131‑1141.

14.                 Bahi-Buisson N, Roze E, Dionisi C, et al. Neurological aspects of hyperinsulinism-hyperammonaemia syndrome. Dev Med Child Neurol. 2008;50:945-9.

15.                Lillioja S, Mott DM, Spraul M, et al. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependant diabetes mellitus: Prospective studies of Pima Indians. N Engl J Med. 1993;329:1988-1992.

16.                Ali M. Oxygen and Aging. (Ist ed.) New York, Canary 21 Press. Aging Healthfully Book 2000.

17.                Ali M. Oxygen governs the inflammatory response and adjudicates the man-microbe conflicts. Townsend Letter for Doctors and Patients. 2005;262:98-103.

18.                Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J. Clin. Invest. 2005;115:1111–1119.

19.                 Ali M. Fayemy AO, Ali O. Dasoju S, et al. Shifting Focus From Glycemic Status to Insulin Homeostasis. .  Townsend Letter-The Examiner of Alternative Medicine. 2017;402:91-96.

20.                 Ali M. The Principles and Practice of Integrative Medicine Volume X: Darwin, Oxygen Homeostasis, and Oxystatic Therapies. 3 rd. Edi. (2009) New York. Institute of Integrative Medicine Press.

21.                 Ali M. The Principles and Practice of Integrative Medicine Volume XI: Darwin, Dysox, and Disease. 2000. 3rd. Edi. 2008. New York. (2009) Institute of Integrative Medicine Press.

22.                 Ali M. The Principles and Practice of Integrative Medicine Volume XII: Darwin, Dysox, and Integrative Protocols. New York (2009). Institute of Integrative Medicine Press.

23. Ali M. The Philosophy and Science of Healing. APPNA Journal. 2015;25:18-19.

24.                Nath D, Heemels M-T, Lesley Anson L Obesity and diabetes. Nature. 2006;444, 839.

25.                Das S. Identity of Lean-NIDDM: Clinical, metabolic and hormonal status. In: Kochupillai N, ed. Advances in Endocrinology, Metabolism, and Diabetes. Vol. 2. Delhi, India: Macmillian; 1994:42-53.

26.                 Wellen KE, Hotamisligil GS. Inflammation, stress, and diabetes. J. Clin. Invest. 2005;115:1111–1119.

27.                Patti ME, Butte AJ, Crunkhorn S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PGC1 and NRF1. Proc Natl Acad Sci U S A. 2003;100:8466-8471.

28.                 von Herrath M. Insulin trigger for diabetes. Nature. 2005;435:151-152.

29.                Ali M. Oxygen governs the inflammatory response and adjudicates the man-microbe conflicts. Townsend Letter for Doctors and Patients. 2005;262:98-103.

30.                Xu H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J. Clin. Invest. 2003;112:1821–1830.

31.                 Stanley SA, Kelly L, Kaasmashri N, et al. Bidirectional electromagnetic control of the hypothalamus regulates feeding and metabolism. Nature. 2016  531:647–650.

32.                Ali M. Autism. Nature

33.                Ali M. Ali M. Molecular basis of autism and dysautonomia. Townsend Letter-The examiner of Alternative Medicine. 2017 (in press).

34.                Ali M. Lab ranges www.alidiabetes.org

35.                 Kaveeshwar SA, Cornwell J. The current state of diabetes mellitus in India. Australas Med J. 2014;7:45-48.

36.                 Lesley J, Manning LA, Ogle GD. A survey of diabetes services in hospitals in Ali Papua New Guinea. P N G Med J. 2001: 44:88-95.))

37.                 Xu Y, Wang L, He J, et al. Prevalence and control of diabetes in Chinese adults. JAMA. 2013; 310: 948-59.

38.                 Ali M.  Oxygen model of hyperinsulinism.  xxxx

39.                 Ali M. Dysox Model of Diabetes and De-Diabetization Potential. Townsend Letter-The examiner of Alternative Medicine. 2007; 286:137-145.

40.                 Ali M. Plan for Reversing Diabetes. New York, Canary 21 Press. Aging Healthfully Book 2011.

41.                 Ali M. Importance of Subtyping Diabetes Type 2 Into Diabetes Type 2A and Diabetes Type 2B. Townsend Letter-The Examiner of Alternative Medicine. 2014; 369:56-58.

42.                 Chouchani ET, Victoria R. Pell VR, Edoardo Gaude E, et. al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature 515, 431–435.

43.                 Ali M. Succinate Retention. In: Chouchani ET. Pel VR,  Gaude E, et al.Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature;2014;515:431. (commentary after references).

44.                 185. Ali M. Succinate Retention: The Core Krebs Dysfunction in Immune-Inflammatory Disorders. Townsend Letter. 2015;388:84-85.  

Dementia Is Rooted in Insulin Brain Toxicity

Majid Ali, M.D.

All Known risk factors of dementia are first known risk factors of hyperinsulinism (insulin toxicity and then of Dementia.


Dementia Is rooted in insulin toxicity. I support my view by showing here that all known risk factors of dementia are rooted in insulin toxicity excess – hyperinsulinism, by another name.


 

Insulin Toxicity Can Be Reliably Detected Only by Blood Insulin Tests

The only direct and reliable method of detecting insulin toxicity is timed measurements of blood insulin concentrations after a glucose challenge. Employing this insulin test, in 2017, my colleagues and I documented a prevalence rate of hyperinsulinism of 75.1% in the general population in New York metropolitan area.1 This was not surprising since four years earlier the Chinese, employing blood glucose tests had reported a combined prevalence rate of prediabetes and diabetes of 50.1%.2

The core message of this short article, I state at the beginning, is: find out if you are insulin-toxic with blood insulin tests, and if this be the case, and you and on the path to dementia, clear insulin toxicity. For this purpose, I suggest my 3D Insulin Protocol comprising diet, detox, and dysox plans, and are presented in detail at www.alidiabetes.org.

 

Dementia Is rooted in insulin excess – hyperinsulinism, in the medical jargon is the term for it – which precedes Type 2 diabetes (T2D) by five, ten, or more years. This, succinctly stated, is the basic relationship between dementia, diabetes, insulin resistance and hyperinsulinism.

 

As for the cause of dementia, my assertion that insulin toxicity is the root cause of dementia was one of the prediction of both oxygen model of hyperinsulinism and the oxygen model of dementia. I put forth these models in 19951 as extensions of my oxygen model of aging proposed in 19802. These models were based on my studies of mitochondrial dysfunction and respiratory-to-fermentative shift in chronic immune-inflammatory and other disorders proposed on 1980.

Diabetes Is Rooted In Insulin Toxicity – Part Two

Majid Ali, M.D.

Diabetes Begins 15–20 years before it is diagnosed


 

Text Reproduced From An Important Published Paper
Article: Hulsegge G, Spijkerman AMW, van der Schouw, et al. Trajectories of metabolic risk factors and biochemical markers prior to the onset of type 2 diabetes: the population-based longitudinal Doetinchem study.  Nutrition & Diabetes (2017) 7, e270; doi:10.1038/nutd.2017.23

Background:
Risk factors often develop at young age and are maintained over time, but it is not fully understood how risk factors develop over time preceding type 2 diabetes. We examined how levels and trajectories of metabolic risk factors and biochemical markers prior to diagnosis differ between persons with and without type 2 diabetes over 15–20 years.
Methods:
A total of 355 incident type 2 diabetes cases (285 self-reported, 70 with random glucose 11.1mmoll−1) and 2130 controls were identified in a prospective cohort between 1987–2012. Risk factors were measured at 5-year intervals. Trajectories preceding case ascertainment were analysed using generalised estimating equations.
Results:
Among participants with a 21-year follow-up period, those with type 2 diabetes had higher levels of metabolic risk factors and biochemical markers 15–20 years before case ascertainment. Subsequent trajectories were more unfavourable in participants with type 2 diabetes for body mass index (BMI), HDL cholesterol and glucose (P<0.01), and to a lesser extent for waist circumference, diastolic and systolic blood pressure, triglycerides, alanine aminotransferase, gamma glutamyltransferase, C-reactive protein, uric acid and estimated glomerular filtration rate compared with participants without type 2 diabetes. Among persons with type 2 diabetes, BMI increased by 5–8% over 15 years, whereas the increase among persons without type 2 diabetes was 0–2% (P<0.01). The observed differences in trajectories of metabolic risk factors and biochemical markers were largely attenuated after inclusion of BMI in the models. Results were similar for men and women.
Conclusions: 
Participants with diabetes had more unfavourable levels of metabolic risk factors and biochemical markers already 15–20 years before diagnosis and worse subsequent trajectories than others. Our results highlight the need, in particular, for maintenance of a healthy weight from young adulthood onwards for diabetes prevention.

Text continued
Although it has been well established that adverse levels of risk factors often develop early in life and are maintained over time,123456 it is not fully understood how they progress to type 2 diabetes (T2D). For example, T2D might be preceded by a gradual accumulation of the adverse effects of risk factors starting at a young age, or by a relatively sudden deterioration in risk factors before disease onset, or by a combination of both. The comparison of long-term trajectories of risk factors between those who do and those who do not develop T2D may help to identify at which time point these trajectories start to deviate before the development of overt disease. Such insight into the timing and the extent of pathophysiological changes before symptoms occur may provide indications for the optimal timing of preventive actions. Trajectories of BMI and waist circumference are of particular importance since these are strong modifiable risk factors of T2D.78 Other relevant factors associated with T2D include glucose levels,9 β-cell function,10 insulin resistance,10 blood pressure,8lipids,8 liver fat markers,1112 markers of chronic inflammation13 and kidney function.14
Several studies have described gradual changes in β-cell function, insulin resistance, fasting glucose and 2-h post-load glucose many years before diagnosis of T2D with steeper unfavourable changes 3–5 years before diagnosis.1516171819 Only a few studies, mainly among men, have examined progressive changes of other risk factors, such as BMI, but so far findings have been inconsistent. The Whitehall II study showed that adults who developed T2D had similar trajectories of BMI and C-reactive protein (CRP) but more unfavourable trajectories of systolic blood pressure and high-density lipoprotein (HDL) cholesterol compared with adults without T2D, over a period of ~14 years.2021 In contrast, a small study of 177 men observed larger changes in BMI, but no differences in blood pressure, HDL cholesterol and liver fat markers in men who developed impaired fasting glucose compared with men who did not, over a 9-year period.22 A short-term study (that is, over 1.5 years) observed differences in changes of alanine aminotransferase (ALT) and triglycerides but not in blood pressure, total cholesterol and HDL cholesterol between high-risk men with incident T2D and controls.17
A longer follow-up period in a population-based study and inclusion of other metabolic risk factors and biochemical markers is needed for more insight in the physiological changes preceding the onset of T2D. There is also a need to investigate differences between men and women since previous studies reported several sex-related differences in the associations of risk factors such as systolic blood pressure, HDL cholesterol and uric acid with T2D.2324 Therefore, we examined whether trajectories of metabolic risk factors and biochemical markers among initially healthy men and women differed for those who developed T2D and those who did not over a period of up to 15–20 years.

More Information at Dr. Ali’s Diabetes Library linked below:

Majid ali Insulin Neuropathy diabetes hyperinsulinemia nerve damage …

Posts about Majid ali Insulin Neuropathy diabetes hyperinsulinemia nerve damage Reversed With Natural Remedies written by.

Majid Ali pre-diabetes diabetes hyperinsulinemia Insulin Toxicity – A …

Oct 8, 2012 – Majid Ali, M.D. The subject of insulin toxicity is almost universally ignored by doctors.Insulin-toxic individuals pay a huge price for such neglect.

The Oxygen Model of Insulin Toxicity – Majid Ali, M.D. | The Ali …

Aug 4, 2012 – in my book “Dr. Ali’s Plan for Reversing Diabetes,” I presented the following 3-M schema of the development of insulin toxicity. In this schema …

Ali Diabetes | Preventing and Reversing Diabetes With Insulin Literacy

Shifting Focus From Glycemic Status to Insulin Homeostasis for Stemming Global Tides ofHyperinsulinism and Type 2 Diabetes by Majid Ali, MD, FRCS (Eng), …

Shifting Focus From Glycemic Status to Insulin Homeostasis (Jan 2017 …

Shifting Focus From Glycemic Status to Insulin Homeostasis for Stemming Global Tides ofHyperinsulinism and Type 2 Diabetes by Majid Ali, MD, FRCS (Eng), …

Dr. Ali’s Insulin Reduction Protocol

Dr. Ali’s Insulin Reduction Protocol. For Improving Insulin Efficiency. Majid Ali, M.D.. To reverse pre-diabetes and diabetes (completely or partially), my primary …

Dr. Ali’s Diabetes Reversal program – Dr. Ali’s Virtual Medical Library

drali1.org/dr__ali’s_diabetes_reversal_guidelines.htm

Dr. Ali’s Diabetes Reversal Guidelines. Majid Ali, M.D.. The science and philosophy of reversing diabetesType 2 associated with excess insulin is simple to …

Reversing Diabetes – Majid Ali – AliAcademy.org

aliacademy.org/reversing_diabetes.htm

In this 40-minute seminar, Professor Majid Ali, M.D. Presents his reasons for why … Simply stated,diabetes Type 2A is a state of insulin toxicity created by insulin …

Dr. Ali’s Breakfast for Losing Weight, Reversing Diabetes, and Staying …

Aug 28, 2014 – Majid Ali, M.D.A Breakfast for Insulin-Smart Eating and Healthful Aging There is never a valid reason for missing breakfast. So strong is my …

Low Insulin Levels – Good and Bad – alihealing.org

alihealing.org/2017/05/24/low-insulin-levels-good-and-bad/

May 24, 2017 – Shifting Focus From Glycemic Status to Insulin Homeostasis for Stemming Global Tides of Hyperinsulinism and Type 2 Diabetes by Majid Ali, …

Majid Ali MD | Ali Academy | Page 4

Sep 16, 2014 – Diabetes Reversal Case Study 2 – Diabetes Reversal With Control of Hyperinsulinism Majid Ali, M.D. This article describes a case of reversal …

Reporting a comment for the article : Acetate mediates a microbiome …

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Jun 9, 2016 – Majid Ali said: … The plans for hyperinsulinism modification and Type 2 diabetestreatment in this model are based on the simplicity of …

Majid Ali MD, Dr. Ali’s Book on Reversing Diabetes – Dr. Ali’s Plan for …

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Nov 6, 2014

I outline the contents of this book on reversing diabetes Type 2. I explain how it begins with insulin toxicity …

Majid Ali, M.D. * Insulin Toxicity De-mystifies the Metabolic Syndrome …

Jun 28, 2012 – Uploaded by majid ali

The true mature of the metabolic syndrome is insulin toxicity. The term … Majid Ali, M.D. * Insulin Toxicity …

https://alidiabetes.org/2015/03/07/insulin-respon…betes-reversal …

Apr 2, 2015 – Majid Ali, M.D. (Published in Town send Letter April 2014) In a previous column, I presented The Oxygen Model of Diabetes and the …

Just got my results back from a glucose tolerance test – Page 3 …

Oct 6, 2014 – 10 posts – ‎6 authors

There’s a doctor (Majid Ali, MD), who tests or has tested insulin levels of many patients with or withoutdiabetes. He has found, over years of …

[PDF]Oxygen, Insulin Toxicity, Inflammation, and the … – ENCOGNITIVE.COM

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by Majid Ali, MD majidalimd@aol.com … Insulin Reduction and EDTA Chelation: Two Potent … 2diabetes that is characterized by hyperinsulinemia. I did not see …

Dr. Ali Course On Insulin Toxicity — Blogs, Pictures, and more on …

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Shifting Focus From Glycemic Status to Insulin Homeostasis for Stemming Global Tides of Hyperinsulin and Type 2 Diabetes. Majid Ali, M.D.. Article Published in …

Oxygen, Ozone, & Hydrogen Peroxide by Dr Majid Ali

educate-yourself.org/cancer/ozonebymajidli17jul03.shtml

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Jul 17, 2003 – By Majid Ali, M.D.<majidalimd@aol.com> ….. Diabetes 1994;43:580-6. 89. … Insulin-like activity of coconcanavalin A and wheat agerm …

Beyond insulin resistance and syndrome X:

Majid Ali, M.D.

Oxidative – Dysoxygenative Model

of Insulin Toxicity and DiabetesHomeostasis (2001)


 

Beyond insulin resistance and syndrome X: tThe oxidative-dysoxygenative insulin dysfunction (ODID) modelof Insulin Toxicity--Part II. 

Nitric Oxide Dynamics and ODID

Reactive oxygen species (ROS) induce production of reactive nitrogen species (RNS). RNS, in turn, stimulate the generation of reactive oxygen species. The feedback loops provided by ROS-RNS dynamics feed the oxidative fires and inflict oxidative cellular injury. Under physiologic conditions, superoxide dismutase, catalase, glutathione peroxidase, and a host of enzymes support the reduction arm of redox equilibrium. In hyperinsulinemic and hyperglycemic states, the ROS/RNS loops significantly add to cumulative oxidosis. (158-160)

Endothelium-derived nitric oxide exerts several homeostatic effects in the vascular ecology, including regulation of vasomotor tone, inhibition of platelet aggregation, and prevention of adhesion of leukocytes to the endothelial surface (Vane 1990). In animal models as well as in both type 1 and type 2 diabetes, nitric oxide-dependent vasodilation is impaired. (158) Ascorbic acid improved the vasodilatory response in both types of diabetes. (29,30) Endothelium-dependent vasodilation is impaired in healthy subjects after six hours of hyperglycemic clamp. (159) Studies with incremental brachial artery administration of methacholine chloride during euglycemia and hyperglycemia support one of the core tenets of oxidative insulin dysfunction in that hyperglycemia contributes to abnormal endothelial function through production of superoxide anion. (37)

Higher concentrations of insulin in the blood increase blood flow to the skeletal muscle. (164-170) Some of the increase in the cellular glucose uptake has been attributed to that effect of insulin on the blood flow. The precise mechanism of action of insulin in blood vessel musculature has not been elucidated, but the role of nitric oxide in it has been postulated. (167) Other data suggest that the vasodilatory effect in the skeletal muscle is dependent on hyperinsulinemia and not consequent upon changes in carbohydrate metabolism. There is also evidence there is a reduction in insulin-induced vasodilation in insulin resistance associated with obesity. (165,169,170) in other words, insulin facilitates its own delivery to the cell membrane and degradation.

Activation of endothelial NO-synthase in higher concentration is deemed necessary for initiation of the oxidative cascade in endothelial cells that leads to production of excess reactive oxygen species and induction of NF-[kappa]B.

Tumor Necrosis Factor (TNF-[alpha]) and ODID

The secretion of TNT-[alpha] by adipocytes is of special interest to me in the context of the proposed oxidative insulin dysfunction model

of insulin resistance and type 2 diabetes. This cytokine plays many well-established and crucial roles in the inflammatory and immune responses. (94,171-176) It is expressed in excess in adipocytes of obese patients and is known to cause insulin resistance through its effects on insulin-mediated cellular signaling pathways.

Tumor necrosis factor [alpha] (TNF-[alpha]) is a potent inhibitor of insulin signaling in myocytes and adipocytes. (174) Since serum concentrations of TNF-[alpha] are very low in lean as well as obese subjects, this cytokine produced in the muscle and fat cells appears to function in a paracrine fashion. TNT-[alpha] expression is high in the muscle and fat cells of obese and diabetic subjects. Furthermore, the administration of antibodies that neutralize TNF-[alpha] to genetically obese Zucker (fa/fa) rats reverses insulin resistance. (171) That creates another mechanism of insulin resistance in mice. Interestingly, administration of the same antibodies to diabetic patients did not reverse insulin resistance. (175)

All known inflammatory and immunologic responses are initially triggered as well as regulated by oxidative and oxygenative phenomena. (173-175) Blockade of TNF-[alpha] can ameliorate, albeit for limited periods of time, both experimental and clinical forms of antoimmune disorders, such as Crohn's colitis and rheumateid arthritis. (177-180) Hypersecretory TNF-[alpha] responses induced by oxidative stresses are likely to play a role in insulin homeostasis in states of oxidosis associated with hyperinsulinism.

NF-[kappa]B, Endothelial Cells, and ODID

NT-[kappa]B is a potent proinflammatory molecule. (181-133) Blockade of NF-[kappa]B decreases inflammatory responses in experimental and such as Crohn's colitis and rheumatoid arthritis. (184-186) All inflammatory responses create regional oxidosis and most also lead to systemic oxidosis. Such theoretical considerations strongly suggest that NF[kappa]B might play some roles in the pathogenesis of oxidative-dysoxygenative insulin dysfunction.

Thus, it comes as no surprise that high concentrations of glucose (10-30 mM) result in excess generation of reactive oxygen species which, in turn, activate NF-[kappa]B and induce endothelial cell apoptosis. (187) Studies with 3O-methyl-D-glucose (a glucose derivative which is taken up but not metabolized by cells) and L-glucose have shown that endothelial reactivity is mediated by glucose-specific pathways. This finding is of direct relevance to the pathogenesis of oxidative coagulopathy in uncontrolled diabetics. Endothelial apoptosis results in denudation of the nonthrombogenic inner lining of the vessel wall, resulting in the exposition of highly thrombogenic subendothelial matrix.

IGF-1, IGF-2, and ODID

Both insulin-like growth factor 1 (IGF-1) and insulin-like growth factor 2 (IGF-2) have insulin-like effects on glucose transport in the myocyte and adipocyte. (188-190) That is not unexpected in light of close sequence homologies between insulin and both IGF-1 and IGF-2. In addition, there is also a high degree of sequence homology between the insulin receptor and the IGF-1 receptor. Again, not surprisingly, intracellular signaling pathways activated by both receptors are similar. Like insulin, IGF-1 affects translocation of GLUT-4 to the myocyte surface in vitro (188) and exerts a potent hypoglycemic effect. (191)

In health, the glucoregulatory roles of IGF-1 and IGF-2 have been thought not to be significant since these factors arc sequestered by specific binding proteins and their serum concentrations in a free state are low. IGF-1 bypasses the insulin receptor and, under those conditions, exerts a significant glucoregulatory role by facilitating glucose uptake in the myocyte and adipocyte. (192) This has been shown in persons with type 1 and type 2 diabetes as well as in instances of mutations in the insulin receptor.

In the oxidative insulin dysfunction states, however, oxidatively induced alterations in the structure and function of those binding proteins are likely to occur. Indeed, there is some evidence that is so in patients with severe insulin resistance, hyperinsulinemia, and poorly controlled diabetes.

PPAR[gamma] and ODID

Adipocytes are rich in nuclear factor called peroxisome proliferation activator receptor-[gamma] (PPAR[gamma]). This receptor is an important determinant of adipogenesis and stimulates adipogenesis in fibroblasts. (193) Persons heterozygous for a dominant-negative PPAR[gamma] allele suffer from severe insulin resistance. (194) Mice heterozygous for a null PPAR[gamma] allele on a high-fat diet have increased insulin sensitivity and develop adipocyte hypertrophy. (195)

Ligands for PPAR[gamma] include thiazolidinediones (TZDs), a class of drugs for diabetes (discussed later). PPAR[gamma] binding in vitro correlates well with in vivo lowering of blood glucose levels. Non-TZD PPAR[gamma] ligands also increase insulin sensitivity. Furthermore, activators of the PPAR[gamma] heterodimer partner, retinoid X receptor, also increase insulin sensitivity and exert antidiabetic effects. (196)

The antidiabetic effects of some drugs, such as those in the thiazotidinedione class, are due to their ability to decrease insulin resistance. This effect is mediated by a nuclear receptor protein called peroxisome proliferator activated receptor-[gamma] (PPAR[gamma]). This protein is involved in the differentiation of adipocytes and is found in large quantities in those cells. PPAR[gamma] also affects insulin sensitivity by mechanisms that are presumed to involve altered gene dynamics in adipocytes. Specifically, it was thought that some factor like PPAR[gamma] might switch on and off some adipocyte-specific gene involved in insulin-mediated signaling pathways. …

Insulin Homeostasis

Majid Ali, M.D.

 


 

Dr. Ali’s Insulin Homeostasis Course

Restoring Insulin Homeostasis, Reversing Diabetes

Majid Ali, M.D.

The Work of True Physicians Does Not Belong to Them, just As Their Words Do Not Belong to Them.  

The Healing of True Physician’s Belongs to Their Patients, ,Just As the Words of True Writers Belong to Their Readers.


First Things First

I.  There are two true markers of real enduring health:

                                                         1. Oxygen health

                                                         2.  Insulin health

II. To understand health is to understand oxygen health and insulin health.  

III. To understand disease is to understand inflammation.

IV. No healing is possible without physiological healing.

V. No disease is possible without pathologic inflammation.

VI. Pathologic inflammation results from disrupted oxygen and insulin signaling.


Insulin Health

Dr. Ali’s Diabetes Library 

Dr. Ali’s Diabetes Course – Part 1: The Basics of Diabetes
https://alidiabetes.org/2016/06/27/dr-alis-diabetes…-part-one-basics/ ‎
 
Dr. Ali’s Diabetes Course – Part 2: Insulin Detox – Beyond Sugar Talk
https://alidiabetes.org/2016/07/11/dr-alis-diabetes-course-part-two-2/ ‎
 
Dr. Ali’s Diabetes Course – Part 3:
https://alidiabetes.org/2016/07/25/dr-alis-3-part-d…ourse-part-three/ 
 
Diabetes Recipes
 Reversing Diabetes – Lesson One
 Reversing Diabetes – Lesson Two
 Reversing Diabetes – Lesson Three
Reversing Diabetes – Lesson Four
Reversing Diabetes – Lesson Five
Reversing Diabetes – Lesson Six
 Diabetes Recipes

Dr. Ali’s Insulin Library

Spiritual Healing Course byMajid Ali, M.D.
 What Is Insulin? What Are Its Functions?
 
 Insulin Detox for Wight Loss and Diabetes Reversal
 
 I’m Hungery After Meals. Why?
 Insulin Buddy and Fatty Liver
 
 What is the Evidence That Neuropathy Is Caused by Insulin Toxicity?
 
Obesity Is Cellular Inflammation
 
Dr. Ali’s Best Anti-Insulin Toxicity Breakfast
 
 Gestational Diabetes Is Insulin Toxicity of the Unborn – Part Two
Your Child – Hyperactive or Hypoglycemic?
 
Why Do I Consider Blood Insulin Test to be the Most Important Test for Metabolism and Diabetes 
Insulin-Toxic Obesity
What Is the Most Important Question in Science, Health, and Healing
 
What Is the Second Most Important Question in Science, Health, and Healing
 
Insulin Videos
 
 
What is Diabetes
Insulin Toxicity De-mystifies Syndrome X
Don’t Trust A1c for Diabetes Diagnosis, Please!
 
 Recipes for Insulin Toxicity – Majid Ali, MD
 
 
Almond Butter Snack for Losing Weight and Reversing Diabetes, An Excellent Choice
 
 
Peanut Butter or Hemp Seed Butter Peanut Butter Snack for Weight Loss and Diabetes Reversal
  
 
 Dr. Ali’s Insulin Course, Basics
 
What Is the Problem With Calorie Counting?
Is a Calorie a Calorie a Calorie?
 
 
Is Insulin Excess Bad for the Heart?
 
 
 
What Is Diabetes? Majid Ali, M.D. With Ben Svoboda
 
Is Excess Insulin Toxic to Nerves
 
 
 
 
Majid Ali, M.D. – Is a Calorie a Calorie a Calorie?
 
I’m Hungry After Meals. Why?
 
 
Recipes for Insulin Toxicity – Majid Ali, MD
 
 
 
Almond Butter Snack for Losing Weight and Reversing Diabetes, An Excellent Choice
 
 
Peanut Butter or Hemp Seed Butter Peanut Butter Snack for Weight Loss and Diabetes Reversal
 
 
 
 Diabetes and insulin Majid Ali MD
Why Do I Consider Blood Insulin Test to be the Single Most Important Test
 
What Is Your Child’s Peak Insulin Level? Is She or He Insulin-Toxic?
 
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